Pathogenesis of Renal Changes in Experimental Prolonged Shock*

Abstract

IntroductionKnowledge about the complex syndrome shock with its many clinical and pathophysiological states in animal and man has increased significantly in recent years. The set of pathological and anatomical problems has changed accordingly (29). By standardized animal experiments, in particular, it has been possible to obtain details about the intravascular processes during the acute phase of shock (11,14,18,40). Disturbances in the microcirculation (17, 2O, 31,42) result in lesions of the endothelium (13,24) which in turn lead to interstitial oedema in various organs such as lung (19, 28), kidney (4, central nervous system (5, 6), or the gastrointestinal system (12). In the later stages of shock the lungs and kidneys of man, in particular, show massive perivascular and interstitial reactions in the form of cellular infiltration and fibrosis (21,34). Compared with other animal species, the rat possesses marked resistance to endotoxin and is thus especially suitable for experiments on protracted shock (47). In pigs the neurotoxin from Escherichia coli 0 139 : K 82 (B), designated vasotoxin (3), induces oedema disease which is shock-like in its course. After the application of this toxin in rats and pigs, severe shock-induced vascular damage was found in diverse organs (7,9).The aim of this study was to record the light microscopical and ultrastructural changes in the interstitial regions of rat kidney for which a study of changes in the mesangial area has already been published (32). In particular, the sequence of perivascular and interstitial processes was determined and the relationship between the kind of cellular infiltration and the duration and intensity of shock was demonstrated. Material and MethodsFor the experiments 130 specific pathogen-free Han : Wistar rats weighing between 120 and 240 g were used. Thirty animals served as controls. Shock was induced by intravenous injection (tail vein) of neurotoxin from the Escherichiu coli strain EB 170, serotype 0 139 : K 82 (B) which had been produced by the extraction method (41). The ram received 1 to 4 or 8 neurotoxin injections at a dosage of 0.35mYkg body weight (12LDx, mouse); the controls received a corresponding mount of physiological s h e . In three different experimental series the interval between injections varied * Supported by the Deutsche Forschungsgemeinschaft, SFB 54, D 4. U.S. Copyright C l e m c e Center Code Statement: 07214981/84/310&-061~$02.5~/0 612 KAUP, DROMMER, LANCER and ROSENBRUCH between 2 and 31 days. The best results were obtained with one week between injections. The animals were sacrificed 6 hours to 79 days after the first injection. 27 animals died acutely within 24 hours after a neurotoxin injection; the others showed acute symptoms of shock after every injection, with ruffling of the fur, twisted body posture, dyspnoea and a high degree of apathy. This condition lasted as long as 5 days after each injection and was accompanied by severe weight loss up to 25 % of body weight. Most of the experimental animals were fixed whi...