Name: measurement of myocardial lactate production for diagnosis of coronary microvascular spasm
Uploaded: 2021-09-17T13:30:00
Description: Watch this Scientific Journal Video about Measurement of Myocardial Lactate Production for Diagnosis of Coronary Microvascular Spasm at JoVE.com

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

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.
<p class="jove_titl...

<ol>
	<li>Kunadian, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+EAPCI+expert+consensus+document+on+ischaemia+with+non-obstructive+coronary+arteries+in+collaboration+with+European+Society+of+Cardiology+Working+Group+on+Coronary+Pathophysiology+&amp;+Microcirculation+endorsed+by+Coronary+Vasomotor+Disorders+International+Study+Group.">An EAPCI expert consensus document on ischaemia with non-obstructive coronary arteries in collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology &amp; Microcirculation endorsed by Coronary Vasomotor Disorders International Study Group.</a> European Heart Journal. 41 (37), 3504-3520 (2020).</li><li>Ong, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis+of+coronary+microvascular+dysfunction+in+the+clinic.">Diagnosis of coronary microvascular dysfunction in the clinic.</a> Cardiovascular Research. 116 (4), 841-855 (2020).</li><li>Mohri, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angina+pectoris+caused+by+coronary+microvascular+spasm.">Angina pectoris caused by coronary microvascular spasm.</a> Lancet. 351 (9110), 1165-1169 (1998).</li><li>Sun, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+microvascular+spasm+causes+myocardial+ischemia+in+patients+with+vasospastic+angina.">Coronary microvascular spasm causes myocardial ischemia in patients with vasospastic angina.</a> Journal of the American College of Cardiology. 39 (5), 847-851 (2002).</li><li>Ong, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=International+standardization+of+diagnostic+criteria+for+microvascular+angina.">International standardization of diagnostic criteria for microvascular angina.</a> International Journal of Cardiology. 250, 16-20 (2018).</li><li>Matsuyama, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+plasma+level+of+endothelin-1-like+immunoreactivity+during+coronary+spasm+in+patients+with+coronary+spastic+angina.">Increased plasma level of endothelin-1-like immunoreactivity during coronary spasm in patients with coronary spastic angina.</a> American Journal of Cardiology. 68 (10), 991-995 (1991).</li><li>Goldberg, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+hemodynamic+and+myocardial+metabolic+alterations+accompanying+coronary+spasm.">Coronary hemodynamic and myocardial metabolic alterations accompanying coronary spasm.</a> American Journal of Cardiology. 43 (3), 481-487 (1979).</li><li>Odaka, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Plasma+concentration+of+serotonin+is+a+novel+biomarker+for+coronary+microvascular+dysfunction+in+patients+with+suspected+angina+and+unobstructive+coronary+arteries.">Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries.</a> European Heart Journal. 38 (7), 489-496 (2017).</li><li>J. C. S. Joint Working Group. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+diagnosis+and+treatment+of+patients+with+vasospastic+angina+(Coronary+Spastic+Angina)+(JCS+2013).">Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013).</a> Circulation Journal. 78 (11), 2779-2801 (2014).</li><li>Kaikita, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determinants+of+myocardial+lactate+production+during+acetylcholine+provocation+test+in+patients+with+coronary+spasm.">Determinants of myocardial lactate production during acetylcholine provocation test in patients with coronary spasm.</a> Journal of American Heart Association. 4 (12), (2015).</li><li>Sueda, S., Kohno, H., Ochi, T., Uraoka, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overview+of+the+acetylcholine+spasm+provocation+test.">Overview of the acetylcholine spasm provocation test.</a> Clinical Cardiology. 38 (7), 430-438 (2015).</li></ol>

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...

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 intracoronary ACh3. 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). Additionally, MVS also seems to be involved in angina in a quarter of patients with vasospastic angina (VSA) due to epicardial coronary spasm4.
Since no technique is available for visualizing coronary microvessels in humans in vivo, MVS is defined as ischemic ECG changes associated with the reproduction of usual chest pain in the absence of epicardial spasm (90%) intracoronary provocation testing5. Usually, upon the development of ischemia, myocardial lactate consumption decreases, and a shift to lactate production occurs as myocardial ischemia increases in severity6,7. Thus, an additional myocardial lactate production measurement is considered to be useful in confirming ACh-induced microvascular myocardial ischemia during provocation testing3,4,8. Here, the current protocol presents coronary sinus (CS) lactate measurements for the diagnosis of MVS.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>ABL8000 FLEX blood gas analyzer</td>
			<td>RADIOMETER, Copenhagen, Denmark</td>
			<td>k041874</td>
			<td>The automatic lactate analyzer</td>
		</tr>
		<tr>
			<td>OUTLOOK</td>
			<td>Terumo Corp, Tokyo, Japan</td>
			<td>RQ-5JL4000</td>
			<td>The Judkins-left catheter for coronary angiography</td>
		</tr>
		<tr>
			<td>Ovisot for injection</td>
			<td>Daiichi sankyo company, limited, Tokyo, Japan</td>
			<td>871232</td>
			<td>Injectable product of acetylcholine chloride for acetylcholine provocation testing</td>
		</tr>
		<tr>
			<td>Supersheath</td>
			<td>MEDIKIT CO., LTD., Tokyou, Japan</td>
			<td>CS50P11TSM</td>
			<td>The sheath for insertion of a catheter</td>
		</tr>
		<tr>
			<td>Technowood SoftNAV Catheter</td>
			<td>Technowood Corp, Tokyo, Japan</td>
			<td>H710-FL445SH</td>
			<td>The Amplatz-left catheter for blood sampling from coronary sinus</td>
		</tr>
	</tbody>
</table>

measurement of myocardial lactate production for 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 &#956;g) 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.

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 &#181;g 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...

Watch this Scientific Journal Video about Measurement of Myocardial Lactate Production for Diagnosis of Coronary Microvascular Spasm at JoVE.com

Measurement of Myocardial Lactate Production for Diagnosis of Coronary Microvascular Spasm

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 ...

Research

JoVE Journal

Medicine

A Research Method For Detecting Transient Myocardial Ischemia In Patients With Suspected Acute Coronary Syndrome Using Continuous ST-segment Analysis

Each year, an estimated 785,000 Americans will have a new coronary attack, or acute coronary syndrome (ACS). The pathophysiology of ACS involves rupture ...

Isolating and Using Sections of Bovine Mesenteric Artery and Vein as a Bioassay to Test for Vasoactivity in the Small Intestine

Mammalian gastrointestinal systems are constantly exposed to compounds (desirable and undesirable) that can have an effect on blood flow to and from that ...

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It ...

Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by ...

Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats

Coronary artery disease is the leading cause of death worldwide. After an acute myocardial infarction, early and successful myocardial intervention via ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...

Postconditioning with Lactate-enriched Blood for Cardioprotection in ST-segment Elevation Myocardial Infarction

The beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) is attenuated by reperfusion injury. No approach has ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in GÃƒÆ’Ã‚Â¶ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...

Testing Acetylcholine Followed by Adenosine for Invasive Diagnosis of Coronary Vasomotor Disorders

More than 50% of patients with signs and symptoms of myocardial ischemia undergoing coronary angiography have unobstructed coronary arteries. Coronary ...

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In ...