Search PubMed⌕ Search

Biomedical subjects

J R Parratt

Publications and source records attributed to J R Parratt.

247 records · Page 14Linked to original sources
PubMedDate not supplied

The effects of distension of the small intestine on myocardial blood flow in anaesthetised cats: possible relevance to coronary vasospasm.

The haemodynamic effects of distending the small intestine (with a balloon in the lumen) were examined in cats anaesthetised with chloralose. Particular attention was paid to blood flow changes in localised areas of the left ventricular wall (as assessed using the heated thermocouple technique). Intestinal distension led to an increase in systemic blood pressure but usually to a reduction in myocardial blood flow; no cardiac dysrhythmias were observed. When the effect of increased systemic (perfusion) pressure on blood flow was eliminated (using partial correlation coefficients) flow then bore a negative relationship to intestinal pressure, probably indicating constriction of the myocardial blood vessles. This may indicate that distension of hollow organs can lead to a visceral-cardiac reflex. The resulting coronary vasospasm might be one cause of pain in certain patients with angina pectoris.

Animals↗
PubMedDate not supplied

The effects of prolonged oral administration of a new antidysrhythmic drug (Org 6001) on coronary artery ligation dysrhythmias in conscious and anesthetized rats.

We determined the antidysrhythmic activity of acute or prolonged administration of Org 6001 on dysrhythmias following coronary artery ligation in conscious and anesthetized rats. Intravenous doses of 5 and 10 mg/kg of Org 6001 markedly protected against postligation dysrhythmias in anesthetized rats, whereas a single oral dose of 10 mg/kg given 1 hr prior to ligation did not. Prolonged oral administration of Org 6001, 10 mg/kg twice daily for 10 days, the last dose given 1 hr before ligation, reduced the incidence of ventricular fibrillation and increased survival in both conscious and anesthetized animals. This effective antidysrhythmic dose regimen resulted in drug concentrations of 335 +/- 68 ng/ml in plasma and 2,940 +/- 408 ng Org 6001/g in the whole heart. At 24 hr after the last dose no protection against the dysrhythmias remained, and drug levels in both plasma and heart tissue were low. A good correlation was observed between the levels of Org 6001 in the heart and the reduction in the rate of rise of phase zero of cardiac action potentials obtained from drug-pretreated animals. It is concluded that prolonged administration of Org 6001 is effective against postligation dysrhythmias and that this effect may be associated with the drug's Class I activity.

Administration, Oral↗
PubMedDate not supplied

Creatine phosphate suppresses ventricular arrhythmias resulting from coronary artery ligation.

The effects of various doses of creatine phosphate have been examined in a rat model of acute myocardial ischaemia. When given directly into the lumen of the left ventricle in pentobarbitone-anaesthetised male rats, creatine phosphate (50 and 100 mg/kg) markedly reduced the incidence of ventricular ectopic beats, and especially the incidence and duration of ventricular tachycardia and fibrillation which normally resulted from acute coronary artery ligation in this model. This protection was observed even if 1 of 2 h elapsed between creatine phosphate administration and coronary artery ligation. Electrophysiological studies on papillary muscles removed from rats 1 h after administration showed that creatine phosphate both decreased the maximum rate of depolarisation and prolonged the duration of the action potential. These results confirm our previous work in dogs that creatine phosphate is effective against early postinfarction ventricular arrhythmias, at least if given locally. It is suggested that these effects are due, at least in part, to a prolongation of the cardiac muscle action potential. Whether this is the result of maintaining energy production early in myocardial ischaemia is unclear.

Action Potentials↗
PubMedDate not supplied

Nifedipine reduces arrhythmias but does not alter prostanoid release during coronary artery occlusion and reperfusion in anaesthetised greyhounds.

We examined the effects of nifedipine, a calcium slow-channel blocking drug, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Fifteen minutes after commencing treatment with nifedipine (5 micrograms/kg + 0.67 micrograms kg-1 min-1), there were significant reductions in arterial blood pressure, left ventricular end-diastolic pressure, and vascular resistance, with increases in cardiac output and stroke volume. Although coronary artery blood flow was unchanged, oxygen extraction was decreased, indicating that nifedipine reduced oxygen consumption. Nifedipine prevented the haemodynamic changes that occur in control dogs during acute myocardial ischaemia and markedly reduced the number of arrhythmias during coronary artery occlusion. The incidence of ventricular fibrillation induced by release of the occlusion was significantly reduced from 88% in the control group to 22% in the group receiving nifedipine. The release of thromboxane B2 and 6-keto PGF1 alpha (stable breakdown products of thromboxane A2 and prostacyclin, respectively) from the acutely ischaemic myocardium was not altered by nifedipine. It is concluded that this low dose of nifedipine had marked antiarrhythmic activity during both coronary artery occlusion and reperfusion. The relationship to dosage and possible mechanisms for this effect are discussed.

Animals↗
PubMedDate not supplied

Prostacyclin--antiarrhythmic or arrhythmogenic? Comparison of the effects of intravenous and intracoronary prostacyclin and ZK36374 during coronary artery occlusion and reperfusion in anaesthetised greyhounds.

The effects of prostacyclin and ZK36374, a more stable analogue of prostacyclin, were examined in greyhounds anaesthetised with chloralose. Intravenous drug administration (100 ng kg-1 min-1) exacergbated the arrhythmias induced by occlusion of the left anterior descending coronary artery. The incidence of ventricular fibrillation (VF) was 50% in both drug groups compared with 10% in controls. An antiarrhythmic effect was observed when a lower dose (5 ng kg-1 min-1) was infused directly into the coronary circulation. The number of extrasystoles occurring during the first 30 min of occlusion was reduced from 720 +/- 136 in the controls to 327 +/- 167 in the prostacyclin group and 309 +/- 110 (p less than 0.05) in the dogs receiving ZK36374. The only haemodynamic change observed in the dogs receiving intracoronary drug infusions was a small decrease in systemic arterial blood pressure. In the intravenous groups systemic hypotension was accompanied by tachycardia, suggesting that there may have been a reflex increase in sympathetic drive. Increased catecholamine release could account for the higher incidence of VF in the dogs treated with intravenous prostacyclin or ZK36374. The intracoronary administration of both drugs markedly reduced the incidence of VF induced by the release of a 40-min coronary artery occlusion. This latter result suggests that the release of endogenous prostacyclin may have protective effects during reperfusion of the ischaemic myocardium.

Anesthesia↗
PubMedDate not supplied

Effects of prolonged administration of oxprenolol on severity of ischaemic arrhythmias, enzyme leakage, infarct size, and intracellular cardiac muscle action potentials.

We examined the effects of prolonged oral administration of oxprenolol (twice daily for 6 weeks) to male Sprague-Dawley rats. At two times (1 or 16-18 h) after the last oral dose, the rats were anaesthetised and subjected to acute coronary artery ligation, and the severity of the resulting arrhythmias was assessed. Ischaemic damage was measured histochemically (using frozen section analysis by toluidine blue dye in nitrobluetetrazolium ) and by myocardial enzyme release. Cardiac muscle (atria and papillary muscle) was also removed and the transmembrane action potentials recorded using conventional microelectrode techniques. When coronary artery ligation was performed 1 h after the last oral dose (at which time there was evidence of substantial myocardial beta 1-adrenoceptor blockade), there was significant reduction in the severity of early arrhythmias, but no evidence that the severity of ischaemic damage was reduced or that the intracellular cardiac action potentials were modified. No protection was observed when coronary artery ligation was carried out 16 h after the last oral dose of oxprenolol. These results support our previous studies with acutely administered beta-adrenoceptor blocking drugs that myocardial beta-adrenoceptor blockade is the main factor involved in the protection afforded by such drugs against early ischaemic arrhythmias and that other possible effects, such as membrane stabilisation and action potential prolongation, are relatively unimportant in this model.

Action Potentials↗
PubMedDate not supplied

Relationships between the severity of myocardial ischaemia, reperfusion-induced ventricular fibrillation, and the late administration of dazmegrel or nifedipine.

We examined the effects of late administration of the thromboxane synthetase inhibitor dazmegrel (UK 38485) and the calcium channel blocker nifedipine in anaesthetised greyhounds subject to occlusion of the left anterior descending coronary artery with reperfusion after 40 min of ischaemia. Administration of dazmegrel, 3 mg/kg i.v., or nifedipine, 5 micrograms/kg + 1 microgram kg-1 min-1 i.v., 25 min after coronary artery occlusion failed to reduce the incidence of reperfusion-induced ventricular fibrillation (controls, 70%; dazmegrel, 50%; nifedipine, 70%; n = 10). Measurement of plasma prostanoid concentrations indicated that within 5 min of receiving dazmegrel there was a significant reduction in thromboxane B2 concentrations in the local coronary vein draining the ischaemic myocardium. The results suggest that the occurrence of reperfusion-induced ventricular fibrillation depends upon the severity of changes occurring during ischaemia. Analysis of various factors suggested that the number of ischaemia-induced arrhythmias, heart rate, and the magnitude of changes in local coronary venous PO2 may be important predictors of reperfusion-induced ventricular fibrillation.

Animals↗
PubMedDate not supplied

Antiarrhythmic and electrophysiological effects of ICS 205-930, an antagonist of 5-hydroxytryptamine at peripheral receptors.

We assessed the antiarrhythmic activity of ICS 205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], a selective antagonist at neuronal 5-hydroxytryptamine M-receptors, against the arrhythmias that occur following occlusion of the left main coronary artery in anaesthetised rats and subsequent release (reperfusion). The incidence of reperfusion-induced ventricular fibrillation and ventricular tachycardia was significantly reduced by pretreatment with ICS 205-930 (0.3 and 1.0 mg kg-1 i.v. and 10 and 30 mg kg-1 p.o.). The arrhythmias that occurred during 30 min of coronary artery occlusion were also less severe in animals given ICS 205-930 (1.0 and 5.0 mg kg-1 i.v.). Arterial blood pressure was not altered by the drug, and heart rate was only slightly reduced by the highest intravenous dose. In vitro, ICS 205-930 reduced the maximum rate of rise of phase 0 of normal sheep Purkinje fibre action potentials in concentrations from 0.5 to 5.0 mg L-1. Action potentials depressed by superfusion with a physiological salt solution modified to mimic the conditions occurring during mild ischaemia were similarly affected by ICS 205-930. The highest drug concentration studied under these conditions was 1.5 mg L-1 since, in combination with the modified physiological salt solution, this rendered some of the Purkinje fibres inexcitable. These results indicate that ICS 205-930 possesses marked antiarrhythmic activity against ischaemia-induced arrhythmias in anaesthetised rats and that a direct electrophysiological effect of the drug may, at least in part, underlie its protective action.

Action Potentials↗
PubMedDate not supplied

Do alterations in prostanoid or catecholamine release influence the antiarrhythmic activity of nicergoline?

We examined the effects of nicergoline, an alpha-adrenoceptor blocking drug and an inhibitor of platelet phospholipase, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid and catecholamine release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Twenty-five minutes after commencing the intravenous infusion of nicergoline (50 micrograms kg-1 min-1) there were significant reductions in heart rate, arterial blood pressure, left ventricular dP/dtmax, and cardiac output. Nicergoline also increased the 0(2) extraction by the myocardium both before and during coronary artery occlusion. In contrast to control animals, heart rate decreased but there were no further reductions in arterial blood pressure during the occlusion period. Nicergoline improved survival (from 17 in control dogs to 50%) following the combined period of myocardial ischaemia and reperfusion and appeared to suppress the phase 1b occlusion-induced arrhythmias. The release of thromboxane B2 from the ischaemic myocardium was partially suppressed by nicergoline, and the ratio of 6-keto PGF1 alpha/thromboxane B2 (the stable breakdown products of prostacyclin and thromboxane A2, respectively) was increased. The washout of noradrenaline and adrenaline from the ischaemic myocardium following release of the occlusion was slightly enhanced by nicergoline. It is concluded that the beneficial metabolic and prostacyclin-promoting properties of nicergoline may be opposed by its action on noradrenaline washout, thus limiting its antiarrhythmic effectiveness.

6-Ketoprostaglandin F1 alpha↗