Right ventricular hypertrophy and failure abolish cardioprotection by ischaemic pre-conditioning

Abstract

Aims: We aimed to investigate the response to ischaemia-reperfusion (IR) and ischaemic pre-conditioning (IPC) in the hypertrophic and failing right heart.

Methods and results: Male Wistar rats underwent sham operation, moderate pulmonary trunk banding (mPTB), or severe PTB (sPTB). Four weeks after surgery, hearts were quick-frozen (n = 28) for biochemical analysis of key salvage pathways or isolated and perfused in a Langendorff set-up (n = 46). We randomized perfused hearts to IPC (2 × 5 min of global ischaemia) or no preceding ischaemia (CON), before 40 min of global ischaemia and 120 min of reperfusion. The infarct size/area at risk (IS/AAR) ratio and post-ischaemic right ventricular (RV) function were used to evaluate the effect of IPC. mPTB induced compensated RV hypertrophy and sPTB induced RV hypertrophy with failure. Hypertrophy of the right ventricle increased IS in hearts from mPTB and sPTB animals compared with sham (IS/AAR, 73.1 ± 2.9% and 59.3 ± 2.4% vs. 35.6 ± 2.9%, P < 0.0001). IPC reduced IS in sham and mPTB hearts (IS/AAR, 35.6 ± 2.9% vs. 17.4 ± 1.2% and 73.1 ± 2.9% vs. 56.9 ± 3.5%, P < 0.01) and improved recovery of RV contractile function. IPC did not alter IS/AAR (59.3 ± 2.4% and 59.3 ± 2.9%, P = 0.999) or haemodynamic recovery in sPTB hearts. RV cyclic guanosine monophosphate (cGMP) and the cGMP-dependent protein kinase were increased after sPTB.

Conclusion: Right ventricular hypertrophy increases IR injury. Cardioprotection by IPC is abolished in the failing but not the compensated hypertrophic right ventricle of the rat heart.

Keywords: Cardioprotection; Congenital heart disease; Heart failure; Ischaemia–reperfusion injury; Right ventricle.