Nicorandil, a KATP Channel Opener, Attenuates Ischemia-Reperfusion Injury in Isolated Rat Lungs.

PURPOSE: Nicorandil is a hybrid between nitrates and KATP channel opener activators. The aim of this study was to evaluate the nicorandil's effects on ischemia-reperfusion (IR) lung injury and examine the mechanism of its effects. METHODS: Isolated rat lungs were divided into 6 groups. In the sham group, the lungs were perfused and ventilated for 150 min. In the IR group, after perfusion and ventilation for 30 min, they were interrupted (ischemia) for 60 min, and then resumed for 60 min. In the nicorandil (N) + IR group, nicorandil 6 mg was added before ischemia (nicorandil concentration was 75 µg ml-1). In the glibenclamide + N + IR group, the L-NAME (Nω-Nitro-L-arginine methyl ester) + N + IR group and ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) + N + IR group, glibenclamide 3 µM, L-NAME 100 µM, and ODQ 30 µM were added 5 min before nicorandil administration, respectively. We measured the coefficient of filtration (Kfc) of the lungs, total pulmonary vascular resistance, and the wet-to-dry lung weight ratio (WW/DW ratio). RESULTS: Kfc was significantly increased after 60 min reperfusion compared with baseline in the IR group, but no change in the sham group. An increase in Kfc was inhibited in the N + IR group compared with the IR group (0.92 ± 0.28 vs. 2.82 ± 0.68 ml min-1 mmHg-1 100 g-1; P < 0.01). Also, nicorandil attenuated WW/DW ratio was compared with IR group (8.3 ± 0.41 vs. 10.9 ± 2.5; P < 0.05). Nicorandil's inhibitory effect was blocked by glibenclamide and ODQ (P < 0.01), but not by L-NAME. CONCLUSIONS: Nicorandil attenuated IR injury in isolated rat lungs. This protective effect appears to involve its activation as KATP channel opener as well as that of the sGC-cGMP pathway.

Inhibition of poly (ADP-ribose) synthetase improves pulmonary arterial endothelium-dependent relaxation after ischemic-reperfusion injury of splanchnic artery in rats.

The role of poly (adenosine diphosphate-ribose) synthetase (PARS) in the contractile and relaxant responses of pulmonary arteries injured by ischemia and reperfusion (IR) of splanchnic artery has not been evaluated. We examined these responses by using 3-aminobenzamide, a pharmacological inhibitor of PARS. IR models in rats were induced by clamping the superior mesenteric artery for 60 min, followed by release of the clamp for 60 min. In the 2 treated groups, 5 or 10 mg/kg of 3-aminobenzamide was administered as an IV bolus at 10 min before reperfusion, followed by infusion rates of 5 and 10 mg.kg(-1).h(-1), respectively, during the period of reperfusion (IR + PARS inhibitor 5 and 10 groups). In the vehicle-treated group, 3-aminobenzamide was not given, but IV saline was administered (IR group). In the control group, surgery was performed, but the superior mesenteric artery was not occluded (sham group). The pulmonary arteries were isolated, and effects of drugs were evaluated in vitro. The IR group showed no attenuation of the contractile responses of the pulmonary artery to phenylephrine. The relaxant responses to endothelium-dependent vasodilators, acetylcholine, and A23187 in the IR group were significantly inhibited when compared with the sham group. The reduction in the relaxant response to endothelium-dependent vasodilators was improved in the IR + PARS inhibitor 5 and 10 groups when compared with the IR group. We concluded that IR attenuated the relaxant responses of the pulmonary artery to endothelium-dependent vasodilators and that PARS inhibitors ameliorate the reduction in the relaxant response.

Use of the bispectral index during the early postresuscitative phase after out-of-hospital cardiac arrest.

Non-invasive and real-time measures of neurological status after cardiac arrest are needed to be able to make an early determination of the postresuscitative outcome. We investigated whether the bispectral index (BIS) predicts the postresuscitative outcome in 10 patients with out-of-hospital cardiac arrest. We measured the BIS after return of spontaneous circulation (ROSC) in the emergency room and on admission to the intensive care unit (ICU). We determined the Glasgow Coma Scale (GCS) on admission to the emergency room and the ICU and the Glasgow Outcome Scale (GOS) on discharge from the ICU. The BIS increased after about 30 min of ROSC or reached a plateau in patients rated as achieving a good recovery or moderate disability, but it did not increase to >80 in patients rated as being in a permanent vegetative state/dead. The GCS on admission to the ICU was the same as that on admission to the emergency room. The BIS values were significantly lower in the nonsurviving group than in the surviving group. There was a positive correlation between the BIS on admission to the ICU and the GOS on discharge from the ICU. The BIS can thus be used to predict the postresuscitative outcome of patients with out-of-hospital cardiac arrest.

Nitrous oxide administration during washout of sevoflurane improves postanesthetic agitation in children.

The use of sevoflurane in pediatric patients, which could enable a more rapid emergence and recovery, is complicated by a high incidence of postanesthetic agitation, probably due to residual sevoflurane during washout. The present study was designed to investigate whether administration of nitrous oxide (N2O) reduces sevoflurane concentration at awakening and suppresses postanesthetic agitation. The study enrolled 20 children classified as ASA physical status I. Anesthesia was induced with 5% sevoflurane and maintained with 2.5% end-tidal sevoflurane and N2O in oxygen. In the control group, sevoflurane and N2O were discontinued immediately after completion of surgery. In the N2O group, inspired N2O was replaced with oxygen after the bispectral index (BIS) had reached 80. The end-tidal concentrations of sevoflurane at awakening were significantly lower (P < 0.05) in the N2O group than in the control group. The BIS at awakening was higher (P < 0.01) in the N2O group than in the control group. The point scores of postanesthetic agitation were significantly lower (P < 0.01) in the N2O group than in the control group. Using N2O during washing out of sevoflurane may improve postanesthetic agitation at awakening in children.

Plasma exchange for hypertriglyceridemic acute necrotizing pancreatitis: report of two cases.

We report two cases of hypertriglyceridemic necrotizing pancreatitis treated by plasma exchange (PE). The outcome of each case was quite different according to the timing of PE. A 36 year old man presented with abdominal pain, and a diagnosis of severe acute pancreatitis was made. His serum triglyceride (TG) level was 6,460 mg/dl. He did not undergo PE at first, however, his condition never improved and PE was performed 20 days after the onset of his illness. Finally, he died of multiple organ failure and sepsis. In contrast, a 52 year old man with acute necrotizing pancreatitis was referred to our department. He received PE quickly after hospital admission. His serum TG level, which was 3,540 mg/dl at hospital admission, dramatically returned to normal limits, and he was discharged from the hospital 62 days after admission. The prognosis of severe necrotizing pancreatitis due to hypertriglyceridemia is extremely poor. PE should be applied for the treatment of hypertriglyceridemic necrotizing pancreatitis immediately after its onset.