Biomedical subjects

G Krumpl

Publications and source records attributed to G Krumpl.

30 records · Page 2Linked to original sources

PubMed1987

Effects of specific bradycardic agents on exercise-induced regional myocardial dysfunction in dogs.

Alinidine and ULFS 49, two specific bradycardic agents were comparatively investigated with propranolol in a model of exercise-induced regional myocardial contractile dysfunction in dogs. Standardized treadmill exercise resulted in a marked decrease in regional function in the myocardium supplied by the critically stenosed circumflex branch of the left coronary artery. All three drugs prevented exercise-induced myocardial dysfunction. The effect on the exercise-induced increase in heart rate and left ventricular dp/dt, however, suggests different modes of action. Propranolol prevents dysfunction by a marked negative inotropy and negative chronotropy, alinidine by a marked negative chronotropy and moderate negative inotropy, but ULFS 49 prevents dysfunction solely by a marked negative chronotropic effect.

Animals↗

PubMed1987

Antihypertensive effects of niguldipine-HCl (B 844-39), a new calcium antagonist in dogs.

B 844-39 is a new dihydropyridine calcium antagonist with a long-lasting antihypertensive action. Preliminary tests in chronically instrumented normotensive dogs revealed that B 844-39 (0.3 mg/kg p.o.) caused a marked decrease in blood pressure which was accompanied by a counterregulatory increase in heart rate. Both effects outlasted the 6-h observation period. There was no sign of cardiac depression in left ventricular positive dP/dtmax or sonomicrometrically evaluated subendocardial systolic shortening. B 844-39 was also tested in renal hypertensive dogs over a period of 12 days to investigate its potential in the long-term treatment of hypertension. A dosage of 0.3 mg/kg given orally twice a day led to a marked and persistent decrease in blood pressure, which was accompanied by a positive chronotropic effect and increases in plasma renin activity and angiotensin II. This initial counterregulatory response was blunted within several days of chronic treatment. After completion of the 12-day treatment period, the blood pressure reduction persisted for greater than 14 days. B 844-39 induced a marked and persistent reduction in blood pressure in hypertensive dogs, even with prolongation of the dosing interval to 24 h. The hypotensive effect of this drug was more pronounced in hypertensive than in normotensive animals.

Animals↗

PubMed1987

The effects of nitroglycerin on exercise-induced regional myocardial contractile dysfunction are not diminished by pretreatment with dihydroergotamine.

1 Because controversy exists regarding the effects of dihydroergotamine (DHE) on the performance of underperfused myocardium, the effects of DHE were investigated in a model of exercise-induced regional myocardial dysfunction in conscious dogs. 2 We also investigated a possible functional antagonism between DHE and nitroglycerin that might reduce the latter drug's antianginal efficacy. 3 Investigations were carried out in conscious dogs. After stenosis of the circumflex branch of the left coronary artery that minimally affected resting myocardial function, treadmill exercise induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular dp/dtmax and left ventricular end-diastolic pressure were registered. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4 DHE (5 micrograms kg-1, i.v.) induced a decrease in left ventricular dp/dtmax at rest and during exercise. DHE did not cause a deterioration in contractile function in the ischaemic myocardium, but led to a slight although not significant improvement in regional myocardial function. 5 After pretreatment with DHE, infusion of nitroglycerin (15 micrograms kg-1, i.v.) induced an improvement in the underperfused myocardial area during treadmill exercise, accompanied by a decrease in diastolic arterial pressure and left ventricular end-diastolic pressure and an increase in left ventricular dp/dtmax. 6 These results suggest that DHE will not worsen exercise-induced angina pectoris, and that the antianginal efficacy of nitroglycerin will not be neutralized by pretreatment with DHE.

Animals↗

PubMed1986

Effects of alinidine on exercise-induced regional contractile dysfunction in dogs.

The effects of the bradycardiac agent alinidine on hemodynamic parameters and regional contractile function were investigated in 6 chronically instrumented dogs trained to submit to 5 consecutive treadmill exercise runs. The experiments were performed during stenosis of the circumflex branch of the left coronary artery (LCX). After 2 control runs which had induced regional contractile dysfunction of comparable intensity, alinidine was infused intravenously at a dosage of 1 mg/kg per 5 min. The drug significantly reduced the resting function of both the LCX area (-16%) and the area perfused by the unstenosed anterior descending branch of the left coronary artery (LAD, -3%). However, the exercise-induced dysfunction of the LCX area was markedly improved in the 1st post-drug run and completely abolished during the 2nd and 3rd post-drug runs. As indicated by the reduction of heart rate (-18%) and positive dp/dtmax (-24%) during peak exercise, this improvement may be attributed to a bradycardiac and a negative inotropic effect of this drug. Further benefit may be ascribed to a decreased in arterial blood pressure after alinidine.

Animals↗

PubMed1986

Can exercise-induced regional contractile dysfunction be prevented by selective bradycardic agents?

Propranolol (0.5 mg X kg-1 X 5 min-1), alinidine (1 mg X kg-1 X 5 min-1) and the benzazepinon UL-FS 49 (0.5 mg X kg-1 X 5 min-1) were investigated in a canine model of exercise-induced transient myocardial dysfunction, mimicking exercise-induced functional impairment during angina pectoris in man. Each drug was infused intravenously, after two control treadmill exercise runs had shown comparable, ultrasonically assessed regional contractile dysfunction in an area supplied by a partly stenosed branch of the left coronary artery. All three drugs abolished exercise-induced regional contractile dysfunction. Propranolol and alinidine comparably decreased heart rate and positive dp/dtmax during exercise. UL-FS 49 showed a marked negative chronotropic effect without affecting positive dp/dtmax. Thus, prevention of exercise-induced regional contractile dysfunction has been shown for the first time using a selective bradycardic agent.

Animals↗

PubMed1986

A model of transient myocardial dysfunction in conscious dogs. Regional shortening in the presence of impaired coronary flow reserve and treadmill exercise.

An experimental model of treadmill exercise-induced regional myocardial dysfunction was developed in conscious dogs to mimic exertional angina pectoris in man. Twenty mongrel dogs, trained to run on a treadmill, were chronically instrumented with a miniature pressure transducer in the left ventricle and a hydraulic occluder placed around the circumflex branch of the left coronary artery. Two pairs of piezoelectric crystals for sonomicrometry were implanted subendocardially to measure regional myocardial function. Experiments were started 1 week after surgery. In the first group of ten dogs exercise with constant work load of 10 km/hr and 10% elevation during partial left coronary artery stenosis, induced by external filling of the occluder, produced comparable episodes of regional dysfunction in the left coronary artery area during five subsequent treadmill runs and recovery of function after each run. The second group of ten dogs, exercised with left coronary artery stenosis and increasing working load, exhibited minimal regional dysfunction in the left coronary artery area while running at 6 km/hr and 6% elevation, but maximal regional dysfunction during peak exercise (10 km/hr and 10% elevation). This load dependency and recovery of function after the runs was demonstrated during five identical consecutive exercise cycles. This model, in contrast to those using ameroid constrictors, enables various drugs to be tested in a single instrumented dog over a period of several weeks.

Angina Pectoris↗

PubMed1986

Bepridil abolishes exercise-induced regional contractile dysfunction in dogs.

The effects of bepridil, a calcium antagonist, on hemodynamic parameters and regional contractile function were investigated in six dogs trained to submit to five treadmill exercise cycles consisting of 4 min of running and 11 min of recovery. The animals were chronically instrumented with a microtip manometer in the left ventricle, two pairs of piezoelectric crystals for sonomicrometry and a hydraulic occluder around the circumflex branch of the left coronary artery and arterial and venous catheters. Experiments were started 1 week after surgery. After a warming-up exercise the vessel was partly stenosed by external filling of the hydraulic occluder. Stenosis was considered adequate and maintained when hemodynamic and functional parameters were virtually unchanged at rest, but episodes of comparable regional contractile dysfunction of the area perfused by the stenosed artery occurred in response to exercise in five subsequent runs; the same degree of stenosis was used for the experiments with bepridil. After two runs with comparable regional contractile dysfunction bepridil was infused intravenously at a dosage of 2 mg/kg per 5 min. The exercise-induced dysfunction was minimally improved in the 1st post-drug run but completely abolished during the 2nd and 3rd post-drug runs. This marked improvement may be partly attributable to the hemodynamic effects of this drug, namely a diminished increase in heart rate and left ventricular end-diastolic pressure and even a reduction in end-diastolic segment length during exercise. These results support the findings of initial clinical trials and suggest a beneficial effect of bepridil in the treatment of exercise-induced angina pectoris in man.

Animals↗

PubMed1986

Effects of long-term administration of propyldazine on blood pressure and counter-regulatory systems in conscious hypertensive dogs.

The counter-regulatory effects in response to blood pressure reduction by propyldazine were studied in conscious dogs with bilateral cellophane perinephritis hypertension. During a 22-day period of chronic treatment, the initial increase in heart rate, plasma renin activity, angiotensin II, aldosterone, and vasopressin, which indicate counter-regulation to the drug induced decrease in blood pressure, vanished. On the fifth day of treatment another, presumably cellular mechanism, had taken over the restitution of blood pressure and thereby led to tolerance towards the action of further propyldazine administration. Seven days after the end of chronic treatment a renewed propyldazine administration did not produce the same effects as obtained with the first administration; after 28 days the hypotensive effect of propyldazine was identical to the one observed before treatment.

Animals↗

PubMedDate not supplied

Transient drug-induced myocardial dysfunction is not ameliorated by PGI2 in dogs.

Prostacyclin (PGI2), a potent vasodilatory substance that effectively inhibits platelet aggregation is under clinical investigation for the treatment of angina pectoris. We studied the effects of PGI2 on transient drug-induced myocardial dysfunction in anesthetized, thoracotomized dogs. Regional myocardial function was assessed using two pairs of piezoelectric transducers and a multidimensional measuring gauge; one pair was implanted in the distribution area of the left circumflex branch (LCX) and the other in the distribution area of the descending branch (LAD) of the left coronary artery. After intravenous injection of isoproterenol (ISO), which led to an increase in systolic shortening in the LCX and LAD areas, a critical stenosis was performed on the LCX and maintained at this level. Intravenous ISO injection now induced regional dysfunction in the LCX-dependent segment with the occurrence of systolic bulging. Infusion of PGI2 at a dosage of 100 ng/kg/min caused a decrease in arterial blood pressure and an increase in heart rate, but had no effect on regional myocardial function. ISO-induced myocardial dysfunction in the critically stenosed LCX segment, which was observed before PGI2 administration, was not ameliorated, but rather aggravated, by PGI2. It may be concluded that PGI2 does not improve normal or ISO-stimulated myocardial function in pressure-dependent perfused areas of the heart.

Animals↗

PubMedDate not supplied

Propranolol ameliorates exercise-induced regional myocardial dysfunction in dogs.

The effects of propranolol (0.5 mg/kg) on exercise-induced regional myocardial dysfunction were investigated in an animal model with limited coronary reserve. Limited coronary reserve was accomplished in conscious, chronically instrumented dogs by external filling of a hydraulic cuff occluder placed on a coronary vessel which did not impair resting myocardial function but induced severe dysfunction during treadmill exercise. Propranolol led to a distinct reduction of heart rate, myocardial contractility and systolic blood pressure, thereby ameliorating exercise-induced regional myocardial dysfunction.

Animals↗

PubMedDate not supplied

Programmed electrical stimulation in conscious dogs: electropharmacologic testing of amrinone.

In order to assess possible proarrhythmic properties of amrinone, serial programmed electrical stimulation was performed via several previously implanted electrodes in 12 conscious dogs during the late reperfusion phase following experimental myocardial infarction. In 6 dogs, programmed electrical stimulation was carried out before and following the administration of amrinone (Wincoram) at cumulative doses of 0.3, 1 and 3 mg/kg, i.v., while the rest served as control group and received matching volumes of saline. Amrinone decreased atrioventricular refractoriness but did not alter ventricular refractory periods in both normal and infarct zones. Amrinone (3 mg/kg) substantially enhanced intraventricular conduction. Induction of ventricular arrhythmias was attempted only at base line and following 3 mg/kg of amrinone. Inducibility was unaltered by amrinone. However, in two experiments we observed more severe forms of arrhythmia to be inducible following drug administration. The number of extrastimuli necessary for the induction of arrhythmias was decreased in two cases during treatment. In the control group, neither the nature of induced arrhythmias nor the number of extrastimuli was changed. We conclude that, in our model, amrinone exerts a moderate proarrhythmic effect when assessed by programmed electrical stimulation. This arrhythmogenic property may be due to an enhancement of intraventricular conduction.

Amrinone↗

PubMedDate not supplied

Effects of niguldipine, a new dihydropyridine calcium antagonist, on regional blood flow, cardiac performance and myocardial metabolism in anaesthetized open-chest dogs.

The haemodynamic and metabolic effects of niguldipine (0.01, 0.025 and 0.5 mumol/kg i.v.), a novel dihydropyridine calcium antagonist, were evaluated in 18 anaesthetized open-chest dogs. The following parameters were continuously measured: heart rate, arterial and pulmonary arterial blood pressure, left and right atrial pressure, left ventricular dp/dtmax, cardiac output, regional blood flow in the circumflex branch of the left coronary artery, and in 1 renal and 1 femoral artery. At predetermined intervals, contents of O2, CO2, H+ ions, glucose, lactate and free fatty acids were determined in blood drawn from the left atrium and a regional cardiac vein. Niguldipine induced a dose-dependent decrease in both systolic and diastolic arterial blood pressure, which led to an increase in heart rate and cardiac output. Mean left atrial pressure was markedly reduced by all doses. Coronary blood flow increased dose-dependently and persistently. Perfusion in the renal and femoral vascular beds also increased, but only transiently and to a lesser extent. Calculation of vascular conductances revealed a preferred vasodilating drug effect on the coronary vascular bed. Right atrial and systolic and diastolic pulmonary artery pressures were not noteworthy altered. Balances of metabolic substrates, O2, CO2 and H+ ions did not indicate any major drug effect of niguldipine on myocardial metabolism.

Anesthesia↗