Whole and Particle-Free Diesel Exhausts Differentially Affect Cardiac Electrophysiology, Blood Pressure, and Autonomic Balance in Heart Failure-Prone Rats

U.S. Environmental Protection Agency, Environmental Public Health Division, PO B143-01, Research Triangle Park, NC 27711, USA.
Toxicological Sciences (Impact Factor: 3.85). 04/2012; 128(2):490-9. DOI: 10.1093/toxsci/kfs162
Source: PubMed


Epidemiological studies strongly link short-term exposures to vehicular traffic and particulate matter (PM) air pollution with adverse cardiovascular (CV) events, especially in those with preexisting CV disease. Diesel engine exhaust is a key contributor to urban ambient PM and gaseous pollutants. To determine the role of gaseous and particulate components in diesel exhaust (DE) cardiotoxicity, we examined the effects of a 4-h inhalation of whole DE (wDE) (target PM concentration: 500 µg/m(3)) or particle-free filtered DE (fDE) on CV physiology and a range of markers of cardiopulmonary injury in hypertensive heart failure-prone rats. Arterial blood pressure (BP), electrocardiography, and heart rate variability (HRV), an index of autonomic balance, were monitored. Both fDE and wDE decreased BP and prolonged PR interval during exposure, with more effects from fDE, which additionally increased HRV triangular index and decreased T-wave amplitude. fDE increased QTc interval immediately after exposure, increased atrioventricular (AV) block Mobitz II arrhythmias shortly thereafter, and increased serum high-density lipoprotein 1 day later. wDE increased BP and decreased HRV root mean square of successive differences immediately postexposure. fDE and wDE decreased heart rate during the 4th hour of postexposure. Thus, DE gases slowed AV conduction and ventricular repolarization, decreased BP, increased HRV, and subsequently provoked arrhythmias, collectively suggesting parasympathetic activation; conversely, brief BP and HRV changes after exposure to particle-containing DE indicated a transient sympathetic excitation. Our findings suggest that whole- and particle-free DE differentially alter CV and autonomic physiology and may potentially increase risk through divergent pathways.

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Available from: Alex P Carll
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    • "It is notable, therefore, that the adverse cardiovascular responses we describe for EC and its subfractions are consistent with HR, HRV and BP responses reported during controlled exposures to whole diesel engine exhaust in the same SH strain of rats we used in the current study [27,28]. While major components of laboratory-generated diesel exhaust are gaseous inorganic compounds (nitrogen oxides, sulfur dioxide, and carbon monoxide), the minor components of particulate EC and of volatile and semivolatile organic compounds (OC) have been linked to stimulation of both sympathetic and parasympathetic cardiovascular effects in SH rats where exposures compared whole versus filtered exhaust [29,30]. A major difference in our field studies compared to laboratory-generated diesel engine exhaust is the atmospheric transformation of EC core particulates that might result in surface adherence of volatile organic hydrocarbons such as carbonyls, or in oxidative modifications that alter the particle’s toxicity [31,32]. "
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    ABSTRACT: Background We tested the hypothesis that cardiovascular responses to PM2.5 exposure will be enhanced in hypertensive rats and linked to specific carbonaceous pollutants in an urban industrial setting. Methods Spontaneously hypertensive rats were exposed by inhalation to concentrated PM2.5 in an industrial area of Dearborn, Michigan, for four consecutive summer days. Blood pressure (BP), heart rate (HR) and HR variability (HRV) metrics (SDNN, RMSSD) were assessed by radiotelemetry and compared to 1 h- and 8 h-averaged fluctuations in PM2.5 composition, with a focus on elemental and organic carbon (EC and OC, respectively), and temperature-resolved subfractions (EC1-EC5, PC (pyrolized carbon), and OC1-OC4), as well as other major and minor PM components. Results Mean HR and BP were increased, while HRV was decreased over 4 days of exposure. Using 1 h averages, EC (1 μg/m3 increase) was associated with increased HR of 11-32 bpm (4-11% increase), 1.2-1.5 ms (22-27%) decreases in SDNN, 3-14 mmHg (1.5-8%) increases in systolic BP, and 5-12 mmHg (4-9%) increases in diastolic BP. By comparison, associations with OC were negligible. Using 8 h averages, EC subfractions were linked with increased heart rate (EC1: 13 bpm; EC2, EC3, PC: <5 bpm) and SDNN (EC1> > EC2 > EC3, EC4, PC), but with decreased RMSSD (EC2, EC5 > EC3, EC4). Minimal effects were associated with OC and OC1. Associations between carbon subfractions and BP were negligible. Associations with non-carbonaceous components and trace elements were generally non-significant or of negligible effect size. Conclusions These findings are the first to describe associations between acute cardiovascular responses and thermally resolved carbon subfractions. We report that cardiovascular responses to PM2.5 carbonaceous materials appear to be driven by EC and its EC1 fraction.
    Full-text · Article · May 2014 · Particle and Fibre Toxicology
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    • "We have previously exposed cultured lung cells to similar multipollutant mixtures in the photochemical reaction chamber and showed that gaseous products elicited biological and biochemical responses in the absence of particles (Sexton et al. 2004). Furthermore, animal studies have shown that spontaneously hypertensive and mildly cardiomyopathic rats exposed to filtered diesel exhaust exhibited either a similar degree or a greater magnitude of electrophysiological changes compared with exposure to whole diesel exhaust (Carll et al. 2012; Lamb et al. 2012), implying that gaseous components of air pollution might be driving the cardiovascular effects. "
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    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.
    Full-text · Article · Oct 2013 · Environmental Health Perspectives
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    • "activity that tend to occur over the course of our chamber exposures (Carll et al., 2012). We saw a hyperthermic response in the current study that was consistent with sympathetic dominance and likely persisted during exposure despite β 1 -blockade because thermogenesis is mediated by sympathetic stimulation of the β 3 -receptor. "
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    ABSTRACT: Background: Cardiac disease exacerbation is associated with short-term exposure to vehicular emissions. Diesel exhaust (DE) might impair cardiac performance in part through perturbing efferent sympathetic and parasympathetic autonomic nervous system (ANS) input to the heart.Objective: We hypothesized that acute changes in ANS balance mediate decreased cardiac performance upon DE inhalation.Methods: Young adult heart failure-prone rats were implanted with radiotelemeters to measure heart rate (HR), HR variability (HRV), blood pressure (BP), core body temperature, and pre-ejection period (PEP, a contractility index). Animals pretreated with sympathetic antagonist (atenolol). parasympathetic antagonist (atropine), or saline, were exposed to DE (500 μg/m(3) PM2.5, 4 hours) or filtered air and then treadmill exercise challenged. At 1 day post-exposure, separate rats were catheterized for left ventricular pressure (LVP), contractility, and lusitropy and assessed for autonomic influence using the sympatho-agonist dobutamine and surgical vagotomy.Results: During DE exposure, atenolol inhibited increases in HR, BP, and contractility, but not body temperature, suggesting a role for sympathetic dominance. During treadmill recovery at 4 hours post-DE exposure, HR and HRV indicated parasympathetic dominance in saline- and atenolol-pretreated groups that atropine inhibited. Conversely, at treadmill recovery 21 hours post-DE exposure, HRV and PEP indicated sympathetic dominance and subsequently diminished contractility that only atenolol inhibited. LVP at 1 day post-exposure indicated that DE impaired contractility and lusitropy while abolishing parasympathetic-regulated cardiac responses to dobutamine.Conclusions: This is the first evidence that air pollutant inhalation both causes time-dependent oscillations between sympathetic and parasympathetic dominance and decreases cardiac performance via aberrant sympathetic dominance.
    Full-text · Article · Jul 2013 · Toxicological Sciences
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