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실험적 급성 허혈성 신부전에서 Verapamil 이 혈중 Polyamine 동태에 미치는 영향
원동준(Dong Jun Won),권현민(Hyun Min Kwon),김용섭(Yong Seop Kim),구자룡(Ja Ryong Gu),권영주(Young Ju Kwon),조원용(Won Yong Cho),김형규(Hyung Kyu Kim) 대한내과학회 1991 대한내과학회지 Vol.40 No.6
It has been proposd that calcium entry from an external medium increases intracellular free calcium to toxic levels during ischemic acute renal failure, and verapamil (ARF) has been suggested as the agentblocking calicium entry into renal cells and protecting renal function during ischemic injury. Polyamines, anorganic cations that play various roles in normal cellular proliferation and differentiation, accumulate in renal failare. Alsa it has been suggested tht the synthesis and metabolism of polyamine are influence by acute changes of the general condition, such as acute renal failure, and are mediated by a calcium influx into the cells. The study was designed to study the protective effects of systemic verapamil pretreatment on renal function and the influence on polyamine metabolism in experimental ischemic ARF in cats. For these purpose, the experimental animals were divided into 2 groups. While Group I (n=5) was an ischemic ARF model by renal artery clamping for 60 minutes, Group II (n=5) was ischemic ARF with systemic verapamil (5 ml/min/kg) pretreatment. The creatinine clearance and plasma and urinary polyamine were measured in each group before and after the renal artery clamp. The results were as follows: 1) Creatinine clearance before and after the renal artery clamp were 10.64±7.18 ml/min/kg and 2.09±1. 70 ml/min/kg in Group I, 4.47±3.38 ml min/kg and 0.60±0.79ml/min/kg in Group II, respectively, So creatinine clearance decreased more significantly in Group II campared with Group I. 2) Plasma polyamine increased after ischemia in Group I. In group I, plasma levels of putrescine, spermidine, and spermine before ischemia were 4.75±0.40 nmol/ml, 0.69±0.09 nmol/ml, and 0.83±0.63 nmol/ml, were elevated to 7.17±2.91 nmol/ml, 9.83±1.46 nmol/ ml, and 2.64±1.14nmol/ml after ischemia. But in Group II, the plasma level of polyamine was not changed, and especially, spermine decreased significantly from 0.83±0.27 before ischemia to 0.49±0.23 nmol/ml after ischenmine (p=0.033). 3) Urine polyamine excretion decreased after ischemia in Group I and Group II. In Group II, urinary excretion of spermidine and spermine before ischemia, 0.13±0.10 nmol/min and 0.17±0.13nmol/min, decreased after ischemia to 0.01±0.01nmol/min (p=0.019) and 0.032±0.26 nmol/min (p=0.0257). 4) In renal tissue, spermine content vas highest. In Group II, preischemic spermine were 397.20 nmol/g and increased to 646.66nmol/g after ischema, But there were no significant changes in the polyamine contents in Group II. From these data, it was suggested that systemic verapamil pretreatment exerts no protective effect on ischemic ARF. Plasma polyamines are elevated in ischemic ARF, and verapamil may protect these elevations.
지속성 외래 복막투석중인 당뇨성 신부전에서 Verapamil 의 복강내 투여가 β2 - Microglobulin 에 미치는 영향
변현주(Hyun Ju Byun),차대룡(Dae Ryong Cha),권현민(Hyun Min Kwon),권영주(Young Ju Kwon),조원용(Won Yong Cho),김형규(Hyoung Kyu Kim) 대한내과학회 1991 대한내과학회지 Vol.41 No.5
In diabetic renal failure, generalized vasculopathy including capillaries is presented, and so there may be some difference in ultrafiltration and mass transport from that of non-diabetic renal failure. Recently, several studies show that intraperitoneal administration of Ca++ antagonist may increase ultrafiltration and mass transport of small molecular weight substance in CAPD. It suspected that the effect of intraperitoneal administration of verapamil on CAPD, may have different response in diabetic and non-diabetic renal failure. In order to evaluate the effects of calcium antagonist (verapamil) on the permeability of the peritoneal membrane in patients on CAPD, serum levels and clearances of creatinine, urea, and β2-Microglobulin, mass transferarea coefficient, ultrafiltration rate and glucose absorption were measured. The study group was devided by 5 non-diabetic (age 33.4+12.4 years, treated for 10.1+8.4 months, Group I) and 5 diabetic (age 53.2+13.7 years, treated for 16.6+15.2 months, Group II) renal failure patients and the study was carried out using 1.65% dextrose dialysate solution for 240 minutes dwell time (phase I), and after the intraperitoneal administration of 10 mg of verapamil the peritoneal dialysis was done by same method as phase I (1phase II). To evaluate the effects of verapamil, percent difference of change between phase I and phase II was calculated. All the values here are mean. The results are: 1) Serum levels of creatinine and β2-Microglobulin were lower in Group II (11.4 vs 6.8 mg/dl, 39.4 vs 18.2 mg/dl) (p<0,01). 2) Peritoneal clearance of creatinine was higher in Group II (6.322 vs 7.072 ml/min), but the increasing rate after instillation of verapamil was slightly lesser than Group I (6.5 vs 4.0%) (not significant). 3) Peritoneal clearance of β2-Microglobulin was higher in Group II (0.626 vs 0.88 ml/min), and the increasing rate after instillation of verapamil was marked in both group, especially in Group I (83.5 vs 36.1%) (not significant). 4) MTAC was higher in Group II (9.7 vs 12.78 ml/min), but the increasing rate of it was greater in Group I (15.4 vs 3.58%) (not significant). The peritoneal permeability was greater in Group 1I probably due to increased permeability and changed structures of peritoneal capillaries in diabetic disease, and the effects of calcium antagonist (verapamil) on peritoneal permeability was lesser in Group II. It suggests that the intraperitoneal administration of verapamil increase the efficiency of CAPD in general, but the benefit may be lesser in diabetic patients.
실험적 허혈성 급성 신부전 모델에 대한 칼슘 길항제의 효과
권영주(Young Joo Kwon),이규백(Kyu Back Lee),권현민(Hyun Min Kyeon),조원용(Won Yong Cho),김형규(Hyoung Kyu Kim),노정우(Chung Woo Noh) 대한내과학회 1989 대한내과학회지 Vol.37 No.4
N/A Recently, much attention has been focused on the role of calcium in mediating or propagating ischemic cell injury. Modifying alterations in cell calcium redistribution or cellular calcium influx with a variety of agents have been beneficial in ameliorating the degree of cell injury in a number of experimental settings. But studies on animal models about ischemic acute renal failure (ARF) produced either by infusion of vasoconstrictors or by interrupting renal artery blood flow have provided conflicting results. The purpose of this study was to evaluate the effect of calcium entry blockers in an ischemic ARF model by the renal artery clamp in rats. Nine cats were anesthetized with pentobarbital sodium (40mg/kg, I.M,) and a tracheostomy, an IV line and a urinary catheter were placed in position. Temperature was maintained at 37.5 degrees C. By an abdominal approach, both renal arteries were isolated. Four cats were used as controls and received saline for 2 hours before bilateral renal artery clamping. Another five cats were treated with verapamil (5㎍/kg/min.) systemically for 2 hours before bilateral renal artery clamping. All nine cats underwent 1 hour of renal artery clamp followed by 3 hours of reperfusion and hydration with saline. Before clamping and after reperfusion, blood and urine were sampled for creatinine, Na and K, and urine volume was measured. The results were as follows: In the control group, the serum creatinine level was 1.28㎍0.33㎎/dl before clamping and increased to 1.63±0.73㎎/dl after clamping; in the experimental group, the serum creatinine level was 1.20±0.33㎎/dl before clamping and increased to 1.75±0.50㎎/dl after clamping. In the control group, the Ccr value was 13.08±9.25ml/min before clamping and decreased to 0.41±0.22ml/min after clamping; in the experimental group, the Ccr value was 6.24±6.18ml/min before clamping and decreased to 0.14±0.09ml/min after clamping. But these results were not significant statistically. Our results suggested that systemic pretreatment with a calcium entry blocker (verapamil) may be ineffective in an ischemic ARF model by renal artery clamping in cats.