Air pollution & cardiovascular disease

Sulfur dioxide (SO2) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed to characterize a) in vivo alterations in heart rate and b) altered activity in brainstem neurons that control heart rate after perinatal SO2 exposure. In addition to identification of neuronal network alterations, the model also enabled the examination of the effects of prenatal versus postnatal exposure to SO2, as well as to define a timeframe for recovery from exposure to SO2. Pregnant Sprague Dawley dams and their pups were exposed to 5 parts per million SO2 for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal heart rate, as well as diving reflex-evoked changes in heart rate, following perinatal SO2 exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO2 exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO2 exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO2 exposure. However the frequency of excitatory glutamatergic neurotransmission was decreased by 50 % upon SO2 exposure, which was tetrodotoxin-sensitive. This action potential-dependent change in activity indicated that SO2 exposure did not alter the synapses between the glutamatergic neurons and the cardiac vagal neurons. Instead, these data suggest a different mechanism is responsible for the impaired activity of the excitatory inputs to cardiac vagal neurons. Modification of the model to compare pups exposed to SO2 only during the prenatal period versus those only exposed during the postnatal period showed, in in vitro recordings, that prenatal exposure only did not diminish excitatory neurotransmission to cardiac vagal neurons. However, postnatal exposure to SO2> significantly decreased the frequency of glutamatergic neurotransmission when compared with control animals. These data were supported by in vivo electrocardiograph recordings showing that there was no alteration in heart rate caused by prenatal exposure alone, but there was a significant increase in heart rate in animals exposed only during the postnatal period. Finally, experiments in which pups were exposed to SO 2 during the postnatal period through postnatal day 5 and were then allowed to recover, revealed that within two days of the last exposure, the decrease in the frequency of glutamatergic neurotransmission to cardiac vagal neurons was no longer significantly blunted, and the glutamatergic excitatory synaptic frequency returned to control levels by postnatal day 9. Electrocardiograms recorded daily from animals exposed only during the postnatal period from P5-9 revealed that the elevation in basal heart rate at P5 was still present at P6, but by P7 and beyond, heart rate recovered and was not significantly different than air-exposed pups. Additionally, diving reflex-evoked parasympathetic activity was found to be significantly blunted in P5-P7 pups exposed to SO 2 postnatally compared to air-exposed pups, but this diminished reflex response recovered and was no longer statistically different from control animals by P8 and P9. These data describe a central mechanism to explain how SO2 elicits tachycardia and blunts a powerful autonomic reflex via diminished excitatory, but unaltered inhibitory, neurotransmission frequency to brainstem parasympathetic cardiac vagal neurons that control heart rate. This impairment can be elicited by postnatal exposure to SO2 alone, and is not induced by permanent changes to the autonomic network as pups recovered from these effects within 2-3 days post exposure.