Sepsis-induced myocardial dysfunction.
Despite the fact that septic patients exhibit altered cardiac function, it is not considered a major pathology during sepsis. Thus, the molecular mechanisms underlying sepsis-induced myocardial dysfunction have not been studied extensively. In a polymicrobial septic rat model, +dP/dt and -dP/dt on day 1 were not altered but found depressed later, i.e., at 3 and 7 days postsepsis. Diastolic dysfunction characterized by an elevation of the time constant of left ventricular relaxation, tau, was evident at 1, 3, and 7 days postsepsis. Recent data from our laboratory demonstrated that sepsis-induced cardiodynamic alterations correlated with upregulation of TNF receptor-associated death domain, Bax, Smac (both mitochondrial and cytosolic fractions), total nuclear factor kappaB expression, p38-mitogen-activated protein kinase and c-Jun N-terminal kinase phosphorylation, and cytochrome c levels in the rat heart at 3 and 7 days postsepsis. Data from various laboratories emphasized that molecular myocardial alteration, which occurs during early and late stages of sepsis, needs to be elucidated thoroughly. A poor understanding of myocardial signaling during early sepsis could be one of the main reasons for limited success of pharmacotherapeutic options for sepsis. We anticipate that an increased understanding of pathophysiological mechanisms leading to sepsis-induced myocardial dysfunction would generate new enthusiasm among various research groups in this area of research.
Sharma
Avadhesh C
AC
Cardionome Laboratory, Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas, Texas 75246, USA. acsharma@bcd.tamhsc.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D018805:Sepsis / Q000503:physiopathology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D019332:Endothelin-1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases