SUMMARY 1. In the present study, we investigated the effect of 1‐(3‐ tert‐butyl‐2‐hydroxy‐5‐methoxyphenyl)‐3‐(3‐pyridylmethyl) urea hydrocloride (T‐0970), a novel water‐soluble low‐molecular weight free radical scavenger, on the generation of hydroxyl radicals in vivo and on myocardial infarct size in an in vivo model of myocardial infarction in rabbits. 2. T‐0970 scavenged hydroxyl radicals generated in the myocardium during reperfusion, as assessed by using a microdialysis technique and HPLC in an in vivo model with 30 min coronary occlusion and 30 min reperfusion in rabbits. 3. Another group of rabbits was subjected to 30 min coronary occlusion and 48 h reperfusion. The control group ( n = 10) was infused with saline for 190 min from 10 min before occlusion to 180 min after reperfusion. The treatment group (T‐0970 group; n = 10) was injected with a bolus 2.5 mg/kg T‐0970 and then infused with T‐0970 for 190 min from 10 min before reperfusion to 180 min after reperfusion at a rate of 100 μg/kg per min. The T‐0970 + CHE group ( n = 5) was given chelerythrine (CHE; a selective inhibitor of protein kinase C (PKC); 5 mg/kg, i.v.) 10 min before the administration of T‐0970. The T‐0970 + 5‐HD group ( n = 5) was given 5‐hydroxydecanoate (5‐HD; an inhibitor of mitochondrial K ATP channels; 5 mg/kg, i.v.) 10 min before the administration of T‐0970. The CHE and 5‐HD groups were given CHE (5 mg/kg, i.v.) and 5‐HD (5 mg/kg, i.v.) 20 min before reperfusion, respectively. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of the area at risk (AAR). In another series of experiments, the control ( n = 5) and T‐0970 ( n = 5) groups were killed 4 h after reperfusion following 30 min coronary occlusion and DNA fragmentation in myocytes was assessed using in situ dUTP nick end‐labelling (TUNEL) at the light microscopic level. 4. Infarct size, as a percentage of AAR, in the T‐0970 group was significantly reduced compared with the control group (21±4 vs 41±4%, respectively; P < 0.05). This reduction of infarct size by T‐0970 was abolished by pretreatment with CHE and 5‐HD. Neither CHE nor 5‐HD alone had any effect on infarct size. The percentage of infarcted myocytes with DNA fragmentation by TUNEL in the T‐0970 group was significantly reduced compared with the number in the control group (4.0±1.5 vs 10.7±1.9%, respectively; P < 0.05). 5. T‐0970, a free radical scavenger, improved reperfusion injury. This effect seemed to be mediated by activation of PKC, the opening of mitochondrial K ATP channels and inhibition of DNA fragmentation.
Perioperative management is critical for positive neurosurgical outcomes. In order to maintain safe and authentic perioperative management, a perioperative management center (PERIO) was introduced to patients of our Neurosurgery Department beginning in June 2014. PERIO involves a multidisciplinary team consisting of anesthesiologists, dentists/dental hygienists/technicians, nurses, physical therapists, pharmacists, and nutritionists. After neurosurgeons decide on the course of surgery, a preoperative evaluation consisting of blood sampling, electrocardiogram, chest X-ray, and lung function test was performed. The patients then visited the PERIO clinic 7-14 days before surgery. One or two days before surgery, the patients without particular issues enter the hospital and receive a mouth cleaning one day before surgery. After surgery, postoperative support involving eating/swallowing evaluation, rehabilitation, and pain control is provided. The differences in duration from admission to surgery, cancellation of surgery, and postoperative complications between PERIO and non-PERIO groups were examined. Eighty-five patients were enrolled in the PERIO group and 131 patients in the non-PERIO group. The duration from admission to surgery was significantly decreased in the PERIO group (3.6 ± 0.3 days), compared to that in the non-PERIO group (4.7 ± 0.2 days). There was one cancelled surgery in the PERIO group and six in the non-PERIO group. Postoperative complications and the overall hospital stay did not differ between the two groups. The PERIO system decreased the duration from admission to surgery, and it is useful in providing high-quality medical service, although the system should be improved so as not to increase the burden on medical staff.
The anti‐diabetic drug miglitol, an α‐glucosidase inhibitor, which is currently used clinically, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the α‐1,6‐glucosidase of glycogen‐debranching enzyme in the heart. Nicorandil, a K ATP channel opener with a nitrate‐like effect, which is also currently used clinically, also reduces the infarct size. Therefore, we hypothesized that combination of nicorandil and submaximal dose of miglitol could markedly reduce myocardial infarct size more than miglitol or nicorandil alone, and investigated the mechanism for the infarct size‐reducing effect. Japanese white rabbits without collateral circulation were subjected to 30 min coronary occlusion followed by 48 h reperfusion. Pre‐ischaemic treatment with submaximal dose of miglitol (5 mg kg −1 , i.v.) and nicorandil alone (100 μg kg −1 min −1 5 min) moderately reduced the infarct size as a percentage of area at risk (24±4 and 25±4%, respectively), and 10 mg kg −1 of miglitol markedly reduced the infarct size (15±2%) compared with the controls (42±2%). Combination of 5 mg kg −1 of miglitol and nicorandil (100 μg kg −1 min −1 5 min), and 10 mg kg −1 of miglitol and nicorandil (100 μg kg −1 min −1 5 min) significantly reduced the infarct size (13±4 and 12±3%, respectively) more than miglitol or nicorandil alone. Pretreatment with 5HD completely abolished the infarct size‐reducing effect of 10 mg kg −1 of miglitol alone (36±7%) and that of combination of 5 mg kg −1 of miglitol and nicorandil (46±2%). Combination of nicorandil and submaximal dose of miglitol markedly reduced the myocardial infarct size more than miglitol or nicorandil alone. This effect was suggested to be related to the opening of mitochondrial K ATP channels. British Journal of Pharmacology (2001) 133 , 1041–1046; doi: 10.1038/sj.bjp.0704166
N-methyl-1-deoxynojirimycin (NMDN), an a-glucosidase inhibitor, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart, in addition to possessing an antihyperglycemic action by blocking alpha-1,4-glucosidase in the intestine. Ischemic preconditioning (PC), which markedly reduces the size of the myocardial infarct, is known to reduce the activity of phosphorylase and reduce the glycogenolytic rate. Therefore, it was hypothesized that a combination of pharmacological inhibition of glycogenolysis by an alpha-1,6-glucosidase inhibitor, NMDN, and PC could markedly reduce myocardial infarct size more than NMDN or PC alone. Japanese white rabbits without collateral circulation were subjected to a 30-min coronary occlusion followed by 48-h reperfusion. The infarct sizes as a percentage of area at risk were significantly reduced by pre-ischemic treatment with either 100mg/kg of NMDN or PC of 5 min ischemia and 5 min reperfusion alone (15.9+/-2.0%, n=8, and 10.3+/-1.2%, n=8, respectively) as compared with the control (43.9+/-2.2%, n=8). However, the combination of 100mg/kg of NMDN and PC significantly reduced the infarct size (4.9+/-1.2, n=8) compared with NMDN or PC alone. Another 40 rabbits, also given 100mg of NMDN, PC, NMDN+PC or saline before ischemia (n=10 in each group), were killed for biochemical analysis after 30 min of ischemia. NMDN and PC preserved the glycogen content and attenuated the lactate accumulation, respectively, as compared with the control. However, the combination of NMDN and PC preserved significantly more glycogen and significantly reduced lactate accumulation than either NMDN or PC alone. The combination of NMDN and PC markedly reduced the myocardial infarct size more than either process alone. The marked preservation of glycogen and marked attenuation of lactate accumulation by the combination of NMDN and PC suggest that the mechanism for this effect of NMDN+PC is related to the inhibition of glycogenolysis.
Sheng-mei-san (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae, has long been used for more than 700 years for patients with coronary heart disease. We attempted to clarify 1) whether SMS reduces myocardial infarct size, and 2) whether the infarct size-reducing effect of SMS is related to activation of protein kinase C and the opening of the mitochondrial KATP channels in Japanese white rabbits without collateral circulation. The results indicate that three days treatment but not acute treatment with SMS reduces myocardial infarct size through activation of protein kinase C and opening of the mitochondrial KATP channels.
Rehabilitation is a medical intervention implemented mainly by therapists under the prescription orders of medical doctors in hospitals. It is difficult to standardize rehabilitation intervention processes because they largely depend on individual therapists rather than medicines or instruments, and there are few quantitative clinical indicators. In such situations, there are differences in intervention processes and outcomes between therapists and hospitals.
