Comparison of the hemodynamic effects of hydroxocobalamin and cobalt edetate at equipotent cyanide antidotal doses in conscious dogs.
OBJECTIVE
The hemodynamic effects of two cyanide antidotes, hydroxocobalamin and cobalt edetate were compared.


METHODS
This experimental study was performed in chronically instrumented conscious dogs and at equipotent cyanide antidotal doses (hydroxocobalamin 70 mg.kg-1; cobalt edetate 10.5 mg.kg-1).


RESULTS
Peak plasma cobalt concentrations did not differ in the two groups (412 +/- 183 vs 400 +/- 160 mumol.l-1). Hydroxocobalamin induced a slight increase in mean arterial pressure (+17 +/- 9%, p < 0.05) and systemic resistance (+19 +/- 15%, p < 0.05). In contrast, cobalt edetate induced an increase in heart rate (+78 +/- 33%, p < 0.05), in cardiac output (+63 +/- 39%, p < 0.05), and in maximum rise of left ventricular pressure (+33 +/- 15%, p < 0.05), did not modify mean arterial pressure, and decreased systemic resistance (-36 +/- 15%, p < 0.05). These hemodynamic effects were associated with an increase in plasma catecholamine concentrations (epinephrine: 2524 +/- 3025 vs. 58 +/- 37 pg.ml-1, p < 0.05; norepinephrine: 1106 +/- 609 vs. 343 +/- 146 pg.ml-1, p < 0.05), which in contrast remained unchanged after hydroxocobalamin administration. Cobalt edetate also induced an increase in blood glucose concentrations (9.9 +/- 1.9 vs. 6.1 +/- 1.2 mmol.l-1, p < 0.05) and a moderate metabolic acidosis, whereas hydroxocobalamin did not. After adrenergic (alpha 1, beta) and cholinergic receptor blockade, cobalt edetate did not modify heart rate and various indices of cardiac function, suggesting that it has no direct cardiac effects.


CONCLUSIONS
Considering its lack of hemodynamically relevant effects, these results indicate that hydroxocobalamin is potentially a safer cyanide antidote than cobalt edetate.
Riou
B
B
Laboratorire de Pharmacologie, Université Paris Sud, Le Bicêtre, France.
Berdeaux
A
A
Pussard
E
E
Giudicelli
J F
JF
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D003035:Cobalt / Q000097:blood / Q000494:pharmacology*; D003486:Cyanides / Q000037:antagonists & inhibitors; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006879:Hydroxocobalamin / Q000494:pharmacology*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D001286:Atropine Derivatives; D002395:Catecholamines; D003486:Cyanides; D010276:Parasympatholytics; D003035:Cobalt; C006649:methylatropine; D011433:Propranolol; D006879:Hydroxocobalamin; D011224:Prazosin