Diazoxid eIncrease sLive ran dKidne yHSP2 5an dHSP70 Afte rShoc kan dStroke

Background. The compound, diazoxide (DZ), is known to induce preconditioning through its effect as a mito- chondrial KATP channel opener and succinate dehydro- genase inhibitor. Our team tested the hypothesis that pharmacological induction of ischemic precondition- ing with DZ can offer cytoprotection and preserve vi- tal tissues after hemorrhagic shock and stroke. Materials and methods. Sprague-Dawley male rats received an intraperitoneal injection of sterile saline or 5 mg/kg DZ in saline 24 h prior t o1h o fhemorrhagic shock, by 40% total blood loss volume (Shock Study), or a permanent unilateral common carotid ligation just before shock (Stroke Shock Study). While re- maining under isoflurane anesthesia, animals then re- ceived 81 mL/kg intravenous sterile saline over the next 45 min for recovery and survived for another 24 h. Results. When DZ was administered 24 h prior to shock, it significantly reduced hyperglycemia, which in vehicle-treated animals persisted after resuscita- tion. DZ also attenuated hyperlactatemia during the 1-h shock period. With more severe trauma from com- bined stroke and shock, DZ also decreased hyperlac- tatemia and hyperglycemia levels but the reduction was only significant for hyperglycemia. The expres- sion levels of heat shock proteins 25 (HSP25) and 70 (HSP70) were used as biomarkers for response of the kidney and liver to DZ and combined stroke and shock. Compared to vehicle-treated animals, DZ- treated rats subjected to shock and stroke exhibited increased HSP25 and HSP70 in kidney and liver tissue.