Cold cardioplegia and the K+ channel modulator aprikalim (RP 52891): improved cardioprotection in isolated ischemic rabbit hearts.
Cellular potassium extrusion is now considered a natural protective mechanism following myocardial ischemia, and newly synthetized molecules mimicking cellular extrusion of K+ (potassium channel activators) appear promising for cardioprotection, although the underlying mechanisms for their beneficial effects have not been fully characterized. Indeed, the cardioprotective efficacy of K+ channel activators at low temperature or in the presence of the high K+ content of standard cardioplegic solution has never been addressed. Therefore the cardioprotective interaction of the thioformamide K+ channel activator aprikalim (RP 52891) and high K+ content, cold cardioplegia was studied in isolated ischemic rabbit hearts. Isolated hearts were perfused according to the Langendorff procedure at a constant pressure (85 cmH2O; 1 cmH2O = 98.1 Pa); systolic and diastolic left ventricular pressures, coronary flow, and heart rate were monitored throughout the study. Cardiac temperature was monitored through a thermocouple microprobe positioned in the left ventricular free wall. Global ischemia was carried out by completely shutting off the perfusate flow for 90 min, and reperfusion was monitored for 30 min. Several groups of isolated hearts (n = 6 per group) were treated before ischemia with either cold cardioplegia (St-Thomas' Hospital cardioplegic solution, 4 degrees C), aprikalim (10 microM), or glibenclamide (1 microM) alone, or with one of the following combinations: cold cardioplegia + aprikalim, cold cardioplegia + glibenclamide, or cold cardioplegia + both aprikalim and glibenclamide. A 10 microM infusion of aprikalim significantly increased coronary flow (33 to 63 mL/min, +90%) without negative chronotropic or inotropic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Pignac
J
J
Département de pharmacologie, Faculté de médecine, Université de Montréal, PQ, Canada.
Bourgouin
J
J
Dumont
L
L
D000818:Animals; D002314:Cardioplegic Solutions; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006324:Heart Arrest, Induced / Q000379:methods*; D066298:In Vitro Techniques; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D002314:Cardioplegic Solutions; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; C061043:aprikalim; D005905:Glyburide