Sulfinpyrazone Improves Myocardial Blood Flow And Inhibits Platelet Release During Exercise In Coronary Disease

Exercise (EX) is associated with activation of the platelet release reaction (REL), and REL during EX is exaggerated in men with coronary disease (CAD). Sulfinpyrazone (SFP) and aspirin (ASA) inhibit REL at rest and during EX. Sixteen men with CAD underwent treadmill EX with measurement of β-thromboglobulin (β-Th) and thromboxane B₂ (TBX) (radioimmunoassay) at rest and just after anginalimited EX. Eight men were randomly assigned to SFP (200 mg po QID) and eight to ASA (300 mg po BID) and EX repeated 7 days later. Placebos were given for 7 days and EX repeated (double blind, cross-over). Myocardial blood flow distribution (MBFD) was measured during EX (²⁰¹Thal1ium; 7-pinhole tomographic image acquisition and analysis). β-Th was elevated at rest (40.±5. ng/ml; N=16; AVE±SEM; normal 18.±2. ng/ml; N=22; p<0.001) and during EX (120.±8. ng/ml; normal 28.±4. ng/ml; p<0.001). TBX was not detected in venous blood at rest, but was present in 14 men during EX (15.±3. pg/ml; N=16; normal 0. pg/ml; N=22). SFP decreased β-Th at rest (control 33.±4. ng/ml; SFP 17.±3. ng/ml; N=8; p<0.001) and during EX (control 121.±14. ng/ml; SFP 46.±7. ng/ml; p<0.001). ASA also decreased β-Th at rest (control 46.±3. ng/ml; ASA 28.±7. ng/ml; N=8; p<0.001) and during EX (control 118.±9. ng/ml; ASA 44.±7. ng/ml; p<0.001). TBX was not detected in any man either at rest or during EX during treatment with SFP and ASA. All men had abnormal MBFD during control EX. SFP improved MBFD (+364.±62. normalized counts; N=8; integrated count rate difference between control and EX with SFP; control vs placebo +17. normalized counts). ASA did not alter MBFD (+140.±29. normalized counts; ASA vs placebo +7 normalized counts). Neither SFP nor ASA altered heart rate, systolic blood pressure or ST segment depression during EX. Results suggest that REL is activated by EX in men with CAD and that SFP and ASA inhibit EX REL, including TBX. SFP has a greater effect on MBFD during EX than ASA.