[Effect of nitrendipine therapy on indicators of the systolic and diastolic function of the left ventricle in patients with arterial hypertension].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
F M Fouad
Publications and source records attributed to F M Fouad.
Left ventricular diastolic function in hypertensive patients.
Left ventricular filling rate has been shown to be depressed in hypertensive patients before any alteration in indexes of systolic function. The mechanism(s) underlying this abnormality is not known. However, several factors were found to influence left ventricular filling rate. The relative importance of these factors is emerging from studies performed at various centers. Of these, the adrenergic drive, coronary blood flow, heart rate, afterload, and calcium reuptake mechanisms seem to be important. Physiologically, the index of left ventricular filling should therefore be normalized to allow comparison between different individuals. Using a normalized index (filling rate/emptying rate), we found in a small group (n = 13) of hypertensive patients that the increase in total peripheral resistance during head-up tilt was blunted in those with reduced left ventricular filling, suggesting that this abnormality in diastolic function accompanying hypertension plays a role in cardiovascular regulation by altering sensitivity of cardiopulmonary reflexes.
Animals↗
Nitrendipine, a calcium-entry blocker. Renal and humoral effects in human arterial hypertension.
Thirteen patients with hypertension and normal renal function received nitrendipine, a calcium entry blocker. Nitrendipine did not modify renal blood flow (RBF) or glomerular filtration rate (GFR), decreased mean arterial pressure (MAP) and total peripheral resistance, and did not significantly change cardiac output. Individual RBF changes did not correlate with MAP or cardiac output modifications. Mean arterial pressure changes were inversely correlated with basal renin levels and directly associated with age. Plasma catecholamines and plasma renin activity increased, but plasma aldosterone and plasma volume did not change significantly. However, the greater decrements of MAP tended to be associated with the greater increases in plasma volume. Data show that long-term calcium entry blockade by nitrendipine does not modify RBF or GFR despite the decreased renal perfusion pressure. Further, nitrendipine may be more effective in older patients and the presence of low renin.
Adult↗
Restoration of cardiac function and structure by converting enzyme inhibition possibilities and limitations of long-term treatment in hypertension and heart failure.
There is no doubt that cardiac function can be restored to a great degree in congestive heart failure treated with converting-enzyme inhibitors, but the mechanism of improvement involves the correction of peripheral abnormalities rather than a direct cardiac effect of the drug. There is some evidence that deterioration of cardiac function and progressive cardiac dilation following myocardial infarction can be prevented by treatment with converting-enzyme inhibitors. Regression of left ventricular hypertrophy (LVH) has been obtained by converting-enzyme inhibitors, both in man and in experimental animals. In animal studies, this regression of LVH was associated with restoration of contractile reserve and of coronary flow reserve to normal. The final significance of this restoration of structure and its functional aspects still needs further studies.
Angiotensin-Converting Enzyme Inhibitors↗
Idiopathic hypovolemia.
Eleven patients with orthostatic intolerance had, for no detectable reason, a marked reduction in blood volume (73 +/- 2.29% [SE] of normal). Head-up tilt caused a pronounced increase in heart rate (+ 39 +/- 6 beats/min); one patient had a vasovagal episode after the initial tachycardia. Extensive diagnostic study excluded pheochromocytoma, hypoaldosteronism, or any obvious cause for hypovolemia (total plasma catecholamines, 372 +/- 53 ng/L; plasma aldosterone level, 14.5 +/- 2.56 ng/100 mL; plasma cortisol level, 18.5 +/- 2.4 ng/100 mL). The supine hemodynamic pattern (decreased cardiac output and increased total peripheral resistance with normal ejection fraction and mean transit time) was markedly different from that of hyperbeta adrenergic states. Acute plasma volume expansion (+ 11 +/- 2%) in ten patients using human serum albumin improved both their symptoms and heart rate response to tilt. After long-term blood volume expansion with florinef (E.R. Squibb, Princeton, New Jersey), 0.1 mg twice a day, and a high-salt diet, the head-up tilt test was repeated in five patients. The response was normal in four patients. These observations outline a syndrome of marked idiopathic hypovolemia with symptomatic labile hypertension and intolerance to head-up tilt, alleviated by volume expansion.
Adult↗
A cooperative multicenter study of captopril in congestive heart failure: hemodynamic effects and long-term response.
The acute hemodynamic effects, long-term clinical efficacy, and safety of the oral angiotensin-converting enzyme inhibitor, captopril, were assessed in a multicenter cooperative study of 124 patients with heart failure resistant to digitalis and diuretics. The cardiac status of most patients was deteriorating prior to the study. Favorable acute hemodynamic effects consistently occurred with captopril. Maximal mean percentage increases in cardiac index, stroke index, and stroke work index were, respectively, 35%, 44%, and 34%. Systemic and pulmonary vascular resistances were each decreased by approximately 40%, as were the filling pressures of the right and left heart. Infusion of nitroprusside in some of the same patients to an end point of a pulmonary capillary wedge pressure of 12 to 18 mm Hg (equivalent to that after captopril) revealed no significant difference in the effect of either drug on the other hemodynamic parameters. Recatheterization after 8 weeks of captopril therapy revealed sustained hemodynamic changes. Significant and sustained improvements in clinical status were observed in most patients as measured by changes in New York Heart Association (NYHA) functional classification and exercise tolerance times. Seventy-nine percent of patients for whom there were adequate NYHA class data improved. Twenty percent remained unchanged and 1% deteriorated. Those patients who had both pretreatment and post-treatment exercise stress testing exhibited a highly significant mean increase in exercise tolerance times of 34% (317 +/- 32 seconds pretreatment to 425 +/- 34 seconds, final measurement). There was no evidence of tachyphylaxis over an 18-month period.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Excitation-contraction coupling in hypertrophied myocardium.
In hypertensive cardiac hypertrophy, inotropic responsiveness of alpha and beta adrenergic stimuli is reduced. We have previously shown that hearts from two-kidney, one-clip renal hypertensive rats (RHR) have increased beta-adrenergic receptor density and a defect in the guanine nucleotide regulatory protein, leading to decreased adenylate cyclase activity. In spontaneously hypertensive rats (SHR), beta-receptor density was decreased with no change in adenylate cyclase. In these present experiments, we have shown that the alpha 1-adrenergic receptor changes are in the opposite direction, decreasing in RHR and increasing in SHR. All these changes are reversible within 4 weeks following removal of the clipped kidney in RHR, at which time blood pressure and heart weight have also returned towards normal. Further studies on the excitation-contraction pathway have indicated that c-AMP-stimulated protein kinase is decreased in SHR with no changes seen in RHR. Subcutaneous infusion of epinephrine leads to some increase of cardiac mass associated with decreased beta-adrenergic receptors element and decreased adenylate cyclase activity. However, following angiotensin II infusion, even though hypertrophy is more pronounced, no changes in receptors or cyclase are detected. We conclude that different models of hypertensive cardiac hypertrophy associated with different biochemical defects in the adrenergic excitation response pathway, and that if some of these changes become irreversible, further cardiac deterioration and even heart failure may ensue.
Age Factors↗
Reversal of cardiac hypertrophy by medical treatment.
Reversal of left ventricular hypertrophy in hypertensive patients has been proven to follow effective blood pressure control by some antihypertensive drugs. This reversal does not depend solely on the degree of pressure reduction but is also modulated by other factors including, among others, stability of blood pressure control, degree of cardioadrenergic stimulation, and individual variations due to genetic background and possible age. Regression of left ventricular hypertrophy is most likely to occur when the reduction in arterial pressure and peripheral resistance can be maintained without induced reflex cardiac stimulation. Left ventricular performance at rest was not depressed by the reduction in cardiac mass but remained normal both in absolute terms and in relation to changes in LV end-systolic stress.
Animals↗
Impaired inotropic responses to alpha-adrenergic stimulation in experimental left ventricular hypertrophy.
We have previously reported that left ventricular hypertrophy in two-kidney, one-clip renal hypertensive rats (2K-1C RHRs) was associated with diminished inotropic responsiveness to isoproterenol and glucagon, suggesting an alteration in the receptor-adenylate cyclase cascade. The present study was performed to investigate the hypothesis that in these same hearts, inotropic responses to alpha-adrenergic stimuli could be enhanced as a compensatory mechanism. alpha-Adrenergic stimulation was achieved by graded phenylephrine infusion (1.02 to 41.2 microM/min) in the presence of propranolol (10(-7) M). The inotropic response was evaluated in the isovolumetric isolated rat heart (Langendorff preparation) paced at 260 beats/min. Results showed a significantly reduced inotropic response to alpha 1-adrenergic stimulation in 2K-1C RHR hearts irrespective of perfusion pressure (50 or 80 mm Hg [PP50 or PP80]) (+427.5 +/- 62.1 vs +1236 +/- 216.4 mm Hg X sec-1 at PP50, p less than .01 and +339 +/- 98.3 vs +1440 +/- 254 mg Hg X sec-1 at PP80, p less than .001) even when comparison was made at equivalent myocardial flow rates (RHR hearts perfused at 80 mm Hg vs control hearts perfused at 50 mm Hg). Quantitative assessment of number of alpha 1-adrenergic receptors (3H-prazosin binding) showed a significant decrease compared with that in age-matched sham-operated normotensive control rats (45 +/- 2.5 vs 64 +/- 1.7 fmol/mg protein, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Orthostatic hypotension. Clinical experience with diagnostic tests.
Explore the source record for details and available documents.
Autonomic Nervous System Diseases↗
Assessment of cardiac status in hypertensive patients.
Evaluation of cardiac participation in hypertension includes much more than determination of the presence or absence of left ventricular hypertrophy by chest X-ray or electrocardiography. Chest X-ray has not proved very useful in the work-up of hypertensive patients in contrast with electrocardiography. Although electrocardiography is highly specific for left ventricular hypertrophy, it is not sensitive enough for many cases nor does it allow functional assessment of cardiac performance. Echocardiography, on the other hand, is a much more powerful tool for the evaluation of both the anatomical and functional aspects of cardiac performance. However, although it cannot be recommended as yet for routine evaluation of all patients, it is rapidly becoming an important examination for many patients. It allows not only quantitative estimate of left ventricular hypertrophy (LVH), but will also determine the distribution of hypertrophy, its effects on both systolic and diastolic functions of the heart and its alteration with therapy. As regards specific tests for myocardial perfusion, coronary reserve and ventricular volume analysis, these techniques are indicated more for clinical research or very special circumstances than for routine use. In summary assessment of cardiac status of a hypertensive patient should include the following: a precise diagnosis of LVH, estimate of cardiac performance, both systolic and diastolic, evaluation of cardiac factors in resistance to antihypertensive therapy and follow-up of regression of structural alterations during antihypertensive treatment.
Cardiomegaly↗
Regulation of renal hemodynamics and glomerular filtration in patients with renovascular hypertension during converting enzyme inhibition with captopril.
Changes in regional hemodynamics and function of the kidney during inhibition of angiotensin converting enzyme were studied in 25 patients with renovascular hypertension. A variety of patterns were observed depending upon (1) the activity of the renin-angiotensin system and concomitant administration of diuretics, and (2) the presence of bilateral renal artery stenosis. Increase in blood flow, glomerular filtration rate and sodium excretion during angiotensin blockade, in some instances, indicated tonic renal vasoconstriction before therapy. Release of the kidney from these effects may explain, in part, the sustained effectiveness of converting enzyme inhibition in chronic congestive heart failure. When compared with blood pressure reduction due to nitroprusside administration, initial captopril therapy in patients with unilateral stenosis produced a selective decrease in glomerular filtration, despite well-preserved renal blood flow. These results confirm the importance of efferent arteriolar vasoconstriction due to angiotensin II in man. Experimental studies demonstrate that angiotensin may become critical to sustaining glomerular filtration rate in the presence of stenosis during vasodilation. In patients with bilateral stenosis, this effect produces a syndrome of functional renal insufficiency. Taken together, these data demonstrate an intrarenal action of angiotensin II in human renovascular hypertension and underscore the importance of evaluating the functional impact of changes in regional hemodynamics.
Adult↗
Regression of left ventricular hypertrophy from systemic hypertension by enalapril.
Reversal of left ventricular (LV) hypertrophy with medical therapy has been studied increasingly in patients with systemic hypertension. However, serial changes of LV function are not found during reversal of LV hypertrophy in hypertensive patients. Seven patients with LV hypertension were studied to evaluate serial changes of LV mass and function after the initiation of the new converting enzyme inhibitor MK-421. LV mass and function were determined serially at the end of a placebo period and at 5 days, 1 month, 3 months and 7 months after the initiation of MK-421, using both 2-dimensional (2-D) guided M-mode echocardiography and radionuclide techniques. All patients except 1 had LV hypertrophy and all had normal LV function (ejection fraction derived from gated blood pool method greater than 49%). There was an inverse relation between LV fractional shortening (percent FS) and end-systolic stress before medication (r = -0.81, p less than 0.05). LV mass decreased significantly at 3 months and at 7 months (-10%, p less than 0.05, and -12%, p less than 0.01, respectively) accompanied with persistent decrease of mean blood pressure, which occurred as early as 5 days after start of therapy (133 +/- 5 mm Hg at control, to 112 +/- 4 mm Hg at day 5). During reversal of LV hypertrophy, the inverse correlation between FS and end-systolic stress remained significant (r = -0.80 to -0.95, p less than 0.025 for all), with no difference from the placebo period and from this relation in the normal group. Moreover, percent FS, ejection fraction and stroke index remained unchanged. Thus, LV hypertrophy in patients with systemic hypertension can be reversed without deterioration of LV function. Moreover, overall LV function is likely to be determined by afterload even after reversal of LV hypertrophy.
Adult↗
Left ventricular function in coronary artery disease. Evaluation of slope of end-systolic pressure-volume line (Emax) and ratio of peak systolic pressure to end-systolic volume (P/Ves).
Left ventricular function was assessed by measurement of systolic pressure-volume variables and ejection fraction in seven normal subjects (group I), five patients with coronary artery disease and normal symmetric left ventricular wall motion (group II) and eight patients with remote myocardial infarction and segmental akinesia (group III). Left ventricular volumes were obtained from right anterior oblique ventriculograms and pressures from catheter-tip micromanometer (14 patients) or fluid-filled catheters (6 patients) at two different systolic loads. P/Ves was calculated as the ratio of peak systolic pressure (P) to end-systolic volume (Ves) at rest, Emax as the slope of the end-systolic pressure volume line constructed at two systolic loads, and Vo as the volume axis intercept of this line. Emax was significantly (p less than 0.01) lower in patients with segmental akinesia (group III) (5.0 +/- 0.5) than in normal subjects (group I) (10.4 +/- 0.8) or patients with coronary artery disease and normal wall motion (group II) (9.9 +/- 0.8). In contrast, there was no significant difference in P/Ves among the three groups (6 +/- 1.0 in group I, 5 +/- 0.8 in group II, 3.7 +/- 0.5 in group III). Similarly, Ves and Vo failed to separate the three groups. Although ejection fraction was significantly (p less than 0.05) lower in group III (0.56 +/- 0.03) than in groups I and II (0.67 +/- 0.03 in both groups), there was considerable overlap of individual values in the three groups. In eight patients, measurements were repeated during isometric exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac Output↗
Left ventricular diastolic function in hypertension: relation to left ventricular mass and systolic function.
Initial studies of diastolic cardiac function in hypertension demonstrated that slowing of the maximal rate of left ventricular filling occurred before alterations in either ejection fraction or cardiac output. The present study was undertaken to determine: 1) the relation between hypertension, increased left ventricular mass and impaired left ventricular filling, and 2) the correlation between abnormalities in left ventricular diastolic function and its systolic performance. Eleven normal subjects (Group 1), 5 hypertensive patients without evidence of left ventricular hypertrophy (Group 2) and 18 hypertensive patients with increased left ventricular mass by echocardiography (Group 3) were studied by M-mode echocardiography, radionuclide (technetium-99m human serum albumin) first pass technique and gated blood pool scintigraphy. Indexes of systolic function (ejection fraction, maximal rate of ejection and percent left ventricular shortening) were essentially similar in hypertensive and normotensive subjects. No correlation was found between systolic blood pressure and left ventricular mass (r = 0.20, not significant). Maximal rate of left ventricular filling (P dV/dt) and fast filling fraction decreased progressively from Group 1 to Group 3 (2.36 +/- 0.4 [mean +/- standard deviation], 2.17 +/- 0.3 and 1.97 +/- 0.4 s-1, respectively, for P dV/dt and 46 +/- 7, 48 +/- 9 and 38 +/- 11%, respectively, for fast filling fraction); the difference from values in normal subjects reached statistical significance in hypertensive patients with left ventricular hypertrophy. Left ventricular maximal filling rate correlated inversely with left ventricular mass and left ventricular end-systolic diameter (r = -0.74), but positively with left ventricular fractional shortening and ejection fraction (r = 0.70).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical and systemic hemodynamic effects of nitrendipine.
The antihypertensive effects of nitrendipine were evaluated in 12 subjects with hypertension, one of whom could not tolerate the drug for more than 3 days; hence hemodynamics were studied in the 11 subjects who were treated for 2 wk. In one patient taking 40 mg twice a day, blood pressure reduction was associated with a hemodynamic pattern of hyperkinetic circulation. Of the other 10 subjects, all of whom were taking 20 mg twice a day, two did not respond, but 8 had significant reduction in mean arterial pressure (136 +/- 4.3 to 106 +/- 3.2 mm Hg) resulting from a decrease in total peripheral resistance (52 +/- 3.7 to 35 +/- 2.6 U X m2). Changes in cardiac output, heart rate, and cardiopulmonary volume varied widely among subjects, such that average changes did not attain significance. Heart rate and cardiopulmonary volume, however, changed in the same direction, which suggests that the alterations in both were related to the degree of reflex sympathetic stimulation induced by nitrendipine. Plasma renin activity (PRA) increased during treatment (2.6 +/- 1.0 to 9.3 +/- 4.1 ng/ml/hr), whereas the increase in plasma aldosterone (PA) levels did not attain significance (13.7 +/- 1.6 to 21.5 +/- 4.5 ng/dl). As a result, PA/PRA decreased (16.1 +/- 4.9 to 9.4 +/- 2.6). These results suggest that calcium entry blockade might have interfered with steroidogenesis, thus blunting the effect of increased PRA. Finally, blood pressure response to nitrendipine in the whole group correlated inversely with pretreatment PRA (r = -0.88), suggesting greater activity of the drug in low-renin hypertension.
Adult↗
Captopril in congestive heart failure resistant to other vasodilators.
In an attempt to study the possible mechanism(s) by which captopril controls resistant heart failure, sequential haemodynamic studies (radioisotope technique) and humoral measurements (plasma renin activity, plasma aldosterone and plasma catecholamines) were obtained in 11 such patients. The studies were made at the time patients became unresponsive to other vasodilators (hydralazine or prazosin); the vasodilator drug was then discontinued and five days later, the 'no-vasodilator' studies were obtained. Captopril therapy was then started. Optimum daily maintenance dose of captopril varied from 75 to 200 mg in different patients. Studies were again repeated after a period of time equal to the duration of the previous vasodilator therapy. Digitalis and diuretic doses were kept constant throughout. Captopril improved effort tolerance in ten patients. Haemodynamically, mean blood pressure and peripheral resistance were lower than during vasodilator therapy (85 +/- 3.1 v. 92 +/- 3.3 mmHg and 47 +/- 4.4 v. 59 +/- 4.4 U.M2, respectively; p less than 0.05 for both). Cardiac index was higher during captopril treatment (1.95 +/- 0.15 v. 1.63 +/- 0.10 l/m2, p less than 0.01) and pulmonary mean transit was normalized by captopril (14.6 +/- 1.7 v. 18.4 +/- 1.3 s, p less than 0.05). Humoral indices revealed a significant (p less than 0.05) reduction in plasma aldosterone during captopril therapy (25.9 +/- 5.6 ng/dl during captopril, v. 62 +/- 22 ng/dl with no vasodilators and 50.9 +/- 6.1 ng/dl with other vasodilators). Moreover, there was a decrease in circulating plasma catecholamines during captopril treatment, but differences between the three treatment periods were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldosterone↗
Transient renal dysfunction during initial inhibition of converting enzyme in congestive heart failure.
Treatment with captopril in resistant normotensive congestive heart failure is associated with a pronounced reduction in blood pressure, particularly after the first dose. The effects of this reduction on renal function were assessed in 10 patients at the beginning of and during chronic treatment (at one week and three months). Renal plasma flow and glomerular filtration rates were measured by isotope clearance during water diuresis. The first dose of captopril (25 mg) led to a pronounced fall in renal plasma flow and glomerular filtration rates together with a decrease in mean arterial pressure; this fall correlated with baseline plasma renin activity. These changes were paralleled by decreases in water and sodium excretion. In contrast, by the end of the first week of treatment a similar fall in mean arterial pressure occurred together with a pronounced increase in renal plasma flow; the glomerular filtration rate was maintained and there was no decrease in water and sodium excretion. This new response pattern recurred after three months of treatment. The difference in response at different stages of treatment may reflect the balance between the different mechanisms influencing kidney dynamics in heart failure and their alteration by converting enzyme inhibition. The sustained increase in renal plasma flow during chronic treatment with captopril may account for the continued control of heart failure in these patients.
Adult↗