Preserving cardiac and pulmonary function after cardiopulmonary bypass: effects of reactive nitrogen species

The mortality rate for myocardial infarction has declined over the past several decades due to both medical and surgical advances. Novelties in the prevention of ischaemia-reperfusion injury after both acute coronary events and planned surgical procedures will be necessary to ensure that this positive trend continues, and a focus on the perioperative preservation of cardiac function is paramount in reaching this goal. A growing body of data supports that the toxic molecules produced, as the sequelae of ischaemia, reactive oxygen and nitrogen species, play an instrumental role in the myocardial injury seen after successful reperfusion. The ability to limit the production or impact of these toxic molecules is key in myopreservation after periods of ischaemia. In this issue of EJCTS, Radovits et al. [1] demonstrate the catalysis of reactive nitrogen species to be a possible therapeutic option for the prevention of ischaemia-reperfusion injury.

Over the past decade, it has been demonstrated that the reactive nitrogen species peroxynitrite contributes to myocardial cell death and tissue injury [2]. Studies in swine not only demonstrated the generation of reactive nitrogen species to result in organ dysfunction after reperfusion injury, but also the administration of the peroxynitrite decomposition catalyst, FP15, to significantly decrease the infarct size after acute ischaemic events [3]. The administration of FP15 also proved to be protective in models of acute lung ischaemia-reperfusion injury and obliterative bronchiolitis [4, 5]. Even in the absence of acute injury and ischaemic events, FP15 was shown to improve cardiac and vascular functions associated with ageing in a murine model [6].

This novel study, using a large-animal canine model, demonstrated that the administration of FP15, while coming off cardiopulmonary bypass after hypothermic cardiac arrest, leads to significant preservation of cardiac function by several measures, as well as preservation of endothelial function in both the coronary and pulmonary vasculature [1]. This study not only reaffirms the role of toxic nitrogen species in the development of ischaemia-reperfusion injury, but also the first to demonstrate multi-organ system benefit by several measures with the augmented decomposition of peroxynitrite.

Though these results are significant and promising, a cautionary note must be taken as the seemingly simple leap from hugely positive preclinical, large-animal studies to clinical trials in sick cardiac patients has been met largely with disappointment in terms of myocardial preservation and regeneration. That being said, enhancing the decomposition of peroxynitrite with the administration of FP15 has promising clinical implications in the ability of minimizing myocardial hibernation commonly seen after ischaemic events. Limiting ischaemia-reperfusion injury may not only improve the perioperative cardiopulmonary function, but also yield long-term preservation of global myocardial, pulmonary and vascular functions in cardiac patients.