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J R Parratt

Publications and source records attributed to J R Parratt.

At least 163 records · Page 9Linked to original sources
PubMed1981

Exdotoxin-induced metabolic changes in the conscious, unrestrained rat: hypoglycemia and elevated blood lactate concentrations without hyperinsulinemia.

The effects of E coli endotoxin on the plasma concentrations of glucose, lactate, and immunoreactive insulin (IRI) were studied in conscious unrestrained rats. Additionally the effects of endotoxin on glucose-induced elevations in the plasma IRI concentration and on the rate of disappearance of an intravenous glucose load were examined. After a transient and small hyperglycemia endotoxin administration resulted in a progressive, dose-dependent decrease in the plasma glucose concentration and a marked elevation of plasma lactate. The initial hyperglycemia was accompanied by a small, transient increase in the plasma IRI concentration. There was no increase in the plasma IRI concentration during the development of hypoglycemia. The hypoglycemic effect of endotoxin was fully manifest in streptozotocin diabetic rats which displayed low insulin concentrations initially and throughout the experiment. Endotoxin injection produced a significant reduction in the plasma IRI response to glucose administration and a decrease in the rate of disappearance of a glucose load. It is suggested that the metabolic effects of endotoxin in the rat are not mediated by an increase in insulin secretion.

Animals↗
PubMed1980

Coronary artery ligation in anesthetized rats as a method for the production of experimental dysrhythmias and for the determination of infarct size.

Coronary artery ligation in anesthetized rats was assessed as a method for the production of experimental dysrhythmias and for the determination of infarct size. Following occlusion of the left main coronary artery, very marked ventricular dysrhythmias occurred in two distinct phases, an early and a late phase, at 0-30 minutes and at 1 1/2--4 hours after ligation respectively. Infarct size was measured at 4 hours after ligation using nitroblue tetrazolium to stain for the depletion of two cytoplasmic enzymes, lactate dehydrogenase and NADPH diaphorase. In this model, lignocaine (10 mg/kg plus an infusion of 5 mg/kg/hr) and ORG 6001 (10 mg/kg plus an infusion of 2.5 mg/kg/hr) had marked antidysrhythmic activity but neither drug influenced infarct size. The model, because of its simplicity, reproducibility, and low cost, should be useful for the screening of potential antidysrhythmic agents and may also be used to determine infarct size following coronary artery ligation.

Androstanols↗
PubMed1980

A comparison of the cardiovascular effects of dobutamine and a new dopamine derivative (D4975) during shock induced by E. coli endotoxin.

1 The effects of a newly developed dopamine-xanthine derivative, 7-propyl-theophylline-dopamine (D4975) and of dobutamine have been examined in anaesthetized cats before and after the induction of shock with E. coli endotoxin. 2 Both D4975 and dobutamine caused dose-related increases in left ventricular (LV) dP/dtmax (and LVdP/dt at fixed isovolumic pressures. Significantly smaller increases in LVdP/dtmax occurred as early as 0.5 to 1 h after endotoxin, with maximal attenuation at 1 to 2 h and some improvement in sensitivity in cats surviving 2 to 4 h. The maximum response to each drug was markedly reduced in shock. 3 Neither D4975 nor dobutamine had significant effects on heart rate. D4975 caused dose-related increases in systemic arterial blood pressure which were smaller during shock, the changes in responsiveness following those in LVdP/dtmax. 4 Possible mechanisms responsible for changing myocardial sensitivity to these and other agents are discussed. It is concluded that D4975 may be more useful in the treatment of shock than either dopamine or dobutamine because (a) it is more potent during shock than dobutamine (perhaps as a result of phosphodiesterase inhibition by the theophylline component of D4975); (b) its action is longer-lasting than dobutamine or dopamine and (c) like dobutamine, its effect on heart rate is insignificant.

Animals↗
PubMed1980

Prophylactic lignocaine and early post-coronary artery occlusion dysrhythmias in anaesthetized greyhounds.

1. Lignocaine (1 mg kg-1 min-1 infused intravenously for 30 min) greatly reduced the incidence of ventricular ectopic beats that resulted from acute coronary artery ligation in anaesthetized greyhound dogs. However, the incidence of ventricular fibrillation was only slightly reduced by this treatment which caused significant myocardial depression. 2. There is no good evidence from this study that lignocaine is a particularly effective prophylactic in acute myocardial infarction.

Anesthesia↗
PubMed1980

Blockade of adrenaline-induced hyperglycaemia in the anaesthetized cat by continuous infusion of phentolamine and propranolol.

1 The effects of adrenoceptor blocking drugs on the metabolic responses to adrenaline infusion (1 microgram kg-1 min-1) have been studied in the anaesthetized, fasted cat. 2 Propranolol, in doses (0.25 or 1 mg/kg) which prevented completely adrenaline-induced tachycardia, reduced but did not abolish adrenaline-induced hyperglycaemia. 3 Phentolamine infusion, at a rate (15 micrograms kg-1 min-1 after a priming dose of 2.5 mg/kg) which reversed the pressor effect of adrenaline, reduced but did not abolish adrenaline-induced hyperglycaemia. 4 The continuous infusion of a combination of phentolamine (15 micrograms kg-1 min-1 after a priming dose of 2.5 mg/kg) and propranolol (5 micrograms kg-1 min-1 after a priming dose of 0.25 mg/kg) prevented completely the hyperglycaemia response to adrenaline infusion over a 6 h period. 5 The increase in blood lactate concentration produced by adrenaline was prevented completely by the combined infusion of propranolol and phentolamine but was not modified by phentolamine alone.

Anesthesia↗
PubMed1980

The early consequences of myocardial ischaemia and their modification.

This paper attempts to review our studies on the early haemodynamic, metabolic and electrophysiological consequences of acute coronary artery ligation in an experimental model which allows the simultaneous assessment of blood flow and sampling of blood from both normal and acutely ischaemic zones of myocardium. 1. Using local coronary venous sampling, it has been observed that the major metabolic changes which occur in the ischaemic zone during the first 30 min after coronary artery ligation are increases in PCO2, decreases in pH and oxygen content, a shift in lactate handling from extraction to production and an efflux of K+. These changes were not observed in coronary sinus blood draining essentially nonischaemic zones of myocardium. 2. The major haemodynamic change produced by coronary artery ligation was cardiac depression (decreased stroke volume and cardiac work), unchanged LV dP/dt with an elevated filling pressure. 3. Acute ligation of the anterior descending branch of the left coronary artery, l.a.d., resulted in bursts of ventricular ectopic activity which was especially marked 10-20 min after ligation and which frequently resulted in ventricular fibrillation. The incidence of arrhythmias could be modified by the species of dog used, the anaesthetic employed, the arterial oxygen tension and the administration of several antiarrhythmic drugs. The possible relevance observed in the ischaemic myocardium, to the genesis of these arrhythmias is discussed. 4. The changes in the ST-segment of epicardial leads produced by short (3 min) occlusions of the l.a.d. were studied in mongrel dogs. Evidence is presented which suggests that the evolution of ST-segment elevation is linked to the efflux of K+ from ischaemic myocardial cells.

Animals↗
PubMed1980

Reduced myocardial response to calcium during endotoxin shock in the cat.

The hemodynamic effects of short intravenous infusions of calcium chloride were examined in anaesthetized cats before and during shock induced with E coli endotoxin (2 mg/kg). In normal cats calcium (5 mg kg-1 min-1 or 10 mg kg-1 min-1 infused for 5 minutes) increased left ventricular (LV) dP/dtmax, LVdP/dt at fixed isovolumic pressures, systemic arterial blood pressure and, usually, cardiac output. These hemodynamic changes lasted approximately 20 minutes. During endotoxin shock the calcium response (cardiac output, LVdP/dt, blood pressure) was greatly reduced. This diminished responsiveness was evident as early as 0.5--1 hour after endotoxin and lasted throughout the 4-hour shock period. The duration of the hemodynamic response was also decreased during shock. Reduced myocardial sensitivity to a number of cardiac stimulants, including beta-adrenoceptor stimulants and agents augmenting cellular cAMP/levels, occurs in this and other shock models. The present results suggest that this altered sensitivity is attributable to changes in the actual contraction processes rather than beta-adrenoceptor desensitization or a defect in the cAMP system. Since this altered calcium response does not occur in vitro the results might suggest the presence, in shock, of a circulating agent acting at the level of cellular calcium exchange.

Animals↗
PubMed1979

The cardiovascular pharmacology of 7-propyl-theo-phylline-dopamine (D4975); comparison with dopamine and dobutamine.

1 The effects of a newly developed dopamine-xanthine derivative, 7-propyl-theophylline-dopamine (D4975), have been examined in cats anaesthetized with sodium pentobarbitone. When administered intravenously (in doses as low as 0.5 to 1.0 micrograms/kg) it increased systemic arterial pressure, left ventricular (LV) dP/dtmax, dP/dt at fixed ventricular isovolumic pressures and cardiac output. Heart rate effects were minimal. 2 D4975 was about 5 times more active than dopamine or dobutamine in elevating LV dP/dtmax or dP/dt at common peak isovolumic pressures (CPIP) and about 10 times more active than dopamine at increasing systemic arterial blood pressure. The effects of D4975 were also more prolonged than those of the other two agents. 3 The effects of D4975 on LV dP/dtmax were greatly reduced by the prior administration of propranolol. D4975 has no effect on peripheral beta 2-adrenoceptors. 4 It is suggested that the effects of D4975 on the myocardium involve both beta 1-adrenoceptor stimulation and inhibition of phosphodiesterase and that the marked and prolonged pressor response is due to resistance to enzymatic breakdown by monoamine oxidase. 5 The results suggest that D4975 might prove valuable in the treatment of the hypotension and reduced myocardial contractility of shock, especially as it is possible to select a dose that increases LV dP/dtmax without increasing either heart rate of systemic arterial pressure.

Animals↗
PubMed1979

The effects of disopyramide phosphate on early post-coronary artery ligation dysrhythmias and on epicardial ST-segment elevation in anaesthetized dogs.

1 The antidysrhythmic, haemodynamic and metabolic effects of intravenously administered disopyramide phosphate (1 to 5 mg/kg) have been studied in greyhounds, anaesthetized with trichloroethylene. 2 In doses of 2.5 and 5.0 mg/kg, disopyramide significantly reduced the ventricular dysrhythmias that occur in the initial 30-min period following acute coronary artery ligation. None of the disopyramide-treated animals developed ventricular fibrillations. 3 The metabolic consequences of coronary artery ligation, assessed by local coronary venous sampling from the ischaemic area, were not modified by disopyramide except that K+ egress was prevented. 4 There was evidence for substantial disopyramide-induced myocardial depression (decreased cardiac output and left ventricular dP/drmax with elevated ventricular filling pressure and pulmonary oedema and shunting) and it is suggested that great care be taken when the drug is administered intravenously in conditions where cardiac function is already compromised. Disopyramide also reduced myocardial blood flow. 5 In chloralose-anaesthetized mongrel dogs, disopyramide (2.5 mg/kg) significantly reduced the ST-segment elevation (assessed from epicardial recordings) that resulted from short (3 min) coronary artery occlusions. This could indicate a reduction in the extent and severity of myocardial injury or simply reflect decreased K+ efflux (since locally administered K+ itself increased ST-segment elevation).

Animals↗
PubMed1979

The effect of aminosteroid, ORG 6001, on hypothermia induced ventricular fibrillation in the cat.

1 The effect of the antidysrhythmic aminosteroid, ORG 6001, on hypothermia-induced ventricular fibrillation was investigated in cats anaesthetized with pentobarbitone. 2 ORG 6001 (total dose, 10 mg/kg, by intravenous injection) reduced both the incidence of fibrillation and the temperature at which it occurred. The number of animals that survived to 16 degrees C was increased. 3 This protective effect of ORG 6001 could not be explained by changes in respiratory acidosis, plasma concentrations of sodium and potassium, or by changes in the action potential of excised hypothermic ventricular muscle. The hypothermia-induced elevation of blood lactate was less in cats treated with the aminosteroid. 4 Over a limited temperature range, ORG 6001 prolonged the P wave and QRS duration and shortened the QTc interval. ST segment elevation was slightly reduced in the drug-treated group. J deflections were observed but were not correlated with the development of fibrillation. 5 The onset of fibrillation was not considered to be due to temperature differences between the myocardium and arterial blood or between localized areas of the left ventricular wall.

17-Ketosteroids↗
PubMed1979

Haemodynamic effects of the carboxylic ionophore monensin when administered before and during shock induced by E. coli endotoxin.

The haemodynamic effects of the carboxylic ionophore monensin have been examined in cats anaesthetized with sodium pentobarbitone. Marked increases in left ventricular dP/dtmax (and dP/dt at fixed isovolumic pressures) and slight increases in cardiac output and stroke volume occurred, indicating increased myocardial contractility. Heart rate was unchanged but systemic arterial pressure was substantially increased. Satisfactory increases in contractility and arterial pressure were obtained when monensin was infused intravenously in a total dose of 0.25 mg kg-1 over 10 min. Larger doses, especially if rapidly injected, resulted in very marked increases in myocardial contractility leading eventually to cardiac failure. The haemodynamic effects of monensin were markedly reduced during shock induced by E. coli endotoxin and there was unfortunately no evidence to suggest that this extremely potent compound might be potentially beneficial in this form of profound cardiovascular shock.

Animals↗
PubMed1979

Myocardial function in feline endotoxin shock: a correlation between myocardial contractility, electrophysiology, and ultrastructure.

The nature of the myocardial depression observed in patients with septic shock, and in animals late in shock induced by endotoxin, is still under examination. These studies, in cats and kittens administered an LD80 dose of E coli endotoxin, were designed to examine the relationship between changes in myocardial contractility, in cellular electrophysiology and in ultrastructural morphology. There was no difference between tension developed in vitro by cardiac muscle removed from cats five hours after endotoxin administration and from cats not administered endotoxin. There was also no difference in their responses to calcium chloride or to anoxia. The action potential characteristics of ventricular muscle isolated from endotoxin treated cats were also not different from control, and ultrastructural damage was minimal and not extensive. Endotoxin (100 microgram/ml) had no effect on cardiac muscle in vitro, even after a one-hour contact time. It is concluded that the integrity of the myocardium is maintained even late in shock and that endotoxin has no direct effects on the heart.

Action Potentials↗
PubMed1979

Failure of exogenous ATP and creatine phosphate to modify the course of E coli endotoxin shock in the cat.

Exogenous adenosine triphosphate (ATP) (in combination with MgCl2) and also creatine phosphate (CrP), have been administered intravenously to endotoxin-shocked cats. Untreated shocked cats exhibited systemic hypotension during the first hour and again from four hours. Cardiac output fell progressively, and markedly elevated arterial lactate levels were evident within one hour of endotoxin administration. Treatment with ATP (10 mg/kg every 30 minutes) during shock led to rapid hemodynamic deterioration in all cats; most of the cats were dead before completion of dosing (at three hours). Long-lasting systemic hypotension and bradycardia were associated with this ATP administration and marked hypoglycemia developed in the survivors. Neither ATP (62 mg/kg) administered before endotoxin, nor CrP (500 mg/kg; administered either prior to endotoxin, or one hour afterwards) significantly modified the hemodynamic or metabolic changes associated with endotoxin shock in this species. Neither ATP nor CrP increased survival (assessed at five hours). Other workers have demonstrated improved survival from shock with ATP treatment. There may be species differences in the responsiveness to exogenous ATP or, alternatively, a difference in the role of high-energy phosphates in different types of shock.

Adenosine Triphosphate↗
PubMed1978

Are prostaglandins involved in the regulation of coronary blood flow? A review of the evidence.

Prostaglandins (PG's) fulfil most of the criteria required for the metabolic "coupler" linking increases in myocardial activity with increases in coronary blood flow. They are synthesized by the heart and coronary vessels, profoundly modify coronary blood flow in low concentrations and are released under conditions of hypoxia and myocardial ischaemia. Studies with inhibitors of PG-synthetase however provide no firm evidence that PG's are involved in the physiological regulation of myocardial blood flow. These studies are reviewed.

Animals↗
PubMed1977

The haemodynamic and metabolic effects of MG 8926, a prospective antidysrhythmic and antianginal agent.

1 The antidysrhythmic, haemodynamic and metabolic effects of a new prospective antianginal and antidysrhythmic agent, N-(3-3-dipenylpropyl)-alpha-methyl-beta-cyclohexylethylamine hydrochloride (MG 8926), have been compared with the chemically related substance, prenylamine, in anaesthetized greyhounds and guinea-pigs. 2 When given intravenously 20 min beforehand, both MG 8926 and prenylamine (5 mg/kg) significantly suppressed the early dysrhythmias induced by coronary artery ligation in anaesthetized greyhounds. At a dose of 1 mg/kg, MG 8926 also protected anaesthetized guinea-pigs from dysrhythmias induced by ouabain infusions. 3 In dogs pretreated with MG 8926, metabolic changes indicative of myocardial ischaemia (increased PCO2 and potassium efflux, decreased oxygen content and pH) were less marked than those occurring in control animals. 4 Evidence was obtained that MG 8926, when given either before or after coronary occlusion, was capable of decreasing the severity of myocardial ischaemia as assessed by ST-segment changes in epicardial electrocardiograms.

Animals↗