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Background: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles.Methods: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect.Results: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group).Conclusion: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning. [ABSTRACT FROM AUTHOR]

The aim of this study was to define the mechanical determinants of isotonic relaxation of isolated diaphragm muscle in the rat over a load range (n = 30). We tested several hypotheses to determine the effect of i) load conditions (preload, post-load), ii) sudden changes in load during contraction, iii) length of the muscle at peak shortening, iv) maximal amplitude of shortening (delta L) and v) stimulation conditions on peak rate of isotonic reelongation (+dL/dmax). At tetanus at 30 Hz, +dL/dmax was linearly correlated to delta L peak shortening and total load. Variations in preload, peak shortening or postload did not modify the +dL/dmax vs delta L relationship but such variations did affected the relationships +dL/dmax vs total load or +dL/dmax vs peak shortening. For a given value of L, +dL/dmax was weaker for twitch than for tetanus. In conclusion, four findings show that over a wide lad range the maximal amplitude of shortening the main mechanical determinant of the rate of isotonic reelongation of the isolated diaphragm muscle, independently of the length of the muscle at peak shortening, the initial length of the muscle and independently of the load during reelongation.