Search PubMed⌕ Search

Biomedical subjects

M F Rousseau

Publications and source records attributed to M F Rousseau.

At least 37 records · Page 2Linked to original sources
PubMed1993

Nisoldipine in severe ischaemic left ventricular dysfunction.

The use of calcium antagonists in patients with severe dysfunction is controversial because agents like verapamil, diltiazem and nifedipine have been shown to worsen or precipitate congestive heart failure. However, successive improvements in our understanding of the clinical pharmacology of these drugs, of their pharmacokinetics and of their action on several neuro-humoral regulatory mechanisms have led to a continuous improvement of the molecules available. Promising results have been obtained with nisoldipine in patients with ischaemic left ventricular dysfunction (improved exercise tolerance, improved diastolic filling probably related to a relative improvement of chronically ischaemic areas) and other studies are exploring the effects of the combination of nisoldipine with an ACE-inhibitor. Soon, these trials should tell us if there is a real clinical benefit in the use of this agent not only to improve symptoms but also to slow down progression of the ventricular dysfunction.

Coronary Circulation↗
PubMed1993

Effects of long-term enalapril therapy on left ventricular diastolic properties in patients with depressed ejection fraction. SOLVD Investigators.

BACKGROUND: The aim of the present study was to analyze the changes in left ventricular diastolic function that occur in patients with chronic severe left ventricular systolic dysfunction in the absence or presence of prolonged therapy with an angiotensin converting enzyme inhibitor. METHODS AND RESULTS: Left ventricular function data (cineangiography plus Millar, frame-by-frame analysis) and right ventricular volumes (radionuclide angiography) were obtained at baseline and after an average follow-up of 12.4 months in 42 patients with a left ventricular ejection fraction of 35% or less. After baseline measurements, the patients were randomized to placebo (n = 16) or enalapril (10 mg BID, n = 26). In the placebo group, the changes in left ventricular function were characterized by increases in end-diastolic (159 +/- 43 to 170 +/- 44 mL/m2) and end-systolic (119 +/- 38 to 128 +/- 49 mL/m2) volumes accompanied by a downward and rightward shift of the diastolic pressure-volume relation. In contrast, decreases in end-diastolic (166 +/- 43 to 156 +/- 47 mL/m2) and end-systolic (125 +/- 43 to 111 +/- 42 mL/m2) volumes accompanied by a slight upward and leftward shift of the diastolic pressure-volume relation were noted in the enalapril group. These changes in left ventricular volumes were significantly different between groups (both P < .005) but were not attended by changes in left ventricular end-diastolic pressure, in time constant of isovolumic pressure decrease, or in right ventricular volumes. However, the chamber stiffness constant beta decreased from 0.044 +/- 0.027 to 0.032 +/- 0.019 mL-1/m2 in the placebo group, whereas it increased insignificantly in the enalapril group (0.040 +/- 0.028 to 0.041 +/- 0.028 mL-1/m2). These changes in chamber stiffness constant beta between baseline and follow-up were significantly different between placebo and enalapril groups (P < .05). Another index of chamber compliance, delta V/delta P, also confirmed the presence of opposite changes in left ventricular chamber compliance in the placebo group and in the enalapril group. The mean diastolic wall stress increased with placebo but not with enalapril (+51 versus -13 kdyn/cm2; P < .04) whereas left ventricular mass and the indexes of left ventricular sphericity tended to improve in the enalapril group. The changes in plasma levels of norepinephrine, atrial natriuretic peptide, and arginine vasopressin were, however, comparable in both groups. CONCLUSIONS: The data indicate that in patients with severe systolic left ventricular dysfunction, the progressive left ventricular dilatation was accompanied by a decrease in left ventricular chamber stiffness; enalapril therapy was able to prevent or partially reverse these changes and tended to reduce left ventricular mass and ventricular sphericity. Those changes were suggestive of partial reversal of left ventricular remodeling by enalapril administration.

Adult↗
PubMed1993

Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators.

BACKGROUND: Patients with heart failure and reduced left ventricular (LV) ejection fraction (EF) manifest progressive LV dilatation, which is prevented by angiotensin converting enzyme (ACE) inhibitors. In patients with asymptomatic LV systolic dysfunction, in whom there is less activation of the renin-angiotensin system, ventricular remodeling might be less rapid and the benefit of ACE inhibitors less discernible. METHODS AND RESULTS: One hundred eight patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial, with left ventricular ejection fraction < or = 0.35 but without clinical heart failure, underwent radionuclide ventriculograms, and 49 underwent left heart catheterizations. Measurements were made before and after double-blinded randomization to enalapril (2.5 to 20 mg/d) or placebo. Repeated-measures analysis of all time points showed significant differences for change in end-diastolic volume (EDV) between enalapril and placebo groups. Significant difference between the enalapril and placebo groups (P < .05) was present for change in EDV at 1 year within the catheterization study and at a mean of 25 months within the radionuclide study. Radionuclide EDV increased in placebo patients (119 +/- 28 to 124 +/- 33 mL/m2, mean +/- SD) and decreased in enalapril patients (120 +/- 25 to 113 +/- 25 mL/m2). Differences between the two groups were significantly less than previously described in patients with symptomatic heart failure (P < .02), with less increase in LV volumes in the placebo group and less decrease in volumes in the enalapril group. CONCLUSIONS: Chronic ACE inhibitor treatment slows or reverses LV dilatation in patients with asymptomatic LV systolic dysfunction. Compared with symptomatic patients, asymptomatic patients manifest a slower rate of spontaneous LV dilatation and less reduction in LV volumes by enalapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Cardiac mechanics during development of heart failure. SOLVD Investigators.

BACKGROUND: The changes in myocardial performance responsible for the progression from a stage of asymptomatic left ventricular dysfunction toward overt congestive heart failure are still poorly understood. Accordingly, using invasive methods, we examined the differences in baseline left ventricular function between a subgroup of patients enrolled in the treatment arm (presence of congestive heart failure) and in the prevention arm (asymptomatic patients) of the Studies of Left Ventricular Dysfunction. METHODS AND RESULTS: High-fidelity left ventricular pressures and frame-by-frame angiographic volumes were simultaneously obtained under baseline conditions in 65 patients with left ventricular ejection fraction < or = 35%. Sixteen patients had New York Heart Association congestive heart failure (class II or III), whereas the remaining 49 patients had no clinical signs of heart failure and did not receive therapy for this syndrome. A second set of data was obtained an average of 12.4 months later in 42 patients. The group with heart failure had significantly greater end-diastolic and end-systolic volumes than the asymptomatic group (both p < 0.001), but the stroke index at rest was similar in both groups. Accordingly, ejection fraction was significantly lower in the heart failure group (19.6 +/- 7.0% versus 26.3 +/- 7.2%; p < 0.02). Left ventricular end-diastolic pressure was greater and peak +dP/dt was lower in heart failure patients, but the difference did not reach statistical significance after Bonferroni correction for multiple comparisons. Moreover, the individual end-systolic stress/end-systolic volume data of the heart failure patients fell within the 95% confidence interval of the relation observed in the patients without heart failure both at baseline and after 1 year of follow-up irrespective of their changes in functional status. It was also noted that during follow-up, the changes in end-diastolic and end-systolic volumes correlated linearly, as if both dimensions always shifted in parallel, whereas alterations in contractility primarily influence end-systolic volume. CONCLUSIONS: These observations are compatible with the hypothesis that a depression in the mechanical performance of the viable myocardial areas is not the major determinant for the progression from asymptomatic to symptomatic left ventricular dysfunction. Abnormalities in left ventricular diastolic distensibility, on the other hand, might underlie the progressive ventricular dilation and create a vicious cycle through the afterload mismatch.

Adult↗
PubMed1992

Diastolic function of the nonfilling human left ventricle.

OBJECTIVES: To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. BACKGROUND: When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. METHODS: Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. RESULTS: The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (T(asy)) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for T(asy) (37 +/- 9 ms) was significantly smaller than that for TBF (68 +/- 28 ms, p less than 0.001) and the value for the measured diastolic left ventricular asymptote pressure (2 +/- 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 +/- 11 mm Hg, p less than 0.001). T0 (44 +/- 20 ms) was significantly (p less than 0.01) different from TBF but not from T(asy). CONCLUSIONS: During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and T0 was a better measure of T(asy) than was TBF. Reduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart.

Adult↗
PubMed1992

Analysis of the mechanisms underlying the changes in left ventricular filling dynamics during oral nisoldipine therapy in patients with anterior myocardial infarction.

The aim of this study was to clarify the mechanisms responsible for the increase in early filling rate observed during oral nisoldipine therapy in patients with ischaemic left ventricular (LV) dysfunction. For that purpose, the global and regional LV function was analysed before and after 2 months of double-blind monotherapy with nisoldipine (10 mg twice daily) or a placebo, in 17 patients with a previous anterior myocardial infarction. The baseline LV ejection fraction ranged from 34-51% and no patient had heart failure. Compared to the placebo, nisoldipine significantly lowered LV systolic pressure and end-diastolic pressure (-3 mmHg vs +6 with the placebo; P less than 0.01) and the LV pressure at the time of mitral opening (-2.0 +/- 3.4 mmHg vs +3.5 +/- 3.0; P less than 0.01). Despite this reduction in driving pressure, the global LV early peak filling rate improved with nisoldipine only and this improvement was related to a selective increase in expansion rate of the anterior areas, from 1010 +/- 360 to 1339 +/- 496 mm2.s-1 (P less than 0.001). The time to regional peak filling rate (-8%; P less than 0.01), the asynchrony of diastolic wall motion and the regional ejection fraction (33 +/- 10 to 38 +/- 12%; P less than 0.001) also improved in the anterior areas with nisoldipine but not with the placebo. In contrast, in the inferior, control zones, the regional ejection fraction and filling rate remained unchanged, both when compared to baseline and to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of intravenous epinine administration on left ventricular systolic performance, coronary hemodynamics, and circulating catecholamines in patients with heart failure.

Twenty-six patients with mild to moderate heart failure were studied to determine the effects of epinine infusion (at a rate producing plasma levels similar to those measured after oral administration of 100 mg of the prodrug ibopamine) on left ventricular (LV) function (14 patients), and coronary flow and circulating catecholamines (12 patients). The only significant hemodynamic change at an infusion rate of 0.5 microgram/kg/min was a 9% (p less than 0.05) decrease in systemic vascular resistance (SVR). At an infusion rate of 1 microgram/kg/min (mean free epinine plasma levels 14.3 +/- 3.7 ng/ml), heart rate (HR), dP/dtmax (1,405 +/- 255 to 1,490 +/- 320 mm Hg, NS), (dP/dt)/DP40, and the relaxation rate remained unchanged, but the ejection fraction (EF) increased from 32 to 38% (p less than 0.001), cardiac output (CO) increased, and SVR decreased by 22% (p less than 0.05). In a separate group of 12 patients, epinine infusion at rates of 0.5-1 microgram/kg/min produced no significant changes in coronary blood flow or myocardial oxygen uptake. At these infusion rates, arterial norepinephrine (NE) and dopamine (DA) levels decreased slightly and arterial and coronary sinus epinephrine increased. In conclusion, epinine, at concentrations similar to those achieved during therapeutic use of ibopamine, had negligible effect on myocardial contractility and relaxation rate in heart failure patients. Cardiac pump function was improved by a decrease in SVR rather than by inotropic stimulation. The data also suggest that these low concentrations of epinine may modulate the sympathetic nervous system, but further studies are needed to determine whether this effect could have clinical significance.

Adult↗
PubMed1992

Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators.

BACKGROUND: In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure. METHODS AND RESULTS: We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo. CONCLUSIONS: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Effects of prolonged nisoldipine administration on the "hibernating" myocardium.

To assess the effects of nisoldipine on chronically underperfused myocardial areas ("hibernating myocardium"), the global and regional left ventricular (LV) function was analyzed before and after 2 months of double-blind monotherapy with nisoldipine (10 mg twice daily) or placebo in 17 patients with a previous anterior myocardial infarction. The baseline LV ejection fraction ranged from 34 to 51%, and no patient had heart failure. Compared to placebo, nisoldipine significantly lowered the LV systolic pressure and end-diastolic pressure (-3 vs. +6 mmHg with placebo; p < 0.01) and the LV pressure at the time of mitral valve opening (-2.0 +/- 3.4 vs. +3.5 +/- 3.0 mm Hg; p < 0.01). Despite this reduction in driving pressure, the global LV early peak filling rate improved only with nisoldipine and this improvement was related to a selective increase in the expansion rate of the anterior areas, from 1,010 +/- 360 to 1,339 +/- 496 mm2/s (p < 0.001). The time to regional peak filling rate (-8%; p < 0.01), the asynchrony of diastolic wall motion, and the regional ejection fraction (33 +/- 10 to 38 +/- 12%; p < 0.001) also improved in the anterior areas with nisoldipine but not with placebo. In contrast, in the inferior control zones, the regional ejection fraction and filling rate remained unchanged, both when compared to baseline and to placebo. In conclusion, prolonged nisoldipine therapy had no significant effect on the normal myocardium but improved systolic and diastolic function in hypokinetic areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1992

Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem.

Ranolazine (RS 43285) is a new piperazine derivative with anti-ischemic properties attributed to a modulation of myocardial metabolism. Its antianginal action was assessed in 104 patients recruited in a double-blind, crossover, randomized study comparing placebo with a single dose of ranolazine (10, 60, 120, and 240 mg). All patients had chronic stable angina pectoris and remained symptomatic (at least 0.1 mV ST-segment depression and angina during prestudy exercise testing) despite treatment with a beta-blocker or with diltiazem. No significant effects of ranolazine on exercise duration or time to angina were observed after the dose of 10, 60, and 120 mg. After the 240 mg dose, however, significant improvement in exercise duration (+13.1% in the combined group, two-tailed p = 0.002; +14.3% in the beta-blocker group, p = 0.009; +11.9% in the diltiazem group, p = 0.06), in time to angina (+56.8 s, p = 0.008), and in time to 1 mm ST-segment depression was observed. The cumulative proportion of patients who improved their time to angina by at least 30 s above placebo were 25, 42, 50, and 72% with the doses of 10, 60, 120, and 240 mg, respectively. Sixty-seven percent of the patients with ranolazine plasma levels above 500 ng/ml improved their time to angina against 40% at plasma levels below 500 ng/ml and summed ST-segment depression during exercise and recovery was also significantly reduced at these plasma concentrations. Both heart rate and arterial pressure at rest and at peak exercise were unchanged after ranolazine, 240 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetanilides↗
PubMed1991

Difference in mortality between patients treated with captopril or enalapril in the Xamoterol in Severe Heart Failure Study.

The double-blind, placebo-controlled, multinational trial Xamoterol in Severe Heart Failure randomized 290 patients treated with captopril and 217 treated with enalapril to xamoterol or placebo. At the end of the 100-day follow-up period, the cumulative probability of survival in patients with coronary artery disease or with dilated cardiomyopathy decreased in the captopril group (90.3%) when compared with the enalapril group (97.2%). The excess mortality in the captopril group could not be related to the indexes of the severity of heart failure, such as baseline exercise duration, functional class, cardiothoracic ratio, ejection fraction or dose of diuretic drugs. Furthermore, the excess in mortality was seen in all subsets of patients examined as well as across countries. Examination of the dosing regimen used, however, suggests that insufficient daily dosage of captopril or the inadequate schedule of administration, or both, might be responsible for different degrees of angiotensin-converting enzyme inhibition between the enalapril and captopril groups and hence for the difference in mortality. It is important in future clinical trials to determine to what extent complete circadian angiotensin-converting enzyme inhibition is necessary to provide the full benefit of this therapy in heart failure.

Adrenergic beta-Agonists↗
PubMed1991

Dopaminergic drugs in the management of chronic heart failure.

The importance of the dopaminergic system in heart failure is unknown and the therapeutic potential of orally active compounds stimulating dopaminergic receptors has yet to be established. Despite similar acute haemodynamic changes in heart failure and despite a comparable profile of receptor stimulation, oral levodopa (the prodrug of dopamine) and oral ibopamine (the prodrug of epinine) produce opposite effects on plasma norepinephrine and have different pharmacokinetics. Placebo-controlled studies indicate a beneficial effect of ibopamine on exercise tolerance in patients with heart failure, whereas invasive evaluation of left ventricular function indicate that at the doses used in these trials, ibopamine does not act as a positive inotropic drug but rather as a vasodilator. This suggests that DA1 and DA2 receptor stimulation may be beneficial in heart failure. Further studies are, however, needed to specify the exact role of this therapeutic approach in comparison with other agents, such as ACE inhibitors, also able to modulate neuro-humoral activation in heart failure.

Adult↗
PubMed1990

Clinical experience of therapy with xamoterol in patients with severe systolic and diastolic dysfunction.

Xamoterol ('Corwin', 'Carwin', 'Corwil', 'Xamtol', ICI118, 587)*, a partial beta-agonist, has beneficial effects in patients with mild to moderate heart failure. In acute haemodynamic studies in more severe heart failure some patients have shown negative inotropic and chronotropic effects, although treatment with a partial agonist should protect the heart against excessive stimulation, while providing a baseline level of sympathetic drive. This study examined the effects of oral xamoterol in patients with moderate to severe heart failure. Ten patients were studied, nine with ischaemic heart disease. All but one were in New York Heart Association (NYHA) functional Class III. Other treatment, including angiotensin converting enzyme (ACE) inhibitors, was continued. The patients underwent a standard bicycle exercise test, and the following day cardiac catheterization was performed to obtain measurements of ventricular size (by cineangiography) and pressures during the cardiac cycle. The patients began treatment with xamoterol 200 mg b.d. in addition to their baseline therapy, and this was continued for an average of 9 weeks, after which the exercise test and the haemodynamic investigations were repeated. At baseline, all patients had a raised left ventricular end-diastolic pressure (LVEDP) and nine had a low election fraction, raised end-systolic and end-diastolic volume indices and reduced left ventricular (+) dP/dtmax Xamoterol produced a marked reduction in left ventricular filling pressure, a fall in end-systolic volume index and improvements in T1, (+) dP/dtmax and (dP/dt)/DP40 with no change in mean aortic pressure. Duration of exercise increased in four patients, and did not change in the other four tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1990

Illustration of the effects of long-term xamoterol therapy on the time course of left ventricular pressure.

Detailed left ventricular haemodynamic investigations were performed in eight patients with New York Heart Association (NYHA) Class II heart failure, eight with NYHA Class III heart failure with an ejection fraction less than 35%, and six with severe heart failure. Xamoterol (200 mg b.d. for 3 months) caused a fall in left ventricular end-diastolic pressure, an increase in dP/dTmax and a shorter systole in all groups of patients.

Adrenergic beta-Agonists↗