Mechanisms of splenectomy protection in epinephrine-induced renal and cardiac necrosis.
This study was intended to elucidate the mechanism(s) of protection afforded by splenectomy against EPI-induced ATN and myocardial necrosis. Renal function parameters, hematocrit, circulating catecholamines (EPI and NE), serum enzymes (CPK and SGOT), and urinary PGE2 were measured before and during intravenous infusion of EPI (4 micrograms/kg/min for 6 hr) in intact and chronically splenectomized animals. All but serum enzymes were measured in another group of splenectomized animals that were implanted with small fragments of the autologous spleen (autoimplanted animals) 2 weeks prior to EPI infusion. Renal function tests and urinary PGE2 levels were monitored for several hours during the recovery period. The development of ARF in intact animals was accompanied by marked increases in circulating catecholamine levels, hematocrit, and serum enzymes and by a marked decrease in urinary PGE2 levels. These animals had diffuse ATN and hemorrhagic lesions of the heart (myocardial necrosis), and none survived. Chronically splenectomized animals were protected against the adverse effects of EPI infusion. The protected animals showed minimal elevation of circulating catecholamine levels and no changes in urinary PGE2 levels or hematocrit. Serum enzymes and renal and cardiac histopathology remained essentially normal in these animals. Implantation of autologous splenic tissue in splenectomized animals caused reversal of the protective effect of splenectomy. The response of autoimplanted animals to EPI infusion was in all respects similar to that in intact animals with the exception of hematocrit, which did not rise. All autoimplanted animals survived. They showed prompt recovery of renal function associated with significant increase of urinary PGE2 levels during the recovery period. Focal ATN was observed but no hemorrhagic lesion of the heart was found. From these observations we conclude the following: (1) high circulating NE and/or low renal (urinary) PGE2 activity are important in the pathogenesis of EPI-induced ARF, (2) the spleen may release some factor(s) that modulate plasma NE level and/or renal PGE2 activity during EPI infusion, (3) EPI-induced ARF may occur independently of myocardial necrosis, and (4) hematocrit has no major role in EPI-induced ARF.
D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control* / Q000652:urine; D002395:Catecholamines / Q000097:blood; D015232:Dinoprostone; D004285:Dogs; D004837:Epinephrine / Q000008:administration & dosage / Q000009:adverse effects*; D006400:Hematocrit; D007263:Infusions, Parenteral; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000517:prevention & control* / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D009638:Norepinephrine / Q000009:adverse effects; D011458:Prostaglandins E / Q000652:urine; D013156:Splenectomy
D002395:Catecholamines; D011458:Prostaglandins E; D015232:Dinoprostone; D009638:Norepinephrine; D004837:Epinephrine