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Re: Complexities of pulmonary dysfunction following cardiopulmonary bypass

Dear Editor,

We congratulate Elkington and Friedland on their excellent review which gives an overview of matrix metalloproteinases (MMPs) in various destructive pulmonary diseases.[1] MMPs and neutrophil elastase do indeed play instrumental roles in the development of ARDS and lung injury following cardiopulmonary bypass (CPB), however, the mechanisms presented may be too simplified.[2]

Apart from the artificial circuits, CPB intrinsically encompasses many other factors such as global cardiopulmonary ischaemia-reperfusion, hypothermia, heparin-protamine dosage, interrupted lung ventilation and pulmonary artery perfusion, and non-pulsatile flow.[3] It is presumed that each of these factors may play an individual role in the inflammatory cascade and ARDS phenomena associated with cardiac operations. Moreover, their combined effects could even be synergistic in influencing the clinical outcome. Classically, CPB causes pulmonary neutrophil activation and sequestration, which subsequently result in the release of inflammatory mediators including neutrophil elastase, MMPs, and superoxide species. These mediators are responsible for direct pneumocyte and basement membrane injury.[2]

More recently, studies have shown the important role of ischaemia and reperfusion during CPB in the development of lung necrosis, apoptosis and pulmonary dysfunction.[4] MMPs and neutrophil elastase contribute at least in part to the process of lung apoptosis, nevertheless, pulmonary ischaemia and reperfusion are responsible for increased levels of Fas-ligand, inflammatory cytokines, metabolic and oxidant stresses following CPB, which are the main activators of the extrinsic and intrinsic apoptotic pathways respectively.[4] Pulmonary dysfunction following CPB is a complex problem that has so far eluded our complete understanding, and further research is warranted. “The important thing is not to stop questioning.” Albert Einstein (1879-1955)

Kindest regards,
Dr. Calvin S.H. Ng, MBBS(Hons) MRCS
Prof. Song Wan, MD PhD FRCS
Prof. Malcolm J. Underwood, MD FRCS
Prof. Anthony P.C. Yim, MA DM FRCS

References

1) Elkington PTG, Friedland JS. Matrix metalloproteinases in destructive pulmonary pathology. Thorax 2006; 61: 259-266.

2) Ng CS, Wan S, Yim AP, Arifi AA. Pulmonary dysfunction after cardiac surgery. Chest 2002;121:1269-77.

3) Wan S, Yim APC, Ng CSH, Arifi AA. Systematic Organ Protection in Coronary Artery Surgery with or without Cardiopulmonary Bypass. J Card Surg 2002;17:529-35.