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J R Parratt

Publications and source records attributed to J R Parratt.

At least 235 records · Page 13Linked to original sources
PubMed1969

Myocardial and haemodynamic effects of the beta-adrenoceptor blocking drug alprenolol (H56/28) in anaesthetized cats.

1. The effects of the beta-adrenoceptor blocking drug alprenolol (H56/28) on myocardial and general haemodynamics were studied in anaesthetized cats.2. Alprenolol (0.5 mg/kg and 1.0 mg/kg) reduced femoral systolic and diastolic pressures, heart rate and left ventricular systolic pressure. The rate of rise of the left ventricular pressure pulse (dp/dt) was reduced despite a significant elevation of left ventricular end-diastolic pressure. This is evidence for decreased myocardial contractility. On some occasions there was a transient initial increase in +ve dp/dt max. possibly indicative of moderate beta-adrenoceptor stimulant activity.3. Myocardial and liver blood flows were measured using a heated thermocouple technique. Alprenolol slightly decreased both myocardial and liver blood flows (mean of 17% and 15% respectively with a dose of 1.0 mg/kg). Myocardial and liver vascular resistances were only very slightly increased.4. Alprenolol had no direct effect on calculated myocardial and liver metabolic heat production.5. In doses up to 1.0 mg/kg alprenolol had no effect on airway resistance but occasionally decreased (in vivo) intestinal muscle movement.6. Since alprenolol (although reducing calculated myocardial oxygen consumption and the myocardial and metabolic heat stimulant effects of catecholamines) has no significant effect on myocardial vascular resistance, it is suggested that it would be a useful adjunct in the therapy of angina pectoris.

Adrenergic beta-Antagonists↗
PubMed1967

Propranolol.

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Angina Pectoris↗
PubMed1966

A species comparison of the effects of changing perfusion pressure on blood flow and metabolic heat production in the myocardium.

1. A heated thermocouple technique (internal calorimetry) has been used to investigate blood flow and heat production responses in the myocardium to changing blood pressure in monkeys, dogs, rabbits, guinea-pigs and rats. 2. Perfusion experiments (isolated guinea-pig and dog hearts) showed linear relations between conductivity increment and coronary blood flow up to 1 x 5 ml. g(-1) min(-1) (dog heart perfused with blood) and 5 ml. g(-1) min(-1) (guinea-pig heart perfused with saline). This relation was the same in the beating and non-beating heart. 3. In rabbits, guinea-pigs and rats the relation between flow (conductivity increment) and blood pressure was linear. In contrast, in monkeys and dogs, over the range 100-40 mm Hg, little change in blood flow occurred. After the injection of procaine around the stellate ganglion, the relation between pressure and flow in both species was linear. It is suggested that the constancy of blood flow displayed in the monkey and dog over this blood pressure range was due to the activity of adrenergic rasodilator fibres. 4. Evidence is adduced to show an increased myocardial heat production when systemic arterial pressure fell below about 60 mm Hg. This was not affected by cardiac denervation. The possible significance of this effect is discussed.

Animals↗
PubMedDate not supplied

Delayed cardioprotection is associated with the sub-cellular relocalisation of ventricular protein kinase C epsilon, but not p42/44MAPK.

Both noradrenaline administration to rats and rapid cardiac pacing in dogs induces delayed protection of the heart against ischaemia-induced ventricular arrhythmias. In an attempt to establish molecular mechanisms underlying the delayed cardioprotection, we have examined the potential role of two kinases, PKC epsilon and p42/44MAPK. These protein kinases are expressed in the ventricles of the heart and are characterised by their ability to regulate ion-flux and gene transcription. In the rat p42MAPK is predominantly localised in the high-speed supernatant fraction of the ventricle homogenate, whereas p44MAPK is enriched in the nuclear low speed pellet. A small proportion of the p42MAPK is activated even in hearts from control animals. However, neither kinase is relocalised or activated by noradrenaline administration and this provides preliminary evidence the p42/44MAPK may not play a significant role in delayed protection in this species. In contrast, noradrenaline does induce the translocation of PKC epsilon to cell membranes, a response that is sustained for up to 4 h. However, PKC epsilon is down-regulated from the cytoplasm after 24 h post noradrenaline treatment. PKC epsilon is also translocated to the membrane in dogs that have been classically pre-conditioned and cardiac paced. In the latter case, translocation of PKC epsilon from the cytoplasm to the cell membrane is evident 24 h after pacing. These results indicate that the release of endogenous mediators may either inhibit down-regulation or elicit an increase in PKC epsilon mRNA expression. Therefore, in dog heart the subcellular relocalisation of PKC epsilon persists into the 'second window' and may play a central role in the molecular mechanism governing delayed cardioprotection. It is important in the future to identify either the gene products that are induced or the target protein(s) that are phosphorylated by PKC epsilon.

Animals↗
PubMedDate not supplied

Ischaemic preconditioning in the rat heart: the role of G-proteins and adrenergic stimulation.

UNLABELLED: Since recent findings indicate the involvement of G-proteins in the mechanism of ischaemic preconditioning (PC), the present study was aimed to investigate the role of adrenergic mechanisms, such as G-proteins and stimulation of adrenergic receptors, in this phenomenon. For this purpose, isolated Langendorff-perfused rat hearts were subjected to regional ischaemia (30 min occlusion of LAD) followed by reperfusion. The effect of PC (a single 5 min occlusion/reperfusion before a long occlusion) on ischaemia- and reperfusion induced arrhythmias was studied in conjunction with an assessment of G-proteins in the myocardial tissue by means of Western blotting and ADP-ribosylation with bacterial toxins. To follow the link between G-proteins and adrenergic receptors, their stimulation by exogenous norepinephrine (NE) was applied to test whether it can mimic the effect of PC on arrhythmias. Thirty min ischaemia and subsequent reperfusion induced high incidence of ventricular tachycardia (VT) and fibrillation (VF). PC significantly reduced a total number of extrasystoles, incidence of VT and abolished VF. It was, however, insufficient to suppress reperfusion-induced sustained VF. Measurement of G-proteins revealed that PC led to a reduction of stimulatory Gs proteins, whereas inhibitory Gi proteins were increased. NE (50 nmol) introduced a manner of similar to PC (5 min infusion, 10 min normal reperfusion) reduced ischaemic arrhythmias in the same way, as PC. In addition, in NE-pretreated hearts reperfusion induced mostly transient VF, which was spontaneously reverted to normal sinus rhythm. A transient increase in heart rate and perfusion pressure during NE infusion completely waned before the onset of ischaemia, indicating that antiarrhythmic effect was not related to haemodynamic changes and to conditions of myocardial perfusion. CONCLUSION: antiarrhythmic effect of PC may be mediated by a stimulation of adrenergic receptors coupled to appropriate G-proteins. Consequently, the inhibition of adenylate cyclase activity and reduction in cAMP level, as well as the activation of protein kinase C may be considered as two possible pathways leading to a final response.

Adenosine Diphosphate Ribose↗