Recent studies suggest that nitric oxide(NO) may be important in the pathogenesis of brain injury following cerebral ischemia. Despite a number of studies of the effect of inhibition of NO synthesis on focal normothermic cerebral ischemic damage in rodent models and the neurotoxic effect of NO observed in in vitro study, there is continuing controversy regarding the role of NO in cerebral ischemia and much less is known about the role of NO in global ischemia. Therefore, the effects of L-arginine, NO precursor and L-Nitro-Arginine Methyl Ester(L-NAME), NO synthase inhibitor on brain metabolic recovery have been studied in an infant piglet model of deep hypothermic circulatory arrest(DHCA). Forty 2-week old piglets underwent core cooling to 15oC nasopharyngeal temperature and 1 hour of DHCA at 15oC, 45 minutes of rewarming and 3 hours of normothermic reperfusion. Group L-arginine(n=10) received 30 mg/kg of L-arginine intravenously before cardiopulmonary bypass(CPB) and 10 mg/kg/min continuous intravenous infusion of L-arginine during the first 1 hour of reperfusion (Rep). Group L-NAME 10mg/kg(n=10) received 10 mg/kg of L-NAME intravenously before CPB. Group L-NAME+L-arginine(n=10) received both L-NAME and L-arginine in the same way. Group Control(n=10) received no medication. Recovery of cerebral high energy phosphates and pHi was assessed by magnetic resonance spectroscopy in half of the animals in each group. Cerebral blood flow(CBF) and cerebral vascular resistance(CVR) by microspheres, cerebral metabolic rate of oxygen(CMRO2), and the redox state of cytochrome a,a3 by near infrared spectroscopy were assessed in the rest. Brain water content was measured in all animals at the end of the experiment. Results are given as mean+SEM. *:p<0.05 vs. group Control by Student-Newman-Keuls test. min. Rep. Control L-arginine L-NAME L-NAME+L-arginine ATP 45 73.7+15.9 83.5+6.2 28.3+4.3* 45.9+5.4 (% recovery) 225 71.5+5.0 84.3+2.7* 32.0+2.6* 33.2+5.8* pHi 45 6.75+0.05 6.79+0.05 6.62+0.03 6.63+0.05 (Unit) 225 7.23+0.11 7.28+0.04 6.88+0.06* 6.95+0.13 Cytochrome a,a3 45 -7.0+1.1 -2.3+1.3* -11.2+1.2 -11.1+2.3 (~M x DPF) 225 0.4+0.8 1.0+1.4 -12.2+0.9* -10.5+3.8* Mean Arterial 45 45.2+4.1 44.2+3.7 80.0+9.6* 67.4+6.5 Blood Pressure(mmHg) 225 121+8 112+7 154+10* 146+11* CBF 45 17.3+2.3 32.6+5.9* 20.7+4.5 16.4+1.0 (mL/min/100g) 225 50.6+4.7 59.3+9.6 47.3+4.5 49.2+5.2 CVR 45 3.20+0.43 2.02+0.35 5.17+1.48 3.95+0.23 (unit x 100g) 225 2.14+0.17 1.96+0.22 3.57+0.45* 3.19+0.16* Brain water content(%) 81.8+0.3 81.8+0.2 82.7+0.1* 82.4+0.2 L-arginine improved recovery of cerebral ATP, cytochrome a,a3 oxidation, cerebral blood flow. L-NAME reduced recovery of cerebral ATP, pHi and cytochrome a,a3 oxidation and increases mean blood pressure, CVR and brain water content, and these effects of L-NAME were reversed by L-arginine only while L-arginine was infused after reperfusion. These data suggest that NO may be important in in vivo metabolic recovery of the brain after DHCA in infant piglets.
Showing the most recent 10 out of 12 publications
