Detachable glass microelectrodes for recording action potentials in active moving organs
Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue ...
Source: AJP: Heart and Circulatory Physiology - June 9, 2017 Category: Cardiology Authors: Barbic, M., Moreno, A., Harris, T. D., Kay, M. W. Tags: INNOVATIVE METHODOLOGY Source Type: research

Toll-like receptor 2 dominance over Toll-like receptor 4 in stressful conditions for its detrimental role in the heart
It has been suggested that Toll-like receptor (TLR)4 promotes IL-10-mediated cardiac cell survival, whereas another receptor, TLR2, from the same family, is detrimental. Here, we examined the interactive role of these two innate signaling molecules under stressful conditions, including IL-10 knockout (IL-10–/–) mice, global ischemia-reperfusion (I/R) injury in rat hearts, and in vitro short hairpin RNA experimental models in the presence or absence of IL-10 (10 ng/ml). Circulating and myocardial levels of TNF-α as well as apoptosis and fibrosis were higher in IL-10–/– mice. The increase in TLR...
Source: AJP: Heart and Circulatory Physiology - June 9, 2017 Category: Cardiology Authors: Bagchi, A. K., Akolkar, G., Mandal, S., Ayyappan, P., Yang, X., Singal, P. K. Tags: ARTICLES Source Type: research

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation
Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite pre...
Source: AJP: Heart and Circulatory Physiology - June 9, 2017 Category: Cardiology Authors: Sakai, M., Suzuki, T., Tomita, K., Yamashita, S., Palikhe, S., Hattori, K., Yoshimura, N., Matsuda, N., Hattori, Y. Tags: ARTICLES Source Type: research

A comprehensive analysis of myocardial substrate preference emphasizes the need for a synchronized fluxomic/metabolomic research design
This study was performed with a more physiologically relevant perfusate than the previous work. Increasing concentrations of propionate did not cause adverse effects on myocardial metabolism, as evidenced by unchanged O2 consumption, TCA cycle flux, and developed pressures. Propionate at 1 mM was sufficient to achieve significant increases in pyruvate dehydrogenase flux (3x), and anaplerosis (6x), as measured by isotopomer analysis. These results further demonstrate the potential of propionate as an aid for the correct estimation of total carbohydrate oxidative capacity in the heart. However, liquid chromotography/mass spe...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Ragavan, M., Kirpich, A., Fu, X., Burgess, S. C., McIntyre, L. M., Merritt, M. E. Tags: INNOVATIVE METHODOLOGY Source Type: research

Increased amplitude of inward rectifier K+ currents with advanced age in smooth muscle cells of murine superior epigastric arteries
Inward rectifier K+ channels (KIR) may contribute to skeletal muscle blood flow regulation and adapt to advanced age. Using mouse abdominal wall superior epigastric arteries (SEAs) from either young (3–6 mo) or old (24–26 mo) male C57BL/6 mice, we investigated whether SEA smooth muscle cells (SMCs) express functional KIR channels and how aging may affect KIR function. Freshly dissected SEAs were either enzymatically dissociated to isolate SMCs for electrophysiological recording (perforated patch) and mRNA expression or used intact for pressure myography. With 5 mM extracellular K+ concentration ([K+]o), exposur...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Hayoz, S., Pettis, J., Bradley, V., Segal, S. S., Jackson, W. F. Tags: RESEARCH ARTICLE Source Type: research

Anterior cerebral blood velocity and end-tidal CO2 responses to exercise differ in children and adults
Little is known about the response of the cerebrovasculature to acute exercise in children and how these responses might differ with adults. Therefore, we compared changes in middle cerebral artery blood velocity (MCAVmean), end-tidal Pco2 (PETCO2), blood pressure, and minute ventilation (Ve) in response to incremental exercise between children and adults. Thirteen children [age: 9 ± 1 (SD) yr] and thirteen sex-matched adults (age: 25 ± 4 yr) completed a maximal exercise test, during which MCAVmean, PETCO2, and Ve were measured continuously. These variables were measured at rest, at exercise intensities speci...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Ellis, L. A., Ainslie, P. N., Armstrong, V. A., Morris, L. E., Simair, R. G., Sletten, N. R., Tallon, C. M., McManus, A. M. Tags: RESEARCH ARTICLE Source Type: research

Arterial viscoelasticity: role in the dependency of pulse wave velocity on heart rate in conduit arteries
This study aimed to explore a plausible viscoelastic mechanism by which HR exerts an influence on arterial stiffness. A multisegment transmission line model of the human arterial tree incorporating fractional viscoelastic components in each segment was used to investigate the effect of varying fractional order parameter (α) of viscoelasticity on the dependence of aortic arch to femoral artery pulse wave velocity (afPWV) on HR. HR was varied from 60 to 100 beats/min at a fixed mean flow of 100 ml/s. PWV was calculated by intersecting tangent method (afPWVTan) and by phase velocity from the transfer function (afPWVTF) ...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Xiao, H., Tan, I., Butlin, M., Li, D., Avolio, A. P. Tags: RESEARCH ARTICLE Source Type: research

Reduced membrane cholesterol limits pulmonary endothelial Ca2+ entry after chronic hypoxia
Chronic hypoxia (CH)-induced pulmonary hypertension is associated with diminished production of endothelium-derived Ca2+-dependent vasodilators such as nitric oxide. Interestingly, ATP-induced endothelial Ca2+ entry as well as membrane cholesterol (Chol) are decreased in pulmonary arteries from CH rats (4 wk, barometric pressure = 380 Torr) compared with normoxic controls. Store-operated Ca2+ entry (SOCE) and depolarization-induced Ca2+ entry are major components of the response to ATP and are similarly decreased after CH. We hypothesized that membrane Chol facilitates both SOCE and depolarization-induced pulmonary endothe...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Zhang, B., Naik, J. S., Jernigan, N. L., Walker, B. R., Resta, T. C. Tags: RESEARCH ARTICLE Source Type: research

Loss of VEGFB and its signaling in the diabetic heart is associated with increased cell death signaling
Vascular endothelial growth factor B (VEGFB) is highly expressed in metabolically active tissues, such as the heart and skeletal muscle, suggesting a function in maintaining oxidative metabolic and contractile function in these tissues. Multiple models of heart failure have indicated a significant drop in VEGFB. However, whether there is a role for decreased VEGFB in diabetic cardiomyopathy is currently unknown. Of the VEGFB located in cardiomyocytes, there is a substantial and readily releasable pool localized on the cell surface. The immediate response to high glucose and the secretion of endothelial heparanase is the re...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Lal, N., Chiu, A. P.-L., Wang, F., Zhang, D., Jia, J., Wan, A., Vlodavsky, I., Hussein, B., Rodrigues, B. Tags: RESEARCH ARTICLE Source Type: research

Increased hypoxia-inducible factor-1{alpha} in striated muscle of tumor-bearing mice
We examined venous blood gas values in the tumor-bearing mice and found significantly lower oxygen concentration compared with control animals in the third week after tumor inoculation. We also examined select skeletal muscles to determine whether they are similarly affected. In the diaphragm, extensor digitorum longus, and soleus, we found significantly increased HIF-1α in tumor-bearing mice, indicating a hypoxic response, not only in the heart, but also in skeletal muscle. These results indicate that HIF-1α may contribute, in part, to the metabolic changes that occur during cancer cachexia. NEW & NOTEWORT...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Devine, R. D., Bicer, S., Reiser, P. J., Wold, L. E. Tags: RESEARCH ARTICLE Source Type: research

Contribution of two-pore K+ channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes
Two-pore K+ (K2p) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and isc...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Chai, S., Wan, X., Nassal, D. M., Liu, H., Moravec, C. S., Ramirez-Navarro, A., Deschenes, I. Tags: RESEARCH ARTICLE Source Type: research

Cerebral microhemorrhages: mechanisms, consequences, and prevention
The increasing prevalence of multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds") is a significant, newly recognized problem in the aging population of the Western world. CMHs are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function, potentially contributing to cognitive decline, geriatric psychiatric syndromes, and gait disorders. Clinical studies show that aging and hypertension significantly increase prevalence of CMHs. CMHs are also now recognized by the National Institutes of Health as a major factor in Alzheimer’s disease p...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Ungvari, Z., Tarantini, S., Kirkpatrick, A. C., Csiszar, A., Prodan, C. I. Tags: REVIEW Source Type: research

Endothelial dysfunction inhibits the ability of haptoglobin to prevent hemoglobin-induced hypertension
In conclusion, in healthy C57Bl/6 mice with normal endothelium, coadministration of haptoglobin but not hemopexin with cell-free hemoglobin prevents acute hemoglobin-induced systemic hypertension by compartmentalizing cell-free hemoglobin in plasma. In murine diseases associated with endothelial dysfunction, haptoglobin therapy appears to be insufficient to prevent hemoglobin-induced vasoconstriction. NEW & NOTEWORTHY Coadministraton of haptoglobin but not hemopexin with cell-free hemoglobin prevents hemoglobin-induced systemic hypertension in mice with a normal endothelium. In contrast, treatment with the same amount ...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Graw, J. A., Yu, B., Rezoagli, E., Warren, H. S., Buys, E. S., Bloch, D. B., Zapol, W. M. Tags: RAPID REPORT Source Type: research

Inhibition of the mTOR pathway in abdominal aortic aneurysm: implications of smooth muscle cell contractile phenotype, inflammation, and aneurysm expansion
This study provides novel observations that mechanistic target of rapamycin (mTOR) signaling is overactivated in aortic smooth muscle cells and contributes to mouse abdominal aortic aneurysm (AAA) and that rapamycin protects against aneurysm development. Our data highlight the importance of preservation and/or restoration of the smooth muscle cell contractile phenotype and reduction of inflammation by mTOR inhibition in AAA. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Li, G., Qin, L., Wang, L., Li, X., Caulk, A. W., Zhang, J., Chen, P.-Y., Xin, S. Tags: RESEARCH ARTICLE Source Type: research

Impact of RyR2 potentiation on myocardial function
This perspective attempts to shed light on an old and not yet solved controversy in cardiac physiology, i.e., the impact of increasing ryanodine receptor (RyR)2 open probability on myocardial function. Based on an already proven myocyte model, it was shown that increasing RyR2 open probability results in a purely short-lived increase in Ca2+ transient amplitude, and, therefore, it does not increase cardiac contractility. However, potentiation of RyR2 activity permanently enhances fractional Ca2+ release, shifting the intracellular Ca2+ transient versus sarcoplasmic reticulum (SR) Ca2+ content curve to a new state of higher...
Source: AJP: Heart and Circulatory Physiology - June 1, 2017 Category: Cardiology Authors: Lascano, E., Negroni, J., Vila Petroff, M., Mattiazzi, A. Tags: PERSPECTIVES Source Type: research