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Biomedical subjects

J R Parratt

Publications and source records attributed to J R Parratt.

At least 145 records · Page 8Linked to original sources
PubMed1983

Antiarrhythmic actions of meptazinol, a partial agonist at opiate receptors, in acute myocardial ischaemia.

1 The intravenous administration, to anaesthetized rats, of meptazinol (1 and 2 mg kg-1), a partial agonist at opiate receptors, greatly reduced the incidence of ventricular extrasystoles that resulted from acute coronary artery occlusion. The incidence of ventricular fibrillation (VF) was reduced from 50% (in the controls) to 10% and the mortality from 30% to zero. 2 In similar doses, pretreatment with meptazinol also reduced ventricular arrhythmias, including fibrillation, in conscious rats subjected to coronary artery occlusion. In this model, survival at 16 h was increased from 27% in the controls to 50% and 83% respectively in rats pretreated with 1 and 2 mg kg-1 of the drug. 3 In antiarrhythmic doses, meptazinol had little effect on either heart rate or systemic arterial blood pressure. 4 Intracellular action potential recordings from papillary muscle removed from rats given meptazinol (2 mg kg-1) 15 min previously showed an increase in APD50 and APD90 of more than 40%. There was no effect on dV/dtmax. When superfused with meptazinol in vitro normal rat papillary muscle stimulated at 1 or 3 Hz showed an increase in APD90 and a decrease in dV/dtmax. 5 The antiarrhythmic effect of meptazinol in these models can probably be explained by direct actions on the cardiac muscle action potential (increase in APD) although effects on opiate receptors cannot be ruled out. It is suggested that meptazinol might be useful in relieving pain, and in reducing the severity of arrhythmias in the early stages of acute myocardial infarction.

Action Potentials↗
PubMed1983

The release of prostanoids during the acute pulmonary response to E. coli endotoxin in anaesthetized cats.

1 The administration of E. coli endotoxin (2 mg/kg i.v.) to anaesthetized cats results in a characteristic acute pulmonary response. This consists of increases in pulmonary artery pressure and airways resistance and a reduction in lung compliance. 2 Plasma concentrations of prostaglandin E2 (PGE2), PGF2 alpha, thromboxane B2 and 6-keto PGF1 alpha were measured by radioimmunoassay in aortic and pulmonary arterial blood samples before, during and after the acute pulmonary response to endotoxin. 3 Endotoxin administration resulted in the rapid release of PGF2 alpha and thromboxane B2 from the lungs. The time course of this release was parallel to that of the pulmonary hypertensive and airways responses to endotoxin. PGE2 and 6-keto PGF1 alpha were released more gradually and with greater variations between individual animals. 4 During the delayed shock phase (2 h after endotoxin) the concentrations of PGE2, PGF2 alpha and 6-keto PGF1 alpha were once again elevated in both the aorta and pulmonary artery. Thromboxane B2 concentrations were not increased at this time. 5 These results suggest that PGF2 alpha and thromboxane A2 may be mediators of the acute pulmonary responses to endotoxin.

Anesthesia↗
PubMed1983

The effect of a selective 5-HT2 antagonist, ketanserin, on the pulmonary responses to Escherichia coli endotoxin.

5-Hydroxytryptamine (5-HT, 5-160 microgram kg-1) injected intravenously in pentobarbitone-anaesthetized, open-chest cats caused dose-dependent increases in pulmonary arterial and intratracheal pressures. There was also a marked systemic hypotension and bradycardia. The pulmonary effects were completely prevented by ketanserin (0.2 mg kg-1), a selective 5-HT2 blocking drug. Ketanserin (0.2 mg kg-1) itself lowered arterial pressure (by 30-40 mmHg) but this systemic hypotension was relatively transient. Endotoxin (E. coli) administration resulted in pulmonary hypertension, increases in intratracheal pressure and airways resistance and reductions in lung compliance and in arterial PO2. Only the airways resistance response was modified by ketanserin (0.2 mg kg-1), suggesting a relatively unimportant role for 5-HT in mediating the acute, pulmonary effects of endotoxin in this species. The reductions in arterial (mixed venous) pH and in PO2 that resulted from endotoxin administration were not affected by pretreatment with ketanserin.

Animals↗
PubMed1983

The effect of beta-adrenoceptor blocking agents, with differing ancillary properties, on the arrhythmias resulting from acute coronary artery ligation in anaesthetized rats.

The effects of several beta-adrenoceptor blocking agents, [+), (-) and (+/-)-oxprenolol, p-oxprenolol, practolol, propranolol and timolol) were investigated on the ventricular arrhythmias occurring within the first 30 min of acutely ligating the main left coronary artery in anaesthetized rats. The degree of cardiac and vascular beta-adrenoceptor blockade was also assessed. All the compounds exhibited antiarrhythmic activity under these conditions. The degree of cardiac beta-adrenoceptor blockade required for this protection was less for the cardioselective agents, p-oxprenolol and practolol, than for the non-selective beta-adrenoceptor blocking agents. A comparison of the two isomers of oxprenolol demonstrated that the (-)-isomer markedly suppressed ischaemic arrhythmias (ventricular ectopic beats, incidence and duration of ventricular tachycardia and duration of ventricular fibrillation) more effectively than the (+)-isomer. Compounds possessing intrinsic sympathomimetic activity (ISA) caused less marked haemodynamic changes (in equivalent beta-blocking doses) than those that did not possess this ancillary property. The membrane stabilizing activity of oxprenolol and p-oxprenolol did not appear to contribute to the antiarrhythmic activity of these agents; however, the membrane stabilizing activity of propranolol may contribute to its effectiveness. In all the drugs studied, the main pharmacological property required to suppress early postischaemic arrhythmias is blockade of cardiac beta-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1983

The effect of exaprolol (MG 8823) on epicardial ST-segment changes in a feline model of acute myocardial ischaemia.

A model is described (anaesthetized, open-chest cats subjected to acute coronary artery occlusion) which allows the effects of drug interventions to be determined on one major electrocardiographic index of myocardial ischaemia. Epicardial ST-segment changes were continuously recorded from five individual sites on the surface of the left ventricle. Coronary artery occlusion (left anterior descending branch) resulted in marked and consistent elevations of the ST-segment in all sites in nearly all experiments. These changes started within 1 min of the onset of ischaemia and reached a peak at between 30 and 60 min; thereafter there was a gradual reduction over the next 4 h. The one significant haemodynamic effect of coronary artery occlusion was an increase in left ventricular (LV) end-diastolic pressure (LVEDP). Ventricular ectopic activity was not pronounced in this model (about 50 ectopic beats over the initial 30 min post-occlusion period). Exaprolol (1.0 mg kg-1, intravenously) a potent beta-adrenoceptor blocking agent with 'membrane stabilising activity', when given 1 h after the onset of ischaemia, reduced heart rate and LV dP/dtmax and increased LVEDP. These effects were prolonged (i.e. little recovery in heart rate 3 h after administration). Exaprolol decreased total ST-segment elevation immediately after administration; this was significantly different from the effect of intravenous saline and lasted for at least 3 h. The effects appeared to be greater at sites of less pronounced ischaemia. Intramyocardial temperature records were taken to indicate a reduction in blood flow to the ischaemic region; however the alleviation of epicardial ST-segment elevation suggests an improved myocardial oxygen demand:supply ratio. Reperfusion was unsuccessfully attempted after a 4 h occlusion period; reperfusion after a shorter period (30 min) resulted in ventricular ectopic activity but no fibrillation.

Animals↗
PubMed1982

Lidoflazine in the early stages of acute myocardial ischaemia.

1 Pretreatment of anaesthetized rats with intravenously administered lidoflazine (an antianginal agent) reduced the incidence and severity of ventricular arrhythmias which resulted from acute coronary artery ligation. Ventricular fibrillation was completely prevented by doses of 50 micrograms/kg and 2 mg/kg and no animal so treated died ( contrast 50% incidence of fibrillation in the controls and 30% mortality). 2 In anaesthetized greyhound dogs, lidoflazine (2 mg/kg) administration resulted in transient reductions in systemic arterial pressure, LV dP/dt max and cardiac output. Coronary sinus Po2 was markedly increased, indicating pronounced coronary vasodilatation. 3 Lidoflazine pretreatment inhibited the increase in epicardial ST-segment elevation which resulted, in dogs, from short (3 min) occlusions of the left anterior descending coronary artery. This effect was especially marked at sites where, in control occlusions, ST-segment elevation was most pronounced. 4 Lidoflazine greatly reduced the number of ventricular ectopic beats which usually resulted from more prolonged (30 min) periods of acute coronary artery occlusion. There was no ventricular fibrillation in these dogs (contrast 25% incidence in the controls). 5 Lidoflazine did not modify the ventricular fibrillation which results from reperfusion of a previously ischaemic area of the left ventricular wall.

Anesthesia↗
PubMed1982

Naloxone inhibits early arrhythmias resulting from acute coronary ligation.

The intravenous administration of naloxone 15 min before acute coronary artery ligation in both anesthetized and conscious male rats markedly reduced the incidence and severity of the ventricular arrhythmias that occur within 30 min of the onset of myocardial ischaemia. The incidence of ventricular fibrillation was especially reduced and, in conscious rats, the survival 16 h after ligation was increased from 27% (in the controls) to 58 and 73% after 2 and 4 mg/kg naloxone respectively. One possible explanation of these results implies a detrimental effect of released endorphin in the early stages of myocardial ischaemia.

Anesthesia↗
PubMed1981

Calcium antagonists prevent early post-infarction ventricular fibrillation.

The intravenous administration of either nifedipine (in doses of 5-50 microgram/kg), or nisoldipine (5-1000 microgram/kg) markedly reduced, or abolished, the serious ventricular arrhythmias (tachycardia and fibrillation) that result from acute coronary artery artery ligation in pentobarbitone-anaesthetized rats. Ventricular ectopic activity, which is pronounced in the first 30 min post-ligation period in this model, was also significantly decreased by nifedipine and niludipine (10 and 50 microgram/kg) and by the highest dose (1 mg/kg) of nisoldipine. These results demonstrate the marked efficacy of these calcium antagonists in this experimental model and raise the possibility that, if given prophylactically, they might reduce the incidence of sudden cardiac death following re-infarction in patients.

Animals↗
PubMed1981

Aspirin inhibits the early myocardial release of thromboxane B2 and ventricular ectopic activity following acute coronary artery occlusion in dogs.

Acute coronary artery occlusion in anaesthetized open-chest greyhounds led to early release of thromboxane B2 (TxB2) into venous blood draining the ischaemic region. No release occurred from the remainder of the left ventricular wall (coronary sinus sampling). TxB2 release and ventricular ectopic activity were positively correlated (r = 0.863) 2 min post-occlusion. Aspirin (3 mg/kg i.v.) suppressed both local TxB2 release and ectopic activity and prevented ventricular fibrillation. It is suggested that TxB2 release is a factor contributing to early post-infarction arrhythmias.

Animals↗
PubMed1981

Suppression by orally-administered nifedipine, nisoldipine and niludipine of early, life-threatening ventricular arrhythmias resulting from acute myocardial ischaemia.

The oral administration to rats of the calcium antagonists nifedipine, nisoldipine and niludipine (3 mg/kg, 1-1.25 h before acute coronary ligation) greatly reduced the duration of ventricular tachycardia and fibrillation (VF) occurring in the first 30 min post-ligation period. The duration of VF was especially reduced (by 74-92%). None of the animals so treated died compared with a 40% mortality in the controls.

Animals↗
PubMed1981

The effects of prostaglandins E2, F2 alpha, prostacyclin, flurbiprofen and aspirin on arrhythmias resulting from coronary artery ligation in anaesthetized rats.

1 Various prostaglandins and inhibitors of prostaglandin synthesis were administered prior to acute coronary artery ligation in anaesthetized rats and their effects were assessed on the number and severity of the resulting early arrhythmias (ventricular ectopic activity; incidence and duration of ventricular tachycardia and of ventricular fibrillation). 2 Prostaglandin E2 (PGE2), PGF2 alpha and prostacyclin all showed antiarrhythmic activity; in contrast flurbiprofen increased the incidence of ventricular fibrillation and mortality. 3 Both the number of ventricular ectopic beats and the incidence of ventricular fibrillation were reduced by aspirin. 4 The results suggest that the release of endogenous PGE2, PGF2 alpha and prostacyclin could reduce early post-infarction ventricular arrhythmias whilst the protective effect of aspirin in this model adds further support for the hypothesis that thromboxane release is involved in the genesis of these arrhythmias.

Animals↗
PubMed1981

Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin.

1 The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1 h onwards) there was a progressive decrease in cardiac output, a reduced right atrial filling pressure, systemic hypotension and a profound metabolic acidosis (lactate of 30 +/- 1 mg/100 ml at 5 h compared with 5.1 +/- 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 2 Polymyxin B sulphate, given intravenously (1 min before endotoxin) as a bolus injection (5 mg/kg) followed by a continuous intravenous infusion (additional 5 mg/kg given over a 30 min period) prevented the endotoxin-induced pulmonary (right atrial) hypertension but not the acute systemic hypotension. 3 Polymyxin B sulphate reduced the delayed haemodynamic effects of endotoxin (systemic hypotension, decrease in cardiac output); all the eight animals so treated survived 8 h compared with only 1/8 of the controls. 4 Polymyxin B did not prevent the initial (1-3 h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 5 The mechanism of this marked protective effect of the antibiotic and the possible clinical repercussions are discussed; the most likely explanation for the protection is in chemical combination with the lipid A moiety of the endotoxin.

Animals↗