In the present study, we investigated the effects of histidine and vitamin C (alone or in combination) treatments against isoproterenol (aβ-adrenergic receptor agonist)-induced acute myocardial infarction in rats. We used propranolol (a β-adrenergic receptor blocker) to compare the results. Rats were given intraperitoneal injections of histidine (40 mg kg(-1)) and vitamin C (40 mg kg(-1)) alone and combined daily for 21 days. Propranolol (10 mg kg(-1)) was orally administered daily for 10 days (from day 11 to day 21). Myocardial infarction was induced by subcutaneous injections of 150 mg kg(-1) of isoproterenol at an interval of 24 hr on days 20 and 21. Blood and tissue samples were taken for histopathological and biochemicalevaluations following electrocardiography recording on day 21. Isoproterenol elevated ST segment, increased heart weight, heart rate, serum activities of aspartate transaminase, lactate dehydrogenase, creatine kinase-MB and heart tissue content of malondialdehyde, and decreased R wave amplitude andsuperoxide dismutase and catalase activities of heart tissue. Necrosis, edema and inflammatory cells infiltration were observed in myocardial tissue sections. Our results indicated that histidine and vitamin C alone, and especially in combination prevent isoproterenol-induced cardiotoxicity and havesimilar protective effects with propranolol. Cardioprotective effects of histidine and vitamin C may be associated with their ability to reduce free radical-induced toxic effects.

Twenty-six nitrogen balance studies were performed in 15 patients with severe uremia (Ccr mean value 5.1, range 2.3-8.5 ml/min) treated with an unselected protein-poor (16-20 g protein/day corresponding to 2.6-3.2 g N/day) diet and oral supply of the essential amino acids including histidine (2.6 g N/day). The general condition improved and the concentration of serum urea nitrogen decreased. The nitrogen balance, corrected for changes in total urea pool, was negative on the diet alone,-1.46 plus or minus 1.15 g N/day (mean plus or minus SD), but was positive when the essential amino acids were supplied, plus 0.84 plus or minus 0.68 g N/day. In four patients studied after 3 to 26 months of diet and amino acid therapy, during which time a further deterioriation of the renal function had occurred, the nitrogen balance was around zero in three and negative in one patient (-1.2 g N/day). The results show that it is possible with our new regimen to attain positive nitrogen balance or nitrogen equilibrium in severely uremic patients without excessive accumulation of urea in the body fluids.

Twenty-six uremic patients - serum urea nitrogen (SUN) 110 MG/100 ml plus or minus 22.8 (mean plus or minus SD), serum cretinine (S-Creat) 13.2 mg/100 ml plus or minus 2.27, ratio SUN/S-Creat 8.6 plus or minus 2.26, and endogenous creatinine clearance (Ccr) 3.86 plus or minus 1.41 ml/min - were treated for three months or longer with an unselected protein-poor (16-20 g protein/day) diet with oral supply of the essential amino acids including histidine in high doses as coated tablets. The amino acids were instituted after an initial diet only period (mean 0.4 months). The average treatment time was 8.4 months (range 2.7-33.6). An improvement of the general condition was obtained, persisting for several months. SUN and SUN/S-Creat decreased on the diet alone, continued to decrease after one month, and increased slightly again after three months of treatment, but did not reach the initial levels for several months in spite of an almost doubled nitrogen intake. S-Creat increased after six months indicating a further deterioration of the renal function. In patients with initially low serum total protein (smaller than 6.5 g/100 ml, 9 patients), albumin (smaller than 3.5 g/100 ml, 10 patients), and total iron-binding capacity (smaller than 260 mug/100 ml, 11 patients) the values increased after one month on amino acids and were thereafter stable. No signs of bleeding tendency, progressive muscle atrophy, or progressive peripheral neuropathy were observed. - Five patients died due to cardiovascular maladies. A further 13 patients were withdrawn for medical reasons (overhydration, 4 patients; hypertension, 1 patient; nausea and vomiting, 7 patients; and pericarditis, 1 patient). - The renal function improved in one patient. Four patients received home dialysis training, three a kidney transplant. - The results indicate that it is possible to keep severely uremic patients free from uremic symptoms, counteract protein depletion, and even improve the nutritional status during long-term treatment with an unselected protein-poor diet supplementd with essential amino acids.