Diazoxide protects the rabbit heart following cardioplegic ischemia.
K(ATP) channels are present in sarcolemmal and mitochondrial membranes. This study tests the hypothesis that opening mitochondrial K(ATP) channels with Diazoxide (DZ) improves tolerance to cardioplegic ischemia during surgery. Twenty-two rabbit hearts were perfused with Krebs-Henseleit buffer (KHB) on a Langendorff apparatus and underwent 50 min of 37 degrees C global ischemia with St Thomas' cardioplegia (STCP). Hearts were divided into three groups. Ten (control) received no pretreatment. Seven (DZ) received 10 min of 30 microM DZ, a selective mitochondrial K(ATP) opener, in KHB before arrest with STCP containing 30 microM DZ. Five (5-HD + DZ) received 10 min of 100 microM sodium 5-hydroxydecanoate (5-HD), a selective mitochondrial K(ATP) channel blocker, followed by 10 min of 30 microM DZ and 100 microM 5-HD in KHB before arrest with STCP + 30 microM DZ + 100 microM 5-HD. LV developed pressure (LVDP), dP/dt and coronary flow (CF) were measured after 60 min of reperfusion. Diazoxide pretreatment significantly improved the recovery of LV function and coronary flow compared to control (LVDP: 49 +/- 5* vs. 31 +/- 4; +dP/dtmax 927 +/- 93 vs. 507 +/- 85 mmHg/sec*; CF 33 +/- 4 vs. 22 +/- 2 ml/min, *p < 0.05). Mitochondria K(ATP) channel blockade with 5-HD prevented DZ's salutary effect on the recovery of LV and vascular function. Diazoxide pretreatment protects the rabbit heart during cardioplegic ischemia by opening mitochondrial K(ATP) channels. Opening mitochondrial K(ATP) channels may be a new strategy for improving myocardial protection during cardiac surgery.
Feng
Jun
J
Department of Surgery, University of Miami, FL, USA.
Li
Hongling
H
Rosenkranz
Eliot R
ER
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D003971:Diastole / Q000502:physiology; D003981:Diazoxide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006880:Hydroxy Acids / Q000494:pharmacology; D019194:Ischemic Preconditioning; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D015221:Potassium Channels; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left
D000889:Anti-Arrhythmia Agents; D002314:Cardioplegic Solutions; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008565:Membrane Proteins; D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D003981:Diazoxide