Unfavorable Effects of Passive Smoking on Aortic Function in Men

Among other underlying mechanisms, tobacco smoke's effect on the mechanical properties of the arterial wall may play an important role in its catastrophic cardiovascular effects. Previous studies have shown that active smoking influences endothelium-mediated vascular control [1-3], induces coronary artery vasoconstriction [4-7], and increases the stiffness of both muscular and elastic arteries [8-11]. Other investigators have demonstrated that passive smoking is associated with dose-related impairment of endothelium-dependent dilatation and with coronary artery vasoconstriction [12, 13]. The aorta acts as both a conduit and an elastic buffering chamber. By virtue of its elastic properties, this vessel influences left ventricular performance and coronary blood flow [14-23]. Conceivably, any adverse effect of smoking on aortic performance could compromise left ventricular function and coronary blood flow. Previous studies from our laboratory have shown that aortic elastic properties deteriorate acutely during active smoking [24]. In the current study, we investigated aortic elastic properties during passive smoking by using a high-fidelity method suitable for determining the association between aortic pressure and diameter [24-26]. Methods Study Group Potential participants were male patients who underwent diagnostic cardiac catheterization for evaluation of chest pain. Patients with left main-vessel or three-vessel coronary artery disease, arterial hypertension, valvular heart disease, congenital heart disease, left ventricular systolic dysfunction, chronic obstructive pulmonary disease, history of cerebrovascular accident, and diabetes mellitus were excluded from the study. According to these criteria, 16 nonsmokers and 32 current, long-term smokers ( 1 pack per day for 1 year) were enrolled in the study. The nonsmokers were assigned to passive smoking studies, and the smokers were randomly assigned to either active (16 patients) or sham (16 patients) smoking studies. Cardiovascular agents were withheld for at least five half-lives before the study. The institutional ethical committee approved the study protocol, and each patient provided written informed consent. Study Protocol Design The participants did not consume caffeine-containing beverages or meals and refrained from smoking for at least 12 hours before the study. Diagnostic cardiac catheterization and studies of aortic performance were performed during the same catheterization session. After diagnostic catheterization, the participants were allowed to relax in the supine position. An exposure chamber was placed over the heads of the persons in the passive smoking group. Thirty minutes after the last infusion of contrast medium, baseline hemodynamic measurements were obtained. For the passive smoking group, environmental tobacco smoke was then vented into the exposure chamber for 5 minutes; an average carbon monoxide level of 30 parts per million was maintained. The exposure chamber was subsequently removed and patients were allowed to inhale smoke-free room air. Carbon monoxide levels were measured by using a portable carbon monoxide analyzer (Model T15, Langan Products, San Francisco, California). After baseline measurements, the participants in the active smoking group each smoked one filtered cigarette containing 1.0 mg of nicotine under standardized conditions: Every 15 seconds, a puff lasting 5 seconds was taken, and the whole cigarette had to be smoked within 5 minutes. The participants in the sham smoking group performed a similar pattern of inhalation with one unlit cigarette. All variables except cardiac output were measured at baseline and at 1, 2, 3, 4, 5, 10, 15, and 20 minutes after the initiation of passive, active, or sham smoking. Cardiac output was measured by thermodilution at baseline and at 5, 10, and 20 minutes after initiation of passive, active, or sham smoking. Measurement of Aortic Diameters and Pressures Instantaneous aortic diameters were measured at the descending thoracic aorta by a Y-shaped intravascular catheter that was developed in our laboratory and uses sonometry to measure diameter (Figure 1). Aortic pressures were obtained simultaneously at the same point of the aorta by a 3-French catheter-tip micromanometer (Model SPC-330, Millar Instruments, Houston, Texas), as described elsewhere [24-26]. Figure 1. Study instruments. Data Acquisition A VF-1 mainframe (Crystal Biotech, Hopkinton, Massachusetts) was fitted with appropriate modules for measuring aortic diameter and pressure and acquiring an electrocardiogram. Signals were digitized every 5 milliseconds. The digitized data were stored and processed by using Microsoft Excel software (Redmond, Washington). Estimation of Aortic Elastic Properties and Pressure-Diameter Relation The slope of the pressure-diameter loop and aortic distensibility were used as measures of aortic elasticity [24-31]. Statistical Analysis Slope of the Pressure-Diameter Loop The aortic pressure-diameter loop is derived by plotting digitized data for the pressure (ordinate) and the diameter (abscissa) during a single cardiac cycle (Figure 2). The line of this plot during cardiac systole is not identical to the line during cardiac diastole because diameter lags behind pressure as a result of the viscoelastic nature of the aortic wall. Thus, this plot assumes the shape of a clockwise hysteretic loop, the ascending portion of which corresponds to systole and the descending portion of which corresponds to diastole. Multiple loops were obtained for all participants during the study. To characterize the loop, linear regression analysis of pressure versus diameter was done separately in each loop to determine the slope (that is, the regression coefficient b of the following regression equation: pressure = + b x diameter) of the regression line. The slope of this regression line (DeltaP/DeltaD) is an index of aortic elasticity because it gives an inverse measure of the changes in aortic diameter that occur during the cardiac cycle as a response to the changes in distending pressure. With a given change in aortic pressure, a vessel with deteriorated elastic properties responds with a relatively small change in aortic diameter (thus, the slope of the pressure-diameter regression line will be high). In contrast, with a given change in aortic pressure, a vessel with improved elastic properties responds with a relatively large change in aortic diameter (thus, the slope of the pressure-diameter regression line will be low). Figure 2. Representative examples of pressure-diameter loops of three participants (one each from the passive, active, and sham smoking groups). top middle bottom The pressure-diameter loop operates along a hypothetical line of elasticity. Shifting of the pressure-diameter loop to a different hypothetical line of elasticity provides valuable information on the mechanisms involved in the changes in aortic elastic properties (Figure 3). Figure 3. Left. Right. Aortic Distensibility Aortic distensibility was calculated from the following formula: Distensibility = 2Deltad/(d x DeltaP) 106 cm2 dyne1, where d is diastolic aortic diameter, Deltad is the difference between the systolic and diastolic aortic diameters (pulsatile change in aortic diameter), and DeltaP is the difference between the systolic and diastolic aortic pressures (pulse pressure). Large distensibility values represent improved aortic elastic properties, and small values represent deteriorated properties. Data Analysis To obtain individual patient values of aortic pressure and diameter and derived variables at every time point, as well as values of the slope of the pressure-diameter loop regression line, analyses were done on 10 consecutive heartbeats and results were averaged. No values were missing for any variable at any time point. Data are expressed as the mean SD. Repeated-measures analysis of variance (averaged F) was used to detect statistically significant changes in variables within the groups (passive, active, and sham smoking) during the study period, to compare these variables between the passive and sham smoking groups and between the active and sham smoking groups, and to determine whether the time course of these variables differed between the passive and sham smoking groups and between the active and sham smoking groups. To test the univariate homogeneity of variance between the passive and sham smoking groups and between the active and sham smoking groups, the Cochran and Bartlett-Box tests were used. The Box M test was used to assess the equality of the variance-covariance matrices. Greenhouse-Geisser correction was used in the repeated-measures analysis of variance when the Box M test was significant [32]. Normality assumptions, tested by using the Kolmogorov-Smirnoff one-sample test and by calculating the ratio of skewness to the SE of skewness of the sample distribution, were satisfied. P values less than 0.05 were considered statistically significant. Data analysis was done with SPS software, version 7.0 (Chicago, Illinois). Results Baseline Characteristics Three participants in the passive smoking group, three in the active smoking group, and four in the sham smoking group had angiographically normal coronary arteries; the remaining participants had coronary artery disease. Age, baseline hemodynamic measures, and baseline aortic elasticity measures in the three groups are shown in Table 1. Table 1. Baseline Characteristics of the Study Groups* Changes after Passive Smoking Heart Rate, Cardiac Function, and Aortic Pressures Passive smoking was associated with prompt increments in the mean heart rate; cardiac index; and systolic, diastolic, and pulse pressures. Most of these increments occurred during the first 5 minutes. The mean heart rate and cardiac index increased over time in the passive smoking group (peaks at 5 minutes, 76 beats/min [P < 0.001] and 3.6 L/min m2 [P = 0.001]; Table 2) and remained th