Effect of hypoglycemia on postischemic cortical blood flow, hypercapnic reactivity, and interstitial adenosine concentration.
Hypoglycemia increases the vulnerability of the perinatal brain to asphyxia, but it is not known if hypoglycemia-induced changes in cerebral hemodynamics and vascular reactivity underlie this vulnerability. This study tested the hypothesis that hypoglycemia exacerbates postischemic hypoperfusion, and impairs postischemic CO2 reactivity. The authors also examined the hypothesis that postischemic hypoperfusion is associated with a reduction in the interstitial concentration of the vasodilator metabolite adenosine. Global cerebral ischemia of 10 minutes duration was induced in newborn pigs anesthetized with isoflurane by occlusion of subclavian and brachiocephalic arteries; cortical cerebral blood flow (CBF) and interstitial adenosine concentration were evaluated simultaneously using the combined hydrogen clearance/microdialysis technique. Hypoglycemia (blood glucose < 25 mg/dl) was induced by regular insulin (25 IU/kg) administered intravenously 2 hours prior to induction of ischemia. In the eight normoglycemic animals, baseline CBF was 38 +/- 4 ml/min/100 gm and baseline adenosine concentration was 1.2 +/- 0.1 microM; in the eight hypoglycemic animals, these values were 39% (p < 0.05) and 62% (p < 0.05) greater, respectively, under baseline conditions. At 1 hour of postischemic reperfusion in normoglycemic animals, CBF was reduced 39% relative to the preischemic baseline (p < 0.01), concomitant with a 27% reduction (p < 0.05) in adenosine concentration, suggesting that this lowered concentration may underlie delayed hypoperfusion. These postischemic reductions in CBF and interstitial adenosine concentration were significantly greater in hypoglycemic animals, with CBF and adenosine concentration reduced 70% (p < 0.001) and 71% (p < 0.01), respectively, relative to baseline. In nine animals preischemic reactivity to hypercapnia was unaffected by hypoglycemia. Postischemic hypercapnic reactivity was retained in the eight normoglycemic animals, but was attenuated 73% (p < 0.05) in hypoglycemic animals. Thus, in the newborn pig, hypoglycemia exacerbates postischemic cortical hypoperfusion and impairs postischemic cerebrovascular reactivity to hypercapnia.
Kim
Y B
YB
Department of Neurosurgery, St. Louis Children's Hospital, Washington University School of Medicine, Missouri.
Gidday
J M
JM
Gonzales
E R
ER
Shah
A R
AR
Park
T S
TS
D000241:Adenosine / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000502:physiology; D002545:Brain Ischemia / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000097:blood; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D006935:Hypercapnia / Q000097:blood / Q000503:physiopathology*; D007003:Hypoglycemia / Q000503:physiopathology*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000032:analysis / Q000378:metabolism; D007288:Inosine / Q000032:analysis / Q000378:metabolism; D013552:Swine; D019820:Xanthine; D014970:Xanthines / Q000032:analysis / Q000378:metabolism
D007042:Hypoxanthines; D014970:Xanthines; D002245:Carbon Dioxide; D019820:Xanthine; D019271:Hypoxanthine; D007288:Inosine; D000241:Adenosine