Inhaled Fasudil Lacks Pulmonary Selectivity in Thromboxane-Induced Acute Pulmonary Hypertension in Newborn Lambs.

Abstract:

INTRODUCTION:Pulmonary hypertension (PH) is a potentially deadly disease for infants and adults with few existing medical interventions and no cure. In PH, increased blood pressure in the pulmonary artery eventually leads to heart failure. Fasudil, an antagonist of Rho-kinase, causes vasodilation leading to decreased systemic artery pressure and pulmonary artery pressure (PAP). This study compared the effects of fasudil administered as either an intravenous infusion or inhaled aerosol in newborn lambs. HYPOTHESIS:Inhaled aerosol delivery of fasudil will provide selective pulmonary vasodilation when compared with intravenous administration. METHODS:Newborn lambs (∼11 days) were surgically instrumented and mechanically ventilated under anesthesia. A pulmonary artery catheter and ultrasonic flow probe were inserted to measure hemodynamics. Acute PH was pharmaceutically induced via continuous intravenous infusion of thromboxane. After achieving a 2- to 3-fold elevation of PAP, fasudil was administered either as intravenous infusion (2.5 mg/kg) or inhaled aerosol (100 mg of fasudil in 2 mL of saline). Changes in PAP, mean systemic arterial pressure (MABP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), cardiac output, and heart rate were assessed. In addition, plasma concentrations of fasudil were measured. RESULTS:Both routes of fasudil delivery produced significant decreases in PAP and PVR but also produced similar decreases in MABP and SVR. The Cmax for intravenous fasudil was greater than that for inhaled fasudil. CONCLUSIONS:These results suggest inhaled fasudil lacks pulmonary selectivity when compared with intravenous fasudil.

authors

Hanson SFL,Terry MH,Moretta DT,Power GG,Wilson SM,Alam F,Ahsan F,Blood AB,Giri PC

doi

10.1177/1074248418772814

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

472-480

issue

5

eissn

1074-2484

issn

1940-4034

journal_volume

23

pub_type

杂志文章
  • CMX-2043 Efficacy in a Rat Model of Cardiac Ischemia-Reperfusion Injury.

    abstract::α-Lipoic acid (LA) has been shown to offer protection against ischemia-reperfusion injury (IRI) in multiple organ systems. N-[(R)-1,2-dithiolane-3-pentanoyl]-L-glutamyl-L-alanine (CMX-2043), a novel analogue of LA, was studied as part of a preclinical development program intended to identify safe and efficacious drug ...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248416640118

    authors: Baguisi A,Casale RA,Kates SA,Lader AS,Stewart K,Beeuwkes R 3rd

    更新日期:2016-11-01 00:00:00

  • Therapeutic Implications of COVID-19 for the Interventional Cardiologist.

    abstract::Although COVID-19 is viewed primarily as a respiratory disease, cardiovascular risk factors and disease are prevalent among infected patients and are associated with worse outcomes. In addition, among multiple extra-pulmonary manifestations, there has been an increasing recognition of specific cardiovascular complicat...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248420982736

    authors: Kelham M,Choudry FA,Hamshere S,Beirne AM,Rathod KS,Baumbach A,Ahluwalia A,Mathur A,Jones DA

    更新日期:2020-12-17 00:00:00

  • A Quarter of a Century Later: What is Dofetilide's Clinical Role Today?

    abstract::Dofetilide is a class III antiarrhythmic agent approved by the Food and Drug Administration for the conversion of atrial fibrillation and atrial flutter and maintenance of sinus rhythm in symptomatic patients with persistent arrhythmia. Drug trials showed neutral mortality in post-myocardial infarction patients and th...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,评审

    doi:10.1177/1074248418784288

    authors: Wolbrette DL,Hussain S,Maraj I,Naccarelli GV

    更新日期:2019-01-01 00:00:00

  • Effect of Digoxin on Ventricular Remodeling and Responsiveness of beta-Adrenoceptors in Chronic Volume Overload.

    abstract::BACKGROUND: Digoxin improves baroreflex function and reduces neurohumoral activation in severe heart failure, but it is uncertain how digoxin affects ventricular remodeling and progression to left ventricular dysfunction. In addition, the effect of digoxin in in vitro beta-adrenoceptor density and function, and contra...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424849800300403

    authors: Sullebarger JT,D'Ambra PM,Clark LC,Thanikarry L,Fontanet HL

    更新日期:1998-10-01 00:00:00

  • Characterization of cardioprotection mediated by AT2 receptor antagonism after ischemia-reperfusion in isolated working rat hearts.

    abstract:BACKGROUND:Whether cardioprotection induced by the angiotensin II (AngII) type 2 receptor (AT(2)R) antagonist PD123,319 (PD) after ischemia-reperfusion (IR) is influenced by the concentration of PD, presence of AngII, timing of exposure, or inhibition of proton production from glucose metabolism is not known. METHODS ...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1054/JCPT.2000.7451

    authors: Ford WR,Clanachan AS,Jugdutt BI

    更新日期:2000-07-01 00:00:00

  • Curcumin attenuates cardiopulmonary bypass-induced lung oxidative damage in rats.

    abstract:OBJECTIVE:Acute lung injury is a common complication after cardiopulmonary bypass (CPB). Oxidative damage greatly impacts CPB-induced lung ischemic pathogenesis and may represent a target for treatment. We aimed to investigate whether curcumin upregulates heme oxygenase 1 (HO-1) expression and ameliorates lung injury i...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248412442002

    authors: Liu K,Chen HL,Huang H,Jing H,Dong GH,Wu HW,You QS

    更新日期:2012-12-01 00:00:00

  • Comparison of the Electromechanical Effects of Vesnarinone and Amrinone in Isolated Dog Purkinje Strands and Ventricular Trabeculae.

    abstract::BACKGROUND: Conventional microelectrode techniques were used to compare the concentration-dependent effects of vesnarinone (0.1-100 µM) and amrinone (1 µM-1 mM) on action potential duration (APD) and developed force in both isolated dog ventricular trabeculae and Purkinje strands. METHODS AND RESULTS: Both drugs incre...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424849600100207

    authors: Lathrop DA,Nánási PP,Varró A,Schwartz A

    更新日期:1996-04-01 00:00:00

  • Circadian variation of stent thrombosis and the effect of more robust platelet inhibition: a post hoc analysis of the TRITON-TIMI 38 trial.

    abstract:BACKGROUND:The well-described morning peak in the onset of acute coronary syndromes has been partly attributed to increased platelet activity upon arising. It has been suggested that stent thrombosis (ST) exhibits a similar pattern. We assessed whether a diurnal variation in ST occurs, and whether more robust antiplate...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/1074248413497534

    authors: Mogabgab O,Wiviott SD,Cannon CP,Sloan S,Sabatine MS,Antman EM,Braunwald E,Giugliano RP

    更新日期:2013-11-01 00:00:00

  • Nonplatelet effects of aspirin during acute coronary occlusion: electrophysiologic and cation alterations in ischemic myocardium.

    abstract:BACKGROUND:Mortality after acute myocardial ischemia has been reduced by aspirin (ASA) but mechanisms other than the antiplatelet effect have not been established. This article evaluates an antiarrhythmic action during sympathetic stimulation in the intact anesthetized dog with and without ischemia. METHODS AND RESULT...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1053/XV.2000.5492

    authors: Shehadeh AA,Arena J,Moschos CB,Regan TJ

    更新日期:2000-04-01 00:00:00

  • Postconditioning markedly attenuates ventricular arrhythmias after ischemia-reperfusion.

    abstract:BACKGROUND:Brief periods of reocclusion (postconditioning) during early reperfusion reduce myocardial infarct size. Whether postconditioning has an effect on lethal ventricular arrhythmias independent of infarction in an in-vivo regional ischemia model is unknown. The purpose of this study was to determine if postcondi...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424840601100105

    authors: Kloner RA,Dow J,Bhandari A

    更新日期:2006-03-01 00:00:00

  • Effectiveness of oral magnesium in a patient with ventricular tachycardia due to hypomagnesemia.

    abstract::A 12-year-old girl with occasional symptoms of chest discomfort was diagnosed with ventricular tachycardia on cardiac evaluation. No evidence of organic heart disease was apparent, but a laboratory evaluation revealed hypomagnesemia. Ventricular tachycardia disappeared after treatment with 200 mg/day of oral magnesium...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424840501000309

    authors: Tsuji A,Araki K,Maeyama K,Hashimoto K

    更新日期:2005-09-01 00:00:00

  • Effects of Sotalol on the Circadian Rhythmicity of Heart Rate and QT Intervals With a Noninvasive Index of Reverse-Use Dependency.

    abstract::BACKGROUND: The effects of sotalol on the 24-hour profile of the QT interval relative to that of the heart rate (HR) may be helpful in determining the time course of the drug's action in controlling cardiac arhythmias. This has not been previously determined. Thus, the objective of the current study was to evaluate th...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424849900400104

    authors: Sharma PP,Sarma JS,Singh BN

    更新日期:1999-01-01 00:00:00

  • Age-Related Considerations in Cardio-Oncology.

    abstract::Cardio-Oncology has blossomed as a new field in cardiovascular medicine, in large part due to new therapies, which may have cardiovascular sequelae. Despite this, anthracyclines still serve as cornerstone therapy for most pediatric cancers, several solid tumors and hematological malignancies. Cardiotoxicity is the mai...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248420968689

    authors: Screever EM,Meijers WC,Moslehi JJ

    更新日期:2021-03-01 00:00:00

  • Imipramine-induced cardiac depression is responsible for the increase in intracellular magnesium and the activation of ERK 1/2 in rats.

    abstract::Imipramine, an antidepressant drug, can cause potentially lethal cardiotoxic side effects including hypotension, ventricular tachycardia, and decreased cardiac output. This study investigated the mechanism responsible for imipramine-induced cardiac depression in rats. The left ventricular developed pressure (LVDP), ve...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248410366853

    authors: Lee MY,Kim SJ,Kim JS,Kang HS

    更新日期:2010-09-01 00:00:00

  • Effect of simvastatin/ezetimibe 10/10 mg versus simvastatin 40 mg on serum vitamin D levels.

    abstract:BACKGROUND:Low levels of 25-hydroxyvitamin D (25(OH)VitD) have been recognized as an emerging cardiovascular disease (CVD) risk factor. Statins are reported to increase 25(OH)VitD concentration. Animal studies suggest that ezetimibe is a moderate inhibitor of intestinal 25(OH)VitD absorption, but its effect in humans i...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/1074248412470513

    authors: Liberopoulos EN,Makariou SE,Moutzouri E,Kostapanos MS,Challa A,Elisaf M

    更新日期:2013-05-01 00:00:00

  • Differential effects of carvedilol and metoprolol succinate on plasma norepinephrine release and peak exercise heart rate in subjects with chronic heart failure.

    abstract::Dosing equivalency of carvedilol and metoprolol remains a debate. Degree of beta 1-blockade is best assessed by blunting of the exercise-induced heart rate. Accordingly, the authors have investigated dosing equivalency by examining baseline and peak exercise heart rates and norepinephrine levels in subjects with chron...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248407312629

    authors: Vittorio TJ,Zolty R,Kasper ME,Khandwalla RM,Hirsh DS,Tseng CH,Jorde UP,Ahuja K

    更新日期:2008-03-01 00:00:00

  • Repeated Oral or Subcutaneous LMWH Has similar Antithrombotic Activity in a Rat Venous Thrombosis Model: Antithrombotic Activity Correlates With Heparin on Endothelium When Orally Administered.

    abstract::Low-molecular-weight heparins (LMWHs) endure as important drugs for thromboprophylaxis. Although clinical use relies on the subcutaneous (SC) route, our previous studies show that single-dose orally administered LMWHs have antithrombotic activity. Since thromboprophylaxis requires long-term treatment, we examined anti...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248416667601

    authors: Hiebert LM

    更新日期:2017-05-01 00:00:00

  • The cycloxygenase 2 (COX-2) story: it's time to explain, not inflame.

    abstract::Despite initial promising reports that anti-inflammatory properties of cycloxygenase-2 (COX-2) inhibitors may confer anti-atherosclerosis effects and stabilize the atherosclerotic plaque, subsequent data from long-term clinical trials have shown that selective COX-2 inhibitors are associated with increased risk of car...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,评审

    doi:10.1177/1074248407301172

    authors: Salinas G,Rangasetty UC,Uretsky BF,Birnbaum Y

    更新日期:2007-06-01 00:00:00

  • MethotrexaTE THerapy in ST-Segment Elevation MYocardial InfarctionS: A Randomized Double-Blind, Placebo-Controlled Trial (TETHYS Trial).

    abstract:PURPOSE:Methotrexate is an anti-inflammatory drug that has been shown to have anti-ischemic effects. Our aim was to evaluate if methotrexate could reduce infarct size in patients with ST-segment elevation myocardial infarction (STEMI). METHODS:We randomly assigned patients with STEMI to receive either methotrexate or ...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/1074248417699884

    authors: Moreira DM,Lueneberg ME,da Silva RL,Fattah T,Gottschall CAM

    更新日期:2017-11-01 00:00:00

  • Atorvastatin Pretreatment Inhibits Myocardial Inflammation and Apoptosis in Swine After Coronary Microembolization.

    abstract:BACKGROUND/AIM:In addition to its cholesterol-lowering effect, atorvastatin (ATV) has been thought to have multiple cardiovascular benefits, including anti-inflammatory and anti-apoptotic properties. The present study was undertaken to determine whether ATV pretreatment could attenuate myocardial apoptosis and inflamma...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248416662348

    authors: Wang JY,Chen H,Su X,Zhou Y,Li L

    更新日期:2017-03-01 00:00:00

  • Mechanisms of Impaired Endothelial Function Associated With Insulin Resistance.

    abstract::BACKGROUND: The insulin-resistant (IR) syndrome is causally related to hypertension and cardiovascular events; however, the underlying mechanism remains elusive. The current study was designed to determine (1) whether the IR syndrome causes vascular dysfunction and (2) whether insulin resistance alters the activity of...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424849800300205

    authors: Miller AW,Hoenig ME,Ujhelyi MR

    更新日期:1998-04-01 00:00:00

  • Diabetes, heart rate, and mortality.

    abstract::A large body of evidence indicates that a persistently high heart rate is associated with a significant risk for higher mortality and sudden death in individuals with a variety cardiovascular disorders, as well as in the general population. Heart rates elevated beyond a certain threshold have been found to be a risk f...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,评审

    doi:10.1177/107424840200700208

    authors: Singh N

    更新日期:2002-04-01 00:00:00

  • Myocardial energy metabolism during ischemia and the mechanisms of metabolic therapies.

    abstract::The primary effect of ischemia is reduced aerobic adenosine triphosphate (ATP) formation in mitochondria. This triggers accelerated glycolysis and reduced cell pH, Ca(2+) accumulation, K(+) efflux, adenosine formation, and the clinical signs of ischemia: chest pain and a shift in the ST segment. Traditional therapies ...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,评审

    doi:10.1177/107424840400900104

    authors: Stanley WC

    更新日期:2004-09-01 00:00:00

  • Cardiac Arrhythmias Following Intravenous Nicotine: Experimental Study in Dogs.

    abstract::BACKGROUND: Nicotine, the active agent in tobacco, is released into the circulation during cigarette smoking. It elevates plasma catecholamines, heart rate, and arterial blood pressure; produces coronary spasm; and increases myocardial work and oxygen demand with concomitant reduction in oxygen supply. This may genera...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424849700200407

    authors: Mehta MC,Jain AC,Mehta A,Billie M

    更新日期:1997-10-01 00:00:00

  • Conversion of atrial fibrillation to sinus rhythm during treatment with intravenous esmolol or diltiazem: a prospective, randomized comparison.

    abstract::Prior studies have suggested that intravenous diltiazem reduces the probability of spontaneous conversion of atrial fibrillation (AF) to sinus rhythm in the electrophysiology laboratory and in patients with postoperative AF. Whether diltiazem exerts the same effect in patients presenting to the emergency department (E...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/1074248407303792

    authors: Hassan S,Slim AM,Kamalakannan D,Khoury R,Kakish E,Maria V,Ahmed S,Pires LA,Kronick SL,Oral H,Morady F

    更新日期:2007-09-01 00:00:00

  • Sarcoplasmic reticulum adenosine triphosphatase overexpression in the L-type Ca2+ channel mouse results in cardiomyopathy and Ca2+ -induced arrhythmogenesis.

    abstract:BACKGROUND:Overexpression of the L-type voltage-dependent calcium channel alpha(1C)-subunit (L-VDCC OE) in transgenic mice results in adaptive hypertrophy followed by a maladaptive phase associated with a decrease in sarcoplasmic reticulum adenosine triphosphatase (SERCA)2a expression at 8 to 10 months of age. Overexpr...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424840501000404

    authors: Rubio M,Bodi I,Fuller-Bicer GA,Hahn HS,Periasamy M,Schwartz A

    更新日期:2005-12-01 00:00:00

  • Right atrial and ventricular thrombus infiltrated with osteoblastic osteosarcoma.

    abstract::The presenting signs of osteogenic osteosarcoma are commonly pain, local swelling, local warmth, pathologic fracture, and metastatic disease. Deep venous metastasis of osteoblastic osteosarcoma is most often a postmortem diagnosis. This paper describes the case of a previously healthy 18-year-old woman who presented w...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424840300800408

    authors: Shah AP,Parmar S,O'Regan R

    更新日期:2003-12-01 00:00:00

  • Sulfated polysaccharide fucoidan ameliorates experimental autoimmune myocarditis in rats.

    abstract::Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of experimental autoimmune myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidan binds ...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/1074248410378751

    authors: Tanaka K,Ito M,Kodama M,Tomita M,Kimura S,Hoyano M,Mitsuma W,Hirono S,Hanawa H,Aizawa Y

    更新日期:2011-03-01 00:00:00

  • Use of Lipid Drugs With Acute Myocardial Infarction Patients: An Examination of Physician Prescribing Behaviors.

    abstract::BACKGROUND: Clinical trials have shown that the use of lipid-lowering agents in postmyocardial infarction (MI) patients reduces rates of subsequent coronary events, reduces coronary artery bypass surgery rates, and improves survival. Physician decisions to prescribe lipid-lowering drugs is influenced by a number of pa...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424849800300303

    authors: Khan M,Mukkamala A,Taylor DK,Espinosa A,Duff J

    更新日期:1998-07-01 00:00:00

  • The importance of considering trial design when interpreting clinical trial results.

    abstract:BACKGROUND:In recent decades, clinical trials have played an increasingly important role in determining how we practice. Trial results proving that a clinical finding poses risk have led to interventions that try to reduce risk. Clinical trials proving that a particular therapy provides better outcome than another ther...

    journal_title:Journal of cardiovascular pharmacology and therapeutics

    pub_type: 杂志文章

    doi:10.1177/107424840000500103

    authors: Reiffel JA

    更新日期:2000-01-01 00:00:00