An 80-year-old male patient(160 cm, 52 kg) underwent a combined coronary artery bypass graft and aortic valve replacement. He had no history of gastric or esophageal disease. Transesophageal echocardiography(TEE) was used for an intraoperative monitor. At the end of surgery, massive fresh blood was aspirated through a gastric tube after removal of the TEE probe. An urgent esophago-gastroduodenoscopy and computed tomography diagnosed a gastric perforation, for which the patient had to undergo an urgent laparoscopic repair. The surgical repair was successful and the patient was discharged on the postoperative day 21.
JM-1232(−)((−)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta[f] isoindole-1(2H)-one) is a novel isoindoline chemical compound that affects benzodiazepine receptors, and is considered for application as a new sedative or intravenous anesthetic agent. To investigate the safety of JM-1232(−), preclinical studies investigating the pharmacokinetics of normal- and high-dose JM-1232(−) are needed. In this study, we used high performance liquid chromatography(HPLC) to measure the concentration of JM-1232(−) in plasma, and investigated the pharmacokinetics of low- to high-dose JM-1232(−) in rats. The effects of bolus administration of JM-1232(−)(1, 10, 25, 50, and 75 mg/kg) on the pharmacokinetic parameters were assessed in rats. We extrapolated JM-1232(−) to be a one-compartment model within 60 minutes after bolus administration. In the 50 mg/kg group, a significant increase in the elimination rate constant was observed, which is considered to be the saturation of metabolism and/or excretion. The rats were dead in the 75 mg/kg group. Thus, JM-1232(−) administered to rats at doses above 50 mg/kg is likely toxic.
This study was designed to investigate the effects of cannabinoid agonists and antagonists on neutrophil behaviors in response to inflammatory stimulation. The neutrophil behavior was observed in the microvasculature of hamster cheek pouch using a trans-illumination microscope. Superfusion of leukotriene B4 caused an increase in the number of neutrophils migrating through the endothelium outside the venules. The migration induced by leukotriene B4 was significantly attenuated in hamsters receiving WIN55212-2, a synthetic non-selective cannabinoid agonist, prior to the leukotriene B4 superfusion. The inhibitory effect of WIN55212-2 was abolished by AM251, a selective CB1 antagonist, and also by AM630, a selective CB2 antagonist. These results suggest that augmentation of the CB1 and CB2 cannabinoid system could produce the inhibition of neutrophil migration and contribute to suppression of inflammatory derangement.
This study evaluated the comparative effects of three inhalational anesthetic agents on myocardial infarction and arrhythmias in rabbit hearts subjected to a regional ischemia/reperfusion insult. Rabbits received regional ischemia by 30 min of left anterior descending coronary artery(LAD) occlusion and followed by 3 hours of reperfusion under general anesthesia. The anesthetics studied were: ketamine/xylazine(35 mg/kg/hr and 5 mg/kg/hr respectively, Control), halothane(1.0%, H), isoflurane(1.4%, I), and sevoflurane(2.1%, S). At the end of the 3 hrs reperfusion, the area at risk was delineated by Evans blue staining and the infarct size was determined by tetrazolium staining. The area at risk showed no significant differences among the groups. The mean infarct size was 59.3±1.9% of the risk area in Control, and it was significantly greater than those in H, I and S: 36.9±3.3%, 39.1±4.8%, and 23.0±3.2%, respectively(p<0.05 vs. control). The incidence of arrhythmia during myocardial ischemia was 66.7% in Control, 16.7% in H, I, and S. The incidence of arrhythmias during reperfusion was 50.0% in Control, 33.3% in H, 16.7% in I and S. The volatile anesthetics tested in this study could protect the ischemic rabbit heart from infarction, as compared with ketamine/xylazine anesthesia. Sevoflurane may have the most powerful cardioprotection among these volatile anesthetics.