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Biomedical subjects

G Raberger

Publications and source records attributed to G Raberger.

At least 73 records · Page 4Linked to original sources
PubMed1984

Evidence against the adenosine-catecholamine antagonism under in vivo conditions.

Experiments were carried out in anaesthetized, thoracotomized dogs. The dose dependent positive inotropic and chronotropic effects of intracoronary (i.cor.) infusions or bolus injections of isoproterenol (ISO) were neither antagonized by adenosine (0.46, 1.0, and 2.91 x 10(-5) mol/l) nor by the adenosine analogue N6-phenylisopropyl-adenosine (PIA, 3.23 x 10(-7) mol/l). The results indicate, that adenosine and PIA do not have any antagonistic effects on isoproterenol induced positive inotropy and chronotropy in the intact dog heart. Consequently it can be assumed that an adenosine-catecholamine antagonism is of no physiological relevance.

Adenosine↗
PubMed1984

Effects of indomethacin on changes in renal blood flow induced by adenosine and its analogues in conscious dogs.

The effects of indomethacin on changes in renal blood flow induced by adenosine, NECA (adenosine-5'-N-ethyl-carboxamide) and 2',3'-dinitro-NECA were investigated in 6 chronically instrumented conscious dogs. Adenosine (187.5, 375 and 750 nmol/kg, i.v.) induced a dose-dependent initial decrease, followed by a reactive increase in renal blood flow. NECA (1.5 nmol/kg, i.v.) also induced an initial decrease, which was, however, followed by a prolonged reactive increase in renal blood flow. 2',3'-dinitro-NECA (50 nmol/kg, orally) induced only an increase in renal blood flow. Indomethacin (27.9 mumol/kg, i.v.) caused no relevant change of the initial decrease and a significant attenuation of the reactive increase in renal blood flow induced by adenosine. NECA-induced changes in blood flow were affected by indomethacin in the same direction but to a greater extent than were adenosine-induced changes in blood flow. Indomethacin reversed the increase to a decrease in renal blood flow induced by 2',3'-dinitro-NECA. Thus, prostaglandins seem to be involved in mediating the response of renal blood flow to adenosine, NECA and 2',3'-dinitro-NECA.

Adenosine↗
PubMed1984

A canine model of transient myocardial dysfunction regional shortening in the presence of critical stenosis and cardiac stimulation.

An experimental model of exercise-induced angina pectoris was developed in anesthetized dogs. Two i.v. bolus injections of isoproterenol (ISO, 0.25 microgram/kg; time interval: 10 min) were administered, followed by constriction of the circumflex coronary artery (LCX; critical stenosis). Further i.v. bolus injections of ISO were administered before and after i.v. infusion of 0.9% NaCl (control infusion). Stenosis of the LCX did not modify regional function at rest as assessed with ultrasonic crystals implanted subendocardially both in the distribution areas of the circumflex coronary artery and of the left anterior descending coronary artery (LAD). In the presence of critical stenosis, ISO induced a reproducible, transient decrease in systolic shortening and percent systolic shortening in the area supplied by the LCX and a marked increase in systolic shortening and percent systolic shortening in the area supplied by the LAD. During a 60-min observation period following control infusion, no further substantial changes in regional dimensions were observed. The ISO-induced hemodynamic changes were reproducible during this period. The experimental model of exercise-induced angina pectoris presented in this study can be assumed to provide a reliable basis for evaluating the efficacy of various therapeutical interventions.

Anesthesia↗
PubMed1984

Blood pressure response and renin release following 4 days of treatment with dihydralazine and urapidil in conscious dogs.

The magnitude and the persistence of blood pressure reduction by dihydralazine and urapidil were investigated following treatment over a period of 4 days. The experiments were performed on six normotensive dogs, trained to submit to puncture of the femoral artery and to stand quietly in a special frame. The first-dose effects of orally administered dihydralazine (1.42, 7.1 mg X kg-1) and urapidil (2.0, 10.0 mg X kg-1) on heart rate, arterial blood pressure and plasma renin activity (PRA) were compared with the effects of the substances after 4 days of treatment. Both compounds caused a dose-dependent decrease in blood pressure but in contrast to urapidil the effect of dihydralazine was accompanied by large increases in heart rate and PRA. Dose-dependent tolerance to dihydralazine but not to urapidil was observed after treatment over only 4 days. However, basal blood pressure was significantly lowered after 4 days of treatment with urapidil at the high dosage and no further reduction was achieved on the fifth day. The importance of persistent counterregulation in the development of tolerance to the antihypertensive effect of dihydralazine is discussed.

Animals↗
PubMed1983

Acute effects of alinidine on heart rate and blood pressure in healthy subjects and patients with hyperkinetic heart syndrome.

The effects of a single dose of alinidine (0.5 mg/kg i.v.), the N-allyl-derivative of clonidine, on heart rate and blood pressure were investigated in healthy volunteers and in patients with hyperkinetic heart syndrome, at rest and during bicycle exercise. In healthy volunteers plasma catecholamine levels were also determined. Alinidine did not change heart rate at rest in the healthy volunteers but it did significantly reduce exercise-induced tachycardia, whereas blood pressure and plasma catecholamine levels were not significantly affected by alinidine, either at rest or during exercise. In patients with hyperkinetic heart syndrome, alinidine reduced heart rate at rest and during exercise to a similar extent as propranolol (0.1 mg/kg i.v.). The blood pressure did not change with alinidine but it was significantly reduced by propranolol. The observation that an alinidine-induced reduction of heart rate occurs without a concomitant fall in blood pressure, and without a clonidine-like symphatho-inhibitory action, is in line with experimental findings suggesting a specific bradycardic action of alinidine under short-term conditions.

Blood Pressure↗
PubMed1983

Plasma insulin levels and beta-adrenoceptor antagonists. Relevance of the steric configuration of beta-adrenoceptor antagonists to their effect on glucose tolerance.

The relevance of the steric configuration to the effects of two non-selective beta-adrenoceptor antagonists without intrinsic sympathomimetic activity (+)- and (--)-bupranolol (10 and 50 micrograms/kg i.v.) and (4)- and (--)-propranolol (100 and 500 micrograms/kg i.v.) on the i.v. glucose tolerance test (IVGTT) were investigated in conscious, normoglycemic dogs. The effects of the beta-adrenoceptor antagonists on plasma glucose, and insulin levels and insulin-glucagon ratio following IVGTT were evaluated by calculating the respective areas under the curve (AUC). The AUC values for plasma glucose were significantly increased by the (--)-configuration of both beta-adrenoceptor increased by the (--)-configuration of both beta-adrenoceptor antagonists. In the (+)-configuration only propranolol (500 micrograms/kg i.v.) increased the AUC value for plasma glucose significantly. The AUC values for plasma insulin and also for the plasma insulin-glucagon ratio were significantly increased by (--)-propranolol (500 micrograms/kg i.v.) and by (--)-bupranolol (10 and 50 micrograms/kg i.v.). Thus the impairment of glucose tolerance, due to suppression of the plasma insulin level, depends mainly on the beta-adrenoceptor antagonistic activity of the (--)-configuration.

Adrenergic beta-Antagonists↗
PubMed1983

[Effects of morphine on the control of the cardiovascular system by the carotid-sinus-reflex and by the carotid chemoreflex].

The effects of morphine (2 mg/kg i.v.) on the carotid baroreceptor control and the carotid chemoreceptor control of the circulation were examined in 12 chronically instrumented dogs. Bilateral carotid occlusion in conscious dogs with spontaneous ventilation increased heart rate (decrease in cardiac cycle length by 19 +/- 2%; mean +/- S.E.M.), mean arterial pressure (38 +/- 3%) and mean iliac resistance (33 +/- 11%). Morphine, however, failed to change these reactions significantly. Chemoreceptor stimulation, accomplished by intracarotid injections of nicotine (4-8 micrograms), in conscious dogs with spontaneous ventilation elicited complex effects on heart rate and mean iliac resistance--due to secondary stimulation of pulmonary inflation reflexes. Chemoreceptor stimulation in conscious dogs with ventilation controlled increased cardiac cycle length (246 +/- 17%) and elicited intense iliac vasoconstriction, i.e. mean iliac resistance rose by 288 +/- 25%. Morphine significantly (p less than 0.01) attenuated the increase in cardiac cycle length and in iliac resistance with chemoreceptor stimulation (42 +/- 10% and 64 +/- 9%, respectively). Thus, morphine interferes with the carotid chemoreceptor control of the circulation while the efficacy of the carotid-sinus-reflex seems to be well maintained.

Animals↗
PubMed1983

Chemical, pharmacological and oncostatic properties of 5-(4'-hydroxybenzylidenoimino)-4, 6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole (compound IP-10).

Advanced preclinical studies on IP-10 preparation (4,6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole) were carried out. The drug was shown to be devoid of the irritating local effect, mildly toxic and hardly absorbing when administered per os. The toxic effect showed tendency toward cumulation. In the long-term exposure it did not affect either the elements of peripheral blood or parenchymatous organs. It exerted slight hypotensive effect on the circulatory system but only after intravenous administration. In relation to the smooth muscle organs and central nervous system, IP-10 was only slightly active. Weak effect of the compound was observed with bacteria and fungi. In the case of transplantable tumors, its activity was differentiated. It exerted a significant effect in relation to leukemia, melanoma B-16, Ehrlich carcinoma and Nemeth-Kellner lymphoma. As other isothiasole derivatives, IP-10 exhibits an interesting pharmacological, easy to render activity; particular attention should be paid to its oncostatis activity.

Animals↗
PubMed1982

[Cardiac and peripheral vascular effects of the volatile inhalational anaesthetic enflurane in chronically instrumented dogs (author's transl)].

While enflurane is generally held to induce arterial hypotension, its overall effects on left ventricular (LV) performance are less clear. Accordingly, mongrel dogs were chronically instrumented with miniature LV pressure transducers, with aortic and left atrial catheters and with electromagnetic flow probes and hydraulic cuff occluders on a common iliac artery. A pair of ultrasonic transducers was implanted on opposing endocardial surfaces to measure LV internal minor axis diameter. Experiments were performed 2 to 9 weeks after surgery when the animals were resting quietly without premedication. Enflurane (2 and 4 vol.-%) decreased mean arterial pressure by 27% and 36% and led to a progressive, dose-dependent decrease in myocardial contractility and induced striking peripheral vasodilatation, i.e. LV-dP/dtmax was reduced by 32% and 54% and iliac conductance rose by 101% and 163%. However, the decrease in contractility was not associated with an increase in LV preload, i.e. LV-end-diastolic diameter was decreased by 2 vol.-%, while it was not significantly different from control values with 4 vol.-%. Thus, in intact chronically instrumented dogs the direct negative inotropic effect of enflurane is modified by a synchronous decrease in myocardial loading conditions.

Aerosols↗
PubMed1982

Plasma insulin levels and beta-adrenoceptor antagonists. The effects of cardioselective and non-cardioselective beta-adrenoceptor antagonists with and without intrinsic sympathomimetic activity on basal insulin level and insulin level after glucose stimulation in normoglycemic dogs.

The effect of beta-adrenoceptor antagonists on the intravenous glucose tolerance test was investigated in conscious dogs. dl-Celiprolol (cardioselective with ISA = intrinsic sympathomimetic activity) 200 and 1000 microgram/kg i.v., dl-metoprolol (cardio-selective without ISA) 200 and 1000 microgram/kg i.v., dl-pindolol (non-selective with ISA) 5 and 25 microgram i.v. and l-bupranolol (non-selective without ISA) 10 and 50 microgram/kg i.v. were used in the study. The influence of beta-adrenoceptor antagonists on the plasma glucose and immunoreactive insulin following intravenous glucose tolerance test were evaluated by calculating the respective areas under the plasma curve. The present investigation clearly demonstrates the marked difference between the various beta-adrenoceptor antagonists on heart rate and, especially on metabolic parameters. dl-Metoprolol, a beta-adrenoceptor antagonist with cardioselectivity and without ISA can be assumed not to alter plasma insulin level and glucose assimilation. l-Bupranolol, a non-selective beta-adrenoceptor antagonist without ISA reduces plasma insulin level and probably enhances peripheral glucose uptake, resulting in an "unchanged" glucose tolerance. dl-Celiprolol or dl-pindolol, beta-adrenoceptor antagonists with ISA, but cardioselective or non-selective enhance both, basal insulin level and insulin level after glucose stimulation but must be assumed to decrease peripheral glucose uptake since here too glucose tolerance was unchanged.

Adrenergic beta-Antagonists↗
PubMed1982

The effects of NECA (adenosine-5'N-ethylcarboxamide) and of adenosine on glucagon and insulin release from the in situ isolated blood-perfused pancreas in anesthetized dogs.

The effect of adenosine-5'-N-ethylcarboxamide, (NECA), a long-lasting adenosine derivative with pronounced vasoactivity was investigated on glucagon and insulin release from the in situ isolated blood perfused pancreas in the anesthetized dog: NECA (10(-9) to 10(-5) mol/l) led to a dose-dependent glucagon release. Insulin release was inhibited by NECA at low concentrations, but significantly increased at higher concentrations of the adenosine analogue. Similar effects were observed with infusion of adenosine at 10(-7) and 10(-6) mol/l. Aminophylline (10(-4) mol/l) produced a 10-fold attenuation of the actions of NECA. The preponderance of glucagon release at low concentrations of NECA and adenosine in contrast to that of insulin release at high concentrations may represent a local pancreatic regulatory mechanism of adenosine in glucose homeostasis.

Adenosine↗
PubMed1982

Inhibition of the carotid chemoreceptor reflex by enflurane in chronically instrumented dogs.

The effect of the volatile inhalational anaesthetic enflurane (2 vol% and 4 vol%) on the cardiovascular response to carotid chemoreceptor stimulation (CCRS) was studied in 8 chronically instrumented dogs. Intracarotid injections of nicotine were used to evoke CCRS. Ventilation was held constant during the unanaesthetized state as well as the anaesthetized state. In the unanaesthetized state CCRS evoked an increase in iliac vascular resistance, and an increase in cardiac cycle length. Enflurane 2 vol% significantly attenuated the increases both in iliac vascular resistance as well as in cardiac cycle length. Enflurane 4 vol% abolished the response to CCRS.

Animals↗
PubMed1981

Plasma catecholamines, plasma renin activity and haemodynamics during sodium nitroprusside-induced hypotension and additional beta-blockage with bunitrolol.

The effects of beta-blockade on certain physiological and haemodynamic responses to sodium nitroprusside-induced hypotension have been studied in 5 patients, aged 18--54 years, undergoing inner ear surgery. Samples of blood were collected under premedication, following induction of anaesthesia, during neuroleptanalgesia, during a sodium nitroprusside infusion adjusted to produce a 40% fall in blood pressure, during superimposed beta-blockage with bunitrolol and under stable haemodynamic conditions after discontinuation of sodium nitroprusside. The sodium nitroprusside-induced reduction in blood pressure led to a massive increase in plasma noradrenaline and adrenaline and in plasma renin activity. beta-blockade with bunitrolol did not affect the increased catecholamine concentrations, the increase in plasma renin activity was significantly reduced, the increase in heart rate was reversed, and total peripheral resistance and diastolic blood pressure were further reduced. These changes can be attributed to the intrinsic beta-synmpathomimetic activity of bunitrolol in addition to its beta-blocking effect. Since no adverse effect was observed in this study, combined therapy with sodium nitroprusside and beta-receptor blockade should be employed if the effects of increased sympathetic tone are considered to be undesirable.

Adolescent↗
PubMed1981

Cardiovascular effects of dihydroergotamine during epidural anaesthesia in dogs.

The haemodynamic changes during epidural anaesthesia and following the administration of dihydroergotamine (DHE; 10 micrograms/kg i.v.) were studied in 7 dogs (epidural group). Epidural anaesthesia was associated with reductions in mean arterial, mean pulmonary arterial and mean right atrial pressures. Femoral flow was increased by 119.9 +/- 35.0% and femoral resistance fell by 62.7 +/- 7.2%. All these changes were abolished by additional administration of DHE during epidural anaesthesia. In a second group of dogs (control group, n = 8) with intact innervation, i.e. without epidural block, DHE (10 micrograms/kg iv.) also decreased femoral flow and increased femoral resistance which, however, was significantly less pronounced ( p less than 0.01). It is concluded that DHE in epidural anaesthesia constricts arteriolar resistance vessels, mainly within the blocked areas.

Anesthesia, Epidural↗
PubMed1980

The effects of adenosine-5'-ethylcarboxamide on liver blood flow and hepatic glucose, lactate and pyruvate balances in dogs.

The actions of adenosine-5'-ethylcarboxamide (744-96), a long-acting adenosine analogue, on liver, portal and intestinal balances of glucose, lactate and pyruvate and on hepatic and portal blood flow were investigated in 6 chloralose-anaesthetized mongrel dogs. 744-96 led to an increase in portal and hepatic blood flow. Glucose release by the liver and glucose uptake by the non-hepatic splanchnic area (portal balance) were markedly increased by 744-96. Hepatic lactate and pyruvate balances were reversed from uptake to release by the adenosine analogue. The changes in glucose balances compare closely to the actions of glucagon, which is known to be released by 744-96. Apart from these possible glucagon-mediated actions, a direct action of the adenosine analogue must be assume from the changes in lactate metabolism. The results of this study are indicative of a substrate-mobilising action of adenosine in addition to its well-known vasodilatory action.

Adenosine↗
PubMed1980

Plasma concentrations of noradrenaline and adrenaline and plasma renin activity during extradural blockade in dogs.

Anaesthetized dogs (pentobarbitone 25 mg kg-1 + 3 mg kg-1 h-1) with a Teflon catheter inserted to the femoral artery for pressure and heart rate measurement and blood sampling were studied. Extradural puncture was carried out at L7--S1 under x-ray control and 2% lignocaine (1 ml min-1) infused for approximately 10 min. During extradural block a decrease in arterial pressure was accompanied by a simultaneous decrease in plasma noradrenaline concentration (NA) and a compensatory increase in plasma renin activity (PRA), which became significant 15 min after commencing the block when the arterial pressure was at the minimum. Dihydroergotamine (DHE) led to a rapid reversal of the hypotension with no change in heart rate and a decrease in PRA. Hypovolaemia (blood loss 5 ml kg-1) was induced before and during block, respectively, in two further experimental groups. Increased NA and PRA were found under hypovolaemia without extradural block, but only PRA increased with hypovolaemia and a block. The effects of DHE in the later studies were comparable to those observed in the initial study.

Anesthesia, Epidural↗
PubMed1980

[Effects of a long-acting adenosine analogue on insulin and glucagon release (author's transl)].

The adenosine analogue 765-21 (10 micrograms/kg intravenously), substituted at the 5'-position, caused a sustained increase in plasma glucose and a decrease in plasma free fatty acid concentrations in conscious dogs. Concomitantly, plasma glucagon levels rose threefold. Changes in plasma insulin concentration were relatively small and of no statistical significance. A simultaneous fall in arterial blood pressure was also observed. Aminophylline, an adenosine antagonist, inhibited the haemodynamic as well as the metabolic responses evoked by the adenosine analogue. - In collagenase-isolated rat islets of Langerhans 765-21 inhibited glucose-induced insulin release in a dose-dependent manner (concentration range 10(-8) to 10(-5) M). In contrast to the data obtained on conscious dogs, 765-21 did not promote glucagon release from the pancreatic islets. Since stimulation of glucagon secretion was also not observed on decreasing the glucagon concentration in the incubation medium, the collagenase technique of isolation may be responsible for the insensitivity of the islets to glucagon-releasing stimuli. - The results are indicative of a specific inhibition of glucose-induced insulin release by 765-21. The data obtained in vivo additionally suggest a glucagon-releasing activity of the adenosine analogue investigated.

Adenosine↗