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Heart function after severe hemorrhagic shock
J A Kline1, L R Thornton, G D Lopaschuk
1Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
Insights
Severe hemorrhagic shock, even when brief, significantly impairs heart function more than prolonged moderate shock. This cardiac dysfunction stems from energy transfer issues, not substrate or TNF-alpha levels.
Area of Science:
- Cardiovascular Physiology
- Hemorrhagic Shock Research
- Cardiac Metabolism
Background:
- Hemorrhagic hypotension can lead to cardiac dysfunction.
- The relative importance of hypotension depth versus duration on intrinsic heart function is not fully understood.
Purpose of the Study:
- To investigate whether brief, severe hemorrhagic hypotension or prolonged, moderate hemorrhagic hypotension has a greater impact on intrinsic cardiac function.
- To elucidate the underlying mechanisms of post-hemorrhagic cardiac dysfunction.
Main Methods:
- Rats were subjected to either 1 hour of severe hypotension (MAP 25 mm Hg) or 3 hours of moderate hypotension (MAP 40 mm Hg).
- In vitro working heart perfusion was used to assess cardiac function and efficiency.
- Myocardial tissue was analyzed for energy metabolites (CoA esters, ATP) and TNF-alpha.
Main Results:
- Hearts from rats experiencing 1 hour of severe shock generated 20% less hydraulic work compared to controls or those with prolonged moderate shock.
- Cardiac efficiency was significantly reduced in the severe shock group.
- No significant differences in myocardial CoA ester, ATP, or TNF-alpha were found between groups immediately post-shock.
Conclusions:
- The depth of hypotension is a more critical factor than its duration in causing intrinsic cardiac dysfunction.
- Post-hemorrhagic cardiac dysfunction is not attributed to substrate limitation or myocardial TNF-alpha accumulation.
- The findings suggest impaired energy transfer from oxygen to cardiac work is the likely cause.
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-alpha 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-alpha concentrations were not different between control and shocked hearts, although TNF-alpha 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-alpha accumulation, but is more likely a result of impaired transfer of energy from molecular oxygen into external cardiac work.