Pharmacologic attenuation of the hyperdynamic response to supraceliac aortic clamping

BackgroundAortic occlusion is accompanied by a hyperdynamic cardiovascular response secondary to increased systemic vascular resistance and increased cardiac output. This study was designed primarily to determine the safety and cardiovascular response to hydrogen sulfide (H2S; HS) administration with supraceliac aortic cross-clamp and, secondarily, on short-duration resuscitation.MethodsA validated porcine model (five sham swine compared with five controls) demonstrated a significant hyperdynamic cardiovascular response to 35% blood volume hemorrhage, 50-minute suprarenal aortic cross-clamping, and 6-hour resuscitation. Eight additional experimental swine were administered HS at 4 mg/min during aortic cross-clamping.ResultsDuring the cross-clamp period, hemodynamic curves of mean arterial pressure and heart rate demonstrated a blunting effect with HS administration, with a significant decrease being seen with mean arterial pressure at the end of the cross-clamp period (120 vs 149 mm Hg; P = .04). Resuscitation requirements were significantly reduced at 6 hours because the HS cohort received 8 L less crystalloid (P = .001) and 10.4 mg less epinephrine (P < .001). There was not a significant change in cardiac output, systemic vascular resistance, pulmonary vascular resistance, or pathologic liver analysis.ConclusionsThe administration of HS during the 50 minutes of supraceliac aortic cross-clamp significantly reduced stress of the left heart. On clamp release, HS significantly reduced the need for volume and pressors. HS has positive benefits during cross-clamp and subsequent resuscitation, demonstrating that targeted pharmacologic therapy is possible to minimize adverse physiologic changes with aortic occlusion.

Clinical RelevanceHydrogen sulfide (H2S; HS) is a promising new drug that has previously demonstrated benefit in minimizing injury from ischemia-reperfusion insults. For the first time in a large animal model, HS attenuated the adverse hyperdynamic cardiovascular response by minimizing left heart stress after hemorrhage and a 50-minute supraceliac aortic cross-clamp. HS also decreased postclamp resuscitative requirements and demonstrated that targeted pharmacologic therapy is possible to minimize adverse physiologic changes with aortic occlusion.