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Biomedical subjects

R Zelis

Publications and source records attributed to R Zelis.

At least 73 records · Page 4Linked to original sources
PubMed1986

Advances in calcium blocker therapy.

Calcium blockers are drugs that interfere with the entry of calcium ions into cells of a variety of tissues. Three calcium blockers, verapamil, nifedipine, and diltiazem, are currently approved for clinical use in the United States and many others are undergoing clinical trials. All calcium blockers share the effect of dilating blood vessels, although some agents are selective dilators of certain vascular beds, such as the coronary or cerebral circulation. There exist major differences among these drugs in their ability to depress myocardial contraction and inhibit cardiac impulse conduction, as well as other properties. The therapeutic actions of the agents in use, as well as the actions of the investigational calcium blockers, have been reviewed. Although calcium blockers are generally well tolerated and have fewer side effects than many alternative drugs, serious adverse effects are possible in certain clinical settings. The clinical indications for these drugs continue to expand and will likely find many uses in surgical patients, especially in the areas of cardiac surgery, neurosurgery, vascular surgery, and general surgery.

Arrhythmias, Cardiac↗
PubMed1986

Regional vascular adjustments during recovery from myocardial infarction in rats.

Left ventricular function and systemic regional blood flow (radioactive microspheres, 15 +/- 5 mu) were studied 1, 3, 10 or 42 days after left coronary occlusion in conscious rats. One day after coronary occlusion, vascular resistance in the skeletal muscle and cutaneous beds increased while stroke work and left ventricular systolic pressure were depressed. Regional blood flow and hemodynamic data were similar for sham and infarction groups at 3 and 10 days after surgery, except for left ventricular end-diastolic pressure, which was significantly increased in rats with infarction (sham versus infarct: 11.5 +/- 1.0 versus 18.4 +/- 3.2 at day 3 and 12.2 +/- 1.4 versus 19.9 +/- 3.2 at day 10) (p less than 0.05). At 42 days after myocardial infarction, manifest heart failure occurred as documented by decreased cardiac output and left ventricular systolic pressure and elevated left ventricular end-diastolic pressure and vascular resistance in the cutaneous, skeletal muscle and renal beds. In a separate group of animals with moderate (33.2 +/- 2% of left ventricle) and large infarctions (45 +/- 1.3% of left ventricle), regional blood flow was compared with the sham group. Rats with a large infarct demonstrated significant (p less than 0.05) reduction in flow to kidney, gut and liver. In rats with a medium sized infarct, only renal blood flow was significantly reduced. It is concluded that in this model of myocardial infarction, early cardiocirculatory depression is followed by a partially compensated state with increased left ventricular end-diastolic pressure and subsequent systemic and regional vasoconstriction which, in turn, may contribute to late deterioration of heart failure.

Animals↗
PubMed1986

Enhanced maximal metabolic vasodilatation in the dominant forearms of tennis players.

In an effort to evaluate potential peripheral adaptations to training, maximal metabolic vasodilation was studied in the dominant and nondominant forearms of six tennis players and six control subjects. Maximal metabolic vasodilation was defined as the peak forearm blood flow measured after release of arterial occlusion, the reactive hyperemic blood flow (RHBF). Two ischemic stimuli were employed in each subject: 5 min of arterial occlusion (RHBF5) and 5 min of arterial occlusion coupled with 1 min of ischemic exercise (RHBF5ex). RHBF and resting forearm blood flows were measured using venous occlusion strain-gauge plethysmography (ml X min-1 X 100 ml-1). Resting forearm blood flows were similar in both arms of both groups. RHBF5ex was similar in both arms of our control group (dominant, 40.8 +/- 1.2 vs. nondominant, 40.9 +/- 2.1). However, RHBF5ex was 42% higher in the dominant than in the nondominant forearms of our tennis player population (dominant, 48.7 +/- 4.0 vs. nondominant, 34.4 +/- 3.4; P less than 0.05). This intraindividual difference in peak forearm blood flows was not secondary to improved systemic conditioning since the maximal O2 consumptions in the two study groups were similar (controls, 45.4 +/- 3.9 vs. tennis players, 46.1 +/- 1.7). These findings suggest a primary peripheral cardiovascular adaptation to exercise training in the dominant forearms of the tennis players resulting in a greater maximal vasodilatation.

Adult↗
PubMed1986

Endurance training in rats with chronic heart failure induced by myocardial infarction.

The response to exercise was investigated in trained and sedentary rats with moderate compensated heart failure produced by myocardial infarction (MI) and in rats that underwent sham operations. Trained rats ran on a treadmill (10% grade at 20 m/min) for 60 min/day, 5 days/week for 10 to 12 weeks, whereas sedentary rats had only limited activity. Maximal oxygen consumption normalized for body weight (ml kg-1 min-1) was determined for each rat and found to be (1) greater in trained rats when compared with sedentary rats and (2) greater in sham-operated rats when compared with their counterparts that suffered infarction. In addition, skeletal muscle succinate dehydrogenase activities were greater and the blood lactic acid response to submaximal exercise was lower in trained rats compared with sedentary rats. Left ventricular infarct size for sedentary and trained rats with infarction was 36 +/- 3% and 34 +/- 3% of the total endocardial circumference, respectively, and resulted in (1) elevated left ventricular end-diastolic pressures at rest and during exercise, (2) lower mean arterial pressures at rest, and (3) lower maximal heart rates when compared with those in their sham-operated counterparts. However, normalization of mean arterial pressures during submaximal and maximal exercise was found along with a trend toward normalization of maximal heart rate when trained rats with infarction were compared with their sedentary counterparts. Blood flows to the kidneys, organs of the gut, and skeletal muscle during both submaximal and maximal exercise were unaffected by either myocardial infarction or training; no differences between sedentary and trained rats with infarction and sedentary and trained sham-operated rats were found. These results demonstrate that an exercise training program of moderate intensity produces beneficial hemodynamic and metabolic effects in rats with moderate compensated heart failure.

Animals↗
PubMed1986

Relative presynaptic and postsynaptic effects of urapidil on adrenoceptors in the rabbit pulmonary artery.

Urapidil is a new antihypertensive drug which is thought to possess unique antiadrenergic properties. It is definitely a post-synaptic alpha adrenergic antagonist, but it also claimed to be a presynaptic alpha adrenergic agonist resulting in inhibition of norepinephrine release. To test the relative presynaptic and postsynaptic activity and selectivity in an isolated rabbit pulmonary arterial preparation, two series of studies were performed. The first evaluated the effects of urapidil on electrically evoked 3H overflow in the superfused vascular strip preincubated with [3H]norepinephrine. No significant inhibition of 3H overflow was observed. Rather, urapidil appeared to possess relatively weak presynaptic alpha-2 adrenergic antagonistic properties which were reversed by clonidine. The concentration producing a 30% increase in 3H overflow (EC30pre) was 7070 nM. The second series of studies evaluated the effects of urapidil on the concentration-contractile response curve to norepinephrine. Schild plot analysis yielded a pA2 value of 6.24 and a KBpost of 575 nM. One measure of the relative pre- and postsynaptic antagonistic potency is the EC30pre/KBpost ratio. For urapidil, this was 12.3, suggesting that the drug is a partially selective postsynaptic alpha adrenergic antagonist, with approximately 4.5 times the postsynaptic selectivity of phentolamine, but with 1/18 the potency of phentolamine to block postsynaptic alpha receptors.

Animals↗
PubMed1985

[Modification of organ perfusion by calcium blocker and converting enzyme inhibitor in the conscious rat with heart failure].

The present study examined the regional vascular effects (radioactive microspheres) of converting-enzyme inhibition (captopril, 1 mg/kg) and calcium-antagonism (diltiazem, 1 mg/kg) in a rat model of cardiac failure due to large myocardial infarction (n = 18, infarct size 40% of the left ventricle) both at rest and during submaximal treadmill exercise. Diltiazem increased renal, gastrointestinal, coronary and cutaneous blood flow at rest by 29%, 28%, 26% and 37% (p less than 0.05 each) and enhanced skeletal muscle blood flow during exercise by 16% (p less than 0.05). Captopril improved primarily renal and coronary blood flow at rest (by 59% and 23%, respectively, p less than 0.05) and reduced vascular resistance in the gastrointestinal bed by 25% (p less than 0.05) without significant effects in other circulatory beds. We conclude that the regional vascular effects elicited by converting-enzyme inhibition and calcium antagonism differ considerably in this animal model of congestive heart failure and may be clinically important. The favourable regional vascular profile of diltiazem deserves further clinical investigation.

Animals↗
PubMed1985

Inhibition by diltiazem of norepinephrine release from sympathetic nerves in the rabbit pulmonary artery.

In order to determine if the calcium blocker diltiazem could alter excitation-secretion coupling in vascular sympathetic nerves, superfused rabbit pulmonary arterial strips were preincubated with 3H-norepinephrine and stimulated electrically (2-8 Hz) and by KCl (60 mM). Diltiazem significantly inhibited tension development with 4 Hz (1.5 X 10(-5) M) and 8 Hz (1.5 X 10(-6), 1.5 X 10(-5) M) stimuli, but only at 1.5 X 10(-5) M did diltiazem inhibit the 3H overflow evoked by an 8-Hz stimulus. No inhibition of 3H overflow was noted with the 2 and 4 Hz stimuli. With an 8-Hz stimulus the inhibition of tension development (45.4%) by diltiazem (1.5 X 10(-5) M) was significantly greater than the inhibition of 3H overflow (33.8%). A similar relationship was noted with 60 mM KCl stimulation. These data suggest that excitation-secretion coupling in vascular sympathetic nerves can be inhibited by diltiazem.

Animals↗
PubMed1985

Effects of diltiazem on cardiac function and regional blood flow at rest and during exercise in a conscious rat preparation of chronic heart failure (myocardial infarction).

The effects of intravenous infusion of diltiazem on regional blood flow (radioactive microspheres), hemodynamics, and maximum rate of oxygen consumption were evaluated in conscious rats with congestive heart failure caused by large myocardial infarction (n = 10, infarct size 41.8% of left ventricle) and compared with data obtained from rats subjected to sham surgical procedures (n = 9). In both groups data were obtained at rest and during submaximal treadmill exercise during alternate infusion of diltiazem and saline. In the group with heart failure, diltiazem increased stroke volume at rest and during exercise (p less than .05), reduced heart rate (p less than .05), and improved cardiac output during exercise (p less than .05) without increasing left ventricular end-diastolic pressure in any of the animals. Blood flow to renal and splanchnic circulations was reduced in the group with heart failure but was increased by diltiazem to values similar to those observed in sham-operated animals. Although skeletal muscle flow during exercise was significantly increased by the drug, maximal rate of oxygen consumption was not, indicating unchanged oxygen availability within working muscle. Thus diltiazem caused redistribution of blood flow to kidney and gut in animals with myocardial infarction and failure, thereby restoring blood flow to circulatory beds known to be impaired in this setting.

Animals↗
PubMed1985

Effects of nisoldipine on cardiocirculatory dynamics and cardiac output distribution in conscious rats at rest and during treadmill exercise.

This study examined the effects of the dihydropyridine derivative nisoldipine (1.6 micrograms/kg/min) on hemodynamics and regional blood flow (radioactive microspheres, 15 +/- 5 microns) in conscious rats at rest and during treadmill exercises (35 feet/min, 5 min). Nisoldipine significantly reduced systemic vascular resistance (-38%) and mean arterial pressure (-17%) and increased heart rate (P less than .05). Skeletal muscle blood flow was increased and vascular resistances in the skeletal muscle, in renal and coronary arteries and in part of the gut circulations were significantly reduced (all P less than .05). Left ventricular end-diastolic pressure was unchanged by the drug both at rest and during exercise. At exercise, nisoldipine significantly increased skeletal muscle blood flow in four of eight skeletal muscle regions investigated; however, the increase in total skeletal muscle flow was less pronounced compared to the changes at rest. The vasodilator effect of nisoldipine in the renal and splanchnic circulations was markedly attenuated by the exercise-induced vasoconstriction in these circulatory beds. We conclude that nisoldipine is a potent vasodilator of skeletal muscle and coronary and renal arteries. It appears to possess highly selective effects on vascular smooth muscle as compared to its direct cardiac effects.

Animals↗
PubMed1983

Amrinone-mediated thrombocytopenia.

Amrinone, a new cardioactive drug, was administered for, on average, 27.9 d to 12 patients in severe congestive heart failure. Thrombocytopenia occurred in 4 patients, while a progressive decline in platelet numbers developed in 3 additional patients. The mechanism for these adverse effects of amrinone is unclear, but merits further study because of its frequency.

Aminopyridines↗
PubMed1983

Assessment of a cardiovascular education program.

A single education program for teaching principles of the Prudent Diet was assessed for its effectiveness in producing compliance to dietary recommendations. The study population consisted of 50 free-living adults between the ages of 20 and 75. Each adult was a member of a club or organization that had requested to view the program via a local chapter of the AHA. A pretest/post-test format was used for the study. Individuals completed a questionnaire prior to viewing the program and again eight weeks after viewing the program. The questionnaire was designed to measure attitudes, knowledge, and compliance to recommendations. Demographic data regarding age, sex, and exposure to heart disease were also obtained. Results indicated that the study population changed their beliefs about their perceived susceptibility to CHD, becoming more concerned after viewing the program. Attitudes toward diet and CHD became slightly more positive but not significantly so. An overall gain in knowledge occurred that was highly significant. The study group consumed skim milk, lean meats, and broiled meats more often after viewing the program. In addition, they reported trimming all visible fat from meat before preparation and/or consumption. It was concluded that this education program has potential for producing an attitude change and knowledge acquisition and for motivating positive changes in dietary habits toward the recommendations of the Prudent Diet.

Adult↗
PubMed1982

Clinical experience with amrinone in patients with advanced congestive heart failure.

To examine the efficacy of chronic amrinone therapy, the drug was administered to 12 patients with advanced congestive heart failure on average for 27.9 days. The majority of patients had a persistent increase in cardiac index and a persistent decrease in systemic vascular resistance. A decrease in pulmonary arterial diastolic pressure was observed after oral amrinone administration in three patients. However, changes in pulmonary arterial pressure were not consistent in response to intravenous administration of the drug. Thrombocytopenia occurred in four patients, hypogeusia was noted by three patients, and dysosmia developed in two patients. The cumulative survival of the amrinone patients was significantly poorer than that of a second group of patients with congestive heart failure having similar symptoms. These findings indicate that there is a subset of patients with congestive heart failure who do not benefit from chronic amrinone administration and that in such patients its use (especially when given concomitantly with potentially toxic and hypotensive drugs) should be extremely guarded.

Administration, Oral↗
PubMed1982

The treatment of severe Raynaud's phenomenon with verapamil.

Verapamil was evaluated in 16 patients with severe Raynaud's phenomenon. Fifty per cent of patients experienced subjective improvement by history, but only one patient had a substantial reduction in the frequency of Raynaud's phenomenon as assessed by diary analysis. We conclude that verapamil is not effective in most patients with severe Raynaud's phenomenon.

Clinical Trials as Topic↗