Jean-Marc Foult

Coronary vasodilator reserve in untreated and treated hypertensive patients with and without left ventricular hypertrophy

OBJECTIVES This study was initiated to compare the coronary reserve in treated hypertensive patients with and without left ventricular hypertrophy with that in untreated patients. BACKGROUND Coronary reserve is impaired in hypertensive patients with left ventricular hypertrophy and normal coronary arteries. Moreover, basal coronary resistance is elevated in hypertensive patients without left ventricular hypertrophy. METHODS Coronary reserve was measured with a coronary Doppler catheter before and after a maximally vasodilating dose of intracoronary papaverine (peak/rest flow velocity ratio) in 16 control subjects and 37 hypertensive patients with normal epicardial coronary arteries. Among 20 untreated hypertensive patients, myocardial mass was increased in 11 (group 2a) and normal in 9 (group 2b). Seventeen patients had been treated effectively for at least 1 year; nine (group 3a) had persistent left ventricular hypertrophy, and eight (group 3b) had no left ventricular hypertrophy before treatment. Left ventricular volumes and ejection fraction were normal in all groups. RESULTS Coronary reserve was moderately reduced in group 2b (3.5 +/- 0.6 vs. 5.2 +/- 0.8 in control subjects, p < 0.001) and markedly diminished in groups 2a and 3a (2.5 +/- 0.5 and 2.7 +/- 0.4, respectively; all p < 0.001 vs. control subjects). In group 3b, coronary reserve was comparable to that of control subjects (5.1 +/- 1.4). CONCLUSIONS The reduction in coronary reserve observed in untreated hypertensive patients with normal myocardial mass suggests that structural abnormalities of the coronary microvasculature may occur before left ventricular hypertrophy. Treated patients with normal mass before treatment had a coronary reserve comparable to that of normotensive control subjects, whereas normalization of arterial pressure with persistent left ventricular hypertrophy was associated with a marked impairment of coronary reserve.

Direct myocardial and coronary effects of enalaprilat in patients with dilated cardiomyopathy: assessment by a bilateral intracoronary infusion technique.

Angiotensin II elicits contractile responses in the coronary arteries and myocardial tissue, which suggests that blockade of the renin-angiotensin system by specific agents should lead to both coronary vasodilation and an alteration of left ventricular inotropism. The present work was designed to delineate--independently from its systemic effects--the intrinsic actions of an angiotensin converting-enzyme inhibitor on the coronary circulation and left ventricular function. To minimize peripheral effects, a bilateral intracoronary infusion of enalaprilat (0.05 mg.min-1, 1 ml.min-1 in each coronary artery) was performed in 16 patients with dilated cardiomyopathy. All patients had normal coronary arteriograms. In 12 patients (group I) the intracoronary infusion of enalaprilat resulted in minimal peripheral changes, with a 5% reduction in the mean aortic pressure (p less than .05) and no significant alteration in indexes of preload, i.e., left ventricular end-diastolic pressure and volume, or of afterload, i.e., left ventricular end-systolic stress and systemic resistances. Myocardial oxygen consumption was also unaffected by the intracoronary infusion of enalaprilat. Coronary vasodilation was demonstrated by a significant elevation of coronary sinus blood flow (+19%, from 181 +/- 73 to 214 +/- 79 ml.min-1, p less than .001) and a reduction of coronary resistance (-18%, from 0.51 +/- 0.17 to 0.41 +/- 0.15 mm Hg.ml-1.min, p less than .001), with a parallel increase in coronary sinus oxygen content and pressure (both p less than .05). Oxygen extraction by the myocardium was reduced (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Multifactorial determinants of reduced coronary flow reserve after dipyridamole in dilated cardiomyopathy

Coronary sinus blood flow (ml/100 g left ventricular [LV] mass/min) and coronary resistance (mean aortic minus LV mean diastolic pressures/coronary sinus blood flow, mm Hg/[ml/100 g/min]) were studied in 7 control patients and in 11 patients with severe dilated cardiomyopathy (DC) and normal coronary arteriograms. Basal coronary sinus blood flow was not different in the 2 groups. After intravenous administration of dipyridamole (0.14 mg/kg/min X 4 min), coronary sinus blood flow and dipyridamole/basal coronary sinus blood flow ratio were significantly (p less than 0.001) lower in the DC group than in the normal group (coronary sinus blood flow 188 +/- 48 vs 408 +/- 58, respectively; blood flow ratio 1.78 +/- 0.35 vs 4.01 +/- 0.56, respectively), and the coronary resistance was higher in the DC group than in the control group (0.39 +/- 0.15 vs 0.22 +/- 0.03, respectively, p less than 0.01). After administration of dipyridamole in patients with DC, no correlation could be found between coronary sinus blood flow and LV mean diastolic, mean aortic or coronary driving pressures, i.e., mean aortic minus LV mean diastolic pressures. Thus, in DC patients, neither an elevated LV diastolic pressure nor a low coronary perfusion pressure can totally account for the restriction of the coronary flow reserve after dipyridamole.

Acetylcholine-induced coronary vasoconstriction in young, heavy smokers with normal coronary arteriographic findings

PURPOSE Cigarette smoking is a major coronary risk factor. Acetylcholine dilates coronary arteries in normal subjects, but acetylcholine-induced coronary constriction has been reported in patients with normal coronary arteriographic findings and other risk factors for coronary artery disease. The purpose of the present study was to evaluate the epicardial coronary artery response to acetylcholine in young, heavy smokers. SUBJECTS AND METHODS Responses to stepwise infusion of acetylcholine (10(-8)M, 10(-7)M, 10(-6)M, and 10(-5)M) into the left coronary artery were studied in five young, heavy smokers and in five age-matched nonsmokers. All subjects were normotensive and had normal left ventricular function and coronary arteriographic findings. Levels of serum cholesterol, triglycerides, and low-density lipoprotein levels were within normal ranges. Vessel dimensions were measured on four different segments in each subject, with quantitative digital-substracted arteriography. RESULTS In smokers, no change was produced at the 10(-8) M and 10(-7) M concentrations of acetylcholine, but progressive diameter reduction was observed at 10(-6) M and 10(-5) M acetylcholine (-26.6% +/- 13.6%, p < 0.001; -42.2% +/- 9.5%, p < 0.001, respectively). In nonsmokers, a progressive diameter dilation was produced from 10(-8) M to 10(-6) M acetylcholine (+5.3% +/- 3.6%, p < 0.001; +12.4% +/- 6.5%, p < 0.001; +15.9% +/- 6.9%, p < 0.001, respectively), and no change was observed at 10(-5) M acetylcholine. In the two groups, all segments dilated after infusion of intracoronary isosorbide dinitrate. CONCLUSION The abnormal coronary vasoconstriction induced by acetylcholine in young, heavy smokers with angiographically normal coronary arteries suggests an endothelial vasodilator dysfunction. This mechanism may contribute to the pathogenesis of coronary artery disease in cigarette smokers.

Coronary flow and resistance reserve in patients with chronic aortic regurgitation, angina pectoris and normal coronary arteries

Left ventricular hypertrophy has been found to be associated with a reduction of coronary vascular reserve, which could be responsible for episodes of myocardial ischemia. To evaluate coronary flow and resistance reserve in patients with chronic aortic regurgitation, coronary sinus blood flow and coronary resistance were measured before and after an intravenous dipyridamole infusion (0.14 mg/kg per min X 4 min) in eight control subjects and eight patients with aortic regurgitation, exertional angina pectoris and normal coronary arteriograms. Coronary flow reserve, evaluated by the dipyridamole/basal coronary sinus blood flow ratio, and coronary resistance reserve, evaluated by the basal/dipyridamole coronary resistance ratio, were both significantly reduced in patients with aortic regurgitation (1.67 +/- 0.40 versus 4.03 +/- 0.52 in control subjects, p less than 0.001 and 1.71 +/- 0.50 versus 4.38 +/- 0.88 in control subjects, p less than 0.001, respectively). In patients with aortic regurgitation, basal coronary sinus blood flow was higher than in control subjects (276 +/- 81 versus 105 +/- 24 ml/min, respectively, p less than 0.001) and basal coronary resistance was lower (0.31 +/- 0.13 versus 0.95 +/- 0.17 mm Hg/ml per min, respectively, p less than 0.001), but coronary blood flow and resistance after dipyridamole were not significantly different in the two groups (461 +/- 159 versus 418 +/- 98 ml/min in control subjects, 0.19 +/- 0.11 versus 0.22 +/- 0.04 mm Hg/ml per min in control subjects, respectively). These data demonstrate that coronary reserve is severely reduced in patients with chronic aortic regurgitation and exertional angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe impairment of coronary reserve during rejection in patients with orthotopic heart transplant.

The present study analyzed coronary sinus blood flow alterations after dipyridamole induced coronary vasodilation in seven patients whose endomyocardial biopsies evidenced no sign of rejection (group 1) and in five patients with histologic signs of rejection (group 2) after orthotopic heart transplantation. All patients were treated with cyclosporine and prednisone and some with azathioprine and had normal coronary arteriograms. Coronary sinus blood flow and coronary resistance were measured before and after intravenous dipyridamole (0.18 mg/kg/min over 4 minutes). Basal values were similar in groups 1 and 2 for coronary sinus blood flow (166 +/- 34 compared with 181 +/- 39 ml/min, respectively), coronary resistance (0.62 +/- 10 compared with 0.52 +/- 13 mm Hg/ml/min, respectively), coronary sinus blood oxygen content (5.7 +/- 1.6 compared with 4.5 +/- 0.9 ml/100 ml, respectively) and arterial-coronary sinus blood oxygen difference (10.6 +/- 1.3 compared with 10.3 +/- 1.8 ml/100 ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of a normal coronary vascular reserve after rejection therapy in acute human cardiac allograft rejection.

During acute rejection, coronary vascular reserve is severely impaired in human orthotopic heart transplants. To evaluate the effects of rejection therapy on coronary vascular reserve, the ratio of peak-to-resting coronary flow velocity was assessed with a coronary Doppler catheter and a maximally vasodilating dose of intracoronary papaverine (12 mg) in nine allograft recipients without rejection (group 1) and in six recipients before and after treatment of an acute episode of rejection (group 2). All the patients had normal epicardial coronary arteries and were free of left ventricular hypertrophy. In group 2 during rejection, the coronary vascular reserve was significantly lower than in group 1, in which all the patients had a peak-to-resting coronary flow velocity ratio greater than 4 (2.3 +/- 0.5 vs. 5.4 +/- 0.8, respectively, p less than 0.001). In group 2 after treatment of rejection, the peak-to-resting coronary flow velocity ratio was similar to that of group 1 (4.7 +/- 0.8). Heart rate, left ventricular volumes and pressures, hemoglobin concentration, and arterial oxygen pressure were similar in the two groups. This study provides evidence that alterations of coronary vascular reserve because of acute rejection were reversible after treatment of the rejection episode.

Nonlimited exercise test combined with high-dose dipyridamole for thallium-201 myocardial single-photon emission computed tomography in coronary artery disease.

Clinical, electrocardiographic, and thallium-201 single-photon emission computed tomography data were evaluated in 397 consecutive patients divided into 3 groups according to coronary hyperemic stimulation: 186 patients (group I; Ex) had maximal symptom-limited exercise ergometric stress testing, 93 patients (group II; Dip) had intravenous dipyridamole (0.7 to 0.8 mg/kg) stress testing, and 118 patients (group III; Dip+Ex) had dipyridamole (0.7 to 0.8 mg/kg) plus nonlimited (i.e., symptom-limited) exercise stress testing, achieving a maximal workload (mean +/- SD) of 102 +/- 37 W. Clinical tolerance was higher in Ex than in Dip groups (p < 0.01), and tended to be higher in Dip+Ex than in Dip groups (p = NS). Image quality--as judged by signal-to-noise ratios--was superior in Ex and Dip+Ex groups when compared with the Dip group (p < 0.01). Chest pain and electrocardiographic positivity were more frequent in the Dip+Ex group than in the Dip group (p < 0.05), despite more extensive coronary artery disease (CAD) in the Dip group; and reversible scintigraphic defects were more frequent in Dip+Ex versus Dip (p < 0.01) and in Ex versus Dip groups (p < 0.05) in patients with established CAD, as well as for the whole group. We conclude that, in patients unable to achieve 85% of their maximal predicted heart rate, the combination of high-dose dipyridamole plus nonlimited exercise stress testing is superior to dipyridamole stress testing alone, and comparable to maximal exercise testing.

Size dependence of the end-systolic stress/volume ratio in humans: Implications for the evaluation of myocardial contractile performance in pressure and volume overload

The end-systolic stress/volume ratio is currently recognized as a relatively load-independent index of myocardial contractile performance, but its dependence on ventricular size may limit its value for interpatient comparisons. In this study, the relation between the end-systolic stress/volume ratio and left ventricular end-diastolic volume was angiographically analyzed in 104 patients with normal coronary angiograms. Eighteen patients had a normal ventricle, 24 had aortic stenosis, 18 had aortic regurgitation, 9 had mitral regurgitation and 35 had cardiomyopathy. An inverse relation between the end-systolic stress/volume ratio and left ventricular end-diastolic volume was demonstrated in the normal group (r = 0.72, p less than 0.001); subjects with a larger left ventricle had a reduced index but, presumably, the same degree of contractility as that of subjects with a smaller ventricle. Attempts to normalize values by using end-diastolic volume or body surface area were unsuccessful. A similar inverse relation was demonstrated in the aortic stenosis group (r = 0.48, p less than 0.05), probably because hypertrophy helps to keep wall stress normal or low despite progressive ventricular enlargement in these patients. The end-systolic stress/volume ratio was also inversely related to left ventricular chamber size in patients with volume overload due to aortic regurgitation (r = 0.80, p less than 0.001) and in those with cardiomyopathy (r = 0.84, p less than 0.001). However, at a given left ventricular end-diastolic volume, the end-systolic stress/volume ratio was higher in patients with aortic regurgitation than in those with cardiomyopathy, suggesting better contractile performance for a comparable degree of ventricular dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular regional dysfunction induced by intracoronary papaverine in patients with isolated stenosis of the left anterior descending coronary artery

Intracoronary papaverine was administered to eight subjects with normal coronary arteries and to nine patients with single-vessel disease of the left anterior descending coronary artery. All patients had normal left ventricular function at baseline. After papaverine, global and regional ventricular function were unchanged in the normal group. In patients with left anterior descending coronary artery stenosis, intracoronary papaverine resulted in significant wall motion abnormalities and decrease of ejection fraction (from 65 +/- 6% to 54 +/- 9%, p less than 0.01). A full spectrum of responses was observed, however, in these patients, some having almost no change of regional wall motion while others had large anterior dyskinesis. No relationship was found between the severity of the stenosis and the amount of regional dysfunction induced by intracoronary papaverine. These data demonstrate the lack of relationship between the angiographic severity of a stenosis and its impact on left ventricular segmental contraction. This suggests that techniques aimed at producing wall motion abnormalities by means of coronary anterior vasodilation may not be recommended as first-line strategy for the detection of patients with coronary artery disease.