Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free glutathione (42%), protein-bound GSH (17%), and vitamin E (49%). In contrast, catalase or glutathione peroxidase activities were not affected by these experimental conditions. Free radical production in this model was also measured directly using electron spin resonance (ESR) spectroscopy associated with a PBN (alpha-phenyl N-tert-butyl-nitrone) spin trap agent in the venous blood arising from the ischemic kidney. The signal consisted of a triplet of doublets. In contrast, no signal could be detected in control blood samples taken prior to inducing ischemia. The burst of free radical production occurred in the early phase after restoration of flow in the kidneys rendered ischemic, as evidenced by a signal of weak intensity which generally appeared within the third minute after reperfusion and progressively increased to form a well-defined asymmetric signal following 10 min of reperfusion. The precise nature of free radicals trapped by the PBN agent remains, however, to be elucidated, but analysis of the coupling constants (aN = 14.5-15 G; a beta H = 2.5-3 G) and asymmetry of the central doublets suggests that the ESR signal may arise from a nitorxy-radical adduct resulting from the spin trapping by PBN of both oxygen- or carbon-centered radicals of lipid origin. As evidenced by both direct and indirect measurements, exchange of rabbit blood immediately after inducing renal ischemia with 30 ml/kg of Diaspirin Crosslinked Hemoglobin (7.5 g/dl in lactated electrolyte) or human serum albumin (7.5 g/dl in lactated electrolyte) did not exacerbate free radical production mediated by an ischemia reperfusion phenomenon, a typical situation found in a resuscitation setting.
 ...
PMID:Diaspirin crosslinked hemoglobin (DCLHb): absence of increased free radical generation following administration in a rabbit model of renal ischemia and reperfusion. 763 50

Early approaches to the development of oxygen carriers involved the use of stroma-free hemoglobin solutions. These solutions did not require blood typing or crossmatching and could be stored for long periods. In addition, a variety of methods have been developed in chemically modifying and stabilizing the hemoglobin molecule. Several hemoglobin therapeutics are now in clinical trials as temporary alternatives to blood or as therapeutic agents for ischemia. The various hemoglobin products under development are derived from three principal sources: human, bovine and genetically engineered hemoglobin. Diaspirin cross-linked hemoglobin (DCLHb), administered at doses ranging from approximately 20-1000 ml, has been investigated in a number of clinical trials in patients undergoing orthopedic, abdominal aortic repair, major abdominal surgery, cardiac surgery and in critically ill patients with septic shock. In several studies, DCLHb was effective in avoiding the transfusion. However, Baxter Healthcare Corporation (Chicago, Illinois, USA) stopped the development of DCLHb after two unsuccessful trials in trauma patients. Bovine polymerized hemoglobin has also been extensively studied. Several phase II and phase III trials have been performed with this product in hemorrhagic surgery, cardiac surgery and vascular surgery, but data have not yet been published. Hemoglobin therapeutics could provide an important new option as an alternative to blood transfusion. Furthermore, they may be able to provide an immediate on-site replacement for traumatic blood loss, prevent global ischemia and organ failure, treat focal ischemia, and provide effective hemodynamic support for septic shock-induced hypotension.
 ...
PMID:Blood substitutes. Haemoglobin therapeutics in clinical practice. 1109 87