Neri Serneri G G, Gensini G F, Poggesi L, Modesti P A, Rostagno C, Boddi M, Gori A M, Martini F, Ieri A, Margheri M
Clinica Medica I, University of Florence, Italy.
Coron Artery Dis. 1994 Feb;5(2):137-45. doi: 10.1097/00019501-199402000-00007.
The role of thromboxane A2 (TxA2) in unstable angina has not yet been defined. TxA2 receptor antagonists may be of value in studying this role.
To investigate whether TxA2 has a pathogenetic effect on the occurrence of myocardial ischemia and from what source TxA2 originates, we studied TxA2 formation by unstimulated monocytes from patients with unstable angina (n = 40), stable effort angina (n = 20), and controls (n = 20). We also compared the effects of picotamide (1200 mg/day), a TxA2-synthase inhibitor and TxA2-receptor antagonist, with those of aspirin (325 mg/day) on myocardial ischemia and TxA2 formation by monocytes and platelets. The double-blind randomized study was performed on patients with unstable angina on continuous Holter monitoring.
In the presence of autologous lymphocytes, unstimulated monocytes from patients with unstable angina formed significantly (P < 0.001) more TxA2 than those from controls or from patients with effort angina. Although TxA2 formation by circulating monocytes and platelets was inhibited to a greater degree by aspirin than by picotamide (88 +/- 6 and 98 +/- 2%, respectively, versus 65 +/- 2 and 74 +/- 1%, P < 0.001), aspirin failed to affect the occurrence of myocardial ischemia whereas picotamide significantly (P < 0.001) reduced the number of anginal attacks (84.8%), silent ischemic episodes (64.2%), and overall duration of ischemia (69.8%), in comparison to the run-in period.
These results indicate that TxA2 formed by monocytes contributes to the pathogenesis of myocardial ischemia in unstable angina. TxA2 formation occurs mainly in extravascular spaces, probably within the coronary vascular wall. Picotamide appears to control myocardial ischemia effectively in patients with unstable angina.
血栓素A2（TxA2）在不稳定型心绞痛中的作用尚未明确。TxA2受体拮抗剂可能有助于研究这一作用。
为了研究TxA2对心肌缺血发生是否具有致病作用以及TxA2的来源，我们研究了不稳定型心绞痛患者（n = 40）、稳定劳力型心绞痛患者（n = 20）和对照组（n = 20）未受刺激的单核细胞生成TxA2的情况。我们还比较了TxA2合酶抑制剂及TxA2受体拮抗剂匹可托胺（1200毫克/天）与阿司匹林（325毫克/天）对心肌缺血以及单核细胞和血小板生成TxA2的影响。该双盲随机研究在持续进行动态心电图监测的不稳定型心绞痛患者中开展。
在自体淋巴细胞存在的情况下，不稳定型心绞痛患者未受刺激的单核细胞生成的TxA2显著多于对照组或劳力型心绞痛患者（P < 0.001）。虽然阿司匹林比匹可托胺更能抑制循环单核细胞和血小板生成TxA2（分别为88±6%和98±2%，对比65±2%和74±1%，P < 0.001），但阿司匹林未能影响心肌缺血的发生，而匹可托胺与导入期相比，显著减少了心绞痛发作次数（84.8%）、无症状缺血发作次数（64.2%）和缺血总时长（69.8%）（P < 0.001）。
这些结果表明，单核细胞生成的TxA2在不稳定型心绞痛心肌缺血的发病机制中起作用。TxA2的生成主要发生在血管外间隙，可能在冠状动脉血管壁内。匹可托胺似乎能有效控制不稳定型心绞痛患者的心肌缺血。
