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D Hasdai

Publications and source records attributed to D Hasdai.

At least 55 records · Page 3Linked to original sources
PubMed1999

Apoptosis. Basic concepts and implications in coronary artery disease.

Apoptosis is an active form of cell death that is intricately regulated and distinct from necrosis. Data suggest that apoptosis may play a role in the pathophysiology of coronary atherosclerotic disease. Anatomic evidence of apoptosis has been observed in coronary atherosclerosis, restenosis, and transplant arteriopathy, accompanied by an increase in biochemical and genetic markers of apoptosis. Vasoactive substances such as nitric oxide and angiotensin II also regulate vascular smooth muscle cell apoptosis; vasodilating factors may induce apoptosis, whereas vasoconstricting factors may inhibit apoptosis. The aim of this article is to review key points regarding the detection of apoptosis, its regulation, and its possible role in the pathogenesis of coronary artery disease.

Apoptosis↗
PubMed1999

Attenuated in vitro coronary arteriolar vasorelaxation to insulin-like growth factor I in experimental hypercholesterolemia.

Insulin and insulin-like growth factor (IGF) 1 affect coronary vasoactivity. Experimental hypercholesterolemia is associated with coronary atherogenesis and altered vasomotor regulation. Because the IGF axis is altered during atherogenesis, we postulated that experimental hypercholesterolemia is associated with an altered coronary vasoactive response to IGF-1 in vitro. Coronary arteries and arterioles from pigs fed either a normal or high-cholesterol diet for 10 weeks were contracted with endothelin-1 and relaxed with cumulative concentrations of insulin or IGF-1 (10(-12) to 10(-7) mol/L). Control arterioles were also incubated with the nitric oxide synthase inhibitor 10(-4) mol/L N(G)-monomethyl-L-arginine (L-NMMA) or the potassium channel blocker 10(-2) mol/L tetraethylammonium (TEA), contracted with endothelin-1, and relaxed with insulin or IGF-1. Experimental hypercholesterolemia (1) increased serum cholesterol (9.5+/-1.0 versus 1.9+/-0.08 mmol/L; P<0.0001), (2) caused coronary arterial and arteriolar endothelial dysfunction in vitro (attenuated vasorelaxation to bradykinin), (3) did not alter the epicardial response to either insulin (P=0.80) or IGF-1 (P=0.12), and (4) significantly attenuated the arteriolar response to IGF-1 (maximal relaxation of 79+/-6% versus 42+/-8%; P=0.01) but not insulin (43+/-6% versus 53+/-7%; P=0.99). Control arteriolar vasorelaxation to IGF-1 was attenuated by both L-NMMA (P<0.001) and TEA (P=0.01), whereas only L-NMMA attenuated insulin (P<0.001). Staining for IGF-1 and IGF binding protein 2 was increased (P<0.05) in arterioles of cholesterol-fed pigs. IGF-1 and insulin are therefore coronary arteriolar vasorelaxants through different mechanisms. Experimental hypercholesterolemia is associated with resistance to the coronary arteriolar vasorelaxing effects of IGF-1 but not insulin, in conjunction with increased ligand and binding-protein expression. The IGF axis may contribute to the altered coronary vasoactivity in hypercholesterolemia.

Animals↗
PubMed1998

Usefulness of abciximab for treatment of early coronary artery stent thrombosis.

The clinical and angiographic outcomes of 10 patients who received abciximab as part of their therapy for early stent thrombosis was compared with 25 patients (using historical controls) who received conventional therapy. Although the angiographic outcome and the incidence of myocardial infarction in both groups was similar, there were no deaths or referral for emergency coronary bypass surgery in the abciximab-treated group versus 3 deaths and 10 referrals for emergency bypass surgery in the conventionally treated group.

Abciximab↗
PubMed1998

Abciximab administration and outcome after intracoronary stent implantation.

Although adjunctive abciximab therapy improves outcome after angioplasty or atherectomy, there are few data demonstrating its benefit for intracoronary stent implantation. We characterized patients receiving abciximab for stent placement in our practice and determined the impact of abciximab on outcome. Abciximab was introduced to our practice in April 1995 for percutaneous revascularization. Demographic, clinical, and angiographic variables that were independently associated with the use of abciximab for stent placement through 1996 (abciximab era) were examined. We then examined among all patients receiving stents from 1992 through 1996 (preabciximab and abciximab eras) whether the use of abciximab was independently associated with improved outcome (death, nonfatal Q-wave myocardial infarction, coronary bypass surgery, or target vessel percutaneous revascularization) in the hospital and at 30 days. The 30-day event rate was 7% for those who did or did not receive abciximab. The following characteristics were independently associated with the use of abciximab for stent placement in the abciximab era: thrombus before stent placement (chi-square 50.5), > or =2 stents implanted (chi-square 10.8), stent in venous graft (chi-square 7.4), calcific lesion (chi-square 5.8), and hypertension (chi-square 5.5). Among all patients receiving stents in the preabciximab and abciximab eras (n=1,859), the presence of these characteristics was independently associated with worse outcome. Abciximab, however, did not improve outcome in the hospital (odds ratio [95% confidence interval]=0.96 [0.58 to 1.58]) or at 30 days (0.87 [0.53 to 1.41]), even after adjusting for these characteristics. Abciximab for stent placement was used in high-risk patients in our practice but was not associated with improved outcome.

Abciximab↗
PubMed1998

Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement.

Increased basal epicardial tone may attenuate the coronary flow reserve (CFR) by causing vasodilatation of resistance vessels. We examined the effect of basal epicardial tone on the endothelium-independent CFR measurements in subjects with nonobstructive coronary disease. Patients underwent evaluation of endothelium-independent CFR using adenosine (18-36 microg) and endothelium-dependent CFR using acetylcholine (10(-6) M-10(-4) M), both administered intracoronary. CFR to adenosine, presented as the ratio of Doppler flow velocities post- and pre-adenosine, was measured at baseline and after intracoronary nitroglycerin (200 microg). Nitroglycerin increased the coronary artery diameter by 19.7 +/- 2.5%, and decreased the coronary vascular resistance from 3.0 +/- 0.2 mm Hg/ml/min to 1.8 +/- 0.1 mm Hg/ml/min (p < 0.0001). The response to adenosine at baseline and after nitroglycerin was similar (CFR ratio of 2.52 +/- 0.09 and 2.57 +/- 0.10, respectively, p = NS). The effect of nitroglycerin on the response to adenosine did not correlate with coronary endothelial function (r2 = 0.06, p = 0.13). The basal epicardial tone does not affect CFR measurements in patients with angina and nonobstructive coronary disease.

Acetylcholine↗
PubMed1998

Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c.

OBJECTIVE: To examine the hypothesis that insulin and insulin-like growth factor I (IGF-I) attenuate endothelin-induced contraction of porcine coronary epicardial arteries in vitro. BACKGROUND: Endothelin-induced coronary vasoconstriction is mediated by two types of receptors, A (ETA) and B (ETB), resulting in calcium influx. Both insulin and IGF-I attenuate endothelin-induced calcium influx into porcine coronary artery smooth muscle. METHODS: Epicardial arteries harvested from juvenile pigs were contracted with cumulative concentrations of endothelin-1 (ETA- and ETB-receptor agonist; 10(-10)-10(-6) M) or of sarafotoxin-6c (ETB-receptor agonist; 10(-11)-10(-7) M). In additional experiments, endothelin-1 or sarafotoxin-6c were added after incubation with 10(-8) M regular insulin or IGF-I. These experiments were repeated in vessels without endothelium. Contraction for each vessel was calculated relative to the response to 60 mM KCl. RESULTS: The maximal contractions to endothelin-1 in vessels with and without endothelium were 158 +/- 8 and 200 +/- 21%, respectively (p < 0.05 at 10(-8.5)-10(-6.5) M). Both insulin (at 10(-7)-10(-6) M) and IGF-I (at 10(-6.5)-10(-6) M) attenuated the contraction to endothelin-1 in vessels with intact endothelium, as well as in vessels without endothelium (at 10(-7) and 10(-6) M for insulin and 10(-7.5)-10(-6) M for IGF-I). The maximal contractions to sarafotoxin-6c in vessels with and without endothelium were 54 +/- 13 and 84 +/- 7%, respectively (p < 0.05 at 10(-9), 10(-8.5) and 10(-7) M). Insulin and IGF-I did not affect the response to sarafotoxin-6c in vessels with and without endothelium. CONCLUSION: Insulin and IGF-I attenuated ETA-receptor-mediated coronary contraction through an endothelium-independent mechanism. The IGF axis may serve as an endogenous modulator of endothelin-mediated vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Early development of high-degree atrioventricular block in inferior acute myocardial infarction is predicted by a J-point/R-wave ratio above 0.5 on admission.

This study assessed the ability of simple clinical and electrocardiographic (ECG) variables routinely obtained on admission to identify patients with inferior myocardial infarction who are at high risk of developing high-degree atrioventricular (AV) block within the first 24 h of hospitalization in 205 patients. The admission ECGs were classified into two patterns based on the J-point to R-wave amplitude ratio: pattern 1: those with J-point/R-wave ratio <0.5; pattern 2: patients with J-point/R-wave ratio >/=0.5 in >/=2 inferior leads (II, III and aVF). High-degree AV block was found in 10.2% of the patients (21 of 205 patients; 5 and 16% of the patients with initial patterns 1 and 2, respectively, p = 0.014). Multivariate logistic regression analysis revealed that the only variables independently associated with high-degree AV block were the initial ECG pattern 2 versus 1 (odds ratio, OR, 4.47, 95% confidence interval, CI, 1.18-16.9; p = 0.0276), age (OR 1.06, 95% CI 1.01-1.12; p = 0.0254); Killip class >1 (OR 2.33, CI 0.83-6. 54; p = 0.1065) and thrombolytic therapy (OR 0.32, 95% CI 0.11-0.93; p = 0.037).

Adult↗
PubMed1998

Acute endothelin-receptor inhibition does not attenuate acetylcholine-induced coronary vasoconstriction in experimental hypercholesterolemia.

Endothelin (ET) may mediate the enhanced coronary vasoconstriction associated with hypercholesterolemia. We hypothesized that short-term inhibition of ET receptors attenuates the coronary epicardial vasoconstrictor response to acetylcholine in experimental hypercholesterolemia. ET-1 (group I, n=5; 5 ng x kg[-1] x min[-1]) and acetylcholine (group III, n=7; 10[-6] to 10[-4] mol/L) were given by intracoronary infusion in pigs. ET-1 and acetylcholine were also infused with the specific ETA-receptor blocker FR-139317 (5 microg x kg[-1] x min[-1]; group II, n=6; group IV, n=6). Acetylcholine was also infused with the combined ET-receptor blocker, bosentan (0.5 mg/kg plus 1 mg x kg[-1] x h[-1], group V, n=5). The ETB-receptor agonist sarafotoxin 6c (5 ng x kg[-1] x min[-1]; n=4) was also infused. The percentage change in coronary artery diameter (%deltaCAD) to the infusions was measured at baseline and after 10 weeks of high-cholesterol diet in all animals. Sarafotoxin 6c mildly reduced %deltaCAD at baseline and 10 weeks (-10+/-2% and -12+/-3%, respectively). FR-139317 did not attenuate the epicardial vasoconstrictor response to ET-1 at baseline (%deltaCAD -18+/-8% for group I versus -12+/-6% for group II; P=NS) but did at 10 weeks (%deltaCAD -77+/-14% for group I versus -14+/-6% for group II; P<.05). FR-139317 did not affect the response to acetylcholine at baseline (%deltaCAD 5+/-2% for group III versus 7+/-3% for group IV, P=NS) or at 10 weeks (%deltaCAD -23+/-12% for group III versus -19+/-7% for group IV; P=NS). Bosentan did not affect the response to acetylcholine at baseline or 10 weeks. Short-term ET-receptor inhibition in experimental hypercholesterolemia attenuated the enhanced coronary epicardial vasoconstrictor effects of ET-1 but not acetylcholine-induced coronary epicardial vasoconstriction, suggesting that acetylcholine-induced coronary epicardial vasoconstriction may not be mediated by ET receptors.

Acetylcholine↗
PubMed1998

Insulin and insulin-like growth factor-I cause coronary vasorelaxation in vitro.

Insulin and insulin-like growth factor-I (IGF-I) may play a role in the modulation of coronary artery tone, yet there are few data regarding their vasoactive effects on the coronary vascular bed. We evaluated the vasorelaxation effects of insulin and IGF-I on porcine coronary epicardial vessels in vitro and elucidated possible mechanisms. Porcine epicardial arteries were contracted with 10(-7) mol/L endothelin-1 and relaxed with cumulative concentrations of either insulin or IGF-I (10(-12) to 10(-7) mol/L). The above experiments were repeated in vessels without endothelium. Vessels were also incubated with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4) mol/L) with and without 10(-3.5) mol/L L-arginine, the potassium channel blocker tetraethylammonium (TEA; 10(-2) mol/L), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ; 10(-5.5) mol/L); vessels were then contracted with endothelin-1 and relaxed with insulin or IGF-I. Insulin and IGF-I were also added after contraction with 60 mmol/L KCl. Insulin and IGF-I caused a similar decrease in coronary epicardial tension after contraction with endothelin-1 (relaxation of 28+/-4% [n=7] and 25+/-3% [n=8] with insulin and IGF-I, respectively; P<0.0001 for both peptides). Removal of the endothelium did not affect these responses. Incubation with L-NMMA, but not ODQ, attenuated the vasorelaxation response to insulin and IGF in vessels without endothelium. L-Arginine did not reverse this effect of L-NMMA. KCl and TEA attenuated the vasorelaxation effect of both insulin and IGF-I. Thus, both insulin and IGF-I caused non-endothelium-dependent coronary vasorelaxation in vitro, probably through a mechanism involving the activation of potassium channels. These findings suggest that insulin and IGF-I participate in the regulation of coronary vasomotor tone.

Animals↗
PubMed1998

Prevalence of coronary blood flow reserve abnormalities among patients with nonobstructive coronary artery disease and chest pain.

OBJECTIVE: To determine the prevalence of abnormalities in endothelium-dependent and endothelium-independent coronary flow reserve among patients with non-obstructive coronary artery disease and chest pain. MATERIAL AND METHODS: We studied endothelium-dependent (after infusion of 10(-6) M to 10(-4) M of acetylcholine) and endothelium-independent (after administration of 18 to 36 micrograms of adenosine) coronary flow reserve among patients with nonobstructive coronary artery disease and chest pain who were undergoing assessment at Mayo Clinic Rochester. Coronary blood flow was derived from coronary artery diameter assessed by quantitative angiography and Doppler flow velocities. RESULTS: The cohort consisted of 203 patients (158 female and 45 male patients), who ranged in age from 17 to 78 years (mean, 51). Most patients (92%) had at least one risk factor for atherosclerosis; a substantial proportion had undergone extensive cardiac and noncardiac evaluation. Whereas 41.5% of the patients had normal coronary flow reserve, 58.5% had an abnormal response: 11.3% an impaired response to adenosine (flow velocity ratio of 2.5 or less), 29.2% an impaired response to acetylcholine (flow reserve ratio of 1.5 or less), and 18% a combined abnormality. No correlation (r2 = 0.03) was noted between endothelium-dependent and endothelium-independent flow reserve. CONCLUSION: Most study patients with chest pain and nonobstructive coronary artery disease undergoing coronary vasomotor evaluation had risk factors for coronary artery disease and diverse abnormalities in endothelium-dependent or endothelium-independent coronary flow reserve (or both). These findings underscore the need for a comprehensive assessment.

Acetylcholine↗
PubMed1998

Predictors of smoking cessation after percutaneous coronary revascularization.

OBJECTIVE: To identify factors predictive of smoking cessation after successful percutaneous coronary revascularization. MATERIAL AND METHODS: We undertook a case-control study of the smoking status of all patients at Mayo Clinic Rochester from September 1979 through December 1995 who were smokers at the time of an index percutaneous coronary revascularization procedure in the non-peri-infarction setting (no myocardial infarction within 24 hours). Maximal duration of prospective follow-up was 16 years. Patients were classified into those who permanently quit smoking immediately after the procedure (N = 435; mean follow-up, 5.1 +/- 3.7 years) or those who continued to smoke at some time during follow-up (N = 734; mean follow-up, 5.3 +/- 3.7 years). Logistics regression models were formulated to determine independent predictors of smoking cessation. RESULTS: Predictors of continued smoking were greater prior cigarette consumption (odds ratio [OR] = 1.009 for each pack-year; 95% confidence interval [CI] = 1.004 to 1.014) and having one or more risk factors for coronary artery disease other than cigarette smoking (OR = 1.49; 95% CI = 1.15 to 1.93). Older age (OR = 0.98 for each additional year; 95% CI = 0.97 to 0.99) and unstable angina at time of initial assessment (OR = 0.69; 95% CI = 0.52 to 0.91) were associated with less likelihood of continued smoking. CONCLUSION: Younger patients with a worse risk profile and greater prior cigarette consumption were more likely than other patients to continue smoking after percutaneous coronary revascularization in the non-peri-infarction setting. Patients who had unstable angina were more likely to quit smoking than those who had stable angina. Despite the proven benefits of smoking cessation after percutaneous coronary revascularization, a substantial proportion of smokers (63%) continue to smoke; thus, smoking-cessation counseling should be addressed in this population.

Aged↗
PubMed1997

Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects.

BACKGROUND: Coronary endothelial dysfunction may occur in patients with minimally obstructive coronary artery disease and angina, and potentially may cause myocardial ischemia. METHODS AND RESULTS: Coronary endothelium-dependent vasodilation was examined in patients with angina and <50% coronary artery diameter (CAD) stenosis by selectively infusing acetylcholine (10(-6) mol/L to 10(-4) mol/L) into the left anterior descending coronary artery (LAD). Percent change in CAD (%deltaCAD) was measured by quantitative coronary angiography, and percent change in coronary blood flow (%deltaCBF) was calculated using intracoronary flow Doppler. Coronary endothelium-independent vasodilation was examined using intracoronary adenosine and nitroglycerin. 99mTc sestamibi was injected intravenously just prior to the infusion of the highest dose of acetylcholine. Patients were divided blindly into three groups: Perfusion defects in non-LAD territory (group 1, n=6), no perfusion defects (group 2, n=7), and perfusion defects in the LAD territory (group 3, n=7). All patients had intact endothelium-independent vasodilation. In group 1, perfusion defects outside the LAD territory reflected an increase in %deltaCAD and %deltaCBF by 24+/-5% and 241+/-46% in the LAD. In group 2, %deltaCAD decreased by 26+/-5%, but %deltaCBF increased by 54+/-17%. In group 3, perfusion defects were within the LAD territory, reflecting a decrease in %deltaCAD and %deltaCBF by 35+/-5% and 51+/-14%, respectively. CONCLUSIONS: This study demonstrates that coronary endothelial dysfunction in humans may be temporally associated with myocardial perfusion defects and supports a role for the coronary epicardial and microcirculation endothelium in regulating myocardial perfusion. Myocardial ischemia may occur in humans with impaired endothelium-dependent coronary flow reserve of the coronary epicardial and microcirculation.

Acetylcholine↗
PubMed1997

Enhanced endothelin-mediated coronary vasoconstriction and attenuated basal nitric oxide activity in experimental hypercholesterolemia.

BACKGROUND: Experimental hypercholesterolemia is associated with coronary vasomotor dysfunction. This study was designed to test the hypothesis that experimental hypercholesterolemia is characterized by altered coronary vasomotor responses to endothelin and inhibition of the endogenous NO pathway. METHODS AND RESULTS: Endothelin-1 (ET-1) at 5 ng x kg(-1) x min(-1) or N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase (NOS), at 50 microg x kg(-1) x min(-1) was infused into the left anterior descending coronary artery in pigs before and after 10 weeks of cholesterol diet. There was a significant increase in serum cholesterol. At 10 weeks, ET-1 resulted in an accentuated decrease in coronary blood flow (CBF) and coronary artery diameter (CAD) compared with baseline (-88+/-6% versus -45+/-9%, P<.05, and -77+/-14% versus -18+/-8%, P<.05, respectively) and an increase in coronary vascular resistance (CVR) (242+/-18% versus 110+/-17%, P<.05); ET receptor density and binding affinity in epicardial coronary arteries were unchanged. The effect of L-NMMA on CBF, CAD, and CVR was attenuated at 10 weeks (-7+/-8% versus -48+/-4%, -2+/-3% versus -17+/-5%, and 16+/-10% versus 125+/-32%; each P<.05). Immunohistochemistry staining for constitutive NOS revealed a decrease in immunoreactivity in the coronary arteries of hypercholesterolemic pigs. CONCLUSIONS: The present study demonstrates an enhanced coronary vasoconstrictive response to pathophysiological doses of endothelin and an attenuated response to the inhibition of endogenous NO activity, suggesting an alteration in coronary vascular reactivity in experimental hypercholesterolemia.

Acetylcholine↗
PubMed1997

Serum basic fibroblast growth factor levels in patients with ischemic heart disease.

BACKGROUND: Being a potent promoter of endothelial and smooth muscle cell proliferation, basic fibroblast growth factor (bFGF) is presumed to play a key role in coronary collateral development and atherogenesis. PURPOSE: To characterize serum bFGF levels in patients with ischemic heart disease. METHODS: The study population consisted of patients with angina (n=33) and after uncomplicated myocardial infarction (n=12). The number of significantly stenosed (> or = 50%) vessels and angiographic coronary collateral score were noted. Blood was drawn immediately prior to elective coronary angiography in study patients for bFGF levels. Twenty healthy, age-matched subjects served as control for serum bFGF. RESULTS: Serum bFGF levels were undetectable in all 20 control subjects, but were detectable in 15/33 (45%) patients with angina and 3/12 (25%) post-infarction patients, respectively (P=0.002). Serum bFGF levels were detectable in 13/23 (57%) patients with 0- or 1-vessel disease, as compared with 5/22 (23%) patients with 2- or 3-vessel disease (P<0.05). Detectable serum bFGF levels were not in correlation with coronary collateral score (P=1). CONCLUSIONS: Serum levels of bFGF are elevated in patients with ischemic heart disease, particularly in those with minimal coronary artery disease. We postulate that detectable serum bFGF levels reflect active atherogenesis rather than myocardial collateral development.

Aged↗
PubMed1997

Outcome > or = 10 years after successful percutaneous transluminal coronary angioplasty.

Patients (n = 611) after successful percutaneous transluminal coronary angioplasty were prospectively followed over 10 to 16 years for major adverse events. The effect of gender, extent of coronary artery disease, left ventricular dysfunction, and age on occurrence of adverse events were analyzed in detail. The incidence of death, Q-wave myocardial infarction, and coronary bypass surgery was 23.1%, 3.9%, and 32.7%, respectively. Men and women had similar mortality (p = 0.13) and Q-wave myocardial infarction (p = 0.57), but men had more coronary bypass surgery (p = 0.06). Patients with multivessel disease had higher mortality (p < 0.0001), and patients with 3-vessel disease had a higher incidence of Q-wave myocardial infarction (p = 0.04) and coronary bypass surgery (p < 0.001). Left ventricular dysfunction was associated with higher mortality (p < 0.0001) and coronary bypass surgery (p = 0.045), but not Q-wave myocardial infarction (p = 0.99). Mortality was higher in elderly patients (p < 0.0001), but the incidence of Q-wave myocardial infarction was similar (p = 0.64). Older patients underwent coronary bypass surgery less often (p = 0.004). By multivariate analysis, only the extent of coronary disease (relative risk [RR] 1.71, confidence interval [CI] 1.34 to 2.19; p = 0.0001), diabetes mellitus (RR 1.82, CI 1.28 to 2.59; p = 0.001), hypertension (RR 1.30, CI 1.08 to 1.96, p = 0.009), male gender (RR 1.30, CI 0.99 to 1.71, p = 0.058), and prior myocardial infarction (RR 1.44, CI 1.14 to 1.81, p = 0.002) independently influenced the incidence of major adverse events. We conclude that it is possible to identify patients with worse long-term prognosis after percutaneous transluminal coronary angioplasty based on clinical and angiographic parameters.

Aged↗