Wildfire-related smoke inhalation worsens cardiovascular risk in sleep disrupted rats

Abstract

IntroductionAs a lifestyle factor, poor sleep status is associated with increased cardiovascular morbidity and mortality and may be influenced by environmental stressors, including air pollution.MethodsTo determine whether exposure to air pollution modified cardiovascular effects of sleep disruption, we evaluated the effects of single or repeated (twice/wk for 4 wks) inhalation exposure to eucalyptus wood smoke (ES; 964 µg/m3 for 1 h), a key wildland fire air pollution source, on mild sleep loss in the form of gentle handling in rats. Blood pressure (BP) radiotelemetry and echocardiography were evaluated along with assessments of lung and systemic inflammation, cardiac and hypothalamic gene expression, and heart rate variability (HRV), a measure of cardiac autonomic tone.Results and DiscussionGH alone disrupted sleep, as evidenced by active period-like locomotor activity, and increases in BP, heart rate (HR), and hypothalamic expression of the circadian gene Per2. A single bout of sleep disruption and ES, but neither alone, increased HR and BP as rats transitioned into their active period, a period aligned with a critical early morning window for stroke risk in humans. These responses were immediately preceded by reduced HRV, indicating increased cardiac sympathetic tone. In addition, only sleep disrupted rats exposed to ES had increased HR and BP during the final sleep disruption period. These rats also had increased cardiac output and cardiac expression of genes related to adrenergic function, and regulation of vasoconstriction and systemic blood pressure one day after final ES exposure. There was little evidence of lung or systemic inflammation, except for increases in serum LDL cholesterol and alanine aminotransferase. These results suggest that inhaled air pollution increases sleep perturbation-related cardiovascular risk, potentially in part by increased sympathetic activity.

Impact of Wildfires on Cardiovascular Health

“…Combination of both treatments enhanced HR and BP soon after the first transition from light (rest) to dark (activity) compared with sleep disruption alone, and these effects persisted during handling in later days. 120 Sleep-disrupted rats exposed to smoke further exhibited larger stroke volume and cardiac output by the end of the study compared with their baseline, as well as overexpression of genes involved in adrenergic function, oxidative stress, inflammation, and BP regulation with respect to sleep disturbance alone. 120 Collectively, this evidence suggests that autonomic dysregulation following WFS exposure may heighten the sensitivity or exaggerate cardiovascular responses to proinflammatory triggers such as metabolic stress and sleep disturbance, thereby increasing both immediate and long-term vulnerability to CVD (Figure 1).…”

“…120 Sleep-disrupted rats exposed to smoke further exhibited larger stroke volume and cardiac output by the end of the study compared with their baseline, as well as overexpression of genes involved in adrenergic function, oxidative stress, inflammation, and BP regulation with respect to sleep disturbance alone. 120 Collectively, this evidence suggests that autonomic dysregulation following WFS exposure may heighten the sensitivity or exaggerate cardiovascular responses to proinflammatory triggers such as metabolic stress and sleep disturbance, thereby increasing both immediate and long-term vulnerability to CVD (Figure 1). 121 Inhaled Versus Deposited PM Dose Notwithstanding the convenience of PM concentration as a dose metric, respiratory rate depression due to expiratory braking and extended inhalation or exhalation times in mice exposed to laboratory-scale WFS smoke 122 advocate for considering the product of PM concentration and minute volume as a measure of inhaled dose when attempting to align findings from in vivo studies in animal models with epidemiological and clinical evidence.…”

“…The second arc involves the baroreceptor reflex that relies upon stretch-activated receptors in the carotid sinus and aortic arch to preserve homeostatic BP and HR levels, by opposing modulation of sympathetic and parasympathetic tones in a negative feedback fashion. Note that exposure to wood smoke has been consistently linked to elevated BP levels, 82,117,120 and a significant positive association emerged between years of service and self-reported prevalence of hypertension in WLFFs. 122 Evidence of a shift in BRS from an animal model of laboratory-scale WFS inhalation 117 further suggests that…”

“…119 Superposition of smoke inhalation accelerated the pressure rise within the left ventricle (LV) and increased the LV ejection fraction compared with filtered air post-highcarbohydrate oral load, leading to larger cardiac output and stroke work with preserved HR. 119 Complementary to this work, Martin et al 120 exposed sleep-disrupted rats to eucalyptus smoke at 1 mg/m 3 PM concentration over 4 weeks to investigate the role of smoke inhalation as a modifier for the cardiovascular repercussions of sleep disturbances. Combination of both treatments enhanced HR and BP soon after the first transition from light (rest) to dark (activity) compared with sleep disruption alone, and these effects persisted during handling in later days.…”

“…Amid the cardiovascular responses to environmental or laboratory-scale WFS inhalation in both human 82,84,85,91,99 and animal 113,[117][118][119][120] subjects, immediate changes in HRV, BRS, and arrhythmogenic potential, along with adjustments in HR, BP, and cardiac output, portend to shifts in the autonomic control of the heart and blood vessels. 57 Perez et al 152 have postulated that 3 autonomic reflex arcs may converge to regulate cardiovascular function in the context of exposure to environmental pollutants.…”