Pharmacological intervention for renal protection during cardiopulmonary bypass

Abstract

The possibility of minimizing organ damage following cardiopulmonary bypass (CPB) was examined. In the control group, n = 21, upon completion of CPB, elevation of the lysosomal enzyme beta-glucuronidase, which is a sensitive indicator of cellular damage, was affected by the concentration of granulocyte elastase (r = 0.59) or the endothelial-derived constricting factor, endothelin, (r = 0.8). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase) in urine, was also affected by endothelin (r = 0.79, r = 0.56), elastase (r = 0.6, r = 0.71), and by free hemoglobin levels (r = 0.76, r = 0.82). Next, the efficacy of pharmacological intervention for the prevention of renal damage was evaluated. During CPB, the administration of an elastase inhibitor (ulinastatin, 3 x 10(5) IU), n = 8, or a calcium antagonist (nicaldipine HCl, elastase release inhibitor; 5 gamma/kg per min), n = 8, significantly reduced the elevation of beta-glucuronidase and renal tubular enzymes (p < 0.05). Although the ulinastatin and nicardipine groups demonstrated low values of elastase in the Intensive Care Unit (ICU), only the values of the nicardipine group reached statistical significance (p < 0.05). A reduction in endothelin levels compared to the control group was observed in the nicardipine group. However, preventive and counteractive effects of nicardipine against vasoconstriction caused by endothelin were also considered to play an important role in the prevention of renal damage. The addition of haptoglobin (4,000 IU) to the priming solution of the CPB also reduced levels of renal tubular enzymes (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Independent Risk Factors and 2-Year Outcomes of Acute Kidney Injury after Surgery for Congenital Heart Disease

“…Boldt et al [13] reported that kidney damage was significantly more severe in patients with CPB time >90 min compared to those with CPB time <70 min. Renal injury may be caused by the production of free radicals, hydroxyl radicals, endothelin, free plasma hemoglobin, and elastase during CPB [14,15]. Non-pulsatile flow, renal hypoperfusion, and hypothermia were reported to show adverse effects on renal function [16,17].…”

Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins

“…The primary therapeutic effect in these disease states is protection of the kidneys from Hb-induced toxicity. 87 Thus far, no therapeutic experience exists for Hpx in a clinical setting. However, several United States-and European-based pharmaceutical companies have commenced development projects to fractionate Hp and Hpx from human plasma for use as therapeutics during hemolytic diseases.…”

Effects of ulinastatin (urinary trypsin inhibitor) on ATP, intracellular pH, and intracellular sodium transients during ischemia and reperfusion in the rat kidney in vivo

“…Ulinastatin (UTI; urinary trypsin inhibitor) is a Kunitz-type protease inhibitor that inhibits the activity or release of lysosomal enzymes such as elastase and catepsin G [5,6]. It has been reported to help protect against shock and operative stress [7-10] and suppress the deterioration of renal function associated with surgical procedures, chemotherapy, and various types of shock [11][12][13]. However, the effects of UTI on energy metabolism and intracellular Na ϩ levels have not been fully investigated, and its mechanisms for protecting against renal ischemia have not yet been clarified.…”