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Biomedical subjects

F Zannad

Publications and source records attributed to F Zannad.

At least 109 records · Page 6Linked to original sources
PubMed1992

[Comparative effects of angiotensin converting enzyme inhibitors and calcium inhibitors related to baseline ambulatory blood pressure. A French multicenter study].

OBJECTIVE: This multicenter study was aimed at determining whether the baseline ambulatory blood pressure (BP) level does influence the efficacy of angiotensin-converting enzyme inhibitors (CEI) and that of calcium antagonists (CA) to the same degree. METHODS: The BP recordings of 236 patients with mild to moderate hypertension were reviewed: these subjects previously entered clinical trials comprising a mean 2-week placebo period and a mean 6-week active treatment phase (CEI = 115, CA = 121). The 24-hour baseline ambulatory BP was considered as high when greater than 139/87 mmHg, according to Staessen's meta-analysis. RESULTS: In the patients with an high baseline ambulatory BP, CEI and CA have had roughly a similar effect (reduction in systolic = 9.5 +/- 7.8% vs 7.7 +/- 6.3%, NS; reduction in diastolic = 9.8 +/- 8.6% vs 8.3 +/- 5.8%, NS). Conversely, the patients with a baseline ambulatory BP level lower than or equal to 139/87 mmHg experienced a greater reduction in ambulatory BP with CEI than with CA (systolic = 7.9 +/- 7.0% vs 0.6 +/- 6.7%, p = 0.0001; diastolic: 5.0 +/- 7.4% vs 1.9 +/- 7.6%, p = 0.040). Finally, further analysis found the threshold of drug efficacy to be 120/80 and 135/85 mmHg in CEI and CA patients respectively. CONCLUSIONS: 1) CEI are more effective than CA in patients with a low ambulatory BP only. 2) The risk of a visceral hypoperfusion seems however to be limited, since CEI do not reduce diastolic ambulatory BP further, when its baseline level is lower than 80 mmHg.

Adult↗
PubMed1991

Multicentre study of the determination of peak oxygen uptake and ventilatory threshold during bicycle exercise in chronic heart failure. Comparison of graphical methods, interobserver variability and influence of the exercise protocol. The VO2 French Study Group.

Assessment of the ventilatory threshold (VT) has been proposed to assess exercise tolerance more objectively, particularly in clinical trials, but reproducibility, interobserver variability and feasibility of the graphical methods for determination of VT have not been properly studied in patients with chronic heart failure (CHF). Fifty-one patients with mild to moderate CHF (mean peak oxygen uptake (VO2): 20.5 ml.min-1.kg-1) were assessed during two consecutive bicycle exercise tests within 8 days. Two graded exercise protocols were compared with stages of 30 W every 3 min (22 patients) or 10 W/min (29 patients). VT was determined separately by five trained physicians using five different graphical methods. The 'crossing method' (first crossing of the VCO2 and VO2 curves) yielded the highest rate of determination (88%) but tended to overestimate the mean VT. The VE method (disproportionate increase of ventilation relative to VO2) produced the best interobserver agreement (coefficient of variation = 78%). Peak VO2 was very highly reproducible in both exercise protocols (relative difference 2-test 1/test 1 = -0.32% for the 30 W 3 min protocol; +2.18% for the 10 W.min-1 protocol). The reproducibility of VT was slightly lower regardless of the graphical method used to determine it (relative differences varied from -3.3% to +7.3%). Therefore, peak VO2 appears more suitable than VT for assessment of exercise tolerance in CHF.

Adult↗
PubMed1991

Vascular and cardiac actions of aldosterone and spironolactone.

Classical pharmacology confines the mechanism of action of aldosterone and its antagonists to the modulation of ion transport in the distal tubule of the nephron. The purpose of this overview is to examine the evidence for the presence of extrarenal and, namely, vascular and cardiac sites of action for aldosterone and spironolactone. Beside its specific action in primary and secondary hyperaldosteronism, spironolactone is effective in lowering blood pressure in essential hypertension, despite normal levels of aldosterone production, and without necessarily producing significant changes in Na+ and K+ urinary excretion. This is particularly the case when therapy is applied chronically and at relatively low doses. This suggests that spironolactone may act by antagonizing the effects of aldosterone directly on the cardiovascular system. Electrophysiological studies have shown that spironolactone may reduce contractions of rat portal vein strips. This action was found to be mediated by the inhibition of the slow calcium channels. Spironolactone binds to the calcium channels, at sites different from those of dihydropyridines and phenylalkylamines. It interacts at these binding sites in vascular membranes by decreasing their density and accelerating the rate of dissociation of the ligand. In humans, spironolactone 50 mg and 75 mg o.d. produced a dose-dependent decrease of total vascular resistance and in vascular reactivity to vasopressor agents. In the heart, spironolactone produces a direct inotropic action in the mammalian myocardium with an increase of both the amplitude and duration of action potential. Finally, the direct role of aldosterone in promoting fibroblast growth producing cardiac hypertrophy in models of experimental hypertension have been recently emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1990

[Usefulness of exercise tests in the evaluation of the effects of treatment in chronic cardiac insufficiency].

Before it reaches the decompensation stage, heart failure is characterized by symptoms which occur only during exercise. It is therefore rational to believe that the effectiveness of treatments of heart failure should be evaluated by the improvement they produce in tolerance to stress. This tolerance can be evaluated by exercise tests which may take different forms. The most common is a progressive load test on bicycle ergometer or treadmill. Among the indices used to assess tolerance to stress, the total duration of the exercise test until symptoms develop is a variable subject to fluctuations which may be independent of the patient's cardiovascular state. Measurement of oxygen consumption at peak exercise level is usually preferred, being unrelated to the nature of the stress and much more reproducible and sensitive to changes. Among the pharmacological treatments of heart failure, only chronic vasodilator therapy, notably with angiotensin-converting enzyme inhibitors, has proved constantly effective on the various ergometric indices. In the literature, the effects of digitalis compounds, dihydralazine and alpha-blockers are inconstant. Among the new treatments of heart failure, phosphodiesterase inhibitors may improve tolerance to stress, as does Corwin which may prolong the total duration of exercise. Its effect on oxygen consumption has not yet been evaluated. Performance at exercise is almost never improved by acute treatment with any pharmacological agent, and the same remarks applies to short-term heart transplantation. The reason for this is that heart failure is associated with a physical deconditioning syndrome due to abnormalities of the arterial dilatation capacity in skeletal muscles, and with muscular metabolic abnormalities due to a defective oxygen utilization by these muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Digitalis Glycosides↗
PubMed1990

Skeletal muscle metabolism in the leg during exercise in patients with congestive heart failure.

1. Using 31P nuclear magnetic resonance, it has previously been demonstrated that patients with congestive heart failure exhibit a greater than normal phosphocreatine (PCr) depletion in the working skeletal muscles of the arm. We have studied the importance of the work necessary to reach a similar PCr depletion ([PCr]/([PCr] + [Pi]) = 0.5) in calf muscle. Our results show significantly lower values for patients with congestive heart failure in both aerobic and ischaemic conditions (respectively: 0.009 +/- 0.007 vs 0.026 +/- 0.013 W/kg body weight, P less than 0.01; 0.29 +/- 0.16 vs 0.90 +/- 0.25 J/kg body weight, P less than 0.01). 2. This original model of skeletal muscle exercise facilitates a comparison of PCr recovery rate due to a similarity in the PCr depletion and intracellular pH in the two series at the start of recovery. However, the PCr recovery rate is similar after both normoxic and ischaemic exercise, i.e. respective percentages of PCr increase in the first 25 s recovery spectrum were: (a) aerobic exercise, congestive heart failure 133 +/- 18%, control series 138 +/- 18%; (b) ischaemic exercise, congestive heart failure 114 +/- 13%, control series 118 +/- 12%. The absence of a difference in PCr recovery rate and the greater PCr depletion by ischaemic work in patients with congestive heart failure suggest modifications that cannot be explained by a reduced blood flow to the muscle. 3. When comparing the two series, intracellular pH evolved similarly in normoxia and ischaemia during both work and recovery. Thus, no increase in anaerobic glycolytic activity appears when equivalent PCr depletion has occurred.

Adult↗
PubMed1990

The emerging role of ACE inhibitors in the treatment of cardiovascular disease.

Large clinical studies have established the therapeutic benefit of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and chronic congestive heart failure (CHF). In patients with hypertension, ACE inhibitors have been shown to lower blood pressure, with an excellent safety profile. They maintain or enhance the perfusion of vital organs and decrease or reverse cardiac hypertrophy without affecting myocardial contractility or conductivity. ACE inhibitors are safe to use in patients with coexisting conditions such as diabetes and asthma. They maintain or improve quality of life. As a consequence, ACE inhibitors are emerging as first-line drugs for the treatment of hypertension. In the treatment of CHF, ACE inhibitors have been shown to improve symptoms and morbidity, and to decrease mortality in high-risk patients. The possible benefits of early use of ACE inhibitors in the treatment of CHF are currently under investigation. Also of interest is the theoretical benefit that ACE-inhibitor therapy may have on CHF-related arrhythmias.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Calcium antagonists in myocardial infarction.

Calcium antagonists are effective cardioprotective agents in experimental models of myocardial infarction. However, clinical trials in acute myocardial infarction and in postinfarction secondary prevention led to conflicting results related to the small size of the majority of the trials and possible differences among individual agents with distinct ancillary properties. Furthermore, one has to consider separately the trials in patients with Q-wave infarction and in others with non-Q-wave infarction. Q-wave patients do not seem to benefit from therapy with calcium antagonists. However, the efficacy of early administration of verapamil or diltiazem cannot be ruled out as the available data are not conclusive, mainly because of the small size of the trials and the delay in administering the drugs. We have shown encouraging results with diltiazem, which, compared to placebo, decreased the infarct size measured with serial thallium SPECT defect scores, and increased left ventricular ejection fraction in acute Q-wave infarctions. Non-Q-wave infarction is another area where evidence of positive beneficial effects of diltiazem is strong, as shown by a recent trial conducted by Gibson et al. Diltiazem reduced the early reinfarction rate and postinfarction angina and 1-year cardiac mortality and nonfatal reinfarction rate. Consistent with these findings are results from subgroup analysis of the multicenter diltiazem postinfarction trial. Prophylactic use of diltiazem may be useful and should be considered in patients with non-Q-wave infarction along with aspirin, as no other treatment is yet available for this condition, at least for the time being and until the thrombolysis TIMI phase III trial is terminated.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗
PubMed1990

Effects of sustained-release diltiazem on blood pressure and serum lipids: a multicenter, randomized, placebo-controlled study.

A randomized, double-blind dose-response study on the antihypertensive action of sustained-release diltiazem was performed in four parallel groups. The aim of the trial was to evaluate the antihypertensive efficacy of sustained-release diltiazem and its dose-dependent clinical and biological tolerance. The four homogeneous groups consisted of 25 patients each who had presented with mild to moderate hypertension (diastolic blood pressure of 95-115 mm Hg) in the supine position. The study protocol comprised three successive periods: a placebo period lasting 14 days to verify the persistence of arterial hypertension under placebo; a first therapeutic period during which each of the 25 patients of the four groups received a single daily dose every morning at 9 a.m. of a capsule containing 0.240, 300, or 360 mg of sustained-release diltiazem over a period of 28 days; and a second therapeutic period during which the patients of the four groups received 240, 300, 360, and 300 mg, respectively. All other antihypertensive treatment had been suspended at least 15 days before the initial period under placebo. The results were evaluated with respect to clinical parameters such as systolic blood pressure, diastolic blood pressure, and heart rate, which were measured at 9 a.m. 24 h after the last administration of the drug on days 14, 28, and 56. The plasma serum levels of diltiazem were measured on days 28 and 56, the biological parameters, including measurements of hepatic and renal function as well as lipid and glucose levels, on days 14 and 56, and electrocardiography was performed on days 14, 28, and 56.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

[Value and study methods of hemorheology in vascular pathology and pharmacology].

The growth of modern, reliable, reproducible and relatively inexpensive techniques of studying micro and macrorheological changes has confirmed the role of haemorheology in the physiology of the microcirculation and the consequences of its disturbance in vascular and ischemic pathology. These abnormalities can be corrected by pharmacological agents including several vasoactive molecules which owe at least some of their therapeutic effects to their action on blood rheology especially on the red blood cells. Systematic study of the rheological effects of these vasoactive, anti-ischemic substances is now possible and necessary.

Blood Physiological Phenomena↗
PubMed1990

[Symptomatic treatment of chronic cardiac insufficiency].

Given the absence of curative and preventive treatment of cardiac failure, symptomatic therapy is very important. In severe "non-ambulatory" cardiac failure, symptoms depend on the patient's resting hemodynamic status. This can be improved by diuretics, digitalis and vasodilators. A combination of these three drug groups is often required. However, the respective value of each group is unknown. Their use is limited by their specific undesirable secondary effects which are particularly common and severe at this advanced stage. Their effects on survival are unknown with the exception of angiotension converting enzyme inhibitors which have been shown to be beneficial. At the ambulatory stage symptoms occur on effort. In order to improve exercise capacity, the treatment chosen should increase the patient's reserve of cardiac output, limit the increase in pulmonary pressures, respect systemic arterial pressure, decrease venous pressure, dilate the muscular arterioles and improve oxygen extraction by skeletal muscle during physical exercise. Diuretics and angiotensin converting enzyme inhibitors can fulfill these objectives. The effects of the other vasodilators are more variable, due to a vasodilatation which is often inappropriate and to tachyphylaxis related to reflex activation of neuro-hormonal mechanisms. Digitalis and some vasodilator inotropic agents can improve symptoms and effort capacity. However, doubts over possible deleterious effects on mortality have to be cleared by large scale, controlled therapeutic trials. Symptoms of cardiac failure at the ambulatory stage and the effects of treatment on these symptoms should logically be evaluated by appropriate ergometric exercise stress testing, with measurement of the patient's maximum oxygen consumption whenever possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗
PubMed1989

Role of ancillary properties of beta-adrenoceptor antagonists in protecting the heart from anoxia.

The mechanism of the cardioprotective action of beta-blocking drugs against anoxia or ischemia is still not clear. We used beta-blockers (5 x 10(-7) M) of various pharmacodynamic profiles in a model of isolated, perfused working guinea pig heart subjected to 20 min of anoxia to study this. The cardioprotective effects were evaluated by measuring the recovery of the flow indices after 15 min of reoxygenation. There was a significant cardioprotective action (as measured by the effect on stroke volume recovery and on recovery of other flow and work indices) of the beta-blocking properties (nadolol, P less than 0.05), of the membrane-stabilizing property [+)-propranolol, P less than 0.05) and of a combination of these two properties with (+/-)-propranolol, which had a significantly greater effect than nadolol (P less than 0.05). The addition of weak (acebutolol) or strong (pindolol) intrinsic partial agonist activity had no clear unfavourable effect, as the degree of cardioprotection was comparable with that obtained with (+/-)-propranolol. The stroke volume recovery (percent recovery after anoxia) in the control hearts was 42.57 +/- 12.75 compared to 54.84 +/- 6.94 in hearts pretreated with nadolol, 62.99 +/- 11.41 with (+)-propranolol, 71.02 +/- 11.36 with (+/-)-propranolol, 72.63 +/- 13.08 with acebutolol and 68.01 +/- 15.42 with pindolol. In vitro heart protection from anoxia with beta-blockers would appear to be related to beta-blocking activity and/or membrane stabilizing property but not a function of partial agonist activity. These ancillary properties of beta-blockers should thus be taken into account in studies on cardioprotection.

Adrenergic beta-Antagonists↗
PubMed1989

ACE inhibitors in hypertension: a European viewpoint.

The introduction of angiotensin-converting enzyme (ACE) inhibitors has had an appreciable impact upon the treatment of hypertension in Europe, although acceptance of these new agents has not been uniform in all countries. In order to arrive at an understanding of the place of ACE inhibitors in the management of the hypertensive patient, the attitudes of four parties must be considered: the prescriber, the patient, the manufacturer, and the regulatory agency. Physicians in Britain, Germany, and Scandinavia have lagged behind their counterparts in France and Italy in prescribing ACE inhibitors, due to restrictions placed by national regulatory agencies on the first-line use of these agents in hypertension therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

[Hemolytic anemia and cardiac heterografts. Apropos of 2 cases].

Two cases of severe haemolytic anaemia developed after heterograft valve replacement are reported. In one case haemolysis was caused by prosthetic degeneration; in the other case the heterograft was not altered, but a ventricular septal defect had created a high turbulence around the valve which was in pulmonary position. In both cases anaemia subsided after surgical correction of the abnormalities responsible for periprosthetic turbulence. Haemodialysis can only develop in patients with heterograft valve replacement if a change in blood flow rate occurs around the valve, due to its alteration or to an associated cardiac disease.

Adult↗
PubMed1989

[Abnormalities of the peripheral circulation and tolerance to exertion of patients with heart failure].

Chronic heart failure is attended by a number of abnormalities of peripheral circulation. To a great extent, these abnormalities determine the patients' functional symptoms, their tolerance to exercise and their response to treatment, at least in the short term. The response to exercise of heart failure patients depends on their maximal oxygen consumption which is determined by their maximal cardiac output and by various peripheral adjustments, such as distribution of regional blood flow and peripheral oxygen extraction. Abnormalities of peripheral arteriolar and capillary dilatation are determined by hyperstimulation of neurohormonal systems. An increase in maximal muscular blood flow, which determines the patients' capacity of exercise, can be obtained with drugs which increase the muscular perfusion pressure (inotropic drugs) or which decrease muscular resistances without lowering the perfusion pressure (venous or balanced vasodilators, diuretics). Physical rehabilitation may improve maximal oxygen consumption by improving the peripheral use of oxygen. Thus, a better understanding of the physiopathology of heart failure will in the future improve the functional symptoms of these patients and prolong their survival, which has not always been the case with conventional therapies.

Heart Failure↗
PubMed1989

[Reference values of ambulatory arterial pressure in activity and during the night. Multicenter study of 394 normotensive subjects at rest].

The blood pressure pattern and variability were assessed in a population of 394 normotensive subjects (OMS) stratified by age (20 to 75 years) and sex. Ambulatory blood pressure measurements were performed with an automatic device (Spacelabs 5200) every 15 min. from 6 a.m. to 12 p.m., and every 30 min. from 0 a.m. to 6 a.m. The analysis was effected during normal daily activities (from 9 a.m. to 7 p.m.) and during night (from 11 p.m. to 7 a.m.). Blood pressure levels were higher in males than females. During daytime and nighttime, diastolic blood pressure rose with age until 59 years while SBP was not affected, except for the females older than 60 years. After this age, diastolic blood pressure decreased. No epidemiological study has provided a measure of the cardiovascular risk related to ambulatory blood pressure, so that we were unable to define true normal values. However, reference population values provided from two statistical methods: limit of the 95th upper confidence interval for the mean of limit of the 90th percentile value for the total data. These blood pressure distributions according to age and sex may allow a better approach to borderline hypertensive patients.

Adult↗