Selective TNF-α targeting with Infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter

MARCHINI TIMOTEO; DANNUNZIO VERONICA; PAZ ML; CACERES LOURDES; GARCÉS MARIANA; PEREZ VIRGINIA; TASAT DÉBORAH; VANASCO VIRGINIA; MAGNANI NATALIA; GONZALEZ MAGLIO G; GELPI RJ; ALVAREZ SILVIA; EVELSON PABLO

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Año: 2015

0363-6135

Inflammation plays a central role in the onset and progression ofcardiovascular diseases associated with the exposure to air pollutionparticulate matter (PM). The aim of this work was to analyze thecardioprotective effect of selective TNF- targeting with a blockinganti-TNF- antibody (infliximab) in an in vivo mice model of acuteexposure to residual oil fly ash (ROFA). Female Swiss mice receivedan intraperitoneal injection of infliximab (10 mg/kg body wt) or salinesolution, and were intranasally instilled with a ROFA suspension (1mg/kg body wt). Control animals were instilled with saline solutionand handled in parallel. After 3 h, heart O2 consumption was assessedby high-resolution respirometry in left ventricle tissue cubes andisolated mitochondria, and ventricular contractile reserve and lusitropicreserve were evaluated according to the Langendorff technique.ROFA instillation induced a significant decrease in tissue O2 consumptionand active mitochondrial respiration by 32 and 31%, respectively,compared with the control group. While ventricular contractilestate and isovolumic relaxation were not altered in ROFA-exposedmice, impaired contractile reserve and lusitropic reserve were observedin this group. Infliximab pretreatment significantly attenuatedthe decrease in heart O2 consumption and prevented the decrease inventricular contractile and lusitropic reserve in ROFA-exposed mice.Moreover, infliximab-pretreated ROFA-exposed mice showed conservedleft ventricular developed pressure and cardiac O2 consumptionin response to a -adrenergic stimulus with isoproterenol. Theseresults provides direct evidence linking systemic inflammation andaltered cardiac function following an acute exposure to PM andcontribute to the understanding of PM-associated cardiovascular morbidityand mortality.a