Effect of therapeutic hypothermia against renal injury in a rat model of asphyxial cardiac arrest: Α focus on the survival rate, pathophysiology and antioxidant enzymes

Abstract

Although multi-organ dysfunction is associated with the survival rate following cardiac arrest (CA), the majority of studies to date have focused on hearts and brains, and few studies have considered renal failure. The objective of the present study, therefore, was to examine the effects of therapeutic hypothermia on the survival rate, pathophysiology and antioxidant enzymes in rat kidneys following asphyxial CA. Rats were sacrificed one day following CA. The survival rate, which was estimated using Kaplan-Meier analysis, was 42.9% one day following CA. However, hypothermia, which was induced following CA, significantly increased the survival rate (71.4%). In normothermia rats with CA, the serum blood urea nitrogen level was significantly increased one day post-CA. In addition, the serum creatinine level was significantly increased one day post-CA. However, in CA rats exposed to hypothermia, the levels of urea nitrogen and creatinine significantly decreased following CA. Histochemical staining revealed a significant temporal increase in renal injury after the normothermia group was subjected to CA. However, renal injury was significantly decreased in the hypothermia group. Immunohistochemical analysis of the kidney revealed a significant decrease in antioxidant enzymes (copper-zinc superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase and catalase) with time in the normothermia group. However, in the hypothermia group, these enzymes were significantly elevated following CA. Collectively, the results revealed that renal dysfunction following asphyxial CA was strongly associated with the early survival rate and therapeutic hypothermia reduced renal injury via effective antioxidant mechanisms.

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

“…In the present study, we found severe histological changes in kidney tissues. Jawad et al ( 26 ) and Kim et al ( 19 ) have reported the same pattern of histopathological changes in renal tissues after induction of asphyxial CA. Creatinine and BUN are the most frequently utilized endogenous indicators for assessing glomerular function ( 30 ).…”

“…A previous experiment has found that antioxidant enzymes including SOD-1, SOD-2, CAT, and GPx in kidneys exposed to ischemia for 30, 60, 90 min, 2 h, and 24 h are reduced significantly ( 40 ). Kim et al ( 19 ) have shown that immunoreactivity of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) in renal tissues are decreased at 1 day after I/R induction by asphyxial CA and that hypothermia treatment can increase the expression of antioxidants enzymes.…”

“…Mean arterial pressure (MAP) was measured by cannulation of the left femoral artery. To induce CA in rats, intravenous vecuronium bromide (2 mg/kg, Gensia, Sicor Pharmaceuticals, USA) was inserted, and mechanical ventilation was stopped ( 19 ). CA was confirmed by MAP values lower than 25 mmHg after 3-4 min of a stabilization period.…”

“…CA was confirmed by MAP values lower than 25 mmHg after 3-4 min of a stabilization period. Five minutes after induction of CA, epinephrine (0.005 mg/kg, Sigma, USA) and sodium bicarbonate (1 mEq/kg, Sigma) were injected intravenously ( 19 ). Mechanical chest compression (Jeung Do Bio & Plant Co., Ltd., Korea) was done at 300/min with 100% oxygen supply.…”

“…However, in a previous experiment, antioxidant enzymes and their relationships with renal injury were observed only one day after induction of asphyxial CA enzymes (19). A time-course study was not performed.…”