Alden H. Harken

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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)
Surgical resection of the endocardium and subendocardium often abolishes chronic recurrent sustained ventricular tachycardia in patients with healed myocardial infarcts or ventricular aneurysms, presumably by interrupting the reentrant pathway. To define the morphologic characteristics of cells in the reentrant pathway, we studied the histology and(More)
Although monocyte chemotactic protein-1 (MCP-1) is best known for its ability to recruit mononuclear cells, few studies have examined the effects of this chemokine on other events in the vascular response to injury. The purpose of the present study was to determine the influence of MCP-1 on human vascular smooth muscle (VSMC) proliferation. MCP-1 induced(More)
Toll-like receptor 4 (TLR-4), initially identified as an LPS receptor, is critical to the signaling of a variety of danger signals, including heat shock protein 60, fibrinogen, and fibronectin. Recent data also suggest that TLR-4 plays a role in determining survival in both endotoxemia and hemorrhagic shock. We hypothesized that a functional TLR-4 would be(More)
BACKGROUND The heart is a tumor necrosis factor-alpha (TNF-alpha)-producing organ. Recent basic experimental and clinical evidence suggests that TNF-alpha is an important mediator of myocardial injury during acute myocardial infarction, chronic heart failure, cardiac allograft rejection, and cardiopulmonary bypass operations. Although it is known that the(More)
Ischemic preconditioning (PC) attenuates cardiac acidosis during global ischemia. This adaptation to ischemia is detectable before other better known indexes of PC are manifested. Clarification of the endogenous mechanisms may provide insights into how protein kinase C (PKC) signaling might be linked to altered intracellular biochemistry. 31P NMR studies of(More)
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) have been implicated in cardiac dysfunction during endotoxemia. Because IL-18 is a proinflammatory cytokine known to mediate the production of TNF-alpha and IL-1beta and to induce the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(More)
To validate the accuracy of catheter endocardial mapping to localize the origin of ventricular tachycardia (VT), we compared cathether endocardial mapping with intraoperative epicardial and endocardial mapping of 24 morphologically distinct VTs in 18 patients undergoing surgery. Twelve had VT with left bundle branch block morphology and 12 had VT with right(More)
Atherosclerosis represents a spectrum of pathologic lesions with diverse clinical sequelae. In this review, we build upon the paradigm that arteriosclerosis represents an inflammatory disease. By examining mechanisms involved in the response to vascular injury, we can more effectively implement targeted therapy aimed at halting or regressing(More)