Sudden occlusion of a saphenous vein bypass graft relieved by direct injection of nitroglycerine

An unusual case of sudden occlusion of a saphenous vein bypass graft to the right coronary artery, during a coronary angtographlc study, is presented. Such occlusion was relieved by direct intragraft nitroglycerine injection, as typically happens in case of coronary arterial spasm. A possible pathogenetlc mechanism, based on the present knowledge of platelet aggregation and the role of the powerful vasoactive agent Throm-boxane A₂, is discussed.     

Disparity between serotonin- and acetylcholine-provoked coronary artery Spasm

Background and hypothesis: Intrinsic vasoactive substances, such as serotonin and acetylcholine, are known to provoke coronary artery spasm in patients with vasospastic angina. It remains unclear, however, whether these different agents, which activate different receptors, produce spasms at the same sites in these patients. The present study was designed to clarify the disparity of receptor agonist-induced coronary artery spasms in the same patients. Methods: We conducted sequential provocative tests of coronary artery spasm by acetylcholine, serotonin, and ergonovine in 20 patients with rest angina examined with quantitative coronary angiography. Results: Coronary artery spasms were provoked in all patients at 27 spastic sites. In 13 patients, ergonovine provoked spasms and in 10 of 13 patients who were diagnosed with variant angina, both acetylcholine and serotonin provoked spasms at the same sites where ergonovine also did. In 4 of 13 patients, spasms were provoked by serotonin but not by acetylcholine. In the remaining seven patients, whose spasms were induced by ergonovine, spasms were produced by acetylcholine but not by serotonin. On coronary angiography, the spastic sites for both acetylcholine and serotonin, and those for serotonin alone, were located in the proximal segments of coronary arteries, whereas the spastic sites for acetylcholine alone were located in the distal segments. Conclusions: This study documented the disparity between serotonin- and acetylcholine-induced spasms. Provocative tests using agents that activate different receptors may produce coronary artery spasms at the same and/or different sites, and this disparity may reflect the clinical heterogeneity of vasospastic ischemic syndrome.     

Coronary artery spasm during cardiac angiography

Unexpected occurrence of coronary artery spasm is sometimes observed during cardiac catheterization. We report here two cases of coronary artery spasm with hypotension and urticaria subsequent to administration of contrast material. The etiology of coronary artery spasm is discussed.     

Evidence that thromboxane contributes to ventricular fibrillation induced by reperfusion of the ischaemic myocardium

In many victims of sudden cardiac death, resulting from ventricular fibrillation, there is no post-mortem evidence of coronary thrombosis [7] and it is thought that spasm of the coronary arteries or reversal of such spasm may be the cause of the ventricular fibrillation. When coronary vasospasm is reversed, either spontaneously or by other means, arrhythmias are frequently observed when perfusion of the formerly ischaemic area of the myocardium is restored. These “reperfusion arrhythmias” are particularly severe and frequently fatal since they often progress to ventricular fibrillation. They also appear to be resistant to standard antiarrhythmic therapy [5] suggesting that their aetiology may vary from that of arrhythmias observed during myocardial ischaemia. We have reported previously [3] that thromboxane A₂, a potent vasoconstrictor which promotes platelet aggregation, is released during acute myocardial ischaemia and that this release is related to the occurrence of early cardiac arrhythmias. In the present study we have extended our experiments in anaesthetized greyhounds to investigate whether thromboxane plays a role in the reperfusion arrhythmias that occur following the release of a 40 min coronary artery occlusion. Dazoxiben (UK-37, 248), a selective thromboxane synthetase inhibitor [6], markedly increased survival following coronary artery reperfusion suggesting that thromboxane is an important contributory factor in post-reperfusion ventricular fibrillation.     

Correlation of the location of coronary arterial spasm with the lead distribution of ST segment elevation during variant angina

The lead distribution of ST segment elevation produced by severe “spasm” of major coronary arteries was correlated with the specific artery involved in a group of 110 cases of variant angina with single vessel coronary arterial spasm made up from eight cases personally observed and 102 cases abstracted from published literature.The most sensitive and specific lead for ST elevation during anterior descending (LAD) coronary arterial spasm was V₃; V₂ was almost as good. For spasm of either the right (RCA) or circumflex coronary artery (CMFX), Leads 3 and aV_F showed ST elevation most frequently; electrocardiographically it was difficult to distinguish between spasm of these two vessels. ST elevation in Leads V₅ and V₆ was not specific, occurring in some cases of spasm of each of the three major coronary arteries. ST elevation in Lead V₁ occurred in either RCA or LAD spas, but never in CMFX spasm. ST elevation in Lead 1 was never seen with isolated RCA spasm.No single lead can detect all cases of transient ST elevation. Simultaneous monitoring of Leads 3 and V₃ would have detected 98.2% of 333 cases of ST elevation reviewed, and addition of Lead aV_L would have detected most of the remainder. These findings should be considered in lead selection for monitoring to detect ST elevation, and in using the ECG to identify spastic coronary arteries.     

Multiple endothelial injury in epicardial coronary artery induces downstream microvascular spasm as well as remodeling partly via thromboxane A2

OBJECTIVES: The study was undertaken to develop a coronary microvascular spasm model in pigs by repeated epicardial coronary artery endothelial injury. BACKGROUND: The pathophysiologic mechanisms responsible for coronary microvascular spasm remain unclear, in large part because a suitable animal model has yet to be found. METHODS: Balloon endothelial denudation was done just distal to the site of an implanted Doppler flowmeter in the left anterior descending coronary artery (LAD) every two weeks for a total of four times. Changes in LAD blood flow by intracoronary administration of vasoactive agents were assessed before each denudation. RESULTS: In the epicardial LAD endothelial denudation pigs, decreases in LAD blood flow caused by acetylcholine were augmented. Before denudation, it was - 15 +/- 4%, and at week 8 (i.e., two weeks after the fourth denudation) it was -100% (i.e., zero flow [p < 0.01]). The LAD flow changes in response to 5-hydroxytryptamine (5-HT) changed from an increase to a decrease, accompanied by medial thickening of microvessels in the LAD perfusion area. These flow responses were observed without significant changes in LAD diameter. In contrast, the LAD blood flow responses to acetylcholine and 5-HT did not change throughout the experiment in pigs given aspirin and a thromboxane A2 (TXA2) synthase inhibitor orally. CONCLUSIONS: This microvascular spasm model indicates that hypersensitivity to vasoactive substances in the microvascular beds as well as microvascular remodeling are brought about partly through TXA2. This model should be useful for examining the pathophysiology and treatment of microvascular angina.     

The potential role of endothelin as a vasoconstrictor substance in congestive heart failure.

A rapidly growing body of data supports the concept of in situ regulation of vascular tone: the ability of vasoactive substances to regulate vascular tone at their site of production within the wall of the vasculature. Sufficient data exist to suggest that ineffective production or response to endothelium-dependent vasodilator substances, or excessive production or responsiveness to endothelium-dependent vasoconstrictor substances may play an important role in cardiovascular disorders such as hypertension, coronary artery spasm, restenosis following coronary angioplasty, and congestive heart failure. The present review summarizes data which support the concept that endothelin, a potent vasoconstrictor produced by the endothelium, may play a role in the excessive vasoconstriction of heart failure. Increased circulating plasma endothelin may be particularly relevant to the range of pulmonary vasoconstriction encountered in congestive heart failure, with a correlation revealing that the greatest increase of plasma endothelin occurs in patients with marked pulmonary hypertension within the congestive heart failure patients studied.     

Coronary artery spasm induced in miniature swine: angiographic evidence and relation to coronary atherosclerosis

In a swine model of coronary artery spasm, the pathogenetic role of coronary atherosclerosis was examined. Following endothelial balloon denudation of the left circumflex coronary artery (LCX), male miniature swine were fed a laboratory chow diet containing 2% cholesterol. Although there was no difference in the extent of coronary vasoconstrictive response to histamine, serotonin, and ergonovine between the left anterior descending coronary artery (LAD) and the LCX before the denudation, a constrictive response was significantly augmented along the denuded portion of the LCX 1 and 3 months after the denudation. Augmented vasoconstrictive responses to phenylephrine were never evidenced. Histamine was the most potent vasoactive agent, and coronary artery spasm was provoked repeatedly by intracoronary or intravenous administration of histamine in the presence or absence of cimetidine. The spasm was provoked only in the denuded portion of the LCX, the same area which was angiographically normal before the occurrence of the spasm. Histologically, atherosclerotic changes were predominant along the denuded portion of the LCX. Topologic correlation was suggested between the site of the spasm and the site of coronary atherosclerosis. It is concluded that in this swine model of coronary artery spasm, atherosclerotic changes may be an important causative factor, in terms of an activation of multiple receptor-operated calcium channels in the coronary artery.     

内皮素受体表达上调在冠状动脉痉挛中的作用机制

冠状动脉痉挛需要两个局部基本条件:(1)冠状动脉平滑肌高反应性,即冠状动脉对收缩物质刺激的敏感性增高,表现为收缩增强、甚至痉挛;(2)冠状动脉局部有足够可以引起平滑肌痉挛的收缩物质。内皮素1是人体内收缩血管最强的物质。研究证明,冠状动脉痉挛的危险因素(吸烟和高血脂)能激活ERK1/2信号通路,引起冠状动脉平滑肌细胞内皮素受体表达上调,从而导致血管对内皮素1刺激的敏感性和反应性明显增高,表现为收缩增强、甚至痉挛。本文综述了近年来有关内皮素受体表达上调与冠状动脉痉挛分子发病机制研究方面的新进展,为临床防治冠状动脉痉挛提供新思路和药物治疗新靶点。     

Coronary Artery Spasm during Angiography in a Pediatric Heart Transplant Recipient: Subsequent Prevention by Intracoronary Nitroglycerin Administration

Coronary artery spasm can occur during coronary angiography in pediatric heart transplant recipients. The angiographic appearance can suggest allograft vasculopathy. We report coronary artery spasm in a pediatric heart transplant recipient in whom intracoronary nitroglycerin administration prevented a repetition of spasm upon subsequent diagnostic coronary angiography. Additional studies of dose response, particularly in cardiac transplant recipients, may help determine whether lower doses of intracoronary nitrates, such as that administered to our patient, can be effective in preventing coronary artery vasospasm in pediatric heart transplant recipients.Key words: Child, coronary angiography, coronary vasospasm/etiology/pathology/radiography, graft survival, heart transplantation, male, postoperative complications/radiographyCoronary artery spasm has been reported to occur in 4.9% of adult heart transplant recipients during subsequent coronary angiography,¹ but its frequency in children during coronary angiography after heart transplantation is unreported. Because coronary artery spasm can produce generalized luminal narrowing, such spasm can be difficult to distinguish angiographically from cardiac allograft vasculopathy, although this last is morphologically different and at times distinguishable from coronary spasm.²We describe a case wherein coronary spasm resulted from coronary angiography and produced temporary cardiac compromise, leading to a provisional diagnosis of graft vascular disease. Subsequent angiography, preceded by the intracoronary administration of nitroglycerin, showed the affected vessels to be closer to normal in appearance and had no adverse effects, which suggested that transient vasospasm had been responsible for the angiographic appearance of diffuse luminal narrowing.     

乙酰胆碱诱发冠状动脉痉挛试验中缓慢型心律失常的原因探讨

目的探讨乙酰胆碱诱发冠状动脉痉挛试验中缓慢型心律失常的发生原因。方法64例因静息性胸痛而接受冠状动脉造影的患者,排除具有缺血意义的病变后进行乙酰胆碱试验,术中连续记录心电图变化,比较痉挛组和非痉挛组缓慢型心律失常情况,并选择冠状动脉痉挛合并缓慢型心律失常的25例患者分别在冠状动脉内注射硝酸甘油及静脉注射阿托品后重复乙酰胆碱试验,观察冠状动脉痉挛和心律失常的变化情况。结果乙酰胆碱试验痉挛组(46例)和非痉挛组(18例)缓慢型心律失常的发生率无差异(P>0.05),痉挛组中14例经过冠状动脉内注射硝酸甘油后重复乙酰胆碱试验均未能诱发痉挛,但12例仍出现缓慢型心律失常,另11例静脉注射阿托品后重复乙酰胆碱试验均未诱发冠状动脉痉挛,仅1例出现缓慢型心律失常。结论乙酰胆碱试验中的缓慢型心律失常可能与乙酰胆碱的药理作用有关而与冠状动脉痉挛无关。     

非典型性冠状动脉痉挛患者的临床特点及近期预后

目的总结非典型性冠状动脉痉挛患者的临床特点。方法选择临床具有静息性胸痛或胸闷,且冠状动脉造影无显著狭窄的64例患者进行乙酰胆碱冠状动脉痉挛激发试验,将乙酰胆碱试验阳性即冠状动脉痉挛患者根据胸痛或胸闷发作时心电图上是否有ST段抬高分为典型变异型心绞痛组（典型组）和非典型变异型心绞痛性冠状动脉痉挛组（非典型组）,比较两组的临床症状特点（危险因素、心电图和核素心肌灌注显像负荷试验结果以及冠状动脉造影和乙酰胆碱试验的影像学）。结果共有46例（72％,46／64）患者诱发冠状动脉痉挛,其中典型组和非典型组分别为12及34例。典型组的平均年龄偏低（P〈0．05）,血脂代谢紊乱在非典型组更常见,运动心电图试验两组多为阴性,核素灌注心肌显像负荷试验两组均表现有反向再分布,冠状动脉造影典型组多为轻度局限性狭窄或节段性内膜不光滑,肌桥发生率更高,乙酰胆碱试验多诱发节段性痉挛。而非典型组为弥漫性血管细小、内膜不光滑、僵硬,血管迂曲伴远端血流缓慢,乙酰胆碱试验多诱发弥漫性血管痉挛,并可见多支血管同时痉挛。结论非典型性冠状动脉痉挛较典型变异型心绞痛更常见,且具有一定的特征性,应引起临床医生高度重视。     

Vasospastic angina induced by nonsteroidal anti-inflammatory drugs

We report two cases of vasospastic angina associated with anaphylactic reaction caused by nonsteroidal antiinflammatory drugs (NSAIDs). Both patients exhibited anaphylactic manifestations, such as general rash and urticaria, along with angina pectoris with electrocardiographic ST-segment elevations after suppository administration of diclofenac sodium or indomethacin, the most commonly used NSAIDs. Although these patients had normal coronary arteriograms, intracoronary administration of ergonovine or acetylcholine provoked diffuse coronary artery spasms accompanied by chest pain and ischemic ST-segment changes. It is therefore suggested that an allergic mechanism may be involved as a causative factor of the coronary artery spasm induced by NSAIDs.     

Association Between Inflammatory Markers,Hemostatic Markers,and Traditional Risk Factors on Coronary Artery Spasm in Patients with Normal Coronary Angiography

Background

Coronary artery spasm is an important pathophysiological mechanism in some forms of myocardial ischemic disease. The relationship between inflammatory markers, mean platelet volume (MPV), and coronary artery spasm is unclear.

Methods and Results

During coronary angiography, methylergometrin was injected intravenously to 345 patients with chest pain but without significant coronary disease on angiogram to provoke coronary artery spasm. Based on provocation test results, patients were divided into 2 groups: spasm group (60 patients) and nonspasm group (285 patients). Inflammatory markers (C‐reactive protein, CRP; white blood cells; polymorphonuclear neutrophils, PMN; monocytes, MO; lymphocytes, LY), hemostasis markers (MPV; platelet count; fibrinogen [FIB]; D‐dimers), and traditional risk factors (body mass index; hyperlipidemia; triglycerides [TGs]; total, low‐density, and high‐density lipoprotein cholesterol [TC, LDL‐C, and HDL‐C]) were measured and compared between groups. More male patients experienced spasm (23.56% vs. 11.11%, P = 0.002). CRP, PMN, and MO were significantly higher in the spasm group (P < 0.05). There was no significant difference in serum levels of LDL‐C, HDL‐C, TG, TC, LY, MPV, and FIB between groups. Smoking and hyperlipidemia were more common among patients with spasm; males more frequently were smokers (58.04% vs. 46.78%, P = 0.041). By multivariate analysis, smoking, PMN, and MO were significantly associated with coronary artery spasm with odds ratios of 3.52 (95% CI 1.79–6.90, P = 0.0001), 1.21 (95% CI 1.07–1.46, P = 0.04), and 5.35 (95% CI 1.37–21.07, P = 0.01), respectively.

Conclusions

Inflammation may partake in the pathogenesis of coronary artery spasm. Smoking, PMN count, and MO count appear to be clinical risk factors for coronary artery spasm. Conversely, coronary artery spasm does not seem to be associated with abnormalities in thrombogenesis. (J Interven Cardiol 2014;27:29–35)

     

Kounis syndrome with Samter–Beer triad treated with intracoronary adrenaline

Kounis syndrome is a well‐described clinical condition characterized by the simultaneous occurrence of chest pain and an allergic reaction accompanied by clinical and laboratory findings of angina caused by inflammatory mediators released during an allergic insult. We present the case of a 50‐year‐old male with the Samter–Beer triad of asthma, nasal polyps, and salicylate intolerance with an ST elevation myocardial infarction complicated with cardiac arrest due to multi‐vessel coronary artery spasm secondary to aspirin anaphylaxis. Adrenaline is recommended during anaphylaxis but is controversial in Kounis syndrome as it may worsen coronary spasm. We report the use of intracoronary adrenaline in successfully reversing coronary artery spasm in this hemodynamically unstable patient. © 2015 Wiley Periodicals, Inc.     

Platelet depletion in experimental myocardial infarction

Summary Accumulation of platelets in the microvasculature after acute myocardial ischemia may exacerbate tissue injury through the formation of microthrombi and by the release of vasoactive substances. To assess the role of platelets in myocardial ischemic injury and infarction, circulating platelets were reduced by 94±2% (mean±S.E.M.) with sheep antiserum to canine platelets. Regional myocardial ischemia was produced by occlusion of the left circumflex coronary artery (LCCA) for 90 min followed by reperfusion for 5 hours. Infarct size did not differ significantly between antiplatelet serum and nonimmune serum groups: 36±8vs. 43±4% of the area at risk, determined by a post-mortem dual staining technique (p>0.05). A second occlusion-reperfusion control group, sacrificed at 24 hours, did not differ from 5 hr reperfused groups with regard to infarct size. Coronary sinus thromboxane B₂ (TXB₂) concentrations were not altered significantly by platelet depletion. Histopathologic examination confirmed the presence of necrosis in the infarcted myocardium and revealed substantial leukocytic infiltration in both groups. The results suggest that circulating platelets are not required for the full expression of myocardial ischemic injury resulting from temporary coronary artery occlusion followed by reperfusion.     

histamine—can it cause an acute coronary event?

Myocardial infarction (MI) occurring during the course of an allergic urticarial reaction in the absence of systemic hypotension has been rarely reported. This paper reports the case of a 28-year-old woman with no significant risk factors for coronary artery disease who presented with generalized urticaria associated with chest pain and had electrocardiographic and enzymatic evidence of an acute MI. Review of the literature suggests that local histamine release may induce spasm of the coronary vasculature, thus leading to myocardial ischemia and infarction.     

Histamine provocation of clinical coronary artery spasm: Implications concerning pathogenesis of variant angina pectoris

Twelve patients with nonexertional chest pain and nonobstructive fixed coronary disease (< 50% luminal diameter narrowing) were given histamine to investigate the potential role (coronary artery H₁ receptor agonism) of the endogenous agent in producing coronary artery spasm (CAS). Histamine, at intravenous dose of 0.5 to 1.0 μg/kg/min, provoked CAS in four patients. In six patients neither histamine nor ergonovine provoked spasm, and these patients were considered by chronic follow-up evaluation to have noncardiac etiology for their chest pain syndrome. In one patient CAS was provoked with ergonovine but not by histamine, and one ergonovine-positive patient had an equivocally positive histamine result. Pretreatment with cimetidine (H₂ receptor antagonism) was necessary to avoid unpleasant side effects of histamine. Thus these observations indicate that histamine should be included among the specific agents capable of inducing CAS and provide new insight concerning the mechanism(s) causing variant angina pectoris.     

Lethal presentations of coronary artery spasm after an event-free period of six years following initial diagnosis

Isolated coronary artery spasm without atherosclerotic obstruction is an unusual cause of myocardial infarction (MI). A middle-aged woman presented to our institution in 2001 with acute inferior MI due to coronary artery spasm at the mid segment of the dominant left circumflex coronary artery. After being well for 6 years, she was readmitted again in 2007 with the same type of severe retrosternal chest pain. Electrocardiography (ECG) showed ST-segment elevation over the inferior leads. The chest pain resolved with sublingual nitroglycerin and emergency diagnostic coronary angiography showed normal coronary arteries. Two months later, the patient developed another episode of severe retrosternal chest pain at home, followed by cardiac arrest. An onsite ECG showed ventricular fibrillation and immediate defibrillation was carried out. She was readmitted to the hospital and recovered over the next few days. In view of the recurrent coronary artery spasm causing myocardial infarction and ventricular fibrillation, an implantable cardioverter defibrillator was implanted. The patient was well at 2-month follow up.     

Prinzmetal's variant form of angina with arteriographic evidence of coronary arterial spasm

Spasm of the proximal right coronary artery was arteriographically demonstrated during an episode of chest pain in a patient with Prinzmetal's variant form of angina. A right aortocoronary saphenous vein bypass procedure was performed but, despite a patent graft, the angina recurred and the patient died. The only significant finding at autopsy was an eccentric atherosclerotic plaque that narrowed the right coronary artery by 75 percent at the site of the spasm. These findings support Prinzmetal's hypothesis that this variant form of angina is produced by spasm of a coronary artery with a seriously compromised lumen.