Biomedical subjects

C V Leier

Publications and source records attributed to C V Leier.

At least 109 records · Page 6Linked to original sources

PubMed1985

Combining left ventricular systolic time intervals and M-mode echocardiography in the evaluation of primary pulmonary hypertension in women.

Eight patients with primary pulmonary hypertension underwent systolic time intervals, M-mode echocardiography, and direct hemodynamic studies in order to determine the correlation between noninvasive parameters and hemodynamic variables and to evaluate the utility of these noninvasive studies in primary pulmonary hypertension. The ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) of the systolic time intervals was abnormally increased (greater than 0.42) for each subject; the increase in the PEP/LVET was secondary to a shortening of the left ventricular ejection time in four patients, prolongation of the pre-ejection period in one, or a combination of such, noted in three patients. In contrast, echocardiographic parameters of left ventricular function, specifically percent change in the minor axis of the left ventricle with systole, velocity of circumferential fiber shortening, and ejection fraction, were normal. In addition, a very good correlation was noted between PEP/LVET and total pulmonary resistance (r value = -0.89, p less than 0.05), while the echocardiographic parameters correlated well with stroke volume and cardiac output (r values ranged from 0.68 to 0.72, p less than 0.05). These results indicate that in primary pulmonary hypertension, the performance of both systolic time intervals and M-mode echocardiography noninvasively provides useful information concerning the hemodynamic status of these patients. Systolic time intervals provide an estimation of overall cardiac-cardiovascular performance, rather than left ventricular function alone, which in turn, is validly examined by M-mode echocardiography.

Adult↗

PubMed1985

Nitrate tolerance.

The nitrate group of drugs is one of the most commonly used therapeutic modalities. The application of the nitrates is generally directed at ameliorating the symptoms of occlusive coronary artery disease (angina) and/or congestive heart failure. Although studies are available that attempt to refute the concept of nitrate-induced tolerance in angina pectoris, well-designed and well-controlled reports are appearing that convincingly establish the occurrence of one or more expressions of tolerance (e.g., shorter duration of action, loss of intensity of effect) with long-term dosing in this clinical setting. The type and degree of tolerance to nitrate therapy in angina pectoris depend on a number of pharmaceutic-pharmacokinetic considerations, including route of administration, dose strength, dosing frequency, and magnitude and duration of drug delivery. Reports concerning the development of tolerance to nitrates in congestive heart failure are also somewhat conflicting. However, one form and dose of nitrate therapy has been studied rather extensively: isosorbide dinitrate at 40 mg orally every 6 hours. The administration of this preparation over 3 months to a population with heart failure resulted in the development of tolerance to the systemic arterial-arteriolar effects, whereas the pulmonary vascular and venous dilative effects were maintained throughout the long-term dosing period. Exercise tolerance improved for the long-term isosorbide dinitrate group compared to the group receiving long-term placebo therapy. The mechanism(s) of tolerance to the nitrates is not known; altered disposition of reduced sulfhydryl groups at receptor and intracellular sites is the leading hypothesis.

Administration, Oral↗

PubMed1985

Prevention of bedrest-induced physical deconditioning by daily dobutamine infusions. Implications for drug-induced physical conditioning.

The effects of intermittent infusions of dobutamine were studied in young normal male subjects during a period of bedrest deconditioning to determine whether this synthetic catechol affects physical conditioning processes in humans. 24 volunteers were placed at bedrest and randomized to daily 2-h treatments of saline infusions (control), dobutamine infusions, or maintenance exercise (control). Exercise, hemodynamic, and metabolic studies were performed at base line and at the termination of the 3-wk treatment period. Maximal exercise (duration, oxygen consumption, and workload) fell for the saline group and remained unchanged for the dobutamine and exercise groups. Hemodynamics during exercise were maintained the same as pretreatment base line for the dobutamine and exercise groups, whereas stroke volume and cardiac output dropped and heart rate rose for the saline group. The metabolic profile showed an increased blood lactate response at rest and during submaximal exercise after 3 wk of bedrest for the saline group, and essentially no change for the exercise and the dobutamine groups. Extraction of oxygen across the exercising lower limb rose for the dobutamine group, as did the activity of the skeletal muscle oxidative enzymes, citrate synthetase, and succinate dehydrogenase. In contrast to the exercise control group, the saline and dobutamine groups developed orthostatic hypotension, tachycardia, and accentuation of the renin-aldosterone response over the 3-wk treatment period; for the saline group, this is best explained by the observed fall in blood volume and for the dobutamine group, by the blunting of vascular vasoconstrictive responses. During a period of bedrest deconditioning in humans, infusions of dobutamine maintain many of the physiologic expressions of physical conditioning.

Adult↗

PubMed1985

Postural influences on the hemodynamic responses to vasodilating drugs in congestive heart failure.

Supine and upright hemodynamic measurements were performed in 58 patients with congestive heart failure to assess the effects of postural change on the hemodynamic responses to vasodilating drugs. The patient population was divided into three treatment groups and was studied before and after isosorbide dinitrate, nifedipine, or clonidine treatment. When the hemodynamic responses in the upright position were compared with the supine values, isosorbide dinitrate (40 mg orally) evoked a greater reduction in mean systemic blood pressure and stroke volume with augmented increases in heart rate, mean pulmonary artery pressure, and pulmonary vascular resistance while the patient was upright. Nifedipine (10 mg orally) when studied in the upright position caused additional augmentation of cardiac output and stroke volume index with further reduction in total systemic vascular resistance compared with supine values. No position-related changes in hemodynamic measurements were noted with clonidine (0.1 mg orally).

Adult↗

PubMed1984

Factors influencing the one-year mortality of dilated cardiomyopathy.

This study was designed to determine prognostic risk indicators of nonischemic dilated cardiomyopathy (DC). Sixty-nine patients were studied. Each patient underwent physical examination (including a history), electrocardiography, echocardiography, cardiac catheterization, 24-hour monitoring and endomyocardial biopsy. The mortality rate at 1 year was 35% (24 deaths). Univariate analysis revealed that the most powerful predictor of prognosis was the left intraventricular conduction delay (p = 0.003). The pulmonary capillary wedge pressure was also predictive of mortality (p = 0.005). Other significant factors, in order of importance, were ventricular arrhythmias (p = 0.007), mean right atrial pressure (p = 0.008), angiographic ejection fraction (p = 0.03), atrial fibrillation or flutter (p = 0.01) and the presence of an S3 gallop (p = 0.05). Factors such as duration of symptoms, presence of mitral regurgitation, end-diastolic diameter, myocardial cell size and percent fibrosis in the biopsy and treatment with vasodilators, antiarrhythmic and anticoagulant drugs were not significant predictors. Multivariate analysis was used to determine which combination of factors could most accurately predict survival and death. The most important factors were left conduction delay, ventricular arrhythmias and mean right atrial pressure. An equation was derived that can be applied to the prognosis of patients with DC. Thus, the clinical assessment of patients with DC can accurately predict the probability of surviving or dying in 1 year.

Adult↗

PubMed1984

Disopyramide pharmacokinetics and bioavailability following the simultaneous administration of disopyramide and 14C-disopyramide.

The pharmacokinetics and bioavailability of total (bound plus unbound) and unbound disopyramide were compared following the simultaneous administration of an oral dose of disopyramide and an intravenous dose of 14C-disopyramide in five normal volunteers and in 11 patients with congestive heart failure. The binding of disopyramide varied between 60 and 92% in patients and between 81 and 88% in normal subjects at postequilibrium drug concentrations of 10(-7) M. The binding of disopyramide to serum protein was concentration-dependent in all study subjects at serum concentrations achieved following drug administration. The association constant for the first binding site in serum from normal subjects and patients averaged 8.7 X 10(5) M-1 and 4.4 X 10(5) M-1, respectively (p less than 0.05). The unbound clearance of disopyramide averaged 277 ml/min and 209 ml/min in normal subjects and in patients (p less than 0.05). When normalized for body weight, the unbound clearance between patients and normal subjects was not significantly different. The elimination half-life of unbound concentrations in normal subjects and in patients averaged 4.9 and 6.1 h, respectively (p less than 0.05). The clearance and elimination half-life of total disopyramide was the same in both groups. Although the bioavailability of disopyramide averaged 0.85 in both groups, it was more variable in patients owing to the variability in the fraction of the dose absorbed. The unbound renal clearance and volume of distribution at steady state of disopyramide was related to cardiac index. The ratio of elimination half-lives of total and unbound disopyramide was related to the extent of serum protein binding.

Adult↗

PubMed1984

Nifedipine in congestive heart failure: effects on resting and exercise hemodynamics and regional blood flow.

Ten patients with moderate to severe congestive heart failure (CHF) underwent central and regional hemodynamic measurements at rest and central hemodynamic measurements during exercise before and after the oral administration of nifedipine (0.2 mg/kg). Nifedipine significantly decreased systemic blood pressure, systemic vascular resistance, pulmonary artery pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure. Stroke volume and cardiac output increased after nifedipine. The measured parameters of left ventricular inotropy did not change significantly for this calcium channel blocker. While blood flow to renal, hepatic, and limb vascular beds increased (p less than 0.05 for renal and limb) after nifedipine, only limb blood flow increased in proportion to the increase in cardiac output, suggesting preferential dilatation of limb vasculature. Although initial-dose nifedipine did not increase exercise duration, it elicited an improvement in exercise hemodynamics by reducing systemic vascular resistance and pulmonary capillary wedge pressure and increasing stroke volume and cardiac output. The calcium channel blocker, nifedipine, can be administered safely in the setting of ventricular failure and appears to favorably alter resting and exercise hemodynamics. A select number of patients with CHF may benefit from its long-term administration.

Adult↗

PubMed1984

The electrophysiologic effects of upright posture.

In order to determine the effects of upright posture on the electrophysiologic properties of the human heart, 12 patients underwent electrophysiologic studies in the supine and upright positions. Compared to supine, the upright position significantly reduced basic cycle length from 818 +/- 111 to 680 +/- 141 msec, sinoatrial conduction time from 186 +/- 94 to 135 +/- 56 msec, corrected sinoatrial recovery time from 206 +/- 104 to 108 +/- 55 msec, interatrial conduction time from 76 +/- 17 to 70 +/- 16 msec, and the AV nodal conduction time (AH interval) from 88 +/- 19 to 78 +/- 14 msec (all p less than 0.05). Right intra-atrial and His-Purkinje (HV interval) conduction times were not altered. When the subjects assumed the upright position, the effective refractory periods of the right atrium, atrioventricular node, and right ventricle decreased significantly at basic and paced cycle lengths. For the group as a whole, the upright posture did not significantly augment repetitive responses to atrial and ventricular extrastimuli.

Adolescent↗

PubMed1984

Hydralazine therapy in chronic congestive heart failure. Sustained central and regional hemodynamic responses.

Central and regional hemodynamic parameters were evaluated at baseline and following three months of placebo or hydralazine therapy (100 mg orally every eight hours) in 20 patients with idiopathic dilated cardiomyopathy. Both control (placebo) and hydralazine groups were comparable with respect to functional classification (New York Heart Association classes III and IV) and baseline hemodynamic variables. In the hydralazine group, cardiac index increased 25 percent (2.4 +/- 0.4 to 3.0 +/- 0.5 liters/minute/m2), renal blood flow increased 26 percent (648 +/- 199 to 815 +/- 229 ml/minute), and limb blood flow was augmented by 35 percent (6.8 +/- 3.0 to 9.2 +/- 4.6 ml/dl/minute) with long-term therapy. These changes were significant (all p less than 0.05) when compared with both baseline values and values in the control group. Both central and regional hemodynamic parameters remained unaltered in the control group. Long-term hydralazine therapy (three months) elicited a favorable circulatory response in this group of patients with chronic congestive heart failure. Central or regional hemodynamic tolerance to oral hydralazine failed to develop in the majority of patients.

Administration, Oral↗

PubMed1984

Atrial fibrillation in mitral stenosis: histologic, hemodynamic and metabolic factors.

We examined the histologic, hemodynamic and metabolic factors associated with rheumatic mitral stenosis. Eighteen patients comprised three groups: Group I - 7 patients in sinus rhythm; Group II - 5 patients in intermittent atrial fibrillation; Group III - 6 patients in chronic atrial fibrillation. The left atrial dimension was determined by echocardiography. Left atrial pressure, mitral valve gradient, mitral valve area and the presence or absence of calcium in the mitral valve were determined at catheterization. The left atrial appendage was removed during open heart surgery and the tissue was analyzed for cell size, percent fibrosis and content of cyclic AMP and GMP. There was no difference between the groups in pulmonary capillary wedge pressure, mitral valve gradient, mitral valve area or the presence of calcium. The Group I left atrial dimension (51 +/- 2 mm, means +/- SE) was significantly smaller than that of Group III (56 +/- 2 mm, P less than 0.05). Group II was not different from Groups I or III. Although the concentration of cyclic AMP did not differ among the groups, the cyclic GMP was significantly depressed in Group III (0.15 +/- 0.02 fmol/microgram protein) when compared to Group I (0.24 +/- 0.05 fmol/microgram protein, P less than 0.01). Group II had intermediate values which did not differ from Groups I or III. The percent fibrosis was greatest in Group III (34.8 +/- 1.8%) and least in Group I (27.2 +/- 2.8%, P less than 0.05). There was no difference in cell size among the groups. Although atrial fibrillation may lead to some of these irregularities, a depressed cyclic GMP, increased fibrosis and increased left atrial dimension may play a role in the pathogenesis of irreversible atrial fibrillation.

Adult↗

PubMed1984

Oral amrinone for the treatment of chronic congestive heart failure: results of a multicenter randomized double-blind and placebo-controlled withdrawal study.

A placebo-controlled study was employed to evaluate the effects of oral amrinone in patients with congestive heart failure. After a baseline period of at least 4 weeks of standard treatment for refractory congestive heart failure, oral amrinone was added to the treatment regimen of 173 patients. Patients were predominantly male (89%), aged 24 to 76 years (mean 54), with ischemic (52%) or idiopathic (37%) dilated cardiomyopathy, in New York Heart Association functional class II (40%), III (59%) and IV (1%) and having a mean (+/- standard deviation) left ventricular ejection fraction of 25 +/- 15%. Phase 1: After the addition of amrinone (113 +/- 33 mg three times daily), 52 patients (30%) showed a maximal increase in treadmill exercise time exceeding 2 minutes (Naughton protocol), 72 (42%) had a lesser increase, 24 (14%) developed limiting adverse reactions, 20 (12%) died and 5 dropped out of the study. Fifty-two "responders" (30%) who were free of limiting side effects and had a greater than 2 minute increase in exercise time were randomized in double-blind fashion to continued amrinone or switched to placebo (each plus standard treatment) for an additional 12 weeks. Phase 2: Comparison of 31 of these 52 responders who continued to receive amrinone with the remaining 21 randomized to placebo revealed no significant differences in vital signs, indexes of left ventricular size and function, systolic time intervals or maximal exercise time. Continued follow-up study of patients receiving either amrinone or placebo revealed decreases in exercise times of 7 and 10%, respectively (both p less than 0.05 compared with before randomization). Episodes of worsened congestive heart failure severe enough to mandate termination of double-blind treatment were as frequent in patients taking placebo (4[18%] of 21) as in those taking amrinone (4[13%] of 31; p = NS). The average symptom score and functional class of each treatment group remained comparable. Adverse effects such as gastrointestinal and central nervous system complaints were more common with amrinone treatment as were elevations of serum liver enzymes and reduced platelet counts. This large multicenter, randomized double-blind withdrawal study revealed no change in estimates of cardiac performance after the discontinuation of amrinone. These findings suggest that amrinone, in the dosages tested, does not importantly improve cardiac function beyond that provided by standard treatment with digoxin, diuretic drugs and vasodilators.

Adult↗

PubMed1984

Effect of oral amrinone on platelet function and survival.

Amrinone is a cardiotonic agent associated with reversible thrombocytopenia in 20% to 50% of patients. The mechanism of thrombocytopenia is not known and it is not clear whether this effect represents a high-frequency idiosyncratic reaction or an overt manifestation of a toxic effect on platelet survival. We prospectively evaluated the effect of oral amrinone on platelet function and survival in seven subjects who participated in a clinical trial of chronic oral amrinone therapy. There was no consistent effect on either platelet function or platelet survival. Data suggest that amrinone does not have a uniform effect on platelet survival and that the development of thrombocytopenia may represent an idiosyncratic reaction.

Administration, Oral↗

PubMed1984

The evolution of beta-adrenergic dysfunction during the induction of canine cobalt cardiomyopathy.

This study was designed to investigate the changes in the beta adrenergic system during the induction of cobalt cardiomyopathy in dogs. Cobalt sulphate, at a dose of 5 mg X kg-1 X day-1 was administered intravenously with a low protein, low thiamine diet to 13 dogs. The percentage change of the left ventricular minor axis with systole by echocardiogram (% delta D) and dP/dtmax were used to monitor left ventricular function. Noradrenaline (NA) was measured in 24 h urine samples. Left ventricular (LV) free wall biopsies were assayed for noradrenaline (LV-NA), cyclic AMP, cyclic GMP and dopamine beta hydroxylase (LV-DBH). Lymphocytes were assayed for beta-receptor density. All dogs were studied at baseline and seven were studied after a midpoint cumulative dose of 60 to 90 mg X kg-1 of cobalt; the remaining six dogs were studied when they were in heart failure and had received more than 110 mg X kg-1. During the induction of heart failure the heart rate rose from 112 +/- 6 (means +/- SE) at baseline to 154 +/- 9 at the midpoint and 153 +/- 9 (both P less than 0.05) at the final measurement while the % delta D fell from 35 +/- 2% to 31 +/- 3% and 23 +/- 2% (P less than 0.05) and dP/dt fell from 333 +/- 40 kPa X s-1 at baseline to 254 +/- 46 kPa X s-1 (P less than 0.05) and 207 +/- 33 kPa X s-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Combined systolic time intervals and M-mode echocardiography in the evaluation of central hemodynamics in primary pulmonary hypertension.

8 patients with moderate to severe primary pulmonary hypertension underwent systolic time intervals, M-mode echocardiography, and direct hemodynamic studies in order to determine the correlation between noninvasive parameters and hemodynamic variables and to evaluate the utility of these noninvasive studies in primary pulmonary hypertension. The ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) of the systolic time intervals was abnormally increased (greater than 0.42) for each subject; the increase in the PEP/LVET was secondary to a shortening of the left ventricular ejection time in 4 patients, prolongation of the pre-ejection period in 1, or a combination of such, noted in 3. In contrast, echocardiographic parameters of left ventricular function, specifically, percent change in the minor axis of the left ventricle with systole, velocity of circumferential fiber shortening, and ejection fraction, were normal. In addition, a very good correlation was noted between PEP/LVET and total pulmonary resistance (r value = -0.89), while the echocardiographic parameters correlated well with stroke volume and cardiac indices (r values ranged from 0.68 to 0.72). These results indicate that in primary pulmonary hypertension, systolic time intervals provide an estimation of overall cardiac-cardiovascular performance, rather than left ventricular function alone, which in turn, is validly examined by M-mode echocardiography.

Adult↗

PubMed1984

The effect of age on central and regional hemodynamics.

16 normal subjects, ranging in age from 24 to 79 years, underwent simultaneous central and regional (renal, hepatic and limb) hemodynamic measurements; the purpose of this investigation was to determine the relationship between these measurements and age. Cardiac index was inversely related to age, with a correlation coefficient of -0.53 (p less than 0.05). Renal blood flow correlated inversely with age at an r value of -0.52 (p less than 0.05). Although the correlation coefficients did not achieve statistical significance, several trends were noted with increasing age: systemic vascular resistance, renal, hepatic and limb vascular resistances, and mean systemic blood pressure increase and hepatic and limb flows decrease. In normal human subjects, certain central and regional hemodynamic parameters change with age; these changes may ultimately influence function and perhaps, drug disposition (liver and kidney) as well.

Adult↗

PubMed1984

Relationship between central hemodynamics and regional blood flow in normal subjects and in patients with congestive heart failure.

Central and regional (hepatic, renal, and limb) hemodynamic data are presented for a normal population (n = 16) and for a group of patients with congestive heart failure (n = 64). The patient population represented a wide spectrum of severity of congestive heart failure. Various relationships between central and regional hemodynamics were analyzed. The results indicate that in congestive heart failure blood flow to hepatic, renal, and limb regions is significantly decreased, and that this decrease is proportional and linearly related to the reduction in cardiac output. The vascular resistances of these regions correlated directly with systemic vascular resistance. Changes in renal vascular resistance and renal blood flow became attenuated as the severity of the heart failure advanced from moderate to severe and at higher levels of systemic vascular resistance. There was little to no correlation between systemic blood pressure and liver, kidney, and limb blood flow for the range of systemic pressures studied.

Adult↗

PubMed1984

The noninvasive localization of ventricular pacing sites by radionuclide phase imaging.

This study was designed to investigate the potential role of radionuclide angiographic phase imaging in defining ventricular pacing sites. Twenty patients were paced from multiple right ventricular and left ventricular sites. Ten patients had both normal wall motion and normal electrocardiograms (ECGs), while 10 patients had segmental wall motion abnormalities and/or bundle branch block. Both continuous pacing and premature ventricular stimuli were performed. Multiple (two to three) views of each pacing site were obtained by radionuclide angiography and the ventricular site was determined by subsequent phase imaging. Simultaneous 12-lead ECGs were also obtained. The phase-imaging technique accurately localized all 35 right ventricular and 21 of 25 (84%) left ventricular sites to a specific segment. Statistically, this localization ability was independent of baseline wall motion or conduction system disease. In addition, sites as close as 1.5 cm were identified. The 12-lead ECG distinguished left ventricular from right ventricular pacing sites in all patients. Segmental localization by ECG in the right ventricle was accurate in 24 of 35 (69%) and in the left ventricle in 17 of 25 (68%). Thus, radionuclide angiographic phase imaging provides excellent descriptive information regarding the focus of ventricular pacing ectopy and can define both sites of continuous pacing and intermittent premature ventricular stimulation. These findings provide a basis for further assessment of the role of phase imaging in the evaluation of patients with spontaneous ventricular ectopy.

Bundle-Branch Block↗

PubMed1984

Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure.

Rest and exercise systemic hemodynamic parameters, coronary blood flow, and myocardial energetics were assessed before and 15 min after the sublingual administration of 20 mg of nifedipine in 10 patients with idiopathic congestive cardiomyopathy. When compared with control, nifedipine increased rest and exercise cardiac index by 37% and 28%, respectively (p less than .001). Peripheral vasodilation was demonstrated with a drop in systemic arterial pressure, exercise pulmonary capillary wedge pressure, and systemic vascular resistance (p less than .05). The calcium-channel blocker did not alter myocardial oxygen consumption; however, coronary blood flow increased by 32% at rest (p less than .01) while coronary vascular resistance diminished both at rest and after exercise compared with control (p less than .05). Nifedipine elicited a decrease in the rest and exercise aortocoronary sinus oxygen difference while the coronary sinus oxygen saturation increased (p less than .01). In this group of patients with idiopathic congestive cardiomyopathy, nifedipine enhanced myocardial performance while increasing coronary blood flow and favorably altering the myocardial oxygen supply-demand balance.

Adult↗