Problems Encountered with Hemoglobinbased Blood Substitutes during Trials

Although hemoglobin solutions have been well tolerated in human volunteers and in dialysis, septic shock, and cardiac surgery patients, a number of largely unresolved problems were found during preclinical trials and development of some of these hemoglobin-based substitutes. These include cardiovascular/hemodynamic effects, gastrointestinal changes, immune cell activation, coagulation changes, oxidative stress, and decreased host resistance to overwhelming infection. Preclinical studies reported the detection of myocardial lesions in a number of animal models infused with the Baxter Health Care Inc. product, diaspirin cross-linked Hb (DCLHb). These lesions were characterized by a mild to moderate focal myocardial degeneration and/or necrosis in a highly vascularized portion of the myocardium. Baxter has recently terminated its clinical development of this product as a result of increased fatalities in the test group [2]. In this study 46 percent of 52 patients infused with DCLHb died compared to 17 percent of 46 patients infused with saline solution. A dose-response study performed on dogs by Biopure Corporation has shown that Oxyglobin increases arterial oxygen content in the face of normovolemic anemia, but produces transient clinical signs

(skin discoloration, discolored stools, nausea, vomiting). In addition, histopathology of Oxyglobin administration includes activation of tissue macrophages in multiple organs. Hemolink has recently been withdrawn from Phase III clinical trials in cardiac bypass grafting because it produced adverse cardiac events. In addition, numerous animal studies have demonstrated that the administration of extracellular hemoglobin derivatives may lead to a variety of undesirable side effects.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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