The complex pathogenesis of sepsis and septic shock involves myocardial depression, the pathophysiology of which, however, remains unclear. In this study, cellular mechanisms of myocardial depression were addressed in a clinically relevant, large animal (porcine) model of sepsis and septic shock. Sepsis was induced by fecal peritonitis in 8 anesthetized, mechanically ventilated, and instrumented pigs of both sexes and continued for 24 hours. In 8 control pigs, an identical experiment but without sepsis induction was performed. In vitro analysis of cardiac function included measurements of action potentials and contractions in the right ventricle trabeculae, measurements of sarcomeric contractions, calcium transients and calcium current in isolated cardiac myocytes, and analysis of mitochondrial respiration by ultrasensitive oxygraphy. Increased values of modified Sequential Organ Failure Assessment (SOFA) score and serum lactate levels documented the development of sepsis/septic shock, accompanied by hyperdynamic circulation with high heart rate, increased cardiac output, peripheral vasodilation, and decreased stroke volume. In septic trabeculae, action potential duration was shortened and contraction force reduced. In septic cardiac myocytes, sarcomeric contractions, calcium transients, and L-type calcium current were all suppressed. Similar relaxation trajectory of the intracellular calcium-cell length phase-plane diagram indicated unchanged calcium responsiveness of myofilaments. Mitochondrial respiration was diminished through inhibition of Complex II and Complex IV. Defective calcium handling with reduced calcium current and transients, together with inhibition of mitochondrial respiration, appears to represent the dominant cellular mechanisms of myocardial depression in porcine septic shock.

Porcine model of peritonitis-induced sepsis is a well-established clinically relevant model of human disease. Interindividual variability of the response often complicates the interpretation of findings. To better understand the biological basis of the disease variability, the progression of the disease was compared between animals with sepsis and septic shock. Peritonitis was induced by inoculation of autologous feces in fifteen anesthetized, mechanically ventilated and surgically instrumented pigs and continued for 24 h. Cardiovascular and biochemical parameters were collected at baseline (just before peritonitis induction), 12 h, 18 h and 24 h (end of the experiment) after induction of peritonitis. Analysis of multiple parameters revealed the earliest significant differences between sepsis and septic shock groups in the sequential organ failure assessment (SOFA) score, systemic vascular resistance, partial pressure of oxygen in mixed venous blood and body temperature. Other significant functional differences developed later in the course of the disease. The data indicate that SOFA score, hemodynamical parameters and body temperature discriminate early between sepsis and septic shock in a clinically relevant porcine model. Early pronounced alterations of these parameters may herald a progression of the disease toward irreversible septic shock.

Background: aortic valve stenosis is the most frequent cardiac valve pathology in the western world. Surgical aortic valve replacement is the gold standard for the treatment of significant degenerative aortic valve diseases.Case presentation: this case report highlights an unexpected abnormal iatrogenic shortening of the aorto-mitral continuity and its deformity, during traditional AVR using sutured stented aortic prosthesis as the first choice, which caused significant mitral valve regurgitation. The suture-less prosthesis was a rescue choice to restore the geometry and eliminate the deformation of the aorto-mitral continuity.Conclusions: aortic valve replacement using suture-less prosthesis could be a valuable optional choice for lowering the risk of deformation of the aortic annulus and aorto-mitral continuity. It might provide better outcomes in combined procedures.

Aortic valve stenosis is the most frequent cardiac valve pathology in the western world. Surgical aortic valve replacement is the gold standard for the treatment of significant degenerative aortic valve diseases. This case report highlights an unexpected abnormal iatrogenic shortening of the aorto-mitral continuity and its deformity, during traditional AVR using sutured stented aortic prosthesis as the first choice, which caused significant mitral valve regurgitation. The suture-less prosthesis was a rescue choice to restore the geometry and eliminate the deformation of the aorto-mitral continuity. Aortic valve replacement using suture-less prosthesis could be a valuable optional choice for lowering the risk of deformation of the aortic annulus and aorto-mitral continuity. It might provide better outcomes in combined procedures.