J. Taki et al., Increased cardiovascular and metabolic tolerance to acute hypoxia in the rat with increased hemoglobin-O-2 affinity induced by Na-cyanate treatment, JPN J PHYSL, 49(3), 1999, pp. 257-265
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.