Effect of Cigarette Smoking and Breathing Carbon Monoxide on Cardiovascular Hemodynamics in Anginal Patients

Transcription

1 Effect of Cigarette Smoking and Breathing Carbon Monoxide on Cardiovascular Hemodynamics in Anginal Patients By WILBERT S. ARONOW, M.D., JOHN CASSIDY, M.D., JACK S. VANGROW, M.D., HAROLD MARCH, M.D., JOHN C. KERN, M.D., JOHN R. GOLDSMITH, M.D., MAHAVEER KHEMKA, M.D., JAMES PAGANO, M.D., AND MICHAEL VAWTER, M.D. SUMMARY Smoking high-nicotine cigarettes caused a significant increase in systolic and diastolic arterial pressure, heart rate, left ventricular end-diastolic pressure, and coronary sinus, arterial, and venous CO levels, no significant change in left ventricular dp/dt, aortic systolic ejection period, and cardiac index, and a significant decrease in stroke index and coronary sinus, arterial, and venous P02 levels in eight anginal patients with documented coronary disease. One week later, these patients inhaled 150 ppm of carbon monoxide until their increase in coronary sinus CO was similar to that produced after smoking their third cigarette. Inhaling carbon monoxide caused a significant increase in left ventricular end-diastolic pressure and coronary sinus, arterial, and venous CO levels, no significant change in systolic and diastolic arterial pressure, heart rate, and systolic ejection period, and a significant decrease in left ventricular dp/dt, stroke index, cardiac index, and coronary sinus, arterial, and venous PO2 levels. Nicotine caused the increased systolic and diastolic arterial pressure and heart rate after smoking. Carbon monoxide caused the negative inotropic effect which increased the left ventricular end-diastolic pressure and decreased the stroke index after smoking. Additional Indexing Words: Nicotine Heart rate Left ventricular contractility Coronary heart disease Cardiac index MOKING CIGARETTES causes anginal patients to have a significant decrease in exercise performance before the onset of angina pectoris.1-3 Smoking high-nicotine cigarettes",4'5 or low-nicotine cigarettes2'4 causes a significant increase in heart rate and in blood pressure but no significant change in systolic ejection period in anginal patients with documented coronary heart disease. This increase in blood pressure and in heart rate does not occur after smoking non-nicotine cigarettes.3 4,6 However, smoking high-nicotine, low-nicotine, or non-nicotine cigarettes increases the carboxyhemoglobin level3 4' 7 which decreases the amount of oxygen available to the myocardium. Therefore, anginal patients develop angina sooner after exercise follow- From the Cardiology Section, Medical Service, Long Beach Veterans Administration Hospital, the University of California College of Medicine, Irvine, and the California State Department of Public Health, Berkeley, California. Address for reprints: Wilbert S. Aronow, M.D., Chief, Cardiology Section, Veterans Administration Hospital, Long Beach, California Received February 11, 1974; revision accepted for publication March 21, Coronary sinus Arterial pressure Stroke index ing cigarette smoking for at least two reasons: (1) increased myocardial oxygen demand caused by nicotine and (2) reduced oxygen delivery to the myocardium, whether or not nicotine is present. We5 demonstrated in a hemodynamic study that smoking high-nicotine cigarettes significantly increased the systolic and diastolic arterial pressure, heart rate, and left ventricular end-diastolic pressure, did not significantly affect the left ventricular dp/dt, systolic ejection period, and cardiac index, and significantly decreased the stroke index and coronary sinus, arterial, and venous PO2 levels in 10 patients with angina pectoris due to documented coronary heart disease. These data caused us to wonder whether a negative inotropic effect on the myocardium caused by an increase in carboxyhemoglobin level or by nicotine was responsible for the significant decrease in stroke index in our anginal patients after smoking. Therefore, in eight anginal patients with coronary artery disease, we evaluated the effect of cardiovascular hemodynamics of smoking high-nicotine cigarettes and of breathing sufficient carbon monoxide to raise the coronary sinus carboxyhemoglobin level similar to that occurring after smoking. 3 4ir0(culation. Volue.50. Alglst 1.974

2 SMOKING AND CARBON MONOXIDE IN ANGINA Materials and Methods Eight men, mean age 51 6 years, with severe angina pectoris who needed cardiac catheterization and coronary angiography were subjects. All eight patients smoked between 20 and 30 cigarettes daily. Informed consent was obtained from the eight men who participated in this study after the nature of the procedures was fully explained. All eight subjects abstained from smoking for 12 hr prior to their right and left heart cardiac catheterizations, each of which was performed twice, one week apart. The cardiac catheterizations were performed at 8 a.m., with the patients in the fasting state. The patients did not take any medications within 24 hr of their cardiac catheterization. None of the patients received any beta-adrenergic blocking drugs within two weeks of this study. The right and left heart cardiac catheterizations were performed with pressures measured with Statham model P23 Db catheter tip pressure transducers and recorded with an Electronics for Medicine recorder. The maximal rate of left ventricular pressure rise (left ventricular dp/dt) was calculated by electronic means with an Electronics for Medicine RC Differentiator model RC-1. After the pressure measurements were obtained, blood was drawn simultaneously from catheters in the coronary sinus, aorta, and main pulmonary artery and analyzed for P02 with a Beckman 160 physiological gas analyzer and for carboxyhemoglobin with an Instrumentation Laboratory 182 CO-oximeter. Then the cardiac output was determined by the indocyanine green dye dilution method. Duplicate determinations were made. After the above control measurements were made during the first cardiac catheterization, the subject then smoked 4/5 of his first standard brand, nonfilter cigarette (containing 1.8 mg of nicotine) at his normal pace, inhaling the smoke. The cigarettes were marked at the % point. Immediately after this cigarette was smoked, mesurements (except for cardiac output) were obtained in the same order stated above. Five minutes after the subject finished smoking his first cigarette, he smoked 4/5 of his second cigarette. Measurements were then made as after cigarette 1. These measurements were repeated 30 min after smoking cigarette 2 (immediately prior to smoking cigarette 3). Immediately after smoking % of cigarette 3, these measurements and duplicate determinations of the cardiac output were made. ible 1 Aortic Systolic and Diastolic Measurements After in Eight Anginal Patients (mm Hg) After the above control measurements were made during the second cardiac catheterization, the patient then breathed 150 ppm of carbon monoxide from a tank through a mask. We used a Bird Mark 7 Respirator with pressure settings and flow rates reduced and a built-in expiratory leak so that significant positive pressure was not applied. The patients breathed carbon monoxide until their increase in coronary sinus CO was similar to that experienced after smoking their third cigarette. Left ventriculography and coronary angiography were not performed until after completion of the above measurements. Coronary angiography revealed greater than 75% narrowing of one or more major coronary vessels in all eight anginal patients. The t-test for correlated means was used to analyze the data after breathing carbon monoxide and the cardiac index and stroke index data after smoking. An analysis of variance test was done to analyze the data (excluding cardiac index and stroke index) obtained after smoking. In order to test the difference between the means, a least significant difference (LSD) was computed by multiplying the t-table value for the 0.05, 0.01, and levels by the square root of 2 times the mean square error divided by the degrees of freedom for the study periods. A LSD for the 0.05, 0.01, and levels was compared with each difference between the study periods means. If the difference between the study periods means exceeded the LSD at the 0.05, 0.01, or levels, then the difference was significant at that level. Results None of the patients developed angina pectoris during the study periods. The aortic systolic ejection period did not significantly change after smoking or after breathing 150 ppm of carbon monoxide. Table 1 indicates the aortic systolic and diastolic pressure for each anginal patient before and after smoking and before and after breathing 150 ppm of carbon monoxide. The mean aortic systolic pressure was significantly increased after smoking compared to the control period (LSD = 2.9; P < 0.001). The mean aortic diastolic pressure was significantly increased after smoking compared to the control period Smoking atnd After Breathing Carbon Monoxide no. Control cig. 1 cig. 2 eig. 2 cig. 3 Control monoxide 1 140/ /92 152/94 146/90 152/94 134/84 132/ /74 134/82 136/82 126/76 136/82 126/78 132/ /68 126/72 128/74 122/70 130/74 122/70 118/ /70 126/78 126/78 120/72 128/80 116/68 114/67 110/66 120/72 122/74 116/68 122/74 114/70 110/ /78 134/82 136/84 130/80 136/84 124/76 128/ /82 142/88 142/88 138/85 144/90 126/80 126/ /76 132/84 134/84 124/78 132/84 124/80 122/80 Mean SD X , o o6.9 -I I (Circulaztimi, Yo<tlmme}.;(..X1tigitst 1974

3 342 ARONOW ET AL. Table 2 Heart Rate Measurements After Smoking and After Breathing Carbon Monoxide in Patients (beats/min) Eight Anginal 30 min After Mean SD a (LSD = 2.5; P < 0.001). Thirty minutes after smoking cigarette 2, the aortic systolic and diastolic pressure were significantly decreased compared to after cigarette 2 (P < 0.001) but were still significantly increased compared to the control period (P < 0.01 for aortic diastolic pressure; P < for aortic systolic pressure). The mean aortic systolic and diastolic pressure did not significantly change after breathing 150 ppm of carbon monoxide. Table 2 shows the heart rate for each anginal patient before and after smoking and before and after breathing 150 ppm of carbon monoxide. The mean heart rate was significantly increased after smoking compared to the control period (LSD = 3.6; P < 0.001). Thirty minutes after smoking cigarette 2, the mean heart rate was significantly decreased compared to after cigarette 2 (P < 0.001) but was still significantly increased compared to the control period (P < 0.001). The mean heart rate did not significantly change after breathing 150 ppm of carbon monoxide. Table 3 reveals the left ventricular dp/dt for each Table 3 mean left ventricular dp/dt was not significantly changed after smoking compared to the control period but was significantly decreased after breathing 150 ppm of carbon monoxide (t = 18.16; P < 0.001). Table 4 indicates the left ventricular end-diastolic pressure for each anginal patient before and after smoking and before and after breathing 150 ppm of carbon monoxide. The mean left ventricular enddiastolic pressure was significantly increased after smoking cigarette 1 compared to the control period (LSD = 0.8; P < 0.01) and after smoking cigarettes 2 and 3 (LSD = 1.2; P < 0.001) but was not significantly changed 30 minutes after smoking the second cigarette. The mean left ventricular enddiastolic pressure was significantly increased after breathing 150 ppm of carbon monoxide (t = 3.74; P < 0.01). Table 5 shows the cardiac index for each anginal patient before and after smoking and before and after breathing 150 ppm of carbon monoxide. The mean cardiac index was not significantly changed after Left Ventricular dp/dt Measurements After Smoking and After Breathing Carbon Monoxide in Eight Anginal Patients (mm Hg/sec) 30 min After , Mean SD -246 = =219 =205 Circulation, Voltme.50, Autgust 1974

4 SMOKING AND CARBON MONOXIDE IN ANGINA 343 Table 4 Left Ventricular End-Diastolic Pressure Measurements After Smoking and After Breathing Carbon Monoxide in Eight Anginal Patients (mm Hg) 30 min After Mean i 1 SD 11.9 =1.8 i1.5 ' 1.9 i smoking compared to the control period but was significantly decreased after breathing 150 ppm of carbon monoxide (t = 14.44; P < 0.001). Table 6 illustrates the stroke index for each anginal patient before and after smoking and before and after breathing 150 ppm of carbon monoxide. The mean stroke index was significantly decreased after smoking (t = 18.16; P < 0.001) and was significantly decreased after breathing 150 ppm of carbon monoxide (t = 16.80; P < 0.001). Table 7 reveals the coronary sinus CO level for each coronary sinus CO level was significantly increased after smoking compared to the control period (LSD = 0.23; P < 0.001). Thirty minutes after smoking cigarette 2, the coronary sinus CO level was significantly decreased compared to after smoking cigarette 2 (P < 0.001) but was still significantly increased compared to the control period (P < 0.001). A significant increase in mean coronary sinus CO level Table 5 Cardiac Index Measurements After Smoking and After Breathing Carbon Monoxide in Eight Anginal Patients (L/min/m2) After Pt. After carbon no. Control cig. 3 Control monoxide Mean SD Circolation. V'oltme.50. Auigtust 1974 occurred after breathing 150 ppm of carbon monoxide (t = 37.17; P < 0.001). Table 8 reveals the arterial CO level for each arterial CO level was significantly increased after smoking compared to the control period (LSD = 0.17; P < 0.001). Thirty minutes after smoking cigarette 2, the arterial CO level was significantly decreased compared to after smoking cigarette 2 (P < 0.001) but was still significantly increased compared to the control period (P < 0.001). A significant increase in mean arterial CO level occurred after breathing 150 ppm of carbon monoxide (t = 57.67; P < 0.001). Table 9 reveals the venous CO level for each venous CO level was significantly increased after smoking compared to the control period (LSD = 0.17; P < 0.001). Thirty minutes after smoking cigarette 2, the venous CO level was significantly decreased com- Table 6 Stroke Index Measurements After Smoking and After Breathing Carbon Monoxide in Eight Anginal Patients (ml/ beat/rm2) After Pt. After carbon no. Control cig. 3 Control monoxide Mean SD =1=

5 344 ARONOW ET AL. Table 7 Coronary Sinus CO After Smoking and After Breathing Carbon Monoxide in Eight Anginal Patients (%) 30 min After Mean SD -.39 i., pared to after smoking cigarette 2 (P < 0.001) but was still significantly increased compared to the control period (P < 0.001). A significant increase in mean venous CO level occurred after breathing 150 ppm of carbon monoxide (t = 47.62; P < 0.001). Table 10 reveals the coronary sinus PG2 level for each anginal patient before and after smoking and before and after breathing 150 ppm of carbon monoxide. The mean coronary sinus P02 level was significantly decreased after smoking compared to the control period (LSD = 0.81; P < 0.001). Thirty minutes after smoking cigarette 2, the mean coronary Table 8 Arterial CO Measurements After Smnoking and After Breathing Carbon Monoxide in Eight Anginal Patients (%) no. Control cig. 1 cig. 2 eig. 2 cig. 3 Control monoxide i Mean i 1 SD -A = Table 9 Venous CO Measurements After Smoking and After Breathing Carbon Monoxide in Eight Anginal Patients (%) no. Control cig. 1 cig. 2 eig. 2 cig. 3 Control monoxide Mean ) SD =.37 Circulation, Volume 50, August 1974

6 SMOKING AND CARBON MONOXIDE IN ANGINA 345 Table 10 Coronary Sinus P02 Measurements After Smoking and After Breathing Carbon Monoxide in Eight Anginal Paflients (mm Hg) Mean A 1 SD sinus PO2 level was significantly increased compared to after smoking cigarette 2 (P < 0.001) but was still significantly decreased compared to the control period (P < 0.001). A significant decrease in mean coronary sinus P02 level occurred after breathing 150 ppm of carbon monoxide (t = 25.00; P < 0.001). Table 11 shows the arterial P02 level for each mean arterial P02 level was significantly decreased after smoking cigarettes 2 and 3 compared to the control period (LSD = 1.40; P < 0.001). Thirty minutes after smoking cigarette 2, the mean arterial P02 level was significantly increased compared to after smoking cigarette 2 (P < 0.05) but was still significantly decreased compared to the control period (P < 0.001). A significant decrease in mean arterial P02 level occurred after breathing 150 ppm of carbon monoxide (t = 19.86; P < 0.001). Table 12 indicates the venous PO2 level for each mean venous P02 level was significantly decreased after smoking compared to the control period (LSD = 0.86; P < 0.001). Thirty minutes after smoking cigarette 2, the mean venous P02 level was significantly increased compared to after smoking cigarette 2 (P < 0.001) but was still significantly decreased compared to the control period (P < 0.001). A significant decrease in mean venous P02 level occurred after breathing 150 ppm of carbon monoxide (t = 25.97; P < 0.001). Discussion The increase in carboxyhemoglobin levels after smoking34' 7 reduces myocardial oxygen delivery. We found in this study that smoking caused a significant increase in coronary sinus, arterial and venous CO levels and a significant decrease in coronary sinus, arterial, and venous P02 levels with partial recovery within 30 minutes after smoking. Ayres and co-workers8 showed that an acute rise of the venous carboxyhemoglobin level from 0.66% to 8.69% in four patients with coronary heart disease Table 11 Arterial P02 Measurements After Smoking and After Breathing Carbon Monoxide in Eight Anginal Patients (mm Hg) no. Control eig. 1 cig. 2 cig. 2 eig. 3 Control monoxide Mean i 1 SD -2.0 =1= Circuilation, Volutme 50, Atugutst 1974

7 346 ARONOW ET AL. Table 12 Venous P02 Measurements After Smoking aid After Breathing Carbon Monoxide in Eight Anginal Pr.tientt (mm Hg) no. Control rig. 1 cig. 2 rig. 2 eig. 3 Control monoxide o Mean = 1 SD =i= caused a 20% average decrease in mixed venous oxygen tension. This greater reduction in mixed venous oxygen tension relative to the rise in venous carboxyhemoglobin level was due to a leftward shift of the oxyhemoglobin dissociation curve, with tighter binding of oxygen to hemoglobin in the presence of carboxyhemoglobin. Myocardial oxygen extraction and extraction ratios also significantly decreased and the myocardial lactate extraction ratio significantly changed to production in their coronary heart disease patients. Regan and associates" demonstrated a significant increase in mean arterial pressure and in heart rate but no significant change in cardiac index after eight patients with a healed myocardial infarction smoked two standard nonfilter brand cigarettes in about 25 minutes. Pentecost and Shillingford'0 observed a significant increase in heart rate and in arterial pressure, no significant change in cardiac output, and an average reduction of 8% in stroke volume after 14 patients with a previous myocardial infarction smoked one standard brand cigarette. Frankl and co-workers'1 showed a significant rise in heart rate but no significant change in stroke volume or cardiac output after eight patients with a healed myocardial infarction smoked two standard filter tip cigarettes within 10 minutes. Summers and associates12 demonstrated a significant increase in heart rate and in aortic systolic and diastolic pressure but no significant change in systolic ejection period after 15 anginal patients with angiographically documented coronary artery disease smoked two regular commercial cigarettes for a total of eight to 10 minutes. Nicotine absorbed during smoking increases catecholamine discharge from the adrenal medulla and from chromaffin tissue in the heart, causing an increase in blood pressure and in heart rate.`1 Nicotine also acts on chemoreceptors in the carotid and aortic bodies reflexly causing an increased blood pressure and heart rate.'4 In addition, low concentrations of nicotine can stimulate sympathetic ganglion cells. In this study, we observed a significant increase in arterial systolic and diastolic pressure and in heart rate after smoking but not after breathing 150 ppm of carbon monoxide. These hemodynamic changes partially recovered within 30 minutes after smoking. Therefore, the rise in blood pressure and in heart rate after smoking cigarettes can be attributed to absorbed nicotine. We also demonstrated no significant change in left ventricular dp/dt after smoking but a significant decrease in left ventricular dp/dt after inhaling 150 ppm of carbon monoxide. The increase in heart rate, blood pressure, and positive inotropic effect induced by nicotine should have increased the left ventricular dp/dt after smoking. However, these factors were offset by a negative inotropic effect caused by carbon monoxide, resulting in no significant change in left ventricular dp/dt after smoking. The stroke index significantly decreased in our anginal patients both after smoking cigarettes and after breathing 150 ppm of carbon monoxide. The negative inotropic effect on the myocardium caused by an increase in carboxyhemoglobin level after smoking and after breathing 150 ppm of carbon monoxide was responsible for the significant decrease in stroke index in our anginal patients. The nicotine absorbed while smoking did not significantly affect the stroke index because its positive inotropic effect was offset by an increase in heart rate and afterload. The negative inotropic effect caused by inhaling carbon monoxide also significantly raised the left ventricular enddiastolic pressure after smoking. Finally, the cardiac index in our anginal patients did not significantly change after smoking cigarettes but significantly decreased after breathing 150 ppm of carbon monoxide. The rise in heart rate due to nicotine compensated for the decrease in stroke Circulation, Volume.50 Auigust 1974

8 SMOKING AND CARBON MONOXIDE IN ANGINA volume produced by the carbon monoxide inhaled during smoking, resulting in no significant change in cardiac index after smoking. However, the cardiac index was significantly decreased after breathing 150 ppm of carbon monoxide because the inhaled carbon monoxide significantly decreased the stroke index and did not significantly affect the heart rate. Acknowledgment The authors wish to express their appreciation to Michael W. Isbell, C.P.T., for his technical assistance and to Reed Boswell, Ph.D., for biostatistical analysis of the data. References 1. ARONOW WS, KAPLAN MA, JACOB D: Tobacco: A precipitating factor in angina pectoris. Ann Intern Med 69: 529, ARONOW WS, SWANSON AJ: The effect of low-nicotine cigarettes on angina pectoris. Ann Intern Med 71: 599, ARONOW WS, ROKAW SN: Carboxyhemoglobin caused by smoking nonnicotine cigarettes: Effects in angina pectoris. Circulation 44: 782, ARONOW WS, DENDINGERJ, ROKAW SN: Heart rate and carbon monoxide level after smoking high-, low, and non-nicotine cigarettes. A study in male patients with angina pectoris. Ann Intern Med 74: 697, ARONOW WS, GOLDSMITHJR, KERNJC, CASSIDYJ, NELSON WH, 347 JOHNSON LL, ADAMS W: Effect of smoking cigarettes on cardiovascular hemodynamics. Arch Environ Health, In press 6. ARONOW WS, SWANSON AJ: Non-nicotinized cigarettes and angina pectoris. Ann Intern Med 70: 1227, COHEN SI, PERKINS NM, URY HK, GOLDSMITH JR: Carbon monoxide uptake in cigarette smoking. Arch Environ Health 22: 55, AYRES SM, MUELLER HS, GREGORYJJ, GIANELLIS J, PPENNYJL: Systemic and myocardial hemodynamic responses to relatively small concentrations of carboxyhemoglobin (COHB). Arch Environ Health 18: 699, REGAN TJ, FRANK MJ, McGINTY JF, ZOBL E, HELLEMS HK, BING RJ: Myocardial response to cigarette smoking in normal subjects and patients with coronary disease. Circulation 23: 365, PENTECOST B, SHILLINGFORD J: The acute effects of smoking on myocardial performance in patients with coronary arterial disease. Br Heart J 26: 422, FRANKL WS, WINTERS WL, SOLOFF LA: The effects of smoking on the cardiac output at rest and during exercise in patients with healed myocardial infarction. Circulation 31: 42, SUMMERS DN, RICHMOND S, WECHSLERBM: Cigarette smoke: Effects on lactate extraction in the presence of severe coronary atherosclerosis. Am Heart J 82: 458, BURNS HJ: Action of nicotine on the heart. Ann NY Acad Sci 90: 70, COMROE JH JR: The pharmacological actions of nicotine. Ann NY Acad Sci 90: 48, 1960 Circulation. Volume 50, A.Xgutst 1974