tbuckley/cabot-search huggingface dataset:
Mechanism of biphasic contractions in strontium-treated ventricular muscle.
Authors: B WKing, DBose
Journal: Circulation Research (1983)

Biphasic contractions were produced in dog trabeculae by replacing 90-95% of the calcium in the bathing solution with strontium. These conditions produced prolonged action potentials accompanied by contractions with two distinct phasic components. The early component disappeared slowly when the remaining Ca++ was removed, whereas the late component was eliminated quickly when Sr++ was removed. Manganese ion (0.25 mM) preferentially decreased the late component without changing the action potential, whereas caffeine and ryanodine decreased or eliminated the early component. Ryanodine did not alter the action potential. Isoproterenol rapidly increased the early component and, more slowly and to a lesser degree, increased the late component. The results suggest that the early component is caused by intracellular release of activator cation, probably from the sarcoplasmic reticulum, whereas the late component is the result of Sr++ entry across the sarcolemma, possibly by way of the slow inward current.
Termination of sustained ventricular tachycardia by ultrarapid subthreshold stimulation in humans.
Authors: MShenasa, RCardinal, TKus, PSavard, MFromer, PPagé
Journal: Circulation (1988)

Our purpose was to investigate the efficacy, safety, and electrophysiological mechanism of ultrarapid subthreshold electrical stimulation in terminating sustained ventricular tachycardia (VT) in humans. Fifteen patients with inducible sustained hemodynamically stable VT and whose VT cycle length ranged between 295 and 440 msec (337 +/- 60 msec) were included in this study. The stimulation threshold and ventricular myocardial effective refractory period were determined during VT, and the values ranged between 0.4 and 1.2 mA (mean, 0.7 +/- 0.3 mA) and between 185 and 245 msec (mean, 225 +/- 20 msec), respectively. Trains of ultrarapid subthreshold stimulation were delivered with cycle lengths of 100 to 10 msec in decremental steps of 10 msec. A 5-second pause was allowed between each step (decrement). A 2-msec pulse width was used in all patients, and a 4-msec pulse width was also tested in eight patients. Any apparent captured beat was disregarded. In eight (53%) patients, ultrarapid subthreshold stimulati...
Coronary-Artery Stents
Authors: Patrick W. Serruys, Michael J.B. Kutryk, Andrew T.L. Ong
Journal: New England Journal of Medicine (2006)

At present, 90 to 95 percent of percutaneous coronary interventions involve the implantation of a stent, often a drug-eluting stent, though most published data originated in the era of bare-metal stents. This article reviews the indications for and biology of coronary-artery stents, focusing on recent advances in drug-eluting stents.
Stimulation of renal sympathetic activity by static contraction: evidence for mechanoreceptor-induced reflexes from skeletal muscle.
Authors: R GVictor, D MRotto, S LPryor, M PKaufman
Journal: Circulation Research (1989)

Static muscular contraction in anesthetized animals has been firmly established to reflexly increase arterial pressure. Although group III and IV muscle afferents are known to be responsible for this reflex pressor response, there is no evidence that the stimulation of muscle mechanoreceptors, many of which are supplied by group III fibers, plays a role in causing this contraction-induced reflex effect. To provide this evidence, we recorded renal sympathetic nerve activity in chloralose-anesthetized cats while contracting the triceps surae muscles. We found that static contraction tripled renal nerve activity within three seconds of its onset, an increase that was abolished by cutting the L6 and S2 dorsal roots. On average, the contraction-induced increase in renal nerve activity was observed 0.8 +/- 0.1 seconds after the onset of this maneuver. In addition, intermittent tetanic contractions synchronized renal nerve discharge so that a burst of activity was evoked by each contraction. A similarly synchron...
Increased blood flow inhibits neointimal hyperplasia in endothelialized vascular grafts.
Authors: T RKohler, T RKirkman, L WKraiss, B KZierler, A WClowes
Journal: Circulation Research (1991)

Intimal hyperplasia is a primary cause of failure after vascular reconstruction and may be affected by blood flow. We have studied the effects of increased blood flow on intimal hyperplasia in porous polytetrafluoroethylene grafts implanted in baboons. These grafts develop an endothelial lining by 2 weeks and neointimal thickening due to proliferation of underlying smooth muscle cells by 1 month. Creation of a distal arteriovenous fistula increased flow (from 230 +/- 35 to 785 +/- 101 ml/min, p less than 0.001) and mean shear (from 26 +/- 4 to 78 +/- 10 dynes/cm2, p less than 0.001) without causing a drop in pressure across the grafts. Fistula flow did not alter the pattern of endothelial coverage but did cause a marked reduction in the cross-sectional area of the neointima (from 2.60 +/- 0.52 to 0.42 +/- 0.07 mm2 at 3 months, p less than 0.01). Detailed morphometric analysis revealed an equivalent percentage decrease in smooth muscle cells and matrix content, suggesting that the primary effect of increas...
Oscillations of conduction, action potential duration, and refractoriness. A mechanism for spontaneous termination of reentrant tachycardias.
Authors: L HFrame, M BSimson
Journal: Circulation (1988)

The mechanism of cycle length oscillation and its role in spontaneous termination of reentry was studied in an in vitro preparation of canine atrial tissue surrounding the tricuspid orifice. Reentry occurred around a fixed path with incomplete recovery of excitability. Among 18 experiments, there was complete concordance between the occurrence of spontaneous cycle length oscillation and spontaneous terminations; both were observed in 10 experiments and neither in the other eight (p less than 0.001). Local changes in conduction during oscillations resulted from the dependence of both conduction velocity and action potential duration on the preceding local diastolic interval. Interval-dependent changes in action potential duration contributed to the oscillation by altering the next diastolic interval. Because of changes in action potential duration, changes in cycle length were poorly correlated with changes in diastolic interval and, therefore, with local conduction velocity. Complex oscillations resulted ...
Changes in coronary and collateral flows and adequacy of perfusion in the dog following one and three months of circumflex occlusion.
Authors: K WScheel, T AGalindez, BCook, R JRodriguez, L AIngram
Journal: Circulation Research (1976)

We investigated changes in circumflex, left anterior descending (LAD), and right coronary artery flows as well as changes in collateral flows to these vessels after long-term circumflex occlusion. Coronary and collateral flows of each vessel were determined simultaneously in an isolated heart preparation in which the vasculature was maximally dilated with dipyridamole. The resistances as related to total heart weight of the circumflex, LAD, and right coronary arteries of 16 control dogs were found to be 0.59 +/- 0.06, 0.93 +/- 0.09, and 2.37 +/- 0.17 (mean +/- SEM) mm Hg/[(ml/min)/100 g], respectively. Total minimal coronary resistance was 0.21 +/- 0.01. In 10 dogs subjected to occlusion for 1 month no significant change in circumflex coronary resistance was observed, but the resistance of the unimpaired vessels decreased significantly. The resistances of the LAD and right coronary arteries were 0.66 +/-0.04 and 1.72 +/- 0.13, respectively. Both values were considerably less (P less than 0.01) than contro...
Body fat and sympathetic nerve activity in healthy subjects.
Authors: UScherrer, DRandin, LTappy, PVollenweider, EJéquier, PNicod
Journal: Circulation (1994)

BACKGROUNDObesity is associated with an increased incidence of cardiovascular complications, but the underlying mechanism is unknown. In experimental animals, overfeeding is associated with sympathetic activation, and there is evidence that adrenergic mechanisms contribute to cardiovascular complications.METHODS AND RESULTSWe recorded resting postganglionic sympathetic nerve discharge (using intraneural microelectrodes) to skeletal muscle blood vessels in 37 healthy subjects covering a broad spectrum of percent body fat. To assess potential functional consequences of sympathetic nerve discharge, we simultaneously measured calf vascular resistance and energy expenditure. The resting rate of sympathetic nerve discharge to skeletal muscle was directly correlated with body mass index (r = .67, P < .0001) and percent body fat (r = .64, P < .0001). In addition to body fat, muscle sympathetic nerve activity was correlated with age (r = .40, P < .02), plasma insulin concentration (r = .34, P < .04), and plasma la...
Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial
Authors: James Cheng-Chung Wei, Tae-Hwan Kim, Mitsumasa Kishimoto, Naoki Ogusu, Haeyoun Jeong, Shigeto Kobayashi
Journal: Annals of the Rheumatic Diseases (2021)

Objective To investigate the efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA). Methods In a multicentre, placebo-controlled phase 3 study ( NCT02985983 ) conducted at 48 sites across Japan, Korea and Taiwan, patients with axSpA were randomised 1:1 to receive subcutaneous brodalumab 210 mg (n=80) or placebo (n=79) at baseline, weeks 1 and 2 and every 2 weeks thereafter, during the 16-week double-blind period. The primary endpoint was the proportion of patients with Assessment of SpondyloArthritis International Society (ASAS) 40 response at week 16. Secondary endpoints included the proportion of patients with ASAS 20 response and change in Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) at week 16 and safety. Results ASAS 40 response rate (n/N; 95% CI) was 43.8% (35/80; 32.7, 55.3) with brodalumab vs 24.1% (19/79; 15.1, 35.0) with placebo (rate difference, 19.7% (5.3, 34.1); p=0.018 by stratified Cochran-Mantel-Haenszel test). ASAS 20 response rate (n/N; 95% CI) was 67.5% (54/80; 56.1, 77.6) vs 41.8% (33/79; 30.8, 53.4) and least squares mean change (95% CI) from baseline (brodalumab, 2.660; placebo, 2.716) in ASDAS-CRP was –1.127 (–1.322, –0.931) with brodalumab vs –0.672 (–0.872, –0.473) with placebo at week 16. Treatment-emergent adverse events were reported in 44 (55%) and 45 (57%) patients in the brodalumab and placebo groups, respectively. Conclusion Brodalumab demonstrated a significant improvement at week 16 in patients with active axSpA. Safety of brodalumab was consistent with that reported in previous global/Japanese psoriasis studies.
Multi‐omics analyses implicate <i>EARS2</i> in the pathogenesis of atopic dermatitis
Authors: Jaehyun Park, Sharon M. Lutz, Seungil Choi, Sanghun Lee, Sang‐Cheol Park, Kangjin Kim, Hosik Choi, Hansoo Park, So Yeon Lee, Scott T. Weiss, Soo‐Jong Hong, Bong‐Soo Kim, Sungho Won
Journal: Allergy (2021)

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Sensitization of isolated canine coronary arteries to calcium ions after exposure to cholesterol.
Authors: MYokoyama, P DHenry
Journal: Circulation Research (1979)

The abundance of membrane cholesterol is an important determinant of the functional properties of biomembranes. To determine whether arterial smooth muscle acquires altered contractile properties in a high cholesterol environment, isolated canine coronary arteries were exposed to cholesterol in stable aqueous solution. Cholesterol, 10(-12) to 10(-10) M, was an efficacious vasoconstrictor, as maximum contractions equaled those obtained with 15 mM KCl. Antiadrenergic interventions, including chemical sympathectomy in vivo with 6-hydroxydopamine and alpha- and beta-adrenergic blockade with phentolamine and L-propranolol (both 10(-6 M), did not significantly attenuate the contractions. However, responses to cholesterol were abolished completely by (+/-)-verapamil (10(-6) M). Cholesterol in picomolar concentration enhanced the constrictor effects of CaCl2 and KCl, both in the presence and absence of alpha- and beta-adrenergic blockade. Increases in tone in response to graded elevations in the CaCl2 concentrati...
Length dependence of activation studied in the isovolumic blood-perfused dog heart.
Authors: P JTucci, E ABregagnollo, JSpadaro, A CCicogna, M CRibeiro
Journal: Circulation Research (1984)

In studies utilizing the isolated isovolumic blood-perfused canine heart, left ventricular pressure was measured following a sudden expansion of ventricular volume. An increase in performance occurred in two phases: first, there was an instantaneous rise of developed pressure simultaneous with ventricular distension; in the second phase, developed pressure continued to increase for several minutes until a final steady state was reached. The immediate increase in developed pressure occurred with a prolongation of the time-to-peak pressure, and there was no further change of time-to-peak pressure during the time-dependent increase of developed pressure. In another series of experiments, systolic pressure was elevated without changing resting volume, and mechanical performance changed in a different manner: after an increase in systolic load, there was a modest and transient decrease of developed pressure; thereafter, ventricular pressure recovered only to original values. The influence of different degrees ...
Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements.
Authors: D JSahn, ADeMaria, JKisslo, AWeyman
Journal: Circulation (1978)

Four hundred M-mode echocardiographic surveys were distributed to determine interobserver variability in M-mode echocardiographic measurements. This was done with a view toward examining the need and determining the criteria for standardization of measurement. Each survey consisted of five M-mode echocardiograms with a calibration marker, measured by the survey participants anonymously. The echoes were judged of adequate quality for measurement of structures. Seventy-six of the 400 (19%) were returned, allowing comparison of interobserver variability as well as examination of the measurement criteria which were used. Mean measurements and percent uncertainty were derived for each structure for each criterion of measurement. For example, for the aorta, 33% of examiners measured the aorta as an outer/inner or leading edge dimension, and 20% measured it as an outer/outer dimension. The percent uncertainty for the measurement (1.97 SD divided by the mean) showed a mean of 13.8% for the 25 packets of five echo...
Cardiac fatigue after prolonged exercise.
Authors: P SDouglas, M LO'Toole, W DHiller, KHackney, NReichek
Journal: Circulation (1987)

To determine the effects of prolonged exercise on systolic and diastolic left ventricular function, we studied 21 athletes before, at the finish (within 11 +/- 5 min), and during recovery (28 +/- 9 hr) after the Hawaii Ironman Triathlon (2.4 mile swim, 112 mile bike, 26.2 mile run). Two-dimensionally guided M mode echocardiograms were digitized for wall thickness, cavity dimension, fractional shortening, and peak rates of cavity enlargement and wall thinning. Pulsed Doppler left ventricular inflow recordings were analyzed for peak early and late velocities and their ratio. Left ventricular diastolic dimension was reduced at race finish (5.4 +/- 0.6 to 5.1 +/- 0.6 cm) and remained reduced after 1 day of recovery (5.2 +/- 0.6 cm, p less than .05). Fractional shortening fell at race finish (39 +/- 5% to 35 +/- 5%), although systolic blood pressure was unchanged, and rose to 40 +/- 4% after recovery (p less than .05). The return to prerace shortening values after recovery occurred despite continued reduction ...
Pressure-dependent contraction of rat juxtamedullary afferent arterioles.
Authors: C FSanchez-Ferrer, R JRoman, D RHarder
Journal: Circulation Research (1989)

Pressure-diameter relations were studied in rat afferent arterioles using an isolated, juxtamedullary nephron preparation perfused with a saline solution containing 5% albumin. Angiotensin I (10 microM), angiotensin II (0.1 microM), and norepinephrine (10 microM) increased perfusion pressure, and norepinephrine, but not angiotensin I or II, contracted afferent arterioles, indicating that the vessels are reactive. The control diameter of the afferent arterioles that exhibited pressure-dependent contraction (n = 58) averaged 30.8 +/- 1.1 micron at perfusion pressure of 80 mm Hg. When pressure was increased from 80 to 120 and then to 180 mm Hg, the diameter of these arterioles decreased by 16.4 +/- 2.1%. Glomerular capillary pressure was well autoregulated and averaged 45.2 +/- 2.2, 50.2 +/- 2.4, and 53.0 +/- 3.0 mm Hg, respectively, at perfusion pressures of 80, 120, and 180 mm Hg. Administration of vasodilators or a Ca2+-free solution eliminated the contractile response to pressure elevations; rather, the ...
Abstract 14878: Exosomes From Induced Pluripotent Stem Cell-Derived Cardiomyocytes vs Mesenchymal Stem Cells Demonstrate Differential Restoration of Myocardial Function in a Porcine Ischemia Reperfusion Injury Model
Authors: Connor G OBrien, Evgeniya Vaskova, Yuko Tada, Jihye Jung, Gentaro Ikeda, Michelle Santoso, Phillip C Yang
Journal: Circulation (2020)

Introduction: Coronary artery disease is a leading cause of death worldwide. Ischemic injury leads to myocardial dysfunction, resulting in heart failure. Exosomes have emerged as a promising therapeutic for restoring the failing heart. Fundamental questions such as cell of origin and molecular cargo for optimal therapeutic effect are areas of intense research. Our lab has shown that the exosomes from bone marrow derived mesenchymal stem cells (MSC-Ex) and induced pluripotent stem cell derived cardiomyocytes (iCM-Ex) both restore injured murine myocardium. These results led us to compare the therapeutic effects of MSC-Ex vs. iCM-Ex in a porcine myocardial ischemia reperfusion (IR) injury model, a step toward predicting efficacy in humans. Hypothesis: iCM-Ex is superior to MSC-Ex in restoring the injured porcine myocardium. Methods and Results: Pigs underwent ischemia reperfusion (IR) injury, consisting of 1 hour percutaneous balloon occlusion of the proximal left anterior descending artery immediately distal to the first septal artery. Following IR injury, 5 x 10 11 exosomes were delivered in ten, 500μL intramyocardial injections using a BioCardio Helix™ catheter. Biplane ventriculography was used to target the peri-infarct region. At 2- and 4-weeks post-infarct, pigs underwent cardiac MRI (cMRI) with ciné, delayed-enhanced (DEMRI) and manganese-enhanced (MEMRI) MRI. Pigs treated with iCM-Ex (n = 5) demonstrated a 41% improvement in left ventricular ejection fraction (LVEF, p = 0.004) and 35% reduction in indexed left ventricular end diastolic volume (p = 0.008) compared to controls while MSC-Ex (N = 5) did not demonstrate significant functional improvement. Furthermore, DEMRI and MEMRI showed a 21% reduction in myocardial scar (p = 0.14) in iCM-Ex treated animals compared to control while MSC-Ex group showed no difference. RNA-seq of the exosomes and transcriptomic analysis of the ex vivo myocardium will delineate the molecular mechanism of action and the putative intracellular pathway. Conclusion: iCM-Ex is superior to MSC-Ex in improving LVEF and reducing myocardial scar formation following ischemic insult. Comparative analysis between iCM-Ex and MSC-Ex is underway to identify the molecular targets that restore the failing heart.
Abstract 15310: Differences in Somatic Growth and Feeding Regimen by Palliation Strategy for Infants With Ductal-Dependent Pulmonary Blood Flow: Results From the Congenital Catheterization Research Collaborative
Authors: George T Nicholson, Andrew C Glatz, Athar M Qureshi, Christopher J Petit, Jeffery J Meadows, Courtney E McCracken, Michael S Kelleman, Holly D Bauser-Heaton, Ari J Gartenberg, Ronald A Ligon, Varun Aggarwal, Derek B Kwakye, Bryan H Goldstein
Journal: Circulation (2018)

Introduction: In infants with ductal dependent pulmonary blood flow (PBF), initial palliation with ductus arteriosus stent (DAS) or modified Blalock-Taussig shunt (BTS) have comparable mortality bu...
74P EBUS-TBNA/EUS-B for detecting N2/N3 disease in radiologically N0/N1 non–small cell lung cancer
Authors: S. Rodrigues Sousa, M.P. Valério, J.N. Caldeira, M. Santis, P. Matos, A.L. Fonseca, L. Barradas
Journal: Journal of Thoracic Oncology (2021)
Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy.
Authors: JSuzuki, HMatsubara, MUrakami, MInada
Journal: Circulation Research (1993)

Two subtypes of angiotensin II (Ang II) receptors (AT1 and AT2) are distinguished by using the respective specific antagonists. In the present study, we report the regulation of cardiac AT1 type A (AT1A) receptor mRNA levels and the expression pattern of AT1 and AT2 receptors in the growth of the heart and the development and regression of cardiac hypertrophy. The ventricular AT1A mRNA level and the density of Ang II receptors at the neonatal period were significantly increased (3.5-fold and 2.5-fold, respectively) and then downregulated with maturation. The cardiac hypertrophy established in spontaneously hypertensive rats or two-kidney one-clip renovascular hypertensive rats resulted in substantial increases in ventricular AT1A mRNA levels (threefold) and Ang II receptor densities (twofold) as compared with those in respective control rats, whereas the receptor affinity was similar. The proportion of AT1 and AT2 subtypes in the specific Ang II binding in ventricular membranes prepared from normal adult ...
Electron microscopic investigation of endomyocardial biopsy samples in hypertrophy and cardiomyopathy. A semiquantitative study in 48 patients.
Authors: UBaandrup, R AFlorio, FRoters, E GOlsen
Journal: Circulation (1981)

Electron microscopic and statistical analyses of 66 right ventricular biopsies from 48 patients were undertaken to investigate whether quantitative differences exist between those patients with ordinary myocardial hypertrophy and those suffering from a form of cardiomyopathy. The electron microscopic changes were scored and correlated with hemodynamic variables such as ejection fraction (EF), left ventricular end-diastolic pressure (LVEDP) and length of history. The patients were followed for an average of 22.5 months, permitting an assessment of prognosis. The results show that the three diagnostic groups--ordinary hypertrophy, hypertrophic cardiomyopathy (HOCM) and congestive cardiomyopathy (COCM)--overlap, but crossover of sarcomeres is more frequent in patients in whom HOCM is diagnosed. Except for a tenuous relationship between EF, and the electron microscopy (EM) (r = -0.46, p less than 0.1) and between LVEDP and EM score (r = 0.61, p less than 0.01), in the COCM group, no correlation could be e...