Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels and excretion of prostaglandins in stable renal allograft recipients.

AIMS: Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8-week withdrawal phase in pretreated patients. PATIENTS AND METHODS: Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-beta1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other anti-hypertensive drugs. RESULTS: Creatinine clearance as well as TGF-beta1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2. CONCLUSIONS: We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.

Optimization of intraperitoneal injection anesthesia in mice: drugs, dosages, adverse effects, and anesthesia depth.

PURPOSE: The goals of the study were to find a safe intraperitoneal injection anesthesia protocol for medium-duration surgery in mice (e.g., embryo transfer/vasectomy) coupled with a simple method to assess anesthesia depth under routine laboratory conditions. METHODS: Eight anesthetic protocols consisting of combinations of dissociative anesthetics (ketamine, tiletamine), alpha2-agonists (xylazine, medetomidine), and/or sedatives (acepromazine, azaperone, zolazepam) were compared for their safety and efficacy (death rate, surgical tolerance), using observations and reflex tests. The four best protocols were further evaluated during vasectomy: physiologic measurements (respiratory rate, electrocardiogram, arterial blood pressure, body temperature, blood gas tensions, and acid-base balance) were used to characterize the quality of anesthesia. The reactions of physiologic parameters to surgical stimuli were used to determine anesthesia depth, and were correlated with reflex test results. RESULTS: The protocol with the highest safety margin and the longest time of surgical tolerance (54 min) was ketamine/ xylazine/acepromazine. Three further anesthetic combinations were associated with surgical tolerance: ketamine/ xylazine, ketamine/xylazinelazaperone, and tiletamine/xylazine/zolazepam (Telazol/xylazine). The protocols consisting of ketamine/medetomidine and ketamine/azaperone were not associated with clearly detectable surgical tolerance. The most reliable parameter of surgical tolerance under routine laboratory conditions was the pedal withdrawal reflex. CONCLUSIONS: The best intraperitoneal injection anesthesia regimen consisted of ketamine/xylazine/acepromazine. The dose must be adapted to the particulars of each experimental design (mouse strain, sex, age, mutation). This is best done by measuring surgical tolerance, using the pedal withdrawal reflex.