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Objectives: Myocardial dysfunction in sepsis may be associated with changes in left ventricular (LV) size. The goal of this study was to evaluate the impact of myocardial dysfunction and changes in LV diameter on hemodynamics and survival in a murine model of sepsis., Methods: C57Bl/6 mice (N = 30) were used. Septic mice (n = 24) had cecal ligation and puncture (CLP) followed by fluid and antibiotic resuscitation and control mice (n = 6) received sham ligation. Echocardiography with a 30-mHz probe was performed at baseline and at frequent predefined time points after CLP. Stroke volume (SV), cardiac output (CO), LV internal diameter in diastole (LVIDd), and fractional shortening (FS) were measured. LV dilation was prospectively defined as an increase in LVIDd ≥ 5% from baseline values. Septic animals were classified as dilators or nondilators., Results: Among septic animals, 37% were dilators and 63% were nondilators. After CLP, SV and CO decreased early in both groups. With resuscitation, SV and CO improved to a greater extent in dilators than nondilators (for SV, 46.0 ± 8.2 vs 36.1 ± 12.7 μL at 24 h, P = .05; for CO, 20.4 ± 4.8 vs 14.8 ± 6.7 mL/min, P = .04). Survival at 72 h was significantly improved in dilators compared with nondilators (88% vs 40%, P = .01)., Conclusions: In a clinically relevant murine model of sepsis, animals with LV dilation had better cardiovascular performance and increased survival. Our results suggest that LV dilation is associated with improved SV and CO, a pattern resulting in greatly improved survival. These studies highlight the importance of diastolic function in septic shock.

In this review, we start with a general discussion of relevant factors that can determine the validity of a sepsis animal model. We briefly review some of the currently used animal models of sepsis (small animal models and large animal models). We discuss the clinical relevance of animal models in sepsis research today and address potential reasons for the apparent underperformance of animal models in predicting therapeutic success of novel drugs in clinical trials.

Sepsis is associated with cardiovascular changes that may lead to development of tissue hypoperfusion. Early recognition of sepsis and tissue hypoperfusion is critical to implement appropriate hemodynamic support and prevent irreversible organ damage. End points for resuscitation need to be defined and invasive hemodynamic monitoring is usually required. Targets for hemodynamic optimization should include intravascular volume, blood pressure, and cardiac output. Therapeutic interventions aimed at optimizing hemodynamics in patients with sepsis include aggressive fluid resuscitation, the use of vasopressor agents, inotropic agents and in selected cases transfusions of blood products. This review will cover the most important aspects of hemodynamic optimization for treatment of sepsis induced tissue-hypoperfusion.