Modulation of mitochondrial bioenergetics in the isolated Guinea pig beating heart by potassium and lidocaine cardioplegia: implications for cardioprotection.
Mitochondria are damaged by cardiac ischemia/reperfusion (I/R) injury but can contribute to cardioprotection. We tested if hyperkalemic cardioplegia (CP) and lidocaine (LID) differently modulate mitochondrial (m) bioenergetics and protect hearts against I/R injury. Guinea pig hearts (n = 71) were perfused with Krebs Ringer's solution before perfusion for 1 minute just before ischemia with either CP (16 mM K) or LID (1 mM) or Krebs Ringer's (control, 4 mM K). The 1-minute perfusion period assured treatment during ischemia but not on reperfusion. Cardiac function, NADH, FAD, m[Ca], and superoxide (reactive oxygen species) were assessed at baseline, during the 1-minute perfusion, and continuously during I/R. During the brief perfusion before ischemia, CP and LID decreased reactive oxygen species and increased NADH without changing m[Ca]. Additionally, CP decreased FAD. During ischemia, NADH was higher and reactive oxygen species was lower after CP and LID, whereas m[Ca] was lower only after LID. On reperfusion, NADH and FAD were more normalized, and m[Ca] and reactive oxygen species remained lower after CP and LID. Better functional recovery and smaller infarct size after CP and LID were accompanied by better mitochondrial function. These results suggest that mitochondria may be implicated, directly or indirectly, in protection by CP and LID against I/R injury.
Aldakkak
Mohammed
M
Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Stowe
David F
DF
Lesnefsky
Edward J
EJ
Heisner
James S
JS
Chen
Qun
Q
Camara
Amadou K S
AK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006168:Guinea Pigs; D006324:Heart Arrest, Induced; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species; D008012:Lidocaine; D011188:Potassium; D010100:Oxygen; D002118:Calcium