Heart function after severe hemorrhagic shock

Objective: Test whether brief deep hemorrhagic hypotension or prolonged moderate hemorrhagic hypotension impairs intrinsic heart function. Methods: Pentobarbital-anesthetized, non-anticoagulated rats were cannulated via the carotid artery. This study focuses on three main groups: 1) hemorrhage to a mean arterial blood pressure (MAP)=25 mm Hg for 1 h (1 h severe shock), 2) hemorrhage to MAP=40 mm Hg for 3 h (3 h moderate shock), 3) no hemorrhage (control). Hearts were either freeze-clamped in-situ for tissue analysis (n=6 per group) or were removed to study in vitro cardiac function and efficiency using a working heart perfusion (n=12 per group, glucose (11 mM)/palmitate (0.4 mM), 3% BSA buffer). Following perfusion, hearts were freeze-clamped and analyzed for free CoA, acetyl-, succinyl-, and malonyl-CoA, ATP content and for TNF-α content. Results: Isolated working hearts obtained following 1 h of severe shock generated 20% less hydraulic work than hearts obtained from control rats or rats subjected to 3 h of moderate shock. The cardiac efficiency (work/O2 consumption) was also significantly reduced with 1 h severe shock (0.76 ± 0.07 after 15 min perfusion) versus control (0.96 ± 0.06) or 3 h prolonged shock (1.10 ± 0.09). Myocardial Co-A ester, ATP and TNF-α concentrations were not different between control and shocked hearts, although TNF-α concentrations increased significantly in all hearts during ex vivo perfusion. Conclusions: Depth of hypotension is more important than duration in causing intrinsic cardiac dysfunction. This post-hemorrhagic cardiac dysfunction is not a result of substrate limitation to the heart, nor myocardial TNF-α accumulation, but is more likely a result of impaired transfer of energy from molecular oxygen into external cardiac work.