Biomedical subjects

R Seitelberger

Publications and source records attributed to R Seitelberger.

59 records · Page 4Linked to original sources

PubMedDate not supplied

Altered blood pressure response to propyldazine after repeated oral administration in conscious normotensive dogs: role of the renin-angiotensin system.

The magnitude and the persistence of blood pressure reduction by propyldazine (PDZ) was investigated following treatment over a period of 4 days. The experiments were performed on 6 normotensive dogs trained to submit to puncture of the femoral artery and to stand quietly in a special frame over the experimental period of 7 to 8 hours. The first dose effect of orally administered PDZ (0.06, 0.29 and 1.42 mg/kg) on heart rate, arterial blood pressure and plasma renin activity (PRA) was compared with the effect of the substance after treatment at the same respective dosage twice daily over 4 days. The compound caused a dose-dependent decrease in blood pressure accompanied by dose-dependent increases in heart rate and PRA. With 0.06 mg/kg and 0.29 mg/kg PDZ a sustained effect on arterial blood pressure was observed, whereas with 1.42 mg/kg PDZ tolerance occurred after treatment over the 4-day period. A comparison with the effects observed previously with 1.42 and 7.1 mg/kg dihydralazine (DHZ) under identical conditions showed similar results with respect to dose-dependence of blood pressure and counterregulation (1). It is considered that with a low-dose regimen there would be no decrease in activity of PDZ, the long-term hypotensive efficacy of the drug thereby being guaranteed.

Administration, Oral↗

PubMedDate not supplied

Comparison of the effects of dihydroergotamine and ergonovine on functional changes caused by beta-adrenergic stimulation in normally and underperfused canine myocardium.

We studied the effects of dihydroergotamine (DHE) and ergonovine on myocardial function in normally perfused myocardial areas and in myocardial areas with restricted coronary flow. Regional function at rest and during isoproterenol (ISO)-induced cardiac stimulation was assessed by two pairs of piezoelectric transducers. Constriction of the circumflex branch with a decrease in coronary blood flow from 24.9 +/- 2.6 to 18.1 +/- 2.2 ml/min had little effect on resting regional function. Intravenous bolus injection of ISO (0.5 microgram/kg) prior to constriction induced a marked decrease in end-diastolic segment length and an increase in percentage shortening. Intravenous bolus injection of ISO (0.5 microgram/kg) after constriction of the circumflex branch induced transient regional dysfunction, as shown by a maximum decrease of percentage shortening by 54.4% in the underperfused area. Intravenous infusion of DHE (2 micrograms/kg; 5 min) did not significantly affect resting function and effectively inhibited ISO-induced regional dysfunction. This improvement in regional function during ISO-induced cardiac stimulation can be attributed to the fact that DHE decreased heart rate and left ventricular power, thus reducing myocardial oxygen demand and improving the energetic situation in the underperfused myocardium. In contrast, ergonovine (5 micrograms/kg; 5 min) induced an impairment in regional function in both segments at rest and further aggravated ISO-induced transient dysfunction. The present study confirms the adverse effect of ergonovine on blood flow and regional function in underperfused myocardial areas and demonstrates a beneficial effect of DHE on regional function in underperfused myocardial areas during ISO-induced cardiac stimulation.

Animals↗

PubMedDate not supplied

Effects of acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on cardiodynamics and myocardial metabolism in dogs.

An investigation is presented of the effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA; 20 mg/kg i.v.) on cardiodynamics and myocardial metabolism in normoxic, anesthetized dogs. POCA induced an initial increase in pulmonary vascular resistance; pulmonary vascular pressure was increased up to 4 h. All other hemodynamic parameters were unchanged. POCA induced a continuous rise in arterial free fatty acid (FFA) level and a marked initial increase in arterial lactate level. Arterial glucose level decreased. Myocardial FFA uptake was almost completely inhibited by POCA; myocardial lactate uptake increased markedly and myocardial glucose uptake remained unchanged. These changes were accompanied by an increase in respiratory quotient from 0.72 to 1.0 and a decrease in myocardial oxygen consumption by 15-20%. In conscious dogs, POCA (20 mg/kg i.v.) induced similar changes in arterial substrate levels. The increase in arterial FFA level was accompanied by an increase in arterial glucagon. Ketone body levels decreased initially but increased simultaneously with glucagon levels. These findings confirm the efficacy of POCA in inhibiting FFA oxidation and, consequently, in decreasing myocardial oxygen consumption. However, possible deleterious effects of the increase in arterial FFA levels on the ischemic myocardium require further experimental evaluation.

Acyltransferases↗

PubMedDate not supplied

Effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on metabolism and regional function in the underperfused canine myocardium.

We investigated the effects of sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on regional myocardial function and metabolism in anesthetized, thoracotomized dogs subjected to a 53.5% reduction in flow through the circumflex branch of the left coronary artery (LCX). Regional function in the area supplied by the LCX and the left anterior descending coronary artery (LAD) was assessed by means of two pairs of subendocardially inserted ultrasonic transducers. Hemoglobin content, oxygen saturation, pH, PCO2, PO2, lactate, glucose, and free fatty acids were determined in arterial and local venous blood obtained from the area supplied by the LCX. POCA (20 mg/kg/20 min i.v.) induced a transient decrease in left ventricular power and cardiac output. Arterial free fatty acid (FFA) levels increased continuously throughout the experiment, whilst arterial glucose levels showed a continuous decrease. FFA uptake, lactate release, and oxygen uptake were reduced in the underperfused area by POCA. At the same time, POCA induced a transient increase in end-diastolic segment length and a sustained decrease in systolic shortening during the ejection phase in the underperfused area. No changes in regional function were observed in the area perfused by the nonconstricted LAD.

Acyltransferases↗

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↗