Enoximone in heart failure: mechanisms of action.
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Cardiac Output, Low↗
Biomedical subjects
K Chatterjee
Publications and source records attributed to K Chatterjee.
Role of nitrates in silent myocardial ischemia.
Assessment of systemic and coronary hemodynamics, myocardial metabolic and mechanical function and scintigraphic and electrocardiographic studies has provided ample evidence for the existence of asymptomatic silent myocardial ischemia in both acute and chronic coronary artery syndromes. There is growing evidence to suggest that a primary decrease in coronary blood flow, resulting from increased coronary arterial resistance, is the principal cause for spontaneous symptomatic and asymptomatic myocardial ischemia in these patients. The precise mechanism for increased coronary arterial resistance has not been clarified, and it is likely to be different in different angina syndromes but similar for both symptomatic and asymptomatic myocardial ischemia. Since nitroglycerin and nitrates can decrease coronary arterial tone and coronary artery resistance, as well as myocardial oxygen requirements, these agents have the potential to relieve episodes of silent myocardial ischemia in patients with coronary artery syndromes.
Angina Pectoris↗
Potential mechanisms of improved left ventricular function with enoximone in severe congestive heart failure.
Enoximone, a phosphodiesterase inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in systemic hemodynamics in patients with severe chronic congestive heart failure. Cardiac index, stroke volume index and stroke work index increase, and there is a significant decrease in pulmonary capillary wedge pressure. Left ventricular dP/dt increases, despite a decrease in arterial pressure and systemic vascular resistance and without any significant change in heart rate, indicating a positive inotropic effect. A marked decrease in systemic vascular resistance indicates that decreased left ventricular outflow resistance resulting from peripheral vasodilation also contributes to improvement in left ventricular function. In some patients, left ventricular end-diastolic volume increases despite a marked decrease in pulmonary capillary wedge pressure, suggesting an improvement in apparent left ventricular compliance, which may also be contributory to improved left ventricular function.
Cardiotonic Agents↗
Calcium antagonist agents in hypertrophic cardiomyopathy.
Calcium antagonists have emerged as important adjuncts to pharmacotherapy of hypertrophic cardiomyopathy. Calcium antagonists cause significant symptomatic improvement in both obstructive and nonobstructive forms and even in patients refractory to beta-blocker therapy. Exercise hemodynamics and exercise tolerance improve in the majority of patients during long-term therapy with calcium antagonists. Reduction in left ventricular (LV) outflow pressure gradient is not consistent after short- or long-term therapy. The provokable gradient tends to remain unchanged. The changes in LV outflow gradient do not appear to be contributory to symptomatic improvement. LV ejection fraction, mean normalized systolic ejection rate and end-systolic pressure volume ratio remain unchanged, suggesting that calcium antagonists agents do not alter LV systolic function. LV diastolic function and its relaxation properties, however, improve in many patients, which might be contributory to symptomatic improvement and improved exercise tolerance.
Calcium Channel Blockers↗
Angiotensin inhibitors and other vasodilators with special reference to congestive heart failure.
ACE inhibitors have emerged as important pharmacologic agents for treatment of hypertension and heart failure. Attenuation or inhibition of angiotensin mediated vasoconstriction appears to be the principal mechanism for the reduction of arterial pressure and systemic vascular resistance.
Angiotensin-Converting Enzyme Inhibitors↗
Measurement of left ventricular stroke volume using continuous wave Doppler echocardiography of the ascending aorta and M-mode echocardiography of the aortic valve.
A number of reports have described different Doppler echocardiographic methods to calculate left ventricular stroke volume and cardiac output, but the clinical application of the noninvasive measurements of cardiac function remains in the early stages of development. This slow dissemination may be partly explained by the varying success of these ultrasound methods in determining accurate left ventricular stroke volume. The purpose of this study was to improve the simplicity and accuracy of Doppler stroke volume determination so that it could be more easily applied to patient management. Stroke volume was measured using the product of the integral of aortic velocity obtained by continuous wave Doppler technique and the M-mode tracing of the aortic valve, validating the data against cardiac output obtained by thermodilution technique in 41 patients (r = 0.95, SEE = 7 cc). Intra- and interobserver variability was between 9 and 11%. The results of different sampling sites and the temporal relation between Doppler and thermodilution measurements were also studied. Analysis of 21 patients who had M-mode and two-dimensional echocardiographic studies of the aortic root revealed that the method using M-mode measurement of aortic valve area was most accurate in determining left ventricular stroke volume (r = 0.94, SEE = 10 cc), stroke volume being overestimated when area measurements of the ascending aorta were used. In conclusion, maximal ascending aortic velocity determined by continuous wave Doppler echocardiography with M-mode measurement of aortic valve area can be used to calculate left ventricular stroke volume and cardiac output. The simplicity and practicality of this method should enhance the clinical application of Doppler echocardiography as a noninvasive monitoring technique.
Adult↗
Hemodynamic and clinical evaluation of piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure.
To assess the potential utility of piroximone (MDL-19,205), an investigational inotrope-vasodilator agent, in severe heart failure, 15 patients with severe left ventricular failure refractory to conventional agents were enrolled in an acute hemodynamic study. After incremental intravenous dosing (mean total dose 1.8 +/- 0.4 mg/kg body weight), cardiac index increased (1.7 +/- 0.3 to 2.6 +/- 0.6 liters/min per m2; p less than 0.001) and left ventricular filling pressure decreased (25 +/- 7 to 19 +/- 7 mm Hg; p less than 0.001). Also decreasing significantly were right atrial pressure (13 +/- 6 to 7 +/- 5 mm Hg; p less than 0.005) and systemic vascular resistance (1,633 +/- 394 to 1,183 +/- 278 dynes.s.cm-5; p less than 0.001). Heart rate and mean arterial pressure did not change, whereas stroke work index increased significantly (13.3 +/- 4.3 to 21.6 +/- 7.3 g.m/m2; p less than 0.005). The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone. Similar responses were obtained after incremental doses of piroximone in oral solution. After oral doses of piroximone tablets, cardiac index also increased significantly (2.1 +/- 0.6 to 2.4 +/- 0.5 liters/min per m2; p less than 0.05), although this magnitude of increase was comparatively low. In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01).
Aged↗
Enalaprilat, a new parenteral angiotensin-converting enzyme inhibitor: rapid changes in systemic and coronary hemodynamics and humoral profile in chronic heart failure.
Systemic and coronary hemodynamic, metabolic and humoral effects of a new intravenous angiotensin-converting enzyme inhibitor, enalaprilat, were evaluated in 14 patients with chronic heart failure. Onset of hemodynamic action occurred within 15 minutes and persisted for 6 hours. At the time of peak effect, there was a significant reduction in mean arterial pressure (-21%) and pulmonary capillary wedge pressure (-33%). Systemic vascular resistance decreased by 32% and stroke volume index increased by 20%. These systemic hemodynamic changes indicate improved left ventricular function. There was a substantial sustained reduction in rate-pressure product initially without a change in coronary sinus blood flow or myocardial oxygen consumption. There was also reduced myocardial oxygen extraction and augmented coronary sinus oxygen saturation at 30 minutes and 1 hour. In three patients, abnormal myocardial lactate extraction, present before enalaprilat, changed to uptake after enalaprilat, indicating amelioration of myocardial ischemia that was not clinically manifest. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma renin activity increased and plasma aldosterone decreased. These findings suggest that enalaprilat produces inhibition of the angiotensin-converting enzyme and consequent beneficial systemic hemodynamic changes in heart failure. In some patients with heart failure, silent myocardial ischemia at rest can occur and can be alleviated with enalaprilat. Decreased myocardial oxygen extraction, increased coronary sinus oxygen saturation and lack of expected decrease in coronary sinus blood flow despite reduced rate-pressure product suggest transient coronary vasodilation by enalaprilat.
Aged↗
Cardiovascular disease in the elderly. Coronary heart disease.
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Aged↗
Survival in severe left ventricular failure treated with the new nonglycosidic, nonsympathomimetic oral inotropic agents.
Survival in severe left ventricular failure is poor but has not been widely assessed since the introduction of several new nonglycosidic, nonsympathomimetic oral inotropic agents for long-term therapy. We examined retrospectively the survival of 82 patients with severe left heart failure during long-term treatment with oral milrinone (17 patients), posicor (12 patients), enoximone (47 patients), and piroximone (6 patients). Sixty-five patients were in New York Heart Association (NYHA) functional class 4, 15 patients were in class 3, and two patients were in class 2. There were 57 patients with ischemic and 25 patients were in class 2. There were 57 patients with ischemic and 25 patients with nonischemic etiology of left heart failure. Most patients were referred for inotropic therapy after failing to respond to conventional agents, including vasodilators. However, in almost all patients, marked hemodynamic and clinical improvement occurred initially. Overall survival was 36 percent at six months, the majority of deaths occurring during the first three months. Survival in relation to etiology of heart failure showed a trend toward increased mortality in patients associated with ischemic heart disease vs non-ischemic dilated cardiomyopathy. Sudden death mortality was also higher in the ischemic group (28 percent at six months vs 5 percent at six months; p less than 0.05). There was a trend toward reduced sudden death mortality in patients on antiarrhythmic agents during inotropic therapy (p = 0.06). We conclude that overall survival in symptomatic patients with severe left ventricular failure remains very low during long-term therapy with several new oral inotropic agents. Sudden death appears higher in patients with an ischemic etiology during therapy with these agents.
Administration, Oral↗
Lack of association of pleural effusion with chronic pulmonary arterial and right atrial hypertension.
Right atrial hypertension has been considered to have a major physiologic influence on the formation of transudative pleural effusions. Since pleural fluid is thought to be cleared primarily by the parietal pleural lymphatic vessels that empty into the systemic veins, systemic venous hypertension secondary to right atrial hypertension should decrease the lymphatic drainage of the pleural space. We retrospectively studied nine patients and prospectively studied 18 patients with long-term right atrial or pulmonary arterial hypertension (or both). All patients had stable respiratory symptoms, and none had a significantly elevated pulmonary arterial wedge pressure. Our purpose was to determine the relationship of right atrial and pulmonary arterial hypertension to the development of transudative pleural effusions. Posteroanterior and bilateral decubitus chest roentgenograms and ultrasound were used to detect pleural effusions. Pleural effusions were not identified in any of the 27 patients, even in four patients with right atrial pressures greater than 20 mm Hg. We conclude that chronic elevation of right atrial pressure or pulmonary arterial pressure (or both) alone is not a cause of pleural effusion. In contrast, elevation of left atrial and pulmonary arterial wedge pressures is associated with the formation of transudative pleural effusions in man. Thus, if pleural effusions are detected in patients who have cor pulmonale, a search should be made for coexisting left heart failure or a primary cause of pleural inflammation, such as pulmonary emboli or infection.
Blood Pressure↗
Thrombolysis in acute myocardial infarction.
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Angioplasty, Balloon↗
Congestive heart failure and arrhythmias: an overview.
Arrhythmias are common in patients with congestive heart failure (CHF), especially those with concomitant ischemic heart disease. The degree of left ventricular dysfunction is the most important indicator of prognosis in patients with severe heart failure. In general, the better the patient's ventricular function, the greater his chance of survival. In addition, the severity of arrhythmias is also related to survival; patients with simple arrhythmias have higher survival rates than those with complex arrhythmias. All drugs used in the treatment of CHF have a potential proarrhythmic effect. In a study involving the new class of positive inotropic agents, a trend toward higher mortality was evident in CHF patients with ischemic heart disease compared with those with congestive dilated cardiomyopathy. A subgroup of patients also treated with antiarrhythmic agents had lower sudden death rates than those not receiving antiarrhythmics. A double-blind clinical trial of antiarrhythmic agents for patients with CHF is warranted.
Arrhythmias, Cardiac↗
Acute hemodynamic and metabolic effects of ICI 118,587 (Corwin), a selective partial beta 1 agonist, in patients with dilated cardiomyopathy.
The effects of acute intravenous administration of ICI 118,587 (Corwin), a partial beta 1 agonist, were studied in nine patients with dilated cardiomyopathy and symptomatic congestive heart failure. Hemodynamic and metabolic parameters were measured using Swan-Ganz, arterial, and coronary sinus catheters. Repeated doses of Corwin produced no significant change in left ventricular performance, while a trend towards decreased blood pressure and stroke work was seen. No change occurred in coronary sinus blood flow, transmyocardial lactate extraction, or catecholamine release. One patient had significant depression of left ventricular function with hypotension. Thus, acute infusion of Corwin produced no beneficial inotropic responses, but rather produced features suggestive of further myocardial depression.
Adrenergic beta-Agonists↗
Poor correlation between pulmonary arterial wedge pressure and left ventricular end-diastolic volume after coronary artery bypass graft surgery.
The authors studied 12 surgical patients in the intensive care unit post coronary artery bypass graft surgery and ten nonsurgical patients in the coronary care unit with chronic heart failure to determine the usefulness of the pulmonary arterial wedge pressure as an indicator of left ventricular preload. Left ventricular end diastolic volume was derived from concomitant determination of ejection fraction (gated blood pool scintigraphy) and stroke volume (determined from thermodilution cardiac output). In the nonsurgical patients, there was a significant correlation between changes in pulmonary arterial wedge pressure and left ventricular end-diastolic volume (P less than 0.05, r = 0.57). In the 12 patients studied during the first few hours after surgery, there was a poor correlation between changes in pulmonary wedge pressure (range = 4-32 mmHg) and left ventricular end-diastolic volume (range = 25-119 ml/m2), and a poor correlation between pulmonary arterial wedge pressures and stroke work index. In contrast, there was a good correlation between left ventricular end-diastolic volume and stroke work index. The poor correlation between the pulmonary arterial wedge pressure and left ventricular end-diastolic volume was not explained by changes in systemic or pulmonary vascular resistance. The altered ventricular pressure-volume relationship may reflect acute changes in ventricular compliance in the first few hours following coronary artery bypass graft surgery. While measurement of pulmonary arterial wedge pressure remains valuable in clinical management to avoid pulmonary edema, it cannot reliably be used as an index of left ventricular preload while attempting to optimize stroke volume in patients immediately following coronary artery bypass graft surgery.
Aged↗
Effects of captopril and a combination of hydralazine and isosorbide dinitrate on myocardial sympathetic tone in patients with severe congestive heart failure.
Changes in circulating catecholamines and transmyocardial catecholamine balance associated with improved left ventricular function were studied in patients with chronic heart failure after treatment with captopril (10 patients) and hydralazine in combination with isosorbide dinitrate (eight patients). Cardiac performance improved in response to both captopril and hydralazine-nitrate treatment. The systemic haemodynamic effects were also qualitatively similar, but the hydralazine-nitrate combination caused a greater increase in cardiac index and heart rate. Captopril did not change arterial adrenaline concentrations (0.63 to 0.60 nmol/l), arterial noradrenaline (4.2 to 3.9 nmol/l), or net transmyocardial noradrenaline release (390 to 317 pmol/min), while hydralazine-nitrate increased arterial adrenaline (0.91 to 1.47 nmol/l) and transmyocardial noradrenaline release (225 to 554 pmol/min). Although both captopril and hydralazine-nitrate treatment improve left ventricular performance in patients with chronic heart failure, hydralazine-nitrate enhances cardiac sympathetic tone and captopril does not. The clinical relevance of these findings, however, is not known.
Aged↗
Differential long-term intrarenal and neurohormonal effects of captopril and prazosin in patients with chronic congestive heart failure: importance of initial plasma renin activity.
Fifty patients with congestive heart failure received, by infusion, 15 ml/kg body weight water load, and systemic hemodynamic, renal function, and neurohumoral parameters values were measured before, 2 days, and 1 month after randomly allocating patients to prazosin or captopril therapy. Both prazosin and captopril caused similar and persistent hemodynamic changes, but important differences existed between their renal and neurohumoral effects. After 1 month of continuous therapy, captopril increased creatinine clearance from 71 to 84 ml/min/1.73(2) (p less than .05), increased the water load excreted in 5 hr from 50% to 71% (p less than .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p less than .005), Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p less than .005), in plasma epinephrine from 94 to 73 pg/ml (p less than .05), and in plasma aldosterone from 57 to 28 ng/dl (p less than .005), without changing plasma vasopressin. These beneficial effects were greater after 1 month of therapy than after 2 days. The only beneficial effect of prazosin was to increase water excretion from 49% to 59% (p less than .05). The long-term response to captopril was similar in patients with higher (greater than 2.5 ng/ml/hr) and lower renin levels. However, in patients with lower renin levels, prazosin decreased pulmonary capillary wedge pressure (24.8 to 21.8 mm Hg, p less than .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p less than .05), increased water excretion (62% to 85%, p less than .005), and decreased plasma epinephrine (81 to 46 pg/ml, p less than .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.
Captopril↗
Affinity binding of non-histone chromatin proteins to the X chromosome of Drosophila by in situ chromatin reconstitution and its significance.
Cytophotometric analysis of the in situ binding affinity of non-histone chromosomal protein (NHCP) to the polytenic X chromosome and autosome of Drosophila melanogaster has been carried out using Feulgen-Napthol Yellow S staining technique. The results reveal that the mean transformed absorbance ratio (male:female) with a 547 nm interference band filter for the two specific segments of the X chromosome is close to 0.5, while for a specific segment of an autosome it is close to 1.0, in the two sets of control; namely, the positive control (no treatment) and the negative control (treated with 1 M-urea+2M-NaCl) as well as in the reconstituted chromosomal preparations, which received 1 M-urea+2M-NaCl and the NHCP isolated from D. melanogaster. In contrast, the transformed absorbance ratios (male:female) with a 433 nm interference band filter yielded an interestingly different result. The ratios with a 433 nm filter for the X chromosome segments are significantly greater than 0.5 in all three sets of experiments. This finding by itself suggests that the NHCP binding affinity is dissimilar for the X chromosomes of male and female. When the 433 to 547 nm absorbance ratios were compared among the three sets, the data clearly revealed that in both positive control and NHCP reconstituted samples, the absorbance ratios (i.e. 433:547 nm) are significantly different between X chromosomes from males and those from females, while they are different between autosomes from males and females. The ratios are also not significantly different between male and female, either for the X chromosome or for the autosome in the negative control. These findings, therefore, suggest that there is a stronger binding affinity of NHCP for the male X chromosome of Drosophila, and reinstate the view that the X-chromosomal hyperactivity in male Drosophila is the consequence of a regulated organizational change in the DNA template.
Animals↗