Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

Abstract

Purpose: The aim of the study was to compare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R) injury. Materials and Methods: Fifteen farm pigs were submitted to left kidney ischemia and right nephrectomy during the same procedure. Animals were divided into three groups. Group 1 was submitted to warm ischemia; Group 2 was submitted to cold ischemia with ice slush; and Group 3 received trimetazidine 20 mg one day and 4 hours before surgery. Ischemia time was 120 minutes in all three groups. Serum creatinine (SCr) and plasma iohexol clearance (CLioh) were measured before surgery and on postoperative days (PODs) 1,3,7, and 14. Semi-quantitative analyses of histological alterations were performed by a pathologist. A p value of < 0.05 was considered significant. Results: All groups showed elevation of serum creatinine in the first week. Serum creatinine was higher in Group 3 in the first and third postoperative days (Mean Cr: 5.5 and 8.1 respectively). Group 2 showed a lower increase in creatinine and a lower decrease in iohexol clearance than the others. Renal function stabilized in the fourteenth POD in all three groups. Analyses of histological alterations did not reach statistical significance between groups. Conclusion: Trimetazidine did not show protection against renal I/R injury in comparison to warm ischemia or hypothermia in a porcine model submitted to 120 minutes of renal ischemia.

Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model

“…This study showed that the significant reduction in single kidney GFR following one hour of warm ischemia was reversible within a few hours of reperfusion, which was not the case after two hours of warm ischemia time. These observations are supported by other studies [ 6 , 10 , 33 ]. In contrast to previous observations in a porcine renal-transplantation model [ 34 , 35 ] no changes in renal blood flow was observed following I/R-I, neither in the cortex nor the medulla.…”

“…The variation in GFR was reduced following catheterization of the ureters on Day 14, which is essential for the evaluation of the primary endpoint of this study. Other studies avoided this issue by using a single-kidney model [ 10 , 11 ]. Single-kidney nephrectomy allows for measuring the function of the remaining, damaged kidney using total urinary output.…”

“…Furthermore, I/R-I is induced by a variety of methods, including clamping of renal vessels [ 6 ], intra-arterial ballooning of the aorta [ 12 ], or renal autotransplantation [ 13 ]. Some of the studies on attenuation of AKI have produced promising results, but the results have not been conclusive [ 6 , 10 ]. This is probably partly related to lack of a perfect animal model for preclinical trials.…”

Ineffectiveness of Remote Ischemic Renal Preconditioning in a Porcine Solitary-Kidney Model

“…This system was constructed based on previously published methods incorporating the lesion size in the kidney where: 1 = no abnormality, 2 = lesion less than 25% of sample, 3 = lesion 25% to 50%, 4 = lesion 50% to 75%, 5 = lesion greater than 75%. 16 The pathologist was blinded to the study groups.…”

Impact of endogenous hydrogen sulfide on toll-like receptor pathway in renal ischemia/reperfusion injury in rats

“…Renal ischemia-reperfusion injury (IRI) often happens in clinical conditions such as hypovolemic shock, kidney transplantation, partial nephrectomy and vascular surgery. 1,2 Operative interruption of renal blood flow during transplantation can lead to IRI, which may cause acute kidney injury (AKI) and affect recovery of early graft function and graft survival. 3 Thus, it is of great importance to investigate how to prevent and treat IRI induced acute/chronic renal disease.…”