Dobutamine “Stress” Test and Latent Cardiac Susceptibility to Inhaled Diesel Exhaust in Normal and Hypertensive Rats

Abstract

Background: Exercise “stress” testing is a screening tool used to determine the amount of stress for which the heart can compensate before developing abnormal rhythm or ischemia, particularly in susceptible persons. Although this approach has been used to assess risk in humans exposed to air pollution, it has never been applied to rodent studies.Objective: We hypothesized that a single exposure to diesel exhaust (DE) would increase the risk of adverse cardiac events such as arrhythmia and myocardial ischemia in rats undergoing a dobutamine challenge test, which can be used to mimic exercise-like stress.Methods: Wistar-Kyoto normotensive (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters and a chronic intravenous catheter were whole-body exposed to 150 μg/m3 DE for 4 hr. Increasing doses of dobutamine, a β1-adrenergic agonist, were administered to conscious unrestrained rats 24 hr later to elicit the cardiac response observed during exercise while heart rate (HR) and electrocardiogram (ECG) were monitored.Results: A single exposure to DE potentiated the HR response of WKY and SH rats during dobutamine challenge and prevented HR recovery at rest. During peak challenge, DE-exposed SH rats had lower overall HR variability when compared with controls, in addition to transient ST depression. All DE-exposed animals also had increased arrhythmias.Conclusions: These results are the first evidence that rats exhibit stress-induced cardiac dysrhythmia and ischemia sensitivity comparable to humans after a single exposure to a toxic air pollutant, particularly when in the presence of underlying cardiovascular disease. Thus, exposure to low concentrations of air pollution can impair the heart’s ability to respond to stress and increase the risk of subsequent triggered dysfunction.

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

“…To that point, we previously showed that a single exposure to either O 3 or acrolein causes various cardiovascular effects in rodents; these range from electrocardiogram changes, autonomic imbalance, desensitization of baroreflex, to alterations in hypoxia responsiveness (Farraj et al, 2012; Hazari et al, 2009b; Hazari et al, 2014; Perez et al, 2013). Moreover, many of these effects appear to be latent and are only evident if the body is challenged or encounters a subsequent trigger (Hazari et al, 2012), which would suggest the underlying mechanisms involve the disruption of homeostatic controls which maintain equilibrium of vital bodily systems under changing conditions.…”

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

“…As such, a wide range of cardiac responses demonstrated by controlled human and animal PM exposure studies have provided biological plausibility to the health effects of air pollution [ 3 , 8 - 10 ]. Some of these are responses observed using ECG and have been shown to be similar in humans and animals [ 11 , 12 ]. For instance, some human subjects exposed to PM have decreased heart rate variability (HRV), which is a predictor of increased risk [ 13 - 16 ], and enhanced arrhythmogenesis [ 17 ].…”

Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia and pulmonary inflammation in heart failure-prone rats

“…Two candidate mechanisms include the triggering of acute pulmonary irritant reflexes and the activation of myocardial stretch receptors (Carll et al 2013b; Hazari et al 2012). The activation of the transient-receptor potential ankyrin-1 (TRPA1) channel appears partly responsible for pulmonary-derived autonomic imbalance (Hazari et al 2012).…”

“…Two candidate mechanisms include the triggering of acute pulmonary irritant reflexes and the activation of myocardial stretch receptors (Carll et al 2013b; Hazari et al 2012). The activation of the transient-receptor potential ankyrin-1 (TRPA1) channel appears partly responsible for pulmonary-derived autonomic imbalance (Hazari et al 2012). Additionally, left ventricular dilation can trigger parasympathetic mechanoreceptor reflexes and has been observed with inhalation exposures to carbon black or DE that also both increased HRV and AV block (Carll et al 2013b; Tankersley et al 2004; Tankersley et al 2008).…”