Centhaquin Improves Resuscitative Effect of Hypertonic Saline in Hemorrhaged Rats

J Surg Res. 2012 Nov;178(1):415-23. doi: 10.1016/j.jss.2012.02.005. Epub 2012 Apr 2.

Abstract

Background: We observed that centhaquin, a cardiovascular active agent, reduces blood lactate levels. Because blood lactate is an important indicator of end-organ perfusion, we determined the resuscitative effect of centhaquin in hemorrhaged rats.

Materials and methods: Male, adult Sprague-Dawley rats (Harlan, Indianapolis, IN) were anesthetized with urethane, and a pressure catheter SPR-320 was placed in the left femoral artery, and a pressure-volume catheter SPR-869 was placed into the left ventricle through carotid artery. Hemorrhage was induced by withdrawing blood from the right femoral artery, and mean arterial pressure was maintained between 35 and 40 mm Hg for 30 min after which resuscitation was performed using normal saline (control), 3% hypertonic saline, or centhaquin dissolved in 3% hypertonic saline. Arterial blood pH, pO(2), pCO(2), lactate, hematocrit, and cardiovascular parameters were measured before the induction of hemorrhage (baseline), 30 min after induction of hemorrhagic shock, and every 60 min thereafter until the animal expired.

Results: Hypertonic saline was effective in reducing blood lactate levels and improving cardiac output (CO) of hemorrhaged rats. Centhaquin dissolved in hypertonic saline produced a significantly greater decrease in blood lactate and increase in mean arterial pressure and CO compared with hypertonic saline in hemorrhaged rats. Fraction survival at 250 min was 0 when resuscitated with hypertonic saline, whereas it was 0.8 with centhaquin.

Conclusions: Centhaquin significantly improved the resuscitative effect of hypertonic saline by increasing CO, reducing blood lactate, and improving survival time of hemorrhaged rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Carbon Dioxide / blood
  • Cardiac Output / drug effects
  • Cardiac Output / physiology
  • Cardiotonic Agents / pharmacology
  • Drug Synergism
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Hemorrhage / drug therapy*
  • Hemorrhage / mortality
  • Hydrogen-Ion Concentration
  • Lactic Acid / blood
  • Male
  • Oxygen / blood
  • Piperazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Resuscitation / methods*
  • Saline Solution, Hypertonic / pharmacology*

Substances

  • Cardiotonic Agents
  • Piperazines
  • Saline Solution, Hypertonic
  • Carbon Dioxide
  • Lactic Acid
  • centhaquine
  • Oxygen