Klaus Schafferhans

Norepinephrine-Induced Acute Renal Failure: Beneficial Effects of Atrial Natriuretic Factor

The effect of the atrial natriuretic factor (ANF) on early norepinephrine-induced acute renal failure (ARF) was investigated. In anaesthetized female Sprague-Dawley rats, weighing 247 +/- 36 g, ARF of the left kidneys was induced by 40-min intrarenal arterial infusion of norepinephrine (NE; 0.75 micrograms/kg body weight). In each case the right kidney served as a control organ. Inulin clearance was used as an estimate of glomerular filtration rate (GFR). Urine volume (V), GFR and fractional excretion rates of sodium, potassium and chloride were studies in both kidneys. Immediately after NE-induced ARF one group received ANF (alpha-hANaP) and the other groups 5% glucose or isotonic saline; all infusions were administered intrarenally. In the experimental kidney NE-infusion induced anuria. ANF infusion was able to induce complete reversal of the NE effect, and GFR and diuresis improved markedly in the experimental kidney. In addition, a tremendous rise in fractional excretion rates of sodium and potassium after administration of ANF was observed. In the control kidney an additional increase of GFR and diuresis was seen. Following 5% glucose or isotonic sodium chloride infusion, no profound effects were obtained in both kidneys. The results of the present study demonstrate that ANF provides beneficial effects on the functional damage of NE-induced ARF. We conclude that the NE-antagonistic effect of ANF and the consecutive amelioration of GFR may play an important role in the recovery of impaired renal function.

Autonomic Neuropathy in Chronic Renal Insufficiency

Disturbances of peripheral and autonomic nervous system function were evaluated in 37 normal subjects, in 52 patients with non diabetic chronic renal insufficiency (25 predialysis patients, 27 dialysis patients), and in 21 patients with diabetic chronic renal failure (10 predialysis patients, 11 dialysis patients). In nondiabetic patients, the predialysis group showed abnormal test results indicating parasympathetic lesions, in dialysis patients these derangements were nearly normalized. In predialysis diabetic patients, the autonomic alterations were much more extensive, corresponding to alterations of electroneurographical findings; in addition to parasympathetic lesions, sympathetic disturbances were seen. In contrast to the nondiabetic groups, in dialysis patients a deterioration of autonomic lesions was observed. In conclusion, these data indicate that deranged autonomic functions are common in uremia; they improve in dialysis patients with nondiabetic renal failure in contrast to diabetic patients; in this group the autonomic functions worsen in dialysis patients as a function of duration of diabetes and hemodialysis.

Diminished Parathyroid Gland Responsiveness to Hypocalcemia in Diabetic Patients with Uremia

The parathyroid gland responsiveness to hypocalcemia induced by short-term calcium-free hemodialysis in patients with insulin-dependent diabetes mellitus was investigated in comparison with 10 nondiabetic uremic patients and compared with test results from the autonomic nervous system. Diabetic patients had lower C-terminal parathyroid hormone (cPTH) levels before hemodialysis than uremic control patients and showed a significantly smaller increase in cPTH during hypocalcemia. The neurological tests revealed severe disturbances of the autonomic functions in the diabetic group. In conclusion, the disturbances observed in the parathyroid secretory pattern are probably caused by gland dysfunction; it is hypothesized that the defective autonomic nervous system has an additional effect on the development of this hormonal dysfunction.

Hypercalcämie bei malignen Erkrankungen

SummaryHypercalcemia accompanies often malignant diseases. The majority of cases of malignancy complicated by hypercalcemia is induced by metastases involving bone, hypercalcemia may also accompany localised tumors. Various hormones have been implicated in the genesis of malignant hypercalcemia: ectopic secretion of parathyroid hormone by tumor or orthotopic secretion by concomitant primary hyperparathyroidism, prostaglandin activating osteoclasts, production of hypercalcemic factor other than these hormones. This review summarizes current knowledge about endocrine-mediated mechanisms which produce hypercalcemia and about its frequency and mechanism in different types of tumors.Hypercalcemia accompanies often malignant diseases. The majority of cases of malignancy complicated by hypercalcemia is induced by metastases involving bone, hypercalcemia may also accompany localised tumors. Various hormones have been implicated in the genesis of malignant hypercalcemia: ectopic secretion of parathyroid hormone by tumor or orthotopic secretion by concomitant primary hyperparathyroidism, prostaglandin activating osteoclasts, production of hypercalcemic factor other than these hormones. This review summarizes current knowledge about endocrine-mediated mechanisms which produce hypercalcemia and about its frequency and mechanism in different types of tumors.

Psychomental Stress in Tetraplegic Man: Dissociation in Autonomic Variables and Emotional Responsiveness

Tetraplegic patients with physiologically complete cervical spinal cord transsection are classic ablation models of sympathetic denervation. Therefore this study was conducted to investigate the hemodynamic response (blood pressure, cardiac rate) and the plasma catecholamine (adrenaline, noradrenaline) release induced by a standardized psychomental stress model (sonic confuser). Attention was focussed on subjective evaluation of stress experience in spinal man. During psychomental stress, typical pressure reaction was not observed, cardiac rate was elevated insignificantly, and catecholamine release was diminished. The subjective estimates of stress experience, however, did not differ from those of the control group. It appears that psychomental stress in sympathectomized man is not extinguished despite abolished peripheral autonomic feedback modifying the state of the central nervous system. Cognitive processes and cortical arousal seem to be the initial and important steps of emotional experience and they are independent from peripheral autonomic processes. These results lend support to the centralistic view of emotions and the importance of cognitive factors in emotional responsiveness.

Proteases and antiproteases at different vascular sites in renal failure.

A potential role of proteases in the pathogenesis of the catabolic state in patients with post-traumatic acute renal failure (ARF) has been discussed 1-3. It was suggested that active proteases might play a role in protein wasting observed in uremic conditions4. Since trauma itself might lead to increased plasma proteolysis, the present study was performed both in patients with non-traumatic ARF and chronic renal failure (CRF) to examine potential imbalances between proteases and antiproteases in plasma. Some components of plasma proteolytic enzyme systems were also studied. All parameters were measured in plasma taken at different vascular sites in order to establish as to whether there were any arteriovenous differences across various organs indicating local extraction or release.