Abstract
Ischaemia reperfusion injury (IRI) is tissue damage that occurs when blood flow is restored to the myocardium after a period of ischaemia, such as during coronary artery occlusion. IRI develops in two phases: the first mitochondrial phase that generates reactive oxygen species (ROS), followed by the inflammatory phase, which produces ROS that trigger pro-inflammatory signalling leading to degradation of cardiomyocytes and thus, fibrosis, reducing cardiac output. This second phase is characterised by activation of the NLRP3 inflammasome, leading to caspase-1-mediated cleavage of the cytokine precursors pro IL-1β and pro IL-18 into their active forms. This study investigated whether low-dose, non-toxic carbon monoxide (CO) gas exposure modulates NLRP3 inflammasome activity, thereby reducing inflammatory injury after IRI. Ten different experimental rat heart groups were used to collect data about the effect of CO gas exposure following LAD ligation surgery or sham. This study previously demonstrated an improvement in cardiac function and an increase in anti-inflammatory IL-10 in CO-treated groups. Homogenised tissue was analysed by western blotting to quantify key inflammasome components. Preliminary data indicate that low-dose CO gas administered by inhalation does not significantly reduce NLRP3 inflammasome activation in this model of myocardial IRI. These findings suggest that CO does not mediate its cardioprotective and anti-inflammatory effects via the NLRP3 inflammasome at the time points investigated. Further analysis will clarify other potential mechanisms and guide future experiments, including investigations of different CO delivery methods and timing. These results contribute to a deeper understanding of both the inflammatory response to IRI and the therapeutic potential and limitations of low-dose CO exposure in cardiovascular disease.