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Biomedical subjects

G J Haas

Publications and source records attributed to G J Haas.

31 records · Page 2Linked to original sources
PubMed1993

Effects of successful cardiac transplantation on plasma endothelin.

After cardiac transplantation, cyclosporine-treated patients exhibit a high incidence of systemic hypertension, the mechanism of which is not known. Endothelin, a potent vasoconstrictor peptide of endothelial origin, may be activated by cyclosporine-induced endothelial injury and therefore may mediate post-transplant hypertension. In the present study, we tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in the plasma of cardiac transplant recipients and if levels correlated with hemodynamic characteristics, cyclosporine level, or renal function as assessed by serum creatinine. Plasma endothelin was measured in 22 stable cyclosporine-treated patients 9 days to 3 years after successful orthotopic cardiac transplantation before routine hemodynamic assessment and surveillance endomyocardial biopsy. Fifteen patients were receiving chronic therapy for hypertension. Plasma endothelin-1 was 5.2 +/- 1.8 pg/ml (range 3.1 to 10.5), which was increased compared with that in 12 normal subjects (1.9 +/- 0.3 pg/ml; range 1.4 to 2.4); the difference was statistically significant (p < 0.0001). Repeated sampling in 8 patients at weekly intervals identified a persistent increase in endothelin with only modest variability. Endothelin-1 did not correlate with any hemodynamic variable, serum creatinine or cyclosporine level. Thus, endothelin-1 is increased after successful orthotopic cardiac transplantation. In the absence of discrete correlations with hemodynamic variables, serum creatinine or cyclosporine levels, both the characteristics and mechanisms for increased endothelin in recipients of cardiac transplants require further evaluation.

Cyclosporine↗
PubMed1993

Timing of recipient atrial contraction: a major determinant of transmitral diastolic flow in orthotopic cardiac transplantation.

The effect of recipient left atrial contraction on diastolic transmitral flow was studied in eight asymptomatic heart transplant patients (seven men and one woman, mean age 51.8 +/- 9.7 years) with normal left ventricular systolic function. The transmitral flow velocity profile was evaluated in 326 beats (mean 40.8 +/- 12 beats, range 20 to 58 beats/patient). Recipient left atrial contraction was classified as early diastolic, late diastolic, and systolic. Results showed: (1) early diastolic transmitral flow velocity integral (in centimeters) was lower (p < 0.05) following late diastolic recipient left atrial contractions (7.5 +/- 2.1) compared with early diastolic (10.1 +/- 2.7) or systolic (8.5 +/- 1.5) recipient left atrial contractions; (2) late diastolic transmitral flow velocity integral was higher following late diastolic (4.7 +/- 1.8) compared with systolic (4.1 +/- 1.9) recipient left atrial contractions and was virtually abolished (0.45 +/- 14) following early diastolic recipient left atrial contractions; and (3) total diastolic transmitral flow velocity integral was significantly higher (p < 0.05) following late diastolic and systolic (12.2 +/- 2.8 and 12.0 +/- 2.5) compared with early diastolic left atrial contractions (10.5 +/- 2.8). Thus recipient left atrial contraction is a significant determinant of the transmitral diastolic flow pattern in heart transplant patients. Variations in the timing of recipient left atrial contraction may lead to fluctuations of diastolic flow and may compromise cardiac output.

Adult↗
PubMed1992

Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure.

BACKGROUND: Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. METHODS AND RESULTS: We tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14 +/- 0.45 l/m/m2, and pulmonary wedge pressure was increased to 22 +/- 7 mm Hg. The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61 mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07 +/- 4.13 pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals (3.7 +/- 0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically significant (p less than 0.0001). Endothelin-1 significantly correlated with pulmonary pressures (systolic, r = 0.78; mean, r = 0.80; diastolic, r = 0.77; all p less than 0.003) and pulmonary vascular resistance (r = 0.65, p less than 0.01). Endothelin-1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r = 0.88, p less than 0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. CONCLUSIONS: Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation.

Adult↗
PubMed1991

Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure.

Although enhanced sympathetic tone is a well recognized component of the autonomic profile characteristic of congestive heart failure, the contribution of parasympathetic withdrawal to this autonomic imbalance is less well described. The technique of spectral analysis of heart rate variability provides a dynamic map of sympathetic and parasympathetic tone and was thus used to define the nature of sympathetic-parasympathetic interactions in humans with idiopathic dilated cardiomyopathy and in a paced canine model of congestive heart failure. Humans with cardiomyopathy were found to have an augmentation of the sympathetically mediated low frequency area of the power density spectrum. Parasympathetic withdrawal was demonstrated by significant reductions in the parasympathetically mediated high frequency area (p less than 0.05) and the ratio of high to low frequency areas (p less than 0.01). Administration of atropine to normal subjects resulted in a significant reduction in the high frequency area (p less than 0.05) and the high/low frequency area ratio, both of which decreased within the range noted in patients with congestive heart failure. Administration of isoproterenol in normal subjects led to an augmentation of the low frequency area but to only a small decrease in the high/low frequency area ratio. Induction of congestive heart failure in a paced canine model resulted in alterations in the autonomic profile that resembled those seen in humans with ventricular failure. The prominent high frequency region of the spectrum at baseline, indicating a predominance of parasympathetic tone, was absent after the evolution of congestive heart failure, and there was a marked augmentation of the low frequency region of the spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Chronic vasodilator therapy with flosequinan in congestive heart failure.

This study was conducted to determine the long-term effect of flosequinan, a new orally administered arterial and venous dilator, on the clinical course of patients with moderate to severe congestive heart failure. Seventeen patients on chronic digitalis and diuretic therapy were randomized to receive either flosequinan (n = 9) or placebo (n = 8) in a double-blind fashion. Changes in symptomatology, exercise performance, and left ventricular function were assessed serially during the two-month treatment period. During the course of therapy, a modest improvement in the symptom scores and functional classification of the flosequinan-treated patients was observed. Flosequinan evoked a significant increase in maximal exercise capacity. While long-term flosequinan administration also effected a progressive increase in resting heart rate, it did not consistently improve indices of left ventricular systolic function. The addition of chronic vasodilator therapy with flosequinan to standard digitalis-diuretic regimens is capable of inducing clinical improvement in patients with moderate to severe chronic heart failure. Trials involving larger patient populations will be necessary to confirm the results of this preliminary study and to determine the extent of clinical improvement, subpopulations benefited, role in heart failure therapeutics, and so forth.

Adult↗
PubMed1990

Invasive cardiovascular testing in chronic congestive heart failure.

The complexity of the congestive heart failure syndrome often calls for a complete evaluation of the patient's cardiovascular status. Determination of the cause, detection, and grading of surgically treatable lesions, assessment of diastolic dysfunction, and development of a therapeutic plan generally require diagnostic cardiac catheterization and/or placement of a flow-directed pulmonary artery catheter. Each procedure has its value and its limitations.

Cardiac Catheterization↗
PubMed1989

Central and regional hemodynamic effects of flosequinan for congestive heart failure.

The central and regional hemodynamic effects of flosequinan, a new orally administered vasodilator, were examined in 10 patients with moderate to severe congestive heart failure. A single-blind design was used to compare a standard dose of flosequinan (100 mg) with placebo. Flosequinan produced a statistically significant increase in cardiac output, primarily through its augmentation of stroke volume. This response was accompanied by significant reductions in systemic vascular resistances and right and left ventricular filling pressures. A reduction in pulmonary artery pressure and total pulmonary vascular resistance also was observed. The vasodilatory actions of flosequinan improved overall left ventricular performance; the inotropic indexes measured were not altered. There were no significant changes in upper limb, renal or hepatic-splanchnic blood flow or in the vascular resistances of these regions after flosequinan administration. The upper limb venous capacitance increased significantly. First-dose flosequinan evokes favorable central hemodynamic changes and improves overall left ventricular performance in patients with congestive heart failure. The acute augmentation in cardiac output, however, is not accompanied by a preferential alteration of flow to any of the major vascular regions studied.

Adult↗
PubMed1984

Effects of captopril on the development of tolerance to guanethidine.

Guanethidine is a sympatholytic antihypertensive drug used for the treatment of severe or resistant hypertension. Previous clinical studies have documented the development of tolerance to guanethidine in humans and suggested that fluid retention or increased sensitivity of arterioles to endogenous catecholamines may be responsible for the tolerance development. In this study we investigated the role of the renin-angiotensin system in the development of tolerance to guanethidine in one-kidney, one-clip renovascular and spontaneously hypertensive rats (SHR) using the angiotensin-converting enzyme inhibitor captopril. In the one-kidney model, captopril (30 mg/(kg X day), orally) had no effect on the development of tolerance to guanethidine (50 mg/(kg X day), i.p.) when the drugs were coadministered for 2 wk. However, captopril enhanced the day 1 blood pressure-lowering effect and prevented the development of tolerance to guanethidine in male SHR. These results suggest that the renin-angiotensin system plays a major role in the development of tolerance to guanethidine in SHR but not in one-kidney, one-clip renal hypertensive rats. Thus, the etiology of the hypertensive state may dictate which physiological compensatory mechanisms are activated after antihypertensive drug administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Etiology, evaluation, and management of acute myocarditis.

The evaluation and management of acute myocarditis remain two of the most difficult challenges that general internists and cardiologists face today. Although the majority of cases are subclinical and self-limited, the true prevalence of myocarditis in the general population is unknown. In its most severe form, patients with myocarditis may present with rapidly progressive heart failure, cardiogenic shock, or complex arrhythmia. Indeed, acute myocarditis should be in the differential diagnosis of acute heart failure, particularly in young and previously healthy individuals.

Acute Disease↗
PubMedDate not supplied

Thermodilution measures of right ventricular ejection fraction and volumes in heart transplant recipients: a comparison with radionuclide angiography.

A reliable, convenient measure of right ventricular ejection fraction may be a useful adjunct to evaluate cardiac allograft rejection. The purpose of this investigation was to compare two measures of right ventricular ejection fraction: (1) radionuclide angiography with the first-pass technique and (2) thermodilution with a balloon flotation catheter. The study was performed in 26 heart transplant recipients; hemodynamics, thermodilution cardiac output, and right ventricular ejection fraction were measured. First pass radionuclide angiography was performed either simultaneously (n = 11) or within 4 hours (n = 15) of the thermodilution study. Mean thermodilution right ventricular ejection fraction was 39% +/- 8%, and radionuclide angiography ejection fraction was 47% +/- 9%, which represents a highly significant difference (p < 0.001) in techniques. Linear regression showed no correlation between the two techniques (r = 0.3; p = NS). No differences in results were observed in those studied simultaneously versus less than 4 hours. We conclude that the thermodilution technique underestimates right ventricular ejection fraction in heart transplant recipients and that its usefulness as a tool to screen for systolic dysfunction related to rejection is limited.

Cardiac Catheterization↗