{'fraction_non_alphanumeric': 0.04400185270958777, 'fraction_numerical': 0.036591014358499305, 'mean_word_length': 5.371681415929204, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Failure of cyclo-oxygenase inhibition to protect against arrhythmias induced by ischaemia and reperfusion: implications for the role of prostaglandins as endogenous myocardial protective substances.

STUDY OBJECTIVE
It has been suggested that the balance between the release from the heart of prostacyclin and thromboxane A2 is a major determinant of the severity of arrhythmias during ischaemia and reperfusion. This has been examined in a dog model.


DESIGN
Three different cyclo-oxygenase inhibitors in doses adequate to prevent formation of both prostacyclin and thromboxane--aspirin (7 mg.kg-1), flurbiprofen (3 mg.kg-1), and sodium meclofenamate (2 mg.kg-1) with or without nafazatrom or dazmegrel--were given prior to a combined occlusion-reperfusion insult, and the severity of resulting arrhythmias examined.


MATERIAL
Adult greyhound dogs were used: controls n = 29; aspirin n = 10; flurbiprofen n = 10; sodium meclofenamate +/- nafazatrom or dazmegrel n = 22.


MEASUREMENTS AND MAIN RESULTS
None of the interventions modified the severity of ischaemic arrhythmias induced by coronary artery occlusion and release. The numbers of ventricular extrasystoles during the 40 min occlusion period were similar in all groups: controls 653(SEM 109); aspirin 690(187); flurbiprofen 454(132); meclofenamate 833(218). Ventricular fibrillation from the combined occlusion-reperfusion insult was also similar; controls 83%; aspirin 80%; flurbiprofen 80%; meclofenamate 100%. In the doses used all three inhibitors prevented the increase in plasma concentrations of thromboxane A2 [from 104(23) to 166(34) pg.ml-1] and prostacyclin [from 450(80) to 720(110) pg.ml-1] seen in control untreated dogs subjected to coronary artery occlusion. The addition of sodium meclofenamate to either nafazatrom (10 mg.kg-1 orally) or dazmegrel (3 mg.kg-1 intravenously), which when given alone are markedly protective, abolished this protection.


CONCLUSION
The results show the importance of maintaining prostacyclin release in modifying the severity of ischaemic and reperfusion arrhythmias, and again suggest that prostacyclin is an "endogenous antiarrhythmic substance".