BRAIN INJURY IMPAIRS ATP-SENSITIVE K-ARTERIES( CHANNEL FUNCTION IN PIGLET CEREBRAL)

Background and Purpose Traumatic injury is the leading cause of death for infants and children, and mortality is increased with head injury. Previous studies have shown that pial arteries constricted and that r esponses to several nitric oxide (NO)-dependent dilator stimuli were b lunted after fluid percussion injury (FPI) in newborn pigs. Membrane p otential of vascular muscle is a major determinant of vascular tone, a nd activity of K+ channels is a major regulator of membrane potential. Recent data show that the NO releasers sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) and 8-bromo-cGMP elicit dilati on via ATP-sensitive K+ channel (K-ATP) activation. The present study was designed to investigate the effect of FPI on K-ATP channel functio n. Methods Chloralose-anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device that consisted o f a saline-filled cylindrical reservoir and a metal pendulum. Brain in jury of moderate severity (1.9 to 2.1 atm) was produced by allowing th e pendulum to strike a piston on the cylinder. Pial artery diameter wa s measured with a video microscaler. Data were analyzed by repeated me asures ANOVA. An alpha level of P<.05 was considered significant. Resu lts FPI blunted dilation to cromakalim (10(-8), 10(-6) mol/L), a K-ATP agonist (10+/-1% and 27+/-2% versus 3+/-1% and 7+/-2% before and afte r FPI, respectively, n=8). Similarly, FPI blunted dilation to calciton in gene-related peptide, an endogenous K-ATP activator. FPI also blunt ed dilator responses to SNP, S-nitroso-N-acetylpenicillamine, and 8-br omo-cGMP (10(-6) to 10(-8) mol/L) (10+/-1% and 20+/-1% versus 2+/-1% a nd 8+/-2% for SNP before and after FPI; 9+/-1% and 16+/-1% versus 2+/- 1% and 4+/-1% for 8-bromo-cGMP before and after FPI, respectively, n=8 ). In contrast, responses to papaverine and brain natriuretic peptide were unchanged after FPI. Conclusions These data show that K-ATP chann el function is impaired after FPI. Furthermore, these data suggest tha t impaired function of mechanisms distal to NO synthase contribute to altered cerebral hemodynamics after FPI.