Differential hemodynamic effects of oral enoximone in severe congestive heart failure.
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Administration, Oral↗
Biomedical subjects
S Murali
Publications and source records attributed to S Murali.
Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group.
A multicenter double-blind, randomized, placebo-controlled trial of oral enoximone, a phosphodiesterase inhibitor, was conducted in 102 outpatients (50 receiving enoximone and 52 receiving placebo) with moderate to moderately severe congestive heart failure. All were on a long-term regimen of digoxin and diuretics without vasodilators and converting enzyme inhibitors. Symptom score was obtained, and exercise testing was performed monthly for 4 months. There were no differences between groups in symptoms or exercise duration at the end of 4 months. A subgroup undergoing analysis of oxygen consumption with measurement of anaerobic threshold during exercise showed an increase (p less than 0.05) in anaerobic threshold at 1 month with enoximone. (2.7 +/- 0.8 ml O2/kg/min) compared with placebo (-0.8 +/- 1.2 ml O2/kg/min). This improvement was not sustained at 4 months (0.5 +/- 1.7 ml O2/kg/min with enoximone and 0.2 +/- 1.5 ml O2/kg/min with placebo). The dropout rate was significantly higher (p less than 0.02) with enoximone (46%) than with placebo (25%). Adverse effects other than death were slightly, but not significantly, higher with enoximone (32%) than with placebo (22%). During therapy, five deaths occurred in the enoximone group, and none occurred in the placebo group (p less than 0.05). Two deaths were sudden, two were from progressive congestive heart failure, and one was from acute myocardial infarction. With intention-to-treat analysis and inclusion of patients who were removed from therapy because of lack of study drug effect, 10 deaths occurred in the enoximone group, and three occurred in the placebo group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Control of atrial natriuretic peptide secretion in patients with severe congestive heart failure.
Congestive heart failure (CHF) is marked by activation of multiple hormone systems that increased peripheral vasoconstriction and produce sodium and water retention. Plasma atrial natriuretic peptide (ANP) levels are frequently elevated in patients with severe CHF and may act to counterbalance these hormonal actions. To determine whether CHF patients maintain a physiological response to the presumed major stimulus to ANP secretion, atrial stretch, 22 CHF patients and 8 normal volunteers were studied. Atrial distention was produced in 10 CHF patients with a mannitol infusion and in 12 with lower body positive pressure. Eight normal volunteers also underwent a mannitol infusion. Both stimuli provoked increases in plasma ANP levels in the CHF patients, and the relative increase in plasma ANP after mannitol was similar in the CHF patients and the normal volunteers. We conclude that ANP secretion responds to atrial stretch in CHF patients, suggesting maintenance of the physiological release of this peptide.
Adult↗
Resolution of severe pulmonary hypertension after heterotopic cardiac transplantation.
In patients with severe congestive heart failure, a marked elevation in pulmonary vascular resistance limits the success of orthotopic cardiac transplantation, thus providing the rationale for heterotopic transplantation. To determine the changes in pulmonary hemodynamics after heterotopic cardiac transplantation, postoperative right heart pressures were serially measured in five patients who underwent this operation for end-stage congestive heart failure accompanied by severe secondary pulmonary hypertension and elevation in calculated pulmonary vascular resistance. Hemodynamics were compared with those of a matched group of 10 orthotopic cardiac transplant recipients. Preoperatively, pulmonary artery mean and wedge pressures, pulmonary vascular resistance and transpulmonary pressure gradient (pulmonary artery mean minus wedge pressure) were significantly higher in the heterotopic group. Postoperatively, significant improvement in pulmonary hemodynamics occurred in both groups and, by 12 months, the pulmonary artery mean pressure, wedge pressure, pulmonary vascular resistance and transpulmonary pressure gradient were similar in the two groups. These findings suggest that pulmonary hypertension secondary to congestive heart failure, even when severe and associated with a high pulmonary vascular resistance, is to a great extent reversible.
Adult↗
Hemodynamic abnormalities following cardiac transplantation: relationship to hypertension and survival.
The prevalence and long-term implications of hemodynamic abnormalities seen at 1 year following orthotopic heart transplantation and their relationship to post-transplant hypertension were prospectively evaluated in 82 consecutive asymptomatic recipients taking cyclosporine and prednisone who underwent annual catheterization. Abnormal left ventricular end-diastolic pressure (LVEDP), ejection fraction (EF), and left ventricular end-diastolic pressure-volume ratio (R) were the most prevalent hemodynamic abnormalities (27%, 14%, and 23%, respectively, at 1 year). Patients with abnormal LVEDP or R had higher (p less than 0.05) mean systemic arterial pressure (MAP). During follow-up, hemodynamic abnormalities disappeared in some patients while they developed in some others. Transplant patients with abnormal LVEDP, EF, or R at 1 year who normalized at 2 years had a significant (p less than 0.05) decrease in MAP. Likewise, patients with normal LVEDP, EF, or R at 1 year who subsequently developed abnormalities had a significant (p less than 0.05) increase in MAP. The presence of hemodynamic abnormalities at 1 year was not associated with a poorer survival (mean follow-up 2.6 +/- 1.1 years). In summary, hemodynamic abnormalities in asymptomatic transplant recipients taking cyclosporine and prednisone appear to be related to the level of post-transplant hypertension and do not signify an adverse prognosis over the first 3 years.
Adult↗
The acute effect of an oral "inotropic" placebo on the exercise capacity of patients with chronic cardiac failure.
Uncontrolled studies have suggested that the newer oral phosphodiesterase inhibitors milrinone and enoximone acutely improve exercise performance in patients with severe chronic cardiac failure. To determine whether an oral placebo presented as an inotropic agent could acutely enhance exercise capacity, two separate groups of stable heart failure patients were studied by serial exercise testing and respiratory gas exchange analysis. Group 1 had nine patients studied four hours after a single oral dose of placebo, and group 2 had ten patients retested after one to two weeks of placebo therapy. No significant change was seen in the mean exercise time, mean peak oxygen consumption, and the mean oxygen consumption at anaerobic threshold after placebo administration in both group 1 and group 2 patients. Improvements in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold occurred in five patients in group 1 and seven patients in group 2. The improvements exceeded the baseline variability of 10 percent in three group 1 patients. Among group 2 patients, the increase in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold exceeded 10 percent in six, four, and four patients, respectively. Thus, stable chronic heart failure patients can achieve a true baseline exercise capacity. Small improvements in exercise performance seen acutely after oral inotropic drug therapy in individual heart failure patients must be interpreted with caution, as they may be due to a placebo effect.
Aged↗
Acute hemodynamic and hormonal effects of CI-930, a new phosphodiesterase inhibitor, in severe congestive heart failure.
The phosphodiesterase inhibitor CI-930 hydrochloride exerts a positive inotropic and vasodilator effect in experimental animals. The acute hemodynamic and hormonal effects of intravenous CI-930 were studied in 9 patients with severe congestive heart failure. At 60 minutes of drug infusion, there was an increase in cardiac index (2.7 +/- 0.9 vs 2.0 +/- 0.7 liters/min/m2, p less than 0.01) and positive dP/dt (1,390 +/- 470 vs 1,100 +/- 300 mm Hg/s, p less than 0.02). Additionally, there were decreases in mean systemic arterial (78 +/- 16 vs 86 +/- 15 mm Hg, p less than 0.01), mean right atrial (5 +/- 3 vs 9 +/- 4 mm Hg, p less than 0.02), mean pulmonary arterial (27 +/- 11 vs 37 +/- 9 mm Hg, p less than 0.01) and LV end-diastolic (19 +/- 8 vs 28 +/- 6 mm Hg, p less than 0.01) pressures. Heart rate did not change (97 +/- 17 vs 97 +/- 22 beats/min). The inotropic response correlated significantly (r = 0.70, p less than 0.05) with the dose of CI-930. Plasma renin activity did not change significantly (from 16 +/- 9 to 23 +/- 15 ng/ml/hour), nor did plasma norepinephrine or arginine vasopressin levels. The plasma atrial natriuretic peptide level decreased (from 153 +/- 97 to 83 +/- 35 pg/ml, p less than 0.02). These findings suggest that intravenous CI-930 hydrochloride is a useful therapeutic agent in congestive heart failure and that its use does not appear to further activate potentially deleterious hormonal systems.
Heart Failure↗
Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone.
Coronary artery disease (CAD) has been shown in previous uncontrolled studies to be a limiting factor to long-term survival in patients undergoing cardiac transplantation and who were taking conventional immunosuppressive agents. To study the development of CAD after cardiac transplantation in patients taking the newer immunosuppressive agent cyclosporine, we prospectively performed yearly coronary arteriography on all eligible transplantation patients (first year, 57 patients; second year, 30 patients; third year, 14 patients). The prevalence of CAD by life table analysis was 18% at 1 year, 27% at 2 years, and 44% at 3 years. The occurrence of two or more major rejection episodes was associated (p less than .005) with the development of CAD. In two patients who died of CAD, coronary artery histology revealed subintimal inflammatory cellular infiltration in some lesions. These data demonstrate that the prevalence of CAD rises progressively over time and immunologic factors may be important in its development.
Adult↗
Hemicastration-induced changes in the electrophoretic pattern of some enzymes in the brain of the skink, Mabuya carinata.
Hemicastration in the skink induces change in the electrophoretic pattern of some enzymes like LDH, MDH, acid phosphatase and esterases.
Acid Phosphatase↗
Conjugated estrogens acutely abolish abnormal cold-induced coronary vasoconstriction in male cardiac allografts.
BACKGROUND: Transplant-associated coronary arteriopathy is manifested in its early stages by paradoxical coronary artery constriction in response to endothelium-dependent vasodilator stimuli such as the cold pressor test (CPT) and is a major cause of death or retransplantation. Estrogen has vasoactive properties that abolish coronary artery endothelial dysfunction in native hearts. We hypothesized that estrogen attenuates inappropriate coronary artery constriction in cardiac allografts. METHODS AND RESULTS: Coronary artery diameter and systemic hemodynamic responses to a 90-second CPT were measured before and 15 minutes after double-blind, randomized administration of intravenous conjugated estrogens (1.25 mg) or placebo in men with male cardiac allografts. Before estrogen, 9 men exhibited an abnormal 15.1 +/- 3.0% CPT-induced decrease in coronary artery diameter. However, repeat CPT did not induce significant coronary artery constriction when performed 15 minutes after estrogen. CPT responses before and after estrogen were significantly different (P=.02). Placebo did not influence coronary artery responses to CPT in 6 men. Systemic hemodynamic responses to CPT were not influenced by estrogen or placebo. Estrogen was the only significant determinant of changes in coronary artery responses to CPT. CONCLUSIONS: Conjugated estrogens acutely abolish abnormal CPT-induced coronary artery constriction in male cardiac allografts. This favorable vasomotor effect suggests that estrogen may prevent inappropriate coronary artery constriction in men with cardiac transplants.
Cold Temperature↗
Utility of prostaglandin E1 in the pretransplantation evaluation of heart failure patients with significant pulmonary hypertension.
Patients with chronic heart failure frequently have pulmonary hypertension. Because severe preoperative pulmonary hypertension predicts a poor outcome after orthotopic transplantation, pulmonary vasoreactivity is evaluated frequently in the pretransplantation screening of heart failure patients. We prospectively evaluated the utility of the direct pulmonary vasodilator, prostaglandin E1, and compared it to the nonspecific vasodilators, nitroglycerin and sodium nitroprusside, in the evaluation of pulmonary hypertension in 39 heart transplantation candidates. Prostaglandin E1 significantly lowered pulmonary artery pressure, transpulmonary pressure gradient, and pulmonary vascular resistance. An adequate pulmonary vasodilator response (defined as a decline in transpulmonary pressure gradient to less than 15 mm Hg) occurred in 31 patients (79%). In a subgroup of nine patients also tested with nitroglycerin, greater reductions (p less than 0.01) in both transpulmonary pressure gradient and pulmonary vascular resistance occurred with prostaglandin E1, compared to nitroglycerin. Five of six patients who did not respond to nitroglycerin responded to prostaglandin E1. In another subgroup of 12 patients who were also evaluated with sodium nitroprusside, prostaglandin E1 produced a larger decline (p less than 0.05) in transpulmonary pressure gradient and pulmonary vascular resistance than did sodium nitroprusside. Six of eight patients who did not respond to sodium nitroprusside responded to prostaglandin E1. Based on pulmonary vasodilator response to prostaglandin E1, 27 patients were accepted on the transplantation waiting list, and eight patients underwent orthotopic transplantation. Postoperatively, acute right ventricular failure of the donor heart developed in none of these patients. Significant hemodynamic improvement occurred by 24 hours and persisted through 4 weeks of postoperative follow-up in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Alprostadil↗
Cardiac events after heart transplantation: incidence and predictive value of coronary arteriography.
Cardiac events from graft arteriopathy, including myocardial infarction, heart failure resulting from previous myocardial infarction, and sudden death, may limit long-term survival after heart transplantation. To determine the incidence of cardiac events and the use of coronary arteriography in predicting these events, the long-term results (mean follow-up, 3.5 years; standard deviation +/- 2.0) of heart transplantation in 427 patients were reviewed. Cardiac events included 19 cases of myocardial infarction, 13 cases of sudden death, and 10 cases of congestive heart failure. All these events occurred after the first year except for three cases of sudden death and one case of myocardial infarction. Cumulative incidence of cardiac events per patient year was 0.9% within the first year, increasing to 1.9% by 5 years. Cardiac events accounted for 3.8% of the deaths by the end of the first year, rising to 18% of total mortality by 7 years after heart transplantation. In patients dying after the first year of transplantation, deaths from sequelae of coronary artery disease occurred in 36% (20/55). The relative risk ("odds ratio") of any cardiac event was 3.44 (p less than 0.05) in patients with angiographic evidence of obstructive disease compared with those without evidence of disease, risk of cardiac death 4.6 (p less than 0.05) and risk of sudden death, 2.4 (not significant). Of the 13 patients who died suddenly, five seen at autopsy were found to have had a recent myocardial infarction. Of all patients who died of heart disease, recent myocardial infarction was detected in nine who were seen at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Univentricular support results in reduction of pulmonary resistance and improved right ventricular function.
A retrospective analysis was performed to assess the effects of univentricular support on the transpulmonary gradient (TPG), pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and right ventricular ejection fraction (RVEF) in 16 patients who spent from 2 to 144 days (mean, 61) on the Novacor left ventricular assist system ([LVAS] Novacor Corp., Baxter Healthcare, Oakland, CA) as a bridge to cardiac transplantation. Results revealed a significant reduction in the TPR, and improvement in RVEF while patients were on the LVAS. After orthotopic heart transplantation (OHTx), TPG and PVR were significantly lower than when calculated before support. It was concluded, therefore, that the reduction in the TPR and the improvement in the RVEF, seen in patients who were provided univentricular support with the Novacor LVAS, are associated with a significant reduction in the TPG and the PVR, which are persistent after OHTx. Four patients who otherwise would have been considered at higher risk for OHTx because of elevated pulmonary resistance before veniventricular support underwent successful OHTx after LVAS support.
Adolescent↗