Prevention of ischemia reperfusion injury associated with acute myocardial infarc

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DESCRIPTION (provided by applicant): Hope Pharmaceuticals is a small business that distributes Sodium Nitrite Injection and owns patent rights to a recently discovered use for sodium nitrite as a means to prevent ischemia-reperfusion injury. Ischemia-reperfusion injury refers to tissue damage caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and other vital nutrients to an area creates a condition in which the restoration of circulation to the area can result in inflammation and oxidative damage rather than restoration of normal function. Immune cells carried to the area by the newly returning blood release a host of inflammatory factors in response to tissue damage. These inflammatory factors include free radicals that can damage cellular proteins and disrupt cell membranes. Studies in animal models of acute myocardial infarction suggest that lethal ischemia-reperfusion injury can account for approximately 50% of the final size of a myocardial infarct. The cytoprotective properties of sodium nitrite have been demonstrated in several animal models of myocardial infarction. In a murine model of myocardial infarction, intravenous administration of sodium nitrite significantly reduced cardiac infarct size by 67%. In a canine model of extended ischemia, five minutes of sodium nitrite treatment after two hours of ischemia also resulted in approximately 50% reduction in myocardial infarct size. In 2006, over 600,000 people in the United States were hospitalized with an acute myocardial infarction. The current standard of care for an acute myocardial infarction focuses on therapies to restore blood flow quickly. At present, no therapy has been approved by the Food and Drug Administration (FDA) to prevent ischemia-reperfusion injury in these patients. The morbidity and mortality associated with an acute myocardial infarction correlates inversely with infarct size. The goal is to minimize infarct size. If a therapy is proven safe and effective for the prevention of ischemia-reperfusion injury, infarct sizes may be reduced, cardiac function preserved, and quality of life maintained. A Phase 1 clinical study of the safety and pharmacokinetics of a 48-hour intravenous nitrite infusion in healthy volunteers was recently completed. This grant application is intended to support the next study in a clinical development plan: a Phase 2(A) study involving patients with acute myocardial infarction. This study is being conducted at Johns Hopkins Medical Center and has been approved to proceed by both the FDA and the Johns Hopkins' Institutional Review Board. Information from this study will be used to design subsequent Phase 2(B) and Phase 3 clinical trials. PUBLIC HEALTH RELEVANCE: Ischemia-reperfusion injury is a serious complication associated with acute myocardial infarction that is characterized by inflammation and oxidative damage to tissues caused when blood flow is restored after a period of ischemia. Ischemia-reperfusion injury can cause irreversible tissue damage. At present, there is no FDA-approved therapy for this condition. This grant application requests support for a Phase 2A clinical study that is part of a development plan to evaluatesodium nitrite injection as a therapy to prevent ischemia-reperfusion injury and thereby maintain the quality of life of patients who experience an acute myocardial infarction.