Pacing-induced dys-synchrony preconditions rabbit myocardium against ischemia/reperfusion injury

Circulation. 2006 Jul 4;114(1 Suppl):I264-9. doi: 10.1161/CIRCULATIONAHA.105.000893.


Background: Because increased mechanical load induces preconditioning (PC) and dys-synchrony increases loading in late-activated regions, we investigated whether dys-synchrony induced by ventricular pacing (VP) at normal heart rate leads to cardioprotection.

Methods and results: Isolated working rabbit hearts were subjected to 35 minutes of global ischemia and 2 hours of reperfusion. Seven hearts underwent VP PC (3 periods of 5 minutes VP at the posterior left ventricular [LV] wall), 7 hearts underwent ischemic preconditioning (IPC) (3 periods of 5 minutes of global ischemia), and 9 hearts served as control (C). LV pressure and sonomicrometry were used to assess global hemodynamics and segment work (SW) and end-diastolic segment length (EDSL) in anterior and posterior LV myocardium. Myocardial release of lactate and expression of proBNP mRNA were determined to gain insight in molecular processes involved in VP PC (*P<0.05). Infarct size (triphenyl tetrazolium chloride staining) was 18.3+/-13.0% in group C, and was uniformly reduced in the VP PC and IPC groups (1.8+/-0.8%*, and 3.5+/-3.1%*, respectively; and not significant between VP PC and IPC). LV posterior wall pacing (VP PC group) increased EDSL (by 6.3+/-5.8%*) and SW (to 335+/-207%*) in the LV anterior wall, whereas posterior wall SW decreased to negative values (-23+/-63%*). LV pacing did not significantly change lactate release and coronary flow but significantly increased proBNP mRNA expression in both anterior and posterior myocardium as compared with controls.

Conclusions: Intermittent dys-synchrony is equally cardioprotective as "classical" IPC. Stretch-mediated signaling is a more likely trigger for VP PC than ischemia. VP PC is potentially applicable in cardiac surgery.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiac Output
  • Cardiac Pacing, Artificial / methods*
  • Coronary Circulation
  • Female
  • Gene Expression Profiling
  • Heart Rate
  • Heart Ventricles / physiopathology
  • Hemodynamics
  • In Vitro Techniques
  • Ischemic Preconditioning, Myocardial / methods*
  • Lactates / analysis
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / prevention & control*
  • Natriuretic Peptide, Brain / biosynthesis
  • Natriuretic Peptide, Brain / genetics
  • Pressure
  • Protein Precursors / biosynthesis
  • Protein Precursors / genetics
  • RNA, Messenger / biosynthesis
  • Rabbits
  • Stress, Mechanical


  • Lactates
  • Protein Precursors
  • RNA, Messenger
  • Natriuretic Peptide, Brain