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Biomedical subjects

R Zelis

Publications and source records attributed to R Zelis.

At least 127 records · Page 7Linked to original sources

Propranolol rebound--a retrospective study.

To assess the effects of sudden withdrawal of propranolol on inpatients with coronary artery disease, 102 patients admitted for cardiac catheterization were evaluated. Criteria for inclusion in the study were angiographically documented coronary artery disease, propranolol therapy at a mean daily dose of at least 80 mg and abrupt discontinuation of propranolol therapy before catheterization. There were 55 patients (mean age 52.5) who discontinued propranolol therapy (mean daily dose 127 mg) and a control group of 47 patients (mean age 53) who continued to receive propranolol (mean daily dose 143 mg). The criteria for morbidity were death, myocardial infarction or change in pain pattern. In the withdrawal group there were no deaths, one myocardial infarction judged to be related to catheterization and only one instance of a change in pain pattern. Thus, propranolol rebound appears to occur infrequently among hospitalized patients with reduced activity.

Adult↗

Effect of morphine on splanchnic blood flow.

Splanchnic blood flow was measured by the constant infusion of indocyanine green given before and after morphine 0.2 mg/kg (maximum 15 mg) intravenously in 13 patients. Splanchnic blood flow increased from 1012 +/- 98 ml/min to 1200 +/- 118 ml/min after the administration of morphine, a 19 per cent increase (P less than 0.025). Splanchnic vascular resistance decreased from 0.094 +/- 0.010 to 0.081 +/- 0.010 mmHg min/ml, a 16 per cent decrease (P less than 0.001). There was no significant change between baseline and post-morphine values in systemic arterial pressure (92.2 +/- 3.8 and 89.0 +/- 2.9 mmHg), hepatic vein wedge pressure (7.1 +/- 1.0 and 7.8 +/- 0.6 mmHg), or right atrial mean pressure (4.5 +/- 0.6 and 4.3 +/- 0.7 mmHg). This study shows that morphine induced significant splanchnic arteriolar dilatation.

Abdomen↗

Diffuse coronary artery disease in diabetic patients: fact or fiction?

To compare angiographically-determined coronary artery disease in diabetic patients with controls, 1,653 patients coming to cardiac catheterization were reviewed retrospectively to find 37 diabetic and 79 control patients matched for sex, age (+/- 3 years), and risk factors (hypertension, hyperlipidemia, and smoking). The severity of coronary artery disease was assessed using an angiographic grading system. The following results were obtained: 16 of 37 diabetic patients (43%) had three-vessel disease compared to 20 of 79 controls (25%). Seventy-six of 111 (68%) diabetic vessels were diseased compared to 110 of 237 control vessels (46%) (P less than 0.005). The total coronary score reflecting total extent of disease for diabetic patients was 371 (mean 10.0 +/- (SEM) compared to 594 for controls (mean 7.5 +/- 0.7, (P less than 0.01). Diabetic patients had a statistically similar number of diffusely diseased vessels as controls (28% vs 22%). There were only three of 76 diabetic vessels (4%) considered inoperable compared to seven of 110 (6%) control vessels. We conclude that diabetic patients with chest pain have more coronary artery disease than nondiabetics, but no more diffuse or inoperable disease.

Coronary Disease↗

The effects of short-term venous congestion on forearm venous volume and reactive hyperemia blood flow in human subjects.

Congestive heart failure is associated with a reduction in limb venous volume at an effective venous pressure of 30 mm Hg (VV[30]). Further, an attenuated arteriolar dilation in response to a metabolic stimulus has been demonstrated. It was the purpose of this study to determine to what extent the chronic elevation in venous pressure seen in heart failure might explain these abnormalities of the limb circulation. Ten normal human volunteers were subjected to venous congestion of one arm for three hours at 70 mm Hg. A mercury-in-rubber strain gauge plethysmograph was used to measure forearm VV [30] and forearm blood flow at rest after release of five minutes of arterial occlusion (the reactive hyperemia response). Congestion reduced VV [30] 22%, resting forearm blood flow 49% and peak reactive hyperemia blood flow 25%. Thus, chronic venous congestion per se may significantly reduce limb venous volume as well as resting and reactive hyperemia blood flow.

Adult↗

Linear dose response and quantitative attenuation by potassium of the inotropic action of acetylstrophanthidin.

To evaluate the nature of the inotropic dose response of digitalis and to determine the effects of potassium on this response, isometrically contracting isolated supported right ventricular cat papillary muscles were studied relative to their peak tension and peak dT/dt increases to physiologic cumulative doses of acetylstrophanthidin (ACS) in different extracellular potassium concentrations in the muscle bath. The inotropic dose response to ACS was observed to be linear in cumulative glycoside concentrations ranging from 0.40 to 4.23 X 10(-7) M ACS in 3.5 mM K+ medium and from 1.22 to 7.47 X 10(-7) M ACS in 7.0 mM K+ medium. The influence of potassium alterations in the muscle bath from the low to the high K+ concentrations prior to ACS resulted in marked attenuation of the positive inotropic property of ACS. From these data, it is concluded that the dose inotropic response of digitalis is linear, with small doses producing proportionally the same effects as larger doses, and that extracellular potassium markedly influences this linear dose response such that higher K+ concentrations considerably attenuate the positive inotropic response of digitalis.

Animals↗

Effects of isolated right and left ventricular stretch on regional arteriolar resistance.

In order to evaluate right and left ventricular stretch receptors without concomitantly stimulating those of the contralateral ventricle, 12 dogs were placed on total cardiopulmonary bypass. Balloons connected to compliant reservoirs were introduced into the right and left ventricles. Changes in systemic, gracilis muscle, and paw perfusion pressure at a constant flow were used as indices of systemic, muscle, and cutaneous vascular resistance. To induce left ventricular stretch, the balloon in that chanber was rapidly inflated from a mean pressure of 1.33 kPa (10 mmHg) to a mean pressure of 7.32 kPa (55 mmHg) for 15s (6.00 kPa [45mmHg] increment). For right ventricular stretch, the pressure was increased from 0.67 to 4.00 kPa (5 to 30 mmHg) for 30 s (3.34 kPa [25 mmHg] increment). Both left and right ventricular stretch produced a significant fall in systemic (-4.92 kPa [-37 mmHg], -36%) and gracilis muscle (-5.59 kPa [-42 mmHg], -30%) perfusion pressure, with only minimal changes in cutaneous vascular resistance (-0.80 kPa [-6 mmHg], -4%). This reflex was found to be vagally mediated, to have a low threshold for stimulation (left ventricle, 0.67 kPa [5 mmHg] increment; right ventricle, 1.33 kPa [10 mmHg] increment), and to have a neurogenic sympathetic alpha-adrenergic efferent limb. The low threshold for stimulation suggests that these reflexes may play a physiological role with changes in body position and may be important in such pathological conditions as semilunar valvular stenosis and myocardial infarction.

Animals↗

Effects of isoproterenol on adrenergic constriction in vascular smooth muscle.

A series of isolated segments of carotid arteries from Dutch-belted, adult, male rabbits were studied with respect to their response to a beta receptor agonist. Segments of 3-cm length were mounted in a chamber with constant surrounding temperature and pressure and perfused at constant pressure. Inflow pressure, outflow pressure, and flow rate were measured, and values of resistance (R) were calculated. Subsequent to control R, each vessel was exposed to a vasoconstricting concentration of either norepinephrine (NE: 10(-8), 10(-9), 10(-10) M) or potassium (K+: 100mM, 50 mM) followed by three doses of the beta-adrenergic agonist, isoproterenol (IP: 10(-7), 10(-6), 10(-5)M) administered simultaneously with each constrictor. R was not altered by IP during NE infusion but was significantly increased at all levels of IP during both K+ infusions. When the K+ series was repeated with alpha blockade, IP did not alter R. Thus, beta receptors do not appear to be functionally present in the adult rabbit carotid artery.

Animals↗

Balloon-induced right ventricular outflow obstruction: a new approach to control of acute interventricular shunting after myocardial infarction in canines and swine.

Current management of ventricular septal defect (VSD) after myocardial infarction (MI) is aimed at improving left ventricular (LV) performance by afterload reduction as a means of hemodynamic stabilization or shunt control. The current investigation was undertaken to determine whether primary manipulation of right venticular (RV) performance by afterload enhancement was an effective means of reducing MI-VSD shunting. In five open-chest dogs an external LV-RV shunt was created with pulmonary-systemic flow ratios (Qp/Qs) averaging 2.26:1. Inflation of a balloon-tipped catheter in the main pulmonary artery (PA) reduced average QP/Qs to 1.28:1 and shunt flow from 783 to 343 ml/min. However, this increase in RV afterload caused further significant increases in RV systolic and end-diastolic pressure and suggested that deterioration of RV function might be limiting the usefulness of this technique. To investigate whether inotropic support for the RV would overcome this limitation, a similar shunt was created in 11 open-chest swine. We then investigated the effects of dopamine, infused at 24, 60, and 120 mug/min, on QP/QS and other hemodynamic variables both with and without PA balloon inflation. Optimal shunt control was obtained when effects of dopamine were added to those of PA balloon inflation. Shunt flow that had been 1,633 ml/min was reduced to 892 ml/min with the PA balloon and reduced further to 757 ml/min with dopamine, which also lowered RV and LV end-diastolic pressure and reduced total systemic vascular resistance. In four other swine with left anterior descending ligations, PA balloon inflation and dopamine infusion again favorably affected hemodynamics. Epicardial mapping in these swine showed an increase in S-T segment displacement, suggesting that the cumulative effect of these interventions allowed hemodynamic improvement at the expense of enhanced ischemic injury. These data indicate that acute RV outflow obstruction with a balloon catheter is an effective means of temporarily reducing acute ventricular shunting and that dopamine may be a useful pharmacological agent to use with RV afterload manipulation to stabilize a patient prior to transfer to a medical center for more definitive therapy.

Animals↗

The effects of morphine on isolated cutaneous canine vascular smooth muscle.

In order to evaluate the direct effects of morphine sulfate (MS) on vascular smooth muscle (VSM), a helical strip preparation of canine cutaneous VSM was prepared from vessels of approximately 150 to 250 mug internal diameter. When evaluated at a variety of muscle lengths from 20% to 60% above unstretched length, in the absence and in the presence of norepinephrine (2 to 10x10(-4) mg/cc), MS (10(-3) to 10(-1) mg/cc) failed to produce any noticeable effect. Thus, the well-known arteriolar dilator effect of MS is not a direct effect of the drug on VSM and it is not secondary to blockade of vascular alpha-adrenergic receptors.

Animals↗

Probucol: a new cholesterol-lowering drug effective in patients with type II hyperlipoproteinemia.

Type II hyperlipoproteinemia or hyperbetalipoproteinemia (B-HLP), a condition with considerable atherogenic potential, is one of the most difficult lipid disorders requiring treatment. Since this abnormality responds minimally to dietary therapy alone, supplemental drug therapy is usually essential. Although the available bile-sequestering resins are effective in B-HLP, these substances are unpalatable and constipating. Since lifelong drug therapy is necessary as an adjunct to diet in the treatment of B-HLP, the ideal drug should be both effective and well tolerated. Probucol, a new cholesterol-lowering drug in tablet form without serious adverse effects, was evaluated in a 12-wk double-blind crossover trial in 11 patients with B-HLP whose serum cholesterol levels were in excess of 275 mg/dl. Probucol, in a dosage of 500 mg twice daily, produced a 10% or greater reduction in serum cholesterol levels in all 11 patients. Serum cholesterol was lowered (p less than 0.01) from 353 to 291 mg/dl in the entire group receiving probucol. There was no significant change (p greater than 0.1) in serum cholesterol (352 mg/dl) during placebo administration. These were no untoward drug effects during the study, and all patients maintained excellent complicance to the schedule of medication. These results indicate that probucol possesses considerable cholesterol-lowering activity and may be a promising new nontoxic therapeutic agent in type II hyperlipoproteinemia.

Cholesterol↗

Oral terbutaline sulfate--amelioration of exercise-induced bronchospasm.

Bronchospasm can be induced in asthmatics when exercised according to a multistage branching treadmill protocol that allows them to achieve 80 per cent of their age-predicted maximal heart rate. This present study was undertaken to investigate the effect of oral terbutaline sulfate in ameliorating exercise-induced bronchospasm. Ten asthmatics were exercised, and FEV1.0 and MMEFR were assessed while standing, using a Jones Pulmonar II waterless spirometer at 5, 15, and 30 minutes after exercise. Three hours before exercise, the subjects received no medication, oral placebo, or 5 mg terbutaline sulfate orally. At all time intervals after exercise, the pulmonary function of the group pretreated with oral terbutaline was superior when compared to the no-medication group (P less than 0.01) and to the placebo-treated group (P less than 0.05). Oral terbutaline appeared to normalize the exercise tolerance of the asthmatics and restore physiologic pulmonary airway conductance by the parameters of FEV1.0 and MMEFR.

Administration, Oral↗

Angina pectoris. Diagnosis and treatment.

The physician who understands the pathophysiology of angina pectoris can apply rational therapeutic measures based on an appreciation of the determinants of myocardial oxygen supply and demand. Most patients with angina secondary to coronary atherosclerosis can be treated conservatively using a systematic approach that includes correction or removal of underlying causes or precipitating factors and the judicious use of sublingual nitroglycerin. In patients with more resistant angina, use of oral or topical nitroglycerin or sublingual isosorbide dinitrite as well as propranolol can be advised. Aortocoronary bypass surgery can offer significant improvement in carefully selected patients with frequent angina poorly controlled by medical therapy. The most important consideration in the treatment of angina is protection of coronary blood flow reserve by primary prevention of the atherosclerotic process itself. All individuals from families prone to coronary artery disease should be evaluated for alterable risk factors, the most important being cigarette smoking, hypertension, and hypercholesterolemia. Considering the high risk of unheralded sudden death in previously asymptomatic patients with coronary atherosclerosis, angina can, in a sense, be considered a fortunate harbinger of coronary stenosis, identifying candidates for secondary preventive measures aimed at retarding the progression of vascular disease. More importantly, angina serves as an index for detecting families at high risk of coronary artery disease, in whom early application of primary prevention may afford a more promising outlook.

Adrenergic beta-Antagonists↗

Reflex vasodilation induced by coronary angiography in human subjects.

In order to evaluate the reflex peripheral vascular effects of coronary arteriography, forearm blood flow was measured plethysmographically and forearm vascular resistance calculated before and during coronary angiography with Hypaque-M, 75%, and Renografin-76. The injection of Hypaque into the left coronary artery resulted in a forearm vasodilation which could not be duplicated by an injection of a comparable amount of contrast into the ascending aorta, three centimeters above the coronary ostia. Forearm blood flow rose from 2.95 to 5.41 ml/min/100 ml (83.4%) and forearm vascular resistance fell from 35.8 to 19.9 mm Hg/ml/min/100 ml (44.4%). Renografin injected into the left coronary artery resulted in less forearm vasodilation (21% increase in forearm blood flow and 32% decrease in forearm vascular resistance). When coronary arteriography was repeated following injection of atropine into the brachial artery, no forearm vasodilation occurred. It is suggested that in human subjects myocardial or coronary artery receptors can be activated by the intracoronary injection of iodinated contrast media which results in a forearm vasodilation.

Angiocardiography↗

The effects of morphine on venous tone in patients with acute pulmonary edema.

In order to compare the venodilation effect of morphine in normal individuals (22) with that in patients (13) with heart failure morphine sulfate (0.1 mg/kg) was administered to 13 patients with mild pulmonary edema. After morphine congestive symptoms improved and venodilation was induced as determined by two independent techniques: venous pressure fell 10.2 mm Hg by the isolated hand technique and the venous volume of the forearm increased by 0.48 cc/100 ml, measured by equilibration technique. Neither finding differed from those in normal individuals. Reflex venoconstriction noted on the taking of a single deep breath was unaffected by morphine administration and was similar to that observed in normal subjects. Since the drug morphine sulfate does not cause a major pooling of blood in the limbs, the favorable effect of narcotics in patients with pulmonary edema must be caused by other mechanisms such as splanchnic pooling, afterload reduction or reduced breathing effort.

Acute Disease↗

Impaired forearm oxygen consumption during static exercise in patients with congestive heart failure.

In this study, the effects of forearm static exercise were determined on local blood flow and oxygen consumption in 15 normal individuals (NL) and their responses were compared with ten patients in congestive heart failure (CHF). Forearm blood flow was determined by a plethysmographic technique before and during 15% of maximum voluntary contraction of the forearm. Regional arterial and venous oxygen contents were sampled and forearm oxygen consumption calculated by the Fick principle. At rest, forearm blood flow was less in patients with heart failure than in normal individuals; however, this was compensated for by an increased oxygen extraction, thus maintaining forearm oxygen consumption at a normal level. In contrast, during static exercise, forearm blood flow failed to rise normally with heart failure (NL 9.31; CHF 4.35 ml/min-100 ml, P less than 0.001) and the increased oxygen extraction was not sufficient to maintain a normal forearm oxygen consumption (NL .82; CHF .44 ml/min-100 ml, P less than 0.01). Therefore, patients with congestive heart failure demonstrate regional circulatory and metabolic abnormalities during static exercise that are comparable to those present during dynamic exercise. Because of a limited ability of their skeletal muscle resistance vessels to respond to dilator stimuli, they have an attenuation of their exercise hyperemia which leads to an earlier shift to anaerobic metabolism.

Adolescent↗