Stable Exertional Angina Group Research Articles

Increased plasma level of soluble E-selectin in acute myocardial infarction

Background E-selectin, also known as endothelial cell leukocyte adhesion molecule-1, is a member of the selectin family of adhesion molecules and is expressed on vascular endothelial cells in inflammatory reactions. The induction of surface E-selectin expression by endothelial cells is considered a marker of activation. Methods and Results We examined the plasma soluble E-selectin (sE-selectin) level in 41 patients within 6 hours after the onset of acute myocardial infarction (AMI) and in 37 patients with stable exertional angina and 27 control patients. Blood samples were obtained on admission, after reperfusion therapy, and at 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 3 days, 5 days, 1 week, and 2 weeks after admission in the AMI group. In this group, 21 patients had a history of prodromal unstable angina before infarction and 20 had sudden onset of infarction. The plasma sE-selectin level (ng/mL) on admission was higher in the AMI group than in the stable exertional angina group and control group (38.5 ± 3.1 vs 28.5 ± 1.5, P <.01, 26.0 ± 1.8, P <.01, respectively). In addition, plasma sE-selectin levels were higher in the patients with AMI with prodromal unstable angina than in those with a sudden onset of infarction on admission (44.7 ± 5.4 vs 32.0 ± 2.1, P <.05). The plasma sE-selectin level decreased slowly during the chronic phase both in patients with AMI with prodromal unstable angina (from 44.7 ± 5.4 to 33.8 ± 3.4, P <.01) and those with a sudden onset of infarction (from 32.0 ± 2.1 to 24.9 ± 2.4, P <.01). Conclusions These results suggest that an increase of sE-selectin may reflect enhanced endothelial cell activation in patients with AMI. The higher sE-selectin level in patients with AMI with prodromal unstable angina may have been associated with repeated episodes of myocardial ischemia and reperfusion. (Am Heart J 2000;140:243-8.)

Heparin-Releasable Endothelial Cell-Associated Tissue Factor Pathway Inhibitor (Tfpi) is Increased in the Coronary Circulation After Coronary Spasm in Patients with Coronary Spastic Angina

Tissue factor pathway inhibitor (TFPI) is a physiological regulator of the extrinsic coagulation cascade. Coronary spasm can alter endothelial cell properties in the coronary artery with resultant thrombosis. To determine whether coronary spasm affects plasma TFPI level, we measured the heparin-releasable endothelial cell-associated TFPI (heparin-releasable TFPI) (ng/ml) in the coronary sinus and the aortic root before and after coronary spasm induced by an injection of acetylcholine in 18 patients with coronary spastic angina, and before and after myocardial ischemia induced by rapid atrial pacing in 18 patients with stable exertional angina, and in 17 control subjects with normal coronary arteries and no coronary spasm. Heparin-releasable TFPI level in the coronary spastic angina group significantly increased in the coronary sinus (122±46 to 147±63, p<0.001) after the ischemic event but not in the aortic root (113±44 to 121±58). The level in the coronary sinus and the aortic root remained unchanged after the ischemic event in the stable exertional angina group and after the injection of acetylcholine in the control group. The coronary sinus-arterial difference in the amount of the heparin-releasable TFPI significantly increased after the ischemic event only in the coronary spastic angina group (10±18 to 26 ±18, p<0.002). Our result suggested that heparin-releasable TFPI is increased in the coronary circulation after coronary spasm.

Soluble P-Selectin Is Released Into the Coronary Circulation After Coronary Spasm

The glycoprotein P-selectin is an adhesion molecule involved in the property change of leukocytes at the initiation of the inflammatory process. The purpose of the present study was to determine whether acute myocardial ischemia induced by coronary spasm causes an acute inflammatory response in the coronary circulation. We examined plasma soluble P-selectin levels in the coronary sinus and the aortic root simultaneously in 16 patients with coronary spastic angina before and after left coronary artery spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Ten control patients with chest pain but normal coronary arteries and no coronary spasm also received intracoronary acetylcholine. Plasma soluble P-selectin levels were increased significantly in the coronary sinus (32.8 +/- 3.6 to 52.8 +/- 5.9 ng/mL, P < .001) and in the aortic root (34.6 +/- 3.7 to 41.9 +/- 4.4 ng/mL, P < .05) after the attacks in the coronary spastic angina group but remained unchanged in the stable exertional angina group after the attacks and in the control group after the administration of acetylcholine. Furthermore, the coronary sinus-arterial difference of soluble P-selectin increased significantly after the attacks in the coronary spastic angina group (-1.8 +/- 2.2 to 10.9 +/- 2.7 ng/mL, P < .001). Our data indicate that soluble P-selectin is released into the coronary circulation after coronary artery spasm. We conclude that coronary artery spasm may induce the leukocyte adhesion in the coronary circulation and may lead to myocardial damage.

Plasma plasminogen activator inhibitor activity and tissue plasminogen activator levels in patients with unstable angina and those with coronary spastic angina

Plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (TPA) antigen were measured in venous samples in 14 patients with unstable angina consisting of eight patients with organic stenosed coronary arteries and six patients with coronary spastic angina (unstable angina group); in 14 patients with stable exertional angina (stable exertional angina group); and in 14 patients with chest pain syndrome (chest pain syndrome group). The plasma levels of PAI activity were higher ( p < 0.01) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (12.3 ± 1.0 versus 5.1 ± 0.7 and 4.8 ± 0.6 IU/ml). The plasma levels of TPA antigen were also higher ( p < 0.05) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (10.2 ± 1.3 versus 6.5 ± 0.8 and 6.0 ± 0.7 ng/ml). There were no significant differences in PAI activity and TPA antigen levels between the stable exertional angina group and the chest pain syndrome group. Furthermore, both PAI activity and TPA antigen levels in the unstable angina group decreased to the levels in the stable exertional angina group and the chest pain syndrome group after treatment ( p < 0.01). In conclusion, the increased plasma PAI activity in patients with unstable angina and in those with coronary spastic angina indicates that the fibrinolytic system is impaired in these patients.

Fibrinopeptide A is released into the coronary circulation after coronary spasm.

To examine whether acute myocardial ischemia activates the coagulation system and platelet activation in the coronary circulation, we measured plasma levels of fibrinopeptide A and beta-thromboglobulin in the coronary sinus and the aortic root simultaneously in 15 patients with coronary spastic angina before and after the left coronary spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Fifteen patients with chest pain but normal coronary arteries and no coronary spasm served as controls. The coronary sinus-arterial difference of fibrinopeptide A increased markedly (p less than 0.001) from 0.1 +/- 0.2 to 4.3 +/- 0.7 ng/ml after the anginal attacks in the coronary spastic angina group. However, fibrinopeptide A levels remained unchanged after the attacks in the stable exertional angina group and after intracoronary injection of acetylcholine in the control group. Plasma beta-thromboglobulin levels remained unchanged after the attacks in both patient groups and after acetylcholine in the control group. Our data indicate that coronary spasm induces thrombin generation and may lead to thrombus formation in the coronary artery involved, but pacing-induced ischemia does not activate the coagulation system.