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Biomedical subjects

C V Leier

Publications and source records attributed to C V Leier.

At least 73 records · Page 4Linked to original sources
PubMed1988

Hemodynamic responses to different levels of alpha-adrenergic interruption in congestive heart failure.

The effects of prazosin, clonidine, and indoramin on central and regional hemodynamic parameters and left ventricular performance were analyzed in a congestive heart failure population to compare the pharmacodynamic responses to different levels of alpha-adrenergic interruption in this condition. The sympathetic nervous system is blocked at the peripheral alpha1-receptor by prazosin, at central nervous system alpha-receptor sites (via alpha-adrenoceptor agonism) by clonidine, and at peripheral and central sites by indoramin. Prazosin and indoramin produced reductions in total systemic and pulmonary vascular resistances, mean systemic and pulmonary artery pressures, and pulmonary capillary wedge pressure with little change in heart rate. Both agents selectively increased hepatic blood flow. Clonidine also decreased pulmonary artery pressure and vascular resistance, but evoked negative inotropic and chronotropic activity and did not alter regional blood flow. In contrast to prazosin, indoramin and clonidine did not augment cardiac output or stroke volume. In the setting of congestive heart failure, the central and regional hemodynamic effects and the responses in left ventricular performance vary considerably depending on the site of alpha-adrenergic interruption.

Adrenergic alpha-Antagonists↗
PubMed1988

Preservation of the end-systolic pressure/end-systolic dimension relation following pindolol in congestive heart failure.

Beta blockade may adversely affect inotropic state of the ventricle, resulting in exacerbation of congestive heart failure in subjects with reduced ventricular function. In normal subjects, ventricular contractility appears to be preserved following administration of beta blockers with intrinsic sympathomimetic activity (ISA). The inotropic state of the ventricle was assessed in seven subjects with congestive heart failure (mean ejection fraction = 23 +/- 5%) before and after administration of the ISA beta blocker, pindolol, with the use of the noninvasively derived end-systolic pressure/end-systolic dimension (ESP/ESD) relation. The mean slope of the ESP/ESD relation was 36.3 +/- 20.4 mm Hg/cm at baseline and increased to 45.0 +/- 25.2 mm Hg/cm following five consecutive 10 mg oral doses of pindolol (p = ns). Other simultaneously derived inotropic indices that included percent fractional shortening, mean delta P/delta T, velocity of circumferential fiber shortening, and preejection period-to-left ventricular ejection time ratio showed directionally similar changes toward a mild increase in contractility. These results indicate that the slope of the left ventricular ESP/ESD relation is not altered following repeated dosing with pindolol in subjects with congestive heart failure. This reflects a preservation of inotropic state following administration of this ISA beta blocker in a population with severely compromised ventricular function.

Echocardiography↗
PubMed1988

Central and regional hemodynamic effects of oral enoximone in congestive heart failure: a double-blind, placebo-controlled study.

Twelve patients with congestive heart failure underwent a double-blind, placebo-controlled study for the purpose of examining the central and regional hemodynamic effects of first-dose (1 and 2 mg/kg) oral enoximone, a new phosphodiesterase III inhibitor. Enoximone augmented cardiac output, generally through a positive chronotropic response. Indices of left ventricular contractility, specifically stroke volume, delta P/delta t, fractional shortening rate, and the duration of the preejection period, were only modestly enhanced by enoximone. At 2 mg/kg, systemic vascular resistance fell below baseline values without affecting systemic blood pressure; these parameters were not altered by the 1 mg/kg dose. Both pulmonary artery pressure and pulmonary vascular resistance dropped below baseline and below placebo control for the 2 mg/kg dose. Enoximone at 2 mg/kg lowered right and left heart filling pressures below baseline. Examination of regional hemodynamic responses to both doses demonstrated a reduction in limb vascular resistance and an increase in limb blood flow proportional to the concomitant increase in cardiac output. Renal and hepatic-splanchnic blood flow and vascular resistances were not altered by enoximone. First-dose oral enoximone (1 and 2 mg/kg) alters hemodynamics in heart failure by predominant vasodilatation, particularly of limb-musculoskeletal and pulmonary vascular beds, some positive chronotropism, and modest positive inotropism.

Adult↗
PubMed1988

Late systolic indices of ventricular function: noninvasive derivation in congestive heart failure.

The slopes of end-systolic pressure/end-systolic dimension and volume relations have been found to be relatively load-independent indices of left ventricular contractility. Noninvasive determination of these relationships has been performed in normal subjects and has been found to reflect baseline and drug-induced changes in ventricular contractility. Three late systolic indices of ventricular contractility were noninvasively determined in subjects with chronic congestive heart failure to determine the feasibility of the method and to assess the linearity and slopes of the relationships in this population. All relations were linear with individual correlation coefficients ranging from 0.86 to 0.99. The mean +/- SD slope was 42.8 +/- 26.4 mm Hg/cm for the end-systolic pressure-dimension relation, 0.59 +/- .42 mm Hg/ml for the end-systolic pressure-volume relation, and 48.7 +/- 32.2 mm Hg/cm for the peak systolic pressure-end-systolic dimension relation. All slopes were markedly reduced compared to those reported in normal individuals. The relative degree of depression was greater for the pressure-volume slope than for the pressure-dimension slope, which is explained by the relationship between volume and dimension in dilated ventricles. These data indicate that measurement of late systolic indices of ventricular contractility by this noninvasive technique is feasible in subjects with congestive heart failure and yields reduced slopes consistent with the diminished contractile state of this population. Pressure-volume rather than pressure-dimension relations may more accurately reflect inotropic state in dilated ventricles.

Cardiomyopathy, Dilated↗
PubMed1988

Hemodynamic effects of smoking in congestive heart failure.

This study was designed to investigate the hemodynamic effects of smoking in patients with congestive heart failure. Hemodynamic measurements were made in seven patients with heart failure before, during, and after smoking two unfiltered cigarettes (approximately 2.4 mg of nicotine). Smoking significantly (p less than .05) increased heart rate and decreased stroke volume. Cardiac output remained unchanged. Significant increases were noted in systemic systolic and diastolic blood pressures concomitant with significant increases in total systemic vascular resistance and systemic arteriolar resistance. Pulmonary arterial pressure and total pulmonary vascular resistance increased as well. Mean right atrial pressure and pulmonary capillary wedge pressure rose modestly during smoking. Finally, the double product, an index of myocardial oxygen consumption, increased considerably during the smoking and postsmoking periods. Smoking elicits significant hemodynamic effects in patients with congestive heart failure, many unfavorable and potentially detrimental.

Adult↗
PubMed1988

Neurohumoral profile in congestive heart failure: response to beta-blockade.

Beta-blockade has been reported to have beneficial hemodynamic effects in chronic congestive heart failure that may be related to alterations in the abnormal neurohumoral profile characteristic of this population. To determine the relationship of the neurohumoral profile to the hemodynamic response to beta-blockade in patients with chronic congestive heart failure, neurohumoral and hemodynamic variables were measured in 10 subjects having congestive cardiomyopathy at baseline and after administration of the beta-blocker pindolol. Baseline stroke index was noted to have an inverse curvilinear relation with plasma norepinephrine (r = -0.69) and renin (r = -0.71) concentration. Pulmonary vascular resistance demonstrated a direct logarithmic relation with plasma norepinephrine concentration (r = 0.68). Increases in norepinephrine, dopamine, and epinephrine concentrations after dosing were noted, with the most marked increase in norepinephrine concentration being coincident with a significant decline in stroke volume index. Two patients not tolerating beta-blockade were characterized by having baseline norepinephrine concentrations 3 SD higher than those of the remaining patients, more marked increases in epinephrine concentration after dosing, and the most profoundly decompensated heart failure at baseline, as defined by the relationship between neurohumoral and hemodynamic variables. These observations suggest that increases in catecholamines after dosing reflect a compensatory response to the adverse hemodynamic-inotropic effects of beta-blockade in congestive heart failure. The neurohumoral profile and the relationship of neuroendocrine to hemodynamic parameters may be useful in delineating patients at risk for adverse hemodynamic effects of beta-blockade.

Adrenergic beta-Antagonists↗
PubMed1987

A preliminary report of the effects of orally administered enoximone on regional hemodynamics in congestive heart failure.

Twelve patients with moderately severe congestive heart failure underwent the simultaneous determination of central and regional hemodynamics after administration of placebo and enoximone. The regions examined hemodynamically included renal, hepatic-splanchnic and upper limb. Enoximone was studied in 2 doses, 1 and 2 mg/kg, and administered in a double-blind, placebo-controlled, crossover design. At these doses enoximone elicited a significantly greater increase in cardiac output and a greater decrease in systemic vascular resistance than placebo. Systemic blood pressure was not significantly altered. Enoximone did not significantly change the flow or resistance of renal or hepatic-splanchnic vascular beds. Limb vascular resistance decreased modestly after enoximone with a significant augmentation (+12% to 17%) of limb blood flow compared with placebo. The initial oral administration of the 1 and 2 mg/kg doses of enoximone improved central hemodynamic parameters with apparent preferential reduction of limb vascular resistance and augmentation of blood flow to the limb region (peripheral musculoskeletal system).

Administration, Oral↗
PubMed1987

Influence of exercise on coronary sinus blood flow determinations.

Consecutively measured values of coronary sinus blood flow were compared to assess the reproducibility of the coronary sinus thermodilution technique. Values measured at rest and during exercise were evaluated and the influence of the respiratory cycle on reproducibility was studied. Correlation of consecutive values revealed a coefficient of 0.94 at rest and 0.93 during exercise. Differences between mean values of consecutive measurements were nonsignificant. A comparison of the coefficients of variation at rest (8.50 +/- 7.09) and exercise (8.02 +/- 4.75) revealed no significant difference. Variation about mean coronary sinus blood flow due to inspiration and expiration was similar at rest and during exercise (42% and 37%, respectively). Provided that critical variables are closely monitored, the coronary sinus thermodilution technique is a highly reproducible technique in a clinically feasible setting.

Adult↗
PubMed1987

Position as a variable for cardiovascular responses during exercise.

Twenty-one normal young male subjects underwent resting and exercise (bicycle) radionuclide angiography in the full supine and 70 degrees upright tilt positions in order to examine the effects of position on left ventricular size and performance, hemodynamics, and exercise duration. All subjects also underwent full (90 degrees) upright bicycle ergometry with respiratory gas analysis to establish the level of maximal exercise capacity for each. Body position significantly (p less than 0.05) affected resting and exercise cardiovascular parameters. End-diastolic and endsystolic left ventricular volumes and stroke volume were larger in the supine position, both at rest and during exercise. The cardiac output at rest and during exercise were comparable for the two positions; an increase in resting and exercise heart rate in the 70 degrees tilt position compensated for the reduced stroke volume of this posture. At maximal exercise, the 70 degrees upright position was associated with a greater response in left ventricular ejection fraction, otherwise this parameter was not position related. Exercise capacity, in terms of duration and workload, was significantly higher in the supine (1870 +/- 390 s) and full upright (1830 +/- 250 s) positions than in the 70 degrees tilt position (1730 +/- 260 s). Changes in body position significantly alter parameters of ventricular, cardiovascular, and exercise performance.

Adult↗
PubMed1987

Oral enoximone pharmacokinetics in patients with congestive heart failure.

The pharmacokinetics of enoximone and its sulfoxide metabolite were determined following administration of a single oral dose of 1 or 2 mg/kg in seven patients with congestive heart failure, and in two normal volunteers following a single 75-mg capsule, and were compared to those published previously. Plasma concentrations of the metabolite were higher than enoximone, and their terminal slopes were parallel. Enoximone and enoximone sulfoxide plasma concentration-time data were fitted to a simple model that included a lag time. Absorption half-lives in patinets and normal volunteers averaged 17 minutes; the elimination half-life of enoximone in patients averaged 2.9 hours, and was slightly prolonged as compared with normal volunteers. The elimination half-life of enoximone sulfoxide averaged 17 minutes in patients and normal volunteers, and was considerably shorter than that reported in other studies. The oral clearance of enoximone in patients averaged 99 L/hr, and was lower than that observed in normal volunteers. The ratio of the area under the plasma concentration time curve of enoximone sulfoxide to enoximone averaged 4.7 in patients, and was similar to that observed in normal subjects. Enoximone oral clearance and the ratio of metabolite to parent were related to liver blood flow (determined by indocyanine green). Enoximone is 65% bound to albumin, which accounts for most of the drug bound to human plasma protein.

Administration, Oral↗
PubMed1987

Hemodynamic responses to indoramin at rest and during exercise in congestive heart failure.

Twenty patients with congestive heart failure underwent hemodynamic studies before and over 10 hours after the administration of 25, 50, and 75 mg of indoramin, an alpha 1-adrenergic antagonist. Hemodynamic studies were repeated during exercise after the administration of the optimal dose of indoramin. The drug reduced resting and exercise pulmonary capillary wedge pressure, right atrial pressure, systemic blood pressure and vascular resistance, and pulmonary artery pressure and vascular resistance. Resting and exercise stroke volume and cardiac output rose in response to the fall in vascular resistances. Heart rate was not altered at rest or during exercise. The first dose of the alpha 1 blocker indoramin elicits a significant reduction in ventricular preload and afterload and augmentation of ventricular performance in patients with congestive heart failure.

Aged↗
PubMed1987

Diastolic time in congestive heart failure.

Diastolic perfusion time is an important determinant of coronary blood flow and subendocardial perfusion. It has been proposed that subendocardial ischemia may exacerbate and perpetuate left ventricular dysfunction in congestive heart failure. Diastolic perfusion time in relation to heart rate was analyzed in 29 digitalized (group 1) and 12 nondigitalized patients (group 2) with heart failure and in 58 normal control subjects. In group 1 there was a strong negative exponential correlation (r = -0.85) and in group 2 a strong negative logarithmic correlation (r = -0.95) between heart rate and diastolic time; both regressions differed significantly from normal control. There was a 9% increase of diastolic time at a heart rate of 60 bpm in group 1 and a 7% increase in group 2 (both p less than 0.05) compared with normal subjects. The curves intersected the regression line of normal subjects at a heart rate of 98 bpm in group 1 and 93 bpm in group 2. At 120 bpm there was a 10% decrease in diastolic time for both groups with heart failure (both p less than 0.05). Changes in diastolic perfusion time relative to heart rate are more pronounced in congestive heart failure such that at faster heart rates this relationship may further impede subendocardial blood flow.

Adult↗
PubMed1987

An analysis of the determinants of exercise performance in congestive heart failure.

Twenty-nine patients with chronic congestive heart failure underwent symptom-limited maximal exercise to define the determinants and predictors of exercise capacity in this condition. Clinically, the combination of age, cardiothoracic ratio, and left ventricular displacement was moderately predictive of exercise capacity (R2 = 0.44, p = 0.004). Noninvasive and angiographic measurements of ventricular performance failed to predict maximal exercise duration. Resting systemic and pulmonary arteriolar resistances correlated modestly with maximal effort tolerance (supine: R2 = 0.25, p = 0.02; upright: R2 = 0.38, p = 0.002). At a predetermined level of submaximal exercise, changes in heart rate and pulmonary arteriolar resistance plus the absolute value of systemic arteriolar resistance correlated moderately with exercise duration (R2 = 0.44, p = 0.003). For all parameters examined, exercise capacity was most reliably determined during the transition from submaximal to maximal exercise through the combination of changes in heart rate and stroke volume and the exercise end point value of systemic arteriolar resistance (R2 = 0.87, p = 0.0001). Exercise capacity in chronic cardiac failure appears to be best explained by the patient's ability to increase heart rate and stroke volume beyond a set submaximal stage of exercise. Excessive vascular resistances may further restrain cardiac performance and the delivery of blood to exercising structures during exhaustive exercise.

Adult↗
PubMed1987

Long-term indoramin therapy in congestive heart failure: a double-blind, randomized, parallel placebo-controlled trial.

Twenty-one patients with moderately severe congestive heart failure participated in a double-blind, randomized, parallel placebo-controlled trial designed to evaluate the effects of long-term (2 months) indoramin therapy on rest and exercise hemodynamics, exercise capacity and clinical status of patients with this clinical syndrome. The long-term administration of indoramin in patients (mean dose 50 mg every 12 hours) caused a mild reduction from baseline values in supine rest mean systemic blood pressure and, after dosing, elicited a significant reduction in systemic and pulmonary vascular resistances, pulmonary capillary wedge pressure and heart rate as well as a mild increase in stroke volume. Long-term indoramin therapy caused a small decrease, as compared with baseline exercise responses, in systemic and pulmonary vascular resistance and pulmonary capillary wedge pressure at submaximal levels of exercise. It did not alter hemodynamic variables at maximal exercise, exercise capacity or overall clinical status, compared with findings at baseline or with placebo.

Aged↗
PubMed1987

Survival in congestive heart failure during treatment with drugs with positive inotropic actions.

Retrospective studies have shown that patients with severe chronic heart failure who receive long-term treatment with positive inotropic agents have a high mortality rate, but in the absence of controlled trials it remains unclear whether the high incidence of fatal cardiovascular events in these patients is related to treatment or to the severity of the underlying disease. Most of the evidence that suggests a detrimental effect of positive inotropic therapy on survival remains circumstantial. The pooling of data from long-term studies of patients after an acute myocardial infarction suggests that use of digitalis may be associated with an unfavorable effect on survival. The prolonged administration of intravenous or oral catecholamines is associated with a high mortality rate, which may not be seen in similar patients treated conventionally. The presence of intrinsic sympathomimetic activity appears to neutralize the benefits of beta-blockade during the first year after an acute myocardial infarction; treatment with such agents after the first year may increase mortality. Long-term treatment with phosphodiesterase inhibitors is associated with a high mortality rate, which exceeds that reported in earlier years with vasodilator therapy. Nevertheless, most of these studies of positive intropic agents were not performed to evaluate the issue of survival and did not randomly assign patients to treatment groups. Hence, we do not know that the patients entered into these studies were truly comparable to their proposed control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiotonic Agents↗
PubMed1987

Hemodynamic and metabolic responses of the exercising lower limb of humans.

This study was performed to determine the hemodynamic and metabolic responses of the human lower limb during exercise. Blood flow to the lower extremity was measured and sampled for lactate, catecholamines, and oxygen content in 12 normal men at rest, at all stages of bicycle ergometry, and during the postexercise recovery period. Whole body oxygen consumption and cardiac output were recorded throughout the experiment. Limb blood flow increased in a near-linear manner with both whole body and limb oxygen consumption. Although cardiac output rose with increasing whole body oxygen consumption, the increment in cardiac output diminished between submaximal and maximal levels of exercise resulting in a curvilinear relationship between blood flow to the exercising limb and cardiac output; this indicates that a major redistribution of cardiac output to the exercising lower extremity occurs, particularly at maximal levels of exercise. Covariance analysis suggested that limb oxygen consumption was the primary determinant of limb blood flow and limb vascular resistance during exercise. Arterial and venous lactate and catecholamine concentrations, obtained from the exercising lower extremity, could not be implicated as factors having a major influence on blood flow to that limb. The rate of lactate efflux from the limb during and after exercise, however, was directly related to limb blood flow.

Adult↗
PubMed1986

General overview and update of positive inotropic therapy.

Advances in our understanding of the pathophysiology of cardiac-ventricular failure and the pharmacophysiology of adrenergic receptors have greatly improved the short-term therapy of the low-output, hypotensive-hypoperfused, cardiac failure states. Agents are now specifically selected for these conditions on the basis of their predominant effects on the heart (positive inotropy) and the peripheral vasculature (vasodilatation or vasoconstriction). With the addition of dobutamine therapy, the pharmacophysiologic spectrum now includes norepinephrine (predominant vasopressor), dopamine (combined vasopressor-positive inotrope), dobutamine (predominant positive inotrope), and isoproterenol (combined positive inotrope-vasodilator). Digitalis was introduced to the medical profession 200 years ago. In terms of chronically administered positive inotropic therapy, to date, this "old-timer" has not been replaced. The yet experimental phosphodiesterase inhibitors, enoximone and milrinone, appear promising as long-term nonparenteral inotropes; however, the precise role, clinical effectiveness, and safety profile of these agents remain to be determined.

Amrinone↗