Fructose-1,6-bisphosphate and fructose-2,6-bisphosphate do not influence brain carbohydrate or high-energy phosphate metabolism in a rat model of forebrain ischemia.

Phosphorylated fructose compounds have been reported to lessen neuronal injury in in vitro models of hypoxia and in vivo models of ischemia. Although a variety of mechanisms have been proposed to account for this finding, it is unknown if intracellular uptake and incorporation of these compounds into the glycolytic pathway contribute to the benefit. We evaluated phosphorylated fructose administration in an adult rat model of transient, near-complete cerebral ischemia to determine its impact on brain metabolism before, during, and after ischemia. Fifty-four pentobarbital anesthetized rats were randomly assigned to receive IV infusions of either fructose-1,6-bisphosphate, fructose-2,6-bisphosphate, or 0.9% saline. After 2 hours of infusion, 18 rats (6/treatment group) were subjected to brain harvesting before any ischemia, 18 additional rats had brain harvesting at the completion of 10 minutes of forebrain ischemia (2-vessel occlusion plus induced hypotension), and 18 rats had harvesting after ischemia and 15 minutes of reperfusion. Cortical brain samples were analyzed for ATP, ADP, AMP, phosphocreatine, glucose, and glycogen. When compared with placebo, neither phosphorylated fructose compound altered preischemic, intraischemic, or postischemic concentrations of brain high-energy phosphates, glucose, glycogen, or lactate, nor did they influence the intraischemic metabolism of endogenous brain glucose or glycogen. On the basis of these results, we conclude that mechanisms other than augmented carbohydrate metabolism are responsible for previous reports of neuronal protection by the bisphosphonates.

In vitro studies of human hearts.

BACKGROUND: Isolated mammalian hearts have been used in numerous studies that have led to many important discoveries in cardiac physiology, pharmacology, and surgery. Multiple methods of perfusion have been described including retrograde and/or antegrade flows and crystalloid or blood perfusates. Furthermore, multiple species have been utilized for such studies including the following: rat, rabbit, guinea pig, canine, and swine. The objective of this study was to describe a unique isolated heart preparation, utilizing human hearts not viable for transplant, which allows for physiologic perfusion and endocardial imaging. METHODS: Utilizing standard cardiac transplantation procedures, 12 human hearts deemed not viable for transplant were explanted to an isolated heart apparatus. A clear, modified Krebs-Henseleit buffer was used as a blood substitute, which allowed for endocardial imaging utilizing 6.0 mm endoscopic video cameras inserted into the cardiac chambers. The hearts were perfused in Langendorff (retrograde) and/or working (physiologic) mode. RESULTS: Eleven of 12 hearts achieved the following performance in working mode: peak left ventricular pressure of 21.5 to 75.8 mm Hg, with an average of 42.7 +/- 19.9 mm Hg. Intracardiac anatomical imaging was possible in all hearts, providing unique views of normal and pathological endocardial anatomy as well as biomedical device-heart interactions. CONCLUSIONS: We have described a unique isolated heart preparation with which we have successfully reanimated 11 human hearts deemed not viable for transplant, perfused them by working mode, and performed intracardiac anatomical imaging. This approach provides a novel means for obtaining images of functional human cardiac anatomy and various types of unique biomedical assessments.