Halothane anesthetized Sprague-Dawley rats underwent 10 min of bilateral carotid artery occlusion with mean arterial pressure (MAP) held at 30, 50 or 60 mmHg. Sham rats did not undergo ischemia. A 7-day recovery interval was allowed. Intra-ischemic electroencephalographic (EEG) changes, behavioral function (Days 5-7), and histologic injury (Day 7) were evaluated. Under similar conditions, cerebral blood flow was determined after 10 min ischemia by the [3H]nicotine indicator fractionation technique. EEG isoelectricity was observed in 11 of 11.5 of 10, and 2 of 11 rats in the 30 mmHg, 50 mmHg, and 60 mmHg groups respectively. Neither passive avoidance cross-over latencies nor general motor scores were affected by intra-ischemic MAP and no differences from sham performance were observed. The per cent of CA1 neurons counted as dead (left and right hemispheres combined) was significantly affected by intra-ischemic MAP (72, 46 and 28% in the 30 mmHg, 50 mmHg, and 60 mmHg groups, respectively; P < 0.001. A greater than 50% CA1 neuronal mortality rate was present only in those rats exhibiting EEG isoelectricity. However, the number of rats demonstrating greater than a 25% interhemispheric difference in CA1 neuronal loss was greatest in the 50 mmHg group (P < 0.02). Hippocampal blood flow decreased in association with severity of hypotension 8±1.35±8, and 48 + ml/100g/min (mean ∓ S.E.M. for 30, 50, and 60 mmHg, respectively; P <0.01. Again, however, the greatest variability in blood flow was observed at MAP = 50 mmHg. These results indicate that reduction of MAP to 30 mmHg during bilateral carotid artery occlusion will yield the most consistent hemodynamic and electrophysiologic events corresponding to reduced inter- and intra-animal variability in histologic outcome in this model of near-complete forebrain ischemia.
Bibliographical noteFunding Information:
Acknowledgements. This work was supported by USPIIS Grants R20 GM39771 and ROI NS24517 and/tmerican tleart Association-Iowa Affiliate Grant IA-9\[IG37.
- Blood pressure
- Brain ischemia
- Cerebral blood flow
- Delayed neuronal necrosis