Ischemic heart disease: the role of mitochondria--carvedilol prevents lipid peroxidation of mitochondrial membranes.
Depriving heart tissue of their blood supply leads to a decrease in high-energy compounds and many metabolic disturbances. Following short periods of ischemia, heart can recover their physiological functions after reperfusion, but prolonged ischemia injures heart irreversibly. Mitochondrial disfunction is one of the most critical events associated to injury irreversibility because regeneration of a high ATP level is indispensable for recovery of cellular functions. Reperfusion injury is also implicated in the irreversible damage of the ischemic heart. Even after a period of ischemia that is too short to injure the heart, reperfusion can cause further irreversible damage. The formation of oxygen radicals caused by reintroduction of O2 is probably the most important factor of this phenomenon. The mitochondrial redox chain is one of the main sources of O2 radicals responsible for causing damage to mitochondria, and thus mitochondria can be damaged during reperfusion. Most probably the opening of the mitochondrial permeability transition pore due to increased production of oxygen radicals is associated with the irreversible disruption of mitochondria for oxidative phosphorylation. Carvedilol, a potent antioxidant, prevents the lipoperoxidation of mitochondrial membranes what suggest a strong contribution to the known cardioprotective activity of this compound through protection of mitochondrial functions.
Moreno
A J
AJ
Center for Neurosciences of Coimbra, University of Coimbra. AJMMoreno@gemini.ci.uc.pt
Santos
D J
DJ
Palmeira
C M
CM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D002463:Cell Membrane Permeability / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D002118:Calcium