EFFECTS OF ISCHEMIA ON CEREBRAL ARTERIOLAR DILATION TO ARTERIAL HYPOXIA IN PIGLETS

Background and Purpose-Arterial hypoxia mediates cerebral arteriolar d ilation primarily via mechanisms involving activation of ATP-sensitive K+ channels (K-ATP) which we have shown to be sensitive to ischemic s tress. In this study, we determined whether ischemia/reperfusion alter s cerebral arteriolar responses to arterial hypoxia in anesthetized pi glets. Since adenosine plays an important role in cerebrovascular resp onses to hypoxia, we also determined whether adenosine-induced arterio lar dilation is affected by ischemic stress. We tested the hypothesis that reductions in cerebral arteriolar dilator responses after ischemi a would be proportional to the contribution of K-ATP to hypoxia and ad enosine. Methods-Pial arteriolar diameters were measured using a crani al window and intravital microscopy. We examined arteriolar responses to arterial hypoxia (inhalation of 8.5% and 7.5% O-2), to topical aden osine (10(-5) and 10(-4) mol/L) and to arterial hypercapnia (inhalatio n of 5% and 10% CO2 in air) before and after 10 minutes of global isch emia. Ischemia was achieved by increasing intracranial pressure. Arter ial hypercapnia was used as a positive control for the effectiveness o f the ischemic insult. In addition, we evaluated cerebral arteriolar r esponses to 10(-5) and 10(-4) mol/L adenosine applied topically with o r without glibenclamide, a selective inhibitor of K-ATP (10(-5) and 10 (-6) mol/L). Finally, we administered theophylline (20 mg/kg, IV) to a ssess the contribution of adenosine to cerebral arteriolar dilation to arterial hypoxia. Results-Before ischemia, cerebral arterioles dilate d by 19+/-3% to moderate and 29+/-4% to severe hypoxia (n=7; P<.05); 1 3+/-2% to 10(-5) and 20+/-1% to 10(-4) mol/L adenosine (n=9; P<.05); a nd by 17+/-2% to moderate and 28+/-3% to severe hypercapnia (n=6; P<.0 5). After ischemia, cerebral arteriolar responses to hypoxia and adeno sine were unchanged. In contrast, cerebral arteriolar dilation to hype rcapnia was impaired by ischemia (1+/-1% and 2+/-1% at 1 hour; n=6), G libenclamide reduced cerebral arteriolar dilation to adenosine by appr oximately one half (n=7). In addition, blockade of adenosine receptors by theophylline (20 mg/kg, IV) almost totally suppressed cerebral art eriolar dilation to arterial hypoxia (n=6). Conclusions-Cerebrovascula r responsiveness is selectively affected by anoxic stress. In addition , cerebral arteriolar dilation to hypoxia and adenosine is maintained after ischemia despite the expected impairment in K-ATP function.