Reperfusion-induced arrhythmias: mechanisms of protection by glucose and mannitol.
Isolated rat hearts (n = 15/group) were subjected to regional ischemia (10 min) and reperfusion (3 min). Mannitol (5, 11, 25, 50, 55, 61, or 75 mM included in the perfusate throughout) reduced reperfusion-induced sustained ventricular fibrillation (VF) from its control incidence of 93% (14/15) to 80, 80, 40, 27, 47, 80, and 80%, respectively. Addition of glucose (11 mM) potentiated this effect, VF now fell to 87, 47, 33, 7, 7, 7, 13, and 13%, respectively. However, 11 mM glucose alone exerted no antiarrhythmic effects. When hearts (n = 15/group) were perfused with identical osmotic loads of mannitol plus glucose (11 + 50, 50 + 11, 61 + 0, or 0 + 61 mM, respectively), very different antiarrhythmic effects were observed. When given throughout the experimental period, glucose alone (0, 11, 25, 50 or 61 mM) had no effect on the incidence of VF (93, 87, 47, 53, and 20%, respectively), but when glucose was added 2 min before reperfusion, improved protection was observed (VF: 93, 87, 40, 27, and 13%, respectively). Our results suggest that the osmotic and free-radical scavenging properties of hexoses are relatively unimportant in relation to their antiarrhythmic effects. The metabolic effects are complex, suggesting that low concentrations of glucose may be beneficial, whereas high concentrations may be detrimental.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D005947:Glucose / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D009995:Osmosis; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D005609:Free Radicals; D008353:Mannitol; D005947:Glucose