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(Circulation. 1996;93:178-186.)
© 1996 American Heart Association, Inc.

Articles

Rapid Ventricular Pacing Produces Myocardial Protection by Nonischemic Activation of K_ATP⁺ Channels

Monique M.G. Koning, MD; Ben C.G. Gho, MD; Erik van Klaarwater, BS; René L.J. Opstal, BS; Dirk J. Duncker, MD, PhD; Pieter D. Verdouw, PhD

From the Laboratory for Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, Rotterdam, the Netherlands.

Correspondence to Pieter D. Verdouw, PhD, Laboratory for Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, the Netherlands. E-mail Verdouw@tch.fgg.eur.nl.

Background Rapid ventricular pacing reduces the incidence of ventricular arrhythmias during a subsequent sustained period of ischemia and reperfusion. We investigated whether rapid ventricular pacing also limits myocardial infarction and determined the role of K_ATP⁺ channels in the protection afforded by ventricular pacing.

Methods and Results Myocardial infarction was produced by a 60-minute coronary artery occlusion in open chest pigs. Infarct size of pigs subjected to 10 minutes of ventricular pacing at 200 beats per minute followed by 15 minutes of normal sinus rhythm before the occlusion (79±3% of the area at risk, mean±SEM) was not different from control infarct size (84±2%). Thirty-minute pacing followed by 15-minute sinus rhythm resulted in modest reductions in infarct size (71±2%, P<.05 versus control). Thirty minutes of pacing immediately preceding the occlusion without intervening sinus rhythm resulted in considerable limitation of infarct size (63±4%, P<.05), which was abolished by pretreatment with the K_ATP⁺ channel blocker glibenclamide (78±4%, P=NS). K_ATP⁺ channel activation did not appear to involve ischemia: (1) myocardial endocardial/epicardial blood flow ratio was 1.07±0.08, (2) phosphocreatine and ATP levels and arterial-coronary venous differences in pH and PCO₂ were unchanged, (3) end-systolic segment length did not increase and postsystolic shortening was not observed during pacing, and (4) systolic shortening recovered immediately to baseline levels and coronary reactive hyperemia was absent after cessation of pacing. Administration of glibenclamide after 30 minutes of pacing at the onset of 15 minutes of normal sinus rhythm did not attenuate the protection (73±3%, P<.05 versus control), suggesting that K_ATP⁺ channels did not contribute to the moderate degree of protection that was still present 15 minutes after cessation of pacing.

Conclusions Rapid ventricular pacing protects the myocardium against infarction via nonischemic K_ATP⁺ channel activation. Continued activation of K_ATP⁺ channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.

Key Words: blood flow • tachycardia • myocardial infarction

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