Role of Coronary Vasoconstriction in Ischemic Heart Disease and Search for Novel Therapeutic Targets

Maseri, Attilio; Beltrame, John F.; Shimokawa, Hiroaki

doi:10.1253/circj.cj-09-0033

Cited by 82 publications

(29 citation statements)

References 77 publications

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“…The association of MB with CAS was first suggested by Grover and Mancini [10] in 1984 when they reported the development of CAS at the bridged segment in patients during cardiac pacing, and also established the connection between CAS and endothelial dysfunction [11]. The systolic milking of the MB segment in the coronary artery may produce endothelial damage, which may stimulate platelet aggregation and CAS [12,13]. The role of CAS in the development of myocardial ischemia has been clarified [14].…”

Section: Discussionmentioning

confidence: 99%

Angiographic and Clinical Characteristics according to Intracoronary Acetylcholine Dose in Patients with Myocardial Bridge

Rha

Choi

et al. 2013

Cardiology

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Objectives: It is well known that myocardial bridge (MB) is a risk factor of vasospastic angina. However, clinical and angiographic characteristics according to different acetylcholine (ACh) dose in patients with MB are not clarified yet. Methods: A total 483 consecutive patients who had angiographically proven MB underwent the intracoronary ACh provocation test. ACh was injected by incremental doses of 20, 50 and 100 μg into the left coronary artery. We evaluated the clinical and angiographic characteristics of patients with MB according to 3 different ACh doses. Results: The baseline clinical and procedural characteristics are well balanced among the three groups. The MB patients who responded to the lower ACh dose (20 μg) had higher incidence of baseline spasm, severe vasospasm and diffuse long spasms (>30 mm) than those who responded to the higher doses (50 and 100 μg). The incidence of 12-month mortality and recurrent chest pain was higher in the lower ACh dose group (20 μg). Conclusion: The patients with MB significantly reacting at the low ACh dose had more pronounced baseline spasm, severe and diffuse long coronary artery spasm, higher 12-month mortality and recurrent chest pain than those reacting with the higher ACh doses, suggesting that more intensive medical therapy will be required.

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Section: Discussionmentioning

confidence: 99%

Angiographic and Clinical Characteristics according to Intracoronary Acetylcholine Dose in Patients with Myocardial Bridge

Rha

Choi

et al. 2013

Cardiology

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“…1,10 Yet, no definitive experimental evidence has demonstrated that vasospasm triggers coronary arterial plaque injury — due to a dearth of suitable experimental animal preparations. 11,12 Previous investigations have demonstrated disruption of diet-induced brachiocephalic lesions 13,14 and coronary lesions 15 in mice, though these studies did not identify triggers of plaque disruption.…”

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confidence: 99%

Vasospasm of Atherosclerotic Coronary Arteries Precipitates Acute Ischemic Myocardial Damage in Myocardial Infarction–Prone Strain of the Watanabe Heritable Hyperlipidemic Rabbits

Shiomi

Ishida

Kobayashi

et al. 2013

ATVB

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Objective This study tested the hypothesis that vasospasm can trigger of coronary plaque injury and acute ischemic myocardial damage. Approach and Results Hyperlipidemic myocardial infarction–prone rabbits (WHHLMI strain) received an intravenous bolus of ergonovine maleate (0.45 μmol/kg) during intravenous infusion of norepinephrine (12 nmol/kg/min) to provoke coronary spasm in vivo. After this treatment, coronary angiography demonstrated vasospasm, and the electrocardiogram (ECG) showed ischemic abnormalities (ST depression/elevation and T-wave inversion) in 77% of animals (23/30). These changes normalized after nitroglycerin injection. In rabbits that demonstrated these ECG findings for more than 20 minutes, echocardiograms showed left ventricular wall motion abnormality. Serum levels of heart-type fatty acid binding protein, cardiac troponin-I, and myoglobin increased markedly 4 hours after spasm provocation. In coronary lesions of WHHLMI rabbits with provoked coronary spasm, we observed intimal injury in 60.9% in the form of endothelial cell protrusions (39.1%), denudation (30.4%), and macrophage extravasation (56.5%). Plaque disruption with luminal thrombus, however, was only seen in 2/23 animals (8.7%), and mural microthrombus was rarely observed (4.3%). Conclusions These observations show that provocation of vasospasm in WHHLMI rabbits associates with subsequent ischemic myocardial damage. Although treatment with spasmogens altered aspects of plaque morphology, for example endothelial protrusion and macrophage emigration, thrombosis was rare in these animals with chronic atherosclerotic disease.

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“…The present results suggest the onset of angina pectoris-like symptoms and/or non-fatal myocardial infarction; however, the frequency of occlusive thrombi after the disruption of coronary plaques was very low [11]. Previous studies reported that coronary spasm plays an important role in the pathogenesis of not only variant angina, but also ischemic heart disease, including other forms of angina, acute myocardial infarction, arrhythmias, and ischemic sudden death [3, 5, 6, 16, 17, 20]. These findings are consistent with the results of the present study; therefore, we speculated that the WHHLMI rabbit is useful as an animal model of experimentally provoked coronary spasm and subsequent myocardial ischemia.…”

Section: Discussionmentioning

confidence: 54%

“…Based on clinical observations, coronary spasm has been implicated as one of the causes of acute ischemic coronary events [5], such as sudden cardiac death [15], lethal arrhythmia [3], variant angina [6], and acute myocardial infarction [17, 20]. Due to its relationship with coronary heart disease (CHD), the gravity of coronary spasm was reconfirmed in the onset of acute ischemic coronary events in Western countries [8].…”

Section: Introductionmentioning

confidence: 99%

High susceptibility of atherosclerotic coronary arteries to the onset of vasospasm and angina pectoris-like symptoms due to coronary spasm in WHHLMI rabbits

Koike

Tamura

et al. 2016

Exp. Anim.

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We examined the relationship between atherosclerosis and the provocation of coronary spasm as well as the influence of coronary spasm on the onset of acute ischemic myocardial disease. Coronary spasm was provoked in anesthetized normal Japanese white (JW) rabbits and myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for coronary atherosclerosis and myocardial infarction, by injecting ergonovine during the infusion of norepinephrine through a marginal ear vein. A decrease in contrast flow in the left circumflex artery was observed on coronary angiograms. Ischemic changes were observed on the electrocardiograms of 29% (2/7) of JW and 79% (27/34, P=0.007) of WHHLMI rabbits. The frequency of coronary spasm was significantly high in rabbits with severe coronary plaques showing diffuse lesions. Left ventricle motility in vasospasm-positive rabbits, which was evaluated with echocardiograms, was decreased by 29% following the ergonovine injection (P<0.001), and every serum ischemic marker markedly increased 4 h after the provocation of vasospasm. These results demonstrate that atherosclerotic coronary arteries are positively related to the provocation of vasospasm, and vasospasm in severe atherosclerotic coronary segments evokes angina pectoris-like findings and/or non-fatal myocardial infarction. WHHLMI rabbits may be a novel animal model for angina pectoris and acute ischemic heart disease.

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Role of Coronary Vasoconstriction in Ischemic Heart Disease and Search for Novel Therapeutic Targets

Cited by 82 publications

References 77 publications

Angiographic and Clinical Characteristics according to Intracoronary Acetylcholine Dose in Patients with Myocardial Bridge

Angiographic and Clinical Characteristics according to Intracoronary Acetylcholine Dose in Patients with Myocardial Bridge

Vasospasm of Atherosclerotic Coronary Arteries Precipitates Acute Ischemic Myocardial Damage in Myocardial Infarction–Prone Strain of the Watanabe Heritable Hyperlipidemic Rabbits

High susceptibility of atherosclerotic coronary arteries to the onset of vasospasm and angina pectoris-like symptoms due to coronary spasm in WHHLMI rabbits

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