Am J Pub. Health 1966; 56:1061-69. 6 Levine PH. An acute effect of cigarette smoking on platelet function. A possible ... 7 Soliq SR, Mason RG. Some effects of ...
Platelet sensitivity to prostacyclin in smokers and non-smokers. O C Burghuber, C Punzengruber, H Sinzinger, P Haber and K Silberbauer Chest 1986;90;34-38 DOI 10.1378/chest.90.1.34 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/90/1/34
Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1986by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692
Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011 © 1986 American College of Chest Physicians
Platelet Sensitivity to Prostacyclin in Smokers and Non-smokers* 0.C. Burghuber, M.D.;Ch. Punzengruber, M.D.;H. Sinzinger, M.D.; l? Haber, M.D.;and K . Silberbauer, M.D.
Platelet activating effect of cigarette smoking appears to be important in the development of atherosclerosis. We previously demonstrated a reduced sensitivity of platelets to exogenous prostacyclin (PGIJ in d r o from patients with proven atherosclerotic disease, indicating a possible role of altered platelet function in the development of atherosclemsis. We now hypothesize that cigarette smoking might be an important cause of a l t e d platelet sensitivity to PGI, observed in patients with atherosclerosis. To test this hypothesis, the response of platelets to exogenous PGI, was tested in chronic smokers and non-smokers, prior to and
after smoking two cigarettes (active smoking) and prior to and after exposure to a tobacco smoke-contaminated atmosphere (passive smoking). 'Lhis study indicates that platelets of chronic smokers are less sensitive to exogenous PGI, than platelets of non-smokers. In addition, active as well as passive smoking decreases platelet sensitivity to PCI, in non-smokers, whereas chronic smokers exhibit no further decline. We conclude that decreased platelet sensitivity to PGI, might be an important contributing factor to the altered platelet function observed in patients with athemsclerosis.
S
smoking, then we could consider it an additional important mechanism of arterial thrombosis.
moking has been incriminated as a pathogenetic factor in cardiovascular disease.LPTobacco smoking is associated with an increased risk of myocardial infarction;=sudden death and arterial thrombosis occur more frequently in cigarette smoker^.'.^ Because blood platelets appear to play a central role in the initiation of arterial thrombosis, the difference in aggregation behavior in platelets from smokers and non-smokers seems to be important. The influence of nicotine and1 or other cigarette constituents on platelet function has been investigated in several in duo and in d t r o studies. From these studies it is known that smoking induces enhancement of platelet function." Evidence supporting this idea includes an association of smoking with increased ADP-induced platelet aggregation in platelet-rich plasma,' an enhanced tendency of platelets to aggregate in a shortening of platelet s u ~ i v a land ' ~ increased thromboxane ~ y n t h e s i s . ~In" addition there is some evidence that smoking might exert its action by reducing vascular prostacyclin we have previously demon(PGIJ s y n t h e s i ~Since .~ strated reduced platelet sensitivity to exogenous PGI, in uitm in patients with atheros~lerosis,~~ we wondered whether cigarette smoking might decrease platelet sensitivity to PGI,. Because of recent observationsm~ that passive smoking increases the incidence of various diseases primarily associated with active smoking, we also wondered whether even passive smoking could influence platelet sensitivity to PGI,. If platelet sensitivity to PGI, were suppressed by active or passive -
--
-
*From the Second Department of Internal Medicine, University of Vienna, Vienna, Austria. Manuscript received October 21,1985; revision accepted January 20. Rearint reauests: D,:Burehuber. Camisoneapse 13, 11 Medical ~Gartmeni,Uniwdty of-Vienna; Vienna, A&& A-lKW
Acrioe Smoking The subjects of this study were 14 healthy male volunteers whose ages ranged from 28 to 36 years. Seven were non-smokers and seven were moderate-to-heavy smokers (at least one pack a day for at least ten years). Standard commercial brands containing 1.5 mg nicotine and 25 mg tar per gram of cigarette were used. The smokers refrained from smoking for at least four hours prior to the test procedures, and no medication was allowed for two weeks prior to the studies. A 19 gauge plastic cannula was inserted into the antecubital vein 15 min prior to baseline measurements to m i d repeated venous punctures. Then the patients were told to smoke two cigarettes, one &er the other, within 10 rnin. Immediately before and 15 min after smoking twno cigarettes, blood pressure, pulse rate, and ventilatory function tests were performed and blood was drawn. Blood pressure was measured with the Korotkoff method by the same observer. Ventilatory function was assessed by spirometry using a Fleisch pneumotachograph attached to an electronic device (Siregnost FD 10, Siemens Elema; 19)and recorded on an x-y recorder (Hewlett-Packard). Vital capacity (VC, L) was determined by a slow inspiratory effort. This was followed by three attempts of FEV, maneuvers (FEV,, L) AAer completion of these procedures, forced expiratory flow volume curves were obtained. Forced expiratory flows at the moment when 50 percent of the vital capacity had been expelled (FEF,, Usec) and when 75 percent had been expelled (FEF,, Usec) were read directlv from the flow volume curves. The best of three attem~ts was used for calculation. Blood withdrawal was performed from the previously inserted plastic cannula. Nine volumes of blood were mixed with one volume of 3.8 percent hisodium citrate solution to obtain citrated blood. After centdigation at 150g for 5 min, platelet-rich plasma (PRP)was obtained. PRP was then removed and platelet-poor plasma (PPP) produced by further centrihgation of 1500 g for 15 min. PRP was adjusted with PPP to give a platelet count of approximately 250 x 10.'1pl. ADP (in a rather high concentration of 1 mmoM) was used to cause irreversible platelet aggregation measured in a BornRoaaeyclln In Smokers and Non-mokm (Bughubor et d)
Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011 © 1986 American College of Chest Physicians
BP mm Hg
NON SMOKER
SMOKER
I
NS
-J
0
0
FIGURE1. Individual data points and means of systolicand diastolicblood ~ r e s sure (BP; m m ~before ~ ) and after smoking 2 cigarettes in smokers and nonsmokers.
N.S.
( '
BEFORE
BEFORE
AFTER
AFTER
within and between groups respectively. Differences were considered significant when pC0.05.
type aggregometer. On all occasions, second phase of ADP-induced platelet aggregation was seen. The maximal extent of platelet aggregation (ATmax) was calculated assuming that PPP was 100 percent and PRP was 0 percent aggregation. In addition, ADP-induced platelet aggregation was inhibited by increasing concentrations of PGI, (1,2,3 ng/ml) being added 60 sec prior to ADP. From this the sensitivity index of PGI, (SIpcd was calculated @Ipcb=1/ID,; ID, = the concentration of PGI, necessary to inhibit ADP-induced platelet aggregation to 50 percent).
RESULTS Active S m k i n g
Prior to smoking two cigarettes, neither smokers nor non-smokers exhibited any difference in either systolic or diastolic blood pressure (Fig 1)or in heart rate (Fig 2). After smoking two cigarettes, blood pressure remained unchanged (Fig I), whereas a significant increase in heart rate could be observed in both groups (Fig 2). There was no difference in VC and FEV, prior to or after smoking between smokers and non-smokers (Table 1). However, smokers had lower forced expiratory flow rates compared to non-smokers, before as well as after smoking two cigarettes @ble 1).Smoking two cigarettes did not alter any ventilatory parameters studied in either group. Prior to smoking two cigarettes, the aggregation of platelets in response to ADP was the same in smokers
Possioe Smoking Another 22 healthy male volunteers, 13 smokers and nine nonsmokers, whose ages ranged from 25 to 40 years, were exposed to cigarette smoke. Smokers refrained from active smoking for at least four hours before studied. Volunteers were kept for 20 min in an 18 mProom in which testers 'smoked 30 heavy b r k d cigarettes just prior to the exposure period. This concentration was calculated to be that occumna in discos, restaurants etc. Again, blood was drawn before and 15 ;in after the passive smoking period and aggregation studies were performed as previously described. Stdistical Analysis
Paired and unpaired Student'st-tests were used to compare results
NON SMOKER
FIGURE2. Individual data points and means of heart rate (HR; beatslminute) before and after smoking 2 cigarettes in smokers and non-smokers.
)/
-
BEFORE
AFTER
j
BEFORE
AFTER
CHEST 1 9 0 1 1 1 JULY, 1198
Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011 © 1986 American College of Chest Physicians
%
Table 1-Indiddual Lung Function Parameters before and a j b Smoking T w Cigarattes in Non-smokers and Smokers
vc (L) Before
FEV, (L) After
Before
FEF, (Usec)
After
Before
After
FEF, (Usec) Before
After
Non-smokers 1 2 3 4 5 6 7 mean f SEM Smokers 1 2 3 4
5 6
7 mean f SEM *p
