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Measurement of Myocardial Lactate Production for Diagnosis of Coronary Microvascular Spasm

Published: September 17th, 2021



1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

Myocardial lactate production (coronary arterial-venous difference in serum lactate level) during coronary spasm provocation testing is considered as a highly sensitive marker that reflects acetylcholine-induced myocardial ischemia due to microvascular spasm. This article presents the procedures to assess myocardial lactate production for the diagnosis of coronary microvascular spasm.

In about a quarter of patients with angina and non-obstructive coronary arteries, no epicardial spasm is noted on coronary arteriography during an angina attack. Since the pressure-rate product is almost identical at rest and the onset of attack in those patients, the decrease in coronary blood flow rather than increased myocardial oxygen consumption is likely to explain myocardial ischemia, indicating a substantial involvement with coronary microvascular spasm (MVS). Myocardial lactate production, which could be defined as a negative myocardial lactate extraction ratio (ratio of the coronary arterial-venous difference in lactate concentration to arterial concentration), is considered indicative of objective evidence to support the emerging myocardial ischemia. Thus, monitoring of the myocardial lactate production and the emergence of chest pain and ischemic electrocardiographic changes during acetylcholine (ACh) provocation testing is of significant value for detecting the entity of MVS. Practically, 1 min after incremental doses of ACh (20, 50, and 100 μg) are administered into the left coronary artery (LCA), paired samples of 1 mL of blood are collected from the LCA ostium and coronary sinus for measurement of lactate concentration by a calibrated automatic lactate analyzer. Then, the development of MVS could be confirmed by negative myocardial lactate extraction ratio despite the absence of angiographically demonstrable epicardial coronary spasm or before its occurrence throughout ACh provocation testing. In conclusion, assessment of myocardial lactate production is essential and valuable for the diagnosis of MVS.

Recent studies demonstrated that ischemia with non-obstructive coronary arteries (INOCA) is caused mainly by functional coronary vasomotion disorders, including epicardial and microvascular spasms1. The diagnosis of coronary vasoconstrictor dysfunction at the epicardial and/or microvascular levels often requires intracoronary provocation testing with a pharmacological vasoactive agent such as acetylcholine (ACh) during coronary angiography2. Many patients with INOCA have no epicardial spasm on coronary arteriography despite the development of angina attack and ischemic electrocardiographic (ECG) changes in response to in....

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The measurement of myocardial lactate production during ACh provocation testing to evaluate coronary vasoreactivity was conducted following the ethical principles in the Declaration of Helsinki, and the protocol was approved by the Ethics Committees of Tohoku University (No.2016-1-643). All the patients provided written informed consent before the procedure. In this article, ACh provocation testing was performed following the guidelines of the Japanese Circulation Society9.

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A 56-year-old woman with no coronary risk factors suffered from transient chest discomfort at rest. She underwent ACh provocation testing and measurement of myocardial lactate production for diagnosis of MVS. As shown in Figure 2, chest pain, ischemic ECG changes, and negative LER were noted immediately following 100 µg of ACh administration into the LCA. Still, no relevant epicardial coronary spasm was observed on angiography. Thus, she was diagnosed as having MVS. Intriguingly, she ha.......

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Detection of enhanced coronary vasoconstriction is possible by an additional pharmacological provocation testing with ACh or ergometrine during coronary angiography. Even now, there is no technique to directly visualize the coronary microvasculature for evaluation of its function in vivo, the occurrence of coronary spasm at microvascular level could be solely deduced by the reproduction of usual symptoms together with ischemic ECG changes despite the absence of epicardial coronary spasm during ACh provocation te.......

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We thank all the staff of the catheterization laboratory of the Tohoku University Hospital.


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Name Company Catalog Number Comments
ABL8000 FLEX blood gas analyzer RADIOMETER, Copenhagen, Denmark k041874 The automatic lactate analyzer
OUTLOOK Terumo Corp, Tokyo, Japan RQ-5JL4000 The Judkins-left catheter for coronary angiography
Ovisot for injection Daiichi sankyo company, limited, Tokyo, Japan 871232 Injectable product of acetylcholine chloride for acetylcholine provocation testing
Supersheath MEDIKIT CO., LTD., Tokyou, Japan CS50P11TSM The sheath for insertion of a catheter
Technowood SoftNAV Catheter Technowood Corp, Tokyo, Japan H710-FL445SH The Amplatz-left catheter for blood sampling from coronary sinus

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