Segment Of Epicardial Coronary Artery Research Articles

Ondas ultra-sônicas de alta freqüência causam disfunção endotelial em artérias coronárias caninas epicárdicas

Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10(-9)-10(-4) M), Ach (10(-9)-10(-4) M) and NaF (0.5-9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10(-9)-10(-5) M) or SNP (10(-9)-10(-6) M) was unaltered following exposure to either low or high ultrasonic energy outputs. These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.

High-Resolution Imaging of Myocardial Bridging

A 57-year-old man presented with a sudden onset of chest pain, which suggested the possibility of myocardial infarction. Coronary angiography revealed a myocardial bridge in the left anterior descending coronary artery. The myocardial bridge decreased the diameter of the artery substantially during systole (Panel A, with arrow pointing to myocardial bridge). Optical coherence tomography showed no evidence of atherosclerosis but did show vessel patency during diastole (Panel B) and collapse during systole (Panel C). A myocardial bridge is a band of myocardial tissue overlying a segment of epicardial coronary artery. Myocardial bridging is a congenital abnormality that typically occurs in . . .

Role of L-type calcium channels and PKC in active tone development in rabbit coronary artery

The present study investigated active tone development in isolated ring segments of rabbit epicardial coronary artery. Endothelium-denuded (E-) or endothelium-intact (E+) vessels treated with the NO synthase inhibitor N(omega)-nitro-L-arginine (100 microM) developed active tone, which was enhanced by stretch and reversed by the NO donor sodium nitroprusside (SNP; IC(50)=9 nM). Nifedipine abolished active tone and the contractile response to phorbol dibutyrate (PDBu; 10 nM) with the same potency (IC(50)=8 nM), whereas 300 nM PDBu responses were only partially blocked by nifedipine. The classical and novel PKC inhibitors GF-109203X (IC(50)=1-2 microM) and chelerythrine (IC(50)=4-5 microM) and the classical PKC inhibitor Gö-6976 (IC(50)=0.3-0.4 microM) blocked both active tone and 10 nM PDBu responses with similar potency. Active tone development was associated with depolarization of membrane potential (E(m)) and a shift to the left of the E(m)-vs.-contraction relationship determined by varying extracellular potassium. The depolarization and leftward shift were reversed by either chelerythrine (10 microM) or SNP (30 nM). PDBu (100-300 nM) increased peak L-type calcium channel (Ca(v)) currents in isolated coronary myocytes, and this effect was reversed by chelerythrine (1 microM) or Gö-6976 (200 nM). SNP (500 nM) reduced Ca(v) currents only in the presence of the PKA blocker 8-bromo-2'-O-monobutyryl-cAMPS, Rp isomer (10 microM). In conclusion, active tone development in coronary artery is suppressed by basal NO release and is dependent on both enhanced Ca(v) activity and classical PKC activity. Both E(m)-dependent and -independent processes contribute to contraction. Our results suggest that one E(m)-independent process is direct enhancement of Ca(v) current by PKC.

Myocardial Bridging of the Left Anterior Descending Coronary Artery and Anomalous Origin of Circumflex Coronary Artery: Preoperative Assessment with MDCT

WEB This is a Web exclusive article. yocardial bridging is anatomically defined as the muscle overlying the intramural segment of a major epicardial coronary artery—mainly the midportion of the left anterior descending (LAD) coronary artery. This congenital variation has been associated with myocardial ischemia, conduction disturbances, myocardial infarction, and sudden death [1]. The pathophysiology of myocardial bridges is characterized by external phasic systolic vessel compression with a persistent mid to late diastolic diameter reduction [2]. Percutaneous transluminal coronary angioplasty with stent placement, traditional coronary artery bypass grafting, and longitudinal myotomy of the overlying myocardial tissue band have all been used to treat symptomatic patients refractory to medical management [1]. We report the case of a patient with symptomatic myocardial bridging of the LAD coronary artery evaluated using MDCT for preoperative assessment.

Myocardial bridging of the right coronary artery and emotional stress: A fatal link?

Myocardial bridging (MB) is a congenital condition where a segment of a major epicardial coronary artery runs intramurally (tunnelled artery) through the myocardium. [1]. It has been reported in autopsy studies with an incidence rate of 5.4–85.7% [2], while the prevalence varies substantially among studies with much higher rate at autopsy versus angiography (5–12%) [3,4]. The most frequent place of occurrence is the proximal half of the anterior descending branch of the left coronary artery (60%), while the other branches are overbridged less often. The muscular bridges of the branches of the right coronary artery are rarer and more variable in their form of location (2.8–11.4%) [2]. While the course is generally benign, myocardial ischemia, infarction, ventricular arrhythmia and sudden death have been reported, frequently associated with hypertrophic cardiomyopathy and coronary atherosclerosis [3]. We present a case of sudden death of a young man having a right coronary artery myocardial bridging as the only identifiable cause of death. The pathogenesis of the fatal event is discussed with reference to the histological findings.

Anatomical and Functional Evaluation of Myocardial Bridging on the Left Anterior Descending Artery by Cardiovascular Magnetic Resonance Imaging

A myocardial muscle bridge spans a segment of a major epicardial coronary artery that is located in the myocardium. This anatomic configuration can be responsible for angina pectoris, arrhythmias or even death. The current reference standard for diagnosis is conventional x-ray coronary angiography showing systolic compression of an epicardial vessel and the typical angiographic "milking effect." We report the case of a patient with myocardial bridging on the left anterior descending artery, in whom a combination of noninvasive high resolution display of the coronary artery lumen, visualization of the myocardium and functional assessment of blood flow during dobutamine stimulation by cardiovascular magnetic resonance imaging was performed.

Multifocal coronary artery myocardial bridging involving the right coronary and left anterior descending arteries detected by ECG-gated 64 slice multidetector CT coronary angiography

Myocardial bridging is a congenital condition in which a segment of a major epicardial coronary artery has an intramyocardial course. Myocardial bridging is usually confined to a single vessel (typically the mid segment of the left anterior descending artery) and is usually asymptomatic, however, bridging may be associated with chest pain, myocardial infarction, or sudden cardiac death. While more commonly identified at autopsy, myocardial bridging is occasionally diagnosed by coronary angiography with identification of concomitant myocardial bridging involving both the left and right coronary arteries appearing to be uncommon. We present three patients presenting with atypical chest pain symptoms in whom concomitant right coronary artery and left anterior descending artery myocardial bridging was identified by ECG gated multidetector computed tomography (MDCT).

Myocardial bridging

Myocardial bridging, a congenital coronary anomaly, is a clinical condition with several possible manifestations, and its clinical relevance is debated. This article reviews current knowledge about the anatomy, pathophysiology, clinical relevance, and treatment of myocardial bridging. Myocardial bridging is present when a segment of a major epicardial coronary artery, the 'tunnelled artery', runs intramurally through the myocardium. With each systole, the coronary artery is compressed. Myocardial bridging has been associated with angina, arrhythmia, depressed left ventricular function, myocardial stunning, early death after cardiac transplantation, and sudden death. Evidence indicates that the intima beneath the bridge is protected from atherosclerosis, and the proximal segment is more susceptible to development of atherosclerotic lesions because of haemodynamic disturbances. New techniques (e.g. intravascular ultrasonography and intracoronary Doppler studies) have revealed new characteristics and pathophysiologic processes such as diastolic flow abnormalities. Medical treatment generally includes beta-blockers. Nitrates should be avoided because symptoms may worsen. Intracoronary stents and surgery have been attempted in selected patients. Additional research is needed to define patients in whom myocardial bridging is potentially pathologic, and randomized multicentre long-term follow-up studies are needed to assess the natural history, patient selection, and therapeutic approaches.

Comparison of outcomes of percutaneous coronary intervention of ostial versus nonostial narrowing of the major epicardial coronary arteries

Outcomes of percutaneous coronary intervention (PCI) of the ostia of the major epicardial coronary arteries in the modern era of stenting have not been clearly defined. We evaluated data from all PCIs performed from 1998 to 2001 in the proximal segments of the major epicardial coronary arteries entered into a large cardiac database and compared ostial with nonostial PCI outcomes. Of 2,484 patients who underwent PCI of a proximal coronary artery (left anterior descending, left circumflex, or right coronary), 223 patients had ostial narrowing and 2,261 patients had proximal, nonostial narrowing. Baseline characteristics were similar between the 2 groups, except that patients with ostial narrowing tended to be older and have shorter narrowings than did patients with nonostial narrowings. Stenting occurred in 89% of all patients and was similar in patients with ostial or nonostial narrowings. Procedural success was the same for ostial and nonostial PCI (96% vs 95%, p = 0.95). One-year event-free survival rate was lower in patients who underwent ostial PCI (69% vs 80%, p = 0.0019), largely due to a greater need for repeat PCI (19% vs 10%, p <0.0001). Multivariate analysis showed that ostial location, age, angina class, and number of diseased vessels were independent predictors of the occurrence of cardiac events. PCI of ostial narrowings of the major epicardial coronary arteries was relatively safe. However, at 1 year, patients who underwent ostial PCI had an increased rate of repeat revascularization compared with patients who underwent nonostial, proximal PCI.

Diffuse intimal thickening of coronary arteries in slow coronary flow.

Intravascular ultrasound imaging can detect intimal thickening and is suitable for detection of early atherosclerosis, which cannot be detected by conventional angiography. The aim of the present study was to investigate the epicardial coronary morphology and intracoronary pressure in relation to slow coronary flow (SCF). The study population consisted of 19 patients with SCF [11 (57.9%) females; 55.95 +/- 9.42 years]. Proximal, middle, distal and mean total vessel area, lumen area, intima + media area (IMA), percent IMA, and maximal intima + media (I + M) thickness were calculated and compared to healthy subjects. Proximal, middle, distal and mean I + M thickness, IMA, and % IMA of patients with SCF were found to be significantly higher than those of control subjects. Longitudinally extended massive calcification throughout the epicardial arteries was found in 13 (68.49%) patients with SCF and regional calcification was found in 6 (31.6%) patients with SCF. Proximal and distal pressure gradients of patients with SCF were determined to be 15.84 +/- 12.11 mmHg in the intracoronary pressure measurements. Fractional flow reserve values were significantly lower than the normal population (0.83 +/- 0.13, P < 0.0001). This study indicates that patients with SCF have diffuse intimal thickening, widespread calcification along the vessel wall and atheroma which does not cause luminal irregularities in coronary angiography, and a pressure gradient between proximal and distal segments of epicardial coronary arteries with SCF. Based on these results, we believe that SCF may be a form of diffuse atherosclerosis involving both the microvascular system and epicardial coronary arteries.

L -Arginine and Thrombosis

HomeCirculationVol. 104, No. 25l-Arginine and Thrombosis Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBl-Arginine and Thrombosis Dimitris Tousoulis, MD PhD, Costas Tentolouris, MD and Pavlos Toutouzas, MD Dimitris TousoulisDimitris Tousoulis Cardiology Unit, Athens University Medical School, Athens, Greece Search for more papers by this author , Costas TentolourisCostas Tentolouris Cardiology Unit, Athens University Medical School, Athens, Greece Search for more papers by this author and Pavlos ToutouzasPavlos Toutouzas Cardiology Unit, Athens University Medical School, Athens, Greece Search for more papers by this author Originally published17 Dec 2001https://doi.org/10.1161/circ.104.25.e159Circulation. 2001;104:e159To the Editor:Kapostza et al1 reported that the administration of l-arginine (the precursor of nitric oxide synthesis) after surgery resulted in a highly significant reduction in the frequency of embolic signals after carotid endarterectomy in patients who were already being treated with aspirin and heparin. Patients with carotid artery disease usually suffer from coronary atherosclerosis. Therefore, it would be useful to know the impact of l-arginine administration on advanced coronary artery atherosclerosis.We examined,2,3 by quantitative angiography, the vasomotor effects of an intracoronary infusion of l-arginine in epicardial coronary artery segments and in coronary stenoses in patients with coronary artery disease and stable angina. We found that proximal coronary segments and coronary stenoses dilated in response to acute intracoronary administration of l-arginine. The greatest response to l-arginine was at the site of severe coronary stenoses. Moreover, we have shown that stenoses with a complex morphology show a greater dilation compared with those of smooth morphology, whether concentric or eccentric.3 This finding is consistent with stimulation of nitric oxide synthase activity by l-arginine administration. It provides further evidence of preserved nitric oxide synthase activity at the site of coronary stenoses, particularly within stenoses with complex morphology.4 Furthermore, because this effect was also found in nonstenotic segments of diseased coronary arteries, it is either a physiological or a pathological response requiring only minimal coronary disease.Our findings suggest that l-arginine supplementation may have a beneficial effect on diseased epicardial coronary arteries in patients with stable angina. In addition, a recent study5 showed that local l-arginine delivery after balloon angioplasty reduces monocyte binding and induces apoptosis and, therefore, may be beneficial for restenosis. The actions of l-arginine are complex, and the responses of epicardial coronary arteries and carotid arteries to l-arginine may be different. Therefore, further studies are needed to elucidate the impact of l-arginine on atherosclerosis and thrombosis in different parts of the arterial tree. The l-arginine intravenously administered may reduce the embolic signals and dilate coronary stenoses in patients with carotid and coronary artery disease.1 Kaposzta Z, Baskerville PA, Madge D, et al. l-arginine, and S-nitrosoglutathione reduce embolization in humans. Circulation. 2001; 103: 2371–2375.CrossrefMedlineGoogle Scholar2 Tousoulis D, Davies G, Tentolouris C, et al. Coronary stenosis dilatation induced by l-arginine. Lancet. 1997; 349: 1812–13.CrossrefMedlineGoogle Scholar3 Tousoulis D, Davies GJ, Tentolouris C, et al. Vasomotor effects of L- and D-arginine in stenotic atheromatous coronary plaque. Heart. 2001; 86: 296–301.CrossrefMedlineGoogle Scholar4 Goumas G, Tentolouris C, Tousoulis D, et al. Therapeutic modification of the l-arginine-eNOS pathway in cardiovascular diseases. Atherosclerosis. 2001; 154: 255–267.CrossrefMedlineGoogle Scholar5 Niebauer J, Schwarzacher SP, Hayase M, et al. Local l-arginine delivery after balloon angioplasty reduces monocyte binding and induces apoptosis. Circulation. 1999; 100: 1830–1835.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByTweddell J, Hoffman G, Mussatto K, Fedderly R, Berger S, Jaquiss R, Ghanayem N, Frisbee S and Litwin S (2002) Improved Survival of Patients Undergoing Palliation of Hypoplastic Left Heart Syndrome: Lessons Learned From 115 Consecutive Patients, Circulation, 106:12_suppl_1, (I-82-I-89), Online publication date: 24-Sep-2002. December 17, 2001Vol 104, Issue 25 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.104.25.e159PMID: 11748124 Originally publishedDecember 17, 2001 PDF download Advertisement

Cyclic Nucleotide Phosphodiesterase Type 5 Activity Limits Blood Flow to Hypoperfused Myocardium During Exercise

Nitric oxide (NO) causes vasodilation by stimulation of guanylate cyclase in vascular smooth muscle to produce cGMP. The resultant vasodilator effect is regulated by a family of cGMP phosphodiesterases (PDEs). Sildenafil, a selective inhibitor of PDE5 used for treatment of erectile dysfunction, has been found to cause relaxation of isolated epicardial coronary artery segments. The present study examined the effects of sildenafil on coronary blood flow and hemodynamics during exercise in normal and ischemic heart. In chronically instrumented normal dogs, sildenafil 2 mg/kg PO caused a slight but significant increase in left anterior descending (LAD) coronary blood flow during resting conditions, with a nonsignificant trend toward increased coronary flow during treadmill exercise. Exercise in the presence of LAD stenosis that decreased distal coronary pressure to 57+/-2 mm Hg reduced LAD flow during exercise from 69+/-8 to 41+/-7 mL/min (P:<0. 05), with hypoperfusion most severe in the subendocardium. At the same distal coronary pressure, sildenafil increased LAD flow in the ischemic region to 50+/-11 mL/min (P:<0.05). Increase in ischemic region blood flow produced by sildenafil was uniform across the LV wall, given that no change occurred in the transmural distribution of perfusion. Inhibition of PDE5 with sildenafil caused vasodilation of coronary resistance vessels with an increase of blood flow into an ischemic myocardial region during exercise in the presence of coronary artery stenosis.

Effect of sildenafil on coronary active and reactive hyperemia

Sildenafil, a selective inhibitor of phosphodiesterase type 5, produces relaxation of isolated epicardial coronary artery segments by causing accumulation of cGMP. Because shear-induced nitric oxide-dependent vasodilation is mediated by cGMP, this study was performed to determine whether sildenafil would augment the coronary resistance vessel dilation that occurs during the high-flow states of exercise or reactive hyperemia. In chronically instrumented dogs, sildenafil (2 mg/kg per os) augmented the vasodilator response to acetylcholine, with a leftward shift of the dose-response curve relating coronary flow to acetylcholine dose. Sildenafil caused a 6. 7 +/- 2.1 mmHg decrease of mean aortic pressure, which was similar at rest and during treadmill exercise (P < 0.05), with no change of heart rate, left ventricular (LV) systolic pressure, or LV maximal first time derivative of LV pressure. Sildenafil tended to increase myocardial blood flow at rest and during exercise (mean increase = 14 +/- 3%; P < 0.05 by ANOVA), but this was associated with a significant decrease in hemoglobin, so that the relationship between myocardial oxygen consumption and oxygen delivery to the myocardium (myocardial blood flow x arterial O(2) content) was unchanged. Furthermore, sildenafil did not alter coronary venous PO(2), indicating that the coupling between myocardial blood flow and myocardial oxygen demands was not altered. In addition, sildenafil did not alter the peak coronary flow rate, debt repayment, or duration of reactive hyperemia that followed a 10-s coronary occlusion. The findings suggest that cGMP-mediated resistance vessel dilation contributes little to the increase in myocardial flow that occurs during exercise or reactive hyperemia.

Influence of ageing on vasomotor responses of human epicardial coronary arteries.

Vasomotor responses to various agonists were studied on isolated circular segments of human epicardial coronary arteries from three different age groups; 23-38 years, 40-58 years and 63-86 years. Noradrenaline had no or only weak contractile effect on coronary arteries from younger patients but induced contraction of all artery segments from older patients. The Emax value was significantly (P<0.0001) higher in arteries from the oldest group compared to each of the two younger age groups, whereas the potency was similar in all three groups. Linear regression analysis of noradrenaline-induced contraction in individual patients revealed a significantly positive age-correlation (correlation coefficient 0.67, P<0.0001). Contraction induced by endothelin-1 and relaxation induced by substance P, calcitonin gene-related peptide and vasoactive intestinal peptide on arteries precontracted with U46619 showed no significant differences in maximum responses and potencies between the three age groups, and no significant linear age-correlation. These data demonstrate a large variability in contractile responses to noradrenaline with contractions seen mostly in coronary arteries from older patients. It thus seems that sympathetic activation could contribute to coronary ischaemia in some patients.

Effect of atenolol and celiprolol on acetylcholine-induced coronary vasomotion in coronary artery disease

Earlier studies have reported on the potentiated muscarinic vasoconstriction of intracoronary acetylcholine after metoprolol application in patients with coronary artery disease. The present study investigated the effect of celiprolol, atenolol, and placebo on acetylcholine-induced vasomotion in patients with coronary artery disease. Furthermore, direct effects on coronary vasomotion and on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of 6.3 × 10 −7, 2.0 × 10 −6, and 6.3 × 10 −6 M) was given before and after double-blind celiprolol (0.30 mg/kg IV), atenolol (0.15 mg/kg IV), or placebo in 3 × 12 patients. Vasomotion was investigated by quantitative coronary angiography in proximal and distal segments of epicardial coronary arteries, and by the determination of the coronary resistance index based on Doppler-flow measurements. The investigated drugs had no direct affect on the diameter of the epicardial coronary arteries. However, celiprolol, in contrast to atenolol, significantly reduced systemic vascular resistance (change after atenolol: from 1,855 ± 308 to 2,161 ± 550 dyne s cm −5; celiprolol: 1,691 ± 435 to 1,411 ± 343 dyne s cm −5; and placebo: 1,722 ± 215 to 1,710 ± 213 dyne s cm −5, p <0.001) and the coronary resistance index (change after atenolol: 2.52 ± 3.58 to 2.86 ± 4.24; celiprolol: 2.70 ± 1.55 to 2.49 ± 2.26; and placebo: 1.97 ± 1.35 to 1.92 ± 1.25, p <0.01). Celiprolol, atenolol, and placebo did not have different effects on acetylcholine-induced coronary vasomotion of epicardial conductance vessels (diminution of proximal lumen diameter before/after atenolol: 0.42 ± 0.39/0.44 ± 0.39 mm; celiprolol: 0.32 ± 0.26/0.30 ± 0.24 mm; and placebo: 0.36 ± 0.29/0.43 ± 0.40 mm) and of coronary resistance vessels (reduction of coronary resistance index before/after atenolol: 1.95 ± 4.74/1.92 ± 3.74; celiprolol: 0.98 ± 0.73/1.41 ± 1.50; and placebo: 1.16 ± 1.29/1.16 ± 1.04). In contrast to atenolol, celiprolol possesses vasodilative properties in systemic and coronary resistance vessels. There was no direct effect on the diameter of conductance vessels. Acetylcholine-induced coronary vasomotion both in conductance and resistance vessels was not influenced by the β blockers that were studied. This suggests that atenolol and celiprolol do not influence endothelium-dependent, nitric oxide related vasomotion.

Effects of Acute l -Arginine Administration in Coronary Atherosclerosis

To the Editor: Lerman et al1 in their interesting study reported that supplementation with l-arginine (the precursor of nitric oxide synthesis) for 6 months in patients without significant coronary artery stenosis reversed coronary small-vessel endothelial dysfunction and improved symptoms. Furthermore, it decreased plasma endothelin concentrations in patients. However, they did not examine the effects of l-arginine on epicardial coronary arteries and stenoses. We have examined2 3 by quantitative angiography the vasomotor effects of intracoronary infusion of normal saline (2 mL/min) for 2 minutes followed by 50 and 150 μmol/min l-arginine and bolus administration of 250 μg of nitroglycerin on 38 nonstenotic epicardial coronary artery segments and 22 stenoses in patients with coronary artery disease and a positive treadmill exercise test result (≥0.1 mV ST-segment depression at between 5 and 7 metabolic equivalents [METS] using the modified Bruce protocol). The diameter of the stenosis …

Hypomagnesemia Inhibits Nitric Oxide Release From Coronary Endothelium: Protective Role of Magnesium Infusion After Cardiac Operations

Background. Postoperative hypomagnesemia is common in patients who have undergone cardiac operations and is associated with clinically significant morbidity resulting from atrial and ventricular dysrhythmias. Magnesium supplementation may increase the cardiac index in the early postoperative period. Methods. The action of the magnesium cation on coronary vascular reactivity was studied. Segments of canine epicardial coronary artery were suspended in organ chambers to measure isometric force (95% O 2/5% CO 2, 37°C). Results. In coronary segments constricted with prostaglandin F 2α (2 × 10 −6 mol/L), acetylcholine and adenosine diphosphate (10 −9 to 10 −4 mol/L) induced vasodilation in arteries with endothelium (n = 10, each group; p < 0.05). Acetylcholine-mediated vasodilation was blocked by N G-monomethyl- l-arginine (10 −4 mol/L) and N G-nitro- l-arginine (10 −4 mol/L), two inhibitors of nitric oxide synthesis from l-arginine (n = 10, p < 0.05). The removal of magnesium from the organ chamber solution impaired vasodilation in response to acetylcholine and adenosine diphosphate. However, normal endothelium-dependent vasodilation could be restored by return of magnesium to the bathing solution. Vascular relaxation in response to bradykinin (10 −9 to 10 −6 mol/L), which was found to induce endothelium-dependent vasodilation independent of nitric oxide production, was unaffected by magnesium removal (n = 10). Conclusions. Hypomagnesemia selectively impaired the release of nitric oxide from the coronary endothelium. Because nitric oxide is a potent endogenous nitrovasodilator and inhibitor of platelet aggregation and adhesion, hypomagnesemia could promote vasoconstriction and coronary thrombosis in the early postoperative period.

Protective effects of nicaraven, a new hydroxyl radical scavenger, on the endothelial dysfunction after exposure of pig coronary artery to hydroxyl radicals.

Recently, we have reported that a new synthetic compound, 1,2bis(nicotinamido)-propane (nicaraven), improved cardiac function following preservation and reperfusion. In this study, we investigated the efficacy of nicaraven as a radical scavenger by using an in vitro model of oxidative stress, to clarify mechanisms of the protective effect of this new compound on reperfusion injury in rat heart. Ring segments of epicardial right coronary arteries (RCA) of pig were suspended in organ chambers and exposed to hydroxyl radicals (.OH), generated (by two different systems) by 0.28 mM FeSO4/0.28 mM H2O2 and DHF/Fe3+-ADP (2.4 mM, 43 nM, and 1.56 uM, respectively) to the bathing solution for 60 min. Prior exposure of the coronary arteries to .OH significantly produced right-ward shift of the dose-response curves of the bradykinin-induced endothelium-dependent relaxations (an increase in the ED50 value for bradykinin by 4.37 and 1.98 times than control in two different .OH generating systems, respectively), but did not affect the maximum relaxation responses. The presence of nicaraven (10(-4) and 10(-5) M) in the .OH generating system, shifted the dose-response curves to bradykinin to the control level, suggesting a significant hydroxyl radical scavenging effect of the drug. These results indicate that nicaraven, a new hydroxyl radical scavenger, exhibits a protective effect on hydroxyl radical-induced endothelial dysfunctions of pig coronary artery.

Mechanical properties and effects of sympathetic co-transmitters on human coronary arteries and veins.

Active isometric wall tension was studied at different levels of passive wall tension in isolated circular 2 mm long segments of human epicardial coronary arteries and veins, and maximum active wall tension was calculated to 6.60 mN/ mm for arteries and 0.86 mN/mm for veins. Vasomotor responses to sympathetic co-transmitters were studied at resting tension and after precontraction with U46619. Noradrenaline (NA) and adenosine 5'-triphosphate (ATP) induced strong contractions of veins, whereas relaxant responses dominated in arteries. Isoprenaline potently relaxed all arteries and veins. Prazosin and rauwolscine in a concentration of 10(-7) M both competitively antagonized NA-induced contraction of arteries and veins. For uridine 5'-triphosphate (UTP), relaxant responses were demonstrated in most arteries but only some veins. Neuropeptide Y (NPY) elicited no observable vasomotor responses in either arteries or veins. Mechanical removal of the arterial endothelium did not significantly alter relaxant responses to NA, ATP, UTP or isoprenaline. In conclusion, alpha 1- and alpha 2-adrenoceptors mediating contraction and beta-adrenoceptors mediating relaxation seem to be present in both human epicardial coronary arteries and veins. When applied to isolated epicardial coronary vessels, NA and ATP had a stronger influence on vasomotor tone than NPY and UTP, mediating strong contraction of veins but mainly relaxation of coronary arteries, that was independent of an intact endothelium.

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)>