The effect of single and repeated oral doses of isosorbide dinitrate on plasma renin activity and plasma catecholamine levels in conscious dogs.
Explore the source record for details and available documents.
Administration, Oral↗
Biomedical subjects
G Raberger
Publications and source records attributed to G Raberger.
Coronary reactive hyperaemia and coronary dilator action of adenosine during intracoronary infusion of angiotensin II.
Investigations were carried out in chloralose-anesthetized, thoracotomized dogs. The effects of an intracoronary infusion of angiotensin II (3 ng/ml coronary blood) on reactive hyperaemic blood flow and adenosine-induced coronary vasodilation were established. Coronary artery occlusions were performed over periods of 5, 10 and 25 heart beats and adenosine was injected intracoronarily at dosages of 2, 4, and 8 microgram/kg body weight. The vasodilator effect of adenosine and reactive hyperaemia after 10 and 25 heart beats were both significantly diminished by angiotensin II. By contrast, reactive hyperaemia after coronary artery occlusion lasting 5 heart beats remained unchanged. The present results obtained with angiotensin II further confirm that adenosine is only partially involved in mediating reactive hyperaemia and that this involvement takes place only after sufficiently long periods of coronary artery occlusion.
Adenosine↗
Dihydroergotoxine, an ergot alkaloid without marked hypotensive effect, improves blood flow and metabolism in the underperfused canine myocardium.
Regional myocardial blood flow was assessed in 6 anaesthetized dogs using radiolabelled microspheres. Lactate, H+, and O2 content were measured in arterial and local venous blood, obtained from the area supplied by the circumflex branch of the left coronary artery (LCX). Constriction of LCX by 67% led to considerable hemodynamic changes indicative of depressed global myocardial function. A significant release of lactate from the underperfused part of the left ventricle was recorded. Infusion of 0.7 micrograms/kg dihydroergotoxine over a period of 5 min induced a decrease in heart rate, left ventricular dp/dt max, and cardiac output, a sustained increase in total peripheral and femoral resistance and a transient increase in mean arterial blood pressure. Dihydroergotoxine markedly reduced lactate release and even, in some cases, induced lactate uptake and led to a significant increase in the endocardial blood flow both in the underperfused and normally perfused left ventricle. It is concluded that dihydroergotoxine, due to its ability to reduce myocardial oxygen demand and owing to its alpha-sympatholytic activity, which is not accompanied by any marked decrease in arterial blood pressure, causes improvement in blood flow in the underperfused myocardium and a marked amelioration of the impaired metabolic processes.
Animals↗
Effects of dihydroergotamine (DHE) on blood flow and metabolism in the underperfused myocardium in anaesthetized dogs.
The study was carried out in 13 mongrel dogs. Regional myocardial blood flow was measured using radiolabelled microspheres. Lactate, H+-ions, and O2 content were measured in arterial and local venous blood. Partial occlusion of the ramus circumflexus (LCX) led to a decrease in left ventricular dp/dt max, systemic arterial pressure, and a marked release of lactate from the underperfused myocardium. With DHE (2 micrograms/kg infused within 5 min, 8 dogs), a slight decrease in heart rate, left ventricular dp/dt max, LCX-resistance and a small increase in femoral and total peripheral resistance as well as in arterial and left and right atrial pressure was observed. In the normally perfused and in the underperfused part of the left ventricle microsphere assessed blood flow was unchanged or slightly elevated with DHE. Lactate release from the underperfused myocardium was markedly reduced. None of the DHE-induced effects on hemodynamic and metabolic parameters were observed in control experiments with infusion of 0.9% NaCl (5 ml). The results indicate that DHE leads to an amelioration of impaired metabolism in the underperfused myocardium and exerts no vasoconstriction in this area.
Animals↗
The influence of repeated administration of prazosin on its hypotensive effect and on renin release in conscious dogs. A comparison with urapidil.
The effects of prazosin (0.1, 0.5 and 2.5 mg/kg, orally) on blood pressure, heart rate and PRA were investigated after acute and chronic administration in conscious, normotensive dogs. The acute administration of prazosin caused a reduction in both systolic and diastolic blood pressure and an increase in heart rate and PRA. After chronic administration, twice daily for four days, tolerance developed, which was not due to persistent counterregulation. On comparison with urapidil, another alpha-adrenoceptor antagonist, the hypotensive and counterregulatory response to acute administration were similar with both substances; the development of tolerance to prazosin after chronic administration contrasted with the results with urapidil.
Antihypertensive Agents↗
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↗
The determination of the myocardial extracellular space in the cat in vivo: a comparative methodological study.
The myocardial extracellular space (ECS) was determined in cats in vivo by means of the ECS indicators, inulin and sulfanilic acid and, additionally, as glucose space. Experiments were carried out in cats subjected to bilateral kidney ligation (single injection) and in intact cats (single injection or infusion of indicator). The heart was clamped by instant deep-freezing in situ; this technique was compared, in renally-ligated cats, with excision and subsequent freezing of the heart in liquid nitrogen. The myocardial blood content was significantly decreased, and the myocardial lactate concentration significantly increased in excised, as compared with in situ-clamped hearts. Renally-ligated cats showed marked hypotension. The mean myocardial blood content was also significantly lower than in intact animals. A highly significant correlation was found between myocardial blood content and blood pressure for all experiments with instant deep-freezing. The mean inulin ECS value in renally-ligated cats was 22.7 +/- 1.5 ml. In accordance with the fact that the ECS is dependent on the tissure blood content, the corresponding values in intact animals were significantly higher, 25.9 +/- 2.5 ml (single injection) and 26.3 +/- 3.9 ml (infusion), calculated per 100 g tissue wet weight. Similar values were obtained for the glucose and sulfanilic acid ECS. If the interstitial space, an expression independent of the tissue blood content is used as space parameter, no significant differences were found under any of the present experimental conditions.
Animals↗
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↗
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↗
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↗
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↗
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↗
l-NG-nitro-arginine methyl ester in the anesthetized rabbit: venous vasomotion and plasma levels.
Explore the source record for details and available documents.
Animals↗
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↗
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↗
On the renal balances for different lipid fractions in dog.
(1) Six dogs were kept fasting for 12 h and the uptake or release of various lipid fractions by the kidney was determined. (2) Free and esterified fatty acids were generally taken up during the fasting state. More fatty acids were taken up than could be oxidized with respect to the normal oxygen consumption of the kidney. (3) When glucose was infused a release of fatty acids was observed in general. (4) The critical role of endogenous fatty acids for the energy metabolism of the kidney is pointed out.
Animals↗
NG-nitro-L-arginine pharmacokinetics in rats after a single intravascular and oral dose: an appearance of secondary concentration time peaks.
Explore the source record for details and available documents.
Administration, Oral↗
NG-nitro-L-arginine is not involved in enterohepatic cycling in rats.
Explore the source record for details and available documents.
Animals↗