No abstract

The acetylcholine (ACh) spasm provocation test proposed by Yasue, Okumura et al more than a quarter‐century ago has become a popular method for induction of coronary spasm. This test is safe and has a low rate of complications. However, it may be limited in its ability to document attacks in daily life because previously it was the gold‐standard method for diagnosing active variant angina. There may be some clinical issues to modify for the next generation of cardiologists. A maximal ACh dose of 50/100 µg in the right coronary artery/left coronary artery is recommended in the Japanese Circulation Society guidelines. We often experienced the usefulness of a maximal ACh dose of 80/200 µg for the induction of coronary spasm in some cases with low or moderate disease activity. It may be necessary to reconsider the maximal ACh dose as a modified method for today's real‐world clinical practice. In young patients with rest angina, intracoronary injection of ACh is less sensitive for diagnosis; in these cases, we recommend performing sequential spasm provocation tests. Especially in female patients, to document coronary artery spasm we recommend performing ACh tests first, instead of ergonovine tests, due to the supersensitivity of ACh. We also recommend supplementary use of ACh and ergonovine. This review summarizes our experiences with the ACh spasm provocation test over a period of 24 years. We have found it to be a reliable and useful method for contributing a variety of clinical information and recommend it to the next generation of cardiologists.

The spasm provocation tests of ergonovine and acetylcholine have been employed in the cardiac catheterization laboratory. Ergonovine acts through the serotogenic receptors, while acetylcholine acts through the muscarinic cholinergic receptors. Different mediators may have the potential to cause different coronary responses. However, there are few reports concerning the coronary response between ergonovine and acetylcholine in the same patients. Acetylcholine is supersensitive for females; spasm provoked by ergonovine is focal and proximal, whereas provoked spasm by acetylcholine is diffuse and distal. We should use both tests as supplementary in the clinic because ergonovine and acetylcholine have self-limitations to induce coronary spasms during daily life. The maximal pharmacological doses, administration methods, and the angiographical positive definition are remarkably different for each institution in the world. We recommend the pharmacological spasm provocation tests as Class I in the guidelines in patients with vasospastic angina throughout the world.

There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.

Lower ACh doses induced spasms more proximally and focally in the coronary artery, while higher doses of ACh provoked spasms more distally and diffusely.