Studying cardiac dysfunction in septic shock in rat’s isolated perfused heart

Septic shock is a systemic inflammatory response to an infection leading to both cardiovascular dysfunction and cellular metabolic alterations ¹.

In 2017, Marine Ferron et al² investigated cardiac changes associated with sepsis, specifically intrinsic contractility and myocardial responses. Using an isolated working heart system to tightly control conditions, they studied the cardiac function without hormonal influences at various pressures representing several stages of septic shock.

After an in vivo evaluation by echocardiography, cardiac function was assessed under physiological load conditions on isolated hearts from control animals and those suffering from septic shock. Cardiac output, coronary flow, Heart Rate, cardiac cycle, Left Ventricular Pressure, and values for the first derivative of LVP (dP/dt) were measured.

This association of in vivo and ex vivo studies offered new insights and important information for further developments of cardiac therapies. For the first time, cardiac function changes at the early phase of septic shock were shown to be independent of the load conditions or the neurohumoral status and persist after a stabilization period, indicating that the cardiac function is drastically altered by sepsis condition.

Subsequently, Marine Ferron’s team proposed in 2019, a new metabolic approach to treat septic shock³. They demonstrated that acute O-GlcNAc stimulation tends to improve cardiovascular function and global outcome in two different models of septic shock: LPS-induced model, which develops a rapid and reproducible endotoxemic shock (3 h), and a CLP model which develops a longer-term poly-microbial septic shock (24 h).

In this subsequent study, blood analyses, qPCR and western blotting analysis were performed and heart function was evaluated in vivo, by echocardiography and using a pressure catheter inserted into the right carotid artery.

Pressure signal and heart rate were recorded in IOX software, allowing to observe hypotension and tachychardia in both rat models, as well as a restoration of mean arterial pressure and a reduction of heart rate following NButGT supplementation, used to increase the total O-GlcNAc.