The Effect of Fenoldopam Administration Followed by Unclamping of Supraceliac Aortic Cross-Clamping on Renal Ischemic Injury / 대한마취과학회지

BACKGROUND: The overall rate of renal complication after surgery on the suprarenal aorta remains high. In this study, the changes in renal blood flow (RBF), urinary oxygen tension (PuO2), renal vascular resistance (RVR), and urinary volume following fenoldopam administration were investigated in supraceliac aortic cross-clamping and unclamping animal model. METHODS: Twelve dogs were divided into two groups; control group (n = 6), fenodopam group (n = 6). After brachial, femoral, and pulmonary arterial catheterization, midline abdominal incision was made. For the aortic cross-clamping the supraceliac aorta was exposed. A doppler flowmeter probe was placed around right renal artery. A ureteral catheter was positioned at the right renal pelvis to measure urine volume and urinary oxygen tension (PuO2). In fenoldopam group, 0.5microgram/kg/min of fenoldopam was administered immediately before suprarenal aortic reperfusion. Systemic hemodynamics, renal blood flow, renal vascular resistance, PuO2, and urine volume were compared between two groups. RESULTS: The systemic hemodynamics were not significantly different between the two groups throughout the experiment. After aortic reperfusion, the RVR significantly increased in control group, but the RVR in fenoldopam group remained to baseline level. The urine output, RBF, and PuO2 significantly increased in fenoldopam group compared to control group. BUN and serum creatinine were not different between the two groups. CONCLUSIONS: High dose of fenoldopam administration reverse ischemic renal insufficiency after supraceliac aortic cross clamping.

Alteration of Growth Factor Expression after Acute Ischemic Renal Injury

PURPOSE: Regeneration and repair after ischemic renal injury appears to be modulated by circulating or locally produced growth factors. This study examined the changes of serum insulin like growth factor(IGF-I) and renal expression of IGF-I and II, vascular endothelial growth factor(VEGF), transforming growth factor-beta(TGF-beta), and connective tissue growth factor(CTGF) during the active regeneration period after acute ischemic injury. METHODS: Sera and kidney tissue samples(whole kidney, cortex, outer medullae and inner medullae) were obtained before and after one, three, five and seven days of 40 minutes bilateral renal pedicle clamping. Acute renal failure was assessed by measuring the concentration of serum creatinine. Serum IGF-I level was measured by radioimmunoassay. The mRNA expression in kidney was measured by RT-PCR. The distribution of IGF-I and CTGF was detected by immunohistochemistry. RESULTS: Serum IGF-I concentration after one day following acute ischemic renal injury was significantly decreased compared to preischemic value. The mRNA levels of IGF-I, IGF-II, TGF-beta1 and VEGF in whole kidney were temporally decreased on day one of ischemic injury. IGF-I and IGF-II expressions in outer medullae were significantly decreased on day one after ischemic injury. TGF- beta, CTGF and VEGF expressions were markedly decreased in medullae after one day of ischemic injury compared to other kidney sections. IGF-I was markedly decreased in cortical tubules on day one of uremic rat. CTGF was markedly increased on tubule within three days of ischemic injury. CONCLUSION: These findings suggest that IGFs, TGF-beta and CTGF may involve in the pathogenesis or the recovery from acute ischemic renal injury.

Effect of Calcium Channel Blocker on Gene Expression of Renin after lschemic Renal Injury / 대한내과학회지

OBJECTIVES: lschemic acute renal failure(ARF) is characterized by an abrupt and sustained decline in GFR within minutes to days after renal ischemia and not immediately reversed on restoration of renal blood flow. The typical delay of a few days to a few weeks suggests reversible parenchymal damage awaiting cell regeneration for functional recovery. Many potentially cell damaging factors, such as ATP depletion, plasma membrane phospholipid degradatian and superoxide-induced membrane damage, play a central part in ischemic injury. More recently, much attention has been focused on the role of calcium, especially ischemic cell injury and the possible therapeutic role of calcium channel blockers emerged from studies conducted several years ago. In the past, it was thought that activation of renin-angiotensin system plays a role in the pathogenesis of ARF. Now the role of angiotensin in human renal ischemia also appears to be controversial. The following study was done in order to investigate the effect of a calcium channel blocker, nifedipine, on gene expression of renin during acute ischemic renal injury. METHODS: The Sprague-Dawley rats were divided into 4 groups, group I(n=3) as the control, group II (n=3) as the sham operation group, group III(n=15) as the ischemic renal injury group without nifedipine pretreatment, and group IV(n=15) as the ischemic renal injury model by right nephrectomy and left renal artery clamping for 40 minutes with systemic nifedipine pretreatment(10mg/kg), 1n ischemic renal injury model(group III and IV), rats were further divided into three subgroups according to reperfusion time of 1,24,72 hours. The non-ischemic right kidney removed at the time of initial procedure served as paired control. Total renal RNA was extracted by Chomczynskis method and electrophoresis was done in a 1% agarose gel containing 2,2M formaldehyde. Northern was performed at 42degrees C with isotope labeled renin probe for 18 hours, Autoradiographs were obtained and quantitated by a densitometer measured at 530nm. RESULTS: 1) The expression of renin gene was markedly decreased after renal ischemia and slowly recovered to one half of the control level after 72 hours of reperfusion. 2) Renin gene expression pattern of ischemic renal injury with prior nifedipine treatment was similar to the ischemic group without nifedipine pretreatment. CONCLUSION: These findings suggest that the renin gene expression was markedly decreased after renal ischemia and slowly recovered. Systemic nifedipine pretreatment does not have a significant effect on gene expression pattern of renin in ischemic renal injury.