Mild hypothermia to limit myocardial ischemia-reperfusion injury: importance of timing

Ann Thorac Surg. 2009 Jan;87(1):157-63. doi: 10.1016/j.athoracsur.2008.08.012.

Abstract

Background: Hypothermia during ischemia has been shown to reduce myocardial reperfusion injury. We sought to establish the cardioprotective effect of very mild total-body hypothermia (<or= 2.5 degrees C) and to determine whether the application of hypothermia at different points during the ischemia-reperfusion period influenced the degree of myocardial salvage.

Methods: Rabbits were subjected to 30 minutes of myocardial ischemia followed by 3 hours of reperfusion. Twenty-five animals were maintained at normal temperature (39.5 degrees C) throughout the experiment (W-W-W group). All other animals were cooled to reduce left atrial temperature 2.0 degrees C to 2.5 degrees C. Eleven animals reached goal temperature before coronary occlusion (C-C-C group), in 14 animals cooling was initiated at coronary occlusion (W-C0-C group), in 8 animals cooling was initiated 15 minutes after coronary occlusion (W-C15-C group), in 5 animals cooling was initiated 25 minutes after coronary occlusion (W-C25-C group), and in 13 animals cooling was started concurrently with reperfusion (W-W-C group). Infarct size as a percentage of the risk area (I/AR) was determined by a double staining-planimetry technique.

Results: Goal temperature was achieved before reperfusion in the C-C-C and W-C0-C groups but was not achieved until the reperfusion period in the other treatment groups. Infarct size was 59.0 +/- 1.2% in the W-W-W group and was reduced in all cooling groups (C-C-C = 30.4 +/- 4.9%; W-C0-C = 33.4 +/- 5.0%; W-C15-C = 42.4 +/- 1.4%; W-C25-C = 44.1 +/- 2.3%; W-W-C = 50.5 +/- 4.1%). The temperature at reperfusion correlated most strongly with infarct size (r = 0.72, p < 1 x 10(-12)).

Conclusions: Very mild hypothermia affords a significant cardioprotective effect. Temperature at the time of reperfusion most strongly correlates with the degree of myocardial salvage.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Circulation / physiology
  • Disease Models, Animal
  • Hypothermia, Induced / methods*
  • Immunohistochemistry
  • Ischemic Preconditioning, Myocardial / methods
  • Myocardial Ischemia / prevention & control
  • Myocardial Ischemia / therapy*
  • Myocardial Reperfusion / methods
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Probability
  • Rabbits
  • Random Allocation
  • Reference Values
  • Sensitivity and Specificity
  • Time Factors