tbuckley/cabot-search huggingface dataset:
Role of changes in [Ca2+]i in energy deprivation contracture.
Authors: W HBarry, G APeeters, C ARasmussen, M JCunningham
Journal: Circulation Research (1987)

Mechanisms of energy deprivation contracture were investigated in cultured chick embryo ventricular cells. In the presence of zero-extracellular-Na+, (choline chloride substitution)-nominal-zero-Ca2+ [( Ca2+] approximately 5 microM), exposure of ventricular cells to 1 mM cyanide (CN) and 20 mM 2-deoxyglucose (2-DG)-zero-glucose solution resulted in the development of a contracture (video motion detector) in 5.9 +/- 0.5 minutes. Early after contracture development, the resupply of extracellular Na+, in the continued presence of CN + 2-DG, resulted in a rapid partial relaxation (t1/2 = 1.9 +/- 0.3 seconds), associated with an increase in 45Ca efflux, presumably due to transsarcolemmal Ca2+ extrusion due to Na+-Ca2+ exchange. Resupply of glucose and removal of CN + 2-DG, in the continued absence of Na+, resulted in an initially slower (t1/2 = 11.6 +/- 2.5 seconds), but more complete relaxation of contracture, which was not associated with increased Ca2+ efflux. Pretreatment with 20 mM caffeine delayed the on...
Partial versus complete control of blood pressure in the prevention of hypertensive complications.
Authors: JTaguchi, E DFreis
Journal: Circulation Research (1975)

The data from the Veterans Administration Cooperative Study on Antihypertensive Agents Prevention of Morbidity Trial were reviewed from the point of view of the importance of normalizing the blood pressure in preventing cardiovascular complications. The treated group of patients was subdivided into three subgroups on the basis of the diastolic blood pressures recorded at the fourth month after randomization as follows: subgroup A, the poorly controlled patients whose diastolic blood pressures were 90 mm Hg or higher, an intermediate subgroup B with diatolic levels of 81 to 89 mm Hg, and subgroup C, the best controlled patients, all of whom exhibited diastolic blood pressures of 80 mm Hg or less. While the incidence of morbid events was slightly higher in subgroup A than in the other subgroups, the differences were not statistically significant. On the other hand, the incidence of morbid events in subgroup A was significantly lower (P less than 0.05) than in the untreated control patients (14.9% in subgrou...
Effects of calcitonin gene-related peptide on normal and atheromatous vessels and on resistance vessels in the coronary circulation in humans.
Authors: P FLudman, AMaseri, PClark, G JDavies
Journal: Circulation (1991)

BACKGROUNDCalcitonin gene-related peptide (CGRP) is a potent dilator of normal epicardial coronary vessels in humans, but its effects on myocardial blood flow and atheromatous coronary vessel diameter are unknown.METHODS AND RESULTSSeven patients were entered for study of the effects of CGRP on coronary blood flow and 13 for the comparison of its effects on normal and atheromatous coronary arteries. In the first seven patients, left anterior descending artery (LAD) diameter at an angiographically normal site, coronary sinus oxygen saturation (CSO2S), systemic blood pressure, and heart rate were measured during intracoronary infusion of increasing concentrations of CGRP (up to 200 ng/ml at 2 ml/min) followed by intracoronary adenosine (0.267 micrograms/ml at 2 ml/min) and finally intracoronary glyceryl trinitrate (GTN) (5 micrograms/ml at 2 ml/min). CGRP dilated the normal segment of the LAD by 22.6 +/- 8% (mean +/- 95% confidence interval), p less than 0.001, with only a small increase in CSO2S from 40.1 ...
Recurrent sustained ventricular tachycardia. 4. Pleomorphism.
Authors: M EJosephson, L NHorowitz, AFarshidi, S RSpielman, E LMichelson, A MGreenspan
Journal: Circulation (1979)

Two or more morphologically distinct ventricular tachycardias were observed during electrophysiologic study in 14 patients with chronic sustained ventricular tachycardia. Nine of these patients had clinical ventricular tachycardia with multiple morphologies. During the study 13 patients manifested both right bundle branch block (RBBB) and left bundle branch block (LBBB) morphologies. The remaining patient had RBBB with both right and left axis deviation. Changing morphologies were observed spontaneously in four patients and could be produced in all 14 by ventricular stimulation. In 12 patients both RBBB and LBBB originated in the left ventricle, and in 11 of these patients, from within a left ventricular aneurysm. Diastolic fragmented activity representing reentry was unchanged during both morphologies in four patients and during one morphology in five patients. Epicardial mapping confirmed the aneurysm as the site of origin of multiform ventricular tachycardias in two patients. Our data suggest that 1) v...
The long QT syndrome: a prospective international study.
Authors: A JMoss, P JSchwartz, R SCrampton, ELocati, ECarleen
Journal: Circulation (1985)

During the past 4 years 196 patients with the idiopathic long QT syndrome were enrolled in a prospective international study conducted to obtain a better understanding of the clinical course of this unusual repolarization disorder. The mean patient age was 24 years, 64% were female, and 88% had family members with QT prolongation. During an average follow-up of 26 months per patient, four patients died suddenly (1.3% per year) and 27 patients had one or more syncopal episodes (8.6% per year). Multivariate analysis identified congenital deafness, history of syncope, female gender, and a documented episode of torsades de pointes or ventricular fibrillation as independent risk factors for postenrollment syncope or sudden death. Two types of treatment (left stellate ganglionectomy and beta-blocker therapy) were associated with a significant reduction in the occurrence of cardiac events during follow-up.
Pressor response to saralasin (1-sar-8-ala-angiotensin II) bolus injection in hypertensive patients.
Authors: U AWaks, M HMaxwell, LMarks, E TZawada, J JKaufman
Journal: Circulation (1978)

A 10 mg bolus of the angiotensin blocker saralasin was injected 113 times in 68 subjects with essential or renovascular hypertension. Ninety percent of injections caused a transient increase in blood pressure, which correlated with plasma renin activity (PRA) (r = -0.54); Mean increase at 2 minutes was 21/13.4 mm Hg (P less than 0.001) and was independent of pre-injection control blood pressure, with a rapid decrease to or below control values thereafter. Thirty-seven subjects were studied on successive days before and after furosemide-induced sodium depletion (152 +/- 26 mEq [SE] sodium loss). In the low renin group, sodium depletion did not change PRA or the magnitude of the pressor response to saralasin, but significantly decreased control MAP by 13 mm Hg (P less than 0.01). In normal and high renin patients, MAP was unchanged after diuresis, but PRA increased significantly and the pressor response was attenuated. The net effect of sodium depletion was to reduce the pressor response to saralasin in all...
Regulated tissue- and cell-specific expression of the human renin gene in transgenic mice.
Authors: C DSigmund, C AJones, C MKane, CWu, J ALang, K WGross
Journal: Circulation Research (1992)

Transgenic mice containing the human renin gene were constructed with the aim of examining the tissue- and cell-specific expression of human renin. The human renin transgene used consisted of a genomic sequence extending approximately 900 bp upstream and 400 bp downstream of the coding region and included all exon and intron sequences. Two assays were developed to differentiate human renin transcripts from endogenous mouse renin transcripts at the whole-tissue level. High level human renin expression was evident in the kidney, adrenal gland, ovary, testis, lung, and adipose tissue of all four transgenic lines examined. Human renin mRNA could also be detected at lower levels in the submandibular gland and heart of two different individual lines. No expression was evident in the liver or brain of any line tested. In situ hybridization revealed the human renin mRNA to be localized and exquisitely restricted to renal juxtaglomerular cells. Treatment of transgenic mice with captopril resulted in an increase in...
Letter: Cot deaths in Sweden.
Authors: D Freedman
Journal: BMJ (1975)

but the effect on glucose metabolismn of severe intoxication has not been reported.In rodents glucose appears to enhance the toxic effects of fenfluramine, which suggests that it is unlikely to have a therapeutic role in severe intoxication in humans.Although appetite suppressants cost the NHS over £2m in 1973, their efficacy in the long term remains somewhat dubious.Their dangers, however, even when in- dividually wrapped, continue to be demon- strated.
Guideline-Driven Management of Hypertension
Authors: Robert M. Carey, Jackson T. Wright, Sandra J. Taler, Paul K. Whelton
Journal: Circulation Research (2021)

Several important findings bearing on the prevention, detection, and management of hypertension have been reported since publication of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. This review summarizes and places in context the results of relevant observational studies, randomized clinical trials, and meta-analyses published between January 2018 and March 2021. Topics covered include blood pressure measurement, patient evaluation for secondary hypertension, cardiovascular disease risk assessment and blood pressure threshold for drug therapy, lifestyle and pharmacological management, treatment target blood pressure goal, management of hypertension in older adults, diabetes, chronic kidney disease, resistant hypertension, and optimization of care using patient, provider, and health system approaches. Presenting new information in each of these areas has the potential to increase hypertension awareness, treatment, and control which remain essential for the prevention of cardiovascular disease and mortality in the future.
Alterations in preload and ejection phase indices of left ventricular performance
Authors: L SRankin, SMoos, WGrossman
Journal: Circulation (1975)

Ejection phase indices such as mean velocity of circumferential fiber shortening (V-cf), ejection fraction (EF), and mean normalized systolic ejection rate (MSER) are thought to reflect the level of left ventricular (LV) inotropic state. Although known to be influenced by changes in afterload, their response to altered preload is less certain. This question was examined in ten normal subjects studied in the supine position and after 10 min of 75 degree head-up tilt. Echo VL diameter (D) and carotid pulse recordings were used to calculate LV ejection time, V-cf, MSER, LV end-diastolic and stroke volumes (EDV and SV, by D3 formula), and ejection fraction. Systemic blood pressure (BP)was measured by cuff, and heart rate (HR) counted from the ECG. Calculated LVEDV decreased with tilt (115 plus or minus 8 to 82 plus or minus 7 ml, P smaller than 0.001), as did SV (81 plus or minus 6 to 54 plus or minus 6 ml, P smaller than 0.001), and ejection time (0.31 plus or minus 0.01 to 0.27 plus or minus 0.00 sec, P sma...
Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.
Authors: I FMcMurtry, A BDavidson, J TReeves, R FGrover
Journal: Circulation Research (1976)

The role of a transmembrane calcium influx in hypoxic pulmonary vasoconstriction was studied in isolated, blood-perfused, rat lungs. We reasoned that, if the influx of extracellular calcium mediated the hypoxic mechanism, pressor responses to alveolar hypoxia (2.5% O2) would be susceptible to inhibition by the calcium antagonists verapamil (2 X 10(-5) to 2 X 10(-1) mM) and SKF 525A (2.6 to 260 mM). Susceptibility of hypoxic pressor responses to inhibition by these calcium antagonists was contrasted to that of pressor responses elicited by the humoral vasoconstrictors angiotensin II(1 or 0.5 mug) and prostaglandin F2alpha (10 myg). Since neither saralasin (0.5 muM), a competitive antagonist of angiotensin II, nor meclofenamate (6.8 muM), an inhibitor of prostaglandin synthesis, depressed hypoxic pressor responses, it was concluded that these humoral transmitters were not directly involved in the hypoxic mechanism, and therefore served as independent reference agonists. The order of susceptibility of pulmon...
The diastolic viscous properties of cat papillary muscle.
Authors: M INoble
Journal: Circulation Research (1977)

The measurement of ventricular diastolic compliance is complicated by the presence of viscous properties. To approach this problem, cat papillary muscles contracting isometrically at 15/min at 26 degrees C were stretched at different velocities during diastole. At a given length there was no excess of force above that defined by the static force-length curve until velocity of stretch exceeded 1 muscle length/sec. At greater velocities of stretch there was an increase of force with increasing velocity of stretch denoting viscous resistance to stretch. The viscous characteristic was alinear and increased with muscle length. At a given muscle length potentiation of contractile state by paired pulse stimulation caused a change in the diastolic force-length curve but there was no apparent relationship between viscous resistance to stretch and contractile state or the length of the series viscous element. These results lead one to expect viscous resistance to stretch during rapid filling of the intact left ve...
Bias due to Selection on Live Births in Studies of Environmental Exposures during Pregnancy: A Simulation Study
Authors: Michael Leung, Marianthi-Anna Kioumourtzoglou, Raanan Raz, Marc G. Weisskopf
Journal: Environmental Health Perspectives (2021)

Background: Studies of the effects of prenatal environmental exposures on postnatal outcomes are particularly vulnerable to live birth bias; i.e., the bias that arises from the necessary restriction of the analysis to live births when that is influenced by both the exposure under study A and unmeasured factors U that also affect the outcome. Objectives: In the context of a recent publication of nitrogen dioxide (NO2) and autism spectrum disorder (ASD) that found an odds ratio (OR) of 0.77 per 5.85 ppb NO2 during pregnancy, we aimed to examine what parameters would be needed to account for this protective association through live birth bias. Methods: We simulated the magnitude of bias under two selection mechanisms and when both mechanisms co-occur, assuming a true null effect. Simulation input parameters were based on characteristics of the original study and a range of plausible values for the prevalence of unmeasured factor U and the ORs for the selection effects (i.e., the effects of NO2 and U on loss and of U on ASD). Each scenario was simulated 1,000 times. Results: We found that the magnitude of bias was small when NO2 and U independently influenced pregnancy loss (collider-stratification without interaction), was stronger when NO2-induced loss preferentially occurred in U=1 (depletion of susceptibles), and was strongest when both mechanisms worked together. For example, ORs of 3.0 for NO2-loss, U-loss, U-ASD, and U prevalence=0.75 yielded NO2-ASD ORs per 5.85 ppb NO2 of 0.95, 0.89, and 0.75 for the three scenarios, respectively. The bias is amplified with multiple Us, yielding ORs as low as 0.51. Discussion: Our simulations illustrate that live birth bias may lead to exposure–outcome associations that are biased downward, where the extent of the bias depends on the fetal selection mechanism, the strength of that selection, and the prevalence of U. https://doi.org/10.1289/EHP7961
Role of endothelium-derived prostaglandins in hypoxia-elicited arteriolar dilation in rat skeletal muscle.
Authors: E JMessina, DSun, AKoller, M SWolin, GKaley
Journal: Circulation Research (1992)

The aims of the present study were to determine the response of rat cremaster muscle first-order arterioles to hypoxia and the role of endothelium-derived prostaglandins in the response. Isolated arterioles were cannulated, pressurized to 65 mm Hg, and studied in a no-flow condition in a bath containing Krebs' bicarbonate solution, pH 7.4, equilibrated with 21% O2-5% CO2-74% N2 (PO2, 150 mm Hg) or 95% N2-5% CO2 (PO2, 15 mm Hg [hypoxia]). Responses to hypoxia and vasoactive substances were studied before and after removal of the endothelium or blockade of prostaglandin synthesis by the administration of indomethacin (10(-5) M). Addition to the suffusion solution of arachidonic acid (10(-7) and 10(-6) M), prostaglandin E2 (10(-9) and 10(-8) M), acetylcholine (10(-8) and 10(-6) M), or sodium nitroprusside (10(-8) M) evoked significant arteriolar dilation. When the bath PO2 was reduced from 150 to 15 mm Hg, arteriolar diameters increased by 58.8 +/- 9.3 microns (61%). Removal of the endothelium completely inh...
The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention
Authors: A.K. Saikumar Jayalatha, L. Hesse, M.E. Ketelaar, G.H. Koppelman, M.C. Nawijn
Journal: Pharmacology & Therapeutics (2021)

Interleukin-33 (IL-33), a member of the IL-1 family, and its cognate receptor, Interleukin-1 receptor like-1 (IL-1RL1 or ST2), are susceptibility genes for childhood asthma. In response to cellular damage, IL-33 is released from barrier tissues as an ‘alarmin’ to activate the innate immune response. IL-33 drives type 2 responses by inducing signalling through its receptor IL-1RL1 in several immune and structural cells, thereby leading to type 2 cytokine and chemokine production. IL-1RL1 gene transcript encodes different isoforms generated through alternative splicing. Its soluble isoform, IL-1RL1-a or sST2, acts as a decoy receptor by sequestering IL-33, thereby inhibiting IL1RL1-b/IL-33 signalling. IL-33 and its receptor IL-1RL1 are therefore considered as putative biomarkers or targets for pharmacological intervention in asthma. This review will provide an overview of the genetics and biology of the IL-33/IL-1RL1 pathway in the context of asthma pathogenesis. It will discuss the potential and complexities of targeting the cytokine or its receptor, how genetics or biomarkers may inform precision medicine for asthma targeting this pathway, and the possible positioning of therapeutics targeting IL-33 or its receptor in the expanding landscape of novel biologicals applied in asthma management.
Beta-adrenergic stimulation disassembles microtubules in neonatal rat cultured cardiomyocytes through intracellular Ca2+ overload.
Authors: MHori, HSato, MKitakaze, KIwai, HTakeda, MInoue, TKamada
Journal: Circulation Research (1994)

Catecholamine cardiotoxicity is attributable in part to Ca2+ overload. To test whether the cytoskeletal structures of microtubules in cardiomyocytes are reversibly injured by catecholamine through excessive Ca2+ influx, morphological changes in the microtubules of neonatal rat myocytes were studied by immunohistochemical technique during exposure to norepinephrine (NE). In intact myocytes, microtubules appeared as a filamentous network throughout the cytoplasm and around the nucleus. NE exposure (10 mumol/L) for > 30 minutes elicited microtubular disassembly in a duration-dependent fashion without any irreversible change in sarcomere structure, and this abnormality recovered within 24 hours after cessation of stimulation. Microtubular disruption scores obtained by semiquantitative assessment were significantly increased in a dose-dependent manner (10.8 +/- 4.0 in the control condition, 23.4 +/- 4.7 at 60 minutes with 10 mumol/L NE), whereas they were significantly attenuated by pretreatment with propranol...
Echocardiographic detection of left main coronary artery obstruction.
Authors: L DRink, HFeigenbaum, R WGodley, A EWeyman, J CDillon, J FPhillips, J EMarshall
Journal: Circulation (1982)

Advances in two-dimensional echocardiography have improved the prospects of using this technique to detect left main coronary artery (LMCA) obstruction. Using an echocardiograph that had digital gray scale, a 3-MHz transducer and strobe freeze-frame capability and reviewing recordings on an off-line videotape-videodisc analyzer, we retrospectively examined the LMCA in 72 patients who underwent coronary cineangiography. Angiography showed 50% or greater LMCA obstruction in seven patients. All seven had high-intensity echoes in the walls of the LMCA. The high-intensity echoes were irregularly located in the artery and partially occluded it. The LMCA could frequently be recorded proximal and distal to the obstruction. A blinded observer reviewed 28 randomly selected patients from this group and correctly identified the four patients with LMCA obstruction. There was one true and two questionable false-positive diagnoses. In a prospective study of 31 patients, two independent observers correctly identified the...
Machine learning detection of obstructive hypertrophic cardiomyopathy using a wearable biosensor
Authors: R. Ueno, H. Matsui, L. Xu
Journal: npj Digital Medicine (2019)

Green et al. (June 24 issue) 1 developed a machine learning classifier of hypertrophic cardiomyopathy (HCM) patients using a noninvasive optical sensor incorporated in commercial smart watches.The study included 83 patients (19 patients with HCM and 64 healthy controls) and a machine learning classifier was trained with Leave-One-Group-Out cross-validation with nested hyperparameter tuning, achieving a C-statistic of 0.99 (95% CI: 0.99-1.00)for 82 patients.While these results are promising and persuasive enough to facilitate further trial to assess its performance in a larger cohort, we would argue a few statistical concerns with the study.First, the authors argued that they have performed 68-fold, instead of 82fold cross-validation for their Leave-One-Group-Out crossvalidation.Further clarification might be required to avoid any confusion for readers.Second, the confusion matrix includes all the 82 patients from both train and test data, while this table should ideally include only test data. 2Inclusion of train group in this matrix might result in the over-estimate performance of the model.We believe those findings might not invalidate the insightful work by Green et al.Further clarification of such concerns might further reinforce this study to function as a foundation for a larger study.
Effects of lidocaine and procainamide on normal and abnormal intraventricular electrograms during sinus rhythm.
Authors: C GSchmitt, A HKadish, F EMarchlinski, J MMiller, A EBuxton, M EJosephson
Journal: Circulation (1988)

The effect of lidocaine (n = 6) and procainamide (n = 12) on electrogram characteristics from electrically normal right ventricular and electrically abnormal left ventricular endocardial sites was determined in 18 patients with prior myocardial infarction. Bipolar electrograms were recorded during sinus rhythm with No. 6F catheters positioned at a left ventricular abnormal site (electrograms fulfilling two of the following criteria: amplitude less than 3 mV, duration greater than 70 msec, or an amplitude to duration ratio less than .046) and normal sites at the right ventricular apex (RVA) and right ventricular outflow tract (RVOT). All electrograms were recorded from the same location before and after intravenous lidocaine or procainamide administered to obtain mean serum concentrations of 4.2 +/- 0.6 and 9.42 +/- 2 micrograms/ml respectively. Lidocaine and procainamide had no significant effect on sinus cycle length or electrogram amplitude. After lidocaine, no significant change in QRS width (112 +/- 2...