Temporal thresholds for infarction and hypothermic protection in Long-Evans rats: factors affecting apparent 'reperfusion injury' after transient focal ischemia.

Abstract

BACKGROUND AND PURPOSE: Some previous studies in Long-Evans rats noted larger infarcts after transient middle cerebral artery (MCA) occlusions than after permanent occlusions, interpreted to demonstrate "reperfusion injury." Recent experiments failed to reproduce this phenomenon, prompting an investigation of the sources of variability in this animal model. METHODS: Male Long-Evans rats were subjected to surgical occlusion of the right MCA and ipsilateral common carotid artery. Variables tested included duration of occlusion and halothane anesthesia exposure and targeting of proximal or distal MCA occlusion sites. The temporal window for hypothermic protection was also investigated. RESULTS: MCA occlusions at the level of the rhinal fissure produced graded increases in infarct volume with ischemia duration, and lesion size did not differ between 3-hour and permanent occlusions independent of anesthesia duration. Occlusions at a more distal site produced infarcts of comparable size after transient 3-hour occlusions and after permanent occlusions accompanied by prolonged anesthesia, but significantly smaller infarcts were seen when permanent occlusions were followed by rapid anesthesia termination. Hypothermia conferred protection only when initiated before reperfusion after transient proximal occlusions. CONCLUSIONS: These results indicate that previously described "reperfusion injury" after transient MCA occlusions conversely reflects unexpected injury reduction when rats with permanent occlusions experience early anesthesia termination. More rapid blood pressure recovery under such conditions permits improved collateral perfusion. The absence of a detectable postischemic window for hypothermic protection further argues against a significant component of delayed postreperfusion injury in this model.