Saeb KHOURY - Academia.edu (original) (raw)
Papers by Saeb KHOURY
Journal of the American College of Cardiology, 1995
Recent data suggest that phospholamban (PLB) modulates basal and beta agonist-stimulated myocardi... more Recent data suggest that phospholamban (PLB) modulates basal and beta agonist-stimulated myocardial contractility in the isolated heart. To determine the physiological role of PLB in vivo,anesthetized wild type mice (WT, n = 5) and transgenic mice with PLB gene targeted ablation (PLB-KO, n = 4) and overexpression (PLB-DEF, n = 5) were studied with 2D-guided M-mode and Doppler echo using a 9 MHz imaging and 5–7,5 MHz Doppler transducer (Interspec CX 200). Data were acquired in the baseline state (BASE) and after isoproterenol (ISO) injection (1 μg/mg i.p.). Shortening fraction (SF) was calculated from M-mode. The peak early transmitral (Ev) and aortic (Aov) velocities and ejection times were measured using Doppler and the heart ratecorrected velocity of circumferential shortening (Vcfc) was calculated. CON PLB-DEF PLB-OE BASE ISO BASE ISO BASE ISO HR (bpm) 282 ± 49 349 ± 55 * 322 ± 143 424 ± 43 217 ± 34 355 ± 51 * SF (%) 41 ± 3 64 ± 3 * 46 ± 4 62 ± 3 * 41 ± 4 65 ± 4 * Vcfc(circ/s) 10 ± 3 22 ± 3 * 18 ± 7 27 ± 7 7 ± 1 # 20 ± 4 * Ev (cm/s) 40 ± 12 50 ± 3 82 ± l0 † 89 ± 16 † 44 ± 9 # 62 ± 10 *# Aov (cm/s) 65 ± 4 75 ± 17 109 ± 15 † 108 ± 7 † 68 ± 6 # 89 ± 7 * mean ± SD * p l 0.05 vs BASE † p l 0.05 vs CON # vs DEF, ANOVA We conclude: 1) Phospholamban regulates basal left ventricular function in vivoand modulates the sensitivity to βadrenergic stimulation; 2) Assessment of left ventricular function under varying physiological conditions in mice can be performed noninvasively.
Clinical Pulmonary Medicine, 2003
... DD, Abu-Shakra M. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. B... more ... DD, Abu-Shakra M. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol. 1996; 35: 989-993. ... Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). ...
The Journal of invasive cardiology, 2008
One of the commonly used parameters for evaluating aortic regurgitation is the rate of pressure d... more One of the commonly used parameters for evaluating aortic regurgitation is the rate of pressure decay data obtained from echocardiographic evaluation or cardiac catheterization. The measurement of the rate of equalization of pressure between the aorta and the left ventricle and its utility in the setting of aortic insufficiency has been validated. Intuitively, the Doppler equivalent, pressure half-time, is inversely related to the severity of regurgitation. However, this is a phenomenon dependent on multiple variables including blood pressure, heart rate, compliance of the receiving chamber, effects of vasopressors and the volume status of the patient. We report a case of unique hemodynamics obtained during cardiac catheterization due to low filling pressures that was further confounded by elevated systemic vascular resistance in a critically ill patient with angiographically severe aortic regurgitation.
New England Journal of Medicine, 2008
The Journal of invasive cardiology, 2008
The Journal of Vascular Access, 2008
Purpose Although arteriovenous fistulae (AVFs) are currently the preferred mode of permanent hemo... more Purpose Although arteriovenous fistulae (AVFs) are currently the preferred mode of permanent hemodialysis access they do have significant problems due to initial non-maturation and a later venous stenosis. These problems appear to have been exacerbated following a push to increase AVF prevalence in the US. The reasons for both AVF non-maturation and the later venous stenoses are unclear but are thought to be related to abnormal hemodynamic wall shear stress (WSS) profiles. This technical note aims to describe the successful development of measurement techniques that can be used to establish a complete hemodynamic profile in a pig model with two different configurations of AVF. Methods and results The curved and straight AVF configurations were created in an in vivo pig model. Flow and pressure in the AVFs were measured using the perivascular flow probes and Doppler flow wires while the pressure was recorded using a pressure transducer. The anatomical configuration was obtained using...
Circulation, Oct 31, 2006
Journal of Medical Devices, 2007
The objective is to quantify the guidewire (diameter of 0.35mm) flow-obstruction effect in the in... more The objective is to quantify the guidewire (diameter of 0.35mm) flow-obstruction effect in the in vitro model coronary stenoses in relation to trans-stenotic pressure drop, Δp, fractional flow reserve (gFFR; “g” represents FFR measurement with guidewire insertion) and coronary flow reserve (gCFR) for steady and pulsatile physiological flows. The sensor tipped pressure or flow measuring guidewire insertion through stenotic lumen increases the trans-stenotic pressure drop or reduces the pharmacologically induced hyperemic flow in the coronary arteries with plaques. These hemodynamic changes may cause error in true FFR and CFR measurements, especially for intermediate coronary stenosis. To quantify guidewire flow-obstruction effect, simultaneous measurements of trans-stenotic pressures and flow were performed by two methods: (a) guidewire based measurements (gCFR and gFFR by inserting sensor tipped guidewire) and (b) true physiological measurements (CFR by in-line Doppler flow cuff and...
Advances in Bioengineering, 2004
Kidney International, 2008
Journal of Surgical Research, 2008
Background. Functional/physiological evaluation of coronary artery stenoses may be more important... more Background. Functional/physiological evaluation of coronary artery stenoses may be more important than anatomical measurements of severity. Optimization of thresholds for stenosis intervention and treatment endpoints depend on coupling functional hemodynamic and anatomical data. We sought to develop a single prognostic parameter correlating stenosisspecific anatomy, pressure gradient, and velocities that could be measured during catheterization. Materials and methods. In vivo Experiments were performed in six swine (41 ؎ 3 kg). The lumen area of the left anterior descending coronary artery was measured with intravascular ultrasound. An angioplasty balloon was inflated to create the desired intraluminal area obstructions. Fractional flow reserve (FFR), coronary flow reserve (CFR), and hyperemic-stenosisresistance index were measured distal to the balloon at peak hyperemia with 10 mg intracoronary papaverine. A functional index:pressure drop coefficient (CDP) and a combined functional and anatomical index:lesion flow coefficient (LFC) were calculated from measured hyperemic pressure gradient, velocity, and percentage area stenosis. P < 0.05 was considered statistically significant. Results. The CDP and LFC correlated linearly and significantly with FFR and CFR. The CDP (R 2 ؍ 0.72, P < 0.0001) correlated better than LFC (R 2 ؍ 0.19, P < 0.003) with hyperemic-stenosis-resistance index. When LFC was correlated simultaneously with FFR and CFR, R 2 improved to 0.82 (P < 0.0001). Inclusion of percentage area stenoses concurrently with FFR and CFR marginally improved the correlation with LFC. Conclusions. A dimensionless parameter combining measured pressure gradient, velocity, and area reduction data can optimally define the severity of coronary stenoses based on our preliminary results and could prove useful clinically.
Journal of Biomechanics, 2007
Myocardial fractional flow reserve (FFR myo) and coronary flow reserve (CFR), measured with guide... more Myocardial fractional flow reserve (FFR myo) and coronary flow reserve (CFR), measured with guidewire, and quantitative angiography (QA) are widely used in combination to distinguish ischemic from non-ischemic coronary stenoses. Recent studies have shown that simultaneous measurements of FFR myo and CFR are recommended to dissociate conduit epicardial coronary stenoses from distal resistance microvascular disease. In this study, a more comprehensive diagnostic parameter, named as lesion flow coefficient,c, is proposed. The coefficient,c, which accounts for mean pressure drop, Dp, mean coronary flow,Q, and percentage area stenosis, can be used to assess the hemodynamic severity of a coronary artery stenoses. Importantly, the contribution of viscous loss and loss due to momentum change for several lesion sizes can be distinguished usingc. FFR myo , CFR andc were calculated for pre-angioplasty, intermediate and post-angioplasty epicardial lesions, without microvascular disease. While hyperemicc decreased from 0.65 for pre-angioplasty to 0.48 for post-angioplasty lesion with guidewire of size 0.35 mm, FFR myo increased from 0.52 to 0.87, and CFR increased from 1.72 to 3.45, respectively. Thus, reduced loss produced by momentum change due to lower percentage area stenosis decreasedc. For post-angioplasty lesion,c decreased from 0.55 to 0.48 with the insertion of guidewire. Hence, increased viscous loss due to the presence of guidewire decreasedc compared with a lesion without guidewire. Further,c showed a linear relationship with FFR myo , CFR and percentage area stenosis for preangioplasty, intermediate and post-angioplasty lesion. These baseline values ofc were developed from fluid dynamics fundamentals for focal lesions, and provided a single hemodynamic endpoint to evaluate coronary stenosis severity.
ASAIO Journal, 2006
In order to prevent the occurrence of dialysis-related amyloidosis, an immunoadsorption wall base... more In order to prevent the occurrence of dialysis-related amyloidosis, an immunoadsorption wall based on polyacrylamide has been manufactured by a recently developed partially incomplete two-stage polymerization method. During the preparation process, efficient utilization of coupling antibodies is the key to the large scale production of such a toxin removal modality. In this study, we attempted to carry out the ligand coupling procedure after formation of a cyanogen bromide (CNBr)-activated stationary phase using different amounts of anti-beta-2-microglobulin antibodies. Then, maximum ligand coupling density and binding capacity were determined by a mathematical model of saturation kinetics of immunoadsorption reactions. The preliminary results thus obtained could serve as a basis for optimization of formation of an immunoadsorptin wall. Furthermore, the experimental protocols as well as the present methodology could also be helpful for development of a clinically applicable immunoadsorption wall.
American Journal of Obstetrics and Gynecology, 2007
American Journal of Physiology-Heart and Circulatory Physiology, 2005
Hemodynamic analysis was conducted to determine uncertainty in clinical measurements of coronary ... more Hemodynamic analysis was conducted to determine uncertainty in clinical measurements of coronary flow reserve (CFR) and fractional flow reserve (FFR) over pathophysiological conditions in a patient group with coronary artery disease during angioplasty. The vasodilation-distal perfusion pressure (CFR-p̃rh) curve was obtained for 0.35- and 0.46-mm guide wires. Our hypothesis is that a guide wire spanning the lesions elevates the pressure gradient and reduces the flow during hyperemic measurements. Maximal CFR-p̃rh was uniquely determined by the intersection of measured CFR and calculated p̃rh of native and residual epicardial lesions in patients without microvascular disease, during angioplasty. Extrapolation of the linear curve gave a zero-coronary flow mean pressure (p̃zf) of ∼20 mmHg and a corresponding p̃rh of 55 mmHg in the native lesions, which coincided with the level that causes ischemia in human hearts. On this linear curve, values of CFR and FFRmyo (pathophysiological condit...
American Journal of Obstetrics and Gynecology, 2008
The objective of the study was to assess the prognostic value of ejection fraction (EF) at index ... more The objective of the study was to assess the prognostic value of ejection fraction (EF) at index and subsequent pregnancy on long-term outcome in patients with peripartum cardiomyopathy (PPCM). Seventy PPCM patients met inclusion criteria. Patients had echocardiography evaluations at the index pregnancy, at interval follow-up (F/U) or at the beginning of a subsequent pregnancy and the last F/U study available. Outcome data were echocardiographic parameters and the subsequent need for cardiac transplant. Patients were categorized on the basis of their initial EF into EF of 25% or less and EF greater than 25% and stratified on the basis of their pregnancy into the following groups: group 1 (n = 33), no subsequent pregnancy; group 2 (n = 16), subsequent pregnancy with early termination; and group 3 (n = 21), successful subsequent pregnancy. F/U from index pregnancy to final F/U was 3.4+/-1.9 (range, 1-6 years). Groups 1 and 2 had persistent left ventricular dysfunction at all echocardiographic evaluations. In group 3, despite a mean EF greater than 40% at a subsequent pregnancy, 29% had worsening cardiac symptoms. Among 28 patients with EF of 25% or less, 16 (57%) had end-stage cardiac disease. One had a transplant and 15 were on a transplant list. All 16 had a baseline EF 25% or less at index pregnancy: 4 had improved (EF greater than 40%) at interval F/U and 3 at last F/U available. Women with a history of PPCM had a higher rate of progression of symptoms of heart failure in a subsequent pregnancy. A baseline left ventricular EF 25% or less at index pregnancy is associated with a higher rate of cardiac transplant.
Background: The severity of epicardial coronary stenosis can be assessed by invasive measurements... more Background: The severity of epicardial coronary stenosis can be assessed by invasive measurements of transstenotic pressure drop and flow. A pressure or flow sensor-tipped guidewire inserted across the coronary stenosis causes an overestimation in true trans-stenotic pressure drop and reduction in coronary flow. This may mask the true severity of coronary stenosis. In order to unmask the true severity of epicardial stenosis, we evaluate a diagnostic parameter, which is obtained from fundamental fluid dynamics principles. This experimental and numerical study focuses on the characterization of the diagnostic parameter, pressure drop coefficient, and also evaluates the pressure recovery downstream of stenoses. Methods: Three models of coronary stenosis namely, moderate, intermediate and severe stenosis, were manufactured and tested in the in-vitro setup simulating the epicardial coronary network. The trans-stenotic pressure drop and flow distal to stenosis models were measured by non-invasive method, using external pressure and flow sensors, and by invasive method, following guidewire insertion across the stenosis. The viscous and momentum-change components of the pressure drop for various flow rates were evaluated from quadratic relation between pressure drop and flow. Finally, the pressure drop coefficient (CDP e) was calculated as the ratio of pressure drop and distal dynamic pressure. The pressure recovery factor (η) was calculated as the ratio of pressure recovery coefficient and the area blockage. Results: The mean pressure drop-flow characteristics before and during guidewire insertion indicated that increasing stenosis causes a shift in dominance from viscous pressure to momentum forces. However, for intermediate (~80%) area stenosis, which is between moderate (~65%) and severe (~90%) area stenoses, both losses were similar in magnitude. Therefore, guidewire insertion plays a critical role in evaluating the hemodynamic severity of coronary stenosis. More importantly, mean CDP e increased (17 ± 3.3 to 287 ± 52, n = 3, p < 0.01) and mean η decreased (0.54 ± 0.04 to 0.37 ± 0.05, p < 0.01) from moderate to severe stenosis during guidewire insertion. Conclusion: The wide range of CDP e is not affected that much by the presence of guidewire. CDP e can be used in clinical practice to evaluate the true severity of coronary stenosis due to its significant difference between values measured at moderate and severe stenoses.
Circulation Research, 1996
The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on pr... more The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on primate myocardium are poorly understood. Therefore, we studied the effects of thyroid hormone on sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins and myosin heavy chain (MHC) composition at the steady state mRNA and protein level and associated alterations of left ventricular (LV) performance in 8 chronically instrumented baboons. The force-frequency and relaxation-frequency relations were assessed as the response of LV isovolumic contraction (dP/dtmax) and relaxation (Tau), respectively, to incremental atrial pacing. Both the heart rate at which dP/dtmax was maximal and Tau was minimal (critical heart rates) in response to pacing were increased significantly after thyroid hormone. Postmortem LV tissue from 5 thyroid-treated and 4 additional control baboons was assayed for steady state mRNA levels with cDNA probes to MHC isoforms and SR Ca(2+)-cycling proteins. Steady state SR Ca(2+)-ATPase and phospholamban mRNA increased in the hyperthyroid state, and alpha-MHC mRNA appeared de novo, whereas beta-MHC mRNA decreased. Western analysis (4 thyroid-treated and 4 control baboons) showed directionally similar changes in MHC isoforms and a slight increase in SR Ca(2+)-ATPase. In contrast, there was a statistically nonsignificant decrease in phospholamban protein, which resulted in a significant 40% decrease in the ratio of phospholamban to SR Ca(2+)-ATPase. Thus, thyroid hormone increases the transcription of Ca(2+)-cycling proteins and shifts MHC isoform expression in the primate LV. Our data suggest that both transcriptional and posttranslational mechanisms determine the levels of these proteins in the hyperthyroid primate heart and mediate, in part, the observed enhanced basal and frequency-dependent LV performance.
Circulation Research, 1995
We evaluated the ability of M-mode and Doppler echocardiography to assess left ventricular (LV) f... more We evaluated the ability of M-mode and Doppler echocardiography to assess left ventricular (LV) function reliably and repeatedly in mice and tested whether these techniques could detect physiological alterations in phospholamban (PLB)-deficient mice. Anesthetized wild-type mice (n = 7) and mice deficient in PLB (n = 8) were studied with two-dimensional guided M-mode and Doppler echocardiography using a 9-MHz imaging and 5- to 7.5-MHz Doppler transducer. Data were acquired in the baseline state and after intraperitoneal isoproterenol administration (2.0 micrograms/g IP). Interobserver and intraobserver variability and reproducibility were excellent. PLB-deficient mice were associated with significant (P < .05) increases in several physiological parameters (mean +/- SD) compared with wild-type control mice: normalized mean velocity of circumferential shortening (7.7 +/- 2.1 versus 5.5 +/- 1.0 circ/sec), peak aortic velocity (105 +/- 13 versus 75 +/- 9.2 cm/s), mean aortic acceleration (57 +/- 16 versus 31 +/- 4 m/s2), and peak early-diastolic transmitral velocity (80.0 +/- 7.2 versus 66.9 +/- 7.7 cm/s). LV dimensions, shortening fractions, heart rates, late diastolic transmitral (A) velocities, and early to late (E/A) diastolic velocity ratios were similar in both groups. Isoproterenol administration resulted in significant increases in Doppler indices of ventricular function in control but not PLB-deficient mice. These findings indicate that assessment of LV function can be performed noninvasively in mice under varying physiological conditions and that PLB regulates basal LV function in vivo.
Journal of the American College of Cardiology, 1995
Recent data suggest that phospholamban (PLB) modulates basal and beta agonist-stimulated myocardi... more Recent data suggest that phospholamban (PLB) modulates basal and beta agonist-stimulated myocardial contractility in the isolated heart. To determine the physiological role of PLB in vivo,anesthetized wild type mice (WT, n = 5) and transgenic mice with PLB gene targeted ablation (PLB-KO, n = 4) and overexpression (PLB-DEF, n = 5) were studied with 2D-guided M-mode and Doppler echo using a 9 MHz imaging and 5–7,5 MHz Doppler transducer (Interspec CX 200). Data were acquired in the baseline state (BASE) and after isoproterenol (ISO) injection (1 μg/mg i.p.). Shortening fraction (SF) was calculated from M-mode. The peak early transmitral (Ev) and aortic (Aov) velocities and ejection times were measured using Doppler and the heart ratecorrected velocity of circumferential shortening (Vcfc) was calculated. CON PLB-DEF PLB-OE BASE ISO BASE ISO BASE ISO HR (bpm) 282 ± 49 349 ± 55 * 322 ± 143 424 ± 43 217 ± 34 355 ± 51 * SF (%) 41 ± 3 64 ± 3 * 46 ± 4 62 ± 3 * 41 ± 4 65 ± 4 * Vcfc(circ/s) 10 ± 3 22 ± 3 * 18 ± 7 27 ± 7 7 ± 1 # 20 ± 4 * Ev (cm/s) 40 ± 12 50 ± 3 82 ± l0 † 89 ± 16 † 44 ± 9 # 62 ± 10 *# Aov (cm/s) 65 ± 4 75 ± 17 109 ± 15 † 108 ± 7 † 68 ± 6 # 89 ± 7 * mean ± SD * p l 0.05 vs BASE † p l 0.05 vs CON # vs DEF, ANOVA We conclude: 1) Phospholamban regulates basal left ventricular function in vivoand modulates the sensitivity to βadrenergic stimulation; 2) Assessment of left ventricular function under varying physiological conditions in mice can be performed noninvasively.
Clinical Pulmonary Medicine, 2003
... DD, Abu-Shakra M. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. B... more ... DD, Abu-Shakra M. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol. 1996; 35: 989-993. ... Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). ...
The Journal of invasive cardiology, 2008
One of the commonly used parameters for evaluating aortic regurgitation is the rate of pressure d... more One of the commonly used parameters for evaluating aortic regurgitation is the rate of pressure decay data obtained from echocardiographic evaluation or cardiac catheterization. The measurement of the rate of equalization of pressure between the aorta and the left ventricle and its utility in the setting of aortic insufficiency has been validated. Intuitively, the Doppler equivalent, pressure half-time, is inversely related to the severity of regurgitation. However, this is a phenomenon dependent on multiple variables including blood pressure, heart rate, compliance of the receiving chamber, effects of vasopressors and the volume status of the patient. We report a case of unique hemodynamics obtained during cardiac catheterization due to low filling pressures that was further confounded by elevated systemic vascular resistance in a critically ill patient with angiographically severe aortic regurgitation.
New England Journal of Medicine, 2008
The Journal of invasive cardiology, 2008
The Journal of Vascular Access, 2008
Purpose Although arteriovenous fistulae (AVFs) are currently the preferred mode of permanent hemo... more Purpose Although arteriovenous fistulae (AVFs) are currently the preferred mode of permanent hemodialysis access they do have significant problems due to initial non-maturation and a later venous stenosis. These problems appear to have been exacerbated following a push to increase AVF prevalence in the US. The reasons for both AVF non-maturation and the later venous stenoses are unclear but are thought to be related to abnormal hemodynamic wall shear stress (WSS) profiles. This technical note aims to describe the successful development of measurement techniques that can be used to establish a complete hemodynamic profile in a pig model with two different configurations of AVF. Methods and results The curved and straight AVF configurations were created in an in vivo pig model. Flow and pressure in the AVFs were measured using the perivascular flow probes and Doppler flow wires while the pressure was recorded using a pressure transducer. The anatomical configuration was obtained using...
Circulation, Oct 31, 2006
Journal of Medical Devices, 2007
The objective is to quantify the guidewire (diameter of 0.35mm) flow-obstruction effect in the in... more The objective is to quantify the guidewire (diameter of 0.35mm) flow-obstruction effect in the in vitro model coronary stenoses in relation to trans-stenotic pressure drop, Δp, fractional flow reserve (gFFR; “g” represents FFR measurement with guidewire insertion) and coronary flow reserve (gCFR) for steady and pulsatile physiological flows. The sensor tipped pressure or flow measuring guidewire insertion through stenotic lumen increases the trans-stenotic pressure drop or reduces the pharmacologically induced hyperemic flow in the coronary arteries with plaques. These hemodynamic changes may cause error in true FFR and CFR measurements, especially for intermediate coronary stenosis. To quantify guidewire flow-obstruction effect, simultaneous measurements of trans-stenotic pressures and flow were performed by two methods: (a) guidewire based measurements (gCFR and gFFR by inserting sensor tipped guidewire) and (b) true physiological measurements (CFR by in-line Doppler flow cuff and...
Advances in Bioengineering, 2004
Kidney International, 2008
Journal of Surgical Research, 2008
Background. Functional/physiological evaluation of coronary artery stenoses may be more important... more Background. Functional/physiological evaluation of coronary artery stenoses may be more important than anatomical measurements of severity. Optimization of thresholds for stenosis intervention and treatment endpoints depend on coupling functional hemodynamic and anatomical data. We sought to develop a single prognostic parameter correlating stenosisspecific anatomy, pressure gradient, and velocities that could be measured during catheterization. Materials and methods. In vivo Experiments were performed in six swine (41 ؎ 3 kg). The lumen area of the left anterior descending coronary artery was measured with intravascular ultrasound. An angioplasty balloon was inflated to create the desired intraluminal area obstructions. Fractional flow reserve (FFR), coronary flow reserve (CFR), and hyperemic-stenosisresistance index were measured distal to the balloon at peak hyperemia with 10 mg intracoronary papaverine. A functional index:pressure drop coefficient (CDP) and a combined functional and anatomical index:lesion flow coefficient (LFC) were calculated from measured hyperemic pressure gradient, velocity, and percentage area stenosis. P < 0.05 was considered statistically significant. Results. The CDP and LFC correlated linearly and significantly with FFR and CFR. The CDP (R 2 ؍ 0.72, P < 0.0001) correlated better than LFC (R 2 ؍ 0.19, P < 0.003) with hyperemic-stenosis-resistance index. When LFC was correlated simultaneously with FFR and CFR, R 2 improved to 0.82 (P < 0.0001). Inclusion of percentage area stenoses concurrently with FFR and CFR marginally improved the correlation with LFC. Conclusions. A dimensionless parameter combining measured pressure gradient, velocity, and area reduction data can optimally define the severity of coronary stenoses based on our preliminary results and could prove useful clinically.
Journal of Biomechanics, 2007
Myocardial fractional flow reserve (FFR myo) and coronary flow reserve (CFR), measured with guide... more Myocardial fractional flow reserve (FFR myo) and coronary flow reserve (CFR), measured with guidewire, and quantitative angiography (QA) are widely used in combination to distinguish ischemic from non-ischemic coronary stenoses. Recent studies have shown that simultaneous measurements of FFR myo and CFR are recommended to dissociate conduit epicardial coronary stenoses from distal resistance microvascular disease. In this study, a more comprehensive diagnostic parameter, named as lesion flow coefficient,c, is proposed. The coefficient,c, which accounts for mean pressure drop, Dp, mean coronary flow,Q, and percentage area stenosis, can be used to assess the hemodynamic severity of a coronary artery stenoses. Importantly, the contribution of viscous loss and loss due to momentum change for several lesion sizes can be distinguished usingc. FFR myo , CFR andc were calculated for pre-angioplasty, intermediate and post-angioplasty epicardial lesions, without microvascular disease. While hyperemicc decreased from 0.65 for pre-angioplasty to 0.48 for post-angioplasty lesion with guidewire of size 0.35 mm, FFR myo increased from 0.52 to 0.87, and CFR increased from 1.72 to 3.45, respectively. Thus, reduced loss produced by momentum change due to lower percentage area stenosis decreasedc. For post-angioplasty lesion,c decreased from 0.55 to 0.48 with the insertion of guidewire. Hence, increased viscous loss due to the presence of guidewire decreasedc compared with a lesion without guidewire. Further,c showed a linear relationship with FFR myo , CFR and percentage area stenosis for preangioplasty, intermediate and post-angioplasty lesion. These baseline values ofc were developed from fluid dynamics fundamentals for focal lesions, and provided a single hemodynamic endpoint to evaluate coronary stenosis severity.
ASAIO Journal, 2006
In order to prevent the occurrence of dialysis-related amyloidosis, an immunoadsorption wall base... more In order to prevent the occurrence of dialysis-related amyloidosis, an immunoadsorption wall based on polyacrylamide has been manufactured by a recently developed partially incomplete two-stage polymerization method. During the preparation process, efficient utilization of coupling antibodies is the key to the large scale production of such a toxin removal modality. In this study, we attempted to carry out the ligand coupling procedure after formation of a cyanogen bromide (CNBr)-activated stationary phase using different amounts of anti-beta-2-microglobulin antibodies. Then, maximum ligand coupling density and binding capacity were determined by a mathematical model of saturation kinetics of immunoadsorption reactions. The preliminary results thus obtained could serve as a basis for optimization of formation of an immunoadsorptin wall. Furthermore, the experimental protocols as well as the present methodology could also be helpful for development of a clinically applicable immunoadsorption wall.
American Journal of Obstetrics and Gynecology, 2007
American Journal of Physiology-Heart and Circulatory Physiology, 2005
Hemodynamic analysis was conducted to determine uncertainty in clinical measurements of coronary ... more Hemodynamic analysis was conducted to determine uncertainty in clinical measurements of coronary flow reserve (CFR) and fractional flow reserve (FFR) over pathophysiological conditions in a patient group with coronary artery disease during angioplasty. The vasodilation-distal perfusion pressure (CFR-p̃rh) curve was obtained for 0.35- and 0.46-mm guide wires. Our hypothesis is that a guide wire spanning the lesions elevates the pressure gradient and reduces the flow during hyperemic measurements. Maximal CFR-p̃rh was uniquely determined by the intersection of measured CFR and calculated p̃rh of native and residual epicardial lesions in patients without microvascular disease, during angioplasty. Extrapolation of the linear curve gave a zero-coronary flow mean pressure (p̃zf) of ∼20 mmHg and a corresponding p̃rh of 55 mmHg in the native lesions, which coincided with the level that causes ischemia in human hearts. On this linear curve, values of CFR and FFRmyo (pathophysiological condit...
American Journal of Obstetrics and Gynecology, 2008
The objective of the study was to assess the prognostic value of ejection fraction (EF) at index ... more The objective of the study was to assess the prognostic value of ejection fraction (EF) at index and subsequent pregnancy on long-term outcome in patients with peripartum cardiomyopathy (PPCM). Seventy PPCM patients met inclusion criteria. Patients had echocardiography evaluations at the index pregnancy, at interval follow-up (F/U) or at the beginning of a subsequent pregnancy and the last F/U study available. Outcome data were echocardiographic parameters and the subsequent need for cardiac transplant. Patients were categorized on the basis of their initial EF into EF of 25% or less and EF greater than 25% and stratified on the basis of their pregnancy into the following groups: group 1 (n = 33), no subsequent pregnancy; group 2 (n = 16), subsequent pregnancy with early termination; and group 3 (n = 21), successful subsequent pregnancy. F/U from index pregnancy to final F/U was 3.4+/-1.9 (range, 1-6 years). Groups 1 and 2 had persistent left ventricular dysfunction at all echocardiographic evaluations. In group 3, despite a mean EF greater than 40% at a subsequent pregnancy, 29% had worsening cardiac symptoms. Among 28 patients with EF of 25% or less, 16 (57%) had end-stage cardiac disease. One had a transplant and 15 were on a transplant list. All 16 had a baseline EF 25% or less at index pregnancy: 4 had improved (EF greater than 40%) at interval F/U and 3 at last F/U available. Women with a history of PPCM had a higher rate of progression of symptoms of heart failure in a subsequent pregnancy. A baseline left ventricular EF 25% or less at index pregnancy is associated with a higher rate of cardiac transplant.
Background: The severity of epicardial coronary stenosis can be assessed by invasive measurements... more Background: The severity of epicardial coronary stenosis can be assessed by invasive measurements of transstenotic pressure drop and flow. A pressure or flow sensor-tipped guidewire inserted across the coronary stenosis causes an overestimation in true trans-stenotic pressure drop and reduction in coronary flow. This may mask the true severity of coronary stenosis. In order to unmask the true severity of epicardial stenosis, we evaluate a diagnostic parameter, which is obtained from fundamental fluid dynamics principles. This experimental and numerical study focuses on the characterization of the diagnostic parameter, pressure drop coefficient, and also evaluates the pressure recovery downstream of stenoses. Methods: Three models of coronary stenosis namely, moderate, intermediate and severe stenosis, were manufactured and tested in the in-vitro setup simulating the epicardial coronary network. The trans-stenotic pressure drop and flow distal to stenosis models were measured by non-invasive method, using external pressure and flow sensors, and by invasive method, following guidewire insertion across the stenosis. The viscous and momentum-change components of the pressure drop for various flow rates were evaluated from quadratic relation between pressure drop and flow. Finally, the pressure drop coefficient (CDP e) was calculated as the ratio of pressure drop and distal dynamic pressure. The pressure recovery factor (η) was calculated as the ratio of pressure recovery coefficient and the area blockage. Results: The mean pressure drop-flow characteristics before and during guidewire insertion indicated that increasing stenosis causes a shift in dominance from viscous pressure to momentum forces. However, for intermediate (~80%) area stenosis, which is between moderate (~65%) and severe (~90%) area stenoses, both losses were similar in magnitude. Therefore, guidewire insertion plays a critical role in evaluating the hemodynamic severity of coronary stenosis. More importantly, mean CDP e increased (17 ± 3.3 to 287 ± 52, n = 3, p < 0.01) and mean η decreased (0.54 ± 0.04 to 0.37 ± 0.05, p < 0.01) from moderate to severe stenosis during guidewire insertion. Conclusion: The wide range of CDP e is not affected that much by the presence of guidewire. CDP e can be used in clinical practice to evaluate the true severity of coronary stenosis due to its significant difference between values measured at moderate and severe stenoses.
Circulation Research, 1996
The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on pr... more The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on primate myocardium are poorly understood. Therefore, we studied the effects of thyroid hormone on sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins and myosin heavy chain (MHC) composition at the steady state mRNA and protein level and associated alterations of left ventricular (LV) performance in 8 chronically instrumented baboons. The force-frequency and relaxation-frequency relations were assessed as the response of LV isovolumic contraction (dP/dtmax) and relaxation (Tau), respectively, to incremental atrial pacing. Both the heart rate at which dP/dtmax was maximal and Tau was minimal (critical heart rates) in response to pacing were increased significantly after thyroid hormone. Postmortem LV tissue from 5 thyroid-treated and 4 additional control baboons was assayed for steady state mRNA levels with cDNA probes to MHC isoforms and SR Ca(2+)-cycling proteins. Steady state SR Ca(2+)-ATPase and phospholamban mRNA increased in the hyperthyroid state, and alpha-MHC mRNA appeared de novo, whereas beta-MHC mRNA decreased. Western analysis (4 thyroid-treated and 4 control baboons) showed directionally similar changes in MHC isoforms and a slight increase in SR Ca(2+)-ATPase. In contrast, there was a statistically nonsignificant decrease in phospholamban protein, which resulted in a significant 40% decrease in the ratio of phospholamban to SR Ca(2+)-ATPase. Thus, thyroid hormone increases the transcription of Ca(2+)-cycling proteins and shifts MHC isoform expression in the primate LV. Our data suggest that both transcriptional and posttranslational mechanisms determine the levels of these proteins in the hyperthyroid primate heart and mediate, in part, the observed enhanced basal and frequency-dependent LV performance.
Circulation Research, 1995
We evaluated the ability of M-mode and Doppler echocardiography to assess left ventricular (LV) f... more We evaluated the ability of M-mode and Doppler echocardiography to assess left ventricular (LV) function reliably and repeatedly in mice and tested whether these techniques could detect physiological alterations in phospholamban (PLB)-deficient mice. Anesthetized wild-type mice (n = 7) and mice deficient in PLB (n = 8) were studied with two-dimensional guided M-mode and Doppler echocardiography using a 9-MHz imaging and 5- to 7.5-MHz Doppler transducer. Data were acquired in the baseline state and after intraperitoneal isoproterenol administration (2.0 micrograms/g IP). Interobserver and intraobserver variability and reproducibility were excellent. PLB-deficient mice were associated with significant (P < .05) increases in several physiological parameters (mean +/- SD) compared with wild-type control mice: normalized mean velocity of circumferential shortening (7.7 +/- 2.1 versus 5.5 +/- 1.0 circ/sec), peak aortic velocity (105 +/- 13 versus 75 +/- 9.2 cm/s), mean aortic acceleration (57 +/- 16 versus 31 +/- 4 m/s2), and peak early-diastolic transmitral velocity (80.0 +/- 7.2 versus 66.9 +/- 7.7 cm/s). LV dimensions, shortening fractions, heart rates, late diastolic transmitral (A) velocities, and early to late (E/A) diastolic velocity ratios were similar in both groups. Isoproterenol administration resulted in significant increases in Doppler indices of ventricular function in control but not PLB-deficient mice. These findings indicate that assessment of LV function can be performed noninvasively in mice under varying physiological conditions and that PLB regulates basal LV function in vivo.