Mitogen Activated Protein Kinase Phosphatase‐1 Plays an Important Role in Sepsis‐Related Cardiac Dysfunction

Cardiac dysfunction is a major contributor to sepsis related organ failure and mortality and is related to systemic and/or cardiac innate immune responses. Mitogen activated protein kinase phosphatase (MKP)‐1 is a key negative regulator of the innate immune responses. Its role in cardiac myocyte dysfunction during sepsis is not defined. We tested the hypothesis that MKP‐1 deficiency promotes cardiac dysfunction during sepsis. Five‐week old MKP‐1−/− and wild‐type control mice were treated with a single dose of LPS (1.5 mg/kg, ip). Cardiovascular phenotyping was measured at 0, 4 and 24 h after LPS challenge, via echocardiography and 4‐ lead ECG analyses. Blood pressure was measured with a tail cuff monitor. In wild‐type mice LPS caused transient reductions in LV fractional shortening and BP, which returned to baseline values at 24 h (FS%: 55.1, 51.8, and 60.0% for 0, 4, 24 h respectively) (BP: 82.1, 65.1, 70.0; 0, 4, 24 h respectively). MKP‐1−/− mice had more pronounced hemodynamic impairment (FS%: 57.1, 43.2∗, and 40.2∗ for 0, 4,24 h respectively; ∗, p<0.01) (BP: 82.1, 41.5∗, 40.2∗, for 0, 4,24 h respectively; ∗, p<0.01). These data demonstrate that cardiac myocyte MAPK signaling plays an important role in sepsis‐related cardiac dysfunction and it might be related to enhanced cardiac myocyte inflammatory and oxidant mediated injury.