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: 3.84

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.838
2013 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 3.88
Cited half-life 9.10
Immediacy index 0.77
Eigenfactor 0.04
Article influence 1.19
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 can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Conditions
    • Author's Pre-print on pre-print servers
    • 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
    • May link to publisher version with DOI
    • Publisher last reviewed on 03/06/2015
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of capillaries is to serve as the interface for delivery of oxygen and removal of metabolites to/from tissues. During the past decade there has been a proliferation of studies that have advanced our understanding of angiogenesis demonstrating tissue capillary supply is under strict control during health, but poorly controlled in disease - resulting in either excessive capillary growth (pathological angiogenesis) or losses in capillarity (rarefaction). Given that skeletal muscle comprises nearly 40% of body mass in humans, skeletal muscle capillary density has a significant impact on metabolism, endocrine function, and locomotion, and is tightly regulated at many different levels. Skeletal muscle is also high adaptable, and thus one of the few organ systems which can be experimentally manipulated (e.g. by exercise) to study physiologic regulation of angiogenesis. This review will focus on 1) the methodological concerns that have arisen in determining skeletal muscle capillarity, and 2) highlight the concepts that are reshaping our understanding of the angio-adaptation process. We also summarize selected new findings (physical influences, molecular changes and ultrastructural rearrangement of capillaries) that identify areas of future research with the greatest potential to expand our understanding of how angiogenesis is normally regulated, and that may also help to better understand conditions of uncontrolled (pathologic) angiogenesis.
    AJP Heart and Circulatory Physiology 11/2015; DOI:10.1152/ajpheart.00635.2015
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    ABSTRACT: Myocardial electrical impedance is influenced by the mechanical activity of the heart. Therefore, the ischemia induced mechanical dysfunction may cause specific changes in the systolic-diastolic pattern of myocardial impedance but this is not known. This study aimed to analyze the phasic changes of myocardial resistivity in normal and ischemic conditions. Myocardial resistivity was measured continuously during the cardiac cycle using 26 different simultaneous excitation frequencies (1 kHz-1 MHz) in 7 anesthetized open chest pigs. Animals were submitted to 30 minutes regional ischemia by acute left anterior descending coronary artery occlusion. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt and aortic blood flow were recorded simultaneously. Baseline myocardial resistivity depicted a phasic pattern during the cardiac cycle with higher values at the pre-ejection period (4.19±1.09% increase above the mean,p<0.001) and lower values during relaxation phase (5.01±0.85% below the mean,p<0.001). Acute coronary occlusion induced two effects on the phasic resistivity curve: 1) a prompt (5 min ischemia) holosystolic resistivity rise leading to a bell-shaped waveform and to a reduction of the area under the LV pressure-impedance curve (1427±335 Ω•cm•mmHg vs 757±266 Ω•cm•mmHg,p<0.01,41 kHz) and 2) a subsequent (5-10 min ischemia) progressive mean resistivity rise (325±23 Ω•cm vs 438±37 Ω•cm at 30 min,p<0.01,1 kHz). The structural and mechanical myocardial dysfunction induced by acute coronary occlusion can be recognized by specific changes in the systolic-diastolic myocardial resistivity curve. Therefore these changes may become a new indicator (surrogate) of evolving acute myocadial ischemia.
    AJP Heart and Circulatory Physiology 11/2015; DOI:10.1152/ajpheart.00754.2015
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    ABSTRACT: Rationale: Studies of adults with orthostatic intolerance (OI) reveal altered neurohumoral responses to orthostasis, which provide mechanistic insight into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. Objective: Determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Methods and results: Subjects ages 10-18 years were prospectively recruited if they exhibited ≥2 traditional OI symptoms and were referred for tilt testing (HUT). Circulating catecholamines, vasopressin, aldosterone, renin and angiotensins were measured supine and after 15 minutes of 70 degree tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and angiotensin II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), Syncope, and POTS/Syn. Key characteristics included higher HUT-induced norepinephrine in POTS and vasopressin in OH and syncope, and higher supine and HUT aldosterone in OH subjects. Conclusions: Children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of hemodynamic response during orthostatic challenge. Elevated AVP levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher NE levels as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles towards the goal of selecting more focused and mechanistic based treatment options for pediatric patients with OI.
    AJP Heart and Circulatory Physiology 11/2015; DOI:10.1152/ajpheart.00583.2015
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    ABSTRACT: We previously reported that the cardiomyocyte-specific protein, Leucine-rich repeat containing 10 (LRRC10), has critical functions in the mammalian heart. Here, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10 null (Lrrc10(-/-)) mice. Mild pressure overload induces severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice as compared to controls. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte drop-out were not different from control. Lrrc10(-/-) cardiomyocytes also exhibit reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that histidine 150 of LRRC10 is required for interaction with actin and this interaction is reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these studies demonstrate that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis.
    AJP Heart and Circulatory Physiology 11/2015; DOI:10.1152/ajpheart.00717.2014
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    ABSTRACT: Previous studies have reported exaggerated increases in arterial blood pressure during exercise in type 2 diabetes (T2D) patients. However, little is known regarding the underlying neural mechanism(s) involved. We hypothesized that T2D patients would exhibit an augmented muscle metaboreflex activation and this contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in 16 patients with T2D (8 normotensive and 8 hypertensive) and 10 healthy controls. Graded isolation of the muscle metaboreflex was achieved by post-exercise ischemia (PEI) following static handgrip performed at 30% and 40% maximal voluntary contraction (MVC). A cold pressor test (CPT) was also performed as a generalized sympatho-excitatory stimulus. Increases in MAP and MSNA during 30 and 40% MVC handgrip were augmented in T2D patients compared to controls (P<0.05), and these differences were maintained during PEI (MAP: 30% PEI: T2D, Δ16 ± 2 vs. Controls, Δ8 ± 1 mmHg; 40% PEI: T2D, Δ26 ± 3 vs. Controls, Δ16 ± 2 mmHg, both P<0.05). MAP and MSNA responses to handgrip and PEI were not different between normotensive and hypertensive T2D patients (P>0.05). Interestingly, MSNA responses were also greater in T2D patients compared to controls during the CPT (P<0.05). Collectively, these findings indicate that muscle metaboreflex activation is augmented in T2D patients and this contributes, in part, to augmented pressor and sympathetic responses to exercise in this patient group. Greater CPT responses suggest that a heightened central sympathetic reactivity may be involved.
    AJP Heart and Circulatory Physiology 11/2015; DOI:10.1152/ajpheart.00636.2015
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    ABSTRACT: Background: Arrhythmogenic ventricular cardiomyopathy (AVC) is a frequent underlying cause for arrhythmias and sudden cardiac death especially during intense exercise. The mechanisms involved remain largely unknown. Objective: To investigate how chronic endurance exercise contributes to desmoplakin (DSP) mutation-induced AVC pathogenesis. Methods: Transgenic mice with overexpression of desmoplakin, wild-type (Tg-DSP(WT)) or the R2834H mutant (Tg-DSP(R2834H)) along with control non-transgenic (NTg) littermates were kept sedentary or exposed to a daily running regimen for 12 weeks. Cardiac function and morphology were analyzed using echocardiography, electrocardiography, histology, immunohistochemistry, RNA and protein analysis. Results: At baseline, 4-week-old mice from all groups displayed normal cardiac function. When subjected to exercise, all mice retained normal cardiac function and left ventricular morphology; however, Tg-DSP(R2834H) mutants displayed right ventricular (RV) dilation and wall thinning, unlike NTg and Tg-DSP(WT). The Tg-DSP(R2834H) hearts demonstrated focal fat infiltrations in RV and cytoplasmic aggregations consisting of desmoplakin, plakoglobin and connexin43. These aggregates coincided with disruption of the intercalated disks, intermediate filaments and microtubules. Though Tg-DSP(R2834H) mice already displayed high levels of p-GSK3-β(Ser9) and p-AKT1(Ser473) under sedentary conditions, decrease of nuclear GSK3-β and AKT1 levels with reduced p-GSK3-β(Ser9), p-AKT1(Ser473), p-AKT1(Ser308) and loss of nuclear JUP was apparent after exercise. In contrast, Tg-DSP(WT) showed up-regulation of p-AKT1(Ser473), p-AKT1(Ser308) and p-GSK3-β(Ser9) in response to exercise. Conclusions: Our data suggest that endurance exercise accelerates AVC pathogenesis in Tg-DSP(R2834H) mice and this event is associated with perturbed AKT1 and GSK3-β signaling. Our study suggests a potential mechanism-based approach to exercise management in patients with AVC.
    AJP Heart and Circulatory Physiology 11/2015; DOI:10.1152/ajpheart.00295.2015
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    ABSTRACT: The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension. To test this hypothesis, changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to electrical stimulation of mesencephalic locomotor region (MLR; 20-50 μA in 10-μA steps evoking fictive locomotion), a putative component of the central command pathway, were examined in decerebrate, paralyzed normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Tibial nerve discharge during MLR stimulation significantly increased in an intensity-dependent manner in both WKY and SHR but was not different between groups. Stimulation of the MLR evoked significantly larger increases in RSNA and MAP with increasing stimulation intensity in both groups. Importantly, the increases in sympathetic and pressor responses to this fictive locomotion were significantly greater in SHR compared to WKY across all stimulation intensities (e.g. at 50μA, ΔRSNA; WKY, 153±31%, SHR, 287±42%, ΔMAP; WKY, 87±9 mmHg, SHR, 139±7 mmHg). These findings provide the first evidence that central command may be a critical contributor to the exaggerated rise in sympathetic activity and blood pressure during exercise in hypertension.
    AJP Heart and Circulatory Physiology 11/2015; DOI:10.1152/ajpheart.00479.2015
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    ABSTRACT: Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in the vasculature. In this study, we tested the hypothesis that H2S contributes to coronary vasoregulation and evaluated the physiological relevance of two sources of H2S, namely, cystathionine-gamma-lyase (CSE) and 3-mercaptypyruvate sulfertransferase (MPST). MPST was detected in human coronary artery endothelial cells as well as rat and mouse coronary artery; CSE was not detected in the coronary vasculature. Rat coronary artery homogenates produced H2S through the MPST pathway but not the CSE pathway in vitro. In vivo coronary vasorelaxation response was similar in CSE knockout mice, wild-type mice (WT), and WT mice treated with the CSE inhibitor propargylglycine, suggesting that CSE-produced H2S does not have a significant role in coronary vasoregulation in vivo. Ex vivo, MPST substrate 3-mercaptopyruvate (3-MP) and H2S donor sodium hydrosulfide (NaHS) elicited similar coronary vasoreactivity responses. Pyruvate did not have any effects on vasoreactivity. The vasoactive effect of H2S appeared to be NO-dependent: H2S induced coronary vasoconstriction in the presence of NO and vasorelaxation in its absence. Maximal endothelial-dependent relaxation was intact after 3-MP, and or NaHS induced an increase in pre-constriction tone, suggesting that eNOS activity was not significantly inhibited. In vitro, H2Sreacted with NO, which may, in part explain the vasoconstrictive effects of 3-MP and NaHS. Taken together, these data show that MPST rather than CSE generates H2S in coronary artery, mediating its effects through direct modulation of NO. This has important implications for H2S based therapy in healthy and diseased coronary arteries.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00574.2014
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    ABSTRACT: Peripheral rat diaphragmatic lymphatic vessels, endowed with intrinsic spontaneous contractility were in vivo filled with fluorescent dextrans and microspheres and subsequently studied ex vivo in excised diaphragmatic samples. Changes in diameter and lymph velocity were detected, in a vessel segment, during spontaneous lymphatic smooth muscle contraction and upon activation, through electrical whole-field stimulation, of diaphragmatic skeletal muscle fibres. During intrinsic contraction lymph flowed both forward and backward, with a net forward propulsion of 14.1 ± 2.9 µm at an average net forward speed of 18.0 ± 3.6 μm/sec. Each skeletal muscle contraction sustained a net forward-lymph displacement of 441.9 ± 159.2 μm at an average velocity of 339.9 ± 122.7 μm/sec, values significantly higher than those documented during spontaneous contraction. The flow velocity profile was parabolic both during spontaneous and skeletal muscle contraction and the shear stress calculated at the vessel wall at the highest instantaneous velocity never exceeded 0.25 dyne/cm(2). Therefore, we propose that the synchronous contraction of diaphragmatic skeletal muscle fibres recruited at every inspiratory act dramatically enhances diaphragmatic lymph propulsion, while the spontaneous lymphatic contractility might, at least in the diaphragm, be essential in organizing the pattern of flow redistribution within the diaphragmatic lymphatic circuit. Moreover, the very low shear stress values observed in diaphragmatic lymphatics suggest that, in contrast with other contractile lymphatic networks, a likely interplay between intrinsic and extrinsic mechanisms be based on a mechanical and/or electrical connection rather than on nitric oxide release.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00640.2015
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    ABSTRACT: Methods: Cardiac contractility and hemodynamics were assessed using a modified Langendorff system, infarct size evaluated using 2,3,5-Triphenyl-2H-tetrazolium chloride (TTC) staining and levels of phosphorylated and total endothelial NO synthase (eNOS) were determined by Western Blotting. Isolated hearts were subjected to 30 mins of regional ischemia, produced by ligation of left anterior descending (LAD) coronary artery followed by 30 min of reperfusion (n=6). Hearts were also subjected to pacing postconditioning (3 cycles of 30 seconds left ventricle (LV) pacing alternated with 30 seconds right atrium (RA) pacing) and/or treated during reperfusion with Ang-(1-7), L-NAME or Ang-(1-7) receptor (Mas) antagonist ((D-Ala7)-Angiotensin I/II (1-7). Results: PPC-mediated improvement in cardiac contractility and hemodyanamics, infarct size and eNOS phosphorylation were significantly attenuated upon treatment with (D-Ala7)-Angiotensin I/II (1-7) or L-NAME. Treatment with Ang-(1-7) improved cardiac function and reduced infarct size, however, the effects of Ang-(1-7) were not additive with PPC. Conclusions: These data provide novel insights into the mechanisms of PPC in that they involve MAS receptor and eNOS in PPC-mediated cardioprotection.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00121.2015
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    ABSTRACT: Mitochondrial quality control mechanisms have been implicated in protection against cardiac ischemia-reperfusion (IR) injury. Previously, cloxyquin (5-chloroquinolin-8-ol) was identified via phenotypic screening as a cardioprotective compound. Herein, cloxyquin was identified as a mitochondrial uncoupler in both isolated heart mitochondria and adult cardiomyocytes. Additionally, cardiomyocytes isolated from transgenic mice expressing GFP-tagged microtubule-associated protein light chain 3 showed increased autophagosome formation with cloxyquin treatment. The autophagy inhibitor chloroquine abolished cloxyquin-induced cardioprotection in both cellular and perfused heart (Langendorff) models of IR injury. Finally, in an in-vivo murine left anterior descending coronary artery occlusion model of IR injury, cloxyquin significantly reduced infarct size from 31.4 ± 3.4 % to 16.1 ± 2.2 %. In conclusion, the cardioprotective compound cloxyquin simultaneously uncoupled mitochondria and induced autophagy. Importantly, autophagy appears to be required for cloxyquin-induced cardioprotection.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00926.2014
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    ABSTRACT: Sarcolipin (SLN) is a small proteolipid and a regulator of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA). In heart tissue, SLN is exclusively expressed in the atrium. Previously, we inserted Cre recombinase into the endogenous SLN locus by homologous recombination and succeeded in generating the SLN-Cre knock-in (Sln(Cre/+)) mice. This Sln(Cre/+) mouse can be used to generate an atrium-specific gene-targeting mutant, and it is based on the Cre-loxP system. In the present study, we used adult Sln(Cre/+) mice atria and analyzed the effects of heterozygous SLN deletion by Cre knock-in prior to use as the gene targeting mouse. Both SLN mRNA and protein levels were decreased in the Sln(Cre/+) mouse atria, but there were no morphological, physiological or molecular biological abnormalities. The properties of contractility and Ca(2+)handling were similar to wild type (WT) mice and expression levels of several stress markers and SR-related protein levels were not different between Sln(Cre/+) and WT mice. Moreover, there was no significant difference in SERCA activity between the two groups. We showed that Sln(Cre/+) mice were not significantly different from WT mice in all aspects that were examined. The present study provides basic characteristics of Sln(Cre/+) mice and possibly information on the usefulness of Sln(Cre/+) mice as an atrium-specific gene-targeting model.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00411.2015
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    ABSTRACT: The stromal cell-derived factor (SDF)-1:CXCR4 is important in myocardial repair. In this study we tested the hypothesis that early up-regulation of cardiomyocyte CXCR4 (CM-CXCR4) at a time of high myocardial SDF-1 expression could be a strategy to engage the SDF-1:CXCR4 axis and improve cardiac repair. The effects of the HIF hydroxylase inhibitor Dimethyloxalylglycine (DMOG) on CXCR4 expression was tested on H9c2 cells. In mice a myocardial infarction (MI) was produced in CM-CXCR4 null and wild type controls. Mice were randomized to receive injection of DMOG (DMOG group) or saline (Saline group) into the border zone after MI. Protein and mRNA expression of CM-CXCR4 were quantified. Echocardiography was used to assess cardiac function. During hypoxia, DMOG treatment increased CXCR4 expression of H9c2 cells by 29% and 42% at 15 and 24 hours, respectively. In vivo DMOG treatment increased CM-CXCR4 expression at 15 hours post MI in control mice but not in CM-CXCR4 null mice. DMOG resulted in increased ejection fraction in control mice but not in CM-CXCR4 null mice 21 days after MI. Consistent with greater cardiomyocyte survival with DMOG treatment, we observed a significant increase in cardiac myosin-positive area within the infarct zone after DMOG treatment in control mice, but no increase in CM-CXCR4 null mice. Inhibition of cardiomyocyte death in MI through the stabilization of HIF-1a requires downstream CM-CXCR4 expression. These data suggest that engagement of the SDF-1:CXCR4 axis through the early up-regulation of CM-CXCR4 is a strategy for improving cardiac repair after MI.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00449.2015
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    ABSTRACT: Background: Kinetic energy (KE) of intra-cardiac blood may play an important role in cardiac function. The aims of this study were 1) quantify and investigate determinants of KE, 2) compare KE expenditure of intra-cardiac blood between athletes and controls, 3) quantify the amount of KE inside and outside the diastolic vortex. Methods: 14 athletes and 14 volunteers underwent cardiac magnetic resonance imaging including 4-dimensional phase-contrast sequences. KE was quantified in 4 chambers and energy expenditure was calculated by determining mean KE/cardiac index. Results: Left ventricular (LV) mass was an independent predictor of diastolic LVKE (R(2)=0.66, p<0.001) while right ventricular (RV) end-diastolic volume was important for diastolic RVKE (R(2)=0.76, p<0.001). Mean KE/cardiac index did not differ between groups (controls 0.53±0.14, athletes 0.56±0.21mJ/(L/min/m(2)), p=0.98). Mean LV diastolic vortex KE made up 70±1% and 73±2% of total LV diastolic KE in athletes and controls (p=0.18). Conclusion: The characteristics of the LV as a pressure pump and the RV as a volume pump are demonstrated as an association between LVKE and LV mass and between RVKE and end-diastolic volume. This also suggests different filling mechanisms where the LV is dependent on diastolic suction while the RV fills with a basal movement of the atrioventricular-plane over "stationary" blood. Both groups had similar energy expenditure for intra-cardiac blood flow indicating similar pumping efficiency, likely explained by the lower heart rate which cancels the higher KE per heart beat in athletes. The majority of LVKE is found within the LV diastolic vortex in contrast to earlier findings.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00544.2015
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    ABSTRACT: Throughout the United States, air pollution correlates with adverse health outcomes and cardiovascular disease incidence is commonly increased following environmental exposure. In areas surrounding active mountaintop removal mines (MTM) a further increase in cardiovascular morbidity is observed and may be attributed in part to particulate matter (PM) released from the mine. The mitochondrion has been shown to be central in the etiology of many cardiovascular diseases, yet its role in PM related cardiovascular effects are not realized. In this study we sought to elucidate the cardiac processes that are disrupted following exposure to mountaintop removal mining particulate matter (PMMTM). To address this question we exposed male Sprague-Dawley rats to PMMTM, collected within one mile of an active MTM site, using intratracheal instillation. Twenty-four hours following exposure we evaluated cardiac function, apoptotic indices and mitochondrial function. PMMTM exposure, elicited a significant decrease in ejection fraction and fractional shortening compared to controls. Investigation into the cellular impacts of PMMTM exposure identified a significant increase in mitochondrial-induced apoptosis as reflected by an increase in TUNEL positive nuclei and increased caspase-3 and -9 activities. Finally, a significant increase in mitochondrial transition pore opening leading to decreased mitochondrial function was identified following exposure. In conclusion, our data suggest that pulmonary exposure to PMMTM increases cardiac mitochondrial-associated apoptosis and decreases mitochondrial function concomitant with decreased cardiac function. These results suggest that increased cardiovascular disease incidence in populations surrounding MTM mines may be associated with increased cardiac cell apoptosis and decreased mitochondrial function.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00353.2015
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    ABSTRACT: Muscle-restricted coiled-coil protein (MURC), also referred to as Cavin-4, is a member of the cavin family that works cooperatively with caveolins in caveola formation and function. Cavins are cytoplasmic proteins with coiled-coil domains and form heteromeric complexes, which are recruited to caveolae in cells expressing caveolins. Among caveolins, caveolin-3 (Cav3) is exclusively expressed in muscle cells, similar to MURC/Cavin-4. In the heart, Cav3 overexpression contributes to cardiac protection, while its deficiency leads to progressive cardiomyopathy. Mutations in the MURC/Cavin-4 gene have been identified in patients with dilated cardiomyopathy. Here we show the role of MURC/Cavin-4 as a caveolar component in the heart. In H9c2 cells, MURC/Cavin-4 was localized at the plasma membrane, while a MURC/Cavin-4 mutant lacking the coiled-coil domain (ΔCC) was primarily localized to the cytoplasm. ΔCC bound to Cav3 and impaired membrane localization of Cav3 in cardiomyocytes. Additionally, although ΔCC did not alter Cav3 mRNA expression, ΔCC decreased the Cav3 protein level. MURC/Cavin-4 and ΔCC similarly induced cardiomyocyte hypertrophy; however, ΔCC showed higher hypertrophy-related fetal gene expression than MURC/Cavin-4. ΔCC induced ERK activation in cardiomyocytes. Transgenic mice expressing ΔCC in the heart (ΔCC-Tg mice) showed impaired cardiac function accompanied by cardiomyocyte hypertrophy and marked interstitial fibrosis. ΔCC-Tg hearts showed reduction of the Cav3 protein level and the activation of ERK. These results suggest that MURC/Cavin-4 requires its coiled-coil domain to target the plasma membrane and to stabilize Cav3 at the plasma membrane of cardiomyocytes, and that MURC/Cavin-4 functions as a crucial caveolar component to regulate cardiac function.
    AJP Heart and Circulatory Physiology 10/2015; DOI:10.1152/ajpheart.00446.2015