Increased cardiovascular and metabolic tolerance to acute hypoxia in the rat with increased hemoglobin-O-2 affinity induced by Na-cyanate treatment

Cyanate derivatives such as NaOCN have been known to increase the hypoxia t olerance of animals by increasing the affinity of hemoglobin (Hb) to O-2 To clarify the mechanism of this increase in hypoxia tolerance, we examined c hanges in metabolic rate and cardiovascular parameters during a hypoxia tes t in halothane-anesthetized, NaOCN-treated and spontaneously breathing rats (50 mg/kg/d s.c., 10 d). Control animals received saline. The capillary de nsity in the skeletal muscle (sternocleidomastoid muscle), cardiac papillar y muscle and medulla oblongata was also examined histologically. The Hb-O-2 affinity index, P-50, decreased from 38 (control rat) to 24 mmHg in NaOCN- treated rats. During hyperoxic gas breathing, the rat treated with NaOCN sh owed a significantly lower metabolic rate ((V) over dot O-2, (V) over dot C O2), higher cardiac stroke volume, slower heart rate, lower P (V) over bar( O2), and lower O-2 extraction ratio than those in control rats. The NaOCN-t reated rats exhibited well-maintained arterial blood pressure and a larger cardiac output response to reduction in FIo2 to 0.10-0.08. The increase in O-2 extraction ratio with reduction in FIo2 was larger in NaOCN-treated tha n in control rats. The circulatory and metabolic depressions at FIo2 0.05 w ere effectively attenuated in NaOCN-treated rats. The capillary density of the cardiac muscle and medulla oblongata but not the skeletal muscle was si gnificantly higher in NaOCN-treated rats than in control rats. The greater hypoxia tolerance in NaOCN-treated rats is ascribed to the combined effects of left shift of Hb-O-2 dissociation curve, lower basal (V) over dot O-2, higher capillary density in the heart, and brain, and other adaptive mechan isms induced probably by prolonged tissue hypoxia.