7-oxoprostaglandin-i2 and Arrhythmias--Cardiac

The aim was to investigate the late effect of pretreatment with 7-oxo prostacyclin on reperfusion induced arrhythmias in the isolated rat heart.. Forty eight hours after intramuscular administration of drug in vivo (50 micrograms.kg-1 body weight), isolated Langendorff perfused rat hearts were subjected to 30 minutes of regional ischaemia and 5 minutes of reperfusion. Incidence and duration of ventricular arrhythmias in both pretreated and control groups were evaluated on reperfusion. Morphological examination was also performed.. In the untreated group reperfusion induced 75% of sustained ventricular fibrillation. Incidence of ventricular fibrillation, its duration, and arrhythmia score were significantly lower in the pretreated group. Pretreatment with 7-oxo prostacyclin had no effect on heart rate and coronary flow throughout the whole course of perfusion. Neither was the occluded zone size affected. Ultrastructure of ischaemic and reperfused myocardium was better preserved in the pretreated group.. Antiarrhythmic action of 7-oxo prostacyclin was unrelated to changes in haemodynamics, thus suggesting the direct influence of the myocardium. The possible mechanism of action may involve maintenance of intracellular cation homeostasis (particularly of Na+ and Ca2+) due to a stimulation of sarcolemmal Na+ pump activity.

Topics: Animals; Arrhythmias, Cardiac; Epoprostenol; In Vitro Techniques; Male; Microscopy, Electron; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Rats; Rats, Wistar; Tachycardia, Ventricular; Ventricular Fibrillation

The delayed effects of 7-oxo-prostacyclin, protecting the heart against extrasystoles, ventricular fibrillation, and cardiac arrest induced by high doses of ouabain or in ischemia and postischemic reperfusion, have already been described; but little is known about the molecular mechanisms involved. In this study, 50 micrograms.kg-1 7-oxo-prostacyclin administered intramuscularly significantly stimulated the activity of (Na+K+)-ATPase in rat heart sarcolemma 24 and 48 hours after application (p less than 0.01 and p less than 0.001, respectively). Kinetic analysis revealed a mixed type of stimulation of ATPase activity, with increased Vmax and decreased Km values. Cycloheximide (1 mg.kg-1) applied together with 7-oxo-prostacyclin, significantly antagonized the stimulatory effect of 7-oxo-prostacyclin, and had a modulatory effect on the kinetics of the (Na+K+)-ATPase both 24 and 48 hours after administration. The results show that protein synthesis is involved in the mechanism of the increase in enzyme activity.

Topics: Animals; Arrhythmias, Cardiac; Epoprostenol; Male; Myocardial Reperfusion Injury; Myocardium; Premedication; Rats; Rats, Inbred Strains; Sarcolemma; Sodium-Potassium-Exchanging ATPase; Time Factors

Cardioprotective drugs are agents that prevent or moderate harmful consequences of impaired cardiac energetics, such as sudden coronary death (SCD) due to early post-occlusion ventricular fibrillation (EPVF), development of incapacitating myocardial necrosis. Cardioprotection may be due to anti-ischaemic action, correcting the imbalance between vascular supply and myocardial demand for blood, but also to cytoprotective effect, preserving cellular integrity in the presence of factors damaging structure and function of the cardiac cell membrane such as ischaemia, ionic imbalance and that of pH, etc. Neither anti-ischaemic nor cytoprotective effect alone, or in combination, are sufficient to warrant full cardioprotection, i.e. both prevention of SCD and limitation of infarct size. Thus the beta-blocker pindolol which is anti-ischaemic in its effect reducing myocardial O2 demand and protects from SCD and EVFP, failed to limit infarct size. Even interventions of a mainly cytoprotective type of action protecting from SCD and EPVF, such as the linoleic acid-rich diet, or lidocaine, were unable to limit infarct size, 7-oxoPGI2 (anti-ischaemic and cytoprotective) failed to protect from SCD, VF and did not limit infarct size. On the other hand the nonsteroidal anti-inflammatory drugs which, like salicylates or sulfinpyrazon, reduce myocardial O2 demand and protect from post-occlusion SCD and EPVF, effectively limiting infarct size.

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Death, Sudden; Dietary Fats; Epoprostenol; Humans; Lidocaine; Linoleic Acid; Linoleic Acids; Myocardial Infarction; Pindolol