Increase In BUN Levels Research Articles

#1451 Calcimimetics reduce the progression of high-phosphate diet-induced tubular damage

Abstract Background and Aims During chronic kidney disease (CKD) progresses, there is an increased phosphate load and the concentration of the phosphaturic hormones PTH and FGF23 rises. In patients, phosphate and FGF23 are discussed as risk factors for CKD progression. We have recently shown that mice with high phosphate, PTH and FGF23 levels develop Stat3/Kim-1-mediated proximal tubule damage and tubulointerstitial fibrosis associated with increased MCP-1 expression and accumulation of macrophages. Calcimimetics lower PTH and FGF23 levels in hemodialysis patients and are thought to have both cardio- and nephroprotective effects. In a preclinical study, cinacalcet was shown to stabilize podocyte function in proteinuric mice. Therefore, we postulate that calcimimetics also have a positive effect on the progression of tubular damage in mice with high phosphate, PTH and FGF23 levels. Method For the induction of phosphaturic hormones with concomitant tubule damage, male C57BL/6 mice were fed a 2.0% high phosphate diet (HPD) and compared to animals on a 0.8% control phosphate diet (CPD). After four months, one HPD group was additionally treated with 1 mg/kg body weight/day etelcalcetide (KP-2326). Six months after the start of the trial, blood and urine samples as well as kidneys were taken for biochemical, histological and molecular biological examinations. Results KP-2326 treatment reduced HPD-induced PTH and FGF23 levels, but had no effect on increased phosphate excretion or elevated serum phosphate levels. Histologically, tubular damage was not as pronounced in the KP-2326-treated HPD animals as in the HPD group without therapy. The increased BUN levels caused by HPD and the albuminuria were significantly reduced by KP-2326. KP-2326 reduced HPD-mediated activation of Stat3 in proximal tubule cells and decreased Kim-1 synthesis at both mRNA and protein levels. Moreover, KP-2326 significantly reduced the mRNA expression of Ccl2 and the macrophage-specific marker Adgre1 compared to the untreated HPD group, which was histologically reflected in a lower accumulation of F4/80+ macrophages around the damaged tubules. Conclusion Treatment with KP-2326 was able to reduce the progression of HPD-induced tubule damage, at least in part due to the reduction in PTH and FGF23 levels.

Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution.

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells-Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats' general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD-0.67 ± 0.12; 1/5 MAD-0.59 ± 0.07; 1/10 MAD-0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels.

Abstract 13196: Highly Active Antiretroviral Therapy-related Complications And Associated Genetic Susceptibility Variants In Hiv-infected Patients With Pre-existing Heart Failure: A 7-year Prospective Cohort Study

Introduction: HAART-associated metabolic syndromes have been reported, without such risk and genetic markers in patients with pre-existing heart failure (HF) being addressed. Hypothesis: We hypothesize that compared with HIV-infected patients without HF undergoing HAART, patients with pre-existing HF are at higher risk of long-term HAART-related metabolic complications, which is associated with genetic variants. Methods: In this prospective cohort study 172 HIV-infected patients were recruited and followed-up since 2013. Demographic and medical records such as weight, BMI, drug use, lab data of blood and urine, HAART regimens, Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) CVD risk scores, were recorded. Multivariate regression model was used to derive risk of adverse outcomes following HAART in HF patients, compared to matched-patients without HF. GWAS was conducted in HF patients to investigate genetic variants associated with adverse events susceptibility. Results: After matching on baseline, HAART was effective for both patients with or without HF, at a similar viral load (r=0.001, P=0.69) and CD4 count (r=-0.06, P=0.48). D:A:D (R) (r=0.002, P=0.97) and D:A:D (F) (r=0.04, P=0.62) CVD risk scores were comparable in patients with and without HF. Patients with HF presented with higher risks of subsequent T2DM (r = 0.24, P=0.01) and increased total cholesterol (r=0.23, P=0.006), LDL (r=0.18, P=0.04), and uric acid (r=0.35, P=0.004), compared to those without HF. Four independent SNPs in ABCG2 (rs717620), PNPLA3 (rs738409), CYP2A6 (rs28399433), and CYP2B6 (rs2279345) reached genome-wide significance for their associations with HAART-related complications in patients with HF, including ABCG2 for subsequent advanced stages CKD (eGFR < 30), PNPLA3 for increased HDL levels, CYP2A6 for increased BUN levels, and CYP2B6 for hematuria. Conclusions: HAART was equally effective for HIV management in HF patients, and did not result in more subsequent cardiotoxicities, compared with those without HF; however, increased risk of T2DM, and increased levels of CHO, LDL, and uric acid during follow-ups, were observed. Genetic susceptibility variants associated with HAART-related complications in HF patients were demonstrated.

Efek Pemberian Gentamisin Secara Oral Terhadap Kadar Asam Urat, Ureum, dan Kreatinin Tikus Wistar

ABSTRACTGentamicin is an aminoglycoside class of antibiotics which at high doses can cause damage to the kidneys. This research was to determine the levels of BUN, creatinine and amino acids after gentamicin induction. This research is experimental with gentamicin test material given to male rats as much as 0.3 ml/day for 7 and 10 days. Blood serum levels were then measured for BUN, creatinine and amino acids using a photometer microlab 300. The results showed that after doing treatment for 7 days the average value of BUN levels increase from 21.7 to 36.3 mg/dl, creatinine increase from 0, 88 to 1.9 mg/dl, uric acid increase from 1.54 to 4.29 mg/dl. It was concluded that giving of gentamicin as much as 0.3 ml/day for 7 and 10 days increased BUN levels, creatinine and uric acid exceeded the normal limit. Keywords : Gentamicin, urea, creatinine, uric acid, rat.

The association of blood urea nitrogen levels with mortality in acute pulmonary embolism

BackgroundThe aim of this study was to investigate the association of BUN levels with in-hospital and long-term adverse clinical outcomes in acute pulmonary embolism (APE) patients treated with tissue-plasminogen activator (t-PA). MethodsThis retrospective study included 252 consecutive confirmed APE patients treated with t-PA. An admission BUN of 34.5 mg/dL was identified through an ROC analysis as an optimal cutoff value to predict the in-hospital mortality with 85% sensitivity and 91% specificity (AUC: 0.91; 95% CI: 0.84–0.96; P<.001). ResultsOur study showed that an increase in BUN levels was independently associated with a high risk of in-hospital all-cause mortality, low admission systolic blood pressure, use of inotropic drugs, and cardiogenic shock. In-hospital mortality rates were 51.1% in higher BUN group, and 1.9% in lower BUN group (P<.001). ConclusionIn this study, elevated admission BUN level was found to be a predictor of all-cause in-hospital mortality. BUN testing is commonly part of the basic metabolic panel; and it can be used to detect high-risk patients with APE, and it bears little risk, is inexpensive, and easy to perform.

Evaluation of a high or low level of milk replacer, with or without varied intake, on neonatal Holstein calf performance and health

ABSTRACT Neonatal Holstein bull calves (n = 30; age ~ 1 wk; average BW = 39 ± 5.4 kg) were allocated randomly in a 2 × 2 factorial arrangement to evaluate a high or low level of 28% CP, 18% fat milk replacer (MR), with or without varied intake, on calf performance and health. Treatment factors included (1) level (high = 1.13 kg/d or low = 0.45 kg/d) and (2) daily intake (constant or varied). Calves were purchased in 2 blocks and followed for 35 d (block 1) and 42 d (block 2). Intake data and fecal scores were recorded daily; BW data and blood samples were collected weekly. Feeding a high level of milk replacer improved ADG (0.962 vs. 0.858 kg/d), reduced calf starter DMI (0.392 vs. 0.929 kg/d), increased BUN levels (11.62 vs. 9.77 mg/dL; P

Effect of coumaphos on cholinesterase activity, hematology, and biochemical blood parameters of bovines in tropical regions of Mexico

To assess the effect of coumaphos [O-(3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl) O,O-diethyl phosphorothioate] exposure on physiological responses during bovine production, acetylcolinesterase (AChE) and butyrylcholinesterase (BuChE) activities were measured in whole blood, erythrocytes, and plasma of healthy male steers (Bos Taurus x Bos indicus) sprayed with coumaphos at a non-lethal dose of 1 mg kg− 1 body weight per day once every 14 (in vivo group) or 21 days (southern and central groups). Coumaphos topically administered at 1 mg/kg body weight per day to cattle under normal management practices in tropical areas produced a significant inhibition in erythrocyte (RBC) AChE and BuAChE activities when compared to baseline levels. RBC-AChE activity for the in vivo group decreased 71.3% (P < 0.05) and BuChE activity 59.1% (P < 0.05); RBC-AChE activity decreased 55.1% (P < 0.05) (southern group) and 43.4% (P < 0.05) (central group). Compared to the control specimens, steers from in vivo, southern, and central groups after 150 days of exposure had lower (P < 0.05) leukocyte count, absolute lymphocyte, erythrocyte, and platelet counts. Decreases in RBC-AChE activities correlated with decreased lymphocyte (r = 1.000, p = 0.01), erythrocyte (r = 1.000, p = 0.003), and platelet counts (r = 0.841, p = 0.036). Significantly increased BUN levels (P < 0.05) correlated with the decrease in RBC-AChE activities (r = − 0.997, p = 0.047) and with the decrease in absolute red blood cell (r = − 0.883, p = 0.020) and lymphocyte (r = − 0.825, p = 0.043) counts; increased (P < 0.05) total plasma protein levels correlated with the decrease in RBC-AChE activities (r = −0.998, p = 0.043), absolute red blood cell (r = − 0.998, p = 0.040), lymphocyte (r = − 0.893, p = 0.017), and platelet (r = -0.855, p = 0.030) counts. The physiological responses correlated with the erythrocyte acetylcholinesterase inhibition could be considered as early indicators or warning responses of bovine exposures to organophosphorus pesticides (OPs).

Cephaloridine nephrotoxicity in diabetic rats: modulation by insulin treatment

Previous studies have indicated that cephaloridine nephrotoxicity was reduced in diabetic rats. This study determined whether the reduction in toxicity was due to streptozotocin or the diabetic state. Male Fischer-344 rats were injected intraperitoneally with 35 mg/kg streptozotocin to induce diabetes. Insulin (5 U/day, subcutaneously) was begun within 72 h and continued for 10 days. Toxicity was quantitated 48 h after injection of cephaloridine (1500 mg/kg i.p.) in normoglycemic (NC), diabetic (DC) and diabetic animals treated with insulin (DIC). Cephaloridine produced diuresis, glucosuria, proteinuria, elevated kidney weight and decreased renal cortical slice accumulation of organic ions in the NC group. Cephaloridine toxicity was reduced in the DC group since kidney weight, BUN level and renal cortical slice accumulation of organic anions were similar between treated and control animals. Cephaloridine treatment of the DIC group was associated with increased BUN levels, proteinuria and diminished renal cortical slice accumulation of organic cations. These results indicated that the diabetic state, and not streptozotocin, reduced cephaloridine nephrotoxicity.

Nephrotoxicity of para-substituted thiobenzamide derivatives in the rat

Histological examination, plasma urea nitrogen levels (BUN), and renal cortical slice uptake of p-aminohippurate (PAH) or tetraethylammonium (TEA) were used to assess the nephrotoxicity of thiobenzamide and its para-substituted derivatives in Sprague—Dawley rats. Intraperitoneal injection of p-methylthiobenzamide (PMTB) to rats resulted in dose-dependent nephrotoxicity as judged by increased BUN levels, decreased TEA uptake and histologic examination of the kidney. Para-methoxythiobenzamide and PMTB were more potent nephrotoxins than thiobenzamide, which was itself minimally nephrotoxic. Para-methylthiobenzamide- S-oxide (PMTBSO) was more nephrotoxic than PMTB. Rats were pretreated with 1-methyl-1-phenylbenzoylthiourea (MPBTU), a non-toxic arylthiourea which inhibits the metabolism and toxicity of thiocarbonyl compounds. The nephrotoxicity and hepatotoxicity of PMTB was reduced by treatment with MPBTU 30 min prior to PMTB. Pretreatment with MPBTU protected against the renal toxicity of PMTBSO. The results indicate that electron donating para-substituted thiobenzamides produce dose-dependent renal injury, dependent upon oxidative biotransformation.

The role of ortho-bromophenol in the nephrotoxicity of bromobenzene in rats

ortho-Bromophenol (1.92 mmol/kg, ip) caused a 50% decrease in renal glutathione levels within 90 min. In contrast, hepatic glutathione levels remained 80% of control values 5 hr after ortho-bromophenol administration. Renal glutathione was far more susceptible to the initial rapid depleting effects of ortho-bromophenol than was hepatic glutathione, the dose-response curve for hepatic glutathione depletion being shifted to the right. ortho-Bromophenol at doses greater than 1.6 mmol/kg caused severe renal necrosis in noninduced rats, with consequent elevations in BUN levels. This dose was one-fifth as large as that required by bromobenzene to produce a similar necrosis in phenobarbital-treated rats (W. D. Reid, Exp. Mol. Pathol., 19, 197–214, 1973). Phenobarbital pretreatment and depletion of tissue glutathione with diethyl maleate caused significant increases in BUN levels over controls. Pretreatment with piperonyl butoxide decreased the incidence of elevated BUN levels following ortho-bromophenol administration. While liver microsomes converted ortho-bromophenol to covalently bound material, kidney microsomes did not. However, in vivo, ortho-bromophenol covalently bound to kidney protein of control rats four times greater than to liver protein. Phenobarbital pretreatment increased the in vivo covalent binding to kidney protein but not to liver protein. The degree of covalent binding to kidney protein correlated with BUN levels ( r = 0.91, p < 0.001). The nature of the nephrotoxic metabolite of ortho-bromophenol is not known, but an intermediate may be generated in the liver and transported to the kidney. These findings suggest that ortho-bromophenol may play a role in the nephrotoxicity observed following bromobenzene administration.

Dexamethasone suppression of Cushingoid degenerative changes in obese spontaneously hypertensive rats (SHR)

Male and female, young (2 months old) and mature (10 months old), obese and nonobese, spontaneously hypertensive rats (SHR) were treated with dexamethasone, 5 μg/rat and 10 μg/rat, respectively, subcutaneously (SC) 2 times daily for 5 months. Steroid treatment stilled the voracious appetite of the obese SHR, and the massively obese, mature animals were reduced to almost normal size. The young, steroid-treated, obese SHR did not develop their genetically programmed corpulency. The untreated, young and mature, obese SHR ate voraciously, became massively obese, and developed their characteristic Cushing's disease-like spectrum of degenerative changes, eg, hypertension, hyperlipidemia, hyperglycemia, muscle wasting, kidney stones, thin skin, and accelerated aging. The blood pressure of the steroid-treated animals was lowered concomitant with reduced levels of circulating ACTH, β endorphin, insulin, triglycerides, and cholesterol. Dexamethasone caused hyperlipidemia, hyperglycemia, and increased BUN levels in young obese and nonobese SHR only. The mature obese SHR had giant-sized thymus glands that were further enlarged with steroid treatment; dexamethasone was thymolytic in young, obese and nonobese SHR. Desamethasone caused severe reduction of pituitary and adrenal gland size, simulating the condition of hypophysectomy. These findings demonstrate that dexamethasone suppression of the pitutary-adrenal axis palliates and prevents the spontaneous development of Cushingoid degenerative changes in these genetically obese and hypertensive rats.

Upper hemibody infusion of cis-diamminedichloroplatinum (II) followed by systemic antidote, sodium thiosulfate, for lung metastasis in rats.

Effects of a combination chemotherapy using cis-diamminedichloroplatinum (II) (DDP) and its antidote, sodium thiosulfate (STS), on metastatic lung tumour in rats were studied. Rats were given an upper hemibody infusion (UHI) of 15 mg/kg DDP immediately after occlusion of the abdominal aorta and i.v. administration of 1581 mg/kg STS (200-fold molar ratio to DDP) 10 min later. The aortic clamp was released at approximately 11 min after the beginning of UHI when a half volume of STS solution was infused. Antitumour and side effects in this group were compared with those in the respective control groups given 5 mg/kg DDP alone by UHI or by systemic administration. In the group given UHI of DDP (DDP-UHI) in combination with STS, there was a significantly better antitumour effect than seen in the group given DDP alone, as evaluated by the number of lung tumour nodules and survival time after inoculation of the transitional cell carcinoma into the lung. Nephrotoxicity, as assessed by increase in BUN levels, was completely avoided. Haematological toxicity effects assessed by decreases in WBC were slight but body-weight loss due to anorexia was severe.

Resistance of obese and non-obese, spontaneously hypertensive rats to alloxan-induced diabetes

Male, 5 month old, massively obese, spontaneously hypertensive rats (Obese/SHR) were given 10 mg alloxan/100 g b.w., s.c., to induce diabetes. Control Obese and non-obese/SHR were given saline. Insulin therapy was withheld. All of the animals were killed at 6 months of age. Alloxan caused a slight but statistically significant increase in blood pressure, pituitary and adrenal glandular hyperplasia, hyperlipidemia, hyperglycemia, and increased BUN levels. The giant sized islets of Langerhans in Obese/SHR showed only partial degranulation of the insulin-producing beta cells concomitant with residual but apparently adequate blood insulin levels, whereas the islets of non-obese/SHR exhibited virtually total beta cell degranulation and only trace amounts of blood insulin. The alloxanized, non-obese rats were severely emaciated; the alloxanized Obese/SHR maintained their obesity. Alloxan-treated, Obese and non-obese/SHR manifested gross and microscopic degenerative changes suggesting acceleration of the normal aging process. The genetically-programmed pathogenesis of diabetes, obesity, hypertension, and Cushingoid pathophysiology of Obese/SHR may be due to hyperadrenocorticism.

Nonoliguric Acute Renal Failure in the Newborn

Fifteen newborn babies with azotemia without oliguria were studied. Group A infants had increased BUN levels and decreased creatinine clearance (Ccr) for gestational and postnatal age, and were compared with group B infants, who had increased BUN levels and normal Ccr. The Ccr was 0.35 mL/min in group A and 0.76 mL/min in group B. Urine volume during the same period was 2.45 mL/kg/hr in group A and 4.66 mL/kg/hr in group B. No significant differences in fractional sodium excretion; urine to plasma ratios of creatinine, osmolality, and sodium; and renal failure index were present between the two groups. The results suggest that nonoliguric acute renal failure is a diagnostic entity in the newborn. The Ccr is the most useful indicator for defining renal function in the presence of azotemia and normal urine volume.

Altered Magnesium Transport in Slices of Kidney Cortex from Chemically-Induced Diabetic Rats

The uptake of magnesium-28 was measured in slices of kidney cortex from rats with alloxan-diabetes and from rats with streptozotocin-diabetes of increasing durations. In both forms of chemically-induced diabetes, magnesium-28 uptake by kidney cortex slices was significantly increased over uptake measured in kidney cortex slices from control rats. Immediate institution of daily insulin therapy to the diabetic rats prevented the diabetes-induced elevated uptake of magnesium without controlling blood glucose levels. Late institution of daily insulin therapy was ineffective in restoring the magnesium uptake to control values. These alterations in magnesium uptake occurred prior to any evidence of nephropathy (via the classic indices of proteinuria and increased BUN levels). The implications of these findings, together with our earlier demonstrations of altered calcium transport by kidney cortex slices from chemically-induced diabetic rats, are discussed in terms of disordered divalent cation transport being at least part of the basic pathogenesis underlying diabetic nephropathy.

Effectiveness of Insulin Therapy on Altered Renal Calcium Transport in Diabetic Rats

The uptake of 45Ca was measured in slices of kidney cortex from normal rats, streptozotocin-diabetic rats, and streptozotocin-diabetic rats treated early and late with insulin. Insulin therapy was performed such that blood glucose levels were controlled in half the treated diabetic animals but not in the others. Considerably earlier than evidence of nephropathy (i.e., proteinuria and increased BUN levels) in streptozotocin-diabetic rats, there was a significant decrease in active uptake of calcium by the kidney. Insulin therapy, begun immediately upon diagnosis of diabetes, maintained normal calcium transport even when blood glucose levels were not controlled. On the other hand, insulin therapy, begun 1 mo after diabetes was confirmed but before evidence of nephropathy, did not restore calcium transport to normal whether or not blood glucose was controlled. We conclude that this biochemical mechanism, which possibly may be implicated in the pathophysiology of diabetic nephropathy, is clearly influenced by duration of insulin deficiency and not by the degree in hyperglycemia.

A morphologic study of live Escherichia coli organism shock in baboons

This study was designed to examine the response of the baboon during a 24 hr period following live Escherichia coli organism infusion. Experiments were performed on 10 young adult adolescent baboons. Eight of the baboons received a mean concentration of 1.5 × 10 10 organisms/kg infused during a 30 to 360 min period. Two control baboons received anesthesia and 0.9% sodium chloride solution during the 24 hr period. Heart, lung, liver, and kidney were evaluated with both light and electron microscopy and the morphologic data were interrelated with the physiologic data. The acute lung lesion seen in 2 to 6 hr studies was not found in this prolonged shock model. Both the liver and kidney exhibited dysfunction; these pathophysiologic alterations were accompanied by morphologic changes. Sinusoidal fibrin thrombi and hepatocyte damage were observed in the liver, and were associated with increases in LDH, FLDH, and hypoglycemia. Glomerular fibrin thrombi and tubular epithelial changes of cytoplasmic vacuolization and brush border loss were present in the kidney, and an increase in BUN levels was noted. Our data would indicate that the live E. coli infusion baboon model shows pathologic and physiologic derangements quite similar to those reported in the patient in septic shock.

Protective effects of clofibrate on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats

Male and female, arteriosclerotic and non-arteriosclerotic rats were treated with the anti-lipemic agent, clofibrate, for 8 days and then subjected to an acute myocardial infarction by injecting them with two large doses of isoproterenol spaced 24 hours apart. The animals were killed at sequential time intervals during the acute necrosis and early repair phases of myocardial infarction. Pre-treatment with clofibrate caused a definite improvement in survival, less shock and prostration, and ECG evidence of little or no ischemia. Increased SGOT levels, hepatic lipid and necrosis were indicative of advanced liver damage. Although clofibrate-treated animals showed little change in serum lipids during the acute cardiac necrosis phase, they were hyperglycemic and showed the greatest increase in BUN levels. Clofibrate-treated animals had higher serum corticosterone levels than those given isoproterenol alone. Despite superior survival rates, both the arteriosclerotic and non-arteriosclerotic, clofibrate-treated animals exhibited equally severe histopathologic evidence of myocardial damage. It is suggested that the protective effect of prophylactic treatment with clofibrate against isoproterenol-induced myocardial infarction in rats may be due to its ability to change corticosterone levels in the circulation.

Protective effects of propranolol on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats.

Male and female, arteriosclerotic and non-arteriosclerotic rats were treated with the anti-lipemic agent, clofibrate, for 8 days and then subjected to an acute myocardial infarction by injecting them with two large doses of isoproterenol spaced 24 hours apart. The animals were killed at sequential time intervals during the acute necrosis and early repair phases of myocardial infarction. Pre-treatment with clofibrate caused a definite improvement in survival, less shock and prostration, and ECG evidence of little or no ischemia. Increased SGOT levels, hepatic lipid and necrosis were indicative of advanced liver damage. Although clofibrate-treated animals showed little change in serum lipids during the acute cardiac necrosis phase, they were hyperglycemic and showed the greatest increase in BUN levels. Clofibrate-treated animals had higher serum corticosterone levels than those given isoproterenol alone. Despite superior survival rates, both the arteriosclerotic and non-arteriosclerotic, clofibrate-treated animals exhibited equally severe histopathologic evidence of myocardial damage. It is suggested that the protective effect of prophylactic treatment with clofibrate against isoproterenol-induced myocardial infarction in rats may be due to its ability to change corticosterone levels in the circulation.