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

Abstract

AimsWe aimed to investigate the response to ischaemia-reperfusion (IR) and ischaemic pre-conditioning (IPC) in the hypertrophic and failing right heart. Methods and resultsMale Wistar rats underwent sham operation, moderate pulmonary trunk banding (mPTB), or severe PTB (sPTB). Four weeks after surgery, hearts were quick-frozen (n ¼ 28) for biochemical analysis of key salvage pathways or isolated and perfused in a Langendorff set-up (n ¼ 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 ¼ 0.999) or haemodynamic recovery in sPTB hearts. RV cyclic guanosine monophosphate (cGMP) and the cGMP-dependent protein kinase were increased after sPTB. ConclusionRight ventricular hypertrophy increases IR injury. Cardioprotection by IPC is abolished in the failing but not the compensated hypertrophic right ventricle of the rat heart.--

Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure

“…This agrees with previous studies 25,27 and suggests an adaptive remodeling of the right ventricle with preserved systolic function.…”

“…23,24 These findings are comparable to both animals and humans with decompensated RV hypertrophy and failure 5,21,25,26 . Rats subjected to the mild banding presented with elevated RV pressures, increased RV weight, reduced TAPSE, but preserved cardiac output.…”

Specific MicroRNAs comparisons in hypoxia and morphine preconditioning against hypoxia-reoxgenation injury with and without heart failure

“…HF is defined as "a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood" I/R injury has been reported over 3 decades, that the myocardial injury and cardiomyocyte death paradoxically occurs with the acute reperfusion of ischemic myocardium, and one or more cycles of ischemia-reperfusion preconditioning (IPC) or pharmacological conditioning have been considered as powerful cardioprotective strategy for reducing infarct size, attenuating cardiomyocyte injury [6]. However, the cardioprotection of IPC and opiate preconditioning was impaired in pathological myocardium, including postinfarct remodeled hearts [7], hyperglycemia [8], right ventricular hypertrophy and failure [9].…”

Impaired RISK-GSK3β Pathway is Responsible for Comorbidities by Suppressing the Conditioning Cardioprotection

“…The myocardial structural and signal transduction changes will render the heart more sensitive to IRI and suppress the effect of cardioprotective strategies. A very meaningful study performed by Andensern et al (4) demonstrated that right ventricular hypertrophy increased IRI. Cardioprotection by IPC was abolished in the failing but not the compensated hypertrophic right ventricular of the rat hearts.…”

“…Despite these landmark results are consistently proved in experimental models, it is a pity that conditioning application is restricted and the protection is diminished in clinical settings such as cardiac operation and elective percutaneous coronary intervention. The main reason is that the aging population and the growing prevalence of comorbidities such as ageing (4), diabetes (5), hypercholesterolemia (6), and heart diseases (7,8), which are not present in animal studies. It has been speculated that pathological processes resulting in fundamental signaling molecular alteration may affect the development of IRI and the responses to cardioprotective interventions.…”