Effect of verapamil on polycythaemia secondary to hypoxia in rats

1. Polycythaemia occurs in man secondary to chronic hypoxaemia, and may lead to morbidity from hyperviscosity of the blood. Hypoxaemic rats develop similar changes. We have investigated the effect of the calcium antagonist verapamil upon the polycythaemic response to hypoxia in rats. 2. Control groups of 10 male rats breathed air in an environmental chamber for 28 days. Hypoxic groups breathed a normobaric atmosphere of 10% oxygen for 6 h each day, and air for the remaining 18 h. Control and hypoxic groups were treated with intraperitoneal or subcutaneous water, or with intraperitoneal or subcutaneous water plus verapamil. 3. On day 28, packed cell volume (PCV) was measured by a microhaematocrit technique and red cell mass (RCM) by dilution of injected 51Cr-labelled rat erythrocytes. 4. PCV and RCM were significantly higher in all the hypoxic groups compared with the control groups (P < 0.01 in each case). 5. PCV and RCM were significantly lower in the hypoxic groups treated with intraperitoneal or subcutaneous verapamil than in the hypoxic groups treated with intraperitoneal or subcutaneous water (P < 0.01). There were no significant differences between PCV and RCM in verapamil- and water-treated normoxic control groups. Verapamil had no effect on the shift of the oxygen/haemoglobin dissociation curve produced by hypoxia. 6. Verapamil reduces the polycythaemic response to repeated intermittent hypoxia in rats. Venesection is usually performed for excessive secondary polycythaemia in man. Our results suggest a possible therapeutic role for verapamil in such individuals.