Normal Coronary Circulation Research Articles

Hafif Akut Miyokarditli Genç Hastalarda İnteratriyal Blok ve Ventriküler Repolarizasyon Parametreleri

Objective: To evaluate ECG findings regarding interatrial block and ventricular repolarization and certain biochemical parameters in young patients diagnosed as acute myocarditis with normal ventricular functions. Materials and Methods: 405 patients under the age of 35 who underwent diagnostic coronary angiography between January 2014 and January 2020 were retrospectively analyzed. Patients whose ECG records could not be accessed or quality were not suitable for evaluation, with sudden cardiac death, cardiomyopathy, ejection fraction <50%, diabetes mellitus, hypertension, chronic kidney and liver failure were excluded. Patients who underwent diagnostic angiography for the differential diagnosis of acute myocarditis were assigned to myocarditis group (n: 35), and age– and sex–matched subjects with normal coronary circulation and underwent coronary angiography for any other reason were assigned to control group (n: 35). Results: Heart rate, P wave duration, P wave peak time, PR interval, QRS, QT, and Tp–e interval, QTc, Tp–e/QT and Tp–e/QTc ratios did not differ from each other. Whereas troponin (p<0.001), glucose (p=0.004), LDL (p=0.015), AST (p<0.001), ALT (p<0.026), CRP (p<0.001) levels and neutrophil count (p=0.003) were markedly higher in myocarditis group, HDL was lower (p<0.001). Conclusions: Although biochemical parameters display differences in myocarditis group, ECG findings did not differ.

AIFm2 mediated retrograde stress signaling during ischemia‐reperfusion injury in heart: Role of 4‐HNE adduction

Myocardial ischemia‐reperfusion injury results from restoration of normal coronary blood circulation after a prolonged period of circulatory arrest. Oxidative stress is one of the underlying mechanism for the pathogenesis of ischemia‐reperfusion injury. Oxidative stress results from a disturbance in the homeostatic balance between free radicle generation and availability of antioxidant molecule to scavenge them. Manganese superoxide dismutase (MnSOD), mitochondrial based antioxidant is capable of converting superoxide radical (O2•−) into oxygen. Reactive oxygen species cause lipid peroxidation and subsequent production of 4‐hydroxy‐2‐nonenal (4‐HNE) from polyunsaturated fatty acid (PUFA). 4‐HNE can modify signaling by causing adduction of cellular components such as proteins and nucleic acids. Mice lacking MnSOD specifically in cardiomyocyte (Myh6‐SOD2Δ) showed early mortality (~ 4 months) due to mitochondrial dysfunction and subsequent cardiomyopathy. Myh6‐SOD2Δ mice also had decreased mitochondrial respiration and cardiac performance shown by Seahorse XF analyzer and M‐mode echocardiography respectively. Following ischemia‐reperfusion injury, MnSOD expression was reduced shown by Real‐Time PCR array, Immunoblot, and Immunohistochemistry. Immunoblot analysis of AIFm2 showed increased expression in the ischemic heart. Normally AIFm2 localized to mitochondria, however, following ischemia 4‐HNE adducted AIFm2 translocated from mitochondria to nucleus thereby binding to DNA and resultant myocardial apoptosis. With the help of mass spectrometric analysis, it has been shown that His 174 and Cys 187 are two sites of AIFm2 where 4‐HNE adduction occurs. These results identify the role of 4‐HNE adduction in the regulation of mitochondrial retrograde signaling mediator protein apoptosis‐inducing factor associated mitochondrion protein 2 (AIFm2) during myocardial ischemia‐reperfusion injury.Support or Funding InformationNIH‐ AA025744; UL1RR033173; HL141998;NISBRE‐ COBRE1P20GM121307‐01A1; AAA‐FGAP‐5148; AHA ‐ 0950118G; 10SDG4190036This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pickering Syndrome precipitated by Angiotensin Converting Enzyme Inhibitor

Pickering syndrome is an under recognised cardio-renal syndrome where life threatening flash pulmonary edema develops in the setting of diastolic dysfunction of the heart. Renal artery stenosis induced activation of sympathetic nervous system and renin-angiotensin-aldosterone system result in fluid retention; such fluid retention in the setting of diastolic dysfunction results in flash pulmonary edema. Most patients who present with pickering syndrome have normal coronary circulation and left ventricular systolic function. We here present a case of pickering syndrome that was precipitated by initiation of angiotensin converting enzyme inhibitor therapy in a patient with undiagnosed unilateral renal artery stenosis. The incidence of flash pulmonary edema decreases on revascularization of renal artery stenosis. Underlying renal artery stenosis should be suspected in a patient with recurrent flash pulmonary edema as such patients merit from revascularization of renal artery stenosis. To the best of our knowledge we are the first to report angiotensin converting enzyme inhibitors as a precipitator of pickering syndrome.

Theoretical Model of Coronary Blood Flow Regulation: Role of Myocardium Compressive Forces.

Auto-regulatory reserve of coronary blood flow is nonuniformly distributed across the ventricular wall. MCF are thought to play an important role in determining the transmural distribution of myocardium blood flow. Here, impacts of MCF on coronary flow regulation are analyzed using a theoretical model. Coronary microvessels at various depths in the ventricular wall are represented by parallel segments. Nine vessel regions are connected in series to represent one parallel segment, which includes four vasoactive regions regulated by the wall tension, the shear stress and the metabolic demand. The nonuniform distribution of MCF is modeled and its effects on coronary flow regulation are taken into consideration by using a modified tension model and a vessel collapse model. Flow regulation behaviors in both normal and obstructed coronary circulation are simulated. Model-predicted auto-regulatory curve is shifted to the high pressure region by including the effect of MCF. Model-predicted flow distributions in obstructed coronary circulation show that severe stenosis in coronary artery would first impede myocardial blood flow in subendocardial layer. The model results indicate that MCF plays an important role in coronary flow regulation and also in determining the transmural distribution of myocardium blood flow.

Historical aspects and relevance of the human coronary collateral circulation.

In 1669, anastomoses between the right and left coronary artery were first documented by Richard Lower of Amsterdam. Using post-mortem imaging, a debate followed on the existence of structural inter-coronary anastomoses, which was not resolved before the first half of the 20ieth century in case of the presence of coronary artery disease (CAD), and not before the early 1960ies in case of the normal human coronary circulation by William Fulton. Functional coronary collateral measurements during coronary interventions were first performed only in the 1970ies, respectively in the early 1980ies. In humans, the existence of functional coronary collaterals in the absence of CAD has not been documented before 2003.Though the coronary collateral circulation has been recognized as an alternative source of blood supply to ischemic myocardium, its prognostic significance for the CAD population as a whole has been controversial until recently. The debate was due to different populations examined (acute versus chronic CAD, varying severity of CAD), to variable definitions of the term “prognosis”, to insufficient statistical power of the investigation with rare occurrence of prognostic endpoints, to short duration of follow-up and to blunt instruments employed for collateral assessment. Individually, it has been acknowledged that a well functioning collateral supply to a myocardial area at risk for necrosis reduces infarct size, preserves ventricular function, prevents ventricular remodelling and aneurysm formation. Collectively, evidence has accumulated only recently that an extensive coronary collateral circulation is a beneficial prognosticator quoad vitam. In a recent meta-analysis on the topic, the risk ratio to die from any cause for high vs low or absent collateralization in patients with subacute myocardial infarction was 0.53 (95% confidence interval 0.15–1.92; p=0.335), and for patients with acute myocardial infarction, it was 0.63 (95% confidence interval 0.29–1.39; p=0.257)¸ the relative risk to die from any cause for well vs poorly developed collaterals in patients with stable CAD was 0.59 (95% confidence interval 0.39–0.89), p=0.012.

Persistent Thebesian Vessels Involving the Right and Left Ventricles Leading to Coronary Steal Phenomena and Ischemia

We report an extremely rare case of thebesian vein microfistulae to both ventricles. A 65-year-old woman, with no major cardiovascular risk factors, presented with multiple episodes of chest pain. The resting electrocardiogram showed T-wave inversion in leads V(1) -V(4). A Dipyridamole myocardial perfusion imaging revealed large and severe inferior defect with complete reversibility. Coronary angiography showed no coronary artery disease. On contrast injection, an exaggerated capillary blush from the distal portions of the right and left coronary artery systems was seen in both ventricles, mimicking the image of ventriculography. This appearance suggests prominent thebesian vessels, a congenital communication between the coronaries and the two ventricles. The clinical relevance of these myocardial sinusoids is still not well established. Although the majority of these fistulas are small in size and with no clinical significance, they can rarely present with chest pain, cardiac arrhythmia, syncope, myocardial infarction, and/or pulmonary hypertension. These fistulae when excessive can cause significant shunting of blood to the ventricles, leading to coronary steal phenomena and ischemia. This phenomenon is facilitated by the low resistance in these microfistulae as opposed to the higher resistance in the normal coronary circulation. Due to the diffuse nature of these microfistulae, neither surgery nor transcatheter therapy is feasible. This condition can only be managed medically; however, it should be noted that vasodilator agents, such as nitrates, can worsen the coronary steal phenomenon. Our patient was treated with ranolazine with significant improvement in her symptoms, which was not reported previously. Multiple coronary artery microfistulae could be an underestimated condition of angina in patient with normal coronaries.

Risk stratification of patients with normal myocardial perfusion imaging: help comes from the periphery

This editorial refers to ‘Value of reserve pulse pressure in improving the risk stratification of patients with normal myocardial perfusion imaging’, by D. Thomas et al. , doi:10.1093/eurheartj/eht102 Nuclear imaging has an established clinical role in the non-invasive diagnosis of coronary artery disease (CAD), allowing accurate patient stratification and allocation to the best form of treatment. Semi-quantitative assessment of regional myocardial perfusion with single-photon emission computed tomography (SPECT) is a non-invasive, robust, and widely available method of assessing myocardial ischaemia and has a well established role in the clinical setting. One of the recognized strengths of SPECT perfusion imaging is its very high negative prognostic value. The annual rate of death and non-fatal myocardial infarction in patients with normal stress SPECT perfusion imaging is <1% per annum, i.e. similar to that in the general population.1 A recent retrospective study by Rozanski et al .2 reports a decline in the frequency of abnormal perfusion detected by stress myocardial perfusion imaging (MPI) with SPECT in North America over the last two decades. The frequency of an abnormal myocardial perfusion image is now very low in patients able to exercise without typical angina. These findings highlight the need for developing cost-effective diagnostic algorithms for symptomatic patients who are at low risk and do not show inducible myocardial ischaemia during MPI. On the other hand, a normal myocardial perfusion image is not the equivalent of a normal coronary circulation: diffuse atherosclerosis, balanced ischaemia, and microvascular dysfunction hamper the increase of myocardial blood flow during exercise without showing localized perfusion defects. Histopathology studies have shown that atherosclerosis is diffuse in nature, and in symptomatic patients chest pain is often considered non-coronary because no single focal stenosis is found …

Peripartum cardiac chest pain and troponin rise

The incidence of myocardial ischaemia is increasing in the obstetric population. This has been attributed to several factors including greater maternal age, the increasing incidence of obesity and diabetes, and the growing population of patients with grown-up congenital heart disease who now reach adulthood and become pregnant. A number of cases of myocardial ischaemia in pregnant women have been documented, during and after delivery, for which no cause has been established. We present a case of a nulliparous woman who developed cardiac chest pain, bradycardia, hypertension and a raised troponin I after vaginal delivery of twin boys at 36 weeks of gestation. Ischaemic electrocardiogram changes were noted. Detailed investigations demonstrated a normal coronary circulation. A patent foramen ovale was found on bubble echocardiography.

Transcatheter closure of large congenital coronary‐cameral fistulae with Amplatzer devices

To report on the methods and results of treatment of large congenital coronary-cameral fistulae by transcatheter closure with Amplatzer devices. Large coronary-cameral fistulae cause a steal phenomenon from the normal coronary circulation. Surgical closure is an option. However, transcatheter methods allow for temporary occlusion, definition of anatomy, and online assessment of successful closure. Amplatzer devices are compact occluders that can be fully delivered, collapsed, and repositioned until a satisfactory position is attained. Coronary and fistula anatomy were defined by selective coronary angiography with or without temporary occlusion. Device closure of the fistula was performed at the most distal point accessible, often from the cameral side using an arteriovenous loop method. Ten patients of median age 2.6 years (0.5-52.2) and weight 14.4 kg (6.1-67) underwent an attempt at transcatheter closure of a large fistula. In nine patients, the fistula was closed successfully with a device. There were no complications. Transcatheter closure of coronary-cameral fistula with Amplatzer devices is safe and effective.

Letter by Venetucci et al Regarding Article “Effect of High-Dose Intracoronary Adenosine Administration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: A Randomized Controlled Trial”

To the Editor: In a recent article published in the August edition of Circulation: Cardiovascular Interventions , Fokkema et al1 demonstrated that the intracoronary adenosine given during primary percutaneous coronary intervention does not reduce infarct size or the incidence of no reflow phenomenon. In this article, the authors argue that the dose of adenosine they used (240 μg given in 2 120-μg boluses) is sufficient to achieve maximal vasodilation, and they cite an article that suggests 16 μg as the dose sufficient to achieve maximal vasodilatation. This is certainly true for normal coronary circulation. However, we do not feel …

Determinants of microvascular flow

The Hagen–Poiseuille's equation states that flow ( Q ) in a tube can be calculated as follows: (Δ Pπr 4)/(8 lη ), where l and r are the length and radius of the tube, respectively, η the viscosity of the fluid flowing through the tube, and Δ P the pressure gradient across the tube. By analogy with Ohms law, the total resistance R to flow is given by Δ P/Q or Q =Δ P/R . By combining the two equations, we get [(8 l )/( πr 4)] η . In large vessels viscosity plays a minor role. For most clinical cardiologists, whose view of coronary artery flow is limited to that in the epicardial coronary arteries, the term r 4 is all important. Once in a while they also argue about the term l , especially if they see segments with long stenosis or several stenoses in series on coronary angiography. This equation is valid only for laminar flow in straight tubes. At stenoses and bifurcations, resistance is higher than that predicted by this equation due to energy loss through turbulence. In the absence of stenoses, epicardial coronary arteries offer negligible resistance to flow and most of the resistance is at the microvascular level. The filled bars in Figure 1 show the distribution of resistances across the normal coronary circulation at baseline.1 The mean aortic pressure of 90 mmHg is reduced to a pre-capillary pressure of 45 mmHg because of resistance offered by coronary arterioles (150–300 µm in diameter). There is a further 30 mm drop of pressure across the capillary bed (the post-capillary pressure is 15 mmHg). The capillaries are very small in size and offer high resistance, but since they are arranged in parallel, the total capillary resistance decreases with increasing number of capillaries. There are 8 million capillaries in the heart. The … *Corresponding author. Tel: +1 503 494 8750; fax: +1 503 494 8550. E-mail address : kauls{at}ohsu.edu

Role of nitric oxide during coronary endothelial dysfunction after myocardial infarction

This study aimed to investigate whether permanent ischaemia influences subacute vasodilatation responses of non-infarcted rat coronary vasculature, and to characterise these coronary changes. Ischaemia led to a significant impairment of the endothelium-dependent vasodilator response, while coronary vasodilatory capacity remained unaltered. In normal coronary circulation, nitric oxide (NO) and prostanoids contributed to vasodilatation, while basal involvement of endothelium-derived hyperpolarising factor was limited. Vasodilatory impairment following myocardial infarction did not originate from alterations in the prostanoid pathway, and only a slightly increased influence of K + channels was observed. However, NO-mediated vasodilatation was significantly increased after ischaemia, as also confirmed by higher mRNA and protein levels of iNOS and eNOS. Additionally, the amount of superoxide was enhanced following infarction. We conclude that subacute postinfarction remodeling is accompanied by endothelial dysfunction in non-infarcted coronary arteries. Although the NO-mediated response is increased after ischaemia, its final action is restricted due to the presence of superoxide.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Perforation of the atretic pulmonary valve: long-term follow-up

ObjectivesWe evaluated the long-term results of perforation of the pulmonary valve in patients with pulmonary atresia with an intact ventricular septum (PA-IVS). BackgroundInterventional perforation of the pulmonary valve is considered the elective first stage treatment for PA-IVS, particularly in patients with a tripartite right ventricle (RV) and normal coronary circulation. However, the long-term results of this procedure are lacking. MethodsBetween January 1991 and December 2001, 39 newborns with a favorable form of PA-IVS underwent attempted perforation of the pulmonary valve. We evaluated the early and long-term outcomes. ResultsMedian tricuspid and pulmonary zvalues were −1.2 and −2.4, respectively. Perforation was successful in 33 patients. Among them, 17 needed neonatal surgery, 13 did not need any surgery, and 3 had elective surgery after the first month of life. There were two procedure-related deaths, seven nonfatal procedural complications, and four postsurgical deaths. Compared with patients needing neonatal surgery, those having no or elective surgery had a higher incidence of a tripartite RV and a higher median tricuspid zvalue (92% vs. 53%, p = 0.04 and −1.7 vs. −0.5, p = 0.03). At a median follow-up of 5.5 years (range 0.5 to 11.5), survival was 85% and freedom from surgery was 35%. Five patients, four of whom had neonatal surgery, underwent a partial cavo-pulmonary connection. ConclusionsOur results show that this technique, although burdened by non-negligible mortality and morbidity, is effective in selected patients with a normal-sized RV. Preselection of patients allows interventional or surgical biventricular correction in the majority of cases.

Heterogeneity of myocardial blood flow and metabolism: Review of physiologic principles and implications for radionuclide imaging of the heart

Heterogeneity of myocardial blood flow and metabolism is a known feature of the coronary circulation in laboratory animals and has been reported in the normal human coronary circulation as well. This review will describe the types of heterogeneity that have been reported, how they relate to one another, and the extent to which physiologic heterogeneity of myocardial blood flow and metabolism may influence the appearance of both positron emission tomography (PET) and single photon emission computed tomography (SPECT) images of the myocardium.

Heparin and angiogenic therapy.

Collateral circulation is an alternative source of blood supply to the myocardium if this is jeopardized by failure of the original vessel to provide adequate flow. Gradual occlusion, or a high grade stenosis of the coronary arteries, is frequently associated with collateral development in patients with coronary artery disease. Although the existence of collateral circulation in such patients is associated with improved clinical outcomes, the net effect is inadequate to compensate for the flow deficit in the native coronary arteries. Why the flow reserve through collateral circulation is limited to half of that of normal coronary circulation is not clear. However, several pieces of evidence indicate that it is possible to promote collateral development intentionally to alleviate myocardial ischaemia under stressed conditions. Angiogenic therapy is defined as the intervention used to treat or prevent pathological clinical situations characterized by local hypovascularity by stimulating or inducing collateral development. Until our clinical study, there had been no reports, except for an intense year-long exercise training programme, showing enhanced collateral development through some kind of intervention. We have demonstrated for the first time that the combination of heparin and exercise-induced myocardial ischaemia enhances collateral function and growth in patients with stable effort angina. Recently, angiogenic growth factors such as basic fibroblast growth factor and vascular endothelial growth factor were successfully used to stimulate cardiac angiogenesis to improve collateral circulation not only in various animal models but also in clinical settings. Heparin was discovered by McLean in 1916. Since then, many investigators have contributed to elucidate the basic and clinical properties of heparin. It has recently been recognized that heparin potentiates the activity of growth factors. This property of heparin

Lung volume reduction surgery for a patient receiving mechanical ventilation after a complex cardiac operation

Lung volume reduction surgery (LVRS) may be indicated after cardiac operations to improve pulmonary mechanics in patients with severe emphysema who are receiving mechanical ventilation. This intervention facilitates successful weaning. History. A 57-year-old woman who formerly smoked cigarettes had severe mitral stenosis and pulmonary emphysema and was evaluated for mitral valve replacement. She had been receiving long-term home oxygen therapy for 7 months. The patient had been repeatedly hospitalized during the previous year because of exacerbation of chronic obstructive pulmonary disease. At a previous anesthesiologic evaluation, the patient had been considered to be ineligible for operation because a reduction of respiratory function of at least 30% is to be expected in the early postoperative phase after mitral valve replacement. Preoperative cardiac findings. Echocardiograpy documented severe mitral stenosis (mitral valve area 0.8 cm) with an almost immobile mitral valve. The left ventricular ejection fraction was normal (64%). Both atria were dilated. Coronary angiography revealed a normal coronary circulation. Catheterization of the left side of the heart demonstrated slight mitral and aortic insufficiency (regurgitation 20%). The diastolic pressure gradient across the mitral valve was 13 mm Hg. Preoperative pulmonary findings. The patient was extremely limited in her everyday activities. The data on her preoperative pulmonary function are summarized in Table I. Blood gas analysis while she was receiving medical therapy showed an oxygen tension of 54 mm Hg, a carbon dioxide tension of 44.4 mm Hg, and an oxygen saturation of 89% without supplemental oxygen. Computed tomographic scan of the chest revealed moderately heterogenous bilateral distribution of the emphysema, with predominance in the apical segments of the lower lobes and the right upper lobe. Operative procedures and postoperative course. The initial plan was to perform mitral valve replacement with the patient in ventricular fibrillation and without crossclamping of the aorta. This operation was to be followed by bilateral LVRS. During cannulation of the ascending aorta, however, a type A dissection occurred. Therefore, not only was the mitral valve replaced (CarboMedics mitral valve, 27 mm; Sulzer CarboMedics, Inc., Austin, Texas), but the ascending aorta (Vascutec-Gelvave, 26 mm) was as well, with deep hypothermic circulatory arrest (16° C for 17 minutes) and retrograde cerebral perfusion. LVRS was postponed to optimize hemostasis and stabilize hemodynamics. Eight hours after the operation, an unstable early postoperative course necessitated reoperation for pericardial tamponade. Bilateral pneumothorax developed on the first postoperative day, and extubation was impossible. On the left side, a severe air leak persisted. Mechanical ventilation with an inspired oxygen fraction of 1.0 was needed. Bilateral LVRS was performed on the third postoperative day. The left side was operated on through a thoracotomy to ensure the inclusion of the air leak in the area of resection. The right side was operated by means of video-assisted thoracoscopy. The apical segments of the lower lobes on both sides and the most destroyed parts of the upper lobe on the right side (anterior and apical segment) were resected with nonbuttressed endoscopic staples (TLC 45; Ethicon Endo-Surgery, Cincinnati, Ohio). Immediately after LVRS, ventilation became more effective. The tidal volume increased by 40%, and the inspired oxygen fraction could be reduced from 1.0 to 0.65.

Role of nitric oxide in coronary vasomotion during handgrip exercise

Endothelium-dependent modulation of coronary vasomotion during increased sympathetic tone remains unclear in normal and atherosclerotic human coronory arteries. We evaluated the role of endothelium-derived nitric oxide in vasomotion during isometric exercise in normal subjects (n = 7) and in patients with coronary artery disease (CAD) (n = 10). Coronary blood flow and epicardial coronary artery diameter to the handgrip test were measured before and after intracoronary administration of 100 micromol/min of N(G)-monomethyl L-arginine (L-NMMA). Heart rate and aortic blood pressure increased during handgrip test. Handgrip test caused a significant dilation in the diameter of the epicardial coronary artery in normal subjects (9.9% +/- 3.9%, mean +/- SD) and in the diameter of smooth segments of patients with CAD (5% +/- 3.7%, p < 0.05 vs normal subjects). In contrast, the diameter of irregular segments in patients with CAD decreased during handgrip test (-9.8 +/- 3.9%). After L-NMMA, the epicardial coronary artery significantly increased during handgrip test compared with before L-NMMA in normal subjects. L-NMMA did not have any effect on handgrip test induced vasodilation in the smooth segments and vasoconstriction in the irregular segments in the patients with CAD. Handgrip test-induced increases in coronary blood flow did not change after L-NMMA in both groups. Nitric oxide does not play a major role in HNG-induced vasodilation in epicardial and microcirculatory vessels in normal human coronary circulation. Although the decreased release in nitric oxide may modulate the abnormal response of the epicardial coronary artery to handgrip test, this does not explain the paradoxic constrictive response from the depressed but still dilatory response in the patients with CAD.

Importance of Nitric Oxide in the Coronary Artery at Rest and During Pacing in Humans

Objectives. The purpose of this study was to investigate the role of endothelium-dependent vascular regulation in the human coronary circulation during rest and hyperemic states.Background. Evidence of the role of nitric oxide (NO) during metabolic demand is not consistent in animal and human coronary circulation.Methods. NG-Monomethyl-l-arginine (l-NMMA), a specific inhibitor of NO synthesis, was infused into the left anterior descending coronary artery at rest and during rapid atrial pacing in 18 subjects—9 with normal coronary arteries (control) and 9 with atherosclerotic coronary arteries. The diameter of the epicardial coronary artery was measured by quantitative coronary angiography. Vasodilation of the coronary microcirculation was assessed using an intracoronary Doppler FloWire.Results. Infusion of 25 μmol/min of l-NMMA reduced the diameter of the proximal and distal epicardial coronary artery segments by 8 ± 2% (mean ± SE) and 11 ± 2%, respectively (p < 0.05) in the control subjects. The coronary blood flow (CBF) decreased by 33 ± 13% during l-NMMA infusion. l-NMMA caused similar changes in the diameter of the distal epicardial segment and the CBF in patients with coronary artery disease. The proximal vessel diameter did not change significantly during infusion of l-NMMA. During pacing, infusion of l-NMMA caused the same changes in vessel diameter as before pacing in both groups, but did not affect CBF.Conclusions. Our findings indicate that NO synthesis maintains basal vasomotor tone in both conduit and resistance vessels in the normal human coronary circulation. Although NO release was impaired in the large epicardial coronary arteries in patients with atherosclerosis, NO still regulated vascular tone in the small epicardial coronary arteries and arterioles. Our results suggest that vasodilation in arterioles during increased myocardial oxygen demand is mediated by metabolic or myogenic mechanisms, or both, rather than by endothelium-dependent production of NO.(J Am Coll Cardiol 1997;29:85–92)>

Direct vasomotor effects of isoflurane in subepicardial resistance vessels from collateral-dependent and normal coronary circulation of pigs.

The purpose of the current investigation was to determine and compare the direct effect of isoflurane on normal resistance coronary arteries and similarly sized coronary arteries in collateral-dependent (CD) circulation. A differential vasomotor effect of isoflurane might contribute to flow redistribution, either adverse or favorable, between normal and CD regions. The authors used a swine model of chronic coronary occlusion. Six weeks after ameroid occluder placement around the left circumflex artery, the heart was removed. Myocardial blood flow, measured in vivo before the removal, was lower during rapid atrial pacing in the CD region than in the normally perfused region. These in vivo studies established the existence and location of CD circulation. Subepicardial microvessels, measuring approximately 100 microns, were dissected from both the CD region and the normal region. Either with or without preconstriction of the vessels with the thromboxane analogue U46619 1 microM, direct vasomotor effect of isoflurane was examined in vitro by video microscopy. In addition, vasomotor responses to endothelin-1, the endothelium-dependent dilator adenosine 5' diphosphate, and the endothelium-independent dilator sodium nitroprusside were compared between CD and normal resistance vessels. Isoflurane caused greater concentration-dependent constriction of the normal vessels than of the CD vessels (P < 0.05); this constrictive effect was masked by preconstriction of the vessels. Vasodilation of ADP was less in CD vessels than in normal vessels (P < 0.001), but vasodilation to sodium nitroprusside was not significantly different (P = 0.45). Vasoconstriction to endothelin-1 was greater in CD vessels than in normal vessels (P < 0.01). The vasoconstrictive effect of isoflurane normally observed in coronary resistance vessels is impaired in resistance vessels that supply a CD area. The basis of this may be related to endothelial dysfunction.