John S. Floras

The Effect of Air Pollution on Spatial Dispersion of Myocardial Repolarization in Healthy Human Volunteers

OBJECTIVESnWe tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O(3)) would increase dispersion of ventricular repolarization.nnnBACKGROUNDnElevated levels of air pollution are associated with cardiac arrhythmias through mechanisms yet to be elucidated.nnnMETHODSnEach of 25 volunteers (18 to 50 years of age) had four 2-h exposures to 150 μg/m(3) CAP; 120 parts per billion O(3); CAP + O(3); and filtered air (FA). Exposure-induced changes (Δ = 5-min epochs at end-start) in spatial dispersion of repolarization were determined from continuous 12-lead electrocardiographic recording.nnnRESULTSnSpatial dispersion of repolarization assessed by corrected ΔT-wave peak to T-wave end interval increased significantly for CAP + O(3) (0.17 ± 0.03, p < 0.0001) exposure only, remaining significant when factoring FA (CAP + O(3) - FA) as control (0.11 ± 0.04, p = 0.013). The influence on repolarization was further verified by a significant increase in ΔQT dispersion (for CAP + O(3) compared with FA (5.7 ± 1.4, p = 0.0002). When the low-frequency to high-frequency ratio of heart rate variability (a conventional representation of sympathetic-parasympathetic balances) was included as a covariate, the effect estimate was positive for both corrected ΔT-wave peak to T-wave end interval (p = 0.002) and ΔQT dispersion (p = 0.038). When the high-frequency component (parasympathetic heart rate modulation) was included as a covariate with corrected ΔT-wave peak to T-wave end interval, the effect estimate for high frequency was inverse (p = 0.02).nnnCONCLUSIONSnCAP + O(3) exposure alters dispersion of ventricular repolarization in part by increasing sympathetic and decreasing parasympathetic heart rate modulation. Detection of changes in repolarization parameters, even in this small cohort of healthy individuals, suggests an underappreciated role for air pollutants in urban arrhythmogenesis.

Desipramine blocks augmented neurogenic vasoconstrictor responses to epinephrine.

The forearm vasoconstrictor response to lower body negative pressure (LBNP), a reflex stimulus to norepinephrine release, can be augmented by a prior brachial artery infusion of epinephrine. We wished to determine whether this sustained aftereffect of epinephrine could be replicated by systemic infusion and, if so, whether it could be prevented by prior uptake-1 blockade with desipramine. Eight normal men (mean age 30 years) were studied on two separate study days at least 1 week apart, 2.5 hours after taking, at random, either desipramine 125 mg p.o.) or placebo. Forearm vascular resistance was measured at rest and at the end of 6 minutes of LBNP at ‐40 mm Hg. This was done both before and 30 minutes after a 60 -minute infusion of epinephrine (1.5 /ttg/min i.v.). From similar baselines, the forearm vasoconstrictor response to LBNP was significantly augmented 30 minutes after epinephrine on the placebo day (+17±4 vs. +12±3 resistance units, mean±SEM, p < 0.01) but not on the desipramine day (+14±2 vs. +16±3 resistance units). The heart rate response to LBNP was also greater after epinephrine on the placebo day (+20±3 vs. +16±2 beats/min, p < 0.05). Mean arterial pressure was higher after epinephrine infusion on the placebo (p < 0.01) but not on the desipramine day. Thus, transient increases in epinephrine, which has a plasma half-life of only minutes, can have sustained aftereffects, increasing mean arterial pressure and augmenting vasoconstrictor and chronotropic responses to a reflex stimulus to norepinephrine release 30 minutes after its infusion. These effects appear to be mediated through the uptake of epinephrine by sympathetic nerves and its corelease with norepinephrine on subsequent nerve stimulation. Epinephrine then could act on prejunctional /3-adrenergic receptors to facilitate norepinephrine release and augment neurogenic vasoconstriction. These observations provide further support for the concept that increases in plasma epinephrine concentration might contribute to the pathogenesis of essential hypertension by this mechanism.

The Lability of Blood Pressure

Stephen Hales inserted into the carotid artery of a mare a brass pipe ‘and to that the Wind-Pipe of a Goose; to the other end of which a Glass Tube was fixed’. During the course of his investigations he noted that blood pressure varied from beat to beat, often, but not always, in conjunction with respiration. These variations were attributed either to changes in the blood, or in the vascular resistance. Variations in arterial pressure occur during the course of daily activities [2] and sleep [3]. Diehl [4] noted that the variation in measurements obtained over a period of 6 days in 100 students was unrelated to their mean systolic blood pressure.