Transmural electrical dispersion determines the repolarization sequence across the ventricular wall, and plays an important role in the development of arrhythmias under pathological conditions. While it is clear that the transmural gradient of the transient outward current ( I to) underlies the dramatic difference in phase 1 repolarization across the ventricle, its contribution to the transmural action potential duration (APD) dispersion is not clear. We investigated this problem using the dynamic clamp technique in canine ventricular myocytes. The dynamic clamp allows quantitative 'insertion' of simulated conductances in real, biological cells, bridging pure computer modelling and experimental electrophysiology. 'Insertion' of an epicardial level of I to in endocardial cells produced a prominent phase 1 repolarization and a 'spike-and-dome' action potential morphology, but did not significantly affect the APD. Increasingly larger I to densities prolonged, and then dramatically shortened the endocardial APD. We also used the dynamic clamp to subtract, or 'block' the native I to in epicardial cells. Such 'blockade' eliminated the epicardial action potential notch, but had no significant effect on the APD. We conclude that I to, while being a key regulator of phase 1 repolarization, does not significantly affect the APD of canine ventricular myocytes, and that the I to gradient is not a significant contributor to the transmural APD dispersion in the canine ventricle. By allowing computer simulation on a biological background, the dynamic clamp is a new and effective tool to study the ionic basis of the electrical properties of cardiac cells. 相似文献
Background: Preconditioning the brain with relatively safe drugs seems to be a viable option to reduce ischemic brain injury. The authors and others have shown that the volatile anesthetic isoflurane can precondition the brain against ischemia. Here, the authors determine whether isoflurane preconditioning improves long-term neurologic outcome after brain ischemia.
Methods: Six-day-old rats were exposed to 1.5% isoflurane for 30 min at 24 h before the brain hypoxia-ischemia that was induced by left common carotid arterial ligation and then exposure to 8% oxygen for 2 h. The neuropathology, motor coordination, and learning and memory functions were assayed 1 month after the brain ischemia. Western analysis was performed to quantify the expression of the heat shock protein 70, Bcl-2, and survivin 24 h after isoflurane exposure.
Results: The mortality was 45% after brain hypoxia-ischemia. Isoflurane preconditioning did not affect this mortality. However, isoflurane preconditioning attenuated ischemia-induced loss of neurons and brain tissues, such as cerebral cortex and hippocampus in the survivors. Isoflurane also improved the motor coordination of rats at 1 month after ischemia. The learning and memory functions as measured by performance of Y-maze and social recognition tasks in the survivors were not affected by the brain hypoxia-ischemia or isoflurane preconditioning. The expression of Bcl-2, a well-known antiapoptotic protein, in the hippocampus is increased after isoflurane exposure. This increase was reduced by the inhibitors of inducible nitric oxide synthase. Inducible nitric oxide synthase inhibition also abolished isoflurane preconditioning-induced neuroprotection. 相似文献
Purpose To perform an audit of paediatric surgical patients in a provincial general surgical unit. Methodology Data was prospectively recorded using a standardized proforma on all children aged up to 15 yrs, seen between 11th December 2005 and 11th December 2006. Results There were 209 admissions (194 children), median age 8 yrs (6 wks–15 yrs) with 153 (73%) acutes. 37 children (18%) were under 2 yrs. Male : female ratio was 3 : 2. Procedures (n = 119) were appendicectomy (35), inguinal herniotomy (30), skin procedures (29), endoscopy (10), testicular (10) and others (5). The commonest acute and elective operations were appendicectomy and inguinal herniotomy respectively. 51% of operations were acute. There were 10 tertiary hospital transfers (5%) for burns (4), pyloric stenosis (3), intussusseption (1), neonatal inguinal hernia (1) and pyoderma gangrenosum (1). Median age of transfers was 11 months (6 wks–14 yrs). Complications were wound infection (1), post‐operative ileus (2) and infarcted ovary (1). Conclusion There are increasing moves towards centralization in paediatric surgery. 1 With only 4 paediatric tertiary centres in NZ, many general surgeons routinely perform paediatric surgery. A large number of children presented to our surgical department. Around half of these children required surgery and half of operations were acute. There is still a significant need for general paediatric surgery in the provinces and hence close collaboration with specialist paediatric surgeons. 相似文献