Effect of Preischemia Cyclooxygenase Inhibition by Zomepirac Sodium on Reflow, Cerebral Autoregulation, and EEG Recovery in the Cat after Global Ischemia

Abstract

Zomepirac sodium (ZS) (5 mg/kg i.v.) was used to evaluate the effects of preischemia cyclooxygenase inhibition on CBF (as assessed by 133Xe clearance), CBF–PaCO2 responsiveness, and electrophysiologic (EEG) parameters before and after a 15-min period of complete global ischemia produced by four-vessel occlusion and mild hypotension. During the 15-min period of ischemia, CBF was essentially zero. Following reflow all groups displayed an initial hyperemia as compared with control (92 ± 11 vs. 141–146 ml/100 g/min). Saline-treated animals during reflow displayed a delayed hypoperfusion (26 ± 3 ml/100 g/min), which showed no improvement during the 2-h reflow period prior to death. In contrast, ZS-treated animals during reflow displayed significantly higher flows during the hypoperfusion phase (72 ± 9 ml/100 g/min). The CBF–PaCO2 response displayed an approximately sevenfold reduction in slope at 2 h after reflow in saline-treated animals. This decrease in PaCO2 reactivity was not observed in the ZS-pretreated animals. With regard to EEG, all animals showed a total flattening during the 15 min of ischemia. In saline-treated animals only one of seven showed any sign of even marginal recovery. In ZS-treated animals EEG activity showed prominent recovery in seven of seven. Brainstem auditory evoked potentials were monitored and showed prominent recovery of amplitude and latency in ZS but not saline-treated animals during reflow.

Regulation of cerebral blood flow after asphyxia in neonatal lambs.

“…These include impaired vasodilation caused by obstruction of resistance vessels by cerebral edema, excessive production of cerebral vasoconstrictors such as thromboxanes 22 -23 and leukotrienes, 24 or vascular endothelial injury secondary to oxygen free radical production during reperfusion. 23 The generation of cerebral edema would explain both the previously described postasphyxia cerebral hypoperfusion 4 28 who demonstrated an attenuated response of CBF to the vasodilating effects of hypoxia in the presence of cerebral edema. However, my data in newborn lambs did not demonstrate evidence to support gross cerebral edema playing a role.…”