ATP sparing effect of isoflurane during ischaemia and reperfusion of the canine heart

Sustained dysfunction of myocardial contractility after shortperiods of coronary artery occlusion and reperfusion has beentermed "stunned myocardium". Isoflurane may improve the recoveryof regional myocardial contractility in stunned myocardium.The purpose of the present study was to determine if isofluraneprevents depletion of high energy phosphates after myocardialischaemia-reperfusion and if the reduction in cardiac work duringisoflurane anaesthesia contributes to the preservation of highenergy phosphate metabolism in an acute canine model. Mongreldogs were allocated to one of three groups: controls, anaesthetizedwith urethane and chloralose; ISO group, isoflurane administeredbefore ischaemia; and ISOc group, heart rate and mean arterialpressure controlled to approximately match baseline values.The left anterior descending (LAD) coronary artery was occludedfor 15 min and then reperfused for 60 min during 1.5% end-tidalisoflurane anaesthesia. Full thickness samples of myocardiumwere obtained from the reperfused area (supplied by the LAD)and the non-ischaemic area (supplied by the left circumflexcoronary artery). The concentrations of adenosine monophosphate(AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP),creatine phosphate (CP) and lactate in the endocardial portionof the myocardium were measured. Arterial pressure, aortic flowin the ascending aorta and rate-pressure product decreased significantlyafter isoflurane. Although the concentration of ATP of the reperfusedarea in the control group showed a significant reduction 60mm after reperfusion, the ISO and ISOc groups had significantlygreater concentrations. Isoflurane anaesthesia maintained myocardialhigh energy phosphate metabolism in reperfused myocardium. Weconclude that the reduction in cardiac work played only a minorrole in the ATP-sparing effect of isoflurane. (Br. J. Anaesth.1995; 74: 563–568)     

Blockade of ATP-sensitive K+ channel abolishes the anti-ischemic effects of isoflurane in dog hearts

Background: Although isoflurane is reported to have a protective effect against ischemic damage on the myocardium, the mechanisms of this effect are not clear. Activation of adenosine triphosphate sensitive potassium (KATP) channels is indicated to protect myocardium during ischemia. Thus, it was hypothesized that if isoflurane could activate KATP channels, blockade of KATP channels would decrease its cardioprotective effect.
Methods: Mongrel dogs, anesthetized with morphine, urethane, and chloralose, were subjected to 15 min of left anterior descending coronary artery occlusion followed by 60 min reperfusion. The dogs were divided into three groups: the control group (n=8), IS0 group (n=8) and ISOGC group (n=8). In the IS0 and ISOGC groups, 1 MAC of isoflurane was administrated during ischemia and reperfusion. In the ISOGC group, 0.3 mg/ kg of glibenclamide, the KATP channel blocker, was given 45 min before ischemia. Full-thickness samples of myocardium were obtained and the concentrations of adenosine monophosphate, adenosine diphosphate, adenosine triphosphate (ATP), creatine phosphate and lactate in the endocardial portion of the myocardium were measured.
Results: The ischemia-reperfusion caused a 25.4% and 27.6% reduction of myocardial ATP in the control and ISOGC groups, respectively. In contrast, the IS0 group showed only 11.0% reduction of AT, which was significantly lower compared to the other groups ( P < 0.01).
Conclusions: Our results shows that blockade of the KATP channel abolishes cardioprotective effects of isoflurane in myocardial ischemia-reperfusion. The KATP channel may play a role in the ATP-sparing effect of isoflurane.     

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will “talk and deteriorate.” Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.     

Efficacy of a high dosage of donepezil for Alzheimer's disease as examined by single‐photon emission computed tomography imaging

Background: The efficacy of donepezil 10 mg/day against Alzheimer's disease (AD) was examined, with a primary focus on changes in cerebral blood flow (CBF) as determined by single‐photon emission computed tomography imaging. Methods: The subjects were 24 outpatients who had been diagnosed with probable AD, which had progressed to advanced AD. Mini‐Mental State Examination and Alzheimer's Disease Assessment Scale (ADAS) scores were determined before and after the donepezil dosage increase. ^99mTc‐ethylcysteinate dimer single‐photon emission computed tomography was performed to evaluate changes in CBF. Then, a comparative study evaluated changes after the donepezil dosage increased. Results: After the donepezil dosage increase, adverse effects associated with gastrointestinal symptoms were observed in one patient, and irritability was observed in three. The average Mini‐Mental State Examination score changed from15.25 ± 6.24 to 14.67 ± 6.07; significant changes were not observed. Seventeen subjects were evaluated with the Alzheimer's Disease Assessment Scale‐cognitive subscale. After the dosage increase, the average subscale score decreased from 24.52 ± 13.39 to 21.56 ± 9.14, and significant improvement was observed (P= 0.021). With respect to changes in the CBF, the values of all three indicators decreased after the higher dosage increased CBF. However, no significant differences were observed in CBF. Analysis performed after the donepezil dosage increase revealed significant increases in CBF in the right occipital and temporal lobes, left temporal lobe, right parietal lobe, and both parts of the posterior cerebellum. Conclusion: Increasing the donepezil dosage from 5 mg/day to 10 mg/day is effective for the treatment of AD.     

Radiofrequency Catheter Ablation of Left Ventricular Outflow Tract Tachycardia:

Left Ventricular Outflow Tract Tachycardia. Idiopathic ventricular tachycardia (VT) originating from the left ventricular outflow tract (LVOT) is rare. We report two patients whose QRS configuration during VT commonly showed an inferior axis and monophasic R waves in all the precordial leads. The mechanism of these VTs appeared to be triggered activity. From mapping and ablation, the origin of these VTs was determined to be in the most posterior LVOT, corresponding to the aortomitral continuity (left fibrous trigone).     

Dual inverse effects of lipoprotein(a) on the dementia process in Japanese late-onset Alzheimer's disease

Background: The role of lipoprotein metabolism in the dementia process has attracted increasing attention. It is universally accepted that apolipoprotein E4 (ApoE) is a risk factor for late‐onset Alzheimer's disease, however, the role of lipoprotein(a) (Lp(a)) remains unclear. Therefore, we conducted the present study to clarify the association between Lp(a) and dementia. Methods: Lipoprotein(a) serum concentrations were examined in relation to ApoE phenotypes and periventricular lucency (PVL) on brain computed tomography in 150 patients with late‐onset Alzheimer's disease (AD group), compared with 46 patients with vascular dementia (VaD group) and 150 controls without dementia. Results: The incidences of hypertension, hypercholesterolaemia, and severe PVL were significantly higher in the VaD group than in the AD group. The distributions of Lp(a) concentrations showed left‐skewed deviation in each group, but we found the concentration of 40 mg/dL to be the best cut‐off point to distinguish the frequency of Alzheimer's disease from that of the controls. Compared with the frequency of high Lp(a) concentrations of 40 mg/dL or more in the controls (16.7%), that in the AD group (10.0%) was significantly lower, while that in the VaD group (45.7%) was significantly higher. Separating the AD group according to the presence or absence of ApoE4, the same findings were recognized. However, severe PVL was more frequent in the AD group with high Lp(a) concentrations (53.3%) than in the AD group without high Lp(a) concentrations (7.4%) (P < 0.01). Conclusions: These findings suggest the possibility of dual inverse effects of Lp(a) on the occurrence of Japanese late‐onset Alzheimer's disease, via suppression of Alzheimer's related processes and promotion of PVL formation presumably caused by ischemia.