Search PubMed⌕ Search

Biomedical subjects

R Zelis

Publications and source records attributed to R Zelis.

At least 91 records · Page 5Linked to original sources
PubMed1982

Effects of diltiazem on total cardiac output distribution in conscious rats.

The present study was conducted to determine the effect of a "calcium channel blocker," diltiazem (DZ), on cardiovascular dynamics and the distribution of total cardiac output in the conscious rat. Animals were instrumented for right atrial, left ventricular, arterial and venous pressure recordings and the radioactive microsphere technique was used to measure regional blood flow and cardiac output before (control) and during the intravenous infusion of either DZ at three dosage levels (0.4, 2.0, and 10.0 mg/kg/hr) or saline placebo at rates matching those of the DZ protocol (0.015, 0.1 and 0.5 ml/min). Maximum volume infusion rate equaled approximately a 2% increase in blood volume/minute. Systemic vascular resistance, stroke volume, regional vascular resistances and the regional percent distribution of total cardiac output were calculated. In the experimental group (n = 9, body weight = 404 +/- 7 g), DZ, at the highest dose, caused a nonsignificant increase in cardiac output of 61% (cardiac output decreased in one animal) and a significant drop in systemic vascular resistance (45%) while no changes occurred in the control group (n = 5, body weight = 440 +/- 9 g). The major effect of DZ was to increase blood flow and reduce vascular resistance in the coronary circulation (percent distribution of total cardiac output to the coronary circulation, control vs. maximum infusion: saline placebo, 3.9 +/- 0.5 to 4.5 +/- 0.4%; DZ, 3.5 +/- 0.5 to 6.9 +/- 0.5%, P less than .01). The results indicate that DZ does not suppress cardiac function and may actually increase cardiac output secondary to afterload reduction. DZ results in a balanced increase in regional blood flow and no major change in total cardiac output distribution in the conscious rat.

Animals↗
PubMed1981

Cardiocirculatory dynamics in the normal and failing heart.

Congestive heart failure is associated with ventricular hypertrophy and dilatation, increased circulating catecholamines, and peripheral vasoconstriction. The extent to which these changes occur, whether they are a favorable "compensatory mechanism" or contribute to cardiocirculatory dysfunction, depends on the cause and severity of the heart failure. The addition of new sarcomeres through ventricular hypertrophy distributes the excess workload of the failing ventricle over more contractile units. In ventricular pressure overload, hypertrophy primarily increases wall thickness and ventricular volume is not usually increased; the converse is true with ventricular volume overload. Hypertrophy can result in enhanced or depressed contractile performance, depending on the stimulus for hypertrophy and method by which contractility is evaluated. The "ventricular function curve," which relates stroke volume to ventricular filling pressure or volume, overestimates the role played by the "Starling principle" as a compensatory mechanism and underestimates how well contractile performance is preserved. The evaluation of end systolic pressure-volume relationships under conditions of variable afterload closely reflects the isometric length-tension relationship and is therefore a more accurate way to quantitate cardiac muscle performance. Pressure overload hypertrophy usually leads to a depression in contractility whereas volume overload may not. An exaggerated sympathoadrenal response is another hallmark of severe heart failure that enhances contractility, helps initiate hypertrophy, and maintains arterial perfusion pressure. A generalized increase in peripheral vascular resistance occurs and is most prominent in those circulations most susceptible to neurohumoral control (renal, splanchnic, cutaneous). This favors perfusion of the cerebral and coronary circulations. Vasoconstriction is further enhanced by the activation of the renin-angiotensin-aldosterone system and secretion of ADH. This results in sodium retention and plasma volume expansion. In early mild heart failure, vasomotor tone may be normal at rest; however, the sympathoadrenal response to exercise may be intense. Moderate alpha receptor stimulation reduces skeletal muscle blood supply and favors the intramuscular redistribution of blood flow from inactive to active muscle fibers, thereby maintaining a normal oxygen consumption. During the later stages of heart failure, increased vascular stiffness due to increased sodium content and excessive norepinephrine appears to restrict nutritional blood flow to exercising muscle at the conductance-vessel level. Vasodilator drugs may reduce aortic impedance and improve cardiac output, may lower ventricular filling pressure, and relieve congestive symptoms, and may result in complex but favorable changes in the distribution of blood flow to the regional circulations.

Blood Pressure↗
PubMed1981

Diltiazem pretreatment reduces experimental myocardial infarct size in rat.

Diltiazem (DZ) is a calcium channel blocking drug which has been shown to be a potent coronary artery dilating agent in the rat. Since this agent has been shown to reduce heart rate and contractility as well as to inhibit calcium transport in the ischemic myocardium, the present study was conducted to determine if DZ is effective in reducing myocardial infarct (MI) size in a rat model utilizing experimental left coronary artery ligation. Rats were pretreated (30 min presurgery) with either DZ (20 mg/kg i.p.) or saline (SA). At 48 h postsurgery, left ventricles were removed and assayed for total creatine kinase activity (CK). Percent infarct size was calculated and found to be significantly reduced from 14.8% in control SA to 6.7% of the total left ventricle in the DZ-treated group (p less than 0.01). Thus, pretreatment with DZ significantly preserves total CK activity and reduces % infarct size in the left ventricle of rats 48 h after experimental MI.

Animals↗
PubMed1981

Radionuclide imaging of experimental myocarditis.

The ability of 67Ga citrate and 99mTc pyrophosphate cardiac imaging to detect myocarditis was assessed in an experimental rabbit model. Twenty-three rabbits were imaged approximately 72 hours after infusion of i.v. norepinephrine. Diffuse cardiac uptake was found in 13 of 15 rabbits scanned with 67Ga. Tissue distribution studies documented significant myocardial uptake of 67Ga in those with positive scans. Precordial imaging and tissue distribution studies revealed no cardiac uptake in the eight rabbits scanned with 99mTc. Histologic examination of all 23 hearts revealed qualitatively similar, typical lesions of myocarditis. This study suggests that cardiac imaging with 67Ga may be useful in the detection of myocarditis.

Animals↗
PubMed1981

Mechanism of action of nitroglycerin during exercise in a rat model of heart failure. Improvement of blood flow to the renal, splanchnic, and cutaneous beds.

The radioactive microsphere technique was used to trace regional blood flow and total cardiac output distribution in rats in heart failure secondary to biventricular volume overload during acute intravenous infusion of nitroglycerin. Data from rats with heart failure (chronic arteriovenous shunt) were compared to data obtained from rats subjected to sham surgical procedures. In both glycerin and normal saline (control). In heart failure, nitroglycerin slightly increased cardiac output at rest and during exercise, increased stroke volume, and reduced systemic vascular resistance at rest but not during exercise. In the heart failure group, exercise reduced flow to the renal, gastrointestinal, and cutaneous circulations but had little or no effect in the sham group. Nitroglycerin dramatically increased renal, gastrointestinal, and cutaneous blood flow during exercise in the heart failure group but had minimal effects on active hyperemia in the skeletal muscle bed. In the sham group, nitroglycerin decreased blood flow in the renal, gastrointestinal, and cutaneous beds and had no effect on skeletal muscle blood flow. Thus, in the renal, gastrointestinal, and cutaneous circulations during exercise, nitroglycerin increased flow in the heart failure group and decreased flow in the sham group to the extent that the respective values in the two groups were equal.

Animals↗
PubMed1981

Underrepresentation of women in new drug trials.

Young women serve less frequently than young men as subjects in premarketing clinical drug trials. Moral, legal, and medical implications of this underrepresentation of women are considered. Risks of medical harm to female patients can increase because medication is withheld. Also, risks of toxicity increase when women receive certain new drugs only in the postmarketing phase. Remedies to increase participation of young, nonpregnant women in clinical trials are discussed.

Clinical Trials as Topic↗
PubMed1981

Cardiogenic shock due to ventricular rupture. A surgical approach.

Following a posterolateral myocardial infarction, a 57-year-old man developed severe shock which did not respond to catecholamine infusion and intra-aortic balloon counterpulsation. Implantation of a left ventricular assist pump was planned, but at sternotomy free ventricular rupture was identified and repaired. Repair of free-wall ventricular rupture is uncommon because of infrequent antemortem diagnosis. A more aggressive surgical approach of instituting left ventricular assist pumping in those patients with cardiogenic shock refractory to medical therapy and intra-aortic balloon pumping should yield the additional benefit of repair of the rather common but rarely recognized lesion of ventricular rupture.

Heart Rupture↗
PubMed1981

Clinical use of calcium entry blockers.

Recently it has been recognized that coronary vasospasm plays a significant role in precipitating myocardial ischemic pain in a significant minority of individuals with coronary atherosclerosis (approximately 27-35% of patients with angina pectoris at rest). In these individuals normal physiological vasoconstrictor stimuli appear to trigger a spasm of the large epicardial coronary vessels; evidence suggests that it may be caused by the release of increased amounts of calcium from augmented sarcolemmal storage sites. The calcium entry blockers are remarkably effective in preventing coronary spasm by reducing intracellular calcium, but by different mechanisms. Verapamil appears to reduce intracellular and, more specifically, sarcolemmal calcium stores directly. Diltiazem appears to reduce intracellular calcium by stimulating the sarcolemmal sodium-potassium pump and reducing intracellular sodium, and by this mechanism. potentiating passive sodium-calcium exchange. The effects of the calcium entry blockers on myocardial contractility, cardiac pacemaker and conduction tissue, and regional vascular smooth muscle are also different. This makes some of these agents more suitable than others for therapy of other clinical problems such as chronic stable angina pectoris, supraventricular tachycardia, hypertension, hypertropic cardiomyopathy, and protection of the ischemic myocardium during cardiac surgery.

Angina Pectoris↗
PubMed1980

Acute effects of arterio-venous shunt on cardiovascular hemodynamics in rat.

The cardiovascular effects of an acute high cardiac output state (Acute HCO) were determined in rats 24 h after opening an abdominal aorta-caval shunt equal to 50% of total cardiac output (CO). Heart rate (HR), left ventricular peak (LVP), end diastolic (LVEDP), and arterial (AP) pressures, CO, stroke volume (SV), total systemic and regional vascular resistance (VR), regional blood flow (BF) (radioactive microspheres), and tissue fluid content data were collected. In Acute HCO, AP and LVP were reduced while LVEDP was elevated, total CO was increased and total VR was decreased while systemic CO and VR were unchanged. In Acute HCO, HR did not change significantly and SV was significantly increased. Lung water in Acute HCO was significantly greater than control. Regional BF changes in Acute HCO include skeletal muscle reflex vasoconstriction and splanchnic and cerebral dilation. The results in conjunction with previous data on chronic HCO indicate that in the rat (1) increased lung water which is absent after cardiovascular compensation is an acute result of HCO, and (2) the acute phase of cardiac compensation to HCO occurs in the absence of a tachycardia response.

Animals↗
PubMed1980

Thallium-scan myocardial defects and echocardiographic abnormalities in patients with sarcoidosis without clinical cardiac dysfunction. An analysis of 44 patients.

Sarcoidosis of the myocardium, an illness occurring predominantly in young adults, frequently becomes clinically apparent when the disease is far advanced. Since the thallium myocardial perfusion scan (TMPS) is known to be capable of detecting granulomas, it seemed to be promising as a noninvasive means of screening for this complication of sarcoidosis. We, therefore, examined 44 consecutive patients with sarcoidosis, none of whom had clinical evidence of heart disease, utilizing TMPS, echocardiography, electrocardiography, systolic time interval ratios (PEP-LVET) and 24-hour Holter monitoring. TMPS disclosed left ventricular defects in 14 patients (32 per cent) and abnormalities of the right ventricle in an additional four patients. Left ventricular abnormalities on the TMPS were associated with echocardiographic evidence of left ventricular dysfunction (widened mitral E point septal separation) but not with abnormalities on Holter monitoring or electrocardiograms. Systolic time interval ratios were insensitive but highly specific for the presence of abnormalities on the TMPS. We conclude that the TMPS frequently discloses abnormalities in sarcoidosis, which may be a reflection of its sensitivity in this setting.

Adult↗
PubMed1980

Beneficial effect of dexamethasone on the "no reflow" phenomenon in canine myocardium.

The purpose of the present study was to determine if pretreatment with dexamethasone 6 mg.kg-1 would preserve coronary artery blood flow during reperfusion, thus preventing the no reflow phenomenon. Blood flow to small segments of the left ventricle was measured by the use of 15 micrometer tracer microspheres in intact dog hearts. During 2 hours of occlusion of the anterior descending coronary artery by balloon catheter, dexamethasone produced a small increase of the blood flow to perfused myocardium, when compared with untreated animals; this effect was not seen in underperfused segments of the myocardium. In nontreated animals, reperfusion of the underperfused portion of the left ventricle did not lead to a restoration of flow to normal when measured 1 hour later. In fact, the "no reflow" phenomenon resulted in a post reperfusion left ventricular segment which was similar to that measured during coronary arterial occlusion. However in the dexamethasone treated animals there was a decrease in the extent of left ventricular underperfusion from 19 to 6%. It is concluded that dexamethasone protects the border zone of canine myocardium during occlusion, and prevents the no reflow phenomenon in underperfused regions during reperfusion

Animals↗
PubMed1980

Early corticosteroid administration in experimental radiation-induced heart disease.

The ability of dexamethasone (DEX) to reduce the severity of the late stage of radiation-induced heart disease (RIHD) was assessed in 25 New Zealand white rabbits. Ten rabbits served as unirradiated controls (CONT). In Group A, seven rabbits received intravenous DEX prior to irradiation and every 24 hours for three consecutive days. DEX was not administered to the eight rabbits in Group B. At 100 days postirradiation, the severity of the late state was determined by microscopic examination (MICRO) for myocardial fibrosis and determination of myocardial hydroxyproline content (MHP). Myocardial fibrosis was evident in Groups A (40%) and B (80%) while none was present in CONT by MICRO. One rabbit in Group B with no fibrosis by MICRO had abnormally increased MHP. MHP was significantly increased in Groups A and B, as compared to CONT (p less than 0.01). In addition to less fibrosis by MICRO, Group A demonstrated a significant reduction of MHP when compared to Group B (p less than 0.05). Determination of MHP may be superior to MICRO in the detection of the late stage of RIHD. Also, early DEX administration appears to reduce myocardial collagen content (fibrosis) in this experimental model.

Animals↗