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PKC-[member of] is upstream and PKC-[alpha] is downstream of mito[K.sub.ATP] channels in the signal transduction pathway of ischemic preconditioning of human myocardium. Am J Physiol Cell Physiol 287: C 1418-C 1425, 2004. First published August 4, 2004; doi:10.1152/ajpcell.00144. 2004.--Protein kinase C (PKC) is involved in the process of ischemic preconditioning (IPC), although the precise mechanism is still a subject of debate. Using specific PKC inhibitors, we investigated which PKC isoforms were involved in IPC of the human atrial myocardium sections and to determine their temporal relationship to the opening of mitochondrial potassium-sensitive ATP (mito[K.sub.ATP]) channels. Right atrial muscles obtained from patients undergoing elective cardiac surgery were equilibrated and then randomized to receive any of the following protocols: aerobic control, 90-min simulated ischemia/120-min reoxygenation, IPC using 5-min simulated ischemia/5-min reoxygenation followed by 90-min simulated ischemia/120-min reoxygenation and finally, PKC inhibitors were added 10 min before and 10 min during IPC followed by 90-min simulated ischemia/120-min reoxygenation. The PKC isoforms inhibitors investigated were V1-2 peptide, GO-6976, rottlerin, and LY-333531 for PKC-[member of], -[alpha], -[delta] and -[beta], respectively. To investigate the relation of PKC isoforms to mito[K.sub.ATP] channels, PKC inhibitors found to be involved in IPC were added 10 min before and 10 min during preconditioning by diazoxide followed by 90-min simulated ischemia/120-min reoxygenation in a second experiment. Creatine kinase leakage and methylthiazoletetrazolium cell viability were measured. Phosphorylation of PKC isoforms after activation of the sample by either diazoxide or IPC was detected by using Western blot analysis and then analyzed by using Scion image software. PKC-[alpha] and -[member of] inhibitors blocked IPC, whereas PKC-[delta] and -[beta] inhibitors did not. The protection elicited by diazoxide, believed to be via mito[K.sub.ATP] channels opening, was blocked by the inhibition of PKC-[alpha] but not -[member of] isoforms. In addition, diazoxide caused increased phosphorylation of PKC-[alpha] to the same extent as IPC but did not affect the phosphorylation of PKC-[member of], a process believed to be critical in PKC activation. The results demonstrate that PKC-[alpha] and -[member of] are involved in IPC of the human myocardium with PKC-[member of] being upstream and PKC-[alpha] being downstream of mito[K.sub.ATP] channels. cardioprotection; protein kinase C isoforms

Objective: To examine the effects on emergency hospital admissions, length of stay and emergency re-admissions of providing a consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service, based in a highly deprived area in the North West of England.Methods: A longitudinal matched controlled study using difference-in-differences analysis compared the change in outcomes in the intervention population, to the change in outcomes in a matched comparison population that had not received the intervention, 5 years before and after implementation. The outcomes were emergency hospitalisations, length of inpatient stay and re-admission rates for cardiovascular disease (CVD).Results: Findings show that the intervention was associated with 66 fewer emergency CVD admissions per 100 000 population per year (95% CI 22.13 to 108.98) in the post-intervention period, relative to the control group. No significant measurable effects on length of stay or emergency re-admission rates were observed.Conclusion: This consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service was associated with a lower rate of emergency hospital admissions in a highly disadvantaged population. Similar approaches could be an effective component of strategies to reduce unplanned hospital admissions. [ABSTRACT FROM AUTHOR]