OBJECTIVE: To hypothesize that reduced L-type calcium current with consequent shortening of cardiac repolarization is present in a clinically relevant porcine model of hyperdynamic septic shock. Myocardial depression is a well-recognized manifestation of sepsis and septic shock. Reduction of L-type calcium current was demonstrated to contribute to the myocardial depression in endotoxemic rodents. DESIGN: Laboratory animal experiments. SETTING: Animal research laboratory at a university. SUBJECTS: Twenty-two domestic pigs of either gender. INTERVENTIONS: In anesthetized, mechanically ventilated, and instrumented pigs, sepsis was induced by bacteremia (central venous infusion of live Pseudomonas aeruginosa) and continued for 22 hrs. MEASUREMENTS AND MAIN RESULTS: Electrocardiogram was recorded before and 22 hrs after induction of bacteremia. RR, QT, and QTc intervals were significantly shortened by sepsis. In vitro, action potentials were recorded in right ventricular trabeculae. Action potential durations were shortened in septic preparations. Tumor necrosis factor-alpha did not influence action potential durations. L-type calcium current was measured in isolated ventricular myocytes. Peak L-type calcium current density was reduced in myocytes from septic animals (8.3 +/- 0.4 pA/pF vs. 11.2 +/- 0.6 pA/pF in control). The voltage dependence of both L-type calcium current activation and inactivation was shifted to more negative potentials in myocytes from septic animals. Action potential-clamp experiments revealed that the contribution of L-type calcium current to the septic action potential was significantly diminished. In cardiac myocytes incubated with tumor necrosis factor-alpha, L-type calcium current was not further affected. CONCLUSIONS: In a clinically relevant porcine model, hyperdynamic septic shock induced shortening of ventricular repolarization and reduction of L-type calcium current. The contribution of L-type calcium current to the action potential in septic ventricular myocytes was significantly diminished. Tumor necrosis factor-alpha probably did not contribute to this effect.
- MeSH
- akční potenciály fyziologie MeSH
- elektrokardiografie MeSH
- kardiomyocyty fyziologie MeSH
- modely nemocí na zvířatech MeSH
- septický šok patofyziologie MeSH
- srdeční komory patofyziologie MeSH
- Sus scrofa fyziologie MeSH
- TNF-alfa fyziologie MeSH
- vápník fyziologie MeSH
- vápníkové kanály - typ L fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- elektrická vodivost MeSH
- enzymy farmakologie MeSH
- inhibitory enzymů MeSH
- krysa rodu rattus MeSH
- peptid spojený s genem pro kalcitonin farmakologie MeSH
- srdce fyziologie MeSH
- vápníkové kanály - typ L účinky léků MeSH
- vápníkové kanály - typ T účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- akční potenciály MeSH
- elektrofyziologie MeSH
- kočky MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- kuřecí embryo MeSH
- myokard MeSH
- psi MeSH
- srdce fyziologie růst a vývoj MeSH
- vývojová biologie MeSH
- Check Tag
- kočky MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- kuřecí embryo MeSH
- psi MeSH
- Publikační typ
- srovnávací studie MeSH
