The exposure to an environmental particulate matter surrogate rich in transition metals impairs cardiac mitochondrial function and contractile reserve

MARCHINI, TIMOTEO; MAGNANI, NATALIA; D'ANNUNZIO, VERONICA; TASAT, DEBORAH; GELPI, RICARDO; ALVAREZ, SILVIA; EVELSON, PABLO

Punta del Este

Simposio; XII International Symposium on Metal Ions in Biology and Medicine; 2013

Universidad de la República

The exposure to environmental particulate matter (PM) is associated with increased cardiovascular morbidity and mortality. Transition metal content of PM is suggested to play a predominant role, owing to their ability to drive Fenton-like reactions leading to oxidative metabolism alterations. A byproduct of fossil fuel combustion known as residual oil fly ashes (ROFA) is particularly rich in iron, nickel and vanadium, and is frequently used as a PM surrogate to evaluate the contribution of transition metals on PM biological effects. To address this hypothesis, with focus on heart mitochondrial and cardiac function, an in vivo animal model of acute exposure to ROFA was used. Female Swiss mice weighting 25 g were intranasally instilled with a ROFA suspension (1 mg/kg) and hearts were removed after 3 hours. Tissue and isolated mitochondrial oxygen consumption was followed polarographically with a Clark-type oxygen electrode. Mitochondrial membrane potential was evaluated by flow cytometry. Mitochondrial ATP production rate was determined by a chemiluminescent assay. Cardiac contractile reserve was evaluated in isolated perfused hearts at constant flow, as left ventricular developed pressure before and after a β-adrenergic stimulus with isoproterenol. Tissue oxygen consumption was significantly decreased by 38% in ROFA-exposed mice (control: 1180±70 ng-at O/min g tissue, p