Pinacidil pretreatment extends ischemia tolerance of neonatal rabbit hearts.
OBJECTIVE
Activating ATP-sensitive potassium (K(ATP)) channels improves ischemia tolerance of adult rabbit hearts. We hypothesize that (a) endogenous activation of the K(ATP) channel accounts for better ischemia tolerance of neonatal hearts and (b) exogenous K(ATP) channel activation with pinacidil further improves the neonatal heart's tolerance to cardioplegic ischemia.


METHODS
Study 1: Seven (control) neonatal rabbits received intraperitoneal saline, whereas five others (Glib) received 0.3 mg/kg glibenclamide 10 min before sacrifice. They were perfused on Langendorff with Krebs-Henseleit buffer (KHB). Baseline left ventricle (LV) performance and coronary flow (CF) were measured. After 20 min of 37 degrees C ischemia and 10 min of reperfusion, recovery was measured. Study 2: Ten (control) neonatal hearts underwent 90 min of normothermic ischemia with St. Thomas' cardioplegia (STCP) solution administered every 30 min. Ten others were pretreated with a 10-min infusion of 1 microM pinacidil in KHB and received 1 microM pinacidil-enriched STCP. Recovery of LV performance and CF were measured after 60 min of reperfusion.


RESULTS
Study 1: Glib significantly reduced preischemia LV performance by 28%* compared to control hearts. Recovery of Glib-treated hearts was significantly less (67%*) than controls (81%*). Study 2: Pinacidil-treated hearts had significantly better recovery of LV performance (39%*) and CF (78%*) compared to 23 and 52%, respectively, in untreated controls (*P < 0.05 vs control hearts).


CONCLUSIONS
Endogenous K(ATP) channel activation in neonatal hearts contributes to their better tolerance to ischemia. Exogenous K(ATP) channel activation by pinacidil pretreatment and cardioplegic enrichment significantly improved the neonatal rabbit heart's tolerance to cardioplegic ischemia. This may be an important addition to myocardial protection during pediatric cardiac surgery.
Feng
J
J
Division of Cardiothoracic Surgery, Children's Hospital of Buffalo, Buffalo, New York 14222, USA.
Li
H
H
Rosenkranz
E R
ER
D000818:Animals; D000831:Animals, Newborn; D002314:Cardioplegic Solutions / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003971:Diastole / Q000502:physiology; D006324:Heart Arrest, Induced; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left
D002314:Cardioplegic Solutions; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil