Seasonal effects of ambient PM_2.5 on the cardiovascular system of hyperlipidemic mice

Figures & data

Figure 2. ECG waveform definitions. All waveform definitions were defined using ecgAUTO (see text for full definitions). Waveform libraries were assembled for each mouse using data acquired during a one-week baseline period immediately preceding the start of the exposure. Changes in ECG morphology in exposed mice were determined by comparing daily waveform measurements against baseline values. Circled numbers in the ECG trace correspond to defined contraction (orange shading) and relaxation (green shading) events in the heart highlighted on the right of the image.

Figure 1. Schematic of VACES and exposure setup. Red lines indicate CAPs atmosphere. Green lines indicate filtered air exposure.

Table 1. Exposure parameters and atmosphere characteristics for both high and low PCA Concentrated Ambient Particles (CAPs) PM_2.5. Data presented as exposure averages ± standard deviation.

	High PCA CAPs	High PCA ambient air	High PCA filtered air	Low PCA CAPs	Low PCA ambient air	Low PCA filtered air
Exposure dates (Start/End)	23 July 15/11 Sept 15	23 July 15/11 Sept 15	23 July 15/11 Sept 15	23 Aug 16/20 Oct 16	23 Aug 16/20 Oct 16	23 Aug 16/20 Oct 16
Average number concentration (cm^−3)	(8.7 ± 1.2) × 104	(6.8 ± 0.1) × 103	–	(5.6 ± 0.5) × 104	(1.0 ± 0.1) × 104	–
Average mass concentration (µg m−3)	133 ± 20	12.5 ± 0.9	0.08 ± 0.02	134 ± 70	12.2 ± 0.4	0.03 ± 0.04
24-hr average mass equivalence	27 ± 4	27 ± 4	27 ± 4	28 ± 15	28 ± 15	28 ± 15
Average ambient ozone concentration (ppb)	37.1 ± 0.8	37.1 ± 0.8	37.1 ± 0.8	24 ± 1.3	24 ± 1.3	24 ± 1.3
Average mean ambient temperature (°F)	76.1 ± 4.7	76.1 ± 4.7	76.1 ± 4.7	72.1 ± 4.2	72.1 ± 4.2	72.1 ± 4.2
Average dew point (°F)	63.0 ± 2.5	63.0 ± 2.5	63.0 ± 2.5	57.8 ± 4.3	57.8 ± 4.3	57.8 ± 4.3

Table 2. Relevant ambient air quality standards for ozone, PM_2.5, carbon monoxide (CO), and nitrogen dioxide (NO₂). Los Angeles Basin measurements taken 80 m from nearest freeway.

		Ambient air quality standards
		National	California
Ozone (ppb)		70	70
PM2.5 (µg m^−3)	24-hr	75	–
	Annual	12	12
CO (ppm)	1-hr	35	20
	8-hr	9	9
NO2 (ppb)	1 hr	100	180
	Annual	53	30
		Typical Los Angeles basin concentrations
		Summer (High PCA)	Winter (Low PCA)
PM2.5	p/cm^3	2.6 × 10^4	2.7 × 10^4
	µg/m^3	14	12
CO (ppm)		0.23	0.52
NO2 (ppb)		18	32

Figure 3. Oxygen-to-carbon ratios of PM₁ sampled during different seasons compared to UV radiation flux at Earth’s surface. Closed green markers indicate late fall/early winter of 2014, closed purple markers indicate late winter of 2015, closed red markers indicate late spring/early summer of 2016, and closed blue markers indicate late fall/early winter of 2016. Open red and blue markers indicate CAPs measurement for late fall/early winter 2015 and 2016, respectively. UV flux was taken at 30°N latitude (close to Irvine) at 12:00 pm PST accounting for the monthly change in solar zenith angle ³⁹. Exposure periods for this study occurred during periods designated by red and blue dots.

Table 3. Average baseline values for all measured endpoints. Significant differences between cohorts during each experimental period assessed at P≤ 0.05 using Student’s T-test and indicated by italics.

	High PCA					Low PCA
Endpoint	Air		CAPs		P	Air		CAPs		P
Heart rate	561.71	2.12	558.58	3.97	0.50	576.68	3.87	566.98	5.14	0.14
R-R interval	108.20	0.48	109.50	0.86	0.20	105.36	0.76	107.09	1.07	0.19
P-R interval	34.01	0.31	33.18	0.47	0.16	34.10	0.27	34.70	0.53	0.32
QRS interval	13.32	0.12	13.73	0.21	0.10	16.11	0.71	14.97	0.99	0.35
QTcM interval	44.28	0.63	45.46	0.37	0.10	46.54	0.31	45.77	0.34	0.10
T-wave area	−1.48	0.11	−1.80	0.16	0.07	−1.84	0.22	−2.24	0.10	0.10
T-wave amplitude	−0.10	0.01	−0.12	0.01	0.11	−0.14	0.01	−0.14	0.00	0.39
SDNN	4.65	0.46	5.15	0.62	0.11	5.03	0.09	5.05	0.08	0.88
RMSSD	3.31	0.20	3.99	0.27	0.04	4.06	0.10	3.79	0.16	0.20
HF	0.70	0.24	1.11	0.39	0.21	4.80	0.27	4.74	0.22	0.86
LF	4.22	0.38	5.32	0.34	0.06	1.03	0.05	0.93	0.07	0.27
Systolic BP	147.29	5.22	127.31	7.00	0.03	142.01	3.42	147.63	7.11	0.47
Diastolic BP	116.37	4.97	100.05	6.95	0.07	110.29	2.69	118.43	7.04	0.28

Figure 4. Blood pressure changes induced by particle exposure. Data represent weekly aggregates of change from baseline values for control and exposed animals during periods of high or low photochemical activity (± SEM, n = 3–5/group depending on acquisition scheduling). High PCA data set is complete and sporadic due to system availability. Low PCA CAPs data from week 2 is missing due to acquisition program errors. Significance assessed at p ≤ 0.05; *CAPs significantly different than air over the entire exposure period.

Table 4. Summary of ANOVA-derived significant values. Overall differences between control and CAP-exposed animals for both high and low PCA time periods. Partial Eta (η²) is provided and represents the proportion on variance accounted for by each dependent variable. *indicates P ≤ .05 while ^#indicates P ≤ 0.1 by Bonferroni-corrected two-way ANOVA for repeated measures. Italic font indicates significant differences.

	High PCA CAPs vs. Air				Low PCA CAPs vs. Air
Endpoint	F-statistic	P	Partial η2		F-statistic	P	Partial η2
Heart rate	6.586	0.037	0.485	*	0.011	0.919	0.002
R-R interval	1.772	0.231	0.228		0.57	0.819	0.009
P-R interval	0.696	0.432	0.090		0.018	0.897	0.003
QRS interval	0.899	0.050	0.114	*	.103	0.129	0.341
QTcM interval	2.470	0.065	0.261	#	1.951	0.212	0.245
T-wave area	0.562	0.478	0.074		1.454	0.273	0.195
T-wave amplitude	0.345	0.575	0.047		0.005	0.946	0.001
SDNN	0.144	0.711	0.012		0.214	0.653	0.021
RMSSD	6.289	0.078	0.344	#	0.353	0.566	0.034
HF	3.763	0.028	0.255	*	0.301	0.595	0.029
LF	1.191	0.297	0.090		1.282	0.284	0.144
Systolic BP	11.069	0.004	0.409	*	0.024	0.880	0.002
Diastolic BP	11.042	0.004	0.394	*	0.358	0.559	0.023

Figure 5. HRV averages for high and low PCA CAPs exposure. Data represent weekly aggregates of change from baseline values for control and exposed animals during periods of high or low photochemical activity (± SEM, n = 3–5/group depending on acquisition scheduling). Low PCA CAPs data from week 2 is missing due to acquisition program errors. *p ≤ 0.05; CAPs significantly different than air over the entire exposure period. ^# p ≤ 0.1; CAPs significantly different than air over the entire exposure period.

Figure 6. Heart rate-related ECG waveform changes. Data represent weekly aggregates of change from baseline values for control and exposed animals during periods of high or low photochemical activity (± SEM, n = 3-5/group depending on acquisition scheduling). Low PCA CAPs data from week 2 is missing due to acquisition program errors. Significance assessed at * p ≤ 0.05 or ^# p ≤ 0.1 for CAPs compared to controls over the entire exposure period.

Figure 7. T-wave-related ECG waveform changes. Data represent weekly aggregates of change from baseline values for control and exposed animals during periods of high or low photochemical activity (± SEM, n = 3-5/group depending on acquisition scheduling). Low PCA CAPs data from week 2 is missing due to acquisition program errors. Significance assessed at p ≤ 0.05; *CAPs significantly different than air over the entire exposure period.