Cytidine 5 '-diphosphocholine restores blood flow of superior mesenteric and renal arteries and prolongs survival time in haemorrhaged anaesthetized rats

Abstract

1. The aim of the present study was to investigate the effect of the intracerebroventricular (i.c.v.) or intravenous (i.v.) administration of cytidine 5 cent-diphosphocholine (CDP-choline) on superior mesenteric artery (SMA) and renal artery (RA) blood flow, along with the cardiovascular parameters and survival time of anaesthetized rats under conditions of haemorrhagic shock. 2. Rats were anaesthetized with urethane (1.25 g/kg, i.p.) and acute haemorrhage was mimicked by the withdrawal of a total volume of 2-2.1 mL blood/100 g bodyweight over a period of 20 min. The CDP-choline was injected i.c.v. (1.0, 1.5 and 2.0 mmol) or i.v. (250 mg/kg) after the end of haemorrhage. Blood pressure, heart rate, SMA and RA flow values and the survival time of rats were recorded. Changes in blood flow were estimated by laser-Doppler flowmetry. 3. The haemorrhage procedure decreased the blood pressures of rats by 60% and limited their survival time to 22 +/- 2 min. Both SMA and RA flow decreased to approximately 25% of initial values at the end of the haemorrhage procedure. 4. The i.c.v. administration of CDP-choline (1.0, 1.5 and 2.0 mmol) increased blood pressure and partially reversed the hypotension in a dose- and time-dependent manner. At 1.5 and 2.0 mmol, i.c.v., CDP-choline completely restored the decreased flow of the RA and transiently reversed hypoperfusion of the SMA. It also produced an almost fourfold increase in the survival time of rats. 5. The i.v. administration of CDP-choline (250 mg/kg) also completely, but transiently, restored SMA and RA flow, whereas it increased blood pressure by only 40% compared with control values. The survival time of rats in the i.v. CDP-choline group was doubled that of control. 6. These results indicate that both centrally and peripherally injected CDP-choline can restore SMA and RA flow, together with a partial reversal of hypotension and an increase in the survival time of rats.