In hyperthyroid rats octylguanidine protects the heart from reperfusion damage.
Hyperthyroidism sensitizes the heart for reperfusion injury. As known, mitochondrial permeability transition underlies reperfusion heart damage. This study was undertaken to explore the protective effect of octylguanidine (OG), an inhibitor of permeability transition, on hearts from hyperthyroid rats subjected to ischemia/reperfusion. Hyperthyroidism was induced by a daily injection of 2 mg T3/kg body weight for 5 days. OG was injected at a dose of 5 mg/kg body weight. It was found that the amine protects against reperfusion-induced permeability transition, i.e., mitochondria from hyperthyroid rats, treated with OG, retained accumulated Ca(2+), similarly to control mitochondria. OG maintained post reperfusion cardiac frequency in hyperthyroid rats at 429 +/- 16 in comparison to control and T3 treated rats (70 +/- 12 and 71 +/- 2, respectively). We also found that OG diminished the post reperfusion accumulation of IFNgamma from 34.3 +/- 2.5 to 18.7 +/- 1.35, IL-6 from 38.5 +/- 4.5 to 15.1 +/- 0.12, IL-1 from 16.78 +/- 0.73 to 12.19 +/- 1.54, and TNFalpha from 45.05 +/- 3.14 to 29.85 +/- 4.3 (pg/50 microg myocardial tissue). It is concluded that OG inhibits the hypersensitivity of the hyperthyroid myocardium to undergo reperfusion damage due to its inhibitory action on the permeability transition pore.
Pavón
Natalia
N
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1, Col. Sección XVI, Tlalpan, Mexico, D.F. 014080, México.
Aranda
Alberto
A
García
Noemí
N
Hernández-Esquivel
Luz
L
Chávez
Edmundo
E
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D006146:Guanidines / Q000627:therapeutic use*; D006980:Hyperthyroidism / Q000139:chemically induced / Q000150:complications*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006146:Guanidines; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine; C015403:octylguanidine; D007371:Interferon-gamma; D002118:Calcium