Ann Thorac Surg 2005;80:1416
© 2005 The Society of Thoracic Surgeons
Original article: Cardiovascular
Invited commentary
Robert M. Mentzer, Jr, MD
Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, MN264, Lexington, KY40536-0298
(Email: mentzer{at}email.uky.edu).
The authors [1] have nicely demonstrated that a multiple treatment approach that targets various mechanisms underlying ischemia-reperfusion injury can effectively reduce infarct size and post-ischemic myocardial dysfunction. They are to be commended for testing their hypothesis in an in vivo cardiopulmonary bypass porcine preparation that is clinically relevant to heart surgeons. This meticulously conducted study clearly demonstrates that in the preparation used, pretreatments with cariporide (a sodium-hydrogen exchange inhibitor) and diazoxide (a mitochondrial adenosine triphosphate (ATP)-sensitive potassium channel opener), along with controlled reperfusion are associated with a significant decrease in infarct size and an increase in systolic function at the end of 2 hours of reperfusion. However, the findings that relate to the diazoxide substudy should be interpreted with caution. Although the agent has been studied extensively in vitro, very little is known about its cardioprotective effect in vivo. Likewise, it is arguable as to how selective the agent is for mitochondrial ATP-sensitive channels. For example, it has been reported to activate the sarcolemmal channel at high concentrations or when adenosine diphosphate levels are increased [2]. It is also well known that diazoxide inhibits succinate-supported mitochondrial respiration.
However, the significance of this study cannot be overstated as it does address an important area of research, namely the phenomenon of ischemia-reperfusion injury and myocardial protection. Three recently completed, large, randomized clinical trials have demonstrated that the incidence of any myocardial infarction (MI) (Q-wave MI or non-Q-wave MI) after coronary artery bypass graft (CABG) surgery ranges between 12% and 19%. In these studies, postoperative CABG surgery MI was identified as occurring in those patients in whom creatine kinase (CK)-MB release exceeded 10 x upper limits of normal (ULN) or when CK-MB release exceeded 5 x ULN and a new Q-wave occurred. In addition to the compelling evidence that myocardial necrosis after CABG surgery occurs more often than has been previously appreciated, large elevations as defined by CK-MB > 10 x ULN are an independent predictor of death during follow-up beyond 6 months. Thus, this is an important and timely pre-clinical study that demonstrates proof of principle. Studies such as this one could lead to new therapeutic cardioprotective strategies and, ultimately, result in a reduction in short-term myocardial injury and the improvement of long-term survival after heart surgery.
 |
References
|
|---|
- Davies JE, Digerness SB, Killingsworth CR, et al. Multiple treatment approach to limit cardiac ischemia-reperfusion injury Ann Thorac Surg 2005;80:1408-1416.[Abstract/Free Full Text]
- O'Rourke B. Evidence for mitochondrial K+ channels and their role in cardioprotection Circ Res 2004;94:420-432.[Abstract/Free Full Text]
Top
References