tbuckley/cabot-search huggingface dataset:
Nonclinical polymorphic ventricular tachycardia induced by programmed cardiac stimulation: incidence, mechanisms and clinical significance.
Authors: C PReddy, J CSartini
Journal: Circulation (1980)

We analyzed the morphology and rate of ventricular tachycardia induced by programmed cardiac stimulation in 18 patients with recurrent sustained ventricular tachycardia who had only one type of ventricular tachycardia during spontaneous episodes. In nine of 18 patients, we induced only one type of ventricular tachycardia, with a morphology and rate similar to those noted during spontaneous ventricular tachycardia. In the other nine patients, the induced ventricular tachycardia was either different from spontaneous ventricular tachycardia (two patients) or was polymorphic (seven patients). The multiple morphologies were induced in addition to those similar to spontaneous ventricular tachycardia. Seven of these nine patients had ischemic heart disease. Only one patient had a left ventricular aneurysm. The morphology and rate of induced tachycardia could be changed by changing the basic cycle length (two patients), the method of initiation of tachycardia (one patient), and by introducing paced ventricular be...
Warfarin Impairs the Bone Marrow Microenvironment and Hematopoiesis Via the Periostin/Integrin Î²3 Pathway
Authors: Divij Verma, Keertik Fulzele, Kumar Rahul, Christina Karantanou, Raquel Pereira, Kathrin Kunz, Soraya Hoelper, Eva Weissenberger, Paul K. Ziegler, Sara Zia Chahabi, Michaela Fontenay, Paola Divieti Pajevic, Daniela S. Krause
Journal: Blood (2017)
Reversible and irreversible elongation of ischemic, infarcted, and healed myocardium in response to increases in preload and afterload.
Authors: C MConnelly, R JMcLaughlin, W MVogel, C SApstein
Journal: Circulation (1991)

BACKGROUNDLeft ventricular aneurysm formation after myocardial infarction (MI) has been associated with elongation of infarcted tissue in response to wall stress. Such elongation most commonly occurs in acutely infarcted or partially healed regions during the early post-MI period; however, recent reports have indicated that mature (15-week-old) healed infarct regions also undergo elongation after stress.METHODS AND RESULTSTo assess factors contributing to post-MI left ventricular aneurysm formation, we subjected isolated strips (n = 50) of rabbit myocardial tissue from acutely ischemic (noninfarcted left ventricular), acutely infarcted (24 hours after MI), and healed infarct (3 and 15 weeks after MI) regions to a range of loading conditions and measured the reversible and irreversible length changes that occurred. The isolated strips were repetitively stretched for 1 hour at 4 Hz to impose cyclical physiological peak and resting stresses of 2.0 and 0.2 g/mm2. During a second hour, either peak stress (aft...
Effects of dibutyryl cyclic AMP, ouabain, and xanthine derivatives on crossbridge kinetics in rat cardiac muscle.
Authors: J FHoh, G HRossmanith, A MHamilton
Journal: Circulation Research (1991)

In a previous communication, we showed that beta-adrenergic stimulation of cardiac muscles was associated with an increase in the rate of cycling of crossbridges as measured by perturbation analysis in the frequency domain. In this analysis, the frequency at which dynamic stiffness is a minimum (fmin) is taken as a measure of the rate of crossbridge cycling. In this paper, we test the hypothesis that the beta-adrenergic receptor-induced increase in crossbridge cycling rate is mediated by elevation of the intracellular level of cyclic AMP. The approach taken is to compare the effects on fmin in rat papillary muscles during Ba(2+)-activated contractures of 1) an agonist of cyclic AMP that can easily penetrate the cell, namely, dibutyryl cyclic AMP, 2) agents that block cyclic AMP phosphodiesterase, namely, the xanthine derivatives isobutylmethylxanthine and caffeine, and 3) an inotropic agent that does not affect the intracellular level of cyclic AMP, namely, ouabain. Our results showed that dibutyryl cycli...
Elimination of atrioventricular nodal reentrant tachycardia using discrete slow potentials to guide application of radiofrequency energy.
Authors: MHaissaguerre, FGaita, BFischer, DCommenges, PMontserrat, Cd'Ivernois, PLemetayer, J FWarin
Journal: Circulation (1992)

BACKGROUNDAblation of the slow pathway has been performed to eliminate atrioventricular (AV) nodal reentrant tachycardia (AVNRT) either by a surgical approach or by using radiofrequency catheter technique guided by retrograde slow pathway activation mapping. From previous experience of midseptal and posteroseptal mapping, we were aware of the existence of peculiar slow potentials in most humans. Postulating their role in AVNRT, we studied these potentials and the effects of radiofrequency energy.METHODS AND RESULTSSixty-four patients (mean age, 48 +/- 19 years) with the usual form of AVNRT were studied. Slow, low-amplitude potentials were recorded when using the anterograde AV conducting system. Slow potentials occupied all (giving a continuum of electrograms) or some of the time between the atrial and ventricular electrograms. Their most specific patterns were their progressive response to increasing atrial rates, which resulted in a dramatic decline in amplitude and slope, a corresponding increase in du...
In vivo characterization of synthetic thromboxane A2 in canine myocardium.
Authors: H HHolzgrefe, L VBuchanan, SBunting
Journal: Circulation Research (1987)

Recently, total chemical synthesis of thromboxane was achieved. The in vitro activity of synthetic thromboxane A2 is indistinguishable from biologically generated material. The present study describes the in vivo characterization of synthetic thromboxane A2 on the regional blood flow distribution of the canine heart. Local injections of synthetic thromboxane A2 into the coronary vasculature caused marked reductions in coronary blood flow, measured by both radiolabeled microsphere injection and an electromagnetic flow device. The threshold concentration required to bring about this effect varied greatly between dogs and ranged from 0.125 microgram/kg to 2.0 micrograms/kg. Similarly, the dose of thromboxane A2 required to aggregate dog platelets in vitro varied from 30 ng/ml to 1,000 ng/ml. Bolus injections of 2 micrograms/ml thromboxane A2 into the circumflex or left anterior coronary artery resulted in a simultaneous reduction in platelet count in coronary sinus blood of 83 +/- 5.2% (mean +/- SEM, n = 4, ...
Pharmacological inhibition of asparaginyl endopeptidase by δ-secretase inhibitor 11 mitigates Alzheimer’s disease-related pathologies in a senescence-accelerated mouse model
Authors: Ju Wang, Hui-Jie Hu, Zi-Kai Liu, Jing-Jing Liu, Shan-Shan Wang, Qing Cheng, Hong-Zhuan Chen, Mingke Song
Journal: Translational Neurodegeneration (2021)

Abstract Background Currently, there is no cure for Alzheimer’s disease (AD). Therapeutics that can modify the early stage of AD are urgently needed. Recent studies have shown that the pathogenesis of AD is closely regulated by an endo/lysosomal asparaginyl endopeptidase (AEP). Inhibition of AEP has been reported to prevent neural degeneration in transgenic mouse models of AD. However, more than 90% of AD cases are age-related sporadic AD rather than hereditary AD. The therapeutic efficacy of AEP inhibition in ageing-associated sporadic AD remains unknown. Methods The senescence-accelerated mouse prone 8 (SAMP8) was chosen as an approximate model of sporadic AD and treated with a selective AEP inhibitor,: δ-secretase inhibitor 11. Activation of AEP was determined by enzymatic activity assay. Concentration of soluble amyloid β (Aβ) in the brain was determined by ELISA. Morris water maze test was performed to assess the learning and memory-related cognitive ability. Pathological changes in the brain were explored by morphological and western blot analyses. Results The enzymatic activity of AEP in the SAMP8 mouse brain was significantly higher than that in the age-matched SAMR1 mice. The half maximal inhibitory concentration (IC 50 ) for δ-secretase inhibitor 11 to inhibit AEP in vitro is was around 150 nM. Chronic treatment with δ-secretase inhibitor 11 markedly decreased the brain AEP activity, reduced the generation of Aβ 1–40/42 and ameliorated memory loss. The inhibition of AEP with this reagent not only reduced the AEP-cleaved tau fragments and tau hyperphosphorylation, but also attenuated neuroinflammation in the form of microglial activation. Moreover, treatment with δ-secretase inhibitor 11 prevented the synaptic loss and alleviated dendritic disruption in SAMP8 mouse brain. Conclusions Pharmacological inhibition of AEP can intervene and prevent AD-like pathological progress in the model of sporadic AD. The up-regulated AEP in the brain could be a promising target for early treatment of AD. The δ-secretase inhibitor 11 can be used as a lead compound for translational development of AD treatment.
Coronary dilation with standard dose dipyridamole and dipyridamole combined with handgrip.
Authors: J DRossen, ISimonetti, M LMarcus, M DWinniford
Journal: Circulation (1989)

Intravenous dipyridamole is widely used to produce coronary vasodilation during cardiac imaging procedures. However, the routinely used dose of dipyridamole (0.56 mg/kg IV over 4 min) does not always result in maximal coronary dilation. The addition of isometric handgrip during dipyridamole coronary dilation has been reported to substantially increase coronary blood flow over dipyridamole alone. We compared the coronary vasodilation resulting from infusion of the standard dose of dipyridamole with that resulting from a maximally dilating dose of intracoronary papaverine in 12 patients with angiographically normal coronary arteries. We also assessed the effect on coronary blood flow velocity of the addition of isometric handgrip during dipyridamole coronary dilation. Changes in coronary blood flow velocity were measured with a 3F coronary Doppler catheter. The coronary flow reserve (peak/resting coronary flow velocity ratio) after dipyridamole (3.7 +/- 1.2 [mean +/- SD] was less than that seen after papave...
The ability of several short-term measures of RR variability to predict mortality after myocardial infarction.
Authors: J TBigger, J LFleiss, L MRolnitzky, R CSteinman
Journal: Circulation (1993)

BACKGROUNDWe studied 715 patients 2 weeks after myocardial infarction to test the hypothesis that short-term power spectral measures of RR variability (calculated from 2 to 15 minutes of normal RR interval data) will predict all-cause mortality or arrhythmic death.METHODS AND RESULTSWe performed power spectral analyses on the entire 24-hour RR interval time series. To compare with the 24-hour analyses, we selected short segments of ECG recordings from two time periods for analysis: 8 AM to 4 PM and midnight to 5 AM. The former corresponds to the time interval during which short-term measures of RR variability would most likely be obtained. The latter, during sleep, represent a period of increased vagal tone, which may simulate the conditions that exist when patients have a signal-averaged ECG recorded, ie, lying quietly in the laboratory. Four frequency domain measures were calculated from spectral analysis of heart period data over a 24-hour interval. We computed the 24-hour power spectral density and ca...
Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm in a swine model.
Authors: AIto, HShimokawa, RNakaike, TFukai, MSakata, TTakayanagi, KEgashira, ATakeshita
Journal: Circulation (1994)

BACKGROUNDThe intracellular mechanism of coronary artery spasm is still unknown. The pathway mediated by protein kinase C (PKC) is an important intracellular process of various cellular responses, including vascular smooth muscle contraction. Thus, we examined the role of the PKC-mediated pathway in the pathogenesis of coronary artery spasm in our in vivo swine model.METHODS AND RESULTSSeven Gottingen miniature pigs underwent coronary balloon injury and x-ray irradiation to induce atherosclerotic lesion. After 6 to 18 months, intracoronary serotonin (3 micrograms/kg) or histamine (3 micrograms/kg) repeatedly induced coronary artery spasm at the atherosclerotic site. At the spastic site, intracoronary administration of phorbol-12,13-dibutyrate (PDBu) (10(-9) mol/kg), a PKC-activating phorbol ester, also induced coronary artery spasm, which was completely blocked by pretreatment with intracoronary staurosporine (10 micrograms/kg), a PKC inhibitor. Intracoronary administration of an inactive phorbol ester, p...
The Promising Evolution of Targeted Therapeutic Strategies in Cancer
Authors: Solange Peters, Tony Mok, Antonio Passaro, Pasi Antero Jänne
Journal: Cancer Discovery (2021)

The upcoming decade of precision medicine for cancer is moving from the translation of specific genetic findings into clinically relevant improvement to the qualitative analyses of the genomic and immune tumor microenvironment, for an integrated treatment strategy in both metastatic and early disease.
Cooperation between NRF2-mediated transcription and MDIG-dependent epigenetic modifications in arsenic-induced carcinogenesis and cancer stem cells
Authors: Zhuoyue Bi, Qian Zhang, Yao Fu, Akimasa Seno, Priya Wadgaonkar, Yiran Qiu, Bandar Almutairy, Liping Xu, Wenxuan Zhang, Chitra Thakur, Fei Chen
Journal: Seminars in Cancer Biology (2021)

Environmental exposure to arsenic, a well-established carcinogen linked to a number of human cancers, is a public health concern in many areas of the world. Despite extensive studies on the molecular mechanisms of arsenic-induced carcinogenesis, how initial cellular responses, such as activation of stress kinases and the generation of reactive oxygen species, converge to affect the transcriptional and/or epigenetic reprogramming required for the malignant transformation of normal cells or normal stem cells remains to be elucidated. In this review, we discuss some recent discoveries showing how the transcription factor NRF2 and an epigenetic regulator, MDIG, contribute to the arsenic-induced generation of cancer stem-like cells (CSCs) as determined by applying CRISPR-Cas9 gene editing and chromosome immunoprecipitation followed by DNA sequencing (ChIP-seq).
Trends in Nontraumatic Lower-Extremity Amputation Among Privately Insured Adults With Diabetes in the U.S., 2004–2018
Authors: Xilin Zhou, Linda J. Andes, Deborah B. Rolka, Giuseppina Imperatore, Stephen R. Benoit
Journal: Diabetes Care (2020)

Estimates based on the National Inpatient Sample (NIS) showed that diabetes-related nontraumatic lower- extremity amputation (NLEA) rates declined among hospitalized patients between 2000 and 2009, followed by an increasing NLEA rate between 2009 and 2015 (1). The increase was largely observed in young and middle-aged adults (1). However, the NIS dataset includes only inpatient admissions; minor amputation surgeries that were performed in ambulatory settings were not included in these estimates. In addition, NIS data are event-based, and multiple amputations in the same person are considered as a new event each time. In the current study, we used the IBM MarketScan Commercial Database to examine NLEA occurring in inpatient and outpatient settings among privately insured adults 18–64 years of age with diabetes.

The study period is from 2004 to 2018. People with diabetes and NLEA were identified using the International Classification of Diseases and the Current Procedural Terminology codes. NLEAs were categorized as major (amputations above the foot) or minor (foot and toe amputations) (1). For people who had multiple amputations in a year, we assigned the level of amputation based on the highest level …
Origin of body surface QRS and T wave potentials from epicardial potential distributions in the intact chimpanzee.
Authors: M SSpach, R CBarr, C FLanning, P CTucek
Journal: Circulation (1977)

Epicardial and body surface QRS-T wave potential distributions were measured during normal and ectopic sequences in intact chimpanzees. Epicardial potential distributions were used because they provide a comprehensive picture of total cardiac electrical activity for relating heart and body surface events during both ventricular activation and repolarization. When the epicardial potential gradients existed over a distance greater than that to the recording points on the body surface, e.g., as occurred during the overlap of terminal ventricular activation and early repolarization, the epicardial events were mirrored well on the anterior chest surface. However, when the recording points were at a distance greater than that over which the epicardial potential gradients existed, the details of the epicardial events disappeared and their effect was to produce distinct changes in the low-level potentials over broad distant areas. The major manifestations on the body surface of selective epicardial events frequen...
Abstract 11673: Home Monitoring in a Large Contemporary Real-World Atrial Fibrillation Population on Warfarin
Authors: Martin van Zyl, Thomas M Jaeger, Waldemar E Wysokinski, Bernard J Gersh, Robert D McBane
Journal: Circulation (2019)

Introduction: Despite the advent of direct oral anticoagulants (DOACs), many patients with atrial fibrillation remain on warfarin anticoagulation for financial reasons, mechanical valves, renal fun...
Acceleration of recombinant tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by the combination of heparin and the Arg-Gly-Asp-containing peptide bitistatin in a canine model of coronary thrombosis.
Authors: R JShebuski, I JStabilito, G RSitko, M HPolokoff
Journal: Circulation (1990)

The effect of tissue-type plasminogen activator (t-PA) alone or in combination with heparin, the Arg-Gly-Asp-containing peptide bitistatin, or both heparin and bitistatin was evaluated on thrombolysis time and acute reocclusion in a canine model of coronary thrombosis. Thrombus formation was elicited by electrolytic injury with a needle electrode to the endothelial surface of the circumflex coronary artery in the open-chest, anesthetized dog in the presence of a flow-limiting critical stenosis. Thirty minutes after spontaneous coronary artery occlusion, t-PA (1 mg/kg i.v. over 90 minutes) was administered. Group 1 was given t-PA alone; reperfusion occurred at 78.2 +/- 5.6 minutes with a reperfusion incidence of 60% (6/10). Group 2 received t-PA plus heparin (100 units/kg plus 50 units/kg/hr); reperfusion occurred at 61.9 +/- 9.1 minutes with a reperfusion incidence of 90% (9/10). Group 3 received t-PA plus heparin plus bitistatin (30 micrograms/kg plus 3 micrograms/kg/min); reperfusion occurred at 47.3 +/...
Quantitative two-dimensional echocardiographic analysis of regional wall motion in patients with perioperative myocardial infarction.
Authors: TForce, PBloomfield, J EO'Boyle, S FKhuri, MJosa, A FParisi
Journal: Circulation (1984)

Regional left ventricular wall motion was evaluated by two-dimensional echocardiographic techniques with fixed- and floating-axis analytical algorithms in three groups of subjects: normal subjects (n = 15), patients undergoing uncomplicated coronary artery bypass graft surgery (CABG) (n = 10), and patients suffering perioperative myocardial infarction (n = 27). In patients undergoing uncomplicated CABG, fixed-axis analysis in the apical four-chamber view produced septal hypokinesis indistinguishable from the septal hypokinesis seen in patients with anterior myocardial infarction. In addition, fixed-axis analysis enhanced lateral wall motion so that patients with lateral myocardial infarction were classified as normal. Floating-axis analysis corrected these limitations by (1) producing regional left ventricular wall motion in the patients undergoing uncomplicated CABG, which was identical to that in normal subjects, and (2) producing regional left ventricular wall motion in patients with myocardial infarct...
Sympathetic cross-innervation of SHR and genetic controls suggests a trophic influence on vascular muscle membranes.
Authors: P WAbel, KHermsmeyer
Journal: Circulation Research (1981)

We have attempted to differentiate neural from humoral environmental factors as the cause of altered arterial muscle membrane properties in spontaneously hypertensive rats (SHR). This laboratory has previously reported that alterations in membrane electrical properties appear to be responsible for increased NE sensitivity in caudal arteries from SHR. In this study, caudal arteries were transplanted into innervated or denervated anterior eye chambers of the same (KNR in KNR, SHR in SHR) or the opposite (KNR in SHR, SHR in KNR) strain. Seven weeks later, we measured membrane potential (Em) and norepinephrine (NE) contractile sensitivity (EC50) in both transplanted and host caudal arteries. Caudal arteries from 2-week-old donor animals transplanted into hosts reinnervated and developed Em and NE EC50 values characteristic of the host strain, interconverting between SHR and KNR characteristics in cross-transplantations. In other experiments, the superior cervical ganglion ipsilateral to the transplanted eye c...
The philosophical basis of peer review and the suppression of innovation
Authors: D. F. Horrobin
Journal: JAMA (1990)

Peer review can be performed successfully only if those involved have a clear idea as to its fundamental purpose. Most authors of articles on the subject assume that the purpose of peer review is quality control. This is an inadequate answer. The fundamental purpose of peer review in the biomedical sciences must be consistent with that of medicine itself, to cure sometimes, to relieve often, to comfort always. Peer review must therefore aim to facilitate the introduction into medicine of improved ways of curing, relieving, and comforting patients. The fulfillment of this aim requires both quality control and the encouragement of innovation. If an appropriate balance between the two is lost, then peer review will fail to fulfill its purpose. (<i>JAMA</i>. 1990;263:1438-1441)
Imaging and characterization of acute myocardial infarction in vivo by gated nuclear magnetic resonance.
Authors: GWesbey, C BHiggins, PLanzer, EBotvinick, M JLipton
Journal: Circulation (1984)

Imaging by nuclear magnetic resonance (NMR) techniques has been shown to provide high-contrast resolution between soft tissues and characterization of normal and pathologic tissues by differences in magnetic relaxation times. The current study was designed to determine whether electrocardiogram (ECG)-gated NMR imaging of the canine heart in vivo could distinguish normal from infarcted myocardium without the use of intravenous paramagnetic contrast agents. Seven dogs were studied by ECG-gated NMR imaging in vivo (spin-echo technique) with a 0.35 Tesla superconducting magnet at 2 to 7 days after ligation of the left anterior descending coronary artery. In six of the seven dogs, signal intensity was increased in the anterior wall compared with the remainder of the left ventricle; this region of high signal intensity corresponded to the area of myocardial infarction demonstrated at postmortem examination. The signal intensity of the infarcted region was 66 +/- 27% greater than that of normal myocardium (p les...