PURPOSE: Centhaquin, a 2-(2-(4-(3-methylphenyl)-1-piperazinyl) ethyl) quinoline, is a α-2 agonist similar to clonidine. We have previously shown that it increases the expression of Endothelin A (ETA) receptors in the blood vessels and brain. Endothelin-1(ET-1) increases the vascular reactivity of adrenergic receptors by acting on ETA receptors. Hence, centhaquin may have an adjunctive role in resuscitation of hemorrhagic shock (HS). The purpose of this study was to show that adding centhaquin to Lactated Ringer’s (LR) or hypertonic saline may result in more effective resuscitation of HS.
METHODS: Male Sprague Dawley rats were anaesthetized. The femoral vein and femoral artery were cannulated. A calibrated pressure-volume catheter was placed in the left ventricle. Pressure-volume loop data was analyzed to obtain cardiac output(CO) and systemic vascular resistance(SVR). HS was induced by withdrawing blood from the right femoral artery to keep MAP between 35-40 mmHg for 30 minutes. Resuscitation commenced 60 minutes after onset of HS. The animals were divided into four groups, each of which received a different resuscitative measure: Group I, LR solution, volume equal to shed blood volume (SBV); Group II, LR solution, volume equal to SBV plus Centhaquin 0.05mg/kg; Group III, 3% hypertonic saline, volume equal to SBV; Group IV, 3% hypertonic saline, volume equal to SBV plus Centhaquin 0.05mg/kg. Blood gases and lactate were measured before and 60 minutes following HS and at 60-minute intervals after commencement of resuscitation until the animals died.
RESULTS: Sixty minutes post resuscitation, serum lactate dropped in animals in group II (42%), group III (54%) and group IV (72%) whereas increased by 41% in group I animals. MAP increased by 58% in Group II and by 66% in Group IV. MAP did not change in Groups I or III. Cardiac output increased by 180% in group II and by 220% in Group IV. Cardiac output increased by 142% in GroupIII but dropped by 28% in Group I. SVR dropped by 30% in Group II, by 44% in Group IV and by 62% in Group III but did not change in Group I. Survival after HS was 78 minutes in Group I,387 minutes in Group II,144 minutes in Group III and 326 minutes in Group IV.
CONCLUSIONS: Adding centhaquin to resuscitation fluids improves hemodynamic parameters such as MAP, CO and SVR and tissue perfusion as evidenced by reduced blood lactate. This may result in improved survival in victims of hemorrhagic shock.
CLINICAL IMPLICATIONS: Centhaquin may have beneficial effects in resuscitation of HS.
DISCLOSURE: The following authors have nothing to disclose: Stephanie Tolentino, Suresh Havalad, Anil Gulati, Manish Lavhale
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