Studies of platelet factor 4 and beta thromboglobulin release during exercise: lack of relationship to myocardial ischemia.

Abstract

SUMMARY Platelet activation, which results in release of the platelet-specific proteins platelet factor 4 (PF4) and BTG thromboglobulin (BTG), may participate in exercise-induced myocardial ischemia by the formation of intravascular platelet aggregates or the generation of vasoactive substances such as thromboxane A2. We sought to determine if platelet release occurs during exercise-induced ntyocardial ischemia and its relationship to exercise-induced catecholamine release in 10 normal males (mean age 29 + 6 years) and 25 males with proved coronary artery disease (mean age 60 ± 8 years) who performed maximal, symptomlimited treadmill exercise tests. None of the subjects took drugs known to modify platelet behavior; 17 coronary artery disease patients took B-blocking agents. Plasma and urine PF4, plasma BTG and plasma catecholamines were measured before and immediately after exercise. Plasma PF4 and BTG were also measured 30 minutes after exercise. Ischemia, defined as angina or 1 mm or more of horizontal or downsloping ST depression, developed in 14 coronary artery disease patients.In young normal subjects during exercise, plasma PF4 increased from 2.1 ± 1.2 at rest to 4.7 ± 2.6 ng/ml at maximal exercise (p < 0.01 rest vs exercise) and plasma BTG increased from 11.7 ± 5.4 to 16.7 ± 7.7 ng/ ml (p < 0.01 rest vs exercise). Among the 25 coronary artery disease patients, plasma PF4 during exercise increased slightly but significantly, from 2.1 1.4 at rest to 2.6 ± 2.2 ng/ml at exercise (p < 0.01); plasma BTG did not change significantly, from 13.3 6.0 at rest to 14.1 ± 5.8 ng/ml during exercise. The small exercise-induced elevations in plasma PF4 and BTG in all 25 coronary artery disease patients were significantly less than those in the 10 young normal subjects (both p < 0.01 vs normals). Among the subset of 14 coronary artery disease patients with exercise-induced ischemia, neither plasma PF4 nor BTG increased significantly (PF4 from 2.6 1.7 at rest to 3.0 ± 2.9 ng/ml with exercise; plasma BTG from 13.6 ± 6.4 to 14.1 ± 7.1 ng/ml). The 14 coronary artery disease patients with ischemia had less exercise-induced elevation in both plasma PF4 and BTG than normal subjects (both p < 0.05). Plasma PF4 and BTG levels 30 minutes after exercise were not significantly different from rest levels in any subject group. Mean rest, peak exercise, and 30-minute postexercise plasma PF4 and BTG values did not differ significantly between the 17 coronary disease patients taking B-blocking agents and the eight coronary disease patients not taking Bblocking drugs. Furthermore, urinary PF4 did not change significantly with exercise in either norrmal subjects or in any of the coronary artery disease groups. Among all 35 subjects, exercise-induced increases in plasma epinephrine correlated with increases in plasma PF4 (r = 0.35; p = 0.04) and BTG (r = 0.40; p = 0.02). Increases in norepinephrine did not correlate with either increases in plasma PF4 (r = 0.24, p = 0.2) or BTG (r 0.23, p = 0.2).We conclude that exercise-induced release of pl...

Possible interaction of platelets and adrenaline in the early phase of myocardial infarction

“…The second explanation is supported by the results of 8traton et al [32], who found a correlation between adrenaline increase during exercise and both platelet factor 4 and fl-thromboglobulin levels. These authors did not observe any relation between these alterations and pain in patients with ischemic heart disease.…”

Stress and Platelet Activation

“…Thus, the phlebotomy procedure was ac companied by a transient elevation of the plasma concentrations of BTG and PF-4, a finding probably attributable to an in stant release of adrenaline. Therefore, as previously discussed by us and others, it is conceivable that patients suffering from chest pain and psychological stress unre lated to an underlying cardiovascular dis ease, in analogy with the situation in 'hy povolemic stress', would activate the adrenal-medullary system and thereby de monstrate increased platelet activation and secretion [4][5][6].…”

“…4,5]. It has further been suggested that platelet activation is in duced only provided the stress situation is accompanied by increased levels of circu lating adrenaline [6]. Loud noise is a com mon environmental stress factor [7][8][9], Noise stress is known to induce an acute increase in blood pressure, which is medi ated by the sympathetic nervous system [10].…”

Potentiation by adrenaline of human platelet activation and the inhibition by the alpha-adrenergic antagonist nicergoline of platelet adhesion, secretion and aggregation

“…In vivo, platelet activation measured by the secretion of platelet-specific proteins (PF4, ffI'G) or by the formation of thromboxane B2, may occur during exercise [37] and after emotional stress [8,38], which are known to increase the level ofcatecholamines in plasma. The specific inhibition by nicergoline of the activation of platelets by adrenaline in vitro and ex vivo and the reports that nicergoline inhibits platelet-mediated thrombosis in stenosed coronary arteries [11] and cortical arteries [39] in experimental animals in vivo could increase the potential therapeutic applications of nicergoline.…”