Yunlong Zhang - Academia.edu (original) (raw)
Papers by Yunlong Zhang
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was de... more The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6–18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These s...
American journal of physiology. Heart and circulatory physiology, 2002
The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunct... more The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunction. Models of aging have shown that this is due, in part, to increased prostaglandin H synthase (PGHS)-dependent vasoconstriction. We showed previously that inducible PGHS-2-dependent vasoconstriction is increased with aging. In the present study, we hypothesized that estrogen suppresses PGHS-2-dependent constriction in the aged rat. Isolated mesenteric arteries from placebo- or estrogen-treated, ovariectomized aged (24 mo) Fisher rats were assessed for endothelium-dependent relaxation in the absence or presence of PGHS inhibitors. PGHS inhibition (meclofenamate, 1 micromol/l) enhanced methacholine-induced relaxation only in the placebo group. Specific PGHS-2 inhibition (NS-398, 10 micromol/l) increased arterial relaxation to a greater extent than PGHS-1 inhibition (valeryl salicylate, 3 mmol/l). Estrogen prevented the PGHS-dependent constrictor effect but did not enhance nitric oxide-d...
Hypertension, 1999
Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression... more Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression and/or activity and that nitric oxide may play a role in attenuating vasoconstrictor responses. Yet there are still controversies in this field. Our hypothesis was that the role of nitric oxide in modulating vasoconstrictor responses in estrogen-replaced animals depends on the agonist. The aim of the study was to determine the effect of long-term estrogen replacement on vascular reactivity of resistance-sized mesenteric arteries in ovariectomized rats with the use of a variety of vasoconstrictors. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. 17-estradiol pellets (0.5 mg/pellet) were implanted in the estrogen-replaced group (nϭ9) for 4 weeks; placebo pellets were used in the ovariectomized group (nϭ10). Resistance-sized mesenteric arteries were dissected and mounted onto a dual-chamber arteriograph system. Estradiol replacement did not alter the response of mesenteric arteries to either arginine vasopressin or the thromboxane mimetic U46619. Inhibition of nitric oxide synthase with N G-monomethyl-L-arginine (100 mol/L) did not modulate these vasoconstrictor responses in either group of rats. In contrast, the dose-response curve of the adrenergic agonist phenylephrine was significantly attenuated for the estradiol-replaced rats compared with the ovariectomized group (EC 50 ϭ0.90Ϯ0.17 vs 0.44Ϯ0.08 mol/L, PϽ0.05). After incubation with N G-monomethyl-Larginine, the EC 50 of phenylephrine significantly decreased in both groups, but a significant difference remained between the 2 groups (EC 50 ϭ0.41Ϯ0.08 vs 0.28Ϯ0.02 mol/L, PϽ0.05). Importantly, Western immunoblotting demonstrated that the expression of ␣ 1-adrenergic receptors was significantly suppressed by estradiol replacement. We conclude that estrogen may have a specific effect on adrenergic vasoconstriction by modulating its receptors. (Hypertension.
Hypertension, 2000
During aging, the vascular endothelium changes functionally and morphologically. Although previou... more During aging, the vascular endothelium changes functionally and morphologically. Although previous studies have shown that endothelium-derived eicosanoids increase vessel tone in aging, the precise mechanism(s) has not been fully determined. We hypothesized that aging would increase prostaglandin H synthase (PGHS)-dependent vasoconstriction as well as decrease nitric oxide-dependent relaxation. Mesenteric arteries from 3-month-old (nϭ9) and 12-month-old (nϭ14) female Sprague-Dawley rats were studied in a myograph system. Aging significantly blunted the endothelium-dependent relaxation response to methacholine compared with young rats (EC 50 ϭ7.77ϫ10 Ϫ8 versus 2.68ϫ10 Ϫ8 mol/L, PϽ0.05). Nitric oxide synthase inhibition reduced methacholine-induced relaxation in the young (PϽ0.05) but had no effect in the aging group. Specific inhibition of the PGHS-1 isoform did not significantly affect methacholine-mediated relaxation in the young or aged groups. However, PGHS-2 inhibition greatly enhanced relaxation to methacholine (1.59ϫ10 Ϫ8 versus 7.77ϫ10 Ϫ8 mol/L, PϽ0.01) in the aged group only, restoring vessel function to that of the young. In the aged group, inhibition of the prostaglandin H 2 /thromboxane A 2 receptor enhanced methacholine-dependent relaxation similar to that of PGHS-2 inhibition. Moreover, arterial expression of PGHS-2 protein increased with age. In summary, nitric oxide-dependent modulation of vessel function decreased with age, PGHS-1 did not significantly affect vessel tone in either the young or aging group, and PGHS-2 greatly increased vasoconstriction in aging. Thus, we have identified enhanced PGHS-2-mediated vasoconstriction in aging and therefore suggest that inhibition of this isoform is potentially a new target for therapeutic intervention to improve vascular function. (Hypertension. 2000;35:1242-1247.) Key Words: prostaglandins Ⅲ vasculature Ⅲ aging Ⅲ nitric oxide Ⅲ endothelium Methods General Animal Model Female Sprague-Dawley rats (2 months of age) were obtained from Biological Sciences and housed in the facilities at the University of
Hypertension, 1999
Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to... more Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to pregnancy are compromised. Oxidative stress as well as endothelial cell dysfunction have been implicated as pathophysiological features of preeclampsia. Endothelial cells produce the vasorelaxant nitric oxide (NO). However, NO is also known to react with superoxide anions (produced under conditions of oxidative stress), yielding peroxynitrite that may impair vascular function. Our objective was to use immunohistochemical techniques to determine whether there is evidence of peroxynitrite formation in the maternal systemic vasculature of women with preeclampsia. Vessels were obtained from a biopsy of subcutaneous fat at the time of cesarean section from normal pregnant (nϭ7) and preeclamptic (nϭ7) women or at the time of hysterectomy from nonpregnant women (nϭ5). There were significantly more vessels staining with greater intensity for nitrotyrosine and endothelial NO synthase in the endothelium of vessels from women with preeclampsia compared with that of normal pregnant women or nonpregnant women. Both endothelial and smooth muscle cells from all vessels showed evidence for the presence of superoxide dismutase (SOD), an enzyme that scavenges superoxide anions. However, the intensity of staining for SOD in the endothelium was significantly lower in the preeclamptic and nonpregnant women than in normal pregnant women. These data of increased endothelial NO synthase, decreased SOD, and increased nitrotyrosine immunostaining in the maternal vasculature of women with preeclampsia suggest increased peroxynitrite formation. We speculate that peroxynitrite is involved in endothelial cell dysfunction in preeclamptic women and contributes to the pathophysiology of this pregnancy disorder. (Hypertension.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was de... more The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6–18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These s...
American journal of physiology. Heart and circulatory physiology, 2002
The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunct... more The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunction. Models of aging have shown that this is due, in part, to increased prostaglandin H synthase (PGHS)-dependent vasoconstriction. We showed previously that inducible PGHS-2-dependent vasoconstriction is increased with aging. In the present study, we hypothesized that estrogen suppresses PGHS-2-dependent constriction in the aged rat. Isolated mesenteric arteries from placebo- or estrogen-treated, ovariectomized aged (24 mo) Fisher rats were assessed for endothelium-dependent relaxation in the absence or presence of PGHS inhibitors. PGHS inhibition (meclofenamate, 1 micromol/l) enhanced methacholine-induced relaxation only in the placebo group. Specific PGHS-2 inhibition (NS-398, 10 micromol/l) increased arterial relaxation to a greater extent than PGHS-1 inhibition (valeryl salicylate, 3 mmol/l). Estrogen prevented the PGHS-dependent constrictor effect but did not enhance nitric oxide-d...
Hypertension, 1999
Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression... more Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression and/or activity and that nitric oxide may play a role in attenuating vasoconstrictor responses. Yet there are still controversies in this field. Our hypothesis was that the role of nitric oxide in modulating vasoconstrictor responses in estrogen-replaced animals depends on the agonist. The aim of the study was to determine the effect of long-term estrogen replacement on vascular reactivity of resistance-sized mesenteric arteries in ovariectomized rats with the use of a variety of vasoconstrictors. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. 17-estradiol pellets (0.5 mg/pellet) were implanted in the estrogen-replaced group (nϭ9) for 4 weeks; placebo pellets were used in the ovariectomized group (nϭ10). Resistance-sized mesenteric arteries were dissected and mounted onto a dual-chamber arteriograph system. Estradiol replacement did not alter the response of mesenteric arteries to either arginine vasopressin or the thromboxane mimetic U46619. Inhibition of nitric oxide synthase with N G-monomethyl-L-arginine (100 mol/L) did not modulate these vasoconstrictor responses in either group of rats. In contrast, the dose-response curve of the adrenergic agonist phenylephrine was significantly attenuated for the estradiol-replaced rats compared with the ovariectomized group (EC 50 ϭ0.90Ϯ0.17 vs 0.44Ϯ0.08 mol/L, PϽ0.05). After incubation with N G-monomethyl-Larginine, the EC 50 of phenylephrine significantly decreased in both groups, but a significant difference remained between the 2 groups (EC 50 ϭ0.41Ϯ0.08 vs 0.28Ϯ0.02 mol/L, PϽ0.05). Importantly, Western immunoblotting demonstrated that the expression of ␣ 1-adrenergic receptors was significantly suppressed by estradiol replacement. We conclude that estrogen may have a specific effect on adrenergic vasoconstriction by modulating its receptors. (Hypertension.
Hypertension, 2000
During aging, the vascular endothelium changes functionally and morphologically. Although previou... more During aging, the vascular endothelium changes functionally and morphologically. Although previous studies have shown that endothelium-derived eicosanoids increase vessel tone in aging, the precise mechanism(s) has not been fully determined. We hypothesized that aging would increase prostaglandin H synthase (PGHS)-dependent vasoconstriction as well as decrease nitric oxide-dependent relaxation. Mesenteric arteries from 3-month-old (nϭ9) and 12-month-old (nϭ14) female Sprague-Dawley rats were studied in a myograph system. Aging significantly blunted the endothelium-dependent relaxation response to methacholine compared with young rats (EC 50 ϭ7.77ϫ10 Ϫ8 versus 2.68ϫ10 Ϫ8 mol/L, PϽ0.05). Nitric oxide synthase inhibition reduced methacholine-induced relaxation in the young (PϽ0.05) but had no effect in the aging group. Specific inhibition of the PGHS-1 isoform did not significantly affect methacholine-mediated relaxation in the young or aged groups. However, PGHS-2 inhibition greatly enhanced relaxation to methacholine (1.59ϫ10 Ϫ8 versus 7.77ϫ10 Ϫ8 mol/L, PϽ0.01) in the aged group only, restoring vessel function to that of the young. In the aged group, inhibition of the prostaglandin H 2 /thromboxane A 2 receptor enhanced methacholine-dependent relaxation similar to that of PGHS-2 inhibition. Moreover, arterial expression of PGHS-2 protein increased with age. In summary, nitric oxide-dependent modulation of vessel function decreased with age, PGHS-1 did not significantly affect vessel tone in either the young or aging group, and PGHS-2 greatly increased vasoconstriction in aging. Thus, we have identified enhanced PGHS-2-mediated vasoconstriction in aging and therefore suggest that inhibition of this isoform is potentially a new target for therapeutic intervention to improve vascular function. (Hypertension. 2000;35:1242-1247.) Key Words: prostaglandins Ⅲ vasculature Ⅲ aging Ⅲ nitric oxide Ⅲ endothelium Methods General Animal Model Female Sprague-Dawley rats (2 months of age) were obtained from Biological Sciences and housed in the facilities at the University of
Hypertension, 1999
Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to... more Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to pregnancy are compromised. Oxidative stress as well as endothelial cell dysfunction have been implicated as pathophysiological features of preeclampsia. Endothelial cells produce the vasorelaxant nitric oxide (NO). However, NO is also known to react with superoxide anions (produced under conditions of oxidative stress), yielding peroxynitrite that may impair vascular function. Our objective was to use immunohistochemical techniques to determine whether there is evidence of peroxynitrite formation in the maternal systemic vasculature of women with preeclampsia. Vessels were obtained from a biopsy of subcutaneous fat at the time of cesarean section from normal pregnant (nϭ7) and preeclamptic (nϭ7) women or at the time of hysterectomy from nonpregnant women (nϭ5). There were significantly more vessels staining with greater intensity for nitrotyrosine and endothelial NO synthase in the endothelium of vessels from women with preeclampsia compared with that of normal pregnant women or nonpregnant women. Both endothelial and smooth muscle cells from all vessels showed evidence for the presence of superoxide dismutase (SOD), an enzyme that scavenges superoxide anions. However, the intensity of staining for SOD in the endothelium was significantly lower in the preeclamptic and nonpregnant women than in normal pregnant women. These data of increased endothelial NO synthase, decreased SOD, and increased nitrotyrosine immunostaining in the maternal vasculature of women with preeclampsia suggest increased peroxynitrite formation. We speculate that peroxynitrite is involved in endothelial cell dysfunction in preeclamptic women and contributes to the pathophysiology of this pregnancy disorder. (Hypertension.
Circulation Research, 2000
Matrix metalloproteinase (MMP)-2 has been historically associated with the process of vascular re... more Matrix metalloproteinase (MMP)-2 has been historically associated with the process of vascular remodeling through the cleavage of extracellular matrix proteins. However, we recently found that MMP-2 also cleaves the endothelium-derived peptide big endothelin-1, ET-1[1-38] and yields the novel vasoconstrictor ET-1[1-32]. We therefore investigated the effects of MMP-2 inhibitors as potential vasodilators. MMP inhibition with orthophenanthroline (0.3 to 30 mol/L) induced vasorelaxation of isolated rat mesenteric arteries (maximum of relax-ationϭ74.5Ϯ27.6% at 30 mol/L). However, phosphoramidon (0.3 to 30 mol/L), which inhibits some metalloenzymes, but not MMP-2, did not dilate the arteries. Selective inhibition of endogenous MMP-2 with the novel tissue-permeable cyclic peptide CTTHWGFTLC (CTT, 10 mol/L) also caused vasorelaxation (by 85Ϯ6%), whereas STTHWGFTLS (10 mol/L), an inactive CTT analogue, did not dilate the arteries. Interestingly, the vasorelaxation that results from MMP-2 inhibition was endothelium-independent. Thus, we examined whether MMP-2 acted on peptides derived from the smooth muscle or the perivascular nerves. Recombinant human MMP-2 cleaved calcitonin gene-related peptide (CGRP) specifically at the Gly 14-Leu 15 peptide bond and reduced the vasodilatory potency of CGRP by 20-fold. Inhibition of MMP-2 increased the amount of intact CGRP in arteries and enhanced vasorelaxation induced by anandamide, which stimulates CGRP release. Vasorelaxation in response to MMP-2 inhibition was abolished by CGRP[8-37], a selective CGRP receptor antagonist, and by capsaicin, which depletes arterial perivascular nerves of CGRP. We conclude that vascular MMP-2 cleaves endogenous CGRP and promotes vasoconstriction. These data suggest a novel mechanism of regulating the vasoactive and, possibly, the neurohormonal actions of CGRP and establish MMP-2 as a modulator of vascular function.
Circulation Research, 1998
There is evidence that estrogen can upregulate nitric oxide (NO) synthase expression. There is al... more There is evidence that estrogen can upregulate nitric oxide (NO) synthase expression. There is also evidence that NO increases the activity of prostaglandin H synthase (PGHS). Our initial hypothesis was that removal of ovarian steroids would decrease endothelium/NO-dependent relaxation responses but that estrogen replacement would increase NO and PGHS activity, leading to increased vasodilation. Resistance-sized (Ͻ250 m) mesenteric arteries from ovariectomized Sprague-Dawley rats without and with 17-estradiol replacement (0.15 or 0.5 mg/pellet, 60-day release) for 4 weeks were studied in a myograph system. The vasodilator response to methacholine, an endothelium-dependent muscarinic agonist, was reduced in the arteries of the ovariectomized rats compared with estradiol-replaced rats. In the presence of PGHS inhibitors (meclofenamate, valeryl salicylate, and NS-398) or a thromboxane A 2 (TxA 2)/prostaglandin H 2 (PGH 2) receptor blocker (SQ-29548), there was no longer a significant difference among the groups. Contrary to our initial hypothesis, inhibition of the PGHS pathway significantly enhanced the relaxation response in the arteries from the ovariectomized rats, which was similar to the response in the arteries from estradiol-replaced rats, indicating that a PGHS-dependent vasoconstrictor had modified the response to methacholine. Confirming these data, in response to exogenous arachidonic acid, arteries from ovariectomized rats exhibited constriction, whereas the arteries from the estradiol-replaced rats exhibited vasodilation. In the ovariectomized rats, pretreatment with inhibitors of the PGHS pathway reversed the vasoconstriction to a vasodilation. In addition, the vasoconstrictor response to the thromboxane mimetic U-46619 as well as PGH 2 was enhanced in endothelium-denuded arteries from the ovariectomized rats compared with the estradiol-replaced rats. These data demonstrate that removal of ovarian steroids increased endothelium-mediated PGHS-dependent vasoconstriction that was associated with augmented sensitivity of the TxA 2 /PGH 2 receptor. Chronic estrogen replacement in the ovariectomized rat suppressed this PGHS-dependent vasoconstrictor response.
JACC: Cardiovascular Interventions, 2017
BACKGROUND The Absorb everolimus-eluting BVS provides drug delivery and mechanical support simila... more BACKGROUND The Absorb everolimus-eluting BVS provides drug delivery and mechanical support similar to a metallic drug-eluting stent, followed by resorption and restoration of more normal vascular structure with the potential to improve late clinical outcomes. METHODS The ABSORB II, ABSORB III, ABSORB Japan, and ABSORB China trials were pooled. Baseline clinical, angiography, procedural variables, and 2-year outcomes were analyzed by sex and device. RESULTS Among 3,384 randomized patients, 932 (27.5%) were female. Females were older, more often had diabetes and hypertension, but had less everolimus-eluting stent, 3-vessel disease, and smoking compared with males (all p#0.001). The 2-year rates of target lesion failure with BVS versus everolimus-eluting stent in females were 8.9% versus 6.2% (study-level adjusted hazard ratio: 1.47; 95% confidence interval [CI]: 0.88 to 2.46) and 8.9% versus 6.4% in males (HR: 1.40; 95% CI: 1.02 to 1.92; p interaction ¼ 0.85). There were no significant interactions between sex and device type for any of the components of target lesion failure. CONCLUSIONS The relative treatment effects of BVS and everolimus-eluting stent for the 2-year rates of target lesion failure and other cardiovascular outcomes were consistent in females and males.
Journal of the American College of Cardiology, 2003
Background: A defibrillator using rectilinear biphasic waveform (2011) reportedly requires lower ... more Background: A defibrillator using rectilinear biphasic waveform (2011) reportedly requires lower energy for defibdllation than a device using truncated exponential biphasic waveform (Physio). Success rates for cardioversion of atrial fibrillation (AF) were compared between Zoll (with a maximum energy of 2OOJ) and Physio (with a maximum energy of 360J). Methods: Patients (pts) undergoing transthoracic cardioversion for AF were randomly assigned to Zoll or Physio. Shock energy was increased stepwise (5OJ, lOOJ, 15OJ, 200J) until cardioversion or to the maximum level of the device. If AF persisted despite the maximum energy shock, pts were crossed over and received the maximum energy shock by the other device. Results: Of 134 pts (76 males, age 64+/-15). 63 were assigned to Zoll and 71 to Physio.
Hypertension, 2000
Estrogen replacement therapy significantly decreases the incidence of cardiovascular disease in p... more Estrogen replacement therapy significantly decreases the incidence of cardiovascular disease in postmenopausal women. In aging, there is an increase in vascular stiffness along with a decrease in matrix metalloproteinase (MMP) activity. Our hypothesis was that estrogen replacement would increase MMPs and therefore reduce the vascular stiffness that is associated with aging. Female Sprague-Dawley rats were implanted with a placebo or 17-estradiol-containing pellet (0.5 mg/pellet, 60-day release) at 10 months of age (nϭ6, each). Six young rats (3 months old) were also studied. After a 2-month exposure to the pellet, mesenteric arteries were studied on a pressurized arteriograph system. Distensibility and wall thickness were measured in response to stepwise increases in intraluminal pressure in Ca 2ϩ-free physiological saline solution buffer with papaverine (10 Ϫ4 mol/L). In response to increasing pressure, aged placebo rats exhibited a significant decrease in distensibility compared with young rats (PϽ0.05) that was accompanied by an increase in wall thickness (PϽ0.05). Conversely, estrogen replacement increased distensibility and decreased wall thickness in aged rats (old estrogen-replaced versus old placebo, PϽ0.05). Zymography data indicated that MMP-2 activity decreased in aging but was increased by estrogen replacement. In summary, estrogen replacement in aging female rats reduces age-associated vascular remodeling. (Hypertension. 2000;36:970-974.
Europace, 2006
Aims Interval-and morphology-based algorithms have been used in modern implantable cardioverter d... more Aims Interval-and morphology-based algorithms have been used in modern implantable cardioverter defibrillators (ICDs) to discriminate supraventricular tachycardia (SVT) from other rhythms. A newly developed ICD discrimination algorithm, Rhythm ID TM (Guidant Corporation, St Paul, MN, USA), uses both interval-based metrics and an electrogram vector timing and correlation (VTC) algorithm in a dual-chamber ICD. In a single-chamber ICD, Rhythm ID contains only the VTC component. This study conducted a retrospective analysis of the performance of Rhythm ID for the detection of induced and spontaneous rhythms in a single-chamber ICD. Methods and results This study gathered the data from a prospective, multicentre clinical trial. Ninetysix patients were implanted with a dual-chamber ICD. For this study, each episode was analysed to determine the performance of the single-chamber ICD Rhythm ID algorithm. The mean age of the patients implanted with the device was 67 + 11 years. Seventy-eight patients were male. The primary cardiovascular disease was coronary artery disease and the primary tachyarrhythmia was monomorphic ventricular tachycardia (VT). The mean follow-up time was 11.4 months. A total of 369 induced and spontaneous ventricular arrhythmias was analysed. The algorithm detected 100% of ventricular arrhythmias. Four hundred and forty-two SVT episodes were analysed, including 145 induced and 297 spontaneous. The SVTs were atrial fibrillation (n ¼ 199), atrial flutter (n ¼ 135), and 1:1 SVT (n ¼ 108). The single-chamber ICD Rhythm ID algorithm successfully discriminated 403 SVT episodes and achieved a specificity of 91%. Conclusion The single-chamber version of Rhythm ID demonstrated high specificity without compromising sensitivity.
Canadian Journal of Physiology and Pharmacology, 2000
Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inh... more Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inhibition of nitric oxide synthase (NOS) induces some pathological processes characteristic of preeclampsia. The current project sought to study the effect of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10 µg·min-1, sc for 7 days) on plasma volume, plasma atrial natriuretic factor (ANF), plasma endothelin-1 (ET), and plasma renin activity (PRA) during gestation in conscious rats. NOS inhibition caused mean arterial pressure to increase in both virgin and 21-day pregnant rats. Plasma volume fell in the pregnant rats [L-NAME, 4.5 ± 0.3 mL·100 g-1 body wt. (n = 7) vs. D-NAME, 6.8 ± 0.2 mL·100 g-1 body wt. (n = 10); P < 0.05] but not in the virgin rats [L-NAME, 4.3 ± 0.1 mL·100 g-1 body wt. (n = 6) vs. D-NAME, 4.8 ± 0.2 mL·100 g-1 body wt. (n = 8)]. There was no effect of NOS inhibition on plasma ANF levels or PRA in either the virgin or pregnant rats. However, L-NAME did de...
Canadian Journal of Physiology and Pharmacology, 1999
Atrial natriuretic factor (ANF) release was studied in isolated perfused atria prepared from rats... more Atrial natriuretic factor (ANF) release was studied in isolated perfused atria prepared from rats. When the vein-atrial junction (VAJ) was distended with an inflatable balloon, ANF release into the perfusate was greater in intact atria than in appendectomized atria. It was concluded that distention of the VAJ causes ANF release from the atrial appendage. A cascade experiment was then prepared whereby buffer from one isolated atrium perfused a second atrium. Although the VAJ of the first atrium could be distended by balloon, the atrial appendage was ligated so ANF was not secreted into the perfusate. The second atrium was intact, but no balloon was inserted. Despite the fact that there were no changes in intraluminal pressure, ANF secretion from the second atrium increased when the VAJ of the first atrium was distended. This response was blocked by the endothelin (ET) A receptor antagonist BQ-123. However, no distention-induced changes in ET-1 levels could be found in the perfusate f...
Journal of the American College of Cardiology, Jan 6, 2015
The everolimus-eluting bioresorbable vascular scaffold (BVS) is designed to achieve results compa... more The everolimus-eluting bioresorbable vascular scaffold (BVS) is designed to achieve results comparable to metallic drug-eluting stents (DES) at 1 year, with improved long-term outcomes. Whether the 1-year clinical and angiographic results of BVS are non-inferior to current generation DES has not been established. We sought to evaluate the angiographic efficacy and clinical safety and effectiveness of BVS in a randomized trial designed to enable approval of the BVS in China. Eligible patients with 1 or 2 de novo native coronary artery lesions were randomized to BVS or cobalt-chromium everolimus-eluting stents (CoCr-EES) in 1:1 ratio stratified by diabetes and the number of lesions treated. Angiographic and clinical follow-up were planned at 1 year in all patients. The primary endpoint was angiographic in-segment late loss (LL), powered for non-inferiority with a margin of 0.15 mm. A total of 480 patients were randomized (241 BVS vs. 239 CoCr-EES) at 24 sites. Acute clinical device su...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was de... more The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6–18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These s...
American journal of physiology. Heart and circulatory physiology, 2002
The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunct... more The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunction. Models of aging have shown that this is due, in part, to increased prostaglandin H synthase (PGHS)-dependent vasoconstriction. We showed previously that inducible PGHS-2-dependent vasoconstriction is increased with aging. In the present study, we hypothesized that estrogen suppresses PGHS-2-dependent constriction in the aged rat. Isolated mesenteric arteries from placebo- or estrogen-treated, ovariectomized aged (24 mo) Fisher rats were assessed for endothelium-dependent relaxation in the absence or presence of PGHS inhibitors. PGHS inhibition (meclofenamate, 1 micromol/l) enhanced methacholine-induced relaxation only in the placebo group. Specific PGHS-2 inhibition (NS-398, 10 micromol/l) increased arterial relaxation to a greater extent than PGHS-1 inhibition (valeryl salicylate, 3 mmol/l). Estrogen prevented the PGHS-dependent constrictor effect but did not enhance nitric oxide-d...
Hypertension, 1999
Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression... more Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression and/or activity and that nitric oxide may play a role in attenuating vasoconstrictor responses. Yet there are still controversies in this field. Our hypothesis was that the role of nitric oxide in modulating vasoconstrictor responses in estrogen-replaced animals depends on the agonist. The aim of the study was to determine the effect of long-term estrogen replacement on vascular reactivity of resistance-sized mesenteric arteries in ovariectomized rats with the use of a variety of vasoconstrictors. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. 17-estradiol pellets (0.5 mg/pellet) were implanted in the estrogen-replaced group (nϭ9) for 4 weeks; placebo pellets were used in the ovariectomized group (nϭ10). Resistance-sized mesenteric arteries were dissected and mounted onto a dual-chamber arteriograph system. Estradiol replacement did not alter the response of mesenteric arteries to either arginine vasopressin or the thromboxane mimetic U46619. Inhibition of nitric oxide synthase with N G-monomethyl-L-arginine (100 mol/L) did not modulate these vasoconstrictor responses in either group of rats. In contrast, the dose-response curve of the adrenergic agonist phenylephrine was significantly attenuated for the estradiol-replaced rats compared with the ovariectomized group (EC 50 ϭ0.90Ϯ0.17 vs 0.44Ϯ0.08 mol/L, PϽ0.05). After incubation with N G-monomethyl-Larginine, the EC 50 of phenylephrine significantly decreased in both groups, but a significant difference remained between the 2 groups (EC 50 ϭ0.41Ϯ0.08 vs 0.28Ϯ0.02 mol/L, PϽ0.05). Importantly, Western immunoblotting demonstrated that the expression of ␣ 1-adrenergic receptors was significantly suppressed by estradiol replacement. We conclude that estrogen may have a specific effect on adrenergic vasoconstriction by modulating its receptors. (Hypertension.
Hypertension, 2000
During aging, the vascular endothelium changes functionally and morphologically. Although previou... more During aging, the vascular endothelium changes functionally and morphologically. Although previous studies have shown that endothelium-derived eicosanoids increase vessel tone in aging, the precise mechanism(s) has not been fully determined. We hypothesized that aging would increase prostaglandin H synthase (PGHS)-dependent vasoconstriction as well as decrease nitric oxide-dependent relaxation. Mesenteric arteries from 3-month-old (nϭ9) and 12-month-old (nϭ14) female Sprague-Dawley rats were studied in a myograph system. Aging significantly blunted the endothelium-dependent relaxation response to methacholine compared with young rats (EC 50 ϭ7.77ϫ10 Ϫ8 versus 2.68ϫ10 Ϫ8 mol/L, PϽ0.05). Nitric oxide synthase inhibition reduced methacholine-induced relaxation in the young (PϽ0.05) but had no effect in the aging group. Specific inhibition of the PGHS-1 isoform did not significantly affect methacholine-mediated relaxation in the young or aged groups. However, PGHS-2 inhibition greatly enhanced relaxation to methacholine (1.59ϫ10 Ϫ8 versus 7.77ϫ10 Ϫ8 mol/L, PϽ0.01) in the aged group only, restoring vessel function to that of the young. In the aged group, inhibition of the prostaglandin H 2 /thromboxane A 2 receptor enhanced methacholine-dependent relaxation similar to that of PGHS-2 inhibition. Moreover, arterial expression of PGHS-2 protein increased with age. In summary, nitric oxide-dependent modulation of vessel function decreased with age, PGHS-1 did not significantly affect vessel tone in either the young or aging group, and PGHS-2 greatly increased vasoconstriction in aging. Thus, we have identified enhanced PGHS-2-mediated vasoconstriction in aging and therefore suggest that inhibition of this isoform is potentially a new target for therapeutic intervention to improve vascular function. (Hypertension. 2000;35:1242-1247.) Key Words: prostaglandins Ⅲ vasculature Ⅲ aging Ⅲ nitric oxide Ⅲ endothelium Methods General Animal Model Female Sprague-Dawley rats (2 months of age) were obtained from Biological Sciences and housed in the facilities at the University of
Hypertension, 1999
Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to... more Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to pregnancy are compromised. Oxidative stress as well as endothelial cell dysfunction have been implicated as pathophysiological features of preeclampsia. Endothelial cells produce the vasorelaxant nitric oxide (NO). However, NO is also known to react with superoxide anions (produced under conditions of oxidative stress), yielding peroxynitrite that may impair vascular function. Our objective was to use immunohistochemical techniques to determine whether there is evidence of peroxynitrite formation in the maternal systemic vasculature of women with preeclampsia. Vessels were obtained from a biopsy of subcutaneous fat at the time of cesarean section from normal pregnant (nϭ7) and preeclamptic (nϭ7) women or at the time of hysterectomy from nonpregnant women (nϭ5). There were significantly more vessels staining with greater intensity for nitrotyrosine and endothelial NO synthase in the endothelium of vessels from women with preeclampsia compared with that of normal pregnant women or nonpregnant women. Both endothelial and smooth muscle cells from all vessels showed evidence for the presence of superoxide dismutase (SOD), an enzyme that scavenges superoxide anions. However, the intensity of staining for SOD in the endothelium was significantly lower in the preeclamptic and nonpregnant women than in normal pregnant women. These data of increased endothelial NO synthase, decreased SOD, and increased nitrotyrosine immunostaining in the maternal vasculature of women with preeclampsia suggest increased peroxynitrite formation. We speculate that peroxynitrite is involved in endothelial cell dysfunction in preeclamptic women and contributes to the pathophysiology of this pregnancy disorder. (Hypertension.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was de... more The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6–18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These s...
American journal of physiology. Heart and circulatory physiology, 2002
The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunct... more The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunction. Models of aging have shown that this is due, in part, to increased prostaglandin H synthase (PGHS)-dependent vasoconstriction. We showed previously that inducible PGHS-2-dependent vasoconstriction is increased with aging. In the present study, we hypothesized that estrogen suppresses PGHS-2-dependent constriction in the aged rat. Isolated mesenteric arteries from placebo- or estrogen-treated, ovariectomized aged (24 mo) Fisher rats were assessed for endothelium-dependent relaxation in the absence or presence of PGHS inhibitors. PGHS inhibition (meclofenamate, 1 micromol/l) enhanced methacholine-induced relaxation only in the placebo group. Specific PGHS-2 inhibition (NS-398, 10 micromol/l) increased arterial relaxation to a greater extent than PGHS-1 inhibition (valeryl salicylate, 3 mmol/l). Estrogen prevented the PGHS-dependent constrictor effect but did not enhance nitric oxide-d...
Hypertension, 1999
Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression... more Recent studies have shown that estrogen can increase endothelial nitric oxide synthase expression and/or activity and that nitric oxide may play a role in attenuating vasoconstrictor responses. Yet there are still controversies in this field. Our hypothesis was that the role of nitric oxide in modulating vasoconstrictor responses in estrogen-replaced animals depends on the agonist. The aim of the study was to determine the effect of long-term estrogen replacement on vascular reactivity of resistance-sized mesenteric arteries in ovariectomized rats with the use of a variety of vasoconstrictors. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. 17-estradiol pellets (0.5 mg/pellet) were implanted in the estrogen-replaced group (nϭ9) for 4 weeks; placebo pellets were used in the ovariectomized group (nϭ10). Resistance-sized mesenteric arteries were dissected and mounted onto a dual-chamber arteriograph system. Estradiol replacement did not alter the response of mesenteric arteries to either arginine vasopressin or the thromboxane mimetic U46619. Inhibition of nitric oxide synthase with N G-monomethyl-L-arginine (100 mol/L) did not modulate these vasoconstrictor responses in either group of rats. In contrast, the dose-response curve of the adrenergic agonist phenylephrine was significantly attenuated for the estradiol-replaced rats compared with the ovariectomized group (EC 50 ϭ0.90Ϯ0.17 vs 0.44Ϯ0.08 mol/L, PϽ0.05). After incubation with N G-monomethyl-Larginine, the EC 50 of phenylephrine significantly decreased in both groups, but a significant difference remained between the 2 groups (EC 50 ϭ0.41Ϯ0.08 vs 0.28Ϯ0.02 mol/L, PϽ0.05). Importantly, Western immunoblotting demonstrated that the expression of ␣ 1-adrenergic receptors was significantly suppressed by estradiol replacement. We conclude that estrogen may have a specific effect on adrenergic vasoconstriction by modulating its receptors. (Hypertension.
Hypertension, 2000
During aging, the vascular endothelium changes functionally and morphologically. Although previou... more During aging, the vascular endothelium changes functionally and morphologically. Although previous studies have shown that endothelium-derived eicosanoids increase vessel tone in aging, the precise mechanism(s) has not been fully determined. We hypothesized that aging would increase prostaglandin H synthase (PGHS)-dependent vasoconstriction as well as decrease nitric oxide-dependent relaxation. Mesenteric arteries from 3-month-old (nϭ9) and 12-month-old (nϭ14) female Sprague-Dawley rats were studied in a myograph system. Aging significantly blunted the endothelium-dependent relaxation response to methacholine compared with young rats (EC 50 ϭ7.77ϫ10 Ϫ8 versus 2.68ϫ10 Ϫ8 mol/L, PϽ0.05). Nitric oxide synthase inhibition reduced methacholine-induced relaxation in the young (PϽ0.05) but had no effect in the aging group. Specific inhibition of the PGHS-1 isoform did not significantly affect methacholine-mediated relaxation in the young or aged groups. However, PGHS-2 inhibition greatly enhanced relaxation to methacholine (1.59ϫ10 Ϫ8 versus 7.77ϫ10 Ϫ8 mol/L, PϽ0.01) in the aged group only, restoring vessel function to that of the young. In the aged group, inhibition of the prostaglandin H 2 /thromboxane A 2 receptor enhanced methacholine-dependent relaxation similar to that of PGHS-2 inhibition. Moreover, arterial expression of PGHS-2 protein increased with age. In summary, nitric oxide-dependent modulation of vessel function decreased with age, PGHS-1 did not significantly affect vessel tone in either the young or aging group, and PGHS-2 greatly increased vasoconstriction in aging. Thus, we have identified enhanced PGHS-2-mediated vasoconstriction in aging and therefore suggest that inhibition of this isoform is potentially a new target for therapeutic intervention to improve vascular function. (Hypertension. 2000;35:1242-1247.) Key Words: prostaglandins Ⅲ vasculature Ⅲ aging Ⅲ nitric oxide Ⅲ endothelium Methods General Animal Model Female Sprague-Dawley rats (2 months of age) were obtained from Biological Sciences and housed in the facilities at the University of
Hypertension, 1999
Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to... more Preeclampsia is a multisystemic disorder of pregnancy in which the normal vascular adaptations to pregnancy are compromised. Oxidative stress as well as endothelial cell dysfunction have been implicated as pathophysiological features of preeclampsia. Endothelial cells produce the vasorelaxant nitric oxide (NO). However, NO is also known to react with superoxide anions (produced under conditions of oxidative stress), yielding peroxynitrite that may impair vascular function. Our objective was to use immunohistochemical techniques to determine whether there is evidence of peroxynitrite formation in the maternal systemic vasculature of women with preeclampsia. Vessels were obtained from a biopsy of subcutaneous fat at the time of cesarean section from normal pregnant (nϭ7) and preeclamptic (nϭ7) women or at the time of hysterectomy from nonpregnant women (nϭ5). There were significantly more vessels staining with greater intensity for nitrotyrosine and endothelial NO synthase in the endothelium of vessels from women with preeclampsia compared with that of normal pregnant women or nonpregnant women. Both endothelial and smooth muscle cells from all vessels showed evidence for the presence of superoxide dismutase (SOD), an enzyme that scavenges superoxide anions. However, the intensity of staining for SOD in the endothelium was significantly lower in the preeclamptic and nonpregnant women than in normal pregnant women. These data of increased endothelial NO synthase, decreased SOD, and increased nitrotyrosine immunostaining in the maternal vasculature of women with preeclampsia suggest increased peroxynitrite formation. We speculate that peroxynitrite is involved in endothelial cell dysfunction in preeclamptic women and contributes to the pathophysiology of this pregnancy disorder. (Hypertension.
Circulation Research, 2000
Matrix metalloproteinase (MMP)-2 has been historically associated with the process of vascular re... more Matrix metalloproteinase (MMP)-2 has been historically associated with the process of vascular remodeling through the cleavage of extracellular matrix proteins. However, we recently found that MMP-2 also cleaves the endothelium-derived peptide big endothelin-1, ET-1[1-38] and yields the novel vasoconstrictor ET-1[1-32]. We therefore investigated the effects of MMP-2 inhibitors as potential vasodilators. MMP inhibition with orthophenanthroline (0.3 to 30 mol/L) induced vasorelaxation of isolated rat mesenteric arteries (maximum of relax-ationϭ74.5Ϯ27.6% at 30 mol/L). However, phosphoramidon (0.3 to 30 mol/L), which inhibits some metalloenzymes, but not MMP-2, did not dilate the arteries. Selective inhibition of endogenous MMP-2 with the novel tissue-permeable cyclic peptide CTTHWGFTLC (CTT, 10 mol/L) also caused vasorelaxation (by 85Ϯ6%), whereas STTHWGFTLS (10 mol/L), an inactive CTT analogue, did not dilate the arteries. Interestingly, the vasorelaxation that results from MMP-2 inhibition was endothelium-independent. Thus, we examined whether MMP-2 acted on peptides derived from the smooth muscle or the perivascular nerves. Recombinant human MMP-2 cleaved calcitonin gene-related peptide (CGRP) specifically at the Gly 14-Leu 15 peptide bond and reduced the vasodilatory potency of CGRP by 20-fold. Inhibition of MMP-2 increased the amount of intact CGRP in arteries and enhanced vasorelaxation induced by anandamide, which stimulates CGRP release. Vasorelaxation in response to MMP-2 inhibition was abolished by CGRP[8-37], a selective CGRP receptor antagonist, and by capsaicin, which depletes arterial perivascular nerves of CGRP. We conclude that vascular MMP-2 cleaves endogenous CGRP and promotes vasoconstriction. These data suggest a novel mechanism of regulating the vasoactive and, possibly, the neurohormonal actions of CGRP and establish MMP-2 as a modulator of vascular function.
Circulation Research, 1998
There is evidence that estrogen can upregulate nitric oxide (NO) synthase expression. There is al... more There is evidence that estrogen can upregulate nitric oxide (NO) synthase expression. There is also evidence that NO increases the activity of prostaglandin H synthase (PGHS). Our initial hypothesis was that removal of ovarian steroids would decrease endothelium/NO-dependent relaxation responses but that estrogen replacement would increase NO and PGHS activity, leading to increased vasodilation. Resistance-sized (Ͻ250 m) mesenteric arteries from ovariectomized Sprague-Dawley rats without and with 17-estradiol replacement (0.15 or 0.5 mg/pellet, 60-day release) for 4 weeks were studied in a myograph system. The vasodilator response to methacholine, an endothelium-dependent muscarinic agonist, was reduced in the arteries of the ovariectomized rats compared with estradiol-replaced rats. In the presence of PGHS inhibitors (meclofenamate, valeryl salicylate, and NS-398) or a thromboxane A 2 (TxA 2)/prostaglandin H 2 (PGH 2) receptor blocker (SQ-29548), there was no longer a significant difference among the groups. Contrary to our initial hypothesis, inhibition of the PGHS pathway significantly enhanced the relaxation response in the arteries from the ovariectomized rats, which was similar to the response in the arteries from estradiol-replaced rats, indicating that a PGHS-dependent vasoconstrictor had modified the response to methacholine. Confirming these data, in response to exogenous arachidonic acid, arteries from ovariectomized rats exhibited constriction, whereas the arteries from the estradiol-replaced rats exhibited vasodilation. In the ovariectomized rats, pretreatment with inhibitors of the PGHS pathway reversed the vasoconstriction to a vasodilation. In addition, the vasoconstrictor response to the thromboxane mimetic U-46619 as well as PGH 2 was enhanced in endothelium-denuded arteries from the ovariectomized rats compared with the estradiol-replaced rats. These data demonstrate that removal of ovarian steroids increased endothelium-mediated PGHS-dependent vasoconstriction that was associated with augmented sensitivity of the TxA 2 /PGH 2 receptor. Chronic estrogen replacement in the ovariectomized rat suppressed this PGHS-dependent vasoconstrictor response.
JACC: Cardiovascular Interventions, 2017
BACKGROUND The Absorb everolimus-eluting BVS provides drug delivery and mechanical support simila... more BACKGROUND The Absorb everolimus-eluting BVS provides drug delivery and mechanical support similar to a metallic drug-eluting stent, followed by resorption and restoration of more normal vascular structure with the potential to improve late clinical outcomes. METHODS The ABSORB II, ABSORB III, ABSORB Japan, and ABSORB China trials were pooled. Baseline clinical, angiography, procedural variables, and 2-year outcomes were analyzed by sex and device. RESULTS Among 3,384 randomized patients, 932 (27.5%) were female. Females were older, more often had diabetes and hypertension, but had less everolimus-eluting stent, 3-vessel disease, and smoking compared with males (all p#0.001). The 2-year rates of target lesion failure with BVS versus everolimus-eluting stent in females were 8.9% versus 6.2% (study-level adjusted hazard ratio: 1.47; 95% confidence interval [CI]: 0.88 to 2.46) and 8.9% versus 6.4% in males (HR: 1.40; 95% CI: 1.02 to 1.92; p interaction ¼ 0.85). There were no significant interactions between sex and device type for any of the components of target lesion failure. CONCLUSIONS The relative treatment effects of BVS and everolimus-eluting stent for the 2-year rates of target lesion failure and other cardiovascular outcomes were consistent in females and males.
Journal of the American College of Cardiology, 2003
Background: A defibrillator using rectilinear biphasic waveform (2011) reportedly requires lower ... more Background: A defibrillator using rectilinear biphasic waveform (2011) reportedly requires lower energy for defibdllation than a device using truncated exponential biphasic waveform (Physio). Success rates for cardioversion of atrial fibrillation (AF) were compared between Zoll (with a maximum energy of 2OOJ) and Physio (with a maximum energy of 360J). Methods: Patients (pts) undergoing transthoracic cardioversion for AF were randomly assigned to Zoll or Physio. Shock energy was increased stepwise (5OJ, lOOJ, 15OJ, 200J) until cardioversion or to the maximum level of the device. If AF persisted despite the maximum energy shock, pts were crossed over and received the maximum energy shock by the other device. Results: Of 134 pts (76 males, age 64+/-15). 63 were assigned to Zoll and 71 to Physio.
Hypertension, 2000
Estrogen replacement therapy significantly decreases the incidence of cardiovascular disease in p... more Estrogen replacement therapy significantly decreases the incidence of cardiovascular disease in postmenopausal women. In aging, there is an increase in vascular stiffness along with a decrease in matrix metalloproteinase (MMP) activity. Our hypothesis was that estrogen replacement would increase MMPs and therefore reduce the vascular stiffness that is associated with aging. Female Sprague-Dawley rats were implanted with a placebo or 17-estradiol-containing pellet (0.5 mg/pellet, 60-day release) at 10 months of age (nϭ6, each). Six young rats (3 months old) were also studied. After a 2-month exposure to the pellet, mesenteric arteries were studied on a pressurized arteriograph system. Distensibility and wall thickness were measured in response to stepwise increases in intraluminal pressure in Ca 2ϩ-free physiological saline solution buffer with papaverine (10 Ϫ4 mol/L). In response to increasing pressure, aged placebo rats exhibited a significant decrease in distensibility compared with young rats (PϽ0.05) that was accompanied by an increase in wall thickness (PϽ0.05). Conversely, estrogen replacement increased distensibility and decreased wall thickness in aged rats (old estrogen-replaced versus old placebo, PϽ0.05). Zymography data indicated that MMP-2 activity decreased in aging but was increased by estrogen replacement. In summary, estrogen replacement in aging female rats reduces age-associated vascular remodeling. (Hypertension. 2000;36:970-974.
Europace, 2006
Aims Interval-and morphology-based algorithms have been used in modern implantable cardioverter d... more Aims Interval-and morphology-based algorithms have been used in modern implantable cardioverter defibrillators (ICDs) to discriminate supraventricular tachycardia (SVT) from other rhythms. A newly developed ICD discrimination algorithm, Rhythm ID TM (Guidant Corporation, St Paul, MN, USA), uses both interval-based metrics and an electrogram vector timing and correlation (VTC) algorithm in a dual-chamber ICD. In a single-chamber ICD, Rhythm ID contains only the VTC component. This study conducted a retrospective analysis of the performance of Rhythm ID for the detection of induced and spontaneous rhythms in a single-chamber ICD. Methods and results This study gathered the data from a prospective, multicentre clinical trial. Ninetysix patients were implanted with a dual-chamber ICD. For this study, each episode was analysed to determine the performance of the single-chamber ICD Rhythm ID algorithm. The mean age of the patients implanted with the device was 67 + 11 years. Seventy-eight patients were male. The primary cardiovascular disease was coronary artery disease and the primary tachyarrhythmia was monomorphic ventricular tachycardia (VT). The mean follow-up time was 11.4 months. A total of 369 induced and spontaneous ventricular arrhythmias was analysed. The algorithm detected 100% of ventricular arrhythmias. Four hundred and forty-two SVT episodes were analysed, including 145 induced and 297 spontaneous. The SVTs were atrial fibrillation (n ¼ 199), atrial flutter (n ¼ 135), and 1:1 SVT (n ¼ 108). The single-chamber ICD Rhythm ID algorithm successfully discriminated 403 SVT episodes and achieved a specificity of 91%. Conclusion The single-chamber version of Rhythm ID demonstrated high specificity without compromising sensitivity.
Canadian Journal of Physiology and Pharmacology, 2000
Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inh... more Recent studies have shown that nitric oxide (NO) biosynthesis increases in pregnancy and that inhibition of nitric oxide synthase (NOS) induces some pathological processes characteristic of preeclampsia. The current project sought to study the effect of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10 µg·min-1, sc for 7 days) on plasma volume, plasma atrial natriuretic factor (ANF), plasma endothelin-1 (ET), and plasma renin activity (PRA) during gestation in conscious rats. NOS inhibition caused mean arterial pressure to increase in both virgin and 21-day pregnant rats. Plasma volume fell in the pregnant rats [L-NAME, 4.5 ± 0.3 mL·100 g-1 body wt. (n = 7) vs. D-NAME, 6.8 ± 0.2 mL·100 g-1 body wt. (n = 10); P < 0.05] but not in the virgin rats [L-NAME, 4.3 ± 0.1 mL·100 g-1 body wt. (n = 6) vs. D-NAME, 4.8 ± 0.2 mL·100 g-1 body wt. (n = 8)]. There was no effect of NOS inhibition on plasma ANF levels or PRA in either the virgin or pregnant rats. However, L-NAME did de...
Canadian Journal of Physiology and Pharmacology, 1999
Atrial natriuretic factor (ANF) release was studied in isolated perfused atria prepared from rats... more Atrial natriuretic factor (ANF) release was studied in isolated perfused atria prepared from rats. When the vein-atrial junction (VAJ) was distended with an inflatable balloon, ANF release into the perfusate was greater in intact atria than in appendectomized atria. It was concluded that distention of the VAJ causes ANF release from the atrial appendage. A cascade experiment was then prepared whereby buffer from one isolated atrium perfused a second atrium. Although the VAJ of the first atrium could be distended by balloon, the atrial appendage was ligated so ANF was not secreted into the perfusate. The second atrium was intact, but no balloon was inserted. Despite the fact that there were no changes in intraluminal pressure, ANF secretion from the second atrium increased when the VAJ of the first atrium was distended. This response was blocked by the endothelin (ET) A receptor antagonist BQ-123. However, no distention-induced changes in ET-1 levels could be found in the perfusate f...
Journal of the American College of Cardiology, Jan 6, 2015
The everolimus-eluting bioresorbable vascular scaffold (BVS) is designed to achieve results compa... more The everolimus-eluting bioresorbable vascular scaffold (BVS) is designed to achieve results comparable to metallic drug-eluting stents (DES) at 1 year, with improved long-term outcomes. Whether the 1-year clinical and angiographic results of BVS are non-inferior to current generation DES has not been established. We sought to evaluate the angiographic efficacy and clinical safety and effectiveness of BVS in a randomized trial designed to enable approval of the BVS in China. Eligible patients with 1 or 2 de novo native coronary artery lesions were randomized to BVS or cobalt-chromium everolimus-eluting stents (CoCr-EES) in 1:1 ratio stratified by diabetes and the number of lesions treated. Angiographic and clinical follow-up were planned at 1 year in all patients. The primary endpoint was angiographic in-segment late loss (LL), powered for non-inferiority with a margin of 0.15 mm. A total of 480 patients were randomized (241 BVS vs. 239 CoCr-EES) at 24 sites. Acute clinical device su...