Cyclosporine impairs release of endothelium-derived relaxing factors in epicardial and resistance coronary arteries.


BACKGROUND:Cyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds. We wished to determine whether acute cyclosporine administration induces endothelial dysfunction in coronary conductance or resistance arteries. METHODS AND RESULTS:We examined the effect of intracoronary acetylcholine, N omega-nitro-L-arginine methyl ester (L-NAME), L-arginine, nitroglycerin, and adenosine before and after acute cyclosporine administration (3 mg/kg IV over 30 minutes) in anesthetized dogs. Flow velocity was measured with a 0.014-in Doppler wire to assess resistance vessel responses, and epicardial coronary lumen area was simultaneously measured with a 4.3F, 30-MHz imaging catheter inserted over the Doppler wire. In 6 dogs, acetylcholine-induced increase in flow velocity was attenuated by cyclosporine in vehicle (137% to 55% at 10(-5) mol/L, P < .001), as was acetylcholine-induced epicardial vasodilation (14.1% to 6.7% at 10(-5) mol/L, P < .001). Vasodilation in response to intracoronary nitroglycerin (200 micrograms) and adenosine (6 mg) were unchanged by cyclosporine. Epicardial vasoconstriction with L-NAME (10(-4) mol/L) was reduced by cyclosporine (Pre, 7.4 +/- 0.9%; Post, 2.6 +/- 1.2%; P = .04), but L-arginine (10(-4) mol/L) had no effect after cyclosporine. In another 5 dogs, pure cyclosporine impaired acetylcholine-induced vasodilatation to the same degree as cyclosporine in vehicle (Cremophor); vehicle infusion did not impair endothelial function. In 5 more dogs, cyclosporine did not increase either arterial or coronary sinus concentrations of endothelin-1. CONCLUSIONS:The present study shows that cyclosporine acutely impairs release of endothelium-derived relaxing factor in canine conductance and resistance coronary arteries and provides evidence for decreased epicardial nitric oxide release after cyclosporine. The potential contribution of acute cyclosporine-induced coronary endothelial dysfunction to posttransplant vasculopathy needs further study.






Sudhir K,MacGregor JS,DeMarco T,De Groot CJ,Taylor RN,Chou TM,Yock PG,Chatterjee K




Has Abstract


1994-12-01 00:00:00












  • Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow.

    abstract::It has been suggested that the beneficial effects of reperfusing ischemic myocardium might be in part reversed by the occurrence of "reperfusion injury." One possible mechanism could be the generation of oxygen free radicals. Superoxide dismutase enzymatically scavenges superoxide radicals by dismutation to hydrogen p...


    pub_type: 杂志文章


    authors: Ambrosio G,Weisfeldt ML,Jacobus WE,Flaherty JT

    更新日期:1987-01-01 00:00:00

  • Spatiotemporal relation between gap junctions and fascia adherens junctions during postnatal development of human ventricular myocardium.

    abstract:BACKGROUND:The growing postnatal human heart maintains electromechanical function while undergoing substantial changes of cellular topology and myocardial architecture. The capacity for growth and remodeling of ventricular myocardium in adaptation to the hemodynamic changes of early infancy later declines. This decline...


    pub_type: 杂志文章


    authors: Peters NS,Severs NJ,Rothery SM,Lincoln C,Yacoub MH,Green CR

    更新日期:1994-08-01 00:00:00

  • Enzymatically degraded, nonoxidized LDL induces human vascular smooth muscle cell activation, foam cell transformation, and proliferation.

    abstract:BACKGROUND:Enzymatic, nonoxidative modification transforms LDL to an atherogenic molecule (E-LDL) that activates complement and macrophages and is present in early atherosclerotic lesions. METHODS AND RESULTS:We report on the atherogenic effects of E-LDL on human vascular smooth muscle cells (SMC). E-LDL accumulated i...


    pub_type: 杂志文章


    authors: Klouche M,Rose-John S,Schmiedt W,Bhakdi S

    更新日期:2000-04-18 00:00:00

  • Effect of tachycardia heart failure on the restitution of left ventricular function in closed-chest dogs.

    abstract:BACKGROUND:Cardiac mechanical restitution and relaxation restitution are thought to be physiological correlates of the recovery kinetics of Ca2+ release mechanisms and sequestration capacity of the sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca2+ handling, we s...


    pub_type: 杂志文章


    authors: Prabhu SD,Freeman GL

    更新日期:1995-01-01 00:00:00

  • Relationship of oxidized phospholipids on apolipoprotein B-100 particles to race/ethnicity, apolipoprotein(a) isoform size, and cardiovascular risk factors: results from the Dallas Heart Study.

    abstract:BACKGROUND:Elevated levels of oxidized phospholipids (OxPLs) on apolipoprotein B-100 particles (OxPL/apoB) are associated with cardiovascular disease and predict new cardiovascular events. Elevated lipoprotein (a) [Lp(a)] levels are a risk factor for cardiovascular disease in whites and also in blacks if they carry sma...


    pub_type: 杂志文章


    authors: Tsimikas S,Clopton P,Brilakis ES,Marcovina SM,Khera A,Miller ER,de Lemos JA,Witztum JL

    更新日期:2009-04-07 00:00:00

  • Deletion of angiotensin II type 2 receptor exaggerated atherosclerosis in apolipoprotein E-null mice.

    abstract:BACKGROUND:The role of angiotensin II (Ang II) type 2 (AT2) receptor in atherosclerosis was explored with the use of AT2 receptor/apolipoprotein E (ApoE)-double-knockout (AT2/ApoE-DKO) mice, with a focus on oxidative stress. METHODS AND RESULTS:After treatment with a high-cholesterol diet (1.25% cholesterol) for 10 we...


    pub_type: 杂志文章


    authors: Iwai M,Chen R,Li Z,Shiuchi T,Suzuki J,Ide A,Tsuda M,Okumura M,Min LJ,Mogi M,Horiuchi M

    更新日期:2005-09-13 00:00:00

  • Arteriovenous carbon dioxide and pH gradients during cardiac arrest.

    abstract::In a porcine preparation of cardiac arrest, we demonstrated that there is a marked paradox of venous acidemia and arterial alkalemia. This paradox is related to decreased clearance of CO2 from the lungs when pulmonary blood flow is critically reduced. Accordingly, increased venous PCO2 rather than metabolic acidosis d...


    pub_type: 杂志文章


    authors: Grundler W,Weil MH,Rackow EC

    更新日期:1986-11-01 00:00:00

  • Regulation of shear stress in the canine coronary microcirculation.

    abstract:BACKGROUND:Physical forces, such as pressure and flow, are well known to affect vascular function in the coronary circulation. Increases in shear stress produce vasodilation in coronary arterioles in vitro, and constant-flow preparations suggest a role for shear stress-induced vasodilation during adjustments to metabol...


    pub_type: 杂志文章


    authors: Stepp DW,Nishikawa Y,Chilian WM

    更新日期:1999-10-05 00:00:00

  • Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias.

    abstract::We determined the pharmacokinetics, efficacy and therapeutic plasma concentration of encainide, a new antiarrhythmic drug that affects His-Purkinje conduction but not ventricular refractoriness. Nine patients with frequent and complex premature ventricular complexes were studied in a 3-day double-blind protocol. Each ...


    pub_type: 临床试验,杂志文章


    authors: Winkle RA,Peters F,Kates RE,Tucker C,Harrison DC

    更新日期:1981-08-01 00:00:00

  • Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease.

    abstract:BACKGROUND:With MRI, an index of myocardial perfusion reserve (MPRI) can be determined. We assessed the value of this technique for the noninvasive detection of coronary artery disease (CAD) in patients with suspected CAD. METHODS AND RESULTS:Eighty-four patients referred for a primary diagnostic coronary angiography ...


    pub_type: 临床试验,杂志文章


    authors: Nagel E,Klein C,Paetsch I,Hettwer S,Schnackenburg B,Wegscheider K,Fleck E

    更新日期:2003-07-29 00:00:00

  • Modulation of drug effects by regional sympathetic denervation and supersensitivity.

    abstract:BACKGROUND:Regional sympathetic denervation, such as that produced by a myocardial infarction, causes electrophysiological heterogeneity in the ventricles. The purpose of this study was to test the hypothesis that such denervation could cause drugs to exert heterogeneous myocardial effects. METHODS AND RESULTS:Sympath...


    pub_type: 杂志文章


    authors: Stanton MS,Zipes DP

    更新日期:1991-10-01 00:00:00

  • Coronary Artery Calcium to Guide a Personalized Risk-Based Approach to Initiation and Intensification of Antihypertensive Therapy.

    abstract:BACKGROUND:The use of atherosclerotic cardiovascular disease (ASCVD) risk to personalize systolic blood pressure (SBP) treatment goals is a topic of increasing interest. Therefore, we studied whether coronary artery calcium (CAC) can further guide the allocation of anti-hypertensive treatment intensity. METHODS:We inc...


    pub_type: 杂志文章


    authors: McEvoy JW,Martin SS,Dardari ZA,Miedema MD,Sandfort V,Yeboah J,Budoff MJ,Goff DC Jr,Psaty BM,Post WS,Nasir K,Blumenthal RS,Blaha MJ

    更新日期:2017-01-10 00:00:00

  • Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation.

    abstract:BACKGROUND:Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects. Thus, we tested whether (1) postsecretory modifications of LDL (glycation...


    pub_type: 杂志文章


    authors: Devaraj S,Jialal I

    更新日期:2000-07-11 00:00:00

  • Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk.

    abstract:BACKGROUND:Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement. METHODS AND RESULTS:We performed 24-hour ABP monitoring in 5682 participants (mean age 59.0 years; ...


    pub_type: 杂志文章


    authors: Kikuya M,Hansen TW,Thijs L,Björklund-Bodegård K,Kuznetsova T,Ohkubo T,Richart T,Torp-Pedersen C,Lind L,Ibsen H,Imai Y,Staessen JA,International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcom

    更新日期:2007-04-24 00:00:00

  • Endocardial catheter mapping: wire skeleton technique for representation of computed arrhythmogenic sites compared with intraoperative mapping.

    abstract::Guiding surgical therapy of ventricular tachycardia by preoperative endocardial catheter mapping necessitates improvement of the accuracy of localization of the arrhythmogenic site. We therefore used a new mathematical cineradiographic method during catheter mapping to compute the position of left ventricular arrhythm...


    pub_type: 杂志文章


    authors: Hauer RN,de Zwart MT,de Bakker JM,Hitchcock JF,Penn OC,Nijsen-Karelse M,Robles de Medina EO

    更新日期:1986-12-01 00:00:00

  • Truncus arteriosus with unilateral absence of a pulmonary artery. Criteria for operability and surgical results.

    abstract::In 15 of 126 (12%) patients with truncus arteriosus who were catheterized at the Mayo Clinic from 1967 through 1975, natural agenesis of one pulmonary artery was present. Ten truncus patients with either natural or acquired absence of one pulmonary artery have undergone definitive operation. The criteria for operabili...


    pub_type: 杂志文章


    authors: Mair DD,Ritter DG,Danielson GK,Wallace RB,McGoon DC

    更新日期:1977-04-01 00:00:00

  • Altered contractile response in neonatal myocardium to citrate-phosphate-dextrose infusion.

    abstract::The clinical use of citrate-phosphate-dextrose during blood-product transfusion is known to affect ionized calcium levels and can result in depression of myocardial contractility. The immature heart appears to have an intrinsic reduction in contractile state compared with the adult heart and may be more dependent on t...


    pub_type: 杂志文章


    authors: Rebeyka IM,Yeh T Jr,Hanan SA,Borges MR,Lee KF,Tuchy GE,Abd-Elfattah AS,Wechsler AS

    更新日期:1990-11-01 00:00:00

  • Destruction of contrast microbubbles by ultrasound: effects on myocardial function, coronary perfusion pressure, and microvascular integrity.

    abstract:BACKGROUND:Recent experimental data indicate that ultrasound-induced destruction of ultrasound contrast microbubbles can cause immediate rupture of the microvessels in which these microbubbles are located. METHODS AND RESULTS:To examine the functional and morphological significance of these findings in the heart, isol...


    pub_type: 杂志文章


    authors: Ay T,Havaux X,Van Camp G,Campanelli B,Gisellu G,Pasquet A,Denef JF,Melin JA,Vanoverschelde JL

    更新日期:2001-07-24 00:00:00

  • Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III).

    abstract:BACKGROUND:National and international guidelines recommend fasting lipid panel measurement for risk stratification of patients for prevention of cardiovascular events. However, the prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol (LDL-C) is uncertain. METHODS AND RESULTS:Patients enrol...


    pub_type: 杂志文章


    authors: Doran B,Guo Y,Xu J,Weintraub H,Mora S,Maron DJ,Bangalore S

    更新日期:2014-08-12 00:00:00

  • Hirulog in the treatment of unstable angina. Results of the Thrombin Inhibition in Myocardial Ischemia (TIMI) 7 trial.

    abstract:BACKGROUND:Direct thrombin inhibitors are a new class of drugs that may offer a more effective and potentially simpler alternative to heparin. Hirulog is a synthetic peptide based on the leech-derived compound hirudin and, like hirudin, is a highly specific, direct inhibitor of free and clot-bound thrombin. METHODS AN...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Fuchs J,Cannon CP

    更新日期:1995-08-15 00:00:00

  • Long-term survival and repeat coronary revascularization in dialysis patients after surgical and percutaneous coronary revascularization with drug-eluting and bare metal stents in the United States.

    abstract:BACKGROUND:Few published data describe long-term survival of dialysis patients undergoing surgical versus percutaneous coronary revascularization in the era of drug-eluting stents (DES). METHODS AND RESULTS:Using United States Renal Data System data, we identified 23 033 dialysis patients who underwent coronary revasc...


    pub_type: 杂志文章


    authors: Shroff GR,Solid CA,Herzog CA

    更新日期:2013-05-07 00:00:00

  • Peak oxygen uptake correlates with survival without clinical deterioration in ambulatory children with dilated cardiomyopathy.

    abstract:BACKGROUND:Children stable at home with dilated cardiomyopathy remain at risk of death; there is evidence of survival benefit for transplantation out to 4 years postoperatively. The limited supply of donor organs makes risk stratification imperative, but although cardiopulmonary exercise test is well established as a p...


    pub_type: 杂志文章


    authors: Giardini A,Fenton M,Andrews RE,Derrick G,Burch M

    更新日期:2011-10-18 00:00:00

  • Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial.

    abstract:BACKGROUND:Heart rate reduction should benefit patients with chronic stable angina by improving myocardial perfusion and reducing myocardial oxygen demand. This study evaluated the antianginal and antiischemic effects of ivabradine, a new heart rate-lowering agent that acts specifically on the sinoatrial node. METHODS...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Borer JS,Fox K,Jaillon P,Lerebours G,Ivabradine Investigators Group.

    更新日期:2003-02-18 00:00:00

  • The clinical significance of bundle branch block complicating acute myocardial infarction. 2. Indications for temporary and permanent pacemaker insertion.

    abstract::The indication for prophylactic temporary and permanent pacing during acute myocardial infarction (MI) complicated by bundle branch block is high risk of progression via a Type II pattern to second or third degree (high degree) AV block during hospitalization or follow-up. In this study, determinants of high degree AV...


    pub_type: 杂志文章


    authors: Hindman MC,Wagner GS,JaRo M,Atkins JM,Scheinman MM,DeSanctis RW,Hutter AH Jr,Yeatman L,Rubenfire M,Pujura C,Rubin M,Morris JJ

    更新日期:1978-10-01 00:00:00

  • Dose-response of chronic beta-blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators.

    abstract:BACKGROUND:Small-scale clinical investigations have demonstrated that single doses of beta-blocking agents can improve left ventricular function in heart failure from idiopathic dilated cardiomyopathy (IDC). The purpose of this multicenter clinical trial was to determine the dose-effect characteristics of beta-blockade...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Bristow MR,O'Connell JB,Gilbert EM,French WJ,Leatherman G,Kantrowitz NE,Orie J,Smucker ML,Marshall G,Kelly P

    更新日期:1994-04-01 00:00:00

  • Frequency of early occlusion and stenosis in a left internal mammary artery to left anterior descending artery bypass graft after surgery through a median sternotomy on conventional bypass: benchmark for minimally invasive direct coronary artery bypass.

    abstract:BACKGROUND:Uncertainty exists regarding the frequency of early occlusion when the left internal mammary artery (LIMA) is anastomosed to the left anterior descending artery (LAD) through a sternotomy with conventional coronary artery bypass grafting (CABG). The issue has gained importance for comparison with less invasi...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Berger PB,Alderman EL,Nadel A,Schaff HV

    更新日期:1999-12-07 00:00:00

  • Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation.

    abstract::Experimental studies demonstrate that short-term regional perfusion-contraction matching, in which the energy demands of regional myocardial contraction are reduced to match the diminished myocardial substrate supply, occurs during states of low coronary blood flow under resting conditions and during exercise-induced ...


    pub_type: 杂志文章


    authors: Ross J Jr

    更新日期:1991-03-01 00:00:00

  • Disparities in revascularization rates after acute myocardial infarction between aboriginal and non-aboriginal people in Australia.

    abstract:BACKGROUND:This study examined revascularization rates after acute myocardial infarction (AMI) for Aboriginal and non-Aboriginal patients sequentially controlling for admitting hospital and risk factors. METHODS AND RESULTS:Hospital data from the state of New South Wales, Australia (July 2000 through December 2008) we...


    pub_type: 杂志文章


    authors: Randall DA,Jorm LR,Lujic S,O'Loughlin AJ,Eades SJ,Leyland AH

    更新日期:2013-02-19 00:00:00

  • Dispatcher-assisted cardiopulmonary resuscitation. Validation of efficacy.

    abstract::Dispatcher-delivered telephone instruction in cardiopulmonary resuscitation (CPR) has been proposed to increase rates of bystander CPR in cases of out-of-hospital cardiac arrest. We tested the efficacy of a previously developed CPR message using a recording mannikin in a high stress, simulated cardiac arrest scenario....


    pub_type: 杂志文章


    authors: Kellermann AL,Hackman BB,Somes G

    更新日期:1989-11-01 00:00:00

  • Short- and intermediate-term clinical outcomes from direct myocardial laser revascularization guided by biosense left ventricular electromechanical mapping.

    abstract:BACKGROUND:Direct myocardial revascularization (DMR) has been examined as an alternative treatment for patients with chronic refractory myocardial ischemic syndromes who are not candidates for conventional coronary revascularization. Methods and Results-We used left ventricular electromagnetic guidance in 77 patients w...


    pub_type: 杂志文章


    authors: Kornowski R,Baim DS,Moses JW,Hong MK,Laham RJ,Fuchs S,Hendel RC,Wallace D,Cohen DJ,Bonow RO,Kuntz RE,Leon MB

    更新日期:2000-09-05 00:00:00