Biomedical subjects

I Antony

Publications and source records attributed to I Antony.

At least 37 records · Page 2Linked to original sources

PubMed1995

Loss of flow-dependent coronary artery dilatation in patients with hypertension.

BACKGROUND: Abnormal endothelium-dependent coronary response to acetylcholine has been shown in patients with essential hypertension. We tested the hypothesis that flow-dependent dilatation, which has been shown in normal human coronary arteries, is impaired in hypertensive patients. METHODS AND RESULTS: The coronary vasomotor response to maximal increase of blood flow induced by papaverine was studied in 10 control subjects and in 14 hypertensive patients with no other risk factors and angiographically normal coronary arteries. After the injection of papaverine in the midportion of the left anterior descending coronary artery (LAD), the diameter of the proximal LAD (LAD1) was measured by quantitative angiography, whereas that of the proximal circumflex artery (LCx) served as control segment. Estimates of coronary blood flow in the distal LAD (LAD2) were calculated by intracoronary Doppler flow velocity measurements. An increase in LAD2 blood flow of 521 +/- 41% (P < .001) in control subjects was associated with a 17.0 +/- 3.3% dilatation of the LAD1 (P < .001) and with no significant change in the diameter of the LCx. In hypertensive patients, despite a comparable increase in LAD2 blood flow of 406 +/- 32% (P < .001), the LAD1 failed to dilate (-0.4 +/- 0.6%, NS). The dilative response to isosorbide dinitrate was similar in control subjects and hypertensive patients (30.0 +/- 4.1%, P < .001 and 21.9 +/- 1.9%, P < .001, respectively). CONCLUSIONS: Thus, the flow-mediated coronary dilatation is lost in hypertensive patients, and this may impair normal dilatation observed in response to an increase in myocardial metabolic demand.

Adult↗

PubMed1995

Impairment of flow-dependent coronary dilation in hypertensive patients. Demonstration by cold pressor test induced flow velocity increase.

In normal coronary arteries, increased flow velocity induces endothelium-dependent dilation, and dilation in response to sympathetic stimulation evoked by the cold pressor test is partly due to increased flow velocity. In arterial hypertension, angiographically normal coronary arteries were constricted by acetylcholine, an endothelium-dependent vasodilator. To assess the epicardial coronary artery response to the increase blood flow velocity induced by the cold pressor test in hypertensive patients with angiographically normal coronary arteries, coronary artery diameters and flow velocity were measured during cold pressor test in 12 untreated hypertensive patients and in 10 control subjects. Diameters were determined by quantitative angiography on proximal and distal segments of the left anterior descending coronary artery, and flow velocity measurements were made by Doppler testing in the distal segment. In control subjects, the proximal and distal segments dilated during cold pressor test by 12.0 +/- 4.5% and 13.9 +/- 6.5%, respectively (both P < .001), when flow velocity increased by 46.7 +/- 26.1% (P > .05). In hypertensive patients, segments were constricted, respectively, by 10.3 +/- 8.5% (P < .001) and 7.9 +/- 8.6% (P < .01), when the flow velocity was increased by 68.3 +/- 48.2% (P < .001). Intracoronary injection of an endothelium-independent dilator resulted in similar dilation in control subjects (proximal: +30.0 +/- 12.9%; distal: +32.4 +/- 15.2%) and in hypertensive patients (proximal: +22.3 +/- 7.5%; distal: +28.8 +/- 15.4%). In conclusion, in hypertensive patients with angiographically normal coronary arteries and without any other coronary risk factors, endothelium-dependent flow-mediated coronary dilation evoked by the cold pressor test is impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

PubMed1995

Left ventricular diastolic function in asymptomatic and symptomatic human immunodeficiency virus carriers: an echocardiographic study.

Acquired immunodeficiency syndrome (AIDS) is a systemic illness affecting multiple organs, including the heart. Left ventricular (LV) diastolic dysfunction has been reported as the first echocardiographically detectable abnormality in several cardiovascular disorders. We tested the hypothesis that Human Immunodeficiency Virus (HIV) carriers have LV diastolic impairment when studied early in the clinical course of the infection. Doppler echocardiographic and computerized time-motion parameters of LV diastolic function were obtained in 51 HIV patients and in 25 age- and sex-matched healthy controls. The HIV population consisted of 28 totally asymptomatic subjects and 23 patients with incipient AIDS. As compared to controls, the HIV group had similar heart rate, blood pressure level, LV dimensions and fractional shortening, but increased isovolumetric relaxation time (P = 0.03), early filling duration (P < 0.001) and decreased early mitral flow peak velocity (E) (P = 0.02) and EF slope (P < 0.001). HIV patients also showed lower values for posterior wall thinning (PWT, P < 0.01) and peak lengthening velocity of the posterior wall (PVL, P < 0.05), and a trend to a decreased peak rate of LV enlargement in diastole (D+, P = 0.05). Doppler-derived parameters of diastolic function were significantly altered in the asymptomatic HIV group vs controls. The LV diastolic indices were similar in symptomatic and asymptomatic HIV patients except for PWT, which was lower in the symptomatic HIV group (P = 0.04). Since mild and focal wall motion abnormalities were detected in 11 HIV carriers (22%), comparison of LV diastolic indexes between HIV patients and controls was also performed in two subgroups; these included asymptomatic (n = 26) and symptomatic (n = 14) patients with normal contractile state. The two subgroups had abnormalities of diastolic function similar to those of the HIV group as a whole, but with somewhat lower levels of statistical significance. Our data strongly suggest that there is myocardial involvement at the early stage of HIV infection; however, its impact on the clinical course of the disease remains to be clarified.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Coronary vascular reserve in humans: a critical review of methods of evaluation and of interpretation of the results.

The concept of coronary vascular reserve stems from the description of coronary autoregulation by Mosher in 1964. Schematically, the coronary blood flow at rest depends on the determinants of myocardial oxygen demand (heart rate, contractility and ventricular load). If maximal coronary vasodilation is produced, it results in a linear and steep pressure-flow relationship. The increment of coronary flow above its basal value is called the coronary flow reserve, which indicates the flow added to the basal flow for a given coronary perfusion pressure when the coronary vascular bed is maximally dilated. Thus, in the absence of epicardial coronary artery stenosis, the maximal coronary flow is a function of the coronary perfusion pressure and of the maximal surface area of the coronary circulation at the resistance vessel level. Evaluation of the coronary reserve in humans raises three major concerns: (1) methods for measuring or evaluating coronary flow are imprecise and inconvenient (diffusible indicators), invasive (coronary sinus thermodilution, intracoronary Doppler), expensive and require sophisticated technology (ultrafast computed tomography, positron emission tomography), or in the process of being validated (contrast echocardiography, transoesophageal Doppler echocardiography, myocardial scintigraphy: (2) the compounds used to produce maximal coronary vasodilation are administered either by the intracoronary route (papaverine) or intravenously (dipyridamole, adenosine); (3) how to interpret the data: is the alteration of the coronary reserve due to a modification of the basal coronary flow or/and of the maximal coronary flow? Thus, each method has its own limitations and constraints that must be taken into account in order to avoid crude misinterpretations. In conclusion, the measurement of coronary reserve may be an important means of understanding coronary physiology and pathophysiology. Recently developed non-invasive methods (ultrafast computed tomography, positron emission tomography, echography) and the ability to produce maximal coronary vasodilation by the intravenous route are promising.

Angiography, Digital Subtraction↗

PubMed1995

Dipyridamole slows the rate of isovolumic pressure fall in patients with normal coronary arteries.

Dipyridamole is currently used for thallium imaging and stress echocardiography. The coronary and haemodynamic effects of dipyridamole are well documented while its effects on left ventricular relaxation remain to be determined. The aim of the present study was to evaluate the effects of dipyridamole on left ventricular relaxation rate in healthy subjects. High fidelity pressure recordings were obtained at fixed atrial pacing (89 +/- 2 beats.min-1) in 10 subjects with normal left ventricular angiography and coronary arteriograms. Left ventricular pressure was recorded at rest and 5 min after a 4 min infusion of dipyridamole (0.14 mg.kg-1.min-1). Dipyridamole infusion decreased left ventricular systolic pressure (P < 0.01) and time to left ventricular systolic pressure (P < 0.01), with no changes in end-diastolic pressure or peak rate of pressure rise. The peak rate of isovolumic pressure fall decreased (from 1957 +/- 105 to 1488 +/- 100 mmHg.s-1, P < 0.01) and the time constant of isovolumic relaxation increased (from 37 +/- 2 to 44 +/- 3 ms, P < 0.02). In conclusion, our study indicates that acute administration of clinically relevant doses of dipyridamole displays deleterious effects on heart relaxation in healthy humans.

Arteries↗

PubMed1995

[Restoration of normal coronary vasomotricity after intravenous infusion of angiotensin converting-enzyme inhibitor (perindoprilat) in hypertensive patients].

We have previously shown that in hypertensive patients, the response of normal coronary arteries to sympathetic stimulation evoked by the cold-pressor test (CPT), and the endothelial-mediated flow-dependent coronary vasodilation were impaired. The immediate effects of the converting-enzyme inhibitor perindoprilat (PER) have been evaluated in 10 untreated hypertensive patients with angiographically normal coronary arteries and results have been compared to the normal responses of 10 control subjects. Diameter changes of proximal left anterior descending coronary artery (pLAD) and coronary flow velocity in distal LAD have been measured at baseline, during CPT, during recontrol, and after 10 mg papaverine (PAP) injection in the mid portion of the LAD. Measures have been repeated after intravenous infusion of 1 mg PER, and at the end of the procedure after 2 mg intracoronary injection of isosorbide dinitrate (ISDN). Left ventricular dimensions and systolic function, total cholesterol, triglycerides, HDL and LDL-cholesterol were within the normal range. In hypertensive patients before PER, pLAD constricted in response to the CPT and no diameter change was observed after PAP, despite the increase in flow velocity in the 2 conditions (+63 +/- 27%, and +412 +/- 77%, respectively; all p < 0.001). In control subjects, pLAD dilated significantly in these 2 conditions. In hypertensive patients after PER, pLAD dilated similarly to control subjects in the 2 conditions. Endothelium-independent coronary dilation to ISDN was comparable in the 2 groups of patients. In conclusion, PER restores a normal coronary response both to sympathetic stimulation due to CPT and to flow increase in hypertensive patients with angiographically normal coronary arteries and without any other coronary risk factors.

Adult↗

PubMed1995

[Coronary artery caliber is not adapted to myocardial oxygen demand in hypertensive patients with angiographically normal coronary arteries].

Resting myocardial oxygen demand and corresponding coronary blood flow are main determinants of large coronary artery dimensions in humans. To examine the adaptation of epicardial coronary arteries to the increased myocardial oxygen demand, myocardial blood flow, in hypertensive patients, diameters of proximal and distal left anterior descending coronary artery (pLAD and dLAD), and proximal circumflex artery (CX) were determined in 15 untreated hypertensive patients and in 10 control subjects by quantitative angiography. All patients had total cholesterol < or = 5.40 mmol/l, LDL-cholesterol < or = 3.35 mmol/l, and angiographically normal coronary arteries. Measurements were made at base and after 2 mg intracoronary isosorbide dinitrate (ISDN) in order to obtain maximal dimensions of vessels. Coronary flow velocity was measured in distal left anterior descending coronary artery by Doppler. Results show that despite higher rate-pressure product in hypertensive patients, the diameters of the coronary segments were similar in control subjects and in hypertensive patients at base (3.53 +/- 0.84 vs 3.76 +/- 0.48 mm for pLAD; 2.55 +/- 0.50 vs 2.49 +/- 0.52 mm for dLAD; 2.92 +/- 0.40 vs 2.78 +/- 0.83 mm for CX, respectively). After intracoronary ISDN, diameters were also comparable between the 2 groups (4.54 +/- 0.86 vs 4.58 +/- 0.60 mm for pLAD; 3.35 +/- 0.58 vs 3.22 +/- 0.61 mm for dLAD; 3.47 +/- 0.56 vs 3.53 +/- 1.01 mm for CX, respectively). Conversely, coronary flow velocity was significantly higher in hypertensive patients at base (10.72 +/- 2.20 vs 6.48 +/- 2.01 cm/s; p < 0.001) and after ISDN (6.59 +/- 2.62 vs 3.72 +/- 0.87 cm/s; p < 0.001). Despite an elevated myocardial oxygen demand, large coronary artery dimensions are not increased in hypertensive patients resulting in an elevated coronary flow velocity that may increase longitudinal shear stress at the endothelial surface. This might be an important determinant in the pathogenesis of atherosclerosis in hypertensive patients.

Adaptation, Physiological↗

PubMed1994

Coronary artery constriction caused by the cold pressor test in human hypertension.

Hypertensive patients with angiographically normal coronary arteries may have myocardial ischemia when metabolic demand increases. Abnormal epicardial coronary artery vasomotion in response to sympathetic stimulation may contribute to ischemia in such patients. We studied the vasomotor response of smooth coronary arteries to a cold pressor test in 10 hypertensive patients without other risk factors and in 9 control subjects. Vessel dimensions were measured by quantitative angiography, and blood flow was calculated using an intracoronary Doppler catheter in the left anterior descending coronary artery. In response to cold pressor stimulation, arteries of control subjects dilated 13.0 +/- 5.9% (P < .001), and they constricted 8.2 +/- 8.5% in hypertensive patients (P < .001). Rate-pressure product increased from 9466 +/- 1677 to 12,547 +/- 2367 beats per minute (bpm).mm Hg in control subjects (P < .001) and from 13,720 +/- 1823 to 17,353 +/- 2037 bpm.mm Hg in hypertensive patients (P < .001). Coronary blood flow velocity and blood flow increased 51 +/- 26% (P < .05) and 87 +/- 27% (P < .001), respectively, in control subjects and 68 +/- 52% (P < .05) and 36 +/- 33% (P < .01) in hypertensive patients. At peak cold pressor test, despite a significant higher rate-pressure product in hypertensive patients, blood flow was similar in both groups, suggesting an uncoupling between myocardial metabolic demand and supply. Thus, hypertension impairs the vasodilator response of angiographically normal coronary arteries to a cold pressor test. This abnormal response may be due to enhanced catecholamine reactivity and/or impairment of endothelial flow-mediated vasodilator response.

Adult↗

PubMed1994

[Changes in coronary vasodilation in hypertensive patients with angiographically normal coronary arteries].

In normal subjects, coronary arteries dilate in response to sympathetic stimulation evoked by the cold pressor test. Similarly, in normal coronary arteries the increase in blood flow velocity induced by papaverine results in flow-dependent coronary dilation. In order to assess the coronary responses to both stimuli in hypertensive patients, variations of proximal left anterior descending coronary artery diameters and coronary blood flow velocity have been measured using quantitative coronary angiography and intracoronary Doppler in 10 control subjects and in 12 hypertensive patients. All the patients had angiographically normal coronary arteries. Total serum cholesterol, triglycerides, HDL- and LDL-cholesterol were within normal range in all patients. All patients were nonsmokers and none of them had diabetes mellitus. During the cold pressor test (hands immersed in ice water for 120 s), the rate-pressure product and coronary blood flow velocity increased respectively by 33 +/- 9% (p < 0.001) and 51 +/- 26% (p < 0.05) in control subjects, by 28 +/- 18% (p < 0.001) and 68 +/- 52% (p < 0.05) in hypertensive patients. In control subjects, coronary arteries dilated by + 12.0 +/- 4.4% (p < 0.001), and constricted by -10.3 +/- 8.5% (p < 0.001) in hypertensive patients. After injection of 10 mg of papaverine into the distal left anterior descending coronary artery, proximal left anterior descending coronary artery dilated by + 17.0 +/- 10.6% (p < 0.001) in control subjects, and did not vary (-0.7% +/- 10.6%) in hypertensive patients, when blood flow velocity was increased respectively by 449 +/- 97% and 383 +/- 103% (p < 0.001 in both groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Clinical review of perindopril in the treatment of hypertension.

Perindopril is a long acting angiotensin-converting enzyme inhibitor with a perhydroindole group and no sulphydryl radical. Perindopril is a pro-drug that is hydrolyzed to the active metabolite perindoprilat. Perindopril is rapidly absorbed, reaching peak plasma concentrations about 1 h after a single oral dose. Its bioavailability is greater than 70% and is not influenced by meals. Perindoprilat reaches peak plasma concentrations 3 to 4 h after administration. The blood pressure lowering effect of perindopril has been shown in animal models with spontaneous and renovascular hypertension. In hypertensive patients dose response studies have shown a significant and linear relationship between the dose and the activity of perindopril. The antihypertensive efficacy of 4 and 8 mg doses is significantly greater than that of 2 mg or of placebo. The maximal response is attained about 4 to 6 h after the first dose. As demonstrated by 24 h blood pressure recordings in ambulatory patients, the antihypertensive activity of perindopril was still significant 24 h after the last dose. Clinical trials have indicated that perindopril is at least as effective as usual therapeutic doses of captopril, atenolol or a combination of hydrochlorothiazide plus amiloride in mild to moderate essential hypertension. Oral administration of 4 to 8 mg od significantly reduced supine and standing systolic and diastolic blood pressure, and adequate diastolic blood pressure control was attained in about 60 to 70% of patients with monotherapy. In the majority of patients, hypertension was controlled with a daily dose of 4 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗

PubMed1993

Acceptability of perindopril in mild-to-moderate chronic congestive heart failure. Results of a long-term open study in 320 patients.

The long-term acceptability of perindopril in mild-to-moderate chronic heart failure (CHF) was evaluated in a multicenter open study. A total of 320 patients with a mean age of 62 +/- 1 years and CHF of New York Heart Association (NYHA) class I (2 patients), II (204 patients), or III (114 patients) were included after a 2-week run-in period during which time vasodilators were stopped and diuretic and/or digoxin therapy stabilized. Perindopril treatment was started at 2 mg, increasing to 4 mg once daily after 2 weeks if supine systolic blood pressure remained > 100 mm Hg. After this dose titration period, follow-up visits were scheduled at monthly intervals for the first 3 months, then at 3-month intervals with a maximum period of follow-up being 30 months. At the time of analysis, mean duration of treatment was 276 days and 208 patients were treated > or = 6 months. Of the 320 patients, 10 (3.1%) died, 9 (2.8%) were withdrawn for worsening heart failure, and 38 (11.9%) for nonfatal adverse events, including cough (2.8%), dizziness or orthostatic discomfort (1.9%), angina pectoris (1.6%), and cutaneous signs (1.3%). Exercise test duration increased from 516 +/- 14 to 659 +/- 19 sec after 6 months of treatment (p < 0.01). At 6 months, 55.6% of patients improved by at least 1 NYHA class. Supine systolic blood pressure decreased slightly from 137 +/- 2 to 132 +/- 1 mm Hg (p < 0.01) and plasma creatinine levels remained stable from 100 +/- 2 to 102 +/- 2 mumol/liter after 6 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

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.

Acetylcholine↗

PubMed1993

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.

Adult↗

PubMed1993

Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.

OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.

Acetylcholine↗

PubMed1993

[Coronary vasoconstriction induced by acetylcholine in young smokers with normal angiographic coronary vessels].

UNLABELLED: Cigarette smoking is a major risk of coronary artery disease. Acetylcholine-induced coronary artery constriction has been reported in patients with normal coronary arteries and other risk factors. To evaluate coronary artery endothelial function in smokers, coronary artery responses to acetylcholine (10(-8) M to 10(-5) M) were analyzed by quantitative angiography in 5 young heavy-smokers and in 5 age-matched nonsmokers. All patients were normotensive, had normal left ventricular function and coronary arteries. Cholesterol, triglycerides, high- and low-density lipoproteins were within normal range. Vessel dimensions were measured on 4 segments of left coronary artery in all patients. In smokers, no change was produced at 10(-8) M and 10(-7) M acetylcholine concentration, but progressive diameter reduction was observed at 10(-6) M and 10(-5) M acetylcholine concentration. In nonsmokers, a dose-dependent dilation was produced from 10(-8) M to 10(-6) M acetylcholine concentration. No change was observed at 10(-5) M acetylcholine concentration. In the 2 groups, all segments dilated similarly after intracoronary isosorbide dinitrate. CONCLUSION: This study reveals that in heavy-smokers the response of normal coronary arteries to acetylcholine is altered. Thus, endothelial dysfunction may be an early marker for coronary events in cigarette smokers.

Acetylcholine↗

PubMed1992

Myocardial contractility, lusitropy and calcium responsiveness in young (50 days) and hypertrophied (180 days) cardiomyopathic hamsters.

Contractility, lusitropy and responsiveness to the increase of external Ca2+ concentration were studied in left ventricular papillary muscles of normal and cardiomyopathic Syrian hamsters (SCH) from the UM-X 7.1 strain, both at the onset of myolysis (50-day-old animals) and at the cardiac hypertrophy stage (180-day-old animals) in the absence of congestive heart failure. A marked decrease in all indices of systolic performance was observed in 180-day-old myopathic hamsters as compared to age-matched controls. This was associated with (1) an impairment of the relaxation phase, (2) a loss of the load sensitivity of relaxation, and (3) a decrease in the inotropic and lusitropic responsiveness to Ca2+. On the other hand, when some indices of contraction and the inotropic response to Ca2+ were impaired in 50-day-old myopathic hamsters as compared to age-matched controls, relaxation phase and the lusitropic response to Ca2+ did not alter. This study shows that, in the UM-X 7.1 myopathic hamsters at the earlier stage of the disease, alterations in calcium homeostasis and contraction seem to be the first determinant factors of the development of heart failure when relaxation is not impaired. Conversely, when cardiac hypertrophy has developed, impaired relaxation may worsen heart failure.

Age Factors↗

PubMed1992

[Restoring normal coronary reserve in treated hypertension without left ventricular hypertrophy].

UNLABELLED: It has been previously demonstrated that coronary vascular reserve (CVR) was severely impaired in hypertensive patients with left ventricular hypertrophy (LVH), even after anti-hypertensive therapy. To assess if CVR was similarly depressed in hypertensive patients without LVH, peak-to-resting coronary flow velocity ratio (P/R) and a minimal coronary vascular resistance index (MCVRI) were determined with a coronary Doppler catheter placed into the left anterior descending coronary artery and maximally vasodilating dose of intracoronary papaverine (12 mg) in 16 control subjects (C), 7 untreated hypertensives without LVH (G1), and 7 hypertensives without LVH treated for at least one year (G2). All subjects and patients had normal left ventricular angiography and coronary arteriography. Left ventricular and aortic pressures, rate-pressure-product (RPP) were significantly elevated in G1 and were similar to those of control subjects in G2. Results evidenced that P/R was reduced and that MCVRI was increased in G1. However, these alterations were moderate. In G2, these two indices were similar to those of control subjects: [table: see text] CONCLUSIONS: These results suggest: 1) that alterations of coronary microcirculation occur before left ventricular hypertrophy in hypertensive patients; 2) that anti-hypertensive therapy may restore a normal coronary vascular reserve in hypertensive patients without LVH, when coronary vascular reserve remained severely impaired despite normalization of arterial pressure in patients with persistent LVH.

Adult↗

PubMed1991

[Unstable angina: from physiopathology to therapeutics].

Unstable angina is a term which encompasses several clinical syndromes (crescendo angina, angina de novo, resting angina, postinfarction angina), intermediary between stable angina and myocardial infarction. The results of coronary angioscopy have allowed differentiation of accelerated effort angina which seems related to ulceration of an atheromatous plaque from resting angina, more commonly associated with intraluminal thrombosis. The diagnosis of unstable angina is clinical and justifies immediate hospital admission to a coronary care unit because of the risk of myocardial infarction and/or sudden death. Medical management comprises triple anti-ischemic therapy (nitrate derivatives, betablockers, calcium antagonists), anticoagulants and platelet antiagregants. Randomised therapeutic trials versus placebo have shown that this treatment decreases the incidence of refractory angina and myocardial infarction. Several studies are under way to assess the role of thrombolytic therapy in unstable angina. When unstable angina is refractory to maximal medical therapy, emergency coronary angiography should be performed. However the outcome is usually favourable and coronary angiography can be performed several days after the acute event. The coronary lesion responsible for unstable angina is often "complex", an eccentric, irregular, severe stenosis or appearances of thrombosis. Whenever possible, depending on the coronary lesion, myocardial revascularisation by coronary angioplasty or aorto-coronary bypass should be proposed. Surgical treatment has been shown to be more effective (symptomatic relief, improved survival) than medical therapy in patients with triple vessel disease. However, the results of studies comparing medical or surgical treatment with coronary angioplasty are not yet available.

Adrenergic beta-Antagonists↗