Arterial blood nicotine concentration coronary vasoconstrictive effect of low-nicotine cigarette smoking
and
Low-nicotine cigarettes have been advertised to the public as less harmful to the cardiovascular system. We studied the effects of smoking two low-nicotine cigarettes on arterial and venous blood nicotine levels, hemodynamics, and coronary vascular tone in 12 patients referred for diagnostic coronary arteriography. All were chronic smokers as evidenced by their elevated baseline arterial and venous cotinine blood levels (139 f 30 nglml and 155 + 34 rig/ml, respectively). High-resolution coronary angiograms were evaluated “blindly” before and after smoking. An electronic caliper was used to measure the diameter of disease-free coronary segments of the left anterior descending and circumflex arteries. Arterial nicotine levels rose from 5 + 1 rig/ml at baseline to 37 ? 7 nglml (p < 0.01) after the first cigarette was smoked and to 45 f 8 nglml (p < 0.01) after the second cigarette. Venous nicotine levels rose from 8 + 2 ng at baseline to 15 2 3 ngfml (p < 0.05) after the first cigarette and to 20 & 3 ngfml (p < 0.01) after the second cigarette. After the first cigarette heart rate increased 8 ? 2 beatslmin (p < 0.003) and double product 1229 f 400 beatslmin X mm Hg (p < 0.02). Compared to baseline values, after the second cigarette heart rate increased 9 f 1 beatslmin (p < 0.001) and double product 1767 + 486 beats/min X mm Hg (p < 0.01). Systolic, diastolic, and mean blood pressure did not change significantly after either the first or second cigarette. The left anterior descending artery diameter changed from 2.31 + 0.2 mm before smoking to 2.03 + 0.2 mm after the first cigarette was smoked (p < 0.01) and 2.10 ? 0.2 mm after the second cigarette (p < 0.01). The circumflex artery diameter changed from 2.49 + 0.2 mm before smoking to 2.19 f 0.1 mm after the first cigarette (p < 0.01) and to 2.21 f 0.2 mm after the second cigarette (p < 0.01). Correlation of changes in coronary diameter (constriction) with increments in arterial nicotine levels showed a borderline correlation with the first cigarette (r = 0.46, p = 0.049) and a significant correlation with the second cigarette (r = 0.61, p = 0.003). No correlation was found with venous nicotine levels. We conclude that smoking low-nicotine cigarettes evokes significant increases in arterial blood nicotine concentrations, which substantially exceed venous levels, increases heart rate and double product, and induces significant coronary vasoconstriction. Therefore smoking low-nicotine cigarettes produces adverse effects on the cardiovascular system. (AM HEART J 1992;124:392.)
Abel E. Moreyra, MD, Clifton R. Lacy, MD, Alan C. Wilson, PhD, Ashok Kumar, MD, and John B. Kostis, MD New Brunswick, N.J.
Low-nicotine cigarettes have been advertised to the public as being “less hazardous smoking.” Smokers unable to quit the habit frequently self-prescribe these cigarettes under the impression that the risks of smoking-related diseasesare minimized. The concept of low-yield cigarettes derives from figures for nicotine and tar determined by a smoking machine
From ment
the Division of Medicine,
Received
of Cardiovascular UMDNJ-Robert
for publication
Reprint requests: Abel Medical School, Division R. W. Johnson PI.-CN 4/1/38100
392
Oct.
Diseases and Wood Johnson
15. 1991;
accepted
Hypertension, DepartMedical School. Jan.
24, 1992.
E. Moreyra, MD, UMDNJ-Robert Wood Johnson of Cardiovascular Diseases and Hypertension, One 19, New Brunswick, NJ 08903.0019.
used by the United States Federal Trade Commissi0n.l In this machine a syringe draws one 35 ml puff each minute until a set length of cigarette is burned. This is quite dissimilar from the actual human smoking habit. In fact, results of several studies have shown that these machines do not predict nicotine levels of smokers.2-5 Smokers consciously or unconsciously adjust their smoking techniques (i.e., blocking ventilation holes with lips or increasing frequency of puffs) to obtain the desired nicotine leve1.6-gThe degree of compensation is not only for nicotine but also for carbon monoxide and hydrogen cyanide.‘O All previous studies on low-nicotine cigarette smoking have focused on venous blood levels, and no information is available on arterial blood levels. The
Volume
124
Number
2
Nicotine
blood levels and coronary vasotone
393
Table I. Arterial and venous blood levels of nicotine and cotinine Nicotine and cotinine
levels
Baseline
(nglml) Nicotine Arterial Venous Cotinine Arterial Venous
11) blood blood
First cigarette
Second cigarette
End of procedure
(n =
521 Sk2
37 + TV 15 + 3$
45 * s*t 20 + 3*
19 rt 3 16 i: 3
139 t 30 155 f 34
138 t 31 137 k 36
155 +- 36 141 t 37
153 * 37 148 k 38
(n = 12)
blood blood
*p < 0.01 from baseline. ‘rp < 0.01 compared to venous $p < 0.05 from baseline.
level.
purpose of this investigation was to study the differences in arterial and venous plasma nicotine concentrations, systemic hemodynamic changes, and vasomotor responses of epicardial coronary arteries after low-nicot,ine cigarettes are smoked. METHODS Patient selection. Twelve patients (nine men and three women) undergoing diagnostic coronary arteriography for evaluation of chest pain were studied after informed consentwasobtained. All patients were chronic smokersof one to three packs per day. Five patients had normal coronary arteries (no angiographic evidence of atherosclerotic lesions)and sevenhad coronary artery disease.Patients with acute myocardial infarction, unstable angina, or symptoms suggestingvariant angina were excluded. Cardiac catheterization. Left-heart catheterization and coronary arteriography were performed by the Judkins technique. All coronary vasodilators were discontinued 24 hours before catheterization. Patients were in a postabsorptive state with mild sedation (diazepam, 10 mg intramuscularly) when catheterized. Patients were instructed to refrain from smoking for at least 12 hours. Multiple views of the left coronary artery were obtained with an appropriate left Judkins catheter. The right anterior oblique view was chosento optimize visualization of both the left anterior descending and circumflex systems. Diatrizoate (Renografin-76), 6 to 8 ml/angiogram injected manually, was used as contrast medium. The filming rate was 30 frames/set with 12.5cm imageintensification and a 1.2mm focal spot. Arterial blood sampleswere obtained from the angiographic catheter in the left main coronary artery. Venous blood sampleswere obtained from a catheter in the femoral vein. Nicotine and cotinine levels were measuredby high-performance liquid chromatography.” Nicotine blood levels were not obtained from one patient becauseof peak interference in the assay.After control angiography was performed, hemodynamic measurements(systolic, diastolic, and mean aortic pressuresand heart rate) and simultaneous arterial and venous blood sampleswere obtained. Patients were asked to smoke two low-nicotine (0.8 mg) cigarettes consecutively. Each cigarette was smokedin an
averagetime of 6 minutes (range 4 to 8 minutes). An arteriogram, hemodynamic measurements,and simultaneous arterial and venousblood sampleswere obtained immediately after each cigarette was extinguished. To assess delayed nicotine levels, arterial and venousblood samples were also obtained at the end of the procedure (mean 17 minutes, range 11 to 23 minutes after the secondcigarette wasfinished). The patient’s position wasmaintained constant throughout the study. In addition, the relationship between the focal spot, the patient, and the height of the image tube was kept constant. Cineangiographic frames obtained at end diastole were analyzed at baselineand after each cigarette. To ensurethat the samesegmentswere examined, coronary branch points were used as reference points. Midcoronary segmentsfree of diseasewere selected for the measurements.Measurement of the left anterior descendingartery in onepatient and the circumflex artery in another could not be accomplishedbecauseof proximal total occlusion. To control for the effect of contrast material and successivecoronary angiogramson coronary artery diameter, 12 additional patients followed the sameexperimental protocol without smoking. No statistically significant changesin coronary artery diameter were observed. The average diameter of the measured left anterior descending artery segment was 1.96 ? 0.15 mm (mean + SEM) on the baseline angiogram, 1.95 -+ 0.16 mm on the secondangiogram,and 1.94 & 0.15 mm on the third angiogram.The correspondingmeasurementsfor the circumflex artery segment were 2.30 2 0.15 mm, 2.23 i 0.12 mm, and 2.24 + 0.14 mm, respectively. Thus repeated contrast injections did not causedetectable vasoconstriction of the coronary arteries. Measurements of coronary artery diameter. The selected angiographicframeswere enlargedto 203 X 254 mm hard copies and coded for analysis in a blinded fashion. Measurementsof coronary artery diameter were made by a singleobserver with an electronic caliper (DEC, Prodical 1101,Accurex [A2D Ultrasound Inc., Killingworth, Conn.]). The precisionand accuracy of this measuringtechnique for diameter assessment hasbeen well described.12The intraand interobserver variability of the techniques in measuring the diameter of normal coronary segmentswastested in seven patients by four observers who were unaware of
394
Blood nglml
Moreyra
et al.
American
. L
nicotine
60 0
arterial
n venous
betweenlevelsof the independent variable. Student’s f test was used to determine the significance of diflerences between arterial and venous blood nicotine levels. Paired t test wasusedto determine the significanceof differences in hemodynamic parameter changesinduced by cigarette smoking.
L i!3 cig
1
cig
2
RESULTS Nicotine-cotinine
end
Fig. 1. Arterial and venous blood levels of nicotine. Dif ferences in arterial and venous blood nicotine levels were highly significant after first (cig I) and second (cig 2) cigarettes (*p < 0.01). By the end of the procedure (end), arterial and venous blood nicotine levels had equilibrated.
Vessel
Diameter mm rAo.01
I
CONTROL
GIG
1
CIG 2
LAD
CONTROL
CIG 1
CIG 2
cx
Fig. 2. Epicardial coronary artery response to smoking low-nicotine cigarettes. Decreases in vessel lumen diameter for disease-free midsegments of left anterior descending artery (LAD, open bars) and circumflex artery (CX. solid bars). p Values determined by analysis of variance.
other patient data. The intraobserver variability was tested by repeated 10 diameter measurements of a normal coronary segment. The coefficient of variation for intra- and interobserver variability ranged from 1.4”; to 4.3L‘, . In addition, to assure an unbiased measurement of arterial diameter, the observer had no knowledge of whether the hard copy corresponded to baseline, first cigarette, or second cigarette. Actual coronary artery diameter (in millimeters) was calculated by reference to the catheter tip. Percentage decreases in diameter from baseline were calculated for each subject and averaged to provide the mean
decreasein arterial diameter. Statistical analysis. were calculated. Data ance (repeated-measures general linear models Personal Computers, range test was used
August 1992 Heart Journal
Mean values and standard errors were examined by analysis of varidesign) with the use of the SAS procedure (SAS Statistics Guide for SAS Institute). Duncan’s multipleto identify significant differences
blood levels. Differences in arterial and venous blood nicotine levels were highly significant after the first and second cigarettes were smoked (Table I, Fig. 1). Arterial nicotine levels rose from 5 -+ 1 rig/ml at baseline to 37 t 7 rig/ml (p < 0.01) after the first cigarette was smoked and to 45 -+ 8 rig/ml (p < 0.01) after the second cigarette. Venous nicotine levels rose from 8 +- 2 ngjml at baseline to 15 ? 3 rig/ml (p < 0.05) after the first cigarette and to 20 + 3 rig/ml (p < 0.01) after the second cigarette. By the end of the procedure, arterial and venous blood nicotine levels had equilibrated, declining to 19 -t 3 rig/ml and 16 t 3 rig/ml, respectively. These differences in arterial and venous concentrations were not statistically significant. Cotinine blood levels did not change during smoking (Table I). The baseline arterial cotinine level was 139 -t 30 rig/ml and it remained unchanged throughout the procedure (range 138 to 155 rig/ml). The baseline venous cotinine level was 155 i 34 rig/ml (not, significantly different from the baseline arterial cotinine level) and it also remained unchanged (range 137 t.0 148 rig/ml). Hemodynamics. Hemodynamic changes induced by smoking are shown in Table II. After the first cigarette was smoked, heart rate increased an average of 8 + 2 beats/min (p < 0.003) and double product 1229 i- 400 beats/min x mm Hg (p < 0.02). Compared to baseline values, after the second cigaret.te heart rate increased an average of 9 i 1 beatslmin (p < 0.001) and double product 1767 t 486 units (p < 0.01). Systolic, diastolic, and mean arterial blood pressure did not, change significantly after either the first or second cigarette. Changes in coronary artery diameter. The average diameter of the measured left anterior descending artery segments was 2.31 + 0.2 mm before smoking, 2.03 -_t0.2 mm after the first cigarette was smoked (p < O.Ol), and 2.10 + 0.2 mm after the second cigarette (p < 0.01). The average diameter of the measured circumflex segments was 2.49 i 0.2 mm before smoking,
2.19 i- 0.1
mm
after
the
first
cigarette
(p < O.Ol), and 2.21 + 0.2 mm after the second cigarette (p < 0.01) (Fig. 2). There was no significant difference in coronary diameters when measurements after the first and second cigarettes were compared.
Analysis of changes in coronary
artery
diameter
Volume124 Number
Nicotine
2
0
20
40
60
blood levels and coronary
vasotone
395
100
80
ARTERIAL NICOTINE INCREASE (ng/mL) 3. Coronary artery vasoconstriction in relation to increasesin arterial blood nicotine concentration from baselineafter secondcigarette. Open circles, Left anterior descendingartery; filled circles, circumflex artery. Fig.
II. Changesfrom baselinein heart rate and systolic, diastolic, and mean arterial blood pressureinduced by smoking
Table
First
Hemodynamics
HR (beats/min) DP (heats/minx mmHg) SBP (mmHg) DBP (mmHg) MBP (mmHg) HR. Heart rate: DP. double product:
p Value
cigurette
8-t”
and
Low-nicotine cigarettes have been advertised to the public as less harmful to the cardiovascular system. We studied the effects of smoking two low-nicotine cigarettes on arterial and venous blood nicotine levels, hemodynamics, and coronary vascular tone in 12 patients referred for diagnostic coronary arteriography. All were chronic smokers as evidenced by their elevated baseline arterial and venous cotinine blood levels (139 f 30 nglml and 155 + 34 rig/ml, respectively). High-resolution coronary angiograms were evaluated “blindly” before and after smoking. An electronic caliper was used to measure the diameter of disease-free coronary segments of the left anterior descending and circumflex arteries. Arterial nicotine levels rose from 5 + 1 rig/ml at baseline to 37 ? 7 nglml (p < 0.01) after the first cigarette was smoked and to 45 f 8 nglml (p < 0.01) after the second cigarette. Venous nicotine levels rose from 8 + 2 ng at baseline to 15 2 3 ngfml (p < 0.05) after the first cigarette and to 20 & 3 ngfml (p < 0.01) after the second cigarette. After the first cigarette heart rate increased 8 ? 2 beatslmin (p < 0.003) and double product 1229 f 400 beatslmin X mm Hg (p < 0.02). Compared to baseline values, after the second cigarette heart rate increased 9 f 1 beatslmin (p < 0.001) and double product 1767 + 486 beats/min X mm Hg (p < 0.01). Systolic, diastolic, and mean blood pressure did not change significantly after either the first or second cigarette. The left anterior descending artery diameter changed from 2.31 + 0.2 mm before smoking to 2.03 + 0.2 mm after the first cigarette was smoked (p < 0.01) and 2.10 ? 0.2 mm after the second cigarette (p < 0.01). The circumflex artery diameter changed from 2.49 + 0.2 mm before smoking to 2.19 f 0.1 mm after the first cigarette (p < 0.01) and to 2.21 f 0.2 mm after the second cigarette (p < 0.01). Correlation of changes in coronary diameter (constriction) with increments in arterial nicotine levels showed a borderline correlation with the first cigarette (r = 0.46, p = 0.049) and a significant correlation with the second cigarette (r = 0.61, p = 0.003). No correlation was found with venous nicotine levels. We conclude that smoking low-nicotine cigarettes evokes significant increases in arterial blood nicotine concentrations, which substantially exceed venous levels, increases heart rate and double product, and induces significant coronary vasoconstriction. Therefore smoking low-nicotine cigarettes produces adverse effects on the cardiovascular system. (AM HEART J 1992;124:392.)
Abel E. Moreyra, MD, Clifton R. Lacy, MD, Alan C. Wilson, PhD, Ashok Kumar, MD, and John B. Kostis, MD New Brunswick, N.J.
Low-nicotine cigarettes have been advertised to the public as being “less hazardous smoking.” Smokers unable to quit the habit frequently self-prescribe these cigarettes under the impression that the risks of smoking-related diseasesare minimized. The concept of low-yield cigarettes derives from figures for nicotine and tar determined by a smoking machine
From ment
the Division of Medicine,
Received
of Cardiovascular UMDNJ-Robert
for publication
Reprint requests: Abel Medical School, Division R. W. Johnson PI.-CN 4/1/38100
392
Oct.
Diseases and Wood Johnson
15. 1991;
accepted
Hypertension, DepartMedical School. Jan.
24, 1992.
E. Moreyra, MD, UMDNJ-Robert Wood Johnson of Cardiovascular Diseases and Hypertension, One 19, New Brunswick, NJ 08903.0019.
used by the United States Federal Trade Commissi0n.l In this machine a syringe draws one 35 ml puff each minute until a set length of cigarette is burned. This is quite dissimilar from the actual human smoking habit. In fact, results of several studies have shown that these machines do not predict nicotine levels of smokers.2-5 Smokers consciously or unconsciously adjust their smoking techniques (i.e., blocking ventilation holes with lips or increasing frequency of puffs) to obtain the desired nicotine leve1.6-gThe degree of compensation is not only for nicotine but also for carbon monoxide and hydrogen cyanide.‘O All previous studies on low-nicotine cigarette smoking have focused on venous blood levels, and no information is available on arterial blood levels. The
Volume
124
Number
2
Nicotine
blood levels and coronary vasotone
393
Table I. Arterial and venous blood levels of nicotine and cotinine Nicotine and cotinine
levels
Baseline
(nglml) Nicotine Arterial Venous Cotinine Arterial Venous
11) blood blood
First cigarette
Second cigarette
End of procedure
(n =
521 Sk2
37 + TV 15 + 3$
45 * s*t 20 + 3*
19 rt 3 16 i: 3
139 t 30 155 f 34
138 t 31 137 k 36
155 +- 36 141 t 37
153 * 37 148 k 38
(n = 12)
blood blood
*p < 0.01 from baseline. ‘rp < 0.01 compared to venous $p < 0.05 from baseline.
level.
purpose of this investigation was to study the differences in arterial and venous plasma nicotine concentrations, systemic hemodynamic changes, and vasomotor responses of epicardial coronary arteries after low-nicot,ine cigarettes are smoked. METHODS Patient selection. Twelve patients (nine men and three women) undergoing diagnostic coronary arteriography for evaluation of chest pain were studied after informed consentwasobtained. All patients were chronic smokersof one to three packs per day. Five patients had normal coronary arteries (no angiographic evidence of atherosclerotic lesions)and sevenhad coronary artery disease.Patients with acute myocardial infarction, unstable angina, or symptoms suggestingvariant angina were excluded. Cardiac catheterization. Left-heart catheterization and coronary arteriography were performed by the Judkins technique. All coronary vasodilators were discontinued 24 hours before catheterization. Patients were in a postabsorptive state with mild sedation (diazepam, 10 mg intramuscularly) when catheterized. Patients were instructed to refrain from smoking for at least 12 hours. Multiple views of the left coronary artery were obtained with an appropriate left Judkins catheter. The right anterior oblique view was chosento optimize visualization of both the left anterior descending and circumflex systems. Diatrizoate (Renografin-76), 6 to 8 ml/angiogram injected manually, was used as contrast medium. The filming rate was 30 frames/set with 12.5cm imageintensification and a 1.2mm focal spot. Arterial blood sampleswere obtained from the angiographic catheter in the left main coronary artery. Venous blood sampleswere obtained from a catheter in the femoral vein. Nicotine and cotinine levels were measuredby high-performance liquid chromatography.” Nicotine blood levels were not obtained from one patient becauseof peak interference in the assay.After control angiography was performed, hemodynamic measurements(systolic, diastolic, and mean aortic pressuresand heart rate) and simultaneous arterial and venous blood sampleswere obtained. Patients were asked to smoke two low-nicotine (0.8 mg) cigarettes consecutively. Each cigarette was smokedin an
averagetime of 6 minutes (range 4 to 8 minutes). An arteriogram, hemodynamic measurements,and simultaneous arterial and venousblood sampleswere obtained immediately after each cigarette was extinguished. To assess delayed nicotine levels, arterial and venousblood samples were also obtained at the end of the procedure (mean 17 minutes, range 11 to 23 minutes after the secondcigarette wasfinished). The patient’s position wasmaintained constant throughout the study. In addition, the relationship between the focal spot, the patient, and the height of the image tube was kept constant. Cineangiographic frames obtained at end diastole were analyzed at baselineand after each cigarette. To ensurethat the samesegmentswere examined, coronary branch points were used as reference points. Midcoronary segmentsfree of diseasewere selected for the measurements.Measurement of the left anterior descendingartery in onepatient and the circumflex artery in another could not be accomplishedbecauseof proximal total occlusion. To control for the effect of contrast material and successivecoronary angiogramson coronary artery diameter, 12 additional patients followed the sameexperimental protocol without smoking. No statistically significant changesin coronary artery diameter were observed. The average diameter of the measured left anterior descending artery segment was 1.96 ? 0.15 mm (mean + SEM) on the baseline angiogram, 1.95 -+ 0.16 mm on the secondangiogram,and 1.94 & 0.15 mm on the third angiogram.The correspondingmeasurementsfor the circumflex artery segment were 2.30 2 0.15 mm, 2.23 i 0.12 mm, and 2.24 + 0.14 mm, respectively. Thus repeated contrast injections did not causedetectable vasoconstriction of the coronary arteries. Measurements of coronary artery diameter. The selected angiographicframeswere enlargedto 203 X 254 mm hard copies and coded for analysis in a blinded fashion. Measurementsof coronary artery diameter were made by a singleobserver with an electronic caliper (DEC, Prodical 1101,Accurex [A2D Ultrasound Inc., Killingworth, Conn.]). The precisionand accuracy of this measuringtechnique for diameter assessment hasbeen well described.12The intraand interobserver variability of the techniques in measuring the diameter of normal coronary segmentswastested in seven patients by four observers who were unaware of
394
Blood nglml
Moreyra
et al.
American
. L
nicotine
60 0
arterial
n venous
betweenlevelsof the independent variable. Student’s f test was used to determine the significance of diflerences between arterial and venous blood nicotine levels. Paired t test wasusedto determine the significanceof differences in hemodynamic parameter changesinduced by cigarette smoking.
L i!3 cig
1
cig
2
RESULTS Nicotine-cotinine
end
Fig. 1. Arterial and venous blood levels of nicotine. Dif ferences in arterial and venous blood nicotine levels were highly significant after first (cig I) and second (cig 2) cigarettes (*p < 0.01). By the end of the procedure (end), arterial and venous blood nicotine levels had equilibrated.
Vessel
Diameter mm rAo.01
I
CONTROL
GIG
1
CIG 2
LAD
CONTROL
CIG 1
CIG 2
cx
Fig. 2. Epicardial coronary artery response to smoking low-nicotine cigarettes. Decreases in vessel lumen diameter for disease-free midsegments of left anterior descending artery (LAD, open bars) and circumflex artery (CX. solid bars). p Values determined by analysis of variance.
other patient data. The intraobserver variability was tested by repeated 10 diameter measurements of a normal coronary segment. The coefficient of variation for intra- and interobserver variability ranged from 1.4”; to 4.3L‘, . In addition, to assure an unbiased measurement of arterial diameter, the observer had no knowledge of whether the hard copy corresponded to baseline, first cigarette, or second cigarette. Actual coronary artery diameter (in millimeters) was calculated by reference to the catheter tip. Percentage decreases in diameter from baseline were calculated for each subject and averaged to provide the mean
decreasein arterial diameter. Statistical analysis. were calculated. Data ance (repeated-measures general linear models Personal Computers, range test was used
August 1992 Heart Journal
Mean values and standard errors were examined by analysis of varidesign) with the use of the SAS procedure (SAS Statistics Guide for SAS Institute). Duncan’s multipleto identify significant differences
blood levels. Differences in arterial and venous blood nicotine levels were highly significant after the first and second cigarettes were smoked (Table I, Fig. 1). Arterial nicotine levels rose from 5 -+ 1 rig/ml at baseline to 37 t 7 rig/ml (p < 0.01) after the first cigarette was smoked and to 45 -+ 8 rig/ml (p < 0.01) after the second cigarette. Venous nicotine levels rose from 8 +- 2 ngjml at baseline to 15 ? 3 rig/ml (p < 0.05) after the first cigarette and to 20 + 3 rig/ml (p < 0.01) after the second cigarette. By the end of the procedure, arterial and venous blood nicotine levels had equilibrated, declining to 19 -t 3 rig/ml and 16 t 3 rig/ml, respectively. These differences in arterial and venous concentrations were not statistically significant. Cotinine blood levels did not change during smoking (Table I). The baseline arterial cotinine level was 139 -t 30 rig/ml and it remained unchanged throughout the procedure (range 138 to 155 rig/ml). The baseline venous cotinine level was 155 i 34 rig/ml (not, significantly different from the baseline arterial cotinine level) and it also remained unchanged (range 137 t.0 148 rig/ml). Hemodynamics. Hemodynamic changes induced by smoking are shown in Table II. After the first cigarette was smoked, heart rate increased an average of 8 + 2 beats/min (p < 0.003) and double product 1229 i- 400 beats/min x mm Hg (p < 0.02). Compared to baseline values, after the second cigaret.te heart rate increased an average of 9 i 1 beatslmin (p < 0.001) and double product 1767 t 486 units (p < 0.01). Systolic, diastolic, and mean arterial blood pressure did not, change significantly after either the first or second cigarette. Changes in coronary artery diameter. The average diameter of the measured left anterior descending artery segments was 2.31 + 0.2 mm before smoking, 2.03 -_t0.2 mm after the first cigarette was smoked (p < O.Ol), and 2.10 + 0.2 mm after the second cigarette (p < 0.01). The average diameter of the measured circumflex segments was 2.49 i 0.2 mm before smoking,
2.19 i- 0.1
mm
after
the
first
cigarette
(p < O.Ol), and 2.21 + 0.2 mm after the second cigarette (p < 0.01) (Fig. 2). There was no significant difference in coronary diameters when measurements after the first and second cigarettes were compared.
Analysis of changes in coronary
artery
diameter
Volume124 Number
Nicotine
2
0
20
40
60
blood levels and coronary
vasotone
395
100
80
ARTERIAL NICOTINE INCREASE (ng/mL) 3. Coronary artery vasoconstriction in relation to increasesin arterial blood nicotine concentration from baselineafter secondcigarette. Open circles, Left anterior descendingartery; filled circles, circumflex artery. Fig.
II. Changesfrom baselinein heart rate and systolic, diastolic, and mean arterial blood pressureinduced by smoking
Table
First
Hemodynamics
HR (beats/min) DP (heats/minx mmHg) SBP (mmHg) DBP (mmHg) MBP (mmHg) HR. Heart rate: DP. double product:
p Value
cigurette
8-t”
