Marlin W. Causey, Seth Miller, Niten Singh, Matthew Martin
Madigan Army Medical Center, Ft. Lewis, WA.
OBJECTIVES: Valproic acid (VPA; a histone deacetylase inhibitor) has demonstrated significant decreases in resuscitation requirements as well as minimizing pathologic physiology following short-term aortic occlusion. The purpose of this study was to compare the cardiac and hemodynamic changes with VPA administration following supraceliac aortic occlusion.
METHODS: Nineteen swine were exposed to a 35% blood volume hemorrhage followed by a supraceliac aortic cross clamp only model with valproic acid (400mg/kg) administered as a drip continuously during supraceliac aortic cross clamping (CC, n=9). Hemodynamics were measured with the use of arterial blood pressure monitor and a pulmonary artery thermodilution catheter.
RESULTS: Ten swine were divided into two equal groups: sham and model. In this validation, hemodynamics were significantly different as measured after hemorrhage and cross clamp by mean arterial pressure (MAP; p=0.024), heart rate (p<0.001), cardiac index (CI; p=0.005). In the comparison arm of control and cross clamp group, there was a significant attenuation in the adverse hemodynamic response with administration of VPA (n=9) during cross clamp (MAP= 87+/-28 vs. CC-122+/-43 mmHg, p=0.02; HR= 124+/-23 vs. CC-161+/-32 bpm, p=0.01). Additionally, throughout the cross clamp application, there was a significantly decreased hyperdynamic response with the administration of VPA (Figure 1).
CONCLUSIONS: VPA helps attenuate the adverse hyperdynamic cardiac response following a hemorrhagic event and subsequent aortic occlusion. The hemodynamic response appeared to be not only significant at each time interval, but sustained as cross clamp times increased. Additionally, VPA seemed to minimize pathologic hemodynamic variation and provide cardiac protection through minimizing cardiac stress and work of the heart during aortic occlusion.
AUTHOR DISCLOSURES: M. W. Causey: Nothing to disclose; M. Martin: Nothing to disclose; S. Miller: Nothing to disclose; N. Singh: Nothing to disclose.
Posted April 2013