Bradykinin infusion in long term postoperative parenteral nutrition improves nitrogen balance and protein synthesis.
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Biomedical subjects
Publications and source records attributed to B Günther.
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Generally, the terms peripheral-venous nutrition and hypocaloric parenteral nutrition are synonymous. Both supply the patients with roughly 2 g carbohydrates and 1.0 g-1.5 g amino acids/kg BW/day. In Germany there are so-called 'complete' or 'combination' solutions on the market, which contain these amounts of nutrients in 3-liter-concepts. For peripheral-venous application the osmolality of the solutions is important. Generally, only solutions with an osmolality of twice the concentrations of plasma will be tolerated by peripheral veins. Since osmolality is widely a function of electrolyte concentrations, solutions with a low mineral content are preferable for peripheral-venous use. The main advantage of hypocaloric parenteral nutrition is its easy handling in the early postoperative period. In clinical practice, due to the hazard of intolerance reactions to fructose and sorbit, the use of glucose or xylitol as carbohydrates in hypocaloric parenteral solutions is recommended.
The effect of the angiotensin converting enzyme inhibitor captopril (25 mg by mouth) on glucose metabolism of skeletal muscle and the whole organism was studied in nine normotensive type II (non-insulin dependent) diabetics using a combination of euglycaemic-hyperinsulinaemic glucose-clamp and forearm catheter techniques. The administration of captopril resulted in a significant rise of both the whole-body glucose elimination and utilization rate in the forearm musculature. At the same time the arterial kinin level rose, while the concentrations of insulin, free fatty acids and gluconeogenesis precursors, as well as the number and activity of insulin receptors (measured in an erythrocyte-binding study) remained unchanged. The data support the view that, in type II diabetics, ACE inhibition raises the insulin-stimulated glucose uptake of the whole organism, predominantly due to an increased glucose uptake by the skeletal musculature. The demonstration of an increased kinin level points to this effect possibly being caused by the reduced breakdown of locally liberated kinins.
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The systemic effect of low-dose bradykinin infusion on total body glucose production and arterial substrate concentrations was examined during D5W infusion (1.0 mg/kg/min) in five normal-weight postsurgical subjects and compared to the response in four saline infused control patients, well matched for age, weight, and degree of postoperative stress. The primed-constant infusion of 6,6-d2-glucose was used to determine the rate of endogenous glucose production. After a basal period of 90 minutes, subjects in the study group were infused with bradykinin at increasing rates of 2.0 and 4.0 micrograms/kg/h, each infusion rate lasting for 90 minutes, whereas in controls corresponding amounts of saline were given. After 75 minutes of bradykinin, endogenous glucose production was significantly reduced as compared to basal values (1.63 +/- 0.21 mg/kg/min, P less than .0125 v 2.20 +/- 0.35 basal). This was accompanied by a significant reduction in arterial concentrations of glucose, lactate, pyruvate, and alanine. Corresponding concentrations of insulin, glucagon, glycerol, free fatty acids, and ketone bodies, as well as mean arterial blood pressure and heart rate was not affected by bradykinin. In the control group no significant changes in substrate and hormone concentrations, or the rate of glucose production were observed. The higher bradykinin infusion rate did not further affect substrate metabolism or systemic hemodynamics. These results demonstrate the inhibitory effect of low-dose bradykinin on glucose production in surgically stressed patients. The stimulation of hepatic prostaglandin synthesis by bradykinin may explain the results since prostaglandins are known to exert an inhibitory effect on hormone stimulated gluconeogenesis and glycogenolysis in liver tissue.
To evaluate changes of peripheral ketone body (KB) metabolism after operation, muscle metabolism in postsurgical patients was studied at 3 hours (SI) and 24 hours (SII) after surgery by the forearm catheter technique. Data were compared to those of equivalent fasted controls (CI, CII). In a manner consistent with enhanced mobilization of endogenous substrate stores, arterial concentrations of free fatty acids (FFA), 3-hydroxybutyrate (3-HOB), and acetoacetate (AcAc) were markedly elevated immediately after surgery. This increase was accompanied by a rise in muscular utilization of AcAc (SI: 0.21 +/- 0.05 mumol/100 g/min; CI: 0.08 +/- 0.05, p less than 0.05) and 3-HOB (SI: 0.24 +/- 0.06 mumol/100 g/min; CI: 0.11 +/- 0.01, p less than 0.05). Surprisingly, on the first postoperative day, concentrations of AcAc and 3-HOB fell below those of fasting controls. Concomitantly, the utilization rate of AcAc by muscle (SII: 0.07 +/- 0.03 mumol/100 g/min; CII: 0.27 +/- 0.04, p less than 0.05) was significantly lower in patients than in controls. Reduction of the fractional extraction rate of AcAc (SI: 38.4 +/- 3.8%; SII: 24.0 +/- 6.1%, p less than 0.05), as well as a net production of 3-HOB by muscle (SII: -0.08 +/- 0.05 mumol/100 g/min; CII: 0.49 +/- 0.13, p less than 0.05) 24 hours after surgery indicated a reduced peripheral capacity for KB removal. Since this finding was related to a significantly higher rate of muscular glycerol production (SII: -0.13 +/- 0.03 mumol/100 g/min; CII: -0.06 +/- 0.02, p less than 0.05), one may suggest that increased intramuscular availability of FFA from triglyceride hydrolysis was responsible for the impairment of peripheral KB utilization. These results indicate that KBs contribute little to energy metabolism in skeletal muscle tissue in the late postoperative phase.
Acute stone-related cholecystitis is treated by early cholecystectomy. Percutaneous cholecystostomy seems more and more the preferred treatment of stress-related acalculous cholecystitis. Diagnosis is confirmed by ultrasound. Simultaneous combined operations, i.e. cholecystectomy and common bile duct revision, are performed in patients under 65 years of age without serious concomitant diseases and if the operation is not hazardous. The inhospital mortality amounts to about 3%.
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In a prospective study microvascular reactivity was examined in 12 patients with septic conditions by means of the provocation of reactive hyperemia (RH) for evaluation of microcirculatory function. Data were compared with data from 10 nonseptic, postsurgical patients. At the time of the initial measurement, an adequate hyperemic response could be produced in all patients. In the further course of the disease, in nine of the 12 patients severe multiple organ failure developed. In spite of sufficient values for arterial blood pressure, oxygenation, and the clotting system, RH was absent in these patients (8 +/- 2 days after the initial measurement). Subsequently, seven of these nine patients died (4 +/- 2 days after the onset of microvascular nonreactivity). Until death, RH was absent in each patient, and at this time therapy-resistant hypoxemia, hypotension, and severe disturbances of the clotting system were present. In the two surviving patients RH was restored completely. These results indicate that (1) the septic state per se is not necessarily combined with impaired microvascular reactivity (rather, the absence of RH may be a sign of generally poor clinical conditions); (2) the absence of RH is not related to therapy-resistant hypotension, hypoxia, and severe clotting disorders but precedes these changes; and (3) provocation of RH may be of clinical use for early detection of microcirculatory malfunction in high-risk patients.
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In a 44 year old patient with chronic lymphatic leukemia and secondary antibody deficiency syndrome, a disorder of articulation and a left hemiparesis developed during a thrombocytopenic phase. Computer tomography of the cranium, CSF diagnostics and the electroencephalogram did not provide any indication for the cause of the rapidly progressive cerebral symptoms. In the NMR tomogram, a diffusedly increasing intensity in the T2-weighted tomograms were shown around the central region in the right brain. The patient died of a Pseudomonas septicemia. At autopsy, a typical finding of progressive multifocal leukoencephalopathy was found in the areas altered in the NMR tomography. Papova-like virions could be demonstrated in glial cells by electron microscopy.
To evaluate the effect of the glucose-induced insulin release on peripheral substrate metabolism, we studied muscle metabolism in seven patients after elective surgery and in four healthy volunteers combining the forearm and the euglycemic glucose clamp technique (insulin infusion, 0.2 mU/kg per minute). Arterial and deep venous concentrations of substrates and hormones were determined in the basal period and during steady state of the infusion period. After 90 minutes of insulin infusion, the whole-body glucose infusion rate was significantly lower in patients who had elective surgery, although plasma insulin concentrations were comparable. In both groups this was related to a reduced supply of free fatty acids and ketones in muscle. In controls the resulting lack of substrates in muscle appeared to be compensated by an enhanced uptake of glucose, not seen in the patients who had elective surgery. Surprisingly, as indicated by the significantly reduced lactate production (-0.15 +/- 0.05 vs -0.62 +/- 0.32 mumol/100 g per minute basal), in this group the glucose taken up was oxidized aerobically to a greater extent. However, the total resulting energy gain was small. Thus, a peripheral energy deficit might arise favoring increased oxidation of amino acids. To avoid this undesired side effect, only those substrates should be administered that minimize pancreatic insulin release.
Procedure of choice in the treatment of gastric cancer is total gastrectomy and radical lymphadenectomy. Despite an improvement of long-term results concerning localization, depth of infiltration, lymph node metastasis and histological type of tumor according to Laurén the main determinant of late results is the stage of disease. Suggestions for treatment of cancers on the oesophagogastric junction cannot yet be given. Despite possible advantages of preservation of the spleen for the early result, the impact on late results remains unclear.
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Since the angiotensin converting enzyme (ACE) is identical with kininase II, the reduction of its activity by an ACE-inhibitor such as captopril will not only decrease the concentration of angiotensin II but also elevate the levels of kinins. Although the slight increase of the latter will not contribute to the antihypertensive action of ACE-inhibitors, we are sure today that it exhibits local metabolic effects in cardiac and skeletal muscle tissue. These endogenous kinins have been shown to improve the utilisation of glucose in the human forearm, the whole organism and the isolated perfused rat heart and seem to exhibit their effects via prostaglandins. A cross-over plot of the glycolytic intermediates at the height of phosphofructokinase induced by bradykinin in rat heart and the activation of the purified enzyme from rabbit heart by PGE2 point to an enhanced glycolytic rate as their mode of action. From these findings similar effects under ACE-inhibitors can be assumed. This was investigated in ten non-insulin-dependent diabetics, whose glucose disposal rate was measured by the glucose clamp technique. After 25 mg of captopril their peripheral insulin resistance was significantly improved, which was found to be due to an accelerated rate of glucose uptake into their forearm muscle tissue. To evaluate the clinical relevance of these data, 15 mildly hypertensive, overweight type II-diabetic patients (mean age: 53 years; seven women) were hospitalized. After a seven-day wash-out period, the patients were given 25 mg of captopril twice daily for seven days. During the treatment, systemic kinin concentrations significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)