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Biomedical subjects

B F Uretsky

Publications and source records attributed to B F Uretsky.

At least 109 records · Page 6Linked to original sources

Comparative hemodynamic and hormonal response of enoximone and dobutamine in severe congestive heart failure.

The peak hemodynamic effect and hormonal response of the phosphodiesterase inhibitor enoximone (MDL 17,043) were compared with those of dobutamine in 10 patients with severe congestive heart failure. Both agents significantly (p less than 0.05) increased cardiac index, stroke volume index and heart rate. Enoximone tended to decrease mean systemic arterial and pulmonary artery wedge pressures (0.05 less than p less than 0.1), whereas dobutamine did not. Both agents decreased systemic vascular resistance (p less than 0.05). The increase in heart rate was greater with dobutamine than with enoximone (p less than 0.05). Plasma renin activity increased significantly with dobutamine (from 11.3 +/- 13.5 to 17.8 +/- 15.0 ng/ml/hour, p less than 0.01) and with enoximone (from 13.6 +/- 18.3 to 16.6 +/- 18.8 ng/ml/hour, 0.05 less than p less than 0.1). Dobutamine suppressed plasma norepinephrine level (p less than 0.05) and enoximone did not. Neither agent affected the plasma vasopressin level. These data demonstrate a similar acute hemodynamic and hormonal profile for both enoximone and dobutamine. Further, dobutamine, like other beta agonists, provokes renin secretion and may do so to a greater extent than enoximone.

Aged↗

Noninvasive evaluation of systolic and diastolic function in severe congestive heart failure secondary to coronary artery disease or idiopathic dilated cardiomyopathy.

The usefulness of systolic time intervals, diastolic time intervals and echocardiography in evaluating left ventricular (LV) function was determined in 69 patients with severe congestive heart failure. All systolic time intervals were markedly abnormal (preejection period/LV ejection time 0.59 +/- 0.18 vs 0.30 +/- 0.04, preejection period index 170 +/- 37 vs 117 +/- 11, LV ejection time index 372 +/- 26 vs 410 +/- 17; patients vs control subjects, p less than 0.05). Diastolic time intervals in patients were not different from those in control subjects. Echocardiographic measurements were all markedly abnormal (LV end-diastolic dimension 6.9 +/- 1.0 vs 4.8 +/- 0.4 cm, patients vs control subjects, p less than 0.05). No pattern of abnormalities distinguished ischemic cardiomyopathies from idiopathic dilated cardiomyopathies. The presence of LV conduction delay did not substantially alter results, except that exclusion of patients with LV conduction delay normalized the total time of systole (QA2) index (from 542 +/- 40 to 531 +/- 31 ms) and reduced but did not normalize prolongation in the preejection period index (from 170 +/- 37 to 162 +/- 29 ms). No systolic or diastolic interval strongly correlated with any hemodynamic or other independent measure of LV performance. Twenty-four patients were given inotropic or unloading agents, which significantly improved hemodynamic values. Systolic and diastolic intervals were measured at baseline and at maximal hemodynamic effect. The correlation of changes in hemodynamics with changes in systolic and diastolic intervals was only modest. Thus, although systolic time intervals and associated echocardiographic measurements can detect abnormal LV function, they cannot reliably detect a change in LV function or distinguish gradations of abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Extent of myocardial fibrosis and cellular hypertrophy in dilated cardiomyopathy.

The distribution of fibrosis and cellular hypertrophy was studied in the hearts of patients with dilated cardiomyopathy (DC). Transmural sections were removed from the left and right ventricular free walls and the ventricular septum of 9 patients with heart failure and 6 control subjects. These sections were stained with hematoxylin-eosin (to determine cell size) and trichrome (to determine percent fibrosis). The sections were separated into equal areas from epicardium to endocardium in the free walls and right to left across the septum. Percent fibrosis was greater in patients with DC (20 +/- 4%) than control subjects (4 +/- 1%, p = 0.0001). A pattern of increasing fibrosis in the left ventricular free wall from epicardium (14 +/- 6%) to endocardium (22 +/- 9%, p less than 0.05) was documented. Fibrosis was greater on the left (21 +/- 12%) than the right (15 +/- 6%, p less than 0.05) side of the septum. No pattern was evident in the right ventricular free wall or in the control group. Myocardial cell diameter was greater in the heart failure group (22 +/- 5 micron) than the control group (17 +/- 2 micron, p less than 0.05), but no pattern of hypertrophy across the walls was seen. The increased fibrosis, the pattern of fibrosis and the increased cell diameter in patients with DC help to characterize DC.

Adult↗

Successful reversal by chelation therapy of congestive cardiomyopathy due to iron overload.

A patient who developed severe iron overload cardiomyopathy is described. Venesection could not be performed because the patient had chronic anemia. Deferoxamine mesylate, a chelating agent, was administered daily for more than 2 years and produced significant improvement in ventricular function which was associated with a biopsy-proven decrease in myocardial iron stores. This is the first reported case in which a severe cardiomyopathy due to iron overload was reversed by chelation therapy alone.

Adult↗

Is inotropic therapy appropriate for patients with chronic congestive heart failure? Or is the digitalis leaf withering?

The appropriateness of inotropic therapy in chronic heart failure was examined by critically reviewing five assumptions upon which this form of therapy has been justified. Only the first, that cardiac performance can be acutely improved by inotropic therapy, has been empirically proven. That such acute improvement is sustained appears to be true with non-catecholamine agents whereas the chronic haemodynamic efficacy of oral catecholamines remains in doubt. That any inotropic agent can improve exercise tolerance, make the patient feel better, or effect a change without deleteriously affecting the myocyte is very much in doubt. Thus, although the prospect of using powerful inotropic therapy in the patient with heart failure is theoretically appealing, its utility remains to be proven.

Amrinone↗

Positive inotropic therapy for short-term support and long-term management of patients with congestive heart failure: hemodynamic effects and clinical efficacy of MDL 17,043.

The positive inotropic/vasodilator agent MDL 17,043 was evaluated to determine its usefulness for both short-term support of the failing circulation and long-term treatment of patients with congestive heart failure. Both intravenous and oral administration of MDL 17,043 significantly increased cardiac output, stroke volume, stroke work index, and heart rate, and significantly decreased pulmonary arterial wedge, right atrial, and mean arterial pressures as well as systemic and pulmonary arteriolar resistance. Such hemodynamic responsiveness persisted in patients on long-term oral therapy with MDL 17,043. When compared with dobutamine, the peak hemodynamic effects of MDL 17,043 were similar except for somewhat greater increases in heart rate with dobutamine and somewhat greater decreases in mean pulmonary arterial and wedge pressures with MDL 17,043. Both intravenous and oral MDL 17,043 elevated plasma renin activity. Oral doses were rapidly absorbed, and the drug had an elimination half-life of about 20 hr. Although the majority of patients showed clinical improvement at 1 month, this effect tended to wane over time leading to either recurrent heart failure or death. Mortality rates at 1 year are about 46% in class III patients and 97% in class IV patients on long-term oral MDL 17,043. The results of these studies suggest that MDL 17,043 may be useful in the short-term management of the failing circulation; however, its value in the long-term management of patients with chronic heart failure remains unclear and requires further studies for resolution.

Administration, Oral↗

Human and canine ventricular vasoactive intestinal polypeptide: decrease with heart failure.

Vasoactive intestinal polypeptide (VIP) is a systemic and coronary vasodilator that may have positive inotropic properties. Myocardial levels of VIP were assayed before and after the development of heart failure in two canine models. In the first, cobalt cardiomyopathy was induced in eight dogs; VIP (by radioimmunoassay) decreased from 35 +/- 11 pg/mg protein (mean +/- SD) to 5 +/- 4 pg/mg protein (P less than 0.05). In six dogs with doxorubicin-induced heart failure, VIP decreased from 31 +/- 7 to 11 +/- 4 pg/mg protein (P less than 0.05). In addition, VIP content of left ventricular muscle of resected failing hearts in 10 patients receiving a heart transplant was compared with the papillary muscles in 14 patients (five with rheumatic disease, nine with myxomatous degeneration) receiving mitral valve prostheses. The lowest myocardial VIP concentration was found in the hearts of patients with coronary disease (one patient receiving a transplant and three receiving mitral prostheses) (6.3 +/- 1.9 pg/mg protein). The other patients undergoing transplantation had an average ejection fraction of 17% +/- 6% and a VIP level of 8.8 +/- 3.9 pg/mg protein. The hearts without coronary artery disease (average ejection fraction of this group 62% +/- 10%) had a VIP concentration of 14.1 +/- 7.9 pg/mg protein, and this was greater than in hearts of the patients with coronary disease and the hearts of patients receiving a transplant (P less than 0.05). Myocardial catecholamines were also determined in 14 subjects; a weak correlation (r = 0.57, P less than 0.05) between the tissue concentrations of VIP and norepinephrine was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Modeling the isovolumic relaxation period.

The isovolumic relaxation period of the left ventricular pressure curve in man has been assumed to be best represented by an exponential decay. To determine which model most closely approximates the empiric pressure data of isovolumic relaxation in man, several models were compared. They included linear, exponential with a zero mmHg pressure asymptote, exponential with a variable asymptote, and second-to fifth-order polynomials. In addition, four different methods of computing parameters of isovolumic relaxation by the exponential model with a variable asymptote were tested. It was found that the isovolumic relaxation period approximates an exponential, that the theoretic asymptote is variable, and that the Levenburg-Marquardt algorithm can be used efficiently to model this period.

Adult↗

MDL 17,043 therapy in severe congestive heart failure: characterization of the early and late hemodynamic, pharmacokinetic, hormonal and clinical response.

MDL 17,043, an agent with both inotropic and vasodilator properties, was evaluated in the treatment of chronic severe heart failure. The early and late hemodynamic, hormonal, pharmacokinetic and clinical responses to oral MDL 17,043 were studied in 20 patients. MDL 17,043 acutely increased cardiac output from 3.6 +/- 0.9 to 4.6 +/- 1.0 liters/min (+28%, p less than 0.001) and decreased mean pulmonary artery wedge pressure from 24 +/- 8 to 13 +/- 8 mm Hg (-46%, p less than 0.001), mean right atrial pressure from 10 +/- 5 to 4 +/- 4 mm Hg (-60%, p less than 0.001) and mean arterial pressure from 78 +/- 9 to 70 +/- 11 mm Hg (-10%, p less than 0.001). Hemodynamic improvement was sustained for 8 hours. Plasma renin activity tended to increase (0.10 less than p greater than 0.05), plasma norepinephrine tended to decrease (0.10 less than p greater than 0.05) and arginine vasopressin did not show any directional change. Elimination half-life for MDL 17,043 was approximately 20 hours. Hemodynamic responsiveness was maintained in six patients undergoing restudy at 4 weeks. Initial subjective improvement in the 20 patients occurred in 90%, was present at 4 weeks in 50% and continued longer than 3 months in 25%. Side effects occurred in 75% and required cessation of treatment in 10%. Thirteen (93%) of 14 patients on long-term therapy died (median time after start of MDL 17,043 therapy 39 days). Deaths were sudden in 69%. It is concluded that oral MDL 17,043 produces early and late hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗

Plasma vasopressin response to osmotic and hemodynamic stimuli in heart failure.

Arginine vasopressin (AVP) regulation was studied in 42 patients with severe heart failure (CHF) and 10 patients without CHF during cardiac catheterization. Plasma AVP levels were elevated in CHF compared with non-CHF patients (2.98 +/- 2.48 vs. 1.01 +/- 0.44 pg/ml, P less than 0.01). In non-CHF patients, osmotic loading with angiographic contrast caused increases in plasma osmolality (283 +/- 4 to 290 +/- 5 mosmol/l, P less than 0.05) and AVP (1.01 +/- 0.44 to 1.79 +/- 0.20 pg/ml, P less than 0.001). In 10 CHF patients, similar osmotic loading produced an increase in plasma osmolality (275 +/- 13 to 288 +/- 17 mosmol/l, P less than 0.05) and an exaggerated rise in plasma AVP (3.61 +/- 3.17 to 16.30 +/- 12.17 pg/ml, P less than 0.001). The increase in plasma AVP per unit increase in osmolality was greater (P less than 0.01) in the CHF patients (1.36 +/- 1.25 pg . mosmol-1 . 1(-1)) than in non-CHF patients (0.18 +/- 0.17). To determine whether improved cardiac performance would lower AVP levels, 18 CHF patients received the experimental agent MDL 17,043, with improved cardiac index (1.9 +/- 0.4 to 3.3 +/- 0.7 1 . min-1 . m-2, P less than 0.001). Plasma AVP levels did not change significantly (1.99 +/- 0.74 to 2.81 +/- 2.06 pg/ml), but significant inverse correlations were found between changes in plasma AVP and changes in mean (r = -0.53) and systolic (r = -0.65) arterial pressure after MDL 17,043 infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Long-term hemodynamic follow-up of cardiac transplant patients treated with cyclosporine and prednisone.

To evaluate the long-term hemodynamic results in cardiac transplant patients treated with cyclosporine and prednisone, 19 patients were studied by cardiac catheterization and endomyocardial biopsy 13 +/- 3 months after transplantation. Immunosuppression consisted of 6 +/- 4 mg/kg/day cyclosporine and 20 +/- 8 mg/day prednisone. Eighteen patients were asymptomatic but had developed postoperative systemic hypertension (17 on antihypertensive therapy). These patients were compared with a normotensive control group of 18 patients without cardiovascular disease. Significant differences were found in heart rate; right atrial, pulmonary arterial, pulmonary arterial wedge, systemic arterial, and left ventricular end-diastolic pressures; cardiac index and stroke volume index; systemic and pulmonary vascular resistance; and end-diastolic volume index and left ventricular ejection fraction. The most frequent hemodynamic abnormalities included an elevated arterial pressure in 10 patients (56%), an elevated left ventricular end-diastolic pressure in six patients (33%), and a reduced ejection fraction in five patients (28%). Hemodynamic abnormalities tended to resolve or improve in the five patients restudied 2 years after transplantation. There was no significant relationship between fibrosis or inflammation on endomyocardial biopsy and hemodynamic abnormalities. We conclude that mild-to-moderate hemodynamic abnormalities are common in asymptomatic cardiac transplant patients receiving cyclosporine and prednisone.

Adult↗

Acute hemodynamic effect of oral MDL 17,043 in severe congestive heart failure.

MDL 17,043, when administered intravenously in humans, produces a significant and salutary hemodynamic response. To determine its acute effect when administered orally (3 mg/kg), 10 patients with severe congestive heart failure were studied by right-sided cardiac catheterization for 8 hours. At 4 hours after drug ingestion, there was significant improvement in several hemodynamic measurements. Cardiac index increased 38% over baseline (from 1.9 +/- 0.4 to 2.6 +/- 0.4 liters/min/m2, p less than 0.01), arteriovenous oxygen difference decreased by 30% (from 8.0 +/- 1.4 to 5.6 +/- 1.2 vol%, p less than 0.01), heart rate increased by 8% (from 85 +/- 16 to 92 +/- 16 beats/min, p less than 0.05), stroke volume index increased by 22% (from 23 +/- 5 to 28 +/- 4 ml/beat/m2, p less than 0.05), left ventricular stroke work increased by 24% (from 18 +/- 5 to 22 +/- 5 g-m/m2, p less than 0.01), mean arterial pressure decreased by 10% (from 79 +/- 6 to 71 +/- 9 mm Hg, p less than 0.01), mean right atrial pressure decreased by 40% (from 10 +/- 5 to 6 +/- 4 mm Hg, p less than 0.01), and mean pulmonary artery wedge pressure decreased by 36% (from 22 +/- 5 to 14 +/- 6 mm Hg, p less than 0.01). Cardiac index, arteriovenous oxygen difference, mean arterial pressure, right atrial pressure, and pulmonary artery wedge pressure remained significantly improved at 8 hours. These findings indicate that MDL 17,043 is active when administered orally and produces beneficial hemodynamic effects for as long as 8 hours.

Aged↗

Intermittent mitral regurgitation due to Beall valve dysfunction: analysis of 13 patients with atrial fibrillation.

A unique hemodynamic event was noted in long-term survivors of mitral valve replacement with the Beall prosthesis. The event was a result of intermittent valve dysfunction and transvalvular mitral regurgitation (MR). At cycle lengths longer than 0.9 second that were preceded by shorter cycle lengths, 8 of 13 patients with Beall valve prostheses who had chronic atrial fibrillation (AF) intermittently had a marked unexpected decrease in peak left ventricular systolic pressure and a simultaneous increase in left atrial or pulmonary artery wedge "v" wave pressure. This event, which is a result of intermittent, severe MR, occurred more frequently at longer cycle lengths. In all 8 patients with the finding, severe valve disc wear was found at operation; however, 5 of these patients had only trace or 1+ MR on left ventricular angiography. In contrast, the event did not occur in 11 patients in chronic AF with organic MR or non-Beall valve MR, despite an appropriate number of sufficiently long cycles. The absence of the event in 5 Beall valve patients with significantly faster heart rates than in those with the event may in part be a result of its dependence on cycle length. This hemodynamic event, when present in a Beall valve recipient in AF, is an indication for valve replacement, even in the absence of angiographic evidence of severe MR.

Atrial Fibrillation↗

Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma.

To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thallium defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent [P less than 0.025], and 36 +/- 12 per cent vs. 47 +/- 7 per cent [P less than 0.025], respectively). We conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury.

Adult↗

The hemodynamic effects of intravenous verapamil in patients on chronic propranolol therapy.

Concern exists regarding the negative inotropic and chronotropic effects of verapamil given to patients receiving chronic propranolol therapy. In order to evaluate the safety of combined therapy, the hemodynamic effects of verapamil were investigated in a group of 19 patients on chronic propranolol therapy undergoing cardiac catheterization. Hemodynamic measurements and left ventriculography were performed prior to and 30 minutes after initiation of intravenous administration of verapamil. Verapamil doses varied from 0.025 mg/kg to 0.1 mg/kg intravenous bolus injection followed by an infusion of 0.005 mg/kg/min. Following verapamil administration, systolic, diastolic, and arterial mean pressures and systemic vascular resistance decreased significantly. There was no significant change in left ventricular end-diastolic pressure, mean pulmonary capillary wedge pressure, cardiac index, arteriovenous oxygen difference, heart rate, mean velocity of circumferential fiber shortening (VCF), end-diastolic volume index, end-systolic volume index, stroke volume index, and ejection fraction (EF). Stroke work index decreased significantly. Lack of improvement in cardiac index, VCF, and EF and decrease in stroke work index in spite of constant filling pressure and decreased afterload suggest the additive negative inotropic action of verapamil. The depressant action of propranolol itself was not determined by this study. In spite of the negative inotropic effect of verapamil, it can be administered acutely to patients who have been on propranolol therapy with relative safety if the propranolol has not already produced severe left ventricular dysfunction, relative hypotension, bradyarrhythmia, or conduction abnormalities.

Adult↗

Occult purulent pericarditis detected by indium-111 leukocyte imaging.

Leukocyte imaging with indium-111 is a relatively new technique which, to this point in time, has been discussed almost exclusively in the radiologic literature. Although this procedure has been used mainly to detect intra-abdominal infection, the thorax is routinely imaged along with the abdomen, and therefore detection of cardiac disease may be feasible. This case report is of a young woman after liver transplantation who developed occult purulent pericarditis initially detected by a leukocyte scan with indium-111. This case demonstrates that striking pericardial uptake on a whole-body indium-111 leukocyte scan can occur with purulent pericarditis, and it reemphasizes how insidiously purulent pericarditis may present in an immunosuppressed patient.

Adult↗