Alden Hood Harken

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Catecholamines have been implicated in the phenomenon of ischemic preconditioning. We have previously demonstrated that ischemic preconditioning against postischemic mechanical dysfunction in the isolated rat heart is mediated by the alpha 1-adrenergic receptor. The purpose of this study was to delineate the signal transduction of preconditioning distal to(More)
OBJECTIVE Proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta have been implicated in the pathogenesis of myocardial dysfunction in ischemia-reperfusion injury, sepsis, chronic heart failure, viral myocarditis, and cardiac allograft rejection. Although circulating TNF-alpha and IL-1beta are both often elevated in(More)
BACKGROUND Oxidant stress caused by ischemia or endotoxemia induces myocardial dysfunction and cardiomyocyte death; however, mechanisms responsible remain unknown. We hypothesized that hydrogen peroxide (H2O2) induces myocardial dysfunction and cardiomyocyte death via P38 mitogen-activated protein kinase (MAPK)-mediated myocardial tumor necrosis factor(More)
Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities, as hearts from untreated rats. Hearts isolated from rats pretreated with endotoxin 24 hr before also had increased(More)
The influence of mixed venous oxygen tension (PVO2) on blood flow to the atelectatic left lung was studied at normal and reduced cardiac outputs (CO) using extracorporeal veno-venous bypass in six pentobarbital anesthetized, mechanically ventilated dogs. Aortic and left pulmonary artery flows; airway, left atrial, central venous, pulmonary, and systemic(More)
Preconditioning may find ready applicability in humans facing scheduled global cardiac ischemia-reperfusion (IR) during bypass or transplantation, where such a maneuver is feasible before arrest. Our objective was to delineate and exploit the endogenous preconditioning mechanism triggered by transient ischemia (TI) and thereby attenuate myocardial(More)
Three lines of investigation indicated that hydrogen peroxide (H2O2) from xanthine oxidase (XO) contributes to cardiac dysfunction during reperfusion after ischemia. First, addition of dimethylthiourea (DMTU), a highly permeant O2 metabolite scavenger (but not urea) simultaneously with reperfusion improved recovery of ventricular function as assessed by(More)
PAF has been implicated as a mediator of shock, sepsis and MOF. The results of experimental data demonstrate that PAF induces changes characteristic of endotoxemia and sepsis, including systemic hypotension and diffuse microvascular leakage. These effects are prevented by PAF antagonists. PAF induces many of the characteristic changes of MOF, including(More)
HYPOTHESIS Solid tumor cells bind to ICAM-1 on endothelial surfaces via MUC-1. Tumor binding to ICAM-1 auto-upregulates tumor ICAM-1 at the leading edge of the tumor and promotes release of chemoattractants for circulating macrophages, and circulating macrophages bind to tumor-expressed ICAM-1, invoking propagation of further chemokines and cytokines that(More)
The purpose of this study was to determine whether isolated renal ischemia and reperfusion (I/R) induces renal tumor necrosis factor (TNF) mRNA production, TNF protein expression, or TNF bioactivity and, if so, whether local/early TNF production acts as mediator of ischemia-induced, neutrophil-mediated renal injury. After rats were anesthetized, varying(More)