Table 1. Translational strategies targeting the respiratory chain in cardiac disease.

Clinical Usage	Intervention	Target	Clinical Trials	Ref
Ischaemia-reperfusion injury	Ischaemic conditioning	Complex I, IV; increased uncoupling, RISK, SAFE	AMI, remote preconditioning n=142, myocardial salvage index by perfusion imaging, P=0.03	71
			Elective CABG, remote preconditioning, n=57, Trop-TAUC, P=0.005	73
			Valve replacement surgery, remote preconditioning, n=81, Trop IAUC, P=0.05	72
	Nitrite	Complex I and IV	Currently undergoing- NIAMI,.multi-centre RCT (iv nitrite) NITRITE-AMI, single centre RCT (intracoronary nitrite)	NCT01388504 NCT01584453
	Melatonin	Stabilizes MIM preserving complex I and III function	currently undergoing-single centre MARIA (iv in AMI) two centre (intracoronary in AMI)	NCT00640094 NCT01172171
	Cyclosporine A	mPTP	AMI, n=58, CKAUCP=0.04, trop IAUCP=0.15, MRI P=0.04	59
	TRO40303	Mitochondrial translocator protein (TSPO), delays mPTP opening	Multi-centre RCT	NCT01374321
	Edaravone (MCI-186)	ROS scavenger	AMI, n=80, CKAUCP=0.04, CK-MBAUCP=0.02	62
	Other interventions showing benefit in animal models: Amobarbital,Hydrogen sulfide, Caloric restriction,Resveratrol	Complex I Complex IV Complex I and III Complex I and III		90,91,134 135 128
Heart failure	Coenzyme Q 10	Corrects coenzyme Q deficit	Coenzyme Q10 + Selenium, 5 year follow up, n=443, CV mortality P=0.015, NT-proBNP 0.014, EF 0.03	103
			Symbio multi-center RCT	ISRCTN945062
	Other interventions showing benefit in animal models: Trimetazidine105 SS-31109	Complex I and II Mitochondria selective antioxidant		117 122
LVH	Animal model: Low intensity aerobic exercise	Decreased sensitivity to Ca++ induced mPTP opening		129
Aging	Animal models: Caloric restriction, Melatonin	Complex I electron leak		126
		Preservation of complex I, III , IV activity		109
Hereditary mitochondrial cardiomyopathies	Pre-natal genetic diagnostics & Gene therapy Low intensity exercise	Respiratory chain defects	(Benefit documented in skeletal muscle)	136