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Acute Hemodynamic Effects. of Ci'garette imoking, in Man Assessed by Non-invas3:ve Technics T. Sakurai„ B. Rabinowitz, K. Thorp, G., Huber and W.H. AbeTmann. Presented at the VTlIth World Congress of Cardiology September 21, 197$' Tokyo, .7apan

C C SLIDE 1 thousand known substances found in cigarette smoke, nicotine has beenn considered responsible for the acute cardiovascular effectsr mainly The effect of chronic smoking as a risk factor of coronary heartt disease has been well established by many epidemiologic studies. However, the acute effects of'cigarette smoking upon the cardiovascular system have not yet been fully clarified. Cigarette smoking is known to increase heart rate, blood pressure and coronary blood flow. Among more than a through its stimulatory effect upon sympathetic gangl!ia,, thus increasing, ~ circulatory catecholamines. More recently, carbon monoxide has been paid increasing attentionibecause it interferes with oxygen transport by forming,carboxyhemo.globin and causing potential myocardial ischemia. The present study was designed to measure the acute hemodynamic effect of smokj!ngone, cigarettebryr non,invasivetechnics.Two,different kinds: of cigaretteswere, empLoyed!: onei'~s the Kentucky'ReferenceCigarette, or K, which contains 2.5 milligrams nicotine per cigarette, the other is a Wicotine Free Tobacco,Cigarette or IVF,,which contains less than 0.25 milligrams nicotine. (Slide) Thirty-two h,ealthy volunteers aged' 18 to 35'were the subjects of' this stuwd'y, having giiven their informedi consent. 19 were male and 14 female, 4.were nonsmokers,and all others were either ex-smokers or currerit smokers. After overnight abstinence fromismoking, subjects, in the supine position, were asked toismoke one cigarette, lit and held by ann assistant, at intervals of 20 to 30seconds between puffs, until a totalil of ten puffs were inhaled. About half of the total Tengthlof the

2. 4 cigarette was buraed d'uriiig , this pei^a'ud'. B'ef ore andlimmediately af ter smoking, echocardiograms of the lef t ventricle weretaken,using,a Smith Kline Ekoline 20A withstrip~chart recorder with simultaneous carotid pulse tracing,,, phonocardiogram from the base, and electrocardiogrami. A 2'.25'megaRerz, half-inch focu.sedd transducer was used. Blood pressure was measured by sphygmomanometer, and venous blood samples were,drawn for carboxyhemoglobin determinations bef ore and af ter smoking. Carboxyhemoglobinilevels were measured spectro- photometrically. Two kinds of cigarettes were allocated random]ly in two sessions, heldion two separate days for each suiiject, who was not informed which cigarette was being used. SLIDE 2' The next slide shows a representative recording,and measurements of various parameters. From the recording before and after smoking,, diastolic. and systolicdimensions~„ shown asD'd and Ds, leftventri'cular' ej'ection timeor LVET, Q wave to.second aortic sound interval or Q-II, and heart rate were measured as an average of five cycles. Mean velocity of normalized', circumferentiaL,fiber shortening or Vcf„ Weissler's index or PEP/LVET, andl other parameters were calcu]Lated from these measurements. SLIDE 3 (51ide) In the following figures, the changes after smoking are dis- played as means + SEM'. Data referring to the Kentucky Reference Cigarette are shown on the left of the graph, Nicotine Free Cigarette on the right.. StatisticaL significance was tested by Student's paired't-test for each, cigarette. The significance of the difference between the two cigarettes is displayed below. Now let us look at the results. The carboxyhemoglobin level in venous blood' increased!after smoking by 1.0 percent in K'and, by 0.7 percent in N'F.

s. C SLIDE' 4 The next slide shuws the effect upom heart raite. Ileart rate increased aftcr smoking either c.LZ;arette In all sub;Ject9, but to a ilghcr extent after the Kentucky Cigarette. SLIDE 5 a,SLIDE 6 SLIDE 7 SLIDE 8' (Slidc) Blood pressure showed' similar changes. Both systolic and diastolic pressure increased in all subjects. Althougk1 to a lesser extent than the Kentucky cigarette„ the Nicotine Free Cigarette produced significant increases in b;llood pressure'or afterload. The next slid'e shows the changes in left eentri'cular dimensions. Smoking a Kentucky Reference Cigarette increased both systolic and diastolic dimensions, while the Nicotine Free Cigarette was folLowed by slight decreases in both dimens3:ons. (Slide) Stroke volume,calculated by the cube formula,, showed a significant increase after the Kentucky Cigarette, while there was no significant change after the Nicotine Free Cigarette. Among other para- meters calculated, meanVcf'increased si'gnificantlybysmokingeither cigarette. Corrected ejectionitime was slightly d'ecreased„and Weissler's index or 1''EP/LVETatended to decrease with both cigarettes, but the changes were not statistically significant. The next slide summarizes the observed changes. Smoking either a Kentucky or a Nicotine Free Cigarette is thus seen to constitute a hemody- namic stress. Increased cardiac performance in the face of increased afterload suggests that myocardial contractili'ty was augmented' by smoki'ng ihtheKentucky over the Nicotine FreeCigarette,, and theincreas~edleft ventricular dimensions or preload in the Kentucky Cigarette are reasonably explained p C:.7 by its higher conitent of nicotineande its stimulatory effect upon th~e CJ1 sympathetic nervrous system. The Nicotine Free Cigarette also caused M ~ ~ either cigarette. The larger increases in heart rate and blood pressure. ~

' SLIDE 9' 7 signif3cantincreasesiin hcartraLeond biIood pressure,, which are~ maj'or d'etermd.nants, o~fmyocar~di'all oxygen! consumpti'on.(STiide)i The tension time index„ calculated as an index of oxygen consumption, showed a 35 percent increase after the Kentucky and ail4 percent increase after the Nicotine Free,Cigarette. Since these changes occurred simultaneously with increased carboxyhemoglobin, which reducess available oxygen,, it is suspected that even smoking one cigarette may result in potential myocardial ischemia, especially in the presence of underlying, imbalance between myocardial oxygen dem4nd and supply. The mechanism responsible for the hemodynamic stress produced by smoking a, Nicotine Free Cigarette remains uncertain. Carboxyhemogliobin was increased by the Nicotine Free as well as the Kentucky Cigarette, but carboxyhemoglobin, or carbonimonoxide itself has not been demonstrated to produce detectable hemodiynamic change at the rather low concentrations measured. Continuous recording during, smoking ininine su6jects showed that the heart rate increased right after the first puff and remainedihigh during smoking, but fell rather rapid'lyy after termination of'smoking a Nicotine Free Cigarette. This might suggest that the Nicotine Free Cigarette contains short act3;ng,chronotropic and'inotropi'c substances other than nicotine. The effect of a residual amount of nicotine in this d'e-nicotinized Nicotine Free Cigarette cannot be ruled out,, as such changes were noti noted with a synthetic non-tobacco cigarette or with sham smoking maneuvers in our previous studies.

SLIDE 10 In conclusion (sLide) : C .1. Smolking either a high-nicotine or a nicotine free cigarette increases carboxyhemoglobin, heart rate and blood pressure, causing acute hemodynamic stress. All these chaniges are more prominent initl'ie high nicotine cigarette. 2'. Smoking a high nieotine cigarette also increases preToad„ while the nicotine free cigarette decreases it. 3., Increased'myocardial performance in the face ofelevated afterload' suggests that myocardial contractiilitywas augmentediby smoking either cigarette. 4. T he changes,observedshould increasemyo~cardial oxygen consumption. In view of the co-existent impairment of oxygen supply secondary to increased carboxyhemoglobi'n, smoking may well resuLt inimyrocardiaL ischemia. 5. The mechanism responsible for the effects of the "nicotine free"' .cigarette is not clear. It is suggested that the "nicotine free" cigarette may contain chronorropicand inotropic substances~other than:nlcotine.

fr. All the measurements were done without:knowing the kind of cigarette: emplioyed. These cigarettes employed are specially made for research purposes. Their nicotine contents are about the strongest and the lightest ones commercj!ally available onithe market of the N. S'. 'Both cig;arettes were conditioned in a humid'box more than 12'hours before smoking. Chronic smoking is: a well-known,risk factor for the development of' myocardial infarctioniand~ for the higher mortality rate from sudden death., Although no direct mechanism has been establi'.shed to explain these relations, acute hemodynamic stress and possible myocardial ischemiasuggested by this study cannot be overlooked. Cn' O . OD (z

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