. 2005 Aug 23;390(Pt 2):377–394. doi: 10.1042/BJ20042006

Table 1. Pharmacological and biochemical targets for cardioprotection involving mitochondrial activities.

CPT-1, carnitine palmitoyl transferase-1; DEVD-CHO, acetyl-Asp-Glu-Val-Asp-CHO; PDH, pyruvate dehydrogenase.

Treatment	Effect(s)	Comment(s)	Reference(s)
General Treatments
Fasting and diet	Complex	Lowers glycogen stores	[205–207]
Brief incubation at low O₂	Complex	Ischaemic preconditioning	[208]
Glucose/insulin	Promote glycolysis	May induce protein phosphorylation	[209–211]
Pyruvate	Metabolic substrate, inhibits fatty acid oxidation	Also protects against ROS	[212,213]
Inhibitors of fatty acid metabolism
Trimetazidine, ranolazine	Inhibit fatty acid dehydrogenases		[214]
Oxfenicine and other CPT-I inhibitors	Inhibit fatty acid entry into mitochondria		[206,215]
Malonate	Inhibits fatty acid oxidation		[216,217]
Dichloroacetate	Inhibits PDH kinase	Promotes glucose utilization	[218]
Carnitine and its derivatives	Lowers acetyl-CoA/free CoA, increasing free CoA	Promotes glycolysis by decreasing inhibition of PDH	[219,220]
Niacin	Reduces plasma non-esterified fatty acids	May help NAD recovery	[29,221]
Inhibitors of mitochondrial respiration
Amytal, rotenone	Inhibits electron flow, complex I	Decreases ROS production	[30,222]
Myxothiazole	Inhibits electron flow, complex III	Antimycin and CN⁻ not protective	[223]
Uncouplers (dinitrophenol)	Decrease mitochondrial membrane potential	Time/dose dependence, to avoid energy wastage	[223]
Oligomycin	Inhibits F₁F_o-ATPase	Time/dose dependence, to avoid ATP depletion	[224]
Inhibitors of ion movement
Ruthenium Red	Blocks mitochondrial Ca²⁺ import	Can also block the sarcoplasmic reticulum Ca²⁺-channel	[225,226]
Nisoldipine; gallopamil	Block Ca²⁺ entry into cytoplasm		[227–229]
Tetrodotoxin	Blocks Na⁺ entry into cytoplasm	Damages mitochondria during ischaemia	[63]
Amiloride	Blocks cytoplasmic Na⁺/H⁺ exchanger	Prevents Ca²⁺ overload, therefore protects against reoxygenation-induced hypercontracture	[150,230,231]
Diltiazem; SEA0400 (5-ethoxyaniline derivative)	Inhibits mitochondrial Na⁺/Ca²⁺ exchange		[232–234]
Diazoxide; nicorandil	K⁺-channel opener	Reversed by 5-OH decanoate, decreases ROS and plays roles in other undefined mechanisms	[59,66]
Inhibitors of cell damage mechanisms
Cyclosporin	Prevents MPT opening	May also inhibit Ca²⁺/CAM-dependent protein phosphatase (calcineurin)	[197,235]
Propofol	Traps ROS	ROS promote MPT	[199,236]
DEVD-CHO	Caspase 3 inhibitor (prevents downstream steps in apoptosis)	Only partially effective	[203]
Dipyridamole; carvedilol; natural compounds such as vitamin E and resveratrol; N-acetylcysteine	Antioxidants	Restores GSSG/GSH balance	[237–240]
Chloramphenicol	Inhibits cytochrome P450 mono-oxygenases	Also inhibits mitochondrial protein synthesis	[241]
Effectors of signalling pathways
Sevoflurane and other anaesthetics	NADH increase on ischaemia is reduced, and total [NAD]+[NADH] is preserved	Uncontrolled effects on membrane permeability to ions	[242]
Bromoenol-lactone	Inhibits mitochondrial Ca²⁺-independent phospholipases		[243]
Soluble factors released from preconditioned heart	Includes adenosine, catecholamines, NO, prostanoids, endorphins	See review	[244]
Adenosine	Many effects, including modulation of mK⁺_ATP channel and protein kinase C	Other additional protective mechanisms include phosphorylation to 5′-AMP during reperfusion	[245,246]