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Biomedical subjects

R D Magorien

Publications and source records attributed to R D Magorien.

11 recordsLinked to original sources

Rest and exercise cardiovascular effects of terazosin in congestive heart failure.

This study investigated the acute effects of the alpha 1 antagonist terazosin on myocardial circulatory responses at rest and during exercise. Ten patients with congestive heart failure (class III and IV) underwent hemodynamic evaluation before and after a 5-mg oral dose of terazosin. At rest and during exercise, terazosin significantly decreased pulmonary capillary wedge pressure, systemic vascular resistance and mean arterial pressure while cardiac index increased. Stroke volume index increased (p less than 0.01) during exercise while left ventricular stroke work index remained unchanged in both experimental conditions. Terazosin administration significantly decreased both rest and exercise myocardial oxygen consumption while exercise coronary sinus oxygen content increased and arterial-coronary sinus oxygen difference diminished (p less than 0.05). Parallel with these changes, alpha blockade decreased the ratio of coronary blood flow to total cardiac output. Coronary vascular resistance remained unaltered with alpha blockade both at rest and during exercise. Coronary blood flow tended to diminish with decreased myocardial oxygen demand. Alpha 1 blockade induces systemic vasodilation and improves myocardial circulatory parameters without inducing coronary dilation or altering metabolic autoregulation.

Adrenergic alpha-Antagonists

Influence of exercise on coronary sinus blood flow determinations.

Consecutively measured values of coronary sinus blood flow were compared to assess the reproducibility of the coronary sinus thermodilution technique. Values measured at rest and during exercise were evaluated and the influence of the respiratory cycle on reproducibility was studied. Correlation of consecutive values revealed a coefficient of 0.94 at rest and 0.93 during exercise. Differences between mean values of consecutive measurements were nonsignificant. A comparison of the coefficients of variation at rest (8.50 +/- 7.09) and exercise (8.02 +/- 4.75) revealed no significant difference. Variation about mean coronary sinus blood flow due to inspiration and expiration was similar at rest and during exercise (42% and 37%, respectively). Provided that critical variables are closely monitored, the coronary sinus thermodilution technique is a highly reproducible technique in a clinically feasible setting.

Adult

Aging of the human myocardium: a histologic study based upon endomyocardial biopsy.

This study assesses the effect of aging on human myocardial morphology. Fifteen patients, ranging in age from 28 to 75 with normal cardiac history, physical examination and noninvasive tests of left ventricular function, underwent right ventricular endomyocardial biopsy prior to cancer chemotherapy. Cell diameter, nuclear area and fibrosis were quantified by light microscopy. Semiquantitative methods of electron microscopy were used to grade lipofuscin deposition, tubular dilation, myofibrillar loss, folding of discs and lipid deposition. The results demonstrated that myocardial cell diameter correlated directly with age (r = 0.73, p less than 0.01) and systolic blood pressure (r = 0.51, p less than 0.05). Nuclear area (r = 0.76, p less than 0.01) and folded discs (r = 0.53, p less than 0.05), two signs of increased protein production also correlated with age. Lipid deposition (r = 0.40), tubular dilation (r = 0.31) and lipofuscin deposition (r = 0.20) increased with, but did not correlate significantly with age. Lipid deposition (r = 0.56, p less than 0.05) and tubular dilation (r = 0.43, p less than 0.05) did correlate with cell diameter. Thus, the aging myocardium is characterized by increased cell size and some degenerative changes.

Adult

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

Failure of percutaneous transluminal coronary angioplasty to stimulate platelet and prostaglandin activity.

Platelet function and prostaglandin activity were evaluated in nine patients with coronary artery disease undergoing percutaneous left anterior descending coronary artery angioplasty (PTCA) and compared to nine normal controls. Transcoronary measurements (arterial-coronary sinus) of platelet counts, mean platelet volume, platelet factor 4 (PF4), beta thromboglobulin, thromboxane (B2), and 6-keto-PGF 1 alpha were made. When compared to normal controls, the patients with coronary artery disease had higher circulating baseline levels of PF4 in the coronary sinus. There was no transcardiac production of any factor at baseline or immediately after infusion of nitroglycerin or performance of PTCA. These results suggest that PTCA does not grossly alter arachidonic acid metabolism or platelet activity.

6-Ketoprostaglandin F1 alpha

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

Effect of vasoactive intestinal polypeptide on the canine cardiovascular system.

Our purpose was to determine the effect of vasoactive intestinal polypeptide (VIP) on the cardiovascular system with special emphasis on coronary vascular effects. In section I, VIP was infused into six healthy and six cobalt-cardiomyopathic dogs at two infusion rates (0.02 and 0.05 micrograms/kg/min). Left ventricular end diastolic pressure and mean systemic pressure fell significantly in both groups. Heart rate rose in both, and maximum systolic dP/dt increased in the myopathic group. Cardiac output and regional blood flows were determined by serial left atrial injections of radioactive 15 +/- 3 mum (mean +/- SD) microspheres. In both groups, blood flow increased significantly to the esophagus, pancreas, atria, and ventricles and to the endocardial and epicardial regions of the left ventricular free wall. Blood flow to the brain decreased. In section II, VIP was infused intravenously at 0.1 micrograms/kg/min into six anesthetized dogs with coronary sinus flow, pulmonary artery, and systemic artery catheters inserted. Cardiac index rose from baseline (3.1 +/- 0.5 to 4.8 +/- 1.3 L/min/m2, P less than 0.005), as did coronary blood flow (90 +/- 25 to 159 +/- 54 ml/min, P less than 0.005) during the VIP infusion. Myocardial oxygen consumption rose from 14.1 +/- 3.9 to 19.8 +/- 5.4 ml/min (P less than 0.001), but the aorta-to-coronary sinus O2 difference decreased from 157 +/- 19 ml/L to 132 +/- 42 ml/L (P less than 0.05), and the percent O2 extracted from coronary blood also decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Development of pharmacodynamic tolerance to prozosin in congestive heart failure.

In order to determine and compare the pharmacodynamic responses to single and multiple dose prazosin therapy in cardiac failure, 14 patients with severe low-output heart failure underwent central and regional hemodynamic measurements after random placement in one of two prazosin dosing schedules. A single 5 mg oral dose of prazosin (Group A, no. = 7) significantly increased the cardiac index and stroke volume index while significantly decreasing systemic, pulmonary and pulmonary capillary wedge pressures and vascular resistances. Hepatic plasma flow and limb blood flow increased after the single dose. Striking attenuation of these hemodynamic effects occurred when the same dose was administered after 24 hours of pretreatment with oral prazosin, 2 mg every 8 hours (Group B, no. = 7). The plasma prazosin levels of the two groups, drawn 2 hours after administration, were 24.5 and 30.5 ng/ml, respectively. Repeated administration of prazosin in patients with congestive heart failure results in rapid attenuation of its beneficial central and regional hemodynamic effects. The usefulness of this vasodilator as a preload- and afterload-reducing agent in the clinical setting of chronic congestive heart failure may be limited by the development of pharmacodynamic tolerance.

Administration, Oral

Interatrial conduction (activation) times.

Left atrial electrograms were recorded simultaneously from sites located in the coronary sinus, right pulmonary artery and esophagus in order to determine and correlate the interatrial conduction times obtained from these locations. Ten patients with normal-sized atria and 16 patients with isolated left atrial enlargement were studied. A high correlation existed between the P wave duration and the interatrial conduction times obtained from the coronary sinus and pulmonary artery; good correlations were also found for the interatrial conduction times recorded from the pulmonary artery and esophagus correlated well with those recorded from the distal coronary sinus (the generally accepted standard for the indirect interatrial conduction time measurements). In addition to providing information on the mechanism of atrial arrhythmias, the electrograms obtained from the various indirect left atrial recording sites provide satisfactory quantification of interatrial conduction.

Electrocardiography

Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation.

A 51 year old woman sustained ventricular fibrillation while receiving perphenazine and protriptyline. After successful resuscitation and clinical stabilization, cardiac electrophysiologic studies were performed before and after the administration of each of these medications. Perphenazine widened the ventricular echo zone and facilitated induction of short salvoes of ventricular tachycardia (repetitive ventricular response). Protriptyline also widened the ventricular echo zone and allowed easy induction of long runs of ventricular tachycardia. Both psychotropic agents increased the incidence of ventricular dysrhythmias in this patient. The electrophysiologic study is a useful technique in determining the interaction between psychotropic drugs and life-threatening arrhythmias; it may provide a means of identifying the patients with cardiac disease in whom administration of these agents may be fatal.

Major Depressive Disorder

Regional hemodynamic effects of clonidine in congestive heart failure.

Regional and central hemodynamic variables were ascertained in 10 patients with congestive heart failure before and after the oral administration of clonidine. Following the 0.2 mg dose, renal, hepatic, and limb blood flow remained unaltered, whereas a reduction was noted in heart rate (10%), mean systemic (14%), and pulmonary capillary wedge pressures (27%). Cardiac index and systemic vascular resistance fell slightly, however the changes were not statistically significant. Higher dose clonidine (0.4 mg) elicited similar regional hemodynamic effects whereas systemic vascular resistance significantly diminished (21%) and cardiac index remained unchanged. In congestive heart failure, the central antihypertensive agent, clonidine, effects a significant reduction in preload (left ventricular filling pressure) and afterload (systemic blood pressure) without markedly altering other central and regional hemodynamic variables.

Adult