Direct Vasoconstrictor Effect Research Articles

Predictability of leaf traits with climate and elevation: a case study in Gongga Mountain, China.

Leaf mass per area (Ma), nitrogen content per unit leaf area (Narea), maximum carboxylation capacity (Vcmax) and the ratio of leaf-internal to ambient CO2 partial pressure (χ) are important traits related to photosynthetic function, and they show systematic variation along climatic and elevational gradients. Separating the effects of air pressure and climate along elevational gradients is challenging due to the covariation of elevation, pressure and climate. However, recently developed models based on optimality theory offer an independent way to predict leaf traits and thus to separate the contributions of different controls. We apply optimality theory to predict variation in leaf traits across 18 sites in the Gongga Mountain region. We show that the models explain 59% of trait variability on average, without site- or region-specific calibration. Temperature, photosynthetically active radiation, vapor pressure deficit, soil moisture and growing season length are all necessary to explain the observed patterns. The direct effect of air pressure is shown to have a relatively minor impact. These findings contribute to a growing body of research indicating that leaf-level traits vary with the physical environment in predictable ways, suggesting a promising direction for the improvement of terrestrial ecosystem models.

Neuropeptide Y facilitates P2X1 receptor-dependent vasoconstriction via Y1 receptor activation in small mesenteric arteries during sympathetic neurogenic responses

ATP, norepinephrine and NPY are co-released by sympathetic nerves innervating arteries. ATP elicits vasoconstriction via activation of smooth muscle P2X receptors. The functional interaction between neuropeptide Y (NPY) and P2X receptors in arteries is not known. In this study we investigate the effect of NPY on P2X1-dependent vasoconstriction in mouse mesenteric arteries. Suramin or P2X1 antagonist NF449 abolished α,β-meATP evoked vasoconstrictions. NPY lacked any direct vasoconstrictor effect but facilitated the vasoconstrictive response to α,β-meATP. Mesenteric arteries expressed Y1 and Y4 receptors, but not Y2 or Y5. Y1 receptor inhibition (BIBO3304) reversed NPY facilitation of the α,β-meATP-evoked vasoconstriction. L-type Ca2+ channel antagonism (nifedipine) had no effect on α,β-meATP-evoked vasoconstrictions, but completely reversed NPY facilitation. Electrical field stimulation evoked sympathetic neurogenic vasoconstriction. Neurogenic responses were dependent upon dual α1-adrenergic (prazosin) and P2X1 (NF449) receptor activation. Y1 receptor antagonism partially reduced neurogenic vasoconstriction. Isolation of the P2X1 component by α1-adrenergic blockade allowed faciliatory effects of Y1 receptor activation to be explored. Y1 receptor antagonism reduced the P2X1 receptor component during neurogenic vasoconstriction. α1-adrenergic and P2X1 receptors are post-junctional receptors during sympathetic neurogenic vasoconstriction in mesenteric arteries. In conclusion, we have identified that NPY lacks a direct vasoconstrictor effect in mesenteric arteries but can facilitate vasoconstriction by enhancing the activity of P2X1, following activation by exogenous agonists or during sympathetic nerve stimulation. The mechanism of P2X1 facilitation by NPY involved activation of the NPY Y1 receptor and the L-type Ca2+ channel.

Centruroides margaritatus scorpion complete venom exerts cardiovascular effects through alpha-1 adrenergic receptors

Centruroides margaritatus scorpion stings are common in Colombia. However, the cardiovascular toxicity of the venom has not been clarified. Aim: To study the effect and mechanisms of action of the complete venom of C. margaritatus (CmV) on the murine cardiovascular system. Methods: We evaluated the in vivo effect of CmV LD50 on the mean arterial pressure (MABP), heart rate, and surface electrocardiogram in male adult normotensive Wistar rats. Ex vivo, we evaluated the vascular reactivity of rat aortic rings to increasing concentrations (1 to 60 μg/mL) of CmV using the blockers L-NAME, indomethacin, seratrodast, and prazosin. Results: In the first hour of poisoning, CmV increased the MABP. In the second hour after poisoning, the heart rate decreased as the normalized PR interval and QT corrected increased. After that, cardiovascular shock was demonstrated by a drastic fall in the MABP and signs of cardiac conduction system block. In aortic rings, CmV caused a direct vasoconstrictor effect mediated by alpha-1 adrenergic receptors and counteracted by nitric oxide. Conclusion: The direct vascular and probably the cardiac alpha-1 effects likely explain the transient hypertension and the maintenance of cardiac function, while interval lengthening may be due to K+ channel blockage. Afterwards, the effects of both the alpha-1 pathway and the K+ channel pathway converged, resulting in fatal cardiovascular shock. This knowledge could aid in understanding the dynamics of the effects of the venom and in designing treatments to address its cardiovascular effects.

Optimal harvesting in the presence of predation: An age-structured modelling approach

Predation of wildlife and livestock by large carnivores takes place within many ecological and institutional settings. In this paper, moose predation by wolves is studied within a Norwegian institutional setting where the landowners obtain the moose harvesting value and where the wolf population is strictly controlled by the wildlife authorities. An age-structured model consisting of four categories of the moose population (calves, yearlings and adult females and males) is formulated, and both maximum yield (MY) and maximum economic yield (MEY) harvesting are studied. We find that the direct effect of higher predation pressure on an age-sex category works in the direction of higher harvesting pressure of that group. However, this direct effect is accompanied by indirect effects working through the stock abundance of all age-sex groups, and the net effect is ambiguous. In the numerical analysis, it is shown that harvest of the adult categories typically will be the optimal strategy, irrespective of the fact that calves are the main target of the wolves.

Measuring solubility of a chemotherapy-anti cancer drug (busulfan) in supercritical carbon dioxide

In the current study, the solubility of busulfan which is a chemotherapy drug for treating chronic myelogenous leukemia (CML) is measured in supercritical carbon dioxide (SC-CO2) at pressures between 120 and 400 bar, and temperatures between 308 and 338 K. It was indicated that the solubility of this drug via a static solubility measurement technique coupled with a gravimetric approach was between 3.27 × 10−5 to 8.65 × 10−4 (mole fraction). The measured solubility data reveled the direct effect of pressure on the solubility data, while the temperature has a dual effect of both increasing and decreasing effect considering the shifting point known as cross-over pressure which was measured to be around 160 bar for busulfan. Moreover, a theoretical approach was implemented to predict the solubility data using thermodynamic models. Indeed, five widely used semi-empirical density based correlations namely Kumar-Johnston (KJ), Bartle et al., Mendez-Santiago and Teja (MST), Garlapati and Madras and Chrastil models were used to model solubility data using only pressure, temperature and density of mixture as input parameters. The modeling as well as curve fitting results demonstrated that among the examined models, KJ model introduced more accurate correlative capability with AARD of about 7.57%.

Pressure Effects on the SEIS‐InSight Instrument, Improvement of Seismic Records, and Characterization of Long Period Atmospheric Waves From Ground Displacements

AbstractMars atmospheric pressure variations induce ground displacements through elastic deformations. The various sensors of the InSight mission were designed in order to be able to understand and correct for these ground deformations induced by atmospheric effects. Particular efforts were made, on one hand, to avoid direct pressure and wind effects on the seismometer and, on the other hand, to have a high performance pressure sensor operating in the same frequency range as the seismometer. As a consequence of these technical achievements and the low background seismic noise of Mars, the InSight mission is opening a new science domain in which the ground displacements can be used to perform atmospheric science. This study presents an analysis of pressure and seismic signals and the relations between them. After a short description of the pressure and seismic sensors, we present an analysis of these signals as a function of local time at the InSight location. Then the coherent signals recorded by both pressure and seismic sensors are described and interpreted in terms of atmospheric signals and ground deformation processes. Two different methods to remove the pressure effects recorded by SEIS sensors are presented, and their efficiency is estimated and compared. These decorrelation methods allow the pressure generated noise to be reduced by a factor of 2 during the active day time period. Finally, an analysis of SEIS signals induced by gravity waves demonstrates the interest of ground displacement measurements to characterize their arrival azimuth.

Hydromechanical Modeling of Fault Reactivation in the St. Gallen Deep Geothermal Project (Switzerland): Poroelasticity or Hydraulic Connection?

AbstractIn 2013, fluid injection during the St. Gallen deep geothermal project, Switzerland, induced hundreds of seismic events, including a 3.5 earthquake on a fault hundreds of meters away from the well. Recent studies have suggested the direct pressure effect through permeable hydraulic connections and poroelastic effects as possible mechanisms for inducing seismicity on distant faults. In St. Gallen, operational, seismic, and earthquake data are available to investigate the underlying physical mechanisms using a numerical model. The results show that Coulomb stress changes at the fault can be 3 orders of magnitude greater when a hydraulic connection is present. Combining this with several field observations, we conclude that the direct pressure effect was more likely the predominant mechanism behind the seismicity induced in St. Gallen. The detection of hydraulic connections may be important for future projects as pressure can be driven far from the well and reactivate remote faults.

High hydrostatic pressure induces atrial electrical remodeling through upregulation of inflammatory cytokines

AimsHypertension is an independent risk factor for atrial fibrillation (AF). However, the direct effect of hydrostatic pressure on atrial electrical remodeling is unclear. The present study investigated whether hydrostatic pressure is responsible for atrial electrical remodeling and addressed a potential role of inflammation in this pathology. Main methodsWhole-cell patch-clamp recordings and biochemical assays were used to study the regulation and expression of ion channels in left atrial appendages in patients with AF, spontaneously hypertensive rats (SHRs), and atrium-derived cells (HL-1 cells) exposed to standard (0 mmHg) and elevated (20, 40 mmHg) hydrostatic pressure. Key findingsBoth TNF-α and MIF were highly expressed in patients with AF and SHRs. AF inducibility in SHRs was higher after atrial burst pacing, accompanied by a decrease in the L-type calcium current (ICa,L), an increase in the transient outward K+ current (Ito) and ultra-rapid delayed rectifier K+ current (IKur), and a shortened action potential duration (APD), which could be inhibited by atorvastatin. Furthermore, exposure to elevated pressure was associated with electrical remodeling of the HL-1 cells. The peak current density of ICa,L was reduced, while Ito and IKur were increased. Moreover, the expression levels of Kv4.3, Kv1.5, TNF-α, and MIF were upregulated, while the expression of Cav1.2 was downregulated in HL-1 cells after treatment with high hydrostatic pressure (40 mmHg). Atorvastatin alleviated the electrical remodeling and increased inflammatory markers in HL-1 cells induced by high hydrostatic pressure. SignificanceElevated hydrostatic pressure led to atrial electrical remodeling and increased AF susceptibility by upregulating inflammation.

Portal hypertension evolving from sickled hepatopathy: Could hepatic venous Doppler ultrasound be beneficial in its evaluation?

PurposeSickle cell intrahepatic cholestasis involves sickling within hepatic sinusoids leading to vascular stasis and localized hypoxia resulting in ballooning of the hepatocytes causing a direct back pressure effect with resultant intracanalicular cholestasis. Vascular stasis may ultimately lead to portal hypertension. We proposed to document findings suggestive of portal hypertension evolving from hepatopathy in steady-state sickle cell disease (SCD) patients using hepatic venous Doppler ultrasound. MethodsThis is a prospective case series of 6 SCD subjects in steady-state (median age, 30 years; range, 19–43), comprising of 3 males and 3 females, who underwent a routine Doppler ultrasound evaluation of their hepatic veins and were discovered to have an abnormal biphasic waveform pattern. Venous blood was obtained from all subjects to evaluate for P-selectin, homocysteine, foetal haemoglobin, haematocrit levels, white cell and platelet counts. Doppler ultrasound was also carried out on all subjects to evaluate for the hepatic waveform, right renal artery RI and PI along with the hepatic artery velocities. ResultsAll the 6 subjects had reduced haematocrit (median value of 21.5%; range, 18–25%) and some degree of renal dysfunction (plasma cystatin-C ranged from 1.6 to 12.2 mg/L). Elevated white cell count, hyperhomocysteinemia, reduced SpO2(<94.0%) and reduced estimated GFR (eGFR < 90 ml/min) was also noted in 4 subjects (66.7%). Similarly, 4 subjects (66.7%) had elevated RI in the right kidneys while 3 subjects (50.0%) had elevated PI in the right kidney. ConclusionDoppler ultrasound Hepatic vein waveform analysis may be a useful examination in the evaluation of patients with SCD as it may elicit feature of portal hypertension. Further studies are suggested to confirm this in a larger population of SCD patients using the gold standard.

Cerebrovascular effects of endothelin-1 investigated using high-resolution magnetic resonance imaging in healthy volunteers

Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide released from vascular endothelium. ET-1 plays a major role in cerebrovascular disorders and likely worsens the outcome of acute ischaemic stroke and aneurismal subarachnoid haemorrhage through vasoconstriction and cerebral blood flow (CBF) reduction. Disorders that increase the risk of stroke, including hypertension, diabetes mellitus, and acute myocardial infarction, are associated with increased plasma levels of ET-1. The in vivo human cerebrovascular effects of systemic ET-1 infusion have not previously been investigated. In a two-way crossover, randomized, double-blind design, we used advanced 3 tesla MRI methods to investigate the effects of high-dose intravenous ET-1 on intra- and extracranial artery circumferences, global and regional CBF, and cerebral metabolic rate of oxygen (CMRO2) in 14 healthy volunteers. Following ET-1 infusion, we observed a 14% increase of mean arterial blood pressure, a 5% decrease of middle cerebral artery (MCA) circumference, but no effects on extracerebral arteries and no effects on CBF or CMRO2. Collectively, the findings indicate MCA constriction secondarily to blood pressure increase and not due to a direct vasoconstrictor effect of ET-1. We suggest that, as opposed to ET-1 in the subarachnoid space, intravascular ET-1 does not exert direct cerebrovascular effects in humans.

The Effect of Leadership and Job Pressure on Organizational Performance through Organizational Commitments on PT. NUSATAMA BERKAH

This study aims to determine the effect of leadership and job pressure on organizational performance simultaneously, the influence of leadership on organizational performance partially, the influence of work pressure on organizational performance partially, the influence of organizational commitment on organizational performance partially, the influence of leadership on organizational performance through organizational commitment and the effect of work pressure on organizational performance through organizational commitment. The research was conducted at PT. Nusatama Berkah. Sampling uses accidental samples involving 66 employees. Data analysis using path analysis. Based on the data analysis, it is known that leadership variables and job pressure affect the performance of the organization simultaneously. Leadership variables influence partially on organizational performance. Job stress variables partially influence organizational performance. Organizational commitment variables affect organizational performance partially. The direct influence of leadership on organizational performance is smaller compared to indirect effects through organizational commitment. The direct effect of work pressure on organizational performance is smaller than through organizational commitment. In this case, the organizational commitment variable is an intervening variable.

Basement Fault Reactivation by Fluid Injection Into Sedimentary Reservoirs: Poroelastic Effects

AbstractTo investigate mechanisms of seismic fault reactivation in crystalline basement in response to fluid injection in overlying sedimentary reservoirs, we conducted three‐dimensional finite element simulations to assess the effects of direct pore pressure communication and indirect poroelastic stress transfer on the change in Coulomb failure stress of favorably oriented faults of varying permeability structure in normal, strike‐slip, and reverse faulting stress regimes. We demonstrate that the direct pore pressure effect transmitted along a hydraulically conductive fault exceeds the indirect poroelastic effect, but alone is insufficient for fault reactivation in the basement. The poroelastic effect on the Coulomb failure stress results from induced normal tractions and, to a lesser extent, from induced shear tractions that relate to the flexing of the fault as the reservoir expands poroelastically with fluid injection. Assuming a higher Biot coefficient for reservoir over basement rock as previously reported, the combined direct pore pressure and indirect poroelastic effects result in reactivation of hydraulically conductive faults in the basement in normal and strike‐slip faulting stress regimes and in the reservoir in reverse faulting regimes. Sealing normal faults that are not preferentially conductive also preferentially reactivate in the reservoir. These findings apply to injection in either hanging or footwall of normal and reverse faults. Reducing the contrast in Biot coefficient between reservoir and basement favors fault reactivation in the reservoir for injection in the footwall in normal faulting stress regimes. These simulations demonstrate that geomechanical models without coupled poroelasticity underestimate the potential of fault reactivation in crystalline basement.

Interlay Technique Tympanoplasty: Surgical Difficulties with Variable Grafts

Perforation of the tympanic membrane is most commonly the result of chronic ear disease. However, it can also result from various forms of trauma, which includes iatrogenic and direct physical injuries, burns, scalds and pressure effects. Most of these perforations heal spontaneously, whereas the remaining long-standing perforations that lead to recurrent ear discharge need tympanoplasty. Objectives: the aim of this study was to evaluate the results of interlay technique of tympanoplasty with respect to graft uptake and hearing status and to compare surgical difficulties between variable grafts. Patients and Methods:A total of 20 Patients included in the study were 6 males and 14 females, their age ranged from 10 years to 50 years presented with dry large central tympanic membrane perforations being inactive for at least one month without treatment were operated by interlay myringoplasty . Results:

The relationship between employment pressure and occupational delay of gratification among college students: positive psychological capital as a mediator

This study explored the direct effect of employment pressure among college students on occupational delay of gratification and the intermediary role of positive psychological capital. A stratified cluster-sampling method was used to select 553 university students, who completed the Employment Pressure Scale, Positive Mental Capital Scale, and Occupational Delay of Gratification Scale. Regression analysis and bootstrap methods were used to examine the intermediary role of positive psychological capital between employment pressure and occupational delay of gratification. There were positive correlations between employment pressure and occupational delay of gratification, between employment pressure and positive psychological capital, and between occupational delay of gratification and positive psychological capital (r = .51–.75, p < .01). Employment pressure was a negative predictor of occupational delay of gratification (β = −.391, p < .01), and positive psychological capital was a mediator between employment pressure and occupational delay of gratification; the mediating effect explained 24.18% of the total effect. Thus, positive psychological capital plays an intermediary role between employment pressure and occupational delay of gratification among college students.

Earthquakes Induced by Hydraulic Fracturing Are Pervasive in Oklahoma

AbstractWastewater disposal is generally accepted to be the primary cause of the increased seismicity rate in Oklahoma within the past decade, but no statewide analysis has investigated the contribution of hydraulic fracturing (HF) to the observed seismicity or the seismic hazard. Utilizing an enhanced seismicity catalog generated with multistation template matching from 2010 to 2016 and all available hydraulic fracturing information, we identified 274 HF wells that are spatiotemporally correlated with bursts of seismicity. The majority of HF‐induced seismicity cases occurred in the SCOOP/STACK plays, but we also identified prominent cases in the Arkoma Basin and some more complex potential cases along the edge of the Anadarko Platform. For HF treatments where we have access to injection parameters, modeling suggests that poroelastic stresses are likely responsible for seismicity, but we cannot rule out direct pore pressure effects as a contributing factor. In all of the 16 regions we identified, ≥75% of the seismicity correlated with reported HF wells. In some regions, &gt;95% of seismicity correlated with HF wells and &gt;50% of the HF wells correlated with seismicity. Overall, we found ~700 HF‐induced earthquakes with M ≥ 2.0, including 12 events with M 3.0–3.5. These findings suggest state regulations implemented in 2018 that require operators in the SCOOP/STACK plays to take action if a M &gt; 2 earthquake could have a significant impact on future operations.

Assessing changes in tissue oxygenation by near-infrared spectroscopy following brachial plexus block for arteriovenous fistula surgery: A prospective observational pilot study.

Near-infrared spectroscopy (NIRS) can be used to measure tissue oxygen saturation (StO2) in different sites and in a wide range of clinical scenarios. Peripheral regional anaesthesia induces vascular changes causing increased arterial blood flow and venodilatation, but its effect on StO2 is still under debate. This is especially so for patients undergoing arteriovenous fistula surgery, wherein latest data suggest an improved outcome under brachial plexus block (BPB) compared with local anaesthesia, but no data are available. The aim of this study was to investigate changes in StO2 following BPB prior to arteriovenous fistula surgery using NIRS. A prospective observational study. A secondary teaching hospital from August 2016 to March 2017. Fifteen patients undergoing arteriovenous fistula surgery. Ultrasound-guided BPB in 15 patients undergoing arteriovenous fistula surgery. StO2 at baseline and compared with baseline and the contralateral arm following BPB measured using NIRS of the thenar eminence (NIRSth). Baseline values of StO2 assessed by NIRSth were 42.6 ± 7.7% in the arteriovenous fistula arm and 42.7 ± 9.7% in the contralateral arm. There was no significant difference between the two. Five minutes after BPB, there was a significant increase in StO2 of the blocked arm, compared with the control arm expressed as difference of absolute values (7.1 ± 9.7%). At 60 min, an absolute difference of 21.0 ± 13.5% was reached. The absolute increase in StO2 of the blocked arm compared with baseline reached significance after 5 min (8.8 ± 4.6%) and increased up to 23.2 ± 8.2% after 60 min. NIRSth indicates that BPB significantly increases StO2 of the arteriovenous fistula arm in patients undergoing haemodialysis. Clinicaltrials.gov: NCT03044496.

Was the Mw 7.5 1952 Kern County, California, earthquake induced (or triggered)?

Several recent studies have presented evidence that significant induced earthquakes occurred in a number of oil-producing regions during the early and mid-twentieth century related to either production or wastewater injection. We consider whether the 21 July 1952 Mw 7.5 Kern County earthquake might have been induced by production in the Wheeler Ridge oil field. The mainshock, which was not preceded by any significant foreshocks, occurred 98 days after the initial production of oil in Eocene strata at depths reaching 3 km, within ~1 km of the White Wolf fault (WWF). Based on this spatial and temporal proximity, we explore a potential causal relationship between the earthquake and oil production. While production would have normally be expected to have reduced pore pressure, inhibiting failure on the WWF, we present an analytical model based on industry stratigraphic data and best estimates of parameters whereby an impermeable splay fault adjacent to the main WWF could plausibly have blocked direct pore pressure effects, allowing the poroelastic stress change associated with production to destabilize the WWF, promoting initial failure. This proof-of-concept model can also account for the 98-day delay between the onset of production and the earthquake. While the earthquake clearly released stored tectonic stress, any initial perturbation on or near a major fault system can trigger a larger rupture. Our proposed mechanism provides an explanation for why significant earthquakes are not commonly induced by production in proximity to major faults.

How Is Environmental Proactivity Accomplished? Drivers and Barriers in Firms’ Pro-Environmental Change Process

The contaminating effects of economic activity and the scarcity of natural resources has led firms to a situation in which corporate strategy has been compromised by environmental issues. The objective of this paper is to analyse some of the factors determining the pro-environmental change process by considering the drivers encouraging firms to progress in environmental protection and the barriers that curb this progress. Using a structural equation model implemented on a sample of 303 firms, our results confirm a direct and positive effect of stakeholder pressure and of the expectations of obtaining competitive advantages from the pro-environmental change process. The results also confirmed the indirect effect of stakeholder pressure on pro-environmental change through managers’ expectations of obtaining competitive advantages, which play a mediating role in the firm’s response. Although managers interpret the barriers we have studied as obstacles to adopting environmental protection measures, they do not prevent any firm from reaching advanced levels of pro-environmental change.

Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1

Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1[18–50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93–166]) and CT-proET-1 (ppET-1[169–212]) in conditioned media from cultured endothelial cells. Synthesis of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were elevated in patients with chronic heart failure. Clearance rates of NT-proET-1, ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats. CT-proET-1 had the slowest systemic clearance, hence providing a biological basis for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary conserved endothelin-like domain sequence, which potentially confers biological activity. On isolated arteries ELDP lacked direct vasoconstrictor effects. However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood pressure in anaesthetised rats. ELDP may therefore contribute to disease pathogenesis by augmenting ET-1 responses.

The 2016 Mw5.1 Fairview, Oklahoma earthquakes: Evidence for long-range poroelastic triggering at >40 km from fluid disposal wells

Wastewater disposal in the central U.S. is likely responsible for an unprecedented surge in earthquake activity. Much of this activity is thought to be driven by induced pore pressure changes and slip on pre-stressed faults, which requires a hydraulic connection between faults and injection wells. However, direct pressure effects and hydraulic connectivity are questionable for earthquakes located at large distances and depths from the injectors. Here, we examine triggering mechanisms of induced earthquakes, which occurred at more than 40 km from wastewater disposal wells in the greater Fairview region, northwest Oklahoma, employing numerical and semi-analytical poroelastic models. The region exhibited few earthquakes before 2013, when background seismicity started to accelerate rapidly, culminating in the Mw5.1 Fairview earthquake in February 2016. Injection rates in the ∼2–2.5 km deep Arbuckle formation started to increase rapidly in 2012, about two years before the start of seismicity-increase. Most of the injection activity was concentrated toward the northeast of the study region, generating a relatively cohesive zone of pressure perturbations between 0.1 and 1 MPa. Much of the near-injection seismicity was likely triggered by pressure effects and fault-assisted pressure diffusion to seismogenic depth. Outside of the high-pressure zone, we observed two remarkably detached, linear seismicity clusters, which occurred at 20 to 50 km distance from the initial seismicity and 10 to 40 km from the nearest, high-rate injector. Semi-analytical models reveal that poroelastically-induced Coulomb-stress-changes surpass pore pressure changes at these distances, providing a plausible triggering mechanism in the far-field of injection wells. These results indicate that both pore-pressures and poroelastic stresses can play a significant role in triggering deep and distant earthquakes by fluid injection and should be considered for seismic hazard assessment beyond the targeted reservoir.