Effects of aspirin and prostacyclin on arrhythmias resulting from coronary artery ligation and on infarct size

Johnston, Kathleen M.; MacLeod, Bernard A.; Walker, Michael J.

doi:10.1111/j.1476-5381.1983.tb09359.x

Cited by 34 publications

(18 citation statements)

References 20 publications

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“…We have no evidence that arrhythmogenesis differs in a major way between the early and late periods, based on the antiarrhythmic actions of drugs in the rat (e.g., Johnston et al, 1983), although we do not rule out this possibility.…”

Section: Introductionmentioning

confidence: 94%

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat

Curtis

MacLeod

Walker

1985

British J Pharmacology

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1 The role of the central nervous system (CNS) in arrhythmogenesis in the 4 h period following occlusion of a coronary artery was investigated in rats by use of CNS ablations and other procedures. 2 Ablations in the CNS included pithing, spinalization and decerebration combined with acute and chronic surgical preparation and noradrenaline/adrenaline infusions. 3 All procedures involving acute surgery reduced the incidence and severity of the arrhythmias induced by occlusion. Such reductions were most marked in the second (0.5-4 h post-occlusion) arrhythmic period. 4 The observed reductions in arrhythmias could not be explained in terms of involvement of the CNS or adrenoceptor activation. 5 When circulating leucocytes, platelets and serum potassium were measured in a group ofpithed rats before and after occlusion, reduced levels (20-50%) of both leucocytes and platelets occurred while serum potassium levels rose by 50-100%. 6 Arrhythmias following coronary occlusion may depend in part on factors in the blood such as leucocytes, platelets and serum potassium and these factors may be altered by acute surgery.

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Section: Introductionmentioning

confidence: 94%

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat

Curtis

MacLeod

Walker

1985

British J Pharmacology

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“…Our method of occluding a coronary artery in conscious rats allows responses to ischaemia and infarction to be assessed with precision and accuracy. The model has been used previously to assess established antiarrhythmics (Johnston et al, 1983a), prostacyclin and aspirin (Johnston et al, 1983b), halothane and similar anaesthetics (Jang et al, 1983). Arrhythmias in this model were not reduced by P-blockade or sympathectomy (Botting et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat

Curtis

MacLeod

Walker

1984

British J Pharmacology

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1 The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. 2 Verapamil (2-20mgkg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-'. This dose was effective when given immediately post-occlusion. 3 Severe arrhythmias, as opposed to PVC, were preferentially reduced. 4 In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20mgkg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. 5Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre-or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 + 0.8 ltmol -1 and 0.6±0.1 Mmoll-1 (x±s.e.mean), respectively following post-occlusion administration vs. 2.7 ± 1.2 and 0.24 ± 0.04 for pre-occlusion administration. 6 Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ 7 We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug.

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“…15,16 However, aspirin failed to reduce ischemia-induced VF in conscious rats with a large IZ. 30 Likewise, platelet-activating factor antagonists ameliorated ischemia-induced VF in vivo in 2 study, 31 but not in others. 32,33 Moreover, platelet-activating factor and plateletactivating factor antagonists possess platelet-independent effects on ischemia-induced VF.…”

Section: Platelets and The Pathophysiological Reserve For Vfmentioning

confidence: 99%

Trapped Platelets Activated in Ischemia Initiate Ventricular Fibrillation

Dhanjal

Medina

Leem

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background-We tested the hypothesis that ischemia-induced ventricular fibrillation (VF) is facilitated by platelets, trapped regionally in the ischemic zone and activated to release arrhythmogenic secretome. Methods and Results-In a randomized study in blood-free, buffer-perfused isolated rat hearts, ischemic zone territory (34±1% of left ventricle) was selected so that ischemia evoked VF in only 42% of controls. VF incidence was increased to 91% (P<0.05) by coronary ligation-induced trapping of freshly prepared autologous platelets (infused before and during coronary ligation, with trapping confirmed by 111 In-labeled platelet autoradiographic imaging). Trapping of platelet secretome prepared ex vivo, or platelet-sized fluorospheres, did not increase ischemia-induced VF incidence. Secretome alone did, however, evoke VF in 2 sham coronary-ligated hearts. Perfusion did not activate infused platelets in sham coronary-ligated hearts, whereas ligation activated trapped platelets (assessed by thromboxane release). In a separate study, trapping whole-heparinized blood mimicked the ability of trapped platelets to increase VF incidence. This effect was not prevented by >5 days oral pretreatment in vivo with clopidogrel (10 mg/kg per day) or indomethacin (2.4 mg/kg per day). Conclusions-Platelets facilitate VF during acute ischemia independently of their ability to participate in occlusive thrombosis.Moreover, the effect is unresponsive to antiplatelet drugs commonly used. Labile secretome constituents appear to be responsible. This opens a novel avenue for antiarrhythmic drug research. (Circ Arrhythm Electrophysiol. 2013;6:995-1001.)

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Effects of aspirin and prostacyclin on arrhythmias resulting from coronary artery ligation and on infarct size

Cited by 34 publications

References 20 publications

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat

Trapped Platelets Activated in Ischemia Initiate Ventricular Fibrillation

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