PubMed Health⌕ Search

Biomedical subjects

J R Parratt

Publications and source records attributed to J R Parratt.

At least 199 records · Page 11Linked to original sources
PubMed1974

The effect of indomethacin on the cardiovascular and metabolic responses to E. coli endotoxin in the cat.

1 The response of pentobarbitone-anaesthetized cats to the intravenous administration of E. coli endotoxin (2 mg/kg) consisted of acute pulmonary vasoconstriction (3-5 min after the injection) and a secondary shock phase characterized by delayed systemic hypotension, decreased central venous pressure and cardiac output, and metabolic acidosis with arterial lactate levels three to four times normal. Only one of 25 animals survived 6 hours.2 Indomethacin (10 mg/kg), administered intravenously 30 min before the endotoxin, reduced both systemic arterial pressure and myocardial blood flow. It abolished the pulmonary vasoconstriction induced by endotoxin.3 Indomethacin modified some of the characteristic features of the delayed, endotoxin shock phase. Systemic hypotension was not observed and the blood pressure in the indomethacintreated cats 1, 2 and 4 h after endotoxin was 30 mmHg higher than in those cats administered endotoxin alone. The decrease in arterial pH was also significantly delayed. Six out of 15 animals survived 6 hours.4 It is suggested that indomethacin may abolish the initial pulmonary hypertension and oedema by antagonizing the release, or vasoconstrictor effect, of histamine and that part of its action during the shock phase is due to inhibition of prostaglandin release.

Acidosis↗
PubMed1974

The haemodynamic effects of prolonged oral administration of oxyfedrine, a partial agonist at beta-adrenoceptors: comparison with propranolol.

1 Haemodynamic changes have been studied in cats after the chronic oral administration of oxyfedrine (14 mg/kg for 3-4 weeks) or of placebo (lactose). The initial part of the study was carried out under double-blind conditions. The arterial blood pressure was between 19 mmHg (diastolic) and 27 mmHg (systolic) higher in the oxyfedrine treated animals, but there were no differences between the two groups with regard to cardiac output, left ventricular dP/dt max, heart rate or systolic ejection time.2 In cats similarly treated with propranolol (4 mg/kg) there was a slight (12%), but significant, reduction in cardiac output.3 Isoprenaline dose-response curves were shifted to the right in the cats administered oxyfedrine as well as in those administered propranolol. The degree of shift was five-fold (positive chronotropic response) and 20-fold (decrease in diastolic blood pressure) in the oxyfedrine group and 10- and 80-fold, respectively, in the propranolol group.4 In contrast to the partial blockade of the effects of isoprenaline, the haemodynamic response to oxyfedrine was largely unaltered, both in the cats pretreated with propranolol and in those pretreated with oxyfedrine. The pressor response to noradrenaline was potentiated in the cats pretreated with oxyfedrine.5 These results provide an explanation for the anti-anginal action of oxyfedrine. Some degree of beta-adrenoceptor blockade is achieved without a reduction in cardiac output or left ventricular dP/dt max. The relevance of these findings to the haemodynamic situation in angina is discussed.

Administration, Oral↗
PubMed1973

Myocardial and circulatory effects of E. coli endotoxin; modification of responses to catecholamines.

1. The predominant acute effect of E. coli endotoxin in anaesthetized, ventilated cats was pulmonary hypertension resulting from a 8-12 fold increase in pulmonary vascular resistance. This was followed by decreases in left ventricular (LV) and systemic arterial pressures and in LV dP/dt max. Recovery occurred within 2-4 min and was dependent upon increased sympathetic drive; recovery did not occur in cats treated with the beta-adrenoceptor blocking drug alprenolol.2. The pulmonary vasoconstriction was reduced in cats given compound 48/80 and evidence is presented that it results primarily from histamine release.3. Over the 2-3 h period following endotoxin injection, systemic arterial pressure tended to decrease and heart rate and myocardial metabolic heat production to increase. Myocardial blood flow and LV dP/dt remained fairly stable until the terminal stages of shock.4. The predominant delayed effect of E. coli endotoxin in cats were a markedly reduced stroke volume, an increase in peripheral vascular resistance and a severe metabolic acidosis (arterial base excess-20 mEq/litre). Arterial pO(2) and pCO(2) were not significantly affected. It is concluded that myocardial contractility is maintained at this time through the release of catecholamines and that endotoxin itself depresses contractility.5. The effects of adrenaline and noradrenaline infusions on systolic and diastolic blood pressures, heart rate, cardiac output, myocardial blood flow and LV dP/dt max were markedly reduced in the period 2-3 h after endotoxin. In a few animals some recovery of the response to noradrenaline occurred and was associated with a general circulatory improvement and a reduced metabolic acidosis.

Anaerobiosis↗
PubMed1973

Effects of oxyfedrine on isolated portal vein and other smooth muscles.

1. Oxyfedrine (0.01-1.0 mug/ml), inhibited spontaneous myogenic activity in rat isolated portal vein and carbachol-induced contractions of rat isolated uterus, and relaxed the rabbit duodenum and the guinea-pig tracheal chain preparation. These actions were prevented by the beta-adrenoceptor blocking drug alprenolol. Oxyfedrine was a relatively weak beta-adrenoceptor stimulant (10-100 times less active than isoprenaline) but its actions were more prolonged.2. In the same concentrations, oxyfedrine reduced or prevented the inhibition of myogenic activity of the rat portal vein induced by isoprenaline and by repeated doses of oxyfedrine itself, acting as a partial agonist at beta-adrenoceptor sites.3. Oxyfedrine, 1-12 mug/ml increased myogenic activity in the rat portal vein. This effect was not due to direct or indirect stimulation of alpha-adrenoceptors (because it was unaffected by phentolamine) or to potentiation of acetylcholine or 5-hydroxytryptamine.4. Oxyfedrine (>20 mug/ml) inhibited spontaneous myogenic activity in the portal vein and relaxed the saphenous vein contracted with noradrenaline. This spasmolytic effect of the drug was not due to beta-adrenoceptor stimulation or to inhibition of phosphodiesterase since it was unaffected by alprenolol and by concentrations of imidazole which antagonized the effects of the active phosphodiesterase inhibitor, papaverine. In the portal vein this effect of oxyfedrine was similar to that of the calcium inhibitor iproveratril; some of the effects of oxyfedrine on venous smooth muscle may be mediated through effects on calcium transport.

Adrenergic beta-Agonists↗
PubMed1973

The effects of dipyridamole on blood flow and oxygen handling in the acutely ischaemic and normal canine myocardium.

1. The effects of the intravenous administration of dipyridamole (0.25 mg/kg) were examined in a canine preparation that enabled simultaneous measurements to be made of blood flow in ischaemic and in essentially normal areas of the myocardium and also of oxygen handling (availability, consumption and extraction) in both these regions.2. When administered to dogs anaesthetized with trichlorethylene 2-3 h after acute ligation of the descending branch of the left coronary artery, dipyridamole markedly increased blood flow in essentially normal regions (left circumflex flow) but failed to increase flow in the area supplied by the ligated vessel (measured by (133)xenon clearance and by retrograde flow). In five of the six animals definite decreases in flow (; stealing ') were observed in the ischaemic region. These flow changes were related to the decreased trans-ventricular perfusion pressure (diastolic peripheral coronary pressure minus left ventricular end-diastolic pressure) and were accompanied by electrocardiographic evidence of increasingly severe myocardial ischaemia. The results support the suggestion that only increasing the perfusion gradient will usefully improve blood flow (and hence oxygen availability) to the acutely ischaemic myocardium.3. Despite these effects on ischaemic muscle blood flow, the oxygen tension of the blood draining the infarcting muscle was markedly elevated. The conclusion is drawn that dipyridamole decreases the efficiency of the myocardial circulation by opening up vessels that do not take part in tissue exchange.

Acute Disease↗
PubMed1972

The effects of dipyridamole on the myocardial vasodilator actions of noradrenaline, isoprenaline and adenosine.

1. In anaesthetized cats, intravenous adenosine infusions decreased resistance to blood flow in the myocardial vascular bed. This effect of adenosine was augmented during the 60 min following the intravenous injection of dipyridamole (1 mg/kg).2. In different experiments, intravenous infusions of noradrenaline caused either a slight increase or a slight decrease in myocardial vascular resistance. The dilator component of the action of noradrenaline was not augmented by dipyridamole.3. Isoprenaline infusions decreased the resistance of the myocardial bed. This effect was unaltered after dipyridamole.4. These results do not support the hypothesis that part of the effect of catecholamines on myocardial vascular resistance involves the release of adenosine from hypoxic myocardial cells.

Adenosine↗
PubMed1972

The effects of dipyridamole on coronary post-occlusion hyperaemia and on myocardial vasodilatation induced by systemic hypoxia.

1. The arterial pO(2) of anaesthetized cats was reduced to 33 mmHg by supplying a mixture of oxygen and nitrogen as the respiratory gas. This produced vasodilatation in the myocardial bed which was not increased after the injection of dipyridamole (1 mg/kg).2. Reactive hyperaemia was observed following occlusion of the left anterior descending coronary artery for 10-120 seconds. The duration of the period of reactive hyperaemia was increased after the injection of dipyridamole. This effect of dipyridamole was most pronounced when the longest periods of occlusion were used.3. These results support the hypothesis that myocardial reactive hyperaemia is at least partly caused by adenosine released from hypoxic myocardial cells. The vasodilatation occurring during systemic hypoxia, on the other hand, is probably mediated via a different mechanism.

Animals↗