Table 1 Five hypotheses for sepsis-induced myocardial depression in the setting of inflammation and immune dysfunction. All five are not mutually exclusive

1

Circulating myocardial depressant(s)

Serum from septic shock patients depressed myocyte contractility in vitro. Candidates include bacterial toxins, TNF-α, IL-1β, and interleukin-1 receptor-like 1 (sST2), which may decrease myofilaments’ sensitivity to Ca²⁺ via the induction of excess NO synthesis (blocked by L-NAME). Possible sources of TNF-α and IL-1β are activated monocytes and macrophages.

[120,121,122, 54, 123,124,125, 105]

2

Overexpression of cardiac mitochondrial NOS

Excess NO synthesis (and reactive oxygen species), which may partially open the mitochondrial pore, depolarize the inner membrane, and reduce ATP production for contraction.

[126, 114]

3

Myofilament Ca²⁺ responsiveness

Decrease cardio-myofilament Ca²⁺ sensitivity, reduces cross-bridge cycling responsiveness to reduce contractile activation and force development.

[127, 128]

4

Cardiac β-adrenergic desensitization

Cardiac response to sympathetic hyperactivation and ↑catecholamines. Receptor switching from G_s to G_i, which signals β-2 adrenergic receptors to produce a negative inotropic response, presumably by ↓Ca²⁺ availability.

[129]

5

Downregulation of master genes encoding for sarcomeric and mitochondrial proteins

Reduce cross-bridge cycling and ATP availability generated by oxidative phosphorylation.

[105]