99mTc
: technetium-99m
201TI
: thallium 201
ABCB1
: ATP-binding cassette sub-family B member 1
ABI
: ankle-brachial index
ACC
: American College of Cardiology
ACCF
: American College of Cardiology Foundation
ACCOMPLISH
: Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension
ACE
: angiotensin converting enzyme
ACIP
: Asymptomatic Cardiac Ischaemia Pilot
ACS
: acute coronary syndrome
ADA
: American Diabetes Association
ADP
: adenosine diphosphate
AHA
: American Heart Association
ARB
: angiotensin II receptor antagonist
ART
: Arterial Revascularization Trial
ASCOT
: Anglo-Scandinavian Cardiac Outcomes Trial
ASSERT
: Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial
AV
: atrioventricular
BARI 2D
: Bypass Angioplasty Revascularization Investigation 2 Diabetes
BEAUTIFUL
: Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction
BIMA
: bilateral internal mammary artery
BMI
: body mass index
BMS
: bare metal stent
BNP
: B-type natriuretic peptide
BP
: blood pressure
b.p.m.
: beats per minute
CABG
: coronary artery bypass graft
CAD
: coronary artery disease
CAPRIE
: Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events
CASS
: Coronary Artery Surgery Study
CCB
: calcium channel blocker
CCS
: Canadian Cardiovascular Society
CFR
: coronary flow reserve
CHARISMA
: Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization, Management and Avoidance
CI
: confidence interval
CKD
: chronic kidney disease
CKD-EPI
: Chronic Kidney Disease Epidemiology Collaboration
CMR
: cardiac magnetic resonance
CORONARY
: The CABG Off or On Pump Revascularization Study
COURAGE
: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation
COX-1
: cyclooxygenase-1
COX-2
: cyclooxygenase-2
CPG
: Committee for Practice Guidelines
CT
: computed tomography
CTA
: computed tomography angiography
CV
: cardiovascular
CVD
: cardiovascular disease
CXR
: chest X-ray
CYP2C19*2
: cytochrome P450 2C19
CYP3A
: cytochrome P3A
CYP3A4
: cytochrome P450 3A4
CYP450
: cytochrome P450
DANAMI
: Danish trial in Acute Myocardial Infarction
DAPT
: dual antiplatelet therapy
DBP
: diastolic blood pressure
DECOPI
: Desobstruction Coronaire en Post-Infarctus
DES
: drug-eluting stents
DHP
: dihydropyridine
DSE
: dobutamine stress echocardiography
EACTS
: European Association for Cardiothoracic Surgery
EECP
: enhanced external counterpulsation
EMA
: European Medicines Agency
EASD
: European Association for the Study of Diabetes
ECG
: electrocardiogram
Echo
: echocardiogram
ED
: erectile dysfunction
EF
: ejection fraction
ESC
: European Society of Cardiology
EXCEL
: Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization
FAME
: Fractional Flow Reserve vs. Angiography for Multivessel Evaluation
FDA
: Food & Drug Administration (USA)
FFR
: fractional flow reserve
FREEDOM
: Design of the Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease
GFR
: glomerular filtration rate
HbA1c
: glycated haemoglobin
HDL
: high density lipoprotein
HDL-C
: high density lipoprotein cholesterol
HR
: hazard ratio
HRT
: hormone replacement therapy
hs-CRP
: high-sensitivity C-reactive protein
HU
: Hounsfield units
ICA
: invasive coronary angiography
IMA
: internal mammary artery
IONA
: Impact Of Nicorandil in Angina
ISCHEMIA
: International Study of Comparative Health Effectiveness with Medical and Invasive Approaches
IVUS
: intravascular ultrasound
JSAP
: Japanese Stable Angina Pectoris
KATP
: ATP-sensitive potassium channels
LAD
: left anterior descending
LBBB
: left bundle branch block
LIMA
: Left internal mammary artery
LDL
: low density lipoprotein
LDL-C
: low density lipoprotein cholesterol
LM
: left main
LMS
: left main stem
LV
: left ventricular
LVEF
: left ventricular ejection fraction
LVH
: left ventricular hypertrophy
MACE
: major adverse cardiac events
MASS
: Medical, Angioplasty, or Surgery Study
MDRD
: Modification of Diet in Renal Disease
MERLIN
: Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes
MERLIN-TIMI 36
: Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes: Thrombolysis In Myocardial Infarction
MET
: metabolic equivalents
MI
: myocardial infarction
MICRO-HOPE
: Microalbuminuria, cardiovascular and renal sub-study of the Heart Outcomes Prevention Evaluation study
MPI
: myocardial perfusion imaging
MRI
: magnetic resonance imaging
NO
: nitric oxide
NSAIDs
: non-steroidal anti-inflammatory drugs
NSTE-ACS
: non-ST-elevation acute coronary syndrome
NYHA
: New York Heart Association
OAT
: Occluded Artery Trial
OCT
: optical coherence tomography
OMT
: optimal medical therapy
PAR-1
: protease activated receptor type 1
PCI
: percutaneous coronary intervention
PDE5
: phosphodiesterase type 5
PES
: paclitaxel-eluting stents
PET
: positron emission tomography
PRECOMBAT
: Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease
PTP
: pre-test probability
PUFA
: polyunsaturated fatty acid
PVD
: peripheral vascular disease
QoL
: quality of life
RBBB
: right bundle branch block
REACH
: Reduction of Atherothrombosis for Continued Health
RITA-2
: Second Randomized Intervention Treatment of Angina
ROOBY
: Veterans Affairs Randomized On/Off Bypass
SAPT
: single antiplatelet therapy
SBP
: systolic blood pressure
SCAD
: stable coronary artery disease
SCORE
: Systematic Coronary Risk Evaluation
SCS
: spinal cord stimulation
SES
: sirolimus-eluting stents
SIMA
: single internal mammary artery
SPECT
: single photon emission computed tomography
STICH
: Surgical Treatment for Ischaemic Heart Failure
SWISSI II
: Swiss Interventional Study on Silent Ischaemia Type II
SYNTAX
: SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery
TC
: total cholesterol
TENS
: transcutaneous electrical neural stimulation
TERISA
: Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina
TIME
: Trial of Invasive vs. Medical therapy
TIMI
: Thrombolysis In Myocardial Infarction
TMR
: transmyocardial laser revascularization
TOAT
: The Open Artery Trial
WOEST
: What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing

Guidelines summarize and evaluate all evidence available, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well …

/pdf/2013-esc-guidelines-on-the-management-of-stable-coronary-2178xukyyy.pdf

2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology.

The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed "fragment recruitment," addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed "extreme assembly," made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate-binding gene PstS.

/pdf/the-sorcerer-ii-global-ocean-sampling-expedition-northwest-310cgsz0o9.pdf

The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific

Cyclin D1 provides a link between development and oncogenesis in the retina and breast

It is well known that visual cortical neurons respond vigorously to a limited range of stimulus orientations, while their primary afferent inputs, neurons in the lateral geniculate nucleus (LGN), respond well to all orientations. Mechanisms based on intracortical inhibition and/or converging thalamocortical afferents have previously been suggested to underlie the generation of cortical orientation selectivity; however, these models conflict with experimental data. Here, a 1:4 scale model of a 1700 microns by 200 microms region of layer IV of cat primary visual cortex (area 17) is presented to demonstrate that local intracortical excitation may provide the dominant source of orientation-selective input. In agreement with experiment, model cortical cells exhibit sharp orientation selectivity despite receiving strong iso-orientation inhibition, weak cross-orientation inhibition, no shunting inhibition, and weakly tuned thalamocortical excitation. Sharp tuning is provided by recurrent cortical excitation. As this tuning signal arises from the same pool of neurons that it excites, orientation selectivity in the model is shown to be an emergent property of the cortical feedback circuitry. In the model, as in experiment, sharpness of orientation tuning is independent of stimulus contrast and persists with silencing of ON-type subfields. The model also provides a unified account of intracellular and extracellular inhibitory blockade experiments that had previously appeared to conflict over the role of inhibition. It is suggested that intracortical inhibition acts nonspecifically and indirectly to maintain the selectivity of individual neurons by balancing strong intracortical excitation at the columnar level.

https://www.jneurosci.org/content/jneuro/15/8/5448.full.pdf

An emergent model of orientation selectivity in cat visual cortical simple cells

Chapter 9 Visual adaptation and retinal gain controls

PURPOSE. TO investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. METHODS. Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (^5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3-8-8 /xM) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. RESULTS. Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as —6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. CONCLUSIONS. The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy. (Invest Ophthalmol Vis Sci. 1999;40:1124 -1136)

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

Purpose To better understand the cellular contributions to the human multifocal ERG (mfERG), rhesus monkey and human mfERGs were recorded using the same stimulus conditions. The monkey mfERGs were recorded before and after injections of pharmacologic agents known to selectively block activity of particular cells and circuits in the retina. Methods Photopic mfERGs were recorded with Dawson-Trick-Litzkow (DTL) fiber electrodes from 16 eyes of 10 anesthetized adult rhesus monkeys (Macaca mulatta) and from 4 normal humans. The display consisted of 103 equal-sized hexagons within 17 degrees of the fovea. Monkey mfERGs were obtained before and after inner retinal responses were suppressed with intravitreal injections of tetrodotoxin (TTX), TTX+N-methyl-D-aspartic acid (NMDA), TTX+NMDA with the gamma-aminobutyric acid (GABA(A&C)) antagonist picrotoxin (PTX), or the inhibitory amino acid GABA and after L-2 amino-4-phosphonobutyric acid (APB) to block signal transmission to ON-bipolar cells. Finally, a combination of APB and cis-2,3 piperidine dicarboxylic acid (PDA) was used to isolate the contributions from the cone photoreceptors. Results TTX, which blocks sodium-based action potentials, removes a large contribution from the monkey's mfERG, but it does not remove all inner retinal influences. After administration of TTX, the mfERG is further modified by the addition of NMDA. TTX+NMDA, TTX+NMDA+PTX, or GABA alone have similar effects, suggesting that, at the concentrations used, they are largely removing the inner retinal contributions. After removing the inner retinal influences, the monkey's mfERG is mainly composed of ON- and OFF-bipolar contributions, as revealed after APB and PDA were injected. The leading edge of the first negative potential (N1) is largely shaped by the initial hyperpolarization of the OFF-bipolar cells. The photoreceptors also contribute to the leading edge of N1, but this contribution is small, except in the central 6 degrees. The depolarization of the ON-bipolars and the recovery of the OFF-bipolars contribute to the leading edge of the major positive component (P1), with the recovery of the ON-bipolars being the dominant influence on the trailing edge. The waveform of the human mfERG most closely resembles the rhesus monkey's mfERG after administration of TTX. Conclusions The monkey's mfERG is shaped by large contributions from ON- and OFF-bipolar cells, combined with both spiking and nonspiking inner retinal contributions, and a small contribution from the photoreceptors. In comparison, the human mfERG resembles the monkey's mfERG after reduction of inner retinal contributions. Based on the pharmacologic dissection of the monkey's mfERG, a model of the waveform of the human mfERG is proposed. This model suggests that the waveform can be understood as a combination of overlapping ON- and OFF-bipolar cell contributions combined with smaller contributions from inner retina and photoreceptors.

Retinal Origins of the Primate Multifocal ERG: Implications for the Human Response

The electroretinogram (ERG) of the dark-adapted cat eye in response to brief ganzfeld flashes of a wide range of intensities was recorded after intravitreal injection of n-methyl DL aspartate (NMDLA, cumulative intravitreal concentration of 1.3-3.9 mM) to suppress inner-retinal components, and after intravitreal DL or L-2-amino-4-phosphonobutyric acid (DL-APB, 1-3 mM; L-APB, 1.2 mM) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX, 40-60 μM), to suppress all post-receptoral neuronal responses. Rod PII, the ERG component arising from rod bipolar cells, was derived by subtracting records obtained after APB and CNQX from post-NMDLA records. When we measured the derived response at fixed times after the stimulus, we found that PII initially increased in proportion to stimulus intensity without any sign of a threshold. The leading edge of PII at early times after the stimulus, when the response was still small, was well described by V(t) = kI(t - t d ) 5 where k is a constant, I is the intensity of the stimulus, and t d is a brief delay of about 3 ms. Correspondingly, the time for the response to rise to an arbitrary small criterion voltage V crit was adequately fitted by t crit = t d + (V crit /kI) 1/5 . The time course of the leading edge of the PII response can be interpreted to indicate that the mechanism generating PII introduces three stages of temporal integration in addition to the three stages that are provided by the mechanism of the rod photoreceptors. This finding is consistent with the operation within the rod bipolar cell of a G-protein cascade similar to that in the rods.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0952523800009408

Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram.

The most sensitive response in the dark-adapted electroretinogram (ERG), the scotopic threshold response (STR) which originates from the proximal retina, has been identified in several mammals including humans, but previously not in the mouse. The current study established the presence and assessed the nature of the mouse STR. ERGs were recorded from adult wild-type C57/BL6 mice anaesthetized with ketamine (70 mg kg−1) and xylazine (7 mg kg−1). Recordings were between DTL fibres placed under contact lenses on the two eyes. Monocular test stimuli were brief flashes (λmax 462 nm; -6.1 to +1.8 log scotopic Troland seconds(sc td s)) under fully dark-adapted conditions and in the presence of steady adapting backgrounds (-3.2 to -1.7 log sc td). For the weakest test stimuli, ERGs consisted of a slow negative potential maximal ≈200 ms after the flash, with a small positive potential preceding it. The negative wave resembled the STR of other species. As intensity was increased, the negative potential saturated but the positive potential (maximal ≈110 ms) continued to grow as the b-wave. For stimuli that saturated the b-wave, the a-wave emerged. For stimulus strengths up to those at which the a-wave emerged, ERG amplitudes measured at fixed times after the flash (110 and 200 ms) were fitted with a model assuming an initially linear rise of response amplitude with intensity, followed by saturation of five components of declining sensitivity: a negative STR (nSTR), a positive STR (pSTR), a positive scotopic response (pSR), PII (the bipolar cell component) and PIII (the photoreceptor component). The nSTR and pSTR were approximately 3 times more sensitive than the pSR, which was approximately 7 times more sensitive than PII. The sensitive positive components dominated the b-wave up to > 5 % of its saturated amplitude. Pharmacological agents that suppress proximal retinal activity (e.g. GABA) minimized the pSTR, nSTR and pSR, essentially isolating PII which rose linearly with intensity before showing hyperbolic saturation. The nSTR, pSTR and pSR were desensitized by weaker backgrounds than those desensitizing PII. In conclusion, ERG components of proximal retinal origin that are more sensitive to test flashes and adapting backgrounds than PII provide the ‘threshold’ negative and positive (b-wave) responses of the mouse dark-adapted ERG. These results support the use of the mouse ERG in studies of proximal retinal function.

The Scotopic Threshold Response of the Dark‐Adapted Electroretinogram of the Mouse

PURPOSE. To determine whether the photopic negative response (PhNR) of the electroretinogram (ERG) is reduced in patients with primary open angle glaucoma (POAG). METHODS. ERGs were recorded with DTL electrodes from 62 normal subjects (16 to 82 years), 18 POAG patients (47 to 83 years) and 7 POAG suspects (46 to 73 years) to brief flashes (<6 ms), and also in a few subjects to long (200 ms) red, full-field ganzfeld flashes delivered on a rod-saturating blue background. At the time of ERG measurements, the intraocular pressures of most of the patients were controlled medically. Visual field sensitivities were measured with the Humphrey C24-2 threshold test and optic nerve head cup-to-disc ratio (C/D) was determined by binocular indirect ophthalmoscopy. RESULTS. ERGs of normal subjects contained a slow negative potential following the a- and b-waves, the PhNR, that increased slightly in latency with age. The a- and b-wave amplitudes and implicit times of POAG patients were similar to age-matched controls. In contrast, their PhNRs were small or virtually absent. PhNR amplitudes were reduced even when visual sensitivity losses were small, and were correlated significantly (P < 0.05) with mean deviation (MD), corrected pattern SD (CPSD), and C/D across the population of POAG patients whose MD losses ranged from 1 to 13 dB, CPSDs from 0 to 11 dB and C/Ds from 0.6 to 0.9. PhNRs of most POAG suspects also were small. CONCLUSIONS. PhNR amplitudes in POAG patients are smaller than those of normal subjects. PhNR amplitudes are reduced when visual field sensitivity losses are mild and become even smaller as sensitivity losses increase. There is a potential role for the PhNR in early detection and possibly in monitoring the progression of glaucomatous damage.

Laura J. Frishman

Papers

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

Retinal Origins of the Primate Multifocal ERG: Implications for the Human Response

Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram.

The Scotopic Threshold Response of the Dark‐Adapted Electroretinogram of the Mouse

The photopic negative response of the flash electroretinogram in primary open angle glaucoma.