Effect of mild hypothermia on ischemia-induced release of endothelin-1 in dog brain.

Endothelin-1 (ET-1) plays an important role in the physiologic or pathophysiologic regulation of cerebral circulation. To evaluate the effect of mild hypothermia on the cerebral concentration of ET-1 and on the cerebral metabolism of oxygen after complete global cerebral ischemia, we occluded the ascending aorta and caval veins of 9 dogs for 15 min. A fiberoptic catheter was inserted into the sagittal sinus to monitor venous oxygen saturation (S(SO)2) continuously. Blood samples were collected 30 min before and 30 min, 1 h, 2 h, 4 h and 6 h after the ischemic insult. Concentrations of ET-1 were assayed in the blood of the sagittal sinus and abdominal aorta. Before, during and after the aortic occlusion, we compared findings in a normothermic control Group 1 (pulmonary artery temperature 38.5 degrees C) (n = 4) with those in the mildly hypothermic Group 2 (pulmonary artery temperature 34.0 degrees C) (n = 5) by surface cooling induced before and maintained during and after ischemia for 6 h. Following ischemia, the plasma concentration difference of ET-1 (sagittal sinus--arterial) was significantly decreased in Group 2 (P < 0.05). Differences in S(SO)2 between the two groups were not statistically significant. Mild hypothermia reduced the ET-1 release in the cerebral circulation but did not improve cerebral oxygen metabolism after complete cerebral ischemia. Findings indicated that the decrease in ET-1 induced by mild hypothermia contributes to the improvement of the cerebral microcirculation after ischemia.