Studies of platelet factor 4 and beta thromboglobulin release during exercise: lack of relationship to myocardial ischemia.
Authors: J R Stratton, T W Malpass, J L Ritchie, M A Pfeifer, L A Harker
Journal: Circulation (1982)

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 thrombox- ane 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, symptom- limited 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 B- blocking 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 plasma PF4 and BTG, as measured by sampling peripheral venous blood, is not a marker of myocardial ischemia.The small elevations in plasma PF4 and BTG induced in normal subjects and in coronary artery disease patients by exercise are nonspecific for myocardial ischemia and may be related to the magnitude of epinephrine release.PLATELET ACTIVATION, with the subsequent for- mation of platelet aggregates or the generation of thromboxane A2, has been causally implicated in both resting and exercise myocardial ischemia.1-7 Both platelet factor 4 (PF4) and B thromboglobulin (BTG) are released from platelet a granules during platelet activation.The development of radioimmunoassays for these platelet-specific proteins permits their use as indicators of platelet activation in man.i'7The pres-