Both the increased severity of ischemia and the enhanced energy expenditure induced by dobutamine impair the development of myocardial short-term hibernation and precipitate myocardial infarction.

Action potential (AP) prolongation is a hallmark of failing myocardium. Functional downregulation of K currents is a prominent feature of cells isolated from failing ventricles. The detailed changes in K current expression differ depending on the species, the region of the heart, and the mechanism of induction of heart failure. We used complementary approaches to study K current downregulation in pacing tachycardia-induced heart failure in the rabbit. The AP duration (APD) at 90% repolarization was significantly longer in cells isolated from failing hearts compared with controls (539 +/- 162 failing vs. 394 +/- 114 control, P < 0.05). The major K currents in the rabbit heart, inward rectifier potassium current (I(K1)), transient outward (I(to)), and delayed rectifier current (I(K)) were functionally downregulated in cells isolated from failing ventricles. The mRNA levels of Kv4.2, Kv1.4, KChIP2, and Kir2.1 were significantly downregulated, whereas the Kv4.3, Erg, KvLQT1, and minK were unaltered in the failing ventricles compared with the control left ventricles. Significant downregulation in the long splice variant of Kv4.3, but not in the total Kv4.3, Kv4.2, and KChIP2 immunoreactive protein, was observed in cells isolated from the failing ventricle with no change in Kv1.4, KvLQT1, and in Kir2.1 immunoreactive protein levels. Multiple cellular and molecular mechanisms underlie the downregulation of K currents in the failing rabbit ventricle.

Long-term recovery from severe closed head injury was investigated in predominantly young adults whose Glasgow Coma score was 8 or less at the time of admission. Of the 27 patients studied (median follow-up interval of 1 year), 10 attained a good recovery, 12 were moderately disabled, and five were severely disabled. In contrast to previous studies suggesting that intellectual ability after severe closed head injury eventually recovers to a normal level, our findings showed that residual intellectual level, memory storage and retrieval, linguistic deficit, and personal social adjustment corresponded to overall outcome. All severely disabled patients and several moderately disabled patients exhibited unequivocal cognitive and emotional sequelae after long follow-up intervals. Analysis of persistent neuropsychological deficit in relation to neurological indices of acute injury severity demonstrated the prognostic significance of oculovestibular deficit.

This study evaluated the importance of ATP-dependent potassium channels (KATP) for ischemic preconditioning (IP) in swine. Swine were studied because due to the sparsity of their innate collateral circulation infarct size (IS) development closely resembles that observed in humans. Ninety minutes of ischemia at a blood flow reduction sufficient to reduce regional myocardial work by 90% caused 13.2 +/- 8.9% (SD) IS of the area at risk. A single cycle of 10-min preconditioning ischemia followed by 15-min reperfusion reduced IS after 90 min of ischemia to 2.8 +/- 2.7%. The epicardial monophasic action potential duration at 50% repolarization (MAP50) was decreased more markedly during the initial 10 min of the prolonged ischemia than during the first 10 min of the preconditioning ischemic period (84 +/- 4 vs. 89 +/- 2%). Transmural myocardial adenosine (ADO) uptake was reversed to net release during both ischemic periods and during the initial phase of reperfusion. Glibenclamide (0.5 mg/kg, followed by 50 micrograms/min i.v.) abolished the reduction in MAP50 without altering ADO release. Glibenclamide did not alter IS per se (13.0 +/- 7.6%) but abolished the beneficial effect of IP (IS: 13.6 +/- 6.2%). Thus blockade of KATP with glibenclamide abolishes the IS-reducing effect of IP in swine but does not reduce ADO release.

Both regional hibernating myocardium and stunned myocardium in situ are characterized by a decrease in overall myocardial calcium responsiveness; however, there appears to be no significant myocardial desensitization to calcium.