AJP Heart and Circulatory Physiology (Am J Physiol Heart Circ Physiol)

Publisher: American Physiological Society (1887- ), American Physiological Society

Journal description

The American Journal of Physiology: Heart and Circulatory Physiology publishes original investigations on the physiology of the heart, blood vessels, and lymphatics, including experimental and theoretical studies of cardiovascular function at all levels of organization ranging from the intact animal to the cellular, subcellular, and molecular levels. It embraces new descriptions of these functions and of their control systems, as well as their bases in biochemistry, biophysics, genetics, and cell biology. Preference is given to research that provides significant new insights into the mechanisms that determine the performance of the normal and abnormal heart and circulation.

Current impact factor: 4.01

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 4.012
2012 Impact Factor 3.629
2011 Impact Factor 3.708
2010 Impact Factor 3.88
2009 Impact Factor 3.712
2008 Impact Factor 3.643
2007 Impact Factor 3.973
2006 Impact Factor 3.724
2005 Impact Factor 3.56
2004 Impact Factor 3.539
2003 Impact Factor 3.658
2002 Impact Factor 3.369
2001 Impact Factor 3.232
2000 Impact Factor 3.243
1999 Impact Factor 2.747

Impact factor over time

Impact factor

Additional details

5-year impact 3.86
Cited half-life 8.10
Immediacy index 0.72
Eigenfactor 0.06
Article influence 1.21
Website American Journal of Physiology - Heart and Circulatory Physiology website
Other titles American journal of physiology., Heart and circulatory physiology, Heart and circulatory physiology, AJP: Heart and circulatory physiology, AJP:heart, AJP:heart online
ISSN 1522-1539
OCLC 40069627
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

American Physiological Society

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Conditions
    • NIH, Wellcome Trust, HHMI, MRC and BBSRC authors will on their behalf have the Publisher's version/PDF deposited in PubMed Central for release 12 months after publication
    • Publisher's version/PDF cannot be used
  • Classification
    ​ white

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Dysfunction of the right ventricle (RV) is closely related to prognosis for patients with RV failure. Therefore, strategies to improve failing RV function are significant. In a mouse RV failure model, we previously reported that α1-adrenergic receptor (α1-AR) inotropic responses are increased. The present study determined the roles of both predominant cardiac α1-AR subtypes (α1A and α1B) in upregulated inotropy in failing RV. We used the mouse model of bleomycin-induced pulmonary fibrosis, pulmonary hypertension and RV failure. We assessed the myocardial contractile response in-vitro to stimulation of the α1A-subtype (using α1A-subtype-selective agonist A61603) and α1B-subtype (using α1A-subtype knockout mice and non-subtype-selective α1-AR agonist phenylephrine [PE]). In wild type non-failing RV, a negative inotropic effect of α1-AR stimulation with PE (force decreased ≈50 %) was switched to a positive inotropic effect (PIE) with bleomycin-induced RV injury. Upregulated inotropy in failing RV occurred with α1A-subtype stimulation (force increased ≈200%), but not with α1B-subtype stimulation (force decreased ≈50 %). Upregulated inotropy mediated by the α1A-subtype involved increased activator Ca2+ transients and increased phosphorylation of myosin regulatory light chain (a mediator of increased myofilament Ca2+ sensitivity). In failing RV, the PIE elicited by the α1A-subtype was appreciably less when the α1A-subtype was stimulated in combination with the α1B-subtype, suggesting functional antagonism between α1A- and α1B-subtypes. In conclusion, upregulation of α1-AR inotropy in failing RV myocardium requires the α1A-subtype and is opposed by the α1B-subtype. The α1A subtype might be a therapeutic target to improve the function of the failing RV. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00042.2015
  • AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00500.2015
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    ABSTRACT: Increased oxidative stress and inflammation contribute to impaired walking capacity and endothelial dysfunction in patients with intermittent claudication (IC). The goal of the study was to determine the effects of oral treatment with the antioxidant N-acetylcysteine (NAC) on walking capacity, leg postocclusive reactive hyperemia, circulating levels of inflammatory mediators and whole blood expression of angiogenic mediators in patients with IC. Following a double-blinded randomized crossover design, 10 patients with IC received NAC (1800 mg/day for 4 days plus 2700 mg prior to the experimental session) and placebo (PLA) before undergoing a graded treadmill exercise test. Leg postocclusive reactive hyperemia was assessed before and after the test. Blood samples were taken before and after NAC or PL ingestions, and 5 and 30 min after the exercise test for analysis of circulating inflammatory and angiogenic markers. Although NAC increased the plasma ratio of reduced-to-oxidized glutathione, there were no differences between experimental sessions for walking tolerance and postocclusive reactive hyperemia. Plasma concentrations of sVCAM-1, MCP-1 and ET-1 increased similarly following maximal exercise after PL and NAC (p<0.001). Whole blood expression of pro-angiogenic miRNA-126 increased after maximal exercise in the PL session, but treatment with NAC prevented this response. Likewise, exercise-induced changes in whole blood expression of VEGF, eNOS and PI3KR2 were blunted after NAC. In conclusion, oral NAC does not increase walking tolerance or leg blood flow in patients with IC. In addition, oral NAC prevents maximal exercise-induced increase in the expression of circulating miRNA-126 and other angiogenic mediators in patients with IC. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00158.2015
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    ABSTRACT: Hydrogen sulfide (H2S) is a biologically active endogenous gasotransmitter formed in penile tissue that has been shown to relax isolated cavernosal smooth muscle. In the present study erectile responses to the H2S donors sodium sulfide (Na2S) and sodium hydrosulfide (NaHS) were investigated in the anesthetized rat. Intracavernosal (ic) injections of Na2S in doses of 0.03-1 mg/kg increased intracavernosal pressure (ICP) and transiently decreased mean arterial pressure (MAP) in a dose dependent manner. Blood pressure responses to Na2S were rapid in onset and short in duration. Responses to Na2S and NaHS were similar at doses up to 0.3 mg/kg, after which a plateau in the erectile response to NaHS was reached. Increases in ICP in response to Na2S were attenuated by tetraethylammonium (TEA; K(+) channel inhibitor) and iberiotoxin (large conductance calcium-activated K(+) channel (BKCa) inhibitor), whereas glybenclamide (KATP channel inhibitor) and inhibitors of nitric oxide synthase (NOS), cyclooxygenase, and cytochrome p450 epoxygenase had no effect. These data indicate that erectile responses to Na2S are mediated by a TEA- and iberiotoxin-sensitive mechanism and that KATP channels, NO, or arachidonic acid metabolites are not involved. Na2S did not alter erectile responses to sodium nitroprusside (NO donor) or cavernosal nerve stimulation indicating that neither NO nor cGMP metabolism are altered. Thus, Na2S has erectile activity mediated by BKCa channels. It is suggested that strategies that increase H2S formation in penile tissue may be useful in the treatment of erectile dysfunction when NO bioavailability, KATP channel function, or poor responses to PGE1 are present. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00293.2015
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    ABSTRACT: Myocardial fibrosis is regarded as a pivotal pro-arrhythmic substrate but there have been no comprehensive studies showing a correlation between the severity of fibrosis and ventricular tachyarrhythmias (VTA). Our purpose was to document this relationship in a transgenic (TG) strain of mice with fibrotic cardiomyopathy. TG mice with cardiac overexpression of β2-adrenoceptor (β2-AR) and non-transgenic (NTG) littermates were studied at 4 to 12 months of age. VTA was quantified by ECG telemetry. The effect of pharmacological blockade of β2-AR on VTA was examined. Myocardial collagen content was determined by hydroxyproline assay. NTG and TG mice displayed circadian variation in heart rate, which was higher in TG than NTG mice (P <0.05). Frequent spontaneous ventricular ectopic beats (VEBs) and tachycardia (VT) were prominent in TG but not present in NTG mice. The frequency of VEB and VT episodes in TG mice increased with age (P <0.01). Ventricular collagen content was greater in TG than NTG mice (P <0.001) and correlated with age (r=0.71, P <0.01). The number of VEBs or VT episodes correlated with age (r=0.83 and r=0.73) and the content of total or cross-linked collagen (r=0.62~0.66, all P <0.01). While having no effect in younger β2-TG mice, β2-AR blockade reduced the frequency of VTA in old β2-TG mice with more severe fibrosis. In conclusion, β2-TG mice exhibit interstitial fibrosis and spontaneous onset of VTA, becoming more severe with aging. The extent of cardiac fibrosis is a major determinant for both the frequency of VTA and pro-arrhythmic action of β2-AR activation. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00405.2015
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    ABSTRACT: The abdominal aortic aneurysm (AAA) is a disease process that carries significant morbidity and mortality in the absence of early identification and treatment. While current management includes surveillance and surgical treatment of low- and high-risk aneurysms, respectively, our narrow understanding of the pathophysiology of AAAs limits our ability to more effectively manage and perhaps even prevent the occurrence of this highly morbid disease. Over the past couple of decades, there has been considerable interest in exploring the role of autoimmunity as an etiologic component of AAA. This review covers the current literature pertaining to this immunologic process, focusing on research that highlights the local and systemic immune components found in both human patients and murine models. A better understanding of the autoimmune mechanisms in the pathogenesis of AAAs can pave the way to novel and improved treatment strategies in this patient population. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00273.2015
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    ABSTRACT: Cardiac myofibroblast differentiation, as one of the most important cellular responses to heart injury, plays a critical role in cardiac remodeling and failure. Whilst biochemical cues for this have been extensively investigated, the role of mechanical cues (e.g., extracellular matrix (ECM) stiffness and mechanical strain) has also been found to mediate cardiac myofibroblast differentiation. Cardiac fibroblasts in vivo are typically subjected to a specific spatiotemporally changed mechanical microenvironment. When exposed to abnormal mechanical conditions (e.g., increased ECM stiffness or strain), cardiac fibroblasts can undergo myofibroblast differentiation. To date, the impact of mechanical cues on cardiac myofibroblast differentiation has been studied both in vitro and in vivo. Most of the related in vitro research into this has been mainly undertaken in two-dimensional (2D) cell culture systems, although a few three-dimensional (3D) studies that exist revealed an important role of dimensionality. However, despite remarkable advances, the comprehensive mechanisms for mechano-regulation of cardiac myofibroblast differentiation remain elusive. In this review, we introduce important parameters for evaluating cardiac myofibroblast differentiation and then discuss the development of both in vitro (2D and 3D) and in vivo studies on mechano-regulation of cardiac myofibroblast differentiation. An understanding of the development of cardiac myofibroblast differentiation in response to changing mechanical microenvironment will underlie potential targets for future therapy of cardiac fibrosis and failure. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00299.2015
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    ABSTRACT: Increased central vascular stiffening, assessed in vivo by determination of pulse wave velocity (PWV), is an independent predictor of cardiovascular event risk. Recent evidence demonstrates that accelerated aortic stiffening occurs in obesity; however, little is known regarding stiffening of other disease-relevant arteries or whether regional variation in arterial stiffening occurs in this setting. We addressed this gap in knowledge by assessing femoral PWV in vivo in conjunction with ex vivo analyses of femoral and coronary structure and function in a mouse model of western diet (WD; high-fat/high-sugar)-induced obesity and insulin resistance. WD feeding resulted in increased femoral PWV in vivo. Ex vivo analysis of femoral arteries revealed a leftward shift in the strain-stress relationship, increased modulus of elasticity, and decreased compliance indicative of increased stiffness following WD feeding. Confocal and multiphoton fluorescence microscopy revealed increased femoral stiffness involving decreased elastin/collagen ratio in conjunction with increased femoral transforming growth factor-β (TGF-β) content in WD fed mice. Further analysis of the femoral internal elastic lamina (IEL) revealed a significant reduction in the number and size of fenestrae with WD feeding. Coronary artery stiffness and structure was unchanged by WD feeding. Functionally, femoral, but not coronary, arteries exhibited endothelial dysfunction whereas coronary arteries exhibited increased vasoconstrictor responsiveness not present in femoral arteries. Taken together, our data highlight important regional variations in the development of arterial stiffness and dysfunction associated with WD feeding. Furthermore, our results suggest TGF-β signaling and IEL fenestrae remodeling as potential contributors to femoral artery stiffening in obesity. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00155.2015
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    ABSTRACT: The brain plays a prominent role in the regulation of inflammation. Immune cells are under control of the so-called cholinergic anti-inflammatory reflex, mainly acting via autonomic innervation of the spleen. Activation of this reflex inhibits the secretion of pro-inflammatory cytokines and may reduce the development of atherosclerosis. Therefore, the aim of this study was to evaluate the effects of selective parasympathetic (Px) and sympathetic (Sx) denervation of the spleen on inflammatory status and atherosclerotic lesion development. Female APOE*3-Leiden.CETP mice, a well-established model for human-like lipid metabolism and atherosclerosis, were fed a cholesterol-containing Western-type diet for 4 weeks after which they were sub-divided into three groups receiving either splenic Px, splenic Sx or sham surgery. The mice were subsequently challenged with the same diet for an additional 15 weeks. Selective Px increased leukocyte counts (i.e. dendritic cells, B cells and T cells) in the spleen and increased gene expression of pro-inflammatory cytokines in the liver and peritoneal leukocytes as compared to Sx and sham surgery. Both Px and Sx increased circulating pro-inflammatory cytokines IL-1β and IL-6. However, the increased pro-inflammatory status in denervated mice did not affect atherosclerotic lesion size or lesion composition. Predominantly selective Px of the spleen enhances the inflammatory status, which however does not aggravate diet-induced atherosclerotic lesion development. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00787.2014
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    ABSTRACT: In cardiovascular diseases sympathetic tone has been comprehensively studied whereas parasympathetic tone has received minor attention. The vesicular acetylcholine transporter knockdown homozygous (VAChT KD(HOM)) mouse is a useful model for examining the cardiocirculatory sympathovagal balance. Therefore, it was investigated whether cholinergic dysfunction caused by reduced VAChT expression may adversely impact the hemodynamic parameters - arterial pressure (AP) and heart rate (HR) - daily oscillation, baroreflex sensitivity, hemodynamic variability, sympathovagal balance and cardiovascular reactivity to restraint stress. Wild-type and VAChT KD(HOM) mice were anesthetized to telemetry transmitters implantation and the APs and HRs were recorded ten days after surgical recovery. Changes in HR elicited by methylatropine and propranolol provided the indices of sympathovagal tone. Cardiovascular reactivity in response to a restraint test was examined 24h after continuous recordings of the AP and HR. VAChT KD(HOM) mice exhibited reduced parasympathetic and elevated sympathetic tone. Daily oscillation of the AP and HR, and AP variability were similar between groups. Nevertheless, HR variability, 2UV pattern from symbolic analysis and baroreflex sensitivity were reduced in VAChT KD(HOM) mice. A change in mean AP due to restraint stress was greater in VAChT KD(HOM) mice, whereas the tachycardic response was not. These findings demonstrate that the cholinergic dysfunction present in the VAChT KD(HOM) mouse did not adversely impact basal hemodynamic parameters but promoted autonomic imbalance, attenuation of baroreflex sensitivity, and greater pressure response to restraint stress. These results provide a framework for understanding how autonomic imbalance impacts cardiovascular function. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00114.2015
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    ABSTRACT: Experimental diabetes in rat pregnancy is associated with impaired EDHF-mediated responses of maternal uteroplacental vasculature. Here we explored the role of endothelial cell (EC) Ca(2+)-activated K(+) channels in the diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to 2nd day pregnant rats and confirmed by development of maternal hyperglycemia. Control rats were injected with a citrate buffer. The changes in smooth muscle cell (SMC) [Ca(2+)]i, membrane potential and vasodilation induced by SKCa/IKCa channel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SKCa and IKCa-mediated currents was explored in freshly dissociated ECs. NS309 evoked a potent vasodilation that was effectively inhibited by TRAM-34 but not by apamin. NS309-induced SMC [Ca(2+)]i, MP and dilator responses were significantly diminished by diabetes; CyPPA-evoked responses were not affected. Ca(2+)-activated ion currents in ECs were insensitive to paxilline, markedly inhibited by ChTX, and diminished by apamin. NS309-induced EC currents were generated mostly due to activation of ChTX-sensitive channels. Maternal diabetes resulted in a significant reduction in ChTX-sensitive currents with no effect on apamin-sensitive or CyPPA-induced currents. We concluded that IKCa channels play a prevalent role over SKCa channels in generation of endothelial K(+) currents and vasodilation of uteroplacental arteries. Impaired function of IKCa channels importantly contributes to diabetes-induced uterine endothelial dysfunction. Therapeutic restoration of IKCa channel function may be a novel strategy in improvement of maternal uteroplacental blood flow in diabetic pregnancies. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00901.2014
  • AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00475.2015
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    ABSTRACT: Stroke outcome is improved by therapeutic ultrasound. This benefit is presumed to be principally from ultrasound-mediated thrombolysis. We hypothesized that the therapeutic benefit of ultrasound in stroke may, in part, be mediated by release of beneficial vasoactive substances. Accordingly we investigated the effect of ultrasound on levels of cytochrome P450, lipoxygenase and cyclooxygenase metabolites of arachidonic acid as well as adenosine release and endothelial nitric oxide synthase (eNOS) phosphorylation in primary brain endothelial cells in-vitro. Brain endothelial cells were exposed to 1.05 MHz ultrasound at peak rarefactional acoustic pressure amplitudes of 0.35, 0.55, 0.90 and 1.30 MPa. Epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraenoic acids (HETEs), prostaglandin E2 (PGE2), adenosine, nitrate/ nitrite and eNOS phosphorylation were measured after ultrasound exposure. Levels of 8,9-, 11,12- and 14,15-EET increased by 230 ± 28%, 240± 30% and 246 ± 31% (p<0.05) respectively, whereas 5- and 15-HETE levels were reduced to 24 ± 14% and 10 ± 3% (p<0.05), respectively, compared to cells not exposed to ultrasound. PGE2 levels were reduced to 56 ± 14% of control. Adenosine increased more than six-fold following ultrasound exposure compared to unstimulated cells (1.36 ± 0.22 ng∙mL(-1) versus 0.37 ± 0.10 ng∙mL(-1), p<0.05), nitrate/ nitrite was below levels of quantification and eNOS phosphorylation was not altered significantly. Our results suggest that ultrasound may enhance tissue perfusion during stroke by augmenting the generation of vasodilator compounds and inhibiting that of vasoconstrictors. Such regulation supports a beneficial role for therapeutic ultrasound in stroke independent of its effect on the occlusive thrombus. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00690.2014
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    ABSTRACT: Cardiac and skeletal muscle dysfunction is a recognized effect of cancer-induced cachexia, with alterations in heart function leading to heart failure and negatively impacting patient morbidity. Cachexia is a complex and multifaceted disease state with several potential contributors to cardiac and skeletal muscle dysfunction. Matrix metalloproteinases (MMPs) are a family of enzymes capable of degrading components of the extracellular matrix (ECM). Changes to the ECM cause disruption both in the connections between cells at the basement membrane and in cell-to-cell interactions. In this study, we utilized a murine model of c26 adenocarcinoma-induced cancer cachexia to determine changes in MMP gene and protein expression in cardiac and skeletal muscle. We analyzed MMP-2, -3, -9, and -14 as they have been shown to contribute to both cardiac and skeletal muscle ECM changes and, thereby, to pathology in models of heart failure and muscular dystrophy. In our model, cardiac and skeletal muscles showed a significant increase in RNA and protein levels of several MMPs and TIMPs. Cardiac muscle showed significant protein increase in MMP-2, -3, -9, and -14, while skeletal muscles showed increases in MMP-2,-3, and -14. Furthermore, collagen deposition was increased after c26 adenocarcinoma-induced cancer cachexia as indicated by an increased LV Picro-sirius red positive-stained area. Increases in serum hydroxyproline suggest increased collagen turnover, implicating skeletal muscle remodeling. Our findings demonstrate that cancer cachexia associated matrix remodeling results in cardiac fibrosis and possible skeletal muscle remodeling. With these findings, MMPs represent a possible therapeutic target for treatment of cancer-induced cachexia. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00106.2015
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    ABSTRACT: Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer, throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment and pulmonary hypertension that affects approximately 10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3600 - 4100 m) residents aged 18-25 yrs with excessive erythrocytosis (EE, hemoglobin [Hb] ≥ 18.3 g/dL), a preclinical form of CMS, and 66 controls identified from a community-based survey (n=981). Relative to controls, EE not only had higher Hb and erythrocyte counts but also lower alveolar ventilation, impaired pulmonary diffusion capacity (DLCO), higher systolic pulmonary artery pressure (sPPA), lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy. Compared to controls EE were more often born to mothers experiencing hypertensive complications of pregnancy (HTNPREG) and hypoxic during the perinatal period, with each increasing the risk of developing EE (OR 5.25, p=0.05 and OR 6.44, p=0.04 respectively) after accounting for other factors known to influence EE status. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities in the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00296.2015
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    ABSTRACT: Right ventricular failure (RVF) secondary to pulmonary regurgitation (PR) impairs right ventricular (RV) function and interrupts the interventricular relationship. There are few recommendations for the medical management of severe RVF after prolonged PR. PR was induced in 16 Danish landrace pigs by plication of the pulmonary valve leaflets. Twenty-three pigs served as controls. At re-examination the effect of milrinone, epinephrine and dopamine was evaluated using biventricular conductance and pulmonary catheters. 79 days after PR was induced, RV end-diastolic volume index (EDVI) had increased by 33% (p=0.006) and a severe decrease in the load-independent measurement of contractility (PRSW) (-58%; p=0.003). Lower cardiac index (CI) (-28%; p<0.0001), mean arterial pressure (-15%; p=0.01) and mixed venous oxygen saturation (SvO2) (36%; p<0.0001) were observed compared to the control group. The interventricular septum deviated towards the left ventricle (LV). Milrinone improved RV-PRSW and CI and maintained systemic pressure while reducing CVP. Epinephrine and dopamine further improved biventricular PRSW and CI equally in a dose-dependent manner. Systemic and pulmonary pressures were higher in the dopamine-treated animals compared to epinephrine-treated animals. None of the treatments improved stroke volume index (SVI) despite increases in contractility. Strong correlation was detected between SVI and LV-EDVI, but not SVI and biventricular contractility. In RVF due to PR, milrinone significantly improved CI, SvO2 and CVP and increased contractility in the RV. Epinephrine and dopamine had equal inotropic, but a greater vasopressor effect was observed for dopamine. SV was unchanged due to inability of both treatments to increase LV-EDVI. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00384.2015
  • AJP Heart and Circulatory Physiology 06/2015; 308(12):H1614. DOI:10.1152/ajpheart.00307.2015
  • AJP Heart and Circulatory Physiology 06/2015; 308(12):H1612-3. DOI:10.1152/ajpheart.00286.2015
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    ABSTRACT: The influences of severe heat stroke (HS) on cardiovascular function during recovery are incompletely understood. We hypothesized that HS would elicit a HR increase persisting through 24h of recovery due to hemodynamic, thermoregulatory and inflammatory events necessitating tachycardia to support mean arterial pressure (MAP). Core temperature (Tc), HR and MAP were measured via radiotelemetry in conscious male Fischer 344 rats (n=22; 282.4 ± 3.5g) during exposure to 37°C ambient temperature (Ta) until a Tc,Max of 42.0°C, and during recovery at 20°C Ta through 24h. Rats were divided into MILD, MODERATE and SEVERE groups based on pathophysiology. HS rats exhibited hysteresis relative to Tcwith HR higher for a given Tc during recovery compared to heating (p<0.0001). "Reverse" hysteresis occurred in MAP with pressure during cooling lower than heating per degree Tc (p<0.0001). MILD HS rats showed tachycardia (p<0.01 vs CON) through 8h of recovery, elevated MAP (p< 0.05 vs CON) for the initial 5h of recovery with sustained hyperthermia (p<0.05 vs CON) through 24h. MODERATE HS rats showed significant tachycardia (p<0.01 vs CON), normal MAP (p>0.05 vs CON) and rebound hyperthermia from 4-24h post-HS (p<0.05 vs CON). SEVERE HS rats showed tachycardia (p<0.05 vs CON), hypotension (p<0.01 vs CON) and hypothermia for 24h (p<0.05 vs CON). SEVERE HS rats showed 14- and 12-fold increase in heart and liver iNOS expression, respectively. Hypotension and hypothermia in SEVERE HS rats was consistent with iNOS-mediated systemic vasodilation. These findings provide mechanistic insight into hemodynamic and thermoregulatory impairments during 24h of HS recovery. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00918.2014
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    ABSTRACT: We assessed the atheroprotective efficiency of modified dairy fats in hyperlipidemic hamsters. A systems biology approach was implemented to reveal and quantify the dietary fat-related components of the disease. Three modified dairy fats (40% energy) were prepared from regular butter by mixing with a plant oil mixture, by removing cholesterol alone or by removing cholesterol in combination with reducing saturated fatty acids. A plant oil mixture with regular butter was used as the control diet. The atherosclerosis severity (aortic cholesteryl-ester level) was higher in the regular butter-fed hamsters than in the other four groups (P < 0.05). Eighty-seven of the 1666 variables measured from multi-platform analysis were found to be strongly associated with the disease. When aggregated into 10 biological clusters combined into a multivariate predictive equation, these 87 variables explained 81% of the disease variability. The biological cluster "regulation of lipid transport and metabolism" appeared central to atherogenic development relative to diets. The "vitamin E metabolism" cluster was the main driver of atheroprotection with the best performing transformed dairy fat. Under conditions that promote atherosclerosis, the impact of dairy fats on atherogenesis could be greatly ameliorated by technological modifications. Our modeling approach allowed for identifying and quantifying the contribution of complex factors to atherogenic development in each dietary setup. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 06/2015; DOI:10.1152/ajpheart.00032.2015