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

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.

Fig 1

Protocol schematic demonstrating when cooling was initiated in each group. Initial temperature was recorded rectally at the induction of anesthesia. Baseline and all other temperatures were recorded in the left atrium after the chest was opened. (— = normothermia; … = hypothermia; C = cooling.)

Fig 2

Time course of the core temperature change for each experimental group. Initial temperature was recorded rectally at the induction of anesthesia. Baseline and all other temperatures were recorded in the left atrium after the chest was opened. (— ●— = W-W-W; —○— = C-C-C; —▼— = W-C0-C; — ▽— = W-C15-C; — ■— = W-C25-C; —□— = W-W-C.)

Fig 3

(A) Area at risk as a percentage of the left ventricular (LV) mass for all experimental groups (mean ± SEM). (B) Infarct size as a percentage of the area at risk (AR) for all experimental groups (mean ± SEM). (^ap < 0.05 vs W-W-W; ^bp < 0.05 vs W-W-C.)

Fig 4

Plot of the correlation between left atrial (LA) temperature and infarct size during ischemia and reperfusion. Temperature during late ischemia and early reperfusion correlate most strongly with infarct size. (AR = area at risk; I = infarct.)

Fig 5

Plot of infarct size versus temperature at the time of reperfusion for all animals in all groups. (AR = area at risk.)