Dissociation of platelet activation and spontaneous myocardial ischemia in unstable angina.
A dynamic thrombotic process, coronary spasm or both can be responsible for recurrent episodes of transient reduction of coronary blood flow in unstable angina. We have investigated the temporal relationship between episodic platelet activation, as detected by increased urinary excretion of 11-dehydro-TXB2, and spontaneous myocardial ischemia, assessed by continuous electrocardiographic monitoring and recording in 21 patients with unstable angina pectoris. In order to validate measurements of metabolite excretion as a reflection of intracoronary platelet activation, we have also performed repeated urine sampling from 8 patients undergoing PTCA and from 6 patients with peripheral vascular disease. The latter showed a 16% coefficient of variation in 3 consecutive 8-h urine samples. 11-dehydro-TXB2 increased significantly, by up to 15-fold, in the 2.5- to 5.0-h urine collection encompassing PTCA and decreased by greater than 50% during the following 2-h period. Patients with unstable angina were characterized by episodic increases (greater than 2 SD of controls) in metabolite excretion, in successive 6-8 h specimens. Paired measurements of 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 15 urine samples did not reveal evidence of altered metabolic disposition of endogenously released TXB2. A total of 125 ECG ischemic episodes were recorded, of which 64% asymptomatic. We have compared these biochemical and ECG changes in patients randomized to i.v. low-dose aspirin or i.v. isosorbide dinitrate and oral diltiazem. Twenty-five of 56 (i.e. 45%) urine samples obtained in aspirin-free periods showed increased metabolite excretion as compared to 15 of 88 (i.e. 17%) samples collected during aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
Vejar
M
M
Cardiovascular Research Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Fragasso
G
G
Hackett
D
D
Lipkin
D P
DP
Maseri
A
A
Born
G V
GV
Ciabattoni
G
G
Patrono
C
C
D000293:Adolescent; D000328:Adult; D000787:Angina Pectoris / Q000097:blood* / Q000503:physiopathology*; D000789:Angina, Unstable / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use; D003326:Coronary Circulation / Q000502:physiology*; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D006801:Humans; D007547:Isosorbide / Q000627:therapeutic use; D008875:Middle Aged; D015539:Platelet Activation / Q000502:physiology*; D011863:Radioimmunoassay; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin; D007547:Isosorbide