Photochemically Altered Air Pollution Mixtures and Contractile Parameters in Isolated Murine Hearts before and after Ischemia

Abstract

Background: The cardiopulmonary effects of the individual criteria air pollutants have been well investigated, but little is known about the cardiopulmonary effects of inhaled multipollutant mixtures that more realistically represent environmental exposures.Objectives: We assessed the cardiopulmonary effects of exposure to photochemically altered particle-free multipollutant mixtures.Methods: We exposed mice to filtered air (FA), multipollutant mixtures, or ozone (O3) for 4 hr in a photochemical reaction chamber. Eight hours after exposure, we assessed cardiac responses using a Langendorff preparation in a protocol consisting of 20 min of global ischemia followed by 2 hr of reperfusion. Cardiac function was assessed by measuring the index of left-ventricular developed pressure (LVDP) and contractility (dP/dt) before ischemia. On reperfusion after ischemia, recovery of postischemic LVDP and size of infarct were examined. We used bronchoalveolar lavage (BAL) cell counts to assess lung inflammation.Results: Exposure to the multipollutant mixtures decreased LVDP, baseline rate of left ventricular contraction (dP/dtmaximum), and baseline rate of left ventricular relaxation (dP/dtminimum) compared with exposure to FA. Exposure to O3 also decreased heart rate and dP/dtminimum. Time to ischemic contracture was prolonged in the multipollutant-mixture group relative to that in the FA group. Mice in the multipollutant-mixture group had better recovery of postischemic LVDP and smaller infarct size. Exposure to multipollutant mixtures and to O3 exposure increased numbers of macrophages in the BAL fluid.Conclusions: Exposure to photochemically altered urban air pollution appears to affect cardiac mechanics in isolated perfused hearts. Inhalation of acute multipollutant mixtures decreases LVDP and cardiac contractility in isolated non-ischemic murine hearts, prolongs ischemic contracture, increases postischemic recovery of LVDP, and reduces infarct size.Citation: McIntosh-Kastrinsky R, Diaz-Sanchez D, Sexton KG, Jania CM, Zavala J, Tilley SL, Jaspers I, Gilmour MI, Devlin RB, Cascio WE, Tong H. 2013. Photochemically altered air pollution mixtures and contractile parameters in isolated murine hearts before and after ischemia. Environ Health Perspect 121:1344–1348; http://dx.doi.org/10.1289/ehp.1306609

Ozone co-exposure modifies cardiac responses to fine and ultrafine ambient particulate matter in mice: concordance of electrocardiogram and mechanical responses

“…It appears that the method of exposure significantly impacts the post-ischemia response because even though exposure to FCAPs or UFCAPs + O 3 caused significant pre-ischemia functional decrements, there was no change in coronary flow post-ischemia and there appeared to be an improvement of LVDP recovery (Figure 7 ). These findings are similar to what we observed with inhalation of multipollutant mixtures [ 43 ] and may represent activation of some compensatory mechanism post-exposure that actually protects the heart during ischemic injury. Lastly, although infarct size was not measured in our animals, we theorize that there was probably minimum to no increase particularly given we previously observed a decrease in infarct size with multipollutant mixture inhalation [ 43 ].…”

“…These findings are similar to what we observed with inhalation of multipollutant mixtures [ 43 ] and may represent activation of some compensatory mechanism post-exposure that actually protects the heart during ischemic injury. Lastly, although infarct size was not measured in our animals, we theorize that there was probably minimum to no increase particularly given we previously observed a decrease in infarct size with multipollutant mixture inhalation [ 43 ]. Thus, acute inhalation of fine or ultrafine PM alone or in combination with O 3 may not be potent enough to cause serious ischemia-related damage and that a higher concentration is necessary to overcome this apparent response threshold.…”

“…Brook et al previously showed that PM and O 3 together cause acute arterial vasoconstriction in healthy humans subjects, but so does PM alone [ 3 , 40 ]. However, we observed depression of mechanical function with O 3 alone; although much of the current research is focused on PM as a cardiotoxicant, several studies have also noted the adverse cardiovascular effects of O 3 inhalation; which include decreased HR, alteration of cardiac repolarization, and increased inflammation [ 9 , 41 - 43 ]. As such, the type of cardiac responses following air pollution may be dependent on the type of pollutant, or combination of pollutants, with some degree of overlapping effects.…”

Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution

“…Briefly, Photochemical degradation of SynUrb54 lead to the production of multiple generations of (oxidized) daughter compounds (Ebersviller et al, 2012b). Toxicity studies using A549 cells have shown that atmospheric transformation products resulting from photochemical degradation induce higher toxicity than single compounds or unreacted chemical mixtures (Ebersviller et al, 2012b, McIntosh-Kastrinsky et al, 2013, Sexton et al, 2004). An O 3 concentration for 400ppb was selected since it was previously shown (Ebersviller et al, 2012a) that this concentration produces a robust IL-8 protein increase in the culture medium similar to that observed in the photochemcially aged atmospheres.…”

Inhalation of Simulated Smog Atmospheres Affects Cardiac Function in Mice

“…We [18,19] and others [20] have previously shown that PM exposure enhanced cardiac ischemia/ reperfusion injury in animals. We have also reported that particle free multipollutant mixtures generated in a photochemical reaction chamber under sunlight depressed cardiac function in mice [21]. In the present study, we examined whether photochemically-reacted atmospheres generated from mixtures of gasoline and/or isoprene could affect the cardiovascular system in animals.…”