Effects of Intrarenal Administration of the Cox-2 Inhibitor Parecoxib During Porcine Suprarenal Aortic Cross-Clamping

Abstract

The aim of this study was to investigate the effects of intrarenal administration of the cyclooxygenase-2 inhibitor parecoxib during suprarenal aortic cross-clamping. In a prospective, controlled, blinded, randomized manner, 16 anesthetized and mechanically ventilated pigs were instrumented to measure systemic and right kidney hemodynamics, oxygen exchange, and metabolism. During 45 min of suprarenal aortic cross-clamping, animals received 40 mg of parecoxib (n = 8) or vehicle (n = 8) infused continuously into the right renal artery. Hemodynamic and metabolic data, right kidney venous blood, as well as urine samples were obtained before clamping, as well as before and 75 and 195 min after declamping. Clamping transiently increased mean arterial pressure in both groups. Systemic and renal blood flow did not differ between the pre- and postclamping measurements or between groups. Parecoxib attenuated the otherwise significant fall in right kidney creatinine clearance (controls: from 45 [7;111] to 17 [9;22] mL/min; parecoxib: from 39 [3;59] to 27 [11;45] mL/min, P = 0.039 and P = 0.297, respectively versus before clamping, P = 0.021 versus controls at 195 min) and prevented the impairment of renal lactate balance observed in the control group (controls: from 0.5 [-0.8;3.5] to 0.2 [-0.2;0.6] mumol/kg/min; parecoxib: from 0.6 [-1.0;2.0] to 0.4 [-1.2;0.6] mumol/kg/min, P = 0.038 and P = 0.285, respectively, versus before clamping). In conclusion, intrarenal parecoxib infusion beneficially influenced kidney function in this clinically relevant model of suprarenal aortic cross-clamping.

Nephroprotective Effects of Polydatin against Ischemia/Reperfusion Injury: A Role for the PI3K/Akt Signal Pathway

“…Selective or nonselective inhibition of COX-2 with either rofecoxib or indomethacin ameliorated renal tissue damage induced by I/R injury [ 32 ]. Another study has shown that continuous intrarenal infusion of parecoxib (40 mg per pig) improved renal function in pigs with the operation of suprarenal aortic cross clamping [ 33 ]. These results of previous studies suggested that inhibition of COX-2 has the potential to improve renal function in renal I/R injury.…”

Temporary adrenal dysfunction with descending thoracic aortic occlusion

“…Ischemia-reperfusion renal injury results in impaired postoperative renal function in up to 50% of the cases and this has been also confirmed in a porcine model of suprarenal aortic cross-clamping (19,20). The development of postoperative renal impairment is a major cause of perioperative morbidity and mortality after thoracic aortic surgery.…”

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats

“…Additionally, no effects on the cardiovascular system of treated animals were observed, and the authors concluded that intrarenal parecoxib infusion positively affected kidney function 12 .…”

“…For instance, Patel et al 11 used the concentration of creatinine in ischemia/reperfusion models in rats and showed that parecoxib increases renal dysfunction and injury associated with this form of renal stress. Conversely, Hauser et al 12 showed that parecoxib attenuates renal function impairment during porcine suprarenal aortic cross-clamping.…”