Sodium nitroprusside: factors which attenuate its action. Studies with the isolated gracilis muscle of the dog.

In a laboratory preparation of the isolated, acutely denervated, and separately perfused canine gracilis muscle we have made the following observations: 1. At physiological pH, sodium nitroprusside significantly decreases the vascular resistance; 2. At physiological pH, cyanide significantly attenuates the effect of sodium nitroprusside; 3. In an acidaemic milieu, our data suggest that the effect of sodium nitroprusside may be attenuated. We speculate that patients who manifest resistance to the hypotensive effect of sodium nitroprusside may not normally eliminate the cyanide that is released from the biodegradation of sodium nitroprusside. They accumulate free cyanide which interferes with the action of sodium nitroprusside at the receptor level, leading to administration of more nitroprusside and setting in motion a positive feedback vicious cycle. When one is faced with the problem of an abnormal response to sodium nitroprusside in a fit patient, although many factors may be involved, we suggest that the possibility of rising blood cyanide levels and acidosis be given high priority.