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Original Articles: Adult Cardiac

Very Mild Hypothermia During Ischemia and Reperfusion Improves Postinfarction Ventricular Remodeling

^a Harrison Department of Surgical Research, Glenolden Research Laboratory, Glenolden, Pennsylvania
^b Department of Medicine, University of Pennsylvania, Glenolden, Pennsylvania
^c Department of Cardiovascular Surgery, Faculty of Medicine, Oita University, Oita, Japan

Accepted for publication August 6, 2008.

^_* Address correspondence to Dr Robert C. Gorman, Gorman Cardiovascular Research Group, Glenolden Research Laboratory, University of Pennsylvania, 500 S. Ridgeway Avenue, Glenolden, PA 19036 (Email: gormanr{at}uphs.upenn.edu).

Background: Mild hypothermia (< 4°C) improves myocardial salvage after infarct reperfusion in animals and in early clinical studies. In this experiment the effect of mild hypothermia during ischemia and early reperfusion on long-term postinfarction left ventricular (LV) remodeling was assessed in an ovine infarct model.

Methods: In the initial phase of the experiment the effect of progressive degrees of hypothermia on infarct size was quantified. Thirty-eight male sheep were subjected to 1 hour of ischemia using a standardized anteroapical infarct followed by 3 hours of reperfusion. Temperature was maintained at either 39.5°C (n = 11), 38.5°C (n = 7), 37.5°C (n = 7), 36.5°C (n = 7), or 35.5°C (n = 6) for the entire period of ischemia and reperfusion. The area at risk (AR) and infarct size as a percentage of AR (I/AR) were determined with a double staining and planimetry technique. In the second phase of the study, chronic post-infarction remodeling was assessed in animals with nonreperfused infarcts (n = 6), 1 hour of ischemia followed by reperfusion at 39.5°C (n = 6) and 1 hour of ischemia followed by reperfusion at 37.5°C (n = 6). Remodeling was determined at 8 weeks after infarction using echocardiography.

Results: The I/AR in the 39.5°C, 38.5°C, 37.5°C, 36.5°C, and the 35.5°C groups was 71.8 ± 3.0%, 63.1 ± 1.9%, 49.4 ± 1.4%, 38.7 ± 1.4%, and 21.7 ± 2.2%, respectively (p < 0.05 between all groups). In the chronic study LV end systolic volume at 8 weeks after infarction was 81 ± 8 mL in the nonreperfused group, 57 ± 4 mL in the 39.5°C reperfusion group, and 41 ± 3 mL in the 37.5°C reperfusion group (p < 0.05 for between group differences).

Conclusions: Subtle degrees of hypothermia can significantly improve immediate myocardial salvage and long-term LV remodeling after infarct reperfusion.

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