Variation in echocardiographic and cardiac hemodynamic effects of PM and ozone inhalation exposure in strains related toNppaandNpr1gene knock-out mice

Abstract

Elevated levels of ambient co-pollutants are associated with adverse cardiovascular outcomes shown by epidemiology studies. The role of particulate matter (PM) and ozone (O3) as co-pollutants in this association is unclear. We hypothesize that cardiac function following PM and O3 exposure is variably affected by genetic determinants (Nppa and Npr1 genes) and age. Heart function was measured before and after 2 days each of the following exposure sequence; (1) 2-h filtered air (FA) and 3-h carbon black (CB; 0.5 microg/m(3)); (2) 2-h O3 (0.6 ppm) and 3-h FA; (3) 5-h FA; and, (4) 2-h O3 and 3-h CB. Two age groups (5 and 18 months old (mo)) were tested in C57Bl/6J (B6) and 129S1/SvImJ (129) mice using echocardiographic (echo) and in vivo hemodynamic (IVH) measurements. With echo, posterior wall thickness was significantly (P < 0.01) greater in 129 relative to B6 mice at baseline. With CB exposure, young B6 and older 129 mice show significant (P < 0.01) reductions in fractional shortening (FS) compared to FA. With O3 exposure, FS was significantly (P < 0.01) diminished in young 129, which was attributable to significant increases in end-systolic left ventricular diameter. With O3 and CB combined, notable (P < 0.01) declines in heart rate and end-systolic posterior wall thickness occurred in young 129 mice. The IVH measurements showed striking (P < 0.05) compromises in cardiac function after CB and O3 exposure; however, strain differences were undetectable. These results suggest that PM and O3 exposures, alone and combined, lead to different cardiac functional changes, and these unique changes are age-specific and dependent on Nppa and Npr1 genes.

Inhalation of printer-emitted particles impairs cardiac conduction, hemodynamics, and autonomic regulation and induces arrhythmia and electrical remodeling in rats

“…Thus, declines in both EjeT and CtrI suggested that PEPs exposure may impair contractility despite HRV indicating enhanced sympathetic influence. These findings accord with the negative inotropic effects of exposures at > 2-fold higher PM concentrations of carbon black [33,34], diesel exhaust [31], or concentrated ambient PM [69], which may decrease cardiac output while inducing catecholamine surges to provoke hypertension, pulmonary edema, and intracellular signaling toward cardiac remodeling [65]. Accordingly, PEPs impaired contractility indices during exposure especially on day 21, but these effects rapidly dissipated immediately after exposure when systolic pressure increased-potentially through neurohormonal compensation.…”

“…Exposures to PM aerosols can impair LV systolic performance, indicated by decreases in ejection fraction, fractional shortening, and-assuming unaltered systolic and diastolic pressures-maximum LV pressure slope (dP/dt max ) [31][32][33][34][35]. Declines in these markers, along with LV ejection time [36,37] and contractility index (pressure-normalized dP/dt max ) [35], reflect diminished LV contractility and can denote heart failure: an inability of the LV to perfuse vital tissues.…”

Evaluating Potential Response-Modifying Factors for Associations between Ozone and Health Outcomes: A Weight-of-Evidence Approach

“…Toxicologic studies have reported differences in effects after O 3 exposure among different inbred strains of mice, which indicates that genetic background contributes to differential risk (Chuang et al 2009; Hamade and Tankersley 2009; Hamade et al 2008; Tankersley et al 2010). Inbred strains have been used in genetic linkage and genome-wide association studies to identify candidate genes that lead to increased risk (Cho and Kleeberger 2007), and additional studies have been conducted to validate these candidate genes and other related genes, primarily using mice with targeted gene deletions.…”

“…Toxicologic studies have also shown that oxidative damage and stress may be higher after O 3 exposure in young compared with adult rodents (Fortino et al 2007; Servais et al 2005). In addition, a series of studies reported an association between O 3 exposure and bradycardia that was present among young but not older mice (Hamade et al 2010; Hamade and Tankersley 2009; Tankersley et al 2010). Physiologic changes specific to older adults that have been observed in toxicologic studies include changes in heart structure (i.e., ventricular posterior wall thickness at end systole) (Tankersley et al 2010), wound closure (Lim et al 2006), and neurodegenerative diseases (as measured by higher lipid peroxidation in the hippocampus) (Rivas-Arancibia et al 2000).…”

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

“…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. Tankersley et al [ 44 ] showed that both carbon black particles and O 3 caused reduced cardiac output in mice but due to two different mechanisms. Thus, we speculate that although both particles and gases produce similar cardiac decrements, the mechanisms mediating the response may not be the same (e.g.…”