Whole body periodic acceleration (pGz) improves endotoxin induced cardiomyocyte contractile dysfunction and attenuates the inflammatory response in mice

Abstract

Sepsis-induces myocardial contractile dysfunction. We previously showed that whole body periodic acceleration (pGz), the sinusoidal motion of the supine body head-foot ward direction significantly improves survival and decreases microvascular permeability in a lethal model of sepsis. We tested the hypothesis that pGz improves LPS induced cardiomyocyte contractile dysfunction and decreases LPS pro-inflammatory cytokine response when applied pre- or post-treatment. Isolated cardiomyocytes were obtained from mice that received LPS who had been pre-treated with pGz for three days (pGz-LPS) or control. Peak shortening (PS), maximal velocity of shortening (+dL/dt), and relengthening (-dL/dt) as well as diastolic intracellular calcium concentration ([Ca+2]d), sodium ([Na+]d), reactive oxygen species (ROS), and cardiac troponin (cTnT) production were measured. LPS decreased PS, +dL/dt, and -dL/dt, by 37%, 41% and 35% change respectively (p < 0.01), increased [Ca+2]d, [Na+]d, ROS, and cTnT by 343%, 122%, 298%, and 610% change respectively (p < 0.01) compared to control. pGz pre-treatment attenuated the parameters mentioned above. In a separate cohort, the effects of a lethal dose of LPS on protein expression of nitric oxide synthases (iNOS, eNOS, nNOS), pro- and anti-inflammatory cytokines in hearts of mice was studied in pre-treated with pGz for three days prior to LPS (pGz-LPS) and post-treated with pGz 30 min after LPS (LPS-pGz) were determined. LPS increased expression of early and late iNOS and decreased expression of eNOS, phosphorylated eNOS (p-eNOS), and nNOS. Both pre- and post-treatment with pGz markedly reduced early and late pro-inflammatory surge. Therefore, pre- and post-treatment with pGz improves LPS-induced cardiomyocyte dysfunction, decreases iNOS expression, and increases cytoprotective eNOS and nNOS, with decreased pro-inflammatory response. Such results have potential for translation to benefit outcomes in human sepsis.