**9.7 Mechanism of sepsis-induced cardiomyopathy**

There are two different mechanisms proposed for the etiopathogenesis of SIC. First, based on animal studies, insufficient coronary blood flow is supposed to cause myocardial ischemia [134]. Second, due to the surge of chemical mediators such as cytokines, endotoxins, and nitric oxide (NO) that are released during the dysregulated inflammation may cause SIC. However, in a study done by Cunnion et al, measuring coronary blood flow and myocardial metabolism using coronary sinus thermodilution catheters in seven patients with septic shock to determine whether

*Overview of Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) Support… DOI: http://dx.doi.org/10.5772/intechopen.105838*

myocardial depression was associated with reduced coronary flow [135]; the authors found that coronary blood flow was similar or higher in the patients with septic shock compared to the controls despite the presence of myocardial depression. A recent study by Rudiger and Singer has also shown that SIC cannot be attributed to the disruption in coronary circulation [128].

The role of chemical mediators has also been studied extensively in the pathophysiology of SIC. Studies have implicated the role of endotoxins, interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) in the pathogenesis of SIC [136–138]. Endotoxins induce NO synthase and increase the production and release of NO [136]. Similarly, cytokines such as TNF-α and IL-1β also increase the activity of cyclic guanosine monophosphate (cGMP) and NO [138]. It has been hypothesized that excess NO production causes cardiac dysfunction by reducing the myofibril response to calcium, dysfunction of the mitochondria, and downregulation of β-adrenergic receptors [128, 139, 140]. Several studies have also suggested that NO overproduction and mitochondrial dysfunction may contribute to cardiac dysfunction and mortality [141–144]. Interestingly, using methylene blue an inhibitor of NO production pathway has demonstrated improvement in myocardial depression, maintenance of oxygen transportation, and reduction in the requirement for concurrent adrenergic support [145].

#### **9.8 Diagnosis, treatment options and use of ECMO**

There is a range of tests that are available for diagnosing SIC. These include blood tests such as brain natriuretic peptide (BNP) assay and Troponin Assay as well as use of echocardiogram to check for ventricular dysfunction. While BNP and troponin I, both rise in SIC, their rise is mainly dependent on the severity of illness rather than markers for cardiomyopathy [146–148]. The gold standard for the diagnosis of SIC is echocardiography. Echocardiogram may show normal or reduced ejection fraction, LV diastolic dysfunction, and RV systolic dysfunction, as well as global longitudinal strain (GLS) on myocardial speckle tracking [149–152].
