Biomedical subjects

G Raberger

Publications and source records attributed to G Raberger.

At least 55 records · Page 3Linked to original sources

PubMed1989

Fentanyl inhibits the canine carotid chemoreceptor reflex.

To investigate the impact of fentanyl on the carotid chemoreceptor reflex, nine mongrel dogs were permanently monitored with electromagnetic flow transducers around the right common iliac artery and with heparin-filled catheters in the descending aorta and in one of the main carotid arteries with the tip just proximal to the carotid sinus. Carotid chemoreceptor activation (CCRA) produced by consecutive injections of nicotine (0.2-0.4 micrograms/kg) through the carotid catheter elicited bradycardia, expressed as an increase in cardiac cycle length by 140% +/- 18%, and a 252% +/- 16% increase in mean iliac arterial vascular resistance. These responses were markedly attenuated by fentanyl in a dose-dependent fashion: cardiac cycle length increased only by 50% +/- 7% (P less than 0.01) with 4 micrograms/kg and by 19% +/- 6% (P less than 0.01) with 8 micrograms/kg of intravenous fentanyl. These changes were paralleled by significantly (P less than 0.01) lesser increases in mean iliac arterial resistance (122% +/- 9% and 50% +/- 5%). It is concluded that fentanyl impairs the integrity of the carotid chemoreceptor reflex.

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PubMed1988

Comparison of the haemodynamic effects of the selective bradycardic agent UL-FS 49, with those of propranolol during treadmill exercise in dogs.

1. To clarify whether the bradycardic agent UL-FS 49 exhibits a positive inotropic effect even in the absence of improvement in regional myocardial function of an underperfused myocardial area, this study was undertaken in dogs with unimpaired coronary flow. 2. We also investigated the haemodynamic and functional effects of the negative chronotropic and inotropic beta-adrenoceptor blocker propranolol. 3. UL-FS 49 did not depress total or regional myocardial performance. Moreover, an increase in positive left ventricular dp/dt max at rest suggests a positive inotropic effect of UL-FS 49. 4. Propranolol, in contrast to UL-FS 49, led to a marked reduction in positive dp/dt max, stroke volume and systolic wall thickening at rest and during exercise. Additionally, propranolol decreased the exercise values of cardiac output, left ventricular work and left ventricular power to a far greater extent than UL-FS 49. 5. In contrast to propranolol, the selective bradycardic agent UL-FS 49 did not decrease total or regional ventricular performance and caused less reduction in cardiodynamic parameters during exercise. 6. These results suggest that patients with moderate coronary insufficiency or patients with coronary vessel disease and mild left ventricular failure may attain a higher exercise limit under selective bradycardia with UL-FS 49 in comparison to that possible with a beta-adrenoceptor antagonist, such as propranolol.

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PubMed1988

The effects of nitroglycerin on regional myocardial contractile dysfunction produced by treadmill exercise or isoprenaline stimulation in dogs.

1. To compare different methods of cardiac stress testing that are clinically applied in the management of coronary heart disease, 2 groups of dogs each were chronically instrumented and subjected to treadmill exercise or isoprenaline infusion in the presence of coronary stenosis. 2. It was of interest to determine differences in haemodynamic and regional myocardial contractile parameters, the response to antianginal therapy (nitroglycerin 15 micrograms kg-1 15 min-1, i.v.), and, in particular, whether this response differed according to the mode of cardiac stimulation, i.e. treadmill exercise or isoprenaline infusion. 3. After stenosis of the circumflex branch of the left coronary artery which affected resting myocardial function only minimally, treadmill exercise or isoprenaline infusion induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular end-diastolic pressure and left ventricular dp/dtmax were registered and myocardial oxygen demand was calculated. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4. Treadmill exercise led to an increase in systolic arterial and left ventricular end-diastolic pressure. In contrast, isoprenaline-induced stimulation led to a decrease in diastolic arterial and left ventricular end-diastolic pressure. Regional contractile function in the critically underperfused area showed a deterioration during both modes of stress. Nitroglycerin completely abolished stress-induced contractile dysfunction only in the group where treadmill exercise was employed for stimulation. 5. The inability of nitroglycerin to prevent myocardial dysfunction in the isoprenaline group may be due to exhaustion of the arterial and/or venous vasodilator potency of nitroglycerin in the presence of adrenoceptor vasodilatation induced by isoprenaline. 6. These findings indicate that clinical antianginal drug testing and the evaluation of the course of disease in patients with coronary heart disease may be highly dependent on the test method chosen.

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PubMed1988

Verapamil abolishes exercise-induced regional contractile dysfunction in dogs.

The effects of the Ca++-antagonist verapamil on hemodynamic and regional myocardial functional parameters were studied in a canine model of exercise-induced myocardial dysfunction which mimics exercise-induced angina pectoris. Six dogs, trained to submit to five treadmill exercise cycles, each consisting of 4 min of running and 11 min of recovery, were chronically instrumented with a microtip manometer in the left ventricle, two pairs of crystals for sonomicrometry, a hydraulic occluder around the circumflex branch of the left coronary artery and arterial and venous catheters. Control experiments with coronary stenosis clarified the reproducibility of exercise-induced regional contractile dysfunction and recovery of function in the intervening resting periods. In each individual dog, the same degree of stenosis was used in the subsequent experiments with verapamil. After two control runs which exhibited regional contractile dysfunction of comparable magnitude, verapamil was administered intravenously at a dosage of 0.3 mg/kg over a period of 5 min. Verapamil induced an increase in heart rate at rest due to sympathetic counterregulation secondary to a reduction of systolic and diastolic blood pressure. The exercise-induced increases in heart rate and rate-pressure product were reduced after verapamil, but the exercise-induced increase in left ventricular dp/dtmax was not significantly diminished. The hemodynamic changes led to a marked improvement of regional function during exercise in the area perfused by the stenosed coronary artery. In a study using identical experimental conditions, the Ca++-antagonist bepridil at a dosage of 2 mg/kg/5 min abolished the exercise-induced regional contractile dysfunction to a similar extent as verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1987

Effects of the bradycardic agent UL-FS 49 on exercise-induced regional contractile dysfunction in dogs.

The effects of the bradycardic agent UL-FS 49 on hemodynamic and segmental parameters were studied in a canine model of exercise-induced myocardial dysfunction which mimics exercise-induced angina pectoris. Ten dogs, trained to subunit to five treadmill exercise cycles consisting of 4 min of running and 11 min of recovery, were chronically instrumented with a microtip manometer in the left ventricle, two pairs of crystals for sonomicrometry, a hydraulic occluder around the circumflex branch of the left coronary artery and arterial and venous catheters. Control experiments with coronary stenosis clarified the reproducibility of exercise-induced regional contractile dysfunction and recovery of function in the intervening resting periods. In each individual dog, a similar degree of stenosis was used in the subsequent experiments with UL-FS 49. After two control runs, which exhibited regional contractile dysfunction of comparable magnitude, UL-FS 49 was administered intravenously at a dosage of 0.5 mg/kg/5 min (6 dogs) or 0.25 mg/kg/5 min (4 dogs). Both doses of UL-FS 49 markedly reduced heart rate without alteration of left ventricular positive dp/dtmax at rest and during exercise. A marked improvement of regional function in the area perfused by the stenosed coronary artery was also observed during exercise. This beneficial effect of selective bradycardia, here observed with UL-FS 49, remains to be confirmed in clinical trials.

Angina Pectoris↗

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.

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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.

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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

Erythrocytes as carriers for heparin. Preliminary in vitro and animal studies.

Encapsulation of heparin into resealed carrier erythrocytes may be useful in the prevention of thromboembolism because heparin may be released locally during retraction of fresh thrombi. Heparin encapsulation in human and canine erythrocytes was achieved by hypo-osmotic dialysis with 44% and 36% encapsulation, respectively. Encapsulated heparin did not leak from carrier erythrocytes in vitro. In vivo survival of heparin-loaded carrier erythrocytes in dogs was biphasic: After an initial phase of cell loss the carrier cells survived in circulation with a half-life of 28 h. The present results seem to warrant clinical studies with heparin-loaded carrier erythrocytes.

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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

Immunobiological and antiinflammatory properties of 1-phenylo-2-thioxo-3-diethylo-aminoethylo-4-ox o-7-methylpyrimido- [4,5-c]-pyrimidine hydrochloride (compound I).

Immunological and pharmacological properties of 1-phenylo-2-thioxo-3-diethylo-aminoethylo-4-oxo- 7-methylpyrimido [4,5-c]-pyrimidine hydrochloride were evaluated. The preparation was observed to exert immunotropic, predominantly suppressive effect as well as nonspecific antiinflammatory effect. This was accompanied by hardly perceptible central component and slight, reversible effect on the circulatory system. The trials to elucidate mechanism of activity of the immunotropic preparation revealed that it attacked immunologically committed cells. However, it does not act on suppressor cells.

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.

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PubMed1985

Angiotensin-induced hypertension in conscious dogs: biochemical parameters and baroreceptor reflex.

The effects of a continuous iv infusion (osmotic minipumps) of angiotensin II (80 ng . kg-1 . min-1) and isoprenaline (10 ng . kg-1 . min-1) lasting 28 days were studied in six normotensive, conscious dogs. The parameters measured were systolic and diastolic blood pressure, heart rate, levels of angiotensin II, renin activity, aldosterone and antidiuretic hormone in plasma, baroreceptor reflex sensitivity and body weight. The treatment resulted in an approximately sevenfold increase in plasma angiotensin II level from 62.9 +/- 24.5 pg . ml-1 to 455.3 +/- 95.6 pg . ml-1. Systolic and diastolic blood pressure, measured for the first time 2 days after implanting the minipumps, were markedly increased throughout the infusion period (pretreatment value: 123.8 +/- 5.3/68.3 +/- 3.8 mmHg; after 2 days: 159.8 +/- 12.0/100.5 +/- 9.8 mmHg; after 28 days: 159.8 +/- 7.1/98.3 +/- 6.4 mmHg, whereas the heart rate remained unchanged due to the combined effects of angiotensin II and the concomitantly given isoprenaline. A high correlation was found between angiotensin II level in plasma and mean arterial blood pressure (r = 0.846; p less than 0.001). Furthermore, plasma renin activity was markedly suppressed by the treatment, and aldosterone levels rose. Plasma antidiuretic hormone levels were found to be unchanged at the chosen sampling time. A decrease in baroreceptor reflex sensitivity accompanied the development of the hypertensive state. There was also a loss of body weight during the infusion of angiotensin II and isoprenaline. The data provide evidence for the usefulness of the presented experimental protocol as an alternative model of arterial hypertension in chronically instrumented, conscious dogs.

Aldosterone↗

PubMed1985

Characterization of vasodilators by comparison of their effects on blood pressure, counterregulation and myocardial oxygen demand in conscious normotensive dogs.

Vasodilators were characterized on the basis of their first-dose effect on systolic and diastolic blood pressure, heart rate, on the product of heart rate and systolic blood pressure and on plasma renin activity (PRA) in conscious normotensive dogs. The compounds were given orally to the animals and the effects were studied over a period of 4 h. The arterial vasodilators (propyldazine, dihydralazine and labetalol) caused a marked reduction of systolic and diastolic blood pressure with excessive stimulation of the sympathetic nervous system, leading to an increase in myocardial oxygen demand. The blood pressure effect of urapidil and prazosin resembled more the pattern seen with typical venous dilators (molsidomine and nitrates) and was not accompanied by significant increases in heart rate and in PRA. Hence, the magnitude of diastolic blood pressure reduction seems to be an essential determinant of reflex counterregulation. The results prove that some few parameters can give information about the overall pattern of hemodynamic effects of vasodilators.

Animals↗

PubMed1985

The influence of thymus factor X (TFX) and its fraction V on the haemodynamic and haemopoietic functions.

The activity of crude thymus extract (TFX) and its immunologically most active fraction V were assessed comparatively. It was observed that the circulatory activity occurred only when crude thymus extract was applied and that fraction V was almost completely devoid of this activity. On the other hand, the affinity to hemopoietic stem cells is exhibited by the crude TFX and its fraction V. An assumption is put forward that the haemopoietic activity of TFX may be present also in its fractions considered to be immunologically less active.

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