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Rapid ventricular pacing produces myocardial protection by nonischemic activation of KATP+ channels
M M Koning1, B C Gho, E van Klaarwater
1Laboratory for Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Insights
Rapid ventricular pacing protects the heart from infarction by activating KATP+ channels. This protective effect occurs without causing ischemia and persists even after pacing stops.
Area of Science:
- Cardiology
- Cardiovascular Physiology
- Myocardial Protection
Background:
- Rapid ventricular pacing is known to reduce ventricular arrhythmias during ischemia and reperfusion.
- The potential of rapid ventricular pacing to limit myocardial infarction was investigated.
Purpose of the Study:
- To determine if rapid ventricular pacing limits myocardial infarction.
- To elucidate the role of KATP+ channels in the cardioprotective effects of ventricular pacing.
Main Methods:
- Myocardial infarction was induced by coronary artery occlusion in pigs.
- Different durations of rapid ventricular pacing were applied before occlusion, with and without intervening normal sinus rhythm.
- The effect of KATP+ channel blockade (glibenclamide) on infarct size was assessed.
Main Results:
- Thirty minutes of pacing immediately before occlusion significantly reduced infarct size.
- This protection was abolished by glibenclamide, indicating KATP+ channel involvement.
- Evidence suggested KATP+ channel activation was nonischemic.
Conclusions:
- Rapid ventricular pacing confers myocardial protection against infarction through nonischemic KATP+ channel activation.
- Sustained KATP+ channel activation is not required for the observed protection 15 minutes post-pacing.
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 KATP+ 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 KATP+ channel blocker glibenclamide (78 +/- 4%, P=NS). KATP+ 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 the KATP+ 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 KATP+ channel activation. Continued activation of KATP+ channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.