Antonio L'Abbate - Academia.edu (original) (raw)
Papers by Antonio L'Abbate
European Heart Journal, 2007
Interactive cardiovascular and thoracic surgery, 2003
In patients with left ventricular dysfunction, multivessel coronary disease and viable myocardium... more In patients with left ventricular dysfunction, multivessel coronary disease and viable myocardium, little is known on the differential prognostic effect of coronary artery by pass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). To this purpose, 177 patients with previous myocardial infarction, three-vessel coronary disease and an EF<0.40 underwent CABG (group A, 114 patients) or PTCA (group B, 63 patients). Viability was demonstrated by maintained Thallium-201 uptake in more than 70% of left ventricle in 95/114 and 51/63 patients of groups A and B, respectively. Revascularization was greater in the CABG group (2.9+/-1.2 graft/patient) as compared to the PTCA group (1.3+/-1.2 treated vessel, P<0.05). Intraoperative mortality was 6.7 and 6.3% in groups A and B, respectively. At 6 months, viability was highly predictive of improvement of symptoms and wall motion abnormalities. Survival at 4 years was 90% in CABG and 92% in PTCA patients with maintained ...
To verify the behavior of coronary microvascular tone during spontaneous ischemia in patients wit... more To verify the behavior of coronary microvascular tone during spontaneous ischemia in patients with unstable angina (UA). BACKGROUND In UA, the pathogenetic role of vasoconstriction is classically confined at the stenotic coronary segment. However, microcirculatory vasoconstriction has been also suggested by previous experimental and clinical studies. METHODS The study included 10 patients with UA (recent worsening of anginal threshold and appearance of angina at rest) and single-vessel CAD. Blood flow velocity was monitored by a Doppler catheter in the diseased artery. Transstenotic pressure gradient was monitored by aortic and distal coronary pressure monitoring. Stenosis resistance was calculated as the ratio between pressure gradient and blood flow, microvascular resistance as the ratio between distal pressure and blood flow. Measurements were obtained at baseline, following intracoronary adenosine (2 mg) and during transient ischemia. Aortic and distal coronary pressures were also measured during balloon coronary occlusion. RESULTS Adenosine did not affect stenosis resistance, while it decreased (p Ͻ 0.05) microvascular resistance to 52 Ϯ 22% of baseline. Angina and ischemic ST segment shift were associated with transient angiographic coronary occlusion in 7 of 10 patients; however, in no case was ischemia associated with interruption of flow. Despite markedly different flow values, distal coronary pressure was similar during adenosine and during spontaneous ischemia (48 Ϯ 15 vs. 46 Ϯ 20 mm Hg, respectively, NS). During ischemia, a marked increase in the resistance of both coronary stenosis and coronary microcirculation was observed (to 1,233% Ϯ 1,298% and 671% Ϯ 652% of baseline, respectively, p Ͻ 0.05). Distal coronary pressure was markedly reduced during balloon coronary occlusion (14 Ϯ 7 mm Hg, p Ͻ 0.05 vs. both adenosine and ischemia), suggesting the absence of significant collateral circulation.
Journal of Translational Medicine, 2014
Background: Up-regulation of HO-1 by genetic manipulation or pharmacological pre-treatment has be... more Background: Up-regulation of HO-1 by genetic manipulation or pharmacological pre-treatment has been reported to provide benefits in several animal models of myocardial infarction (MI). However, its efficacy following MI initiation (as in clinical reality) remains to be tested. Therefore, this study investigated whether HO-1 over-expression, by cobalt protoporphyrin (CoPP) administered after LAD ligation, is still able to improve functional and structural changes in left ventricle (LV) in a rat model of 4-week MI. Methods: A total of 144 adult male Wistar rats were subjected to either left anterior coronary artery ligation or sham-operation. The effect of CoPP treatment (5 mg/kg i.p. at the end of the surgical session and, then, once a week for 4 weeks) was evaluated on the basis of survival, electro-and echocardiography, plasma levels of B-type natriuretic peptide (BNP), endothelin-1 and prostaglandin E2, coronary microvascular reactivity, MI size, LV wall thickness and vascularity. Besides, the expression of HO-1 and connexin-43 in different LV territories was assessed by western blot analysis and immunohistochemistry, respectively. Results: CoPP induced an increased expression of HO-1 protein with >16 h delay. CoPP treatment significantly reduced mortality, MI size, BNP concentration, ECG alterations, LV dysfunction, microvascular constriction, capillary rarefaction and restored connexin-43 expression as compared to untreated MI. These functional and structural changes were paralleled by increased HO-1 expression in all LV territories. HO activity inhibition by tin-mesoporphyrin abolished the differences between CoPP-treated and untreated MI animals. Conclusions: This is the first report demonstrating the putative role of pharmacological induction of HO-1 following coronary occlusion to benefit infarcted and remote territories, leading to better cardiac function in a 4-week MI outcome.
Journal of the American Society of Echocardiography, 1998
The purpose of this study was to detect myocardial perfusion defects as a result of coronary occl... more The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.
Journal of the American Society of Echocardiography, 1994
Journal of the American College of Cardiology, 1991
To asszw regmnat coronary reserve tn h>pertrophir ardiemyop athy, regkmat m,oenrdtt Mood (low was... more To asszw regmnat coronary reserve tn h>pertrophir ardiemyop athy, regkmat m,oenrdtt Mood (low was-"red tn 23 patteu
Journal of the American College of Cardiology, 1992
line. ~wo.d~me~s~~flal echocardio es of the left veneuronary arten y to generate tome-~ate~s~ty c... more line. ~wo.d~me~s~~flal echocardio es of the left veneuronary arten y to generate tome-~ate~s~ty curves. The study of myocardial tissue perfusion is still an elusive goal in the clinical setting, and all available methods have significant limitations. Coronary arteriography provides information only on the anatomy of epicardial coronary vessels (I 1. Similarly, Doppler catheters measure coronary flow velocity in the largest coronary arteries without exploring the downstream tissue perfusion (2). Thallium scintigraphy is being semiquantitative and myocardial thallium uptake also reflects the metabolic/histologic state of cells (3). Positron emission tomography accurately measures myocardial tissue perfusion (4); however, high costs and complex organization limit its use. In the last decade, efforts have been made to quantify myocardial perfusion by two-dimensional contrast echocar-From the CNR (Consiglio Nazionale Ricerche) Clinical Physiology Institute and University of Pisa. Pisa. Italy. At the time of the study Dr. DeMaria
Journal of the American College of Cardiology, 1991
Journal of the American College of Cardiology, 1991
Journal of the American College of Cardiology, 1996
higher dsk for a worse early and mid term clinical evolution as wall as mid term LVEF changes aft... more higher dsk for a worse early and mid term clinical evolution as wall as mid term LVEF changes after AML This data may stimulate further research to fully define MRI role in larger trials.
Journal of the American College of Cardiology, 1996
Journal of Cardiovascular Pharmacology, 2002
The aim of the current study was to assess the ability of amlodipine to dilate the coronary vesse... more The aim of the current study was to assess the ability of amlodipine to dilate the coronary vessels in subjects with angiographically normal coronary arteries and normal left ventricular function. Ten patients, six women and four men (mean age 48 +/- 14 years, range 25-67 years) were enrolled. Coronary flow velocity and coronary perfusion pressure were invasively measured at baseline, during intracoronary adenosine (1-mg bolus) and at 5, 15, and 30 min following IV amlodipine (10 or 20 mg). Quantitative coronary angiography was performed at baseline and at 5, 15, and 30 min after amlodipine. Coronary cross-sectional area and mean coronary flow velocity progressively increased after amlodipine administration, resulting in an average increase in coronary flow at 30 min of 76%. On an individual basis, all patients but one showed a consistent trend toward a progressive coronary vasodilator effect of amlodipine over time. The peak effect of amlodipine on baseline mean coronary flow velocity was 43 +/- 12% that of adenosine. This is the first clinical study demonstrating that the IV administration of amlodipine produces a powerful coronary vasodilatation in subjects with angiographically normal coronary arteries and normal ventricular function, besides its known systemic vasodilating effects. The coronary vasodilating properties of amlodipine are particularly expressed at the microcirculatory level.
European Journal of Nuclear Medicine and Molecular Imaging, 2013
Purpose The α v β 3 integrin is expressed in angiogenic vessels and is a potential target for mol... more Purpose The α v β 3 integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel 68 Ga-2,2′,2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI. Methods A straightforward labelling chemistry to attach the radionuclide 68 Ga to a NOTA-based chelating agent conjugated with a cyclic RGD peptidomimetic is described. Affinity for α v β 3 integrin was assessed by in vitro receptor binding assay. The proof-of-concept in vivo studies combined the 68 Ga-NOTA-RGD with the flow tracer 13 N-NH 3 imaging in order to obtain positron emission tomography (PET)/CT imaging of both integrin expression and perfusion defect at 4 weeks after infarction. Hearts were then processed for immunostaining of integrin β 3. Results NOTA-RGD conjugate displayed a binding affinity for α v β 3 integrin of 27.9±6.8 nM. 68 Ga-NOTA-RGD showed stability without detectable degradation or formation of byproducts in urine up to 2 h following injection in the rat. MI hearts exhibited 68 Ga-NOTA-RGD uptake in correspondence to infarcted and border zone regions. The tracer signal drew a parallel with vascular remodelling due to ischaemia-induced angiogenesis as assessed by immunohistochemistry. Conclusion As compared to similar imaging approaches using the 18 F-galacto-derivative, we documented for the first time with microPET/CT imaging the 68 Ga-NOTA-RGD derivative that appears eligible for PET imaging in animal models of vascular remodelling during evolving MI. The simple chemistry employed to synthesize the 68 Ga-based radiotracer may greatly facilitate its translation to a clinical setting.
Echocardiography, 1998
The aim of this study was to evaluate a second-generation echo contrast agent (NC100100) for the ... more The aim of this study was to evaluate a second-generation echo contrast agent (NC100100) for the study of myocardial perfusion. I n eight anesthetized open-chest dogs, this agent was injected intravenously under baseline conditions, during acute coronary thrombosis, and after reperfusion, using both fundamental (FI) and harmonic (HI) imaging, both continuous and intermittent imaging, and both ultrasound (US) and integrated backscatter (IBS) imaging. Contrast injections did not modify the hemodynamic parameters. With all imaging modalities, myocardial contrast enhancement (MCE) was higher with intermittent than with continuous imaging (134 us 82 gray level /pixel using FI, P = 0.02; 62 us 32 acoustic units using US HI, P = 0.02; and 52 us 12 dB using IBS, P = 0.05). MCE equally increased using either US or IBS imaging. The accuracy of MCE in detecting perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis was very good (sensitivity and specificity = 93% and 95% and 89% and 93%, respectively). The extent of myocardial perfusion defects by echo contrast showed a closer correlation with microspheres using HI (r = 0.82) than FI (r = 0.53). Thus, the intravenous administration of NClOOlOO during intermittent HI allows myocardial perfusion abnormalities to be accurately detected during acute myocardial infarction.
Coronary Artery Disease, 2007
Objective We investigated how pathologic Q waves or equivalents predict location, size and transm... more Objective We investigated how pathologic Q waves or equivalents predict location, size and transmural extent of myocardial infarction (MI). Methods MI characteristics, detected by contrastenhanced magnetic resonance imaging, were compared with 12-lead electrocardiogram in 79 patients with previous first MI. Results Q waves involved only the anterior leads (V 1-V 4) in 13 patients: in all patients MI involved the anterior and anteroseptal walls and apex; 81% of scar tissue was within these regions. Q waves involved only the inferior leads (II, III, aVF) in 13 patients: in 12 of these patients MI involved the inferior and inferoseptal walls; however, only 59% of scar occupied these regions. Q waves involved only lateral leads (V 5 , V 6 , I, aVL) in 11 patients: in nine of these patients MI involved the lateral wall but only 27% of scar tissue was within this wall. Q waves involved two electrocardiogram locations in 42 patients. In the 79 patients as a whole, the number of anterior Q waves was related to anterior MI size (r = 0.70); however, the number of inferior and lateral Q waves was only weakly related to MI size in corresponding territories (r = 0.35 and 0.33). A tall and broad R wave in V 1-V 2 was a more powerful predictor of lateral MI size than Q waves. Finally, the number of Q waves accurately reflected the transmural extent of the infarction (r = 0.70) only in anterior infarctions. Conclusion Q waves reliably predict MI location, size and transmural extent only in patients with anterior infarction. A tall and broad R wave in V 1-V 2 reflects a lateral MI. Coron Artery Dis 18:381-389 c 2007 Lippincott Williams & Wilkins.
Clinical Chemistry and Laboratory Medicine, 2002
The American Journal of Cardiology, 1986
ABSTRACT
The American Journal of Cardiology, 1989
The American Journal of Cardiology, 1981
European Heart Journal, 2007
Interactive cardiovascular and thoracic surgery, 2003
In patients with left ventricular dysfunction, multivessel coronary disease and viable myocardium... more In patients with left ventricular dysfunction, multivessel coronary disease and viable myocardium, little is known on the differential prognostic effect of coronary artery by pass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). To this purpose, 177 patients with previous myocardial infarction, three-vessel coronary disease and an EF<0.40 underwent CABG (group A, 114 patients) or PTCA (group B, 63 patients). Viability was demonstrated by maintained Thallium-201 uptake in more than 70% of left ventricle in 95/114 and 51/63 patients of groups A and B, respectively. Revascularization was greater in the CABG group (2.9+/-1.2 graft/patient) as compared to the PTCA group (1.3+/-1.2 treated vessel, P<0.05). Intraoperative mortality was 6.7 and 6.3% in groups A and B, respectively. At 6 months, viability was highly predictive of improvement of symptoms and wall motion abnormalities. Survival at 4 years was 90% in CABG and 92% in PTCA patients with maintained ...
To verify the behavior of coronary microvascular tone during spontaneous ischemia in patients wit... more To verify the behavior of coronary microvascular tone during spontaneous ischemia in patients with unstable angina (UA). BACKGROUND In UA, the pathogenetic role of vasoconstriction is classically confined at the stenotic coronary segment. However, microcirculatory vasoconstriction has been also suggested by previous experimental and clinical studies. METHODS The study included 10 patients with UA (recent worsening of anginal threshold and appearance of angina at rest) and single-vessel CAD. Blood flow velocity was monitored by a Doppler catheter in the diseased artery. Transstenotic pressure gradient was monitored by aortic and distal coronary pressure monitoring. Stenosis resistance was calculated as the ratio between pressure gradient and blood flow, microvascular resistance as the ratio between distal pressure and blood flow. Measurements were obtained at baseline, following intracoronary adenosine (2 mg) and during transient ischemia. Aortic and distal coronary pressures were also measured during balloon coronary occlusion. RESULTS Adenosine did not affect stenosis resistance, while it decreased (p Ͻ 0.05) microvascular resistance to 52 Ϯ 22% of baseline. Angina and ischemic ST segment shift were associated with transient angiographic coronary occlusion in 7 of 10 patients; however, in no case was ischemia associated with interruption of flow. Despite markedly different flow values, distal coronary pressure was similar during adenosine and during spontaneous ischemia (48 Ϯ 15 vs. 46 Ϯ 20 mm Hg, respectively, NS). During ischemia, a marked increase in the resistance of both coronary stenosis and coronary microcirculation was observed (to 1,233% Ϯ 1,298% and 671% Ϯ 652% of baseline, respectively, p Ͻ 0.05). Distal coronary pressure was markedly reduced during balloon coronary occlusion (14 Ϯ 7 mm Hg, p Ͻ 0.05 vs. both adenosine and ischemia), suggesting the absence of significant collateral circulation.
Journal of Translational Medicine, 2014
Background: Up-regulation of HO-1 by genetic manipulation or pharmacological pre-treatment has be... more Background: Up-regulation of HO-1 by genetic manipulation or pharmacological pre-treatment has been reported to provide benefits in several animal models of myocardial infarction (MI). However, its efficacy following MI initiation (as in clinical reality) remains to be tested. Therefore, this study investigated whether HO-1 over-expression, by cobalt protoporphyrin (CoPP) administered after LAD ligation, is still able to improve functional and structural changes in left ventricle (LV) in a rat model of 4-week MI. Methods: A total of 144 adult male Wistar rats were subjected to either left anterior coronary artery ligation or sham-operation. The effect of CoPP treatment (5 mg/kg i.p. at the end of the surgical session and, then, once a week for 4 weeks) was evaluated on the basis of survival, electro-and echocardiography, plasma levels of B-type natriuretic peptide (BNP), endothelin-1 and prostaglandin E2, coronary microvascular reactivity, MI size, LV wall thickness and vascularity. Besides, the expression of HO-1 and connexin-43 in different LV territories was assessed by western blot analysis and immunohistochemistry, respectively. Results: CoPP induced an increased expression of HO-1 protein with >16 h delay. CoPP treatment significantly reduced mortality, MI size, BNP concentration, ECG alterations, LV dysfunction, microvascular constriction, capillary rarefaction and restored connexin-43 expression as compared to untreated MI. These functional and structural changes were paralleled by increased HO-1 expression in all LV territories. HO activity inhibition by tin-mesoporphyrin abolished the differences between CoPP-treated and untreated MI animals. Conclusions: This is the first report demonstrating the putative role of pharmacological induction of HO-1 following coronary occlusion to benefit infarcted and remote territories, leading to better cardiac function in a 4-week MI outcome.
Journal of the American Society of Echocardiography, 1998
The purpose of this study was to detect myocardial perfusion defects as a result of coronary occl... more The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.
Journal of the American Society of Echocardiography, 1994
Journal of the American College of Cardiology, 1991
To asszw regmnat coronary reserve tn h>pertrophir ardiemyop athy, regkmat m,oenrdtt Mood (low was... more To asszw regmnat coronary reserve tn h>pertrophir ardiemyop athy, regkmat m,oenrdtt Mood (low was-"red tn 23 patteu
Journal of the American College of Cardiology, 1992
line. ~wo.d~me~s~~flal echocardio es of the left veneuronary arten y to generate tome-~ate~s~ty c... more line. ~wo.d~me~s~~flal echocardio es of the left veneuronary arten y to generate tome-~ate~s~ty curves. The study of myocardial tissue perfusion is still an elusive goal in the clinical setting, and all available methods have significant limitations. Coronary arteriography provides information only on the anatomy of epicardial coronary vessels (I 1. Similarly, Doppler catheters measure coronary flow velocity in the largest coronary arteries without exploring the downstream tissue perfusion (2). Thallium scintigraphy is being semiquantitative and myocardial thallium uptake also reflects the metabolic/histologic state of cells (3). Positron emission tomography accurately measures myocardial tissue perfusion (4); however, high costs and complex organization limit its use. In the last decade, efforts have been made to quantify myocardial perfusion by two-dimensional contrast echocar-From the CNR (Consiglio Nazionale Ricerche) Clinical Physiology Institute and University of Pisa. Pisa. Italy. At the time of the study Dr. DeMaria
Journal of the American College of Cardiology, 1991
Journal of the American College of Cardiology, 1991
Journal of the American College of Cardiology, 1996
higher dsk for a worse early and mid term clinical evolution as wall as mid term LVEF changes aft... more higher dsk for a worse early and mid term clinical evolution as wall as mid term LVEF changes after AML This data may stimulate further research to fully define MRI role in larger trials.
Journal of the American College of Cardiology, 1996
Journal of Cardiovascular Pharmacology, 2002
The aim of the current study was to assess the ability of amlodipine to dilate the coronary vesse... more The aim of the current study was to assess the ability of amlodipine to dilate the coronary vessels in subjects with angiographically normal coronary arteries and normal left ventricular function. Ten patients, six women and four men (mean age 48 +/- 14 years, range 25-67 years) were enrolled. Coronary flow velocity and coronary perfusion pressure were invasively measured at baseline, during intracoronary adenosine (1-mg bolus) and at 5, 15, and 30 min following IV amlodipine (10 or 20 mg). Quantitative coronary angiography was performed at baseline and at 5, 15, and 30 min after amlodipine. Coronary cross-sectional area and mean coronary flow velocity progressively increased after amlodipine administration, resulting in an average increase in coronary flow at 30 min of 76%. On an individual basis, all patients but one showed a consistent trend toward a progressive coronary vasodilator effect of amlodipine over time. The peak effect of amlodipine on baseline mean coronary flow velocity was 43 +/- 12% that of adenosine. This is the first clinical study demonstrating that the IV administration of amlodipine produces a powerful coronary vasodilatation in subjects with angiographically normal coronary arteries and normal ventricular function, besides its known systemic vasodilating effects. The coronary vasodilating properties of amlodipine are particularly expressed at the microcirculatory level.
European Journal of Nuclear Medicine and Molecular Imaging, 2013
Purpose The α v β 3 integrin is expressed in angiogenic vessels and is a potential target for mol... more Purpose The α v β 3 integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel 68 Ga-2,2′,2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI. Methods A straightforward labelling chemistry to attach the radionuclide 68 Ga to a NOTA-based chelating agent conjugated with a cyclic RGD peptidomimetic is described. Affinity for α v β 3 integrin was assessed by in vitro receptor binding assay. The proof-of-concept in vivo studies combined the 68 Ga-NOTA-RGD with the flow tracer 13 N-NH 3 imaging in order to obtain positron emission tomography (PET)/CT imaging of both integrin expression and perfusion defect at 4 weeks after infarction. Hearts were then processed for immunostaining of integrin β 3. Results NOTA-RGD conjugate displayed a binding affinity for α v β 3 integrin of 27.9±6.8 nM. 68 Ga-NOTA-RGD showed stability without detectable degradation or formation of byproducts in urine up to 2 h following injection in the rat. MI hearts exhibited 68 Ga-NOTA-RGD uptake in correspondence to infarcted and border zone regions. The tracer signal drew a parallel with vascular remodelling due to ischaemia-induced angiogenesis as assessed by immunohistochemistry. Conclusion As compared to similar imaging approaches using the 18 F-galacto-derivative, we documented for the first time with microPET/CT imaging the 68 Ga-NOTA-RGD derivative that appears eligible for PET imaging in animal models of vascular remodelling during evolving MI. The simple chemistry employed to synthesize the 68 Ga-based radiotracer may greatly facilitate its translation to a clinical setting.
Echocardiography, 1998
The aim of this study was to evaluate a second-generation echo contrast agent (NC100100) for the ... more The aim of this study was to evaluate a second-generation echo contrast agent (NC100100) for the study of myocardial perfusion. I n eight anesthetized open-chest dogs, this agent was injected intravenously under baseline conditions, during acute coronary thrombosis, and after reperfusion, using both fundamental (FI) and harmonic (HI) imaging, both continuous and intermittent imaging, and both ultrasound (US) and integrated backscatter (IBS) imaging. Contrast injections did not modify the hemodynamic parameters. With all imaging modalities, myocardial contrast enhancement (MCE) was higher with intermittent than with continuous imaging (134 us 82 gray level /pixel using FI, P = 0.02; 62 us 32 acoustic units using US HI, P = 0.02; and 52 us 12 dB using IBS, P = 0.05). MCE equally increased using either US or IBS imaging. The accuracy of MCE in detecting perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis was very good (sensitivity and specificity = 93% and 95% and 89% and 93%, respectively). The extent of myocardial perfusion defects by echo contrast showed a closer correlation with microspheres using HI (r = 0.82) than FI (r = 0.53). Thus, the intravenous administration of NClOOlOO during intermittent HI allows myocardial perfusion abnormalities to be accurately detected during acute myocardial infarction.
Coronary Artery Disease, 2007
Objective We investigated how pathologic Q waves or equivalents predict location, size and transm... more Objective We investigated how pathologic Q waves or equivalents predict location, size and transmural extent of myocardial infarction (MI). Methods MI characteristics, detected by contrastenhanced magnetic resonance imaging, were compared with 12-lead electrocardiogram in 79 patients with previous first MI. Results Q waves involved only the anterior leads (V 1-V 4) in 13 patients: in all patients MI involved the anterior and anteroseptal walls and apex; 81% of scar tissue was within these regions. Q waves involved only the inferior leads (II, III, aVF) in 13 patients: in 12 of these patients MI involved the inferior and inferoseptal walls; however, only 59% of scar occupied these regions. Q waves involved only lateral leads (V 5 , V 6 , I, aVL) in 11 patients: in nine of these patients MI involved the lateral wall but only 27% of scar tissue was within this wall. Q waves involved two electrocardiogram locations in 42 patients. In the 79 patients as a whole, the number of anterior Q waves was related to anterior MI size (r = 0.70); however, the number of inferior and lateral Q waves was only weakly related to MI size in corresponding territories (r = 0.35 and 0.33). A tall and broad R wave in V 1-V 2 was a more powerful predictor of lateral MI size than Q waves. Finally, the number of Q waves accurately reflected the transmural extent of the infarction (r = 0.70) only in anterior infarctions. Conclusion Q waves reliably predict MI location, size and transmural extent only in patients with anterior infarction. A tall and broad R wave in V 1-V 2 reflects a lateral MI. Coron Artery Dis 18:381-389 c 2007 Lippincott Williams & Wilkins.
Clinical Chemistry and Laboratory Medicine, 2002
The American Journal of Cardiology, 1986
ABSTRACT
The American Journal of Cardiology, 1989
The American Journal of Cardiology, 1981