DCA (dichloroacetate) can improve myocardial function during hemorrhagic shock. To explore the mechanism of this effect, we administered DCA in a large animal model of hemorrhagic shock. Dogs were anesthetized with 1.5% isoflurane and instrumented for hemodynamics, myocardial contractility and substrate utilization. They were hemorrhaged to a mean arterial pressure of 35 mm Hg for 90 minutes or until arterial lactate levels reached 7 mM. Two-thirds of the shed blood volume was returned immediately after giving an equivalent volume of saline. Two hours after the onset of resuscitation, mean arterial pressure was not different between DCA and control groups (79 ± 3 vs. 82 ± 3mm Hg). Arterial lactate levels were significantly reduced by DCA (0.5 ± 0.06 vs. 2.0 ± 0.2 mM). However, DCA treatment was associated with a decreased stroke volume index (0.56 ± 0.06 vs. 0.82 ± 0.08 ml/kg/beat), and a tendency toward a decreased myocardial efficiency (19 vs. 41 liter X mm Hg/ml/100 g tissue). Myocardial lactate consumption was reduced (0.2 ± 0.04 vs. 0.7 ± 0.16 umole/min/100 g tissue), and free fatty acid levels were increased during resuscitation by DCA. We propose that lactate may become limiting following DCA treatment, thus compromising myocardial function following recovery from hemorrhagic shock.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology