Coronary vasomotion in myocardial ischemia

Coronary vasomotion can be characterized with respect to its localization in the coronary vascular tree as segmental (epicardial, collateral, resistive), with respect to its localization in the myocardium as transmural (subendocardial vs subepicardial), or with respect to its mediators (myogenic, metabolic, endothelial, neuronal, humoral). Coronary vessels exhibit a marked coronary dilator reserve which can be recruited to maintain regional myocardial blood flow and contractile function distal to coronary stenoses. Even in the presence of myocardial ischemia, coronary vessels retain a significant dilator reserve which can only be recruited pharmacologically. A critical reduction in blood flow at the level of epicardial coronary arteries is the underlying cause for a range of pathophysiological processes that extends from changes in the hemodynamic severity of a fixed stenosis to dynamic coronary stenosis, and finally to true spasm. These pathophysiological processes differ in the quantitative contribution of active coronary vasoconstriction and fixed mechanical obstruction to the initiation of myocardial ischemia; the mediators of epicardial coronary constriction are largely unclear. Significant alpha 2-adrenergic coronary constriction of the resistive vessels, predominantly in the subendocardium, contributes to the initiation of poststenotic myocardial ischemia during sympathetic activation and exercise in experimental studies. Intracoronary alpha-blockade with phentolamine also attenuates exercise-induced myocardial ischemia in patients with stable angina. Experimental analyses of regional myocardial blood flow and contractile function in ischemic myocardium reveal that a discrepancy between O2-supply (flow) and O2-demand (function) does not exist on a hemodynamic level. Regional myocardial blood flow and function are instead adequately reduced in ischemic myocardium. Thus, absolute regional myocardial blood flow--as a result of coronary vasomotion and blood flow redistribution--is the significant determination of myocardial ischemia.     

Significance of the sympathetic nervous system for the coronary circulation

The activation of sympathetic nerves plays a significant role in the initiation of acute myocardial ischemia. In this review the effects of sympathetic nerves on coronary blood flow are summarized. Under physiological conditions the increase in myocardial performance during sympathetic activation is accompanied by metabolic coronary vasodilation. The resulting increase in coronary blood flow is limited by about 30% by alpha-adrenergic coronary constriction. Extravascular compression and beta-adrenergic coronary dilation are of minor importance during sympathetic activation. With exhausted coronary reserve distal to severe coronary stenoses metabolic vasodilation during sympathetic activation is not possible any more; an alpha 2-adrenoceptor-mediated coronary vasoconstriction now predominates. This coronary constriction induces ischemia of the post-stenotic myocardium. The alpha-antagonists Phentolamine and Rauwolscine as well as the calcium-antagonist Nifedipine prevent poststenotic coronary constriction and myocardial ischemia. Also in the genesis of coronary arterial spasm the sympathetic nervous system may play an important role; the constriction of epicardial coronary arteries is mediated by alpha 1-adrenoceptors. The sympathetic nervous system is not only involved in the initiation of myocardial ischemia, but is also activated by ischemia. This feedback-activation of sympathetic nerves leads to an aggravation of myocardial ischemia.     

Peri-interventional coronary vasomotion

A percutaneous coronary intervention (PCI) is a unique condition to study the effects of ischemia and reperfusion in patients with severe coronary atherosclerosis when coronary vasomotor function is compromised by loss of endothelial and autoregulatory vasodilation. We studied the effects of intracoronary non-selective α-, as well as selective α(1)- and α(2)-blockade in counteracting the observed vasoconstriction in patients with stable and unstable angina and in patients with acute myocardial infarction. Coronary vasoconstriction in our studies was a diffuse phenomenon and involved not only the culprit lesion but also vessels with angiographically not visible plaques. Post-PCI vasoconstriction was reflected by increased coronary vascular resistance and associated with decreased LV-function. α (1)-Blockade with urapidil dilated epicardial coronary arteries, improved coronary flow reserve and counteracted LV dysfunction. Non-selective α-blockade with phentolamine induced epicardial and microvascular dilation, while selective α(2)-blockade with yohimbine had only minor vasodilator and functional effects. Intracoronary α-blockade also attenuated the no-reflow phenomenon following primary PCI. This article is part of a Special Issue entitled "Coronary Blood Flow".     

Louis F. Bishop lecture. Role of coronary artery spasm in symptomatic and silent myocardial ischemia

The revival of the concept of coronary spasm has stimulated research into coronary artery disease. Observations in patients with variant angina have substantially contributed to the appreciation of painless myocardial ischemia. However, the presence or absence of pain during ischemic episodes is not related to the cause of ischemia, because painless ischemia can be observed in variant angina (caused by spasm), in effort-induced angina (caused by increased myocardial demand) and in myocardial infarction (caused by thrombosis). Continuous monitoring initially of patients with variant angina and subsequently of patients with unstable and stable angina proved that often painful and painless ischemic episodes are caused by a transient impairment of regional coronary blood flow rather than by an excessive increase of myocardial demand. The transient impairment of coronary flow appears to be caused by dynamic stenosis of epicardial coronary arteries. This most often occurs at the site of atherosclerotic plaques encroaching on the lumen to a variable extent. Dynamic stenosis can be caused by 1) "physiologic" increase of coronary tone, as in stable angina, 2) spasm, as in variant angina, and 3) thrombosis, usually in combination with "physiologic" changes in tone or with spasm, or both, as in unstable angina. The mechanisms of spasm, as typically observed in variant angina, are different from those of "physiologic" increase of tone; they appear to be related to a local alteration that makes a segment of coronary artery hyperreactive to a variety of constrictor stimuli causing only minor degrees of constriction in other coronary arteries. The nature of this abnormality, which may remain stable for months and years, is yet unknown.     

Reprint of: the paradox of α-adrenergic coronary vasoconstriction revisited

Activation of coronary vascular α-adrenoceptors results in vasoconstriction which competes with metabolic vasodilation during sympathetic activation. Epicardial conduit vessel constriction is largely mediated by α(1)-adrenoceptors; the constriction of the resistive microcirculation largely by α(2)-adrenoceptors, but also by α(1)-adrenoceptors. There is no firm evidence that α-adrenergic coronary vasoconstriction exerts a beneficial effect on transmural blood flow distribution. In fact, α-blockade in anesthetized and conscious dogs improves blood flow to all transmural layers, during normoperfusion and hypoperfusion. Also, in patients with coronary artery disease, blockade of α(1)- and α(2)-adrenoceptors improves coronary blood flow, myocardial function and metabolism. This article is part of a Special Issue entitled "Coronary Blood Flow".     

The paradox of α-adrenergic coronary vasoconstriction revisited

Activation of coronary vascular α-adrenoceptors results in vasoconstriction which competes with metabolic vasodilation during sympathetic activation. Epicardial conduit vessel constriction is largely mediated by α₁-adrenoceptors; the constriction of the resistive microcirculation largely by α₂-adrenoceptors, but also by α₁-adrenoceptors. There is no firm evidence that α-adrenergic coronary vasoconstriction exerts a beneficial effect on transmural blood flow distribution. In fact, α-blockade in anesthetized and conscious dogs improves blood flow to all transmural layers, during normoperfusion and hypoperfusion. Also, in patients with coronary artery disease, blockade of α₁- and α₂-adrenoceptors improves coronary blood flow, myocardial function and metabolism.     

Epicardial coronary artery constriction with intravenous ethanol

Although in vitro studies have demonstrated ethanol-induced coronary artery constriction, in vivo reports suggest an ethanol-related coronary dilator effect with increases in coronary blood flow. The principal difference in these studies is the demonstration of epicardial coronary constriction with ethanol, while dilation is described only in resistance vessels. Clinical studies have noted evidence of myocardial ischemia following ethanol ingestion in patients with coronary artery disease, suggesting ethanol-related constriction of diseased epicardial coronary arteries. This study hypothesized that intravenous ethanol would constrict canine epicardial coronary arteries while producing arteriolar resistance vessel dilatation. Ten closed-chest mongrel dogs weighing 24 +/- 1 kg (mean +/- SEM) were given 8 g of ethanol intravenously over 30 min. Left anterior descending and circumflex proximal artery diameters were measured by quantitative coronary angiography; myocardial flow was measured by Xenon washout, and myocardial flow distribution was measured with radioactive microspheres. Baseline proximal left anterior descending and circumflex artery areas were 6.3 +/- 0.5 and 5.8 +/- 0.4 mm2, respectively. Up to 30% left anterior descending and circumflex proximal artery narrowing was noted at 60 and 90 min following ethanol infusion. The constriction was reversed with nitroglycerin. There was a decrease in left anterior descending artery flow but no change in circumflex artery flow at 60 min. Blood ethanol level varied from 520 micrograms/ml initially to 205 micrograms/ml 90 min after the infusion terminated (intoxication = 1500 micrograms/ml). These data suggest that ethanol has significant vasoconstrictor action in vivo on epicardial coronary arteries.     

Beneficial actions of nitrates in cardiovascular disease

Nitroglycerin and the long-acting nitrates have been used in cardiovascular medicine for > 100 years. Nitrates are widely utilized for the various anginal syndromes and are also used in congestive heart failure and patients with left ventricular dysfunction. The potential mechanisms for relief of myocardial ischemia with nitrates are multiple. The nitrovasodilators are a related group of drugs that result in the formation of nitric oxide (NO) within vascular smooth muscle cells. NO stimulates the enzyme guanylate cyclase, which results in increases in cyclic guanosine monophosphate and vasodilation. In the presence of atherosclerosis, endothelial dysfunction is ubiquitous and associated with decreased NO availability, probably due to increased destruction of NO by free radical anions. Nitrovasodilators, including the nitrates, supply exogenous NO to the vascular wall and improve the vasodilator state. When nitrates are administered, endothelial-dependent stimuli cause relaxation rather than constriction in the setting of endothelial dysfunction. Nitrates also have antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation. This may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction. Nitrate hemodynamic effects have been long known. They are primarily modulated through a decrease in myocardial work that results from smaller cardiac chambers operating with lower systolic and diastolic pressures. These changes are caused by a redistribution of the circulating blood volume away from the heart to the venous capacitance system, with a fall in venous return to the heart. The afterload or arterial effects of nitrates are also useful in decreasing myocardial oxygen consumption. Considerable evidence confirms a variety of mechanisms whereby nitrates increase coronary blood flow, including epicardial coronary artery dilation, stenosis enlargement, enhanced collateral size and flow, improvement of endothelial dysfunction, and prevention or reversal of coronary artery vasoconstriction. These effects help increase nutrient coronary blood flow to zones of myocardial ischemia. Recent data with the nitroglycerin patch confirm that myocardial ischemia is decreased after nitrate administration. Nitroprusside, another nitrovasodilator, is a commonly used intravenous agent for lowering arterial pressure and left ventricular filling pressure. This drug is highly effective for the treatment of acute or severe hypertension and congestive heart failure. However, there are data suggesting that nitroprusside may be deleterious in the presence of acute myocardial ischemia, perhaps by shunting blood away from zones of jeopardized myocardial blood flow. Therefore, nitroprusside cannot be recommended to treat myocardial ischemia; intravenous nitroglycerin should be used in this context.     

Regulation of coronary resistance vessels and large coronary arteries

There is now considerable evidence for alpha-adrenergic regulation of coronary resistance vessels and large coronary arteries based on studies of chronically instrumented, conscious animals. Infusion of norepinephrine at low doses causes reduction of coronary blood flow with a slight increase in arterial pressure, indicating intense coronary vasoconstriction. This coronary constrictor response was reversed to coronary vasodilation with infusion of norepinephrine after alpha-adrenergic blockade. Stimulation of alpha 1- and alpha 2-adrenergic receptors with phenylephrine and B-HT 920, respectively, also increased calculated coronary vascular resistance in the conscious animal. These effects were eliminated by selective alpha 1-adrenergic blockade with prazosin and by selective alpha 2-adrenergic blockade with rauwolscine. Stimulation of the carotid chemoreceptor reflex elicits a period of intense coronary vasoconstriction, characterized by a decrease in coronary blood flow despite increased arterial driving pressure. This response was eliminated by prior alpha-adrenergic blockade or a combination of cardiac sympathetic denervation and adrenalectomy. Using chronically implanted ultrasonic crystals to measure the epicardial coronary diameter instantaneously and continuously in conscious dogs, marked vasodilation of the large coronary arteries was observed with administration of nitroglycerin or calcium-channel antagonists; in contrast, activation of alpha-adrenergic receptors with methoxamine induced substantial constriction, characterized by a reduction in coronary artery diameter in the face of elevated distending pressure. The regulation of large coronary arteries is further complicated by the fact that these vessels are responsive to changes in myocardial metabolic demands and coronary blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacological mechanisms to attenuate sympathetically induced myocardial ischemia

Summary Distal to a coronary stenosis, resting myocardial blood flow and function can be maintained by a compensatory dilation of the poststenotic vascular bed and an increased collateral blood flow from adjacent coronary vessels. Under this condition, electrical stimulation of cardiac sympathetic nerves, as well as their activation during sympathoexcitatory reflexes and exercise, induces a poststenotic alpha₂-adrenoceptor-mediated coronary constriction and a beta-adrenoceptor-mediated, tachycardia-related redistribution of blood flow away from the ischemia myocardium. Thus, activation of cardiac sympathetic nerves can precipitate poststenotic myocardial ischemia.In experimental studies in anesthetized, vagotomized dogs, as well as in conscious chronically instrumented dogs, selective alpha₂-adrenoceptor antagonists and calciumchannel blockade with nifedipine were able to attenuate the sympathetically induced poststenotic myocardial ischemia. Beta-adrenoceptor blockade with atenolol was only proven beneficial as long as there was a heart-rate reduction. Conversely, a specific braydcardic agent (ULFS-49) also exerted beneficial effects.Myocardial ischemia can activate cardiac sympathetic afferents and then, by a spinal reflex, can in turn activate sympathetic efferents and aggravate the severity of myocardial ischemia. This vicious cycle could be interrupted by segmental epidural anesthesia with procaine as well as by blockade of sympathoexcitation at the central nervous level with clonidine in anesthetized dogs.     

Mechanisms of pain in angina pectoris—A critical review of the adenosine hypothesis

Summary Clinical characteristics: Angina pectoris represents a visceral pain caused by reversible myocardial ischemia. The majority of ischemic attacks are symptomless. When pain is manifested, it appears late during the ischemic event. The pain is complex in its quality and bears little relation to the region of myocardial ischemia. Pain shows a sensitive dependence on initial conditions suggesting a mechanism with deterministic chaotic dynamics for the association between myocardial ischemia and pain.Neurophysiological substrate: Ganglia are present within the heart, particularly in epicardial fat. The blood supply of intrinsic cardiac ganglia arises primarily from branches of the proximal coronary arteries. Both afferent and efferent neurons within the intrinsic cardiac nervous system exist, while the majority of neurons in that location may be local circuit neurons. Integration takes place not only in the intrinsic cardiac nervous system, but also in mediastinal, middle cervical, and stellate ganglia. Cardiac afferent receptors are also connected to cell bodies in dorsal root and nodose ganglia, as well as intrathoracic ganglia. Myocardial regions have no spatial representation in these ganglia. Adenosine, among a number of substances, can modulate the activity generated by cardiac afferent nerve endings and intrinsic cardiac neurons. Such effects appear to be exerted at A1 receptors.Adenosine as a pain messenger: During myocardial ischemia adenosine is released in large quantities into the interstitial space. The endothelium takes up the major amount of adenosine. Thus only small increments of adenosine are detected in the blood-stream. Given as an intravenous bolus to healthy volunteers or to patients with ischemic heart disease and angina pectoris, adenosine provokes angina pectorislike pain, which is similar to habitual angina pectoris with regard to quality and location. Pain is provoked in the absence of ECG signs of ischemia. Patients with asymptomatic myocardial ischemia are less sensitive to adenosine, whereas patients with Syndrome X are more sensitive with respect to adenosine-provoked pain. When adenosine is given intraarterially, including into the coronary arteries, pain is provoked in the corresponding vascular bed. Adenosine-provoked pain and ischemic pain are counteracted by previous administration of the adenosine receptor antagonist theophylline. Adenosine-provoked pain is enhanced by nicotine or substance P.Conclusion: Angina pectoris displays complex characteristics at both the clinical and neural substrate levels. Adenosine is the only candidate substance identified that fulfills criteria for a messenger between myocardial ischemia and the genesis of pain. It is concluded that ischemically released adenosine causes specific spatiotemporal neural summation of afferent neuronal activity, which elicits an alarm reaction with manifestation of pain.     

Effects of synthetic human atrial natriuretic peptide on the human coronary circulation in subjects with normal coronary arteries.

Atrial natriuretic peptide (ANP) is recognized as an "endogenous vasodilator". The purpose of this study was to determine the effects of a clinical therapeutic dose of synthetic alpha-human ANP on the coronary circulation in 15 subjects with normal coronary arteries and normal ventricular function. The epicardial coronary arterial diameter was measured by selective coronary arteriography. Coronary blood flow was estimated from the arterial cross-sectional area and the flow velocity determined using an subselective intracoronary Doppler catheter. ANP, 0.03 micrograms/min/kg given intravenously over 15 minutes, caused a dilation of the large epicardial coronary artery (n = 8): the diameter of the proximal left anterior descending artery dilated from 2.6 +/- 0.4 to 3.1 +/- 0.5 mm (p less than 0.01). Mean arterial pressure decreased from 89 +/- 5 to 83 +/- 5 mmHg (p less than 0.01); heart rate did not change during ANP infusion. Estimated coronary blood flow significantly increased (n = 6, p less than 0.01), and thus the coronary vascular resistance decreased after ANP infusion, suggesting an ANP-induced dilation of resistance vessels. The present study demonstrates that in human subjects a clinical dose of ANP by intravenous infusion dilates both the large epicardial and small resistance coronary vessels. These results suggest a potentially beneficial role for ANP in reducing the severity of myocardial ischemia in patients with ischemic heart disease.     

alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans

The use of quantitative coronary angiography, combined with Doppler and PET, has recently been directed at the study of alpha-adrenergic coronary vasomotion in humans. Confirming prior animal experiments, there is no evidence of alpha-adrenergic coronary constrictor tone at rest. Again confirming prior experiments, responses to alpha-adrenoceptor activation are augmented in the presence of coronary endothelial dysfunction and atherosclerosis, involving both alpha(1)- and alpha(2)-adrenoceptors in epicardial conduit arteries and microvessels. Such augmented alpha-adrenergic coronary constriction is observed during exercise and coronary interventions, and it is powerful enough to induce myocardial ischemia and limit myocardial function. Recent studies indicate a genetic determination of alpha(2)-adrenergic coronary constriction.     

Microvascular Angina: Assessment of Coronary Blood Flow,Flow Reserve,and Metabolism

Microvascular angina (MVA) is an often overlooked cause of significant chest pain. Decreased myocardial perfusion secondary to dysregulated blood flow in the microvasculature can occur in the presence or absence of obstructive epicardial coronary artery disease. The corresponding myocardial ischemia and angina is now a well-established diagnosis, made by detection of decreased coronary flow reserve (CFR). Although low CFR and MVA are associated with poor prognosis, there is initial evidence for reversibility of this abnormal vascular regulation with aggressive medical therapy and control of associated risk factors. Current assessment of MVA is carried out predominantly during cardiac catheterization; however, noninvasive techniques to assess CFR are being developed, including PET, MRI, and CT modalities. Quantitative tracer techniques or imaging of metabolic disturbances reflecting ischemia will likely enhance diagnostic approaches for such patients as well as allow more frequent monitoring of response to therapy.     

冠状动脉微循环障碍评估方法的研究进展

微血管性心绞痛(microvascular angina,MVA)是由于冠状动脉微循环血流失调引起心肌灌注减少造成的,是经常受到忽略的一种胸痛,阻塞性和非阻塞性的心外膜冠状动脉疾病均可存在。通过测定冠状动脉血流储备(coronary flow reserve,CFR),MVA可得到明确诊断。目前MVA的评估主要是通过有创的心导管检查,应用冠状动脉内多普勒导丝可以检测冠状动脉微循环的功能,但过程复杂、耗时,还会给患者带来一定的风险。最近,一种新的冠状动脉造影方法通过测定时间密度曲线以计算CFR是可行的,可替代冠状动脉内多普勒超声。然而,评估CFR的非侵入性检查技术也正在逐步发展,其中包括正电子放射断层扫描、MRI和CT等。反应缺血的定量追踪技术和灌注成像技术可能将进一步增强MVA的诊断,同时可长期监测治疗效果。     

Effect of ketanserin on proximal and distal coronary constrictor responses to intracoronary infusion of serotonin in patients with stable angina, patients with variant angina, and control patients.

BACKGROUND. Serotonin, released by aggregating platelets, may contribute to or cause myocardial ischemia by constricting epicardial vessels. Experimental studies suggest that this constriction is mediated by two distinct serotonin receptor subtypes: 5-hydroxytryptamine1-like (S1-like) and 5-hydroxytryptamine2 (S2). METHODS AND RESULTS. To determine the relative contribution of S1-like and S2 receptors to the vasoconstrictor effects of serotonin, we studied the effect of ketanserin (0.75 mg, intracoronary), a selective S2 receptor antagonist, on the constrictor response of human coronary vessels to intracoronary infusions of serotonin. In control patients (n = 7), serotonin (10(-4) mol/l) caused significant (p less than 0.05) constriction only in distal segments, which was significantly (p less than 0.05) inhibited by ketanserin. In stable angina patients (n = 8), serotonin (10(-4) mol/l) caused significant constriction in proximal (p less than 0.01) and distal (p less than 0.01) segments, which was significantly inhibited by ketanserin in proximal (p less than 0.05) but not distal (p = 0.30) segments. In patients with variant angina (n = 3), epicardial occlusion at the site of preexisting stenoses in proximal locations occurred at infused concentrations of 10(-6) (one patient) or 10(-5) (two patients) mol/l. The infusion of the same concentration of serotonin after ketanserin again caused epicardial occlusion. CONCLUSIONS. Our results suggest that functionally important S1-like receptors that mediate vasoconstriction exist in the epicardial vessels of patients with stable or variant angina. Their activation, either at hyperreactive sites in patients with variant angina or in the distal epicardial vessels of patients with chronic stable angina, may contribute to or cause myocardial ischemia when serotonin is released after the intracoronary activation of platelets.     

Current concepts of pathophysiology, circadian patterns, and vasoreactive factors associated with myocardial ischemia detected by ambulatory electrocardiography.

Transient ST-segment changes during continuous ECG monitoring occur not only in many clinical ischemic syndromes, but also in a proportion of the normal population. The pathophysiology of episodes of ST-segment change that represent transient periods of myocardial ischemia varies according to the underlying disease process, which may include stable coronary artery disease, unstable angina, variant angina, and syndrome X. Patients with stable coronary artery disease have episodes of ischemia as a result of an imbalance between increases in myocardial oxygen demands and changes in coronary blood flow due to physiologic changes in coronary vasomotor tone. Both these factors are subject to a circadian rhythm that results in a preponderance of ischemia in the morning hours. Vasospasm, often beyond the physiologic range, in localized segments of epicardial coronary arteries causes ischemia and ST-segment changes in variant angina, whereas luminal thrombosis with superimposed vasoconstriction is an important cause of continued ischemia in unstable angina.     

Beneficial effects of the coronary collateral circulation on tachycardia-induced myocardial ischemia during experimental coronary stenosis

This study was designed to determine whether coronary collaterals have preventive effects on tachycardia-induced myocardial ischemia under partial restriction of proximal coronary artery inflow. Studies were carried out in dogs with developed coronary collaterals and control dogs. ST-elevation in epicardial and intramyocardial electrograms was used for assessing the degree of regional myocardial ischemia. In control dogs with coronary constriction (80% reduction of i.d.) pacing-induced tachycardia produced significant ST-elevation, 1.48 +/- 0.17 mV in the inner layer and 0.79 +/- 0.29 mV in the middle layer at a cardiac rate of 150/min, 3.58 +/- 0.38 mV in the inner layer, 2.73 +/- 0.38 mV in the middle layer, and 1.93 +/- 0.36 mV in the outer layer at a rate of 180/min. In dogs with moderate collaterals ST-segment elevation was only 1.41 +/- 0.18 mV in the inner layer and 0.96 +/- 0.24 mV in the middle layer at a rate of 180/min. In dogs with abundant collaterals there was no significant ST-elevation during tachycardia. These findings indicate that blood supply to the affected myocardium via developed collaterals is sufficient to meet graded increases in metabolic requirements under the condition of limited coronary flow reserve in an experimental model simulating angina pectoris.     

Acute pulmonary edema with normal coronary arteries: mechanism identification by ergonovine stress echocardiography

Coronary spasm is a constriction of the epicardial coronary arteries that produces myocardial ischemia. It is considered the main mechanism of the dynamic coronary artery stenosis. The standard method for diagnosing coronary spasm is the ergonovine test during diagnostic coronary angiography. Another test currently used is stress echocardiography with intravenous ergonovine injection. We present the case of a patient with angina, acute pulmonary edema and normal angiographic coronary arteries in which stress echocardiography with ergonovine demonstrated transient severe mitral regurgitation.     

New insights into the management of myocardial ischemia.

Episodes of ST depression are closely related to transient decreases in regional myocardial perfusion during physical or mental stress. At the onset of these events, there is transient constriction of atherosclerotic stenoses, with an increase in myocardial demand as reflected by increases in heart rate and blood pressure. Recent research has shown that normal epicardial coronary arteries respond to these provocations and to increasing blood flow with progressive vasodilation. In contrast, atherosclerotic vessels lose this ability to dilate and may show paradoxical constriction. This abnormal constriction parallels the response of the arteries to acetylcholine, which can be used to assess the ability of the coronary endothelium to regulate vasodilation. The loss of endothelium-dependent vasodilation appears to be an important functional manifestation of coronary atherosclerosis and a potential triggering mechanism for transient ischemia. Dysfunctional endothelium may also result in a procoagulant surface, with cell adherence and local thrombus formation. Restoration of normal endothelial function is likely to emerge as an important therapeutic objective in the management of myocardial ischemia and coronary atherosclerosis.