Centhaquin is being developed as a small volume hypotensive resuscitative agent. It has significant resuscitative effect and improves the survival of hemorrhaged rats. However, its mechanism of action is not known.
Centhaquin will be an effective resuscitative agent which acts through a unique mechanism of action mediated through α2adrenergic receptors.
Rats were anaesthetized with urethane and the femoral vein and artery were isolated and cannulated. A pressure transducer (SPR-320) and pressure-volume (P-V) transducer (SPR-869) were placed into the femoral artery and left ventricle, respectively. P-V loop data were acquired using PowerLab 16/30 data acquisition system (AD Instruments) and analyzed using LabChart-7.00 and PVAN program (Millar Instruments). After completion of surgery, induction of hemorrhage was initiated by withdrawing blood from the right femoral artery to maintain the mean arterial pressure (MAP) at 35 mmHg for 30 minutes. Arterial blood pO2, pCO2, pH, glucose, and lactate were measured using a blood gas analyzer (GEM Premier 3000). We determined the involvement of α2 adrenergic receptors in the resuscitative effect of centhaquin using specific α2adrenergic antagonists, yohimbine and atipamezole.
Hematocrit decreased by about 32 to 35% in all the groups following hemorrhage. Centhaquin (0.05 mg/kg) reduced blood lactate, improved cardiac output and blood pressure of hemorrhaged rats. The time for blood pressure to fall back to 35 mmHg was increased by three folds in centhaquin treated rats compared to vehicle. Centhaquin significantly decreased blood lactate levels (mmol/L) from 10.1 ± 0.7 at hemorrhage to 4.5 ± 0.4 at 60 min following resuscitation. However, in yohimbine treated rats blood lactate levels were10.3 ± 1.5 at hemorrhage, and 8.4 ± 0.8 at 60 min following resuscitation; while in atipamezole treated rats blood lactate levels were 10.8 ± 0.4 at hemorrhage, and 7.7 ± 1.0 at 60 min following resuscitation.
Centhaquin is an effective resuscitative agent and both yohimbine and atipamezole antagonized the resuscitative effect of centhaquin indicating that α2 adrenergic receptors are involved in the resuscitative effect of centhaquin.