MISCELLANEOUS

Effects on Platelet Aggregation and Fibrinolytic Activity During Upright Posture and Exercise in Healthy Men Kaj Winther, MD, PhD, William Hillegass, MD, Geoffrey H. Tofler, MB, Alfred0 Jimenez, MD, Damian A. Brezinski, MD, Andrew I. Schafer, MD, Joseph Loscalzo, MD, PhD, Gordon H. Williams, MD, and James E. Muller, MD

The circadian variation of acute myocardial infarction suggests that daily activities such as assuming the upright posture and performing different daily activities may trigger the onset of coronary thrombosfs. Such triggering may result from unfavorable alterations in the balance between the prothrombotic and antfthrombotic properties of the blood. The present study compares the effects of 2 common daily activities, assuming the upright posture and exercise, on platelet aggregation and fibrindytfc activity. In healthy male subjects, assuming the upright posture in the morning dgnificantly increased platelet aggregation and produced only a moderate increase in ffbrinolytic activity within 10 minutes. These changes were sttll present after 90 minutes in the upright posture. Supine posture for 45 minutes resulted in levels of ffbrinolytZc actfvfty and platelet aggregation comparable to that observed before initially assuming the upright posture in the morning. Return to the supine posture for 45 minutes resulted in levels of fibrlnofytfc actfvity and platelet aggregation comparable to that observed before the initial assumption of upright posture. The changes recurred when upright posture was taken later in the day. Exercise dkl not increase platelet aggregation to levels beyond that produced by the upright posture, but was assocfated with a marked increase in ffbrinolyttc activity. Thus, exercise and upright posture produce distinctive alterations in the thrombogenfc potential of the blood that may influence the timing of clinfcal vascular events. (Am J Cardiol 1992;70:1051-1055)

he frequenciesof onset of myocardial infarction and sudden cardiac death have a prominent circadian variation, with an increase in the period from 6 A.M. to noon.1,2During this time period, subjects assumethe upright posture and perform physical exertion - 2 activities that activate the sympathetic nervous system and may cause systemic changesin blood clotting that predisposeto coronary artery thrombosis.3,4 Assumption of the upright posture in the morning is associated with increased platelet aggregability.4 However, the ability of the upright posture to increaselibrinolytic activity, a change that would tend to reduce the thrombotic potential of the blood, has not been previously described.Although it is agreed that exercise increaseslibrinolysis,5~6the effects of exerciseon platelet aggregation are controversial.7-11 The goalsof this study, therefore, were to answerthe following questionsconcerning the effectsof the upright posture and exerciseon platelet aggregability and librinolysis: (1) What is the time course of the effect of the upright posture in the morning on platelet aggregability? (2) Does assuming the upright posture at a later time of day causea similar increase?(3) Is the adverse effect, if it occurs, of assuming the upright posture on platelet aggregability counterbalancedby an increasein fibrinolytic activity? (4) Does exercise produce an increasein platelet aggregability beyond that produced by the upright posture? (5) What are the relative profiles of the effects of the upright posture and exercise on these determinants of thrombosis?

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This report describes2 studiesof 12 male volunteers, each drawn from a total pool of 22 subjects,aged 20 to 32 years (mean 24), who were all nonsmokers,and taking no aspirin or other medication in the previous 2 weeks.All had given informed consent. On the day before the study, all subjectswere admitted to the Clinical Research Center of the Brigham and Women’s HospiFrom the Harvard Medical School, Boston,Massachusetts.This study tal. Lights were turned out at midnight, and subjects was supported in part by Grants HL 36045 and HL 40411 from the were awakened at 7:30 A.M. the following morning for National Institutes of Health, Bethesda,Maryland; and grants from the initiation of the study. After arrival at the hospital, the Danish Medical ResearchCouncil, the Danish Heart Foundation,and subjects received a controlled fmed diet. The subjects Sandoz Pharmaceuticals,and was conductedat the Clinical Research Center of the Brigham and Women’s Hospital, Harvard Medical did not drink any coffee,tea or hot chocolate after they School, Boston, Massachusetts,supported by Grant 5MOI-RR02635 were awakened on the study morning. Coffee was not from the National Institutes of Health. The data were analyzed in a provided during the study; however, tea and chocolate CLINFO facility supported by the same grant. Manuscript received were available in the evening before the study. The efJanuary 15, 1992; revised manuscript received and acceptedJune 15, fects of these agents would have have worn off before 1992. Addressfor reprints: Kaj Winther, MD, PhD, Department of Clini- the morning studies, during which 250 ml of juice and drinking water were available. cal Chemistry, Glostrup Hospital, DK-2600 Glostrup, Denmark. POSTURE CHANGE, EXERCISE, PLATELETS AND FIBRINOLYSIS

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Phase I was designed to determine (1) the time course of the effect of the upright posture in the moming on plasma catecholamine levels and platelet aggregability; and (2) whether the upright posture at a later time of day causes similar changes. After waking at 7:30 A.M., the 12 subjects remained supine for 30 minutes. Then, they assumedthe upright posture, remained upright until 9:30 A.M., lay supine until 11:30 A.M., and returned to the upright posture for 90 minutes at the end of the protocol (Figure 1). Blood sampleswere obtained at 8 A.M. while the subjects were still supine in bed, and after 6,45 and 90 minutes in the upright position. Blood sampleswere then obtained after 2 hours in the supine position, and finally 90 minutes after patients had returned to reassumethe upright posture. PhaseII was designedto determine (1) whether the adverseeffect of the upright posture on platelet aggregability is associatedwith an increasein fibrinolytic activity; (2) if exercise produces an increase in platelet aggregability beyond that produced by the upright posture; and (3) the relative profiles of the effects of the 2 activities - upright posture or exercise- on platelet aggregability and librinolytic activity.

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Effects on platelet aggregation and fibrinolytic activity during upright posture and exercise in healthy men.

The circadian variation of acute myocardial infarction suggests that daily activities such as assuming the upright posture and performing different da...
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