Simultaneous measurement of cardiovascular and respiratory systems has become increasingly popular, but their interdependent nature often obscures the individual contributions of each. In this study, we adapted existing rat and rabbit models to non-human primates to develop an anesthetized model enabling simultaneous assessment of both systems. This model aims to identify in vivo liabilities of active compounds. To validate system interdependence, we administered a known neuromuscular blocker (cisatracurium) and a negative inotrope/vasodilator (verapamil).Six anesthetized and mechanically ventilated male and female rhesus macaques were acutely instrumented to simultaneously measure systemic and left ventricular hemodynamics (via catheterization) and respiratory/skeletal muscle function (via strain gauge) in a terminal setting. In four animals, measurements were taken before and during administration of cisatracurium (3 μg/kg/min for 30 min) and verapamil (12.5–100 μg/kg/min in escalating 15-min infusions). The remaining two animals were used to assess model stability over a 5-h period.Cisatracurium elicited a precipitous decline in skeletal, diaphragmatic (respiratory), and peripheral limb (train-of-four) force until complete paralysis was achieved during the 20-min infusion. Function recovered over the next 40–60 min. Diaphragmatic force recovered the fastest, skeletal muscle recovered the slowest, and peripheral limb train-of-four in between. Heart rate and peak left ventricular pressures were unaffected by cisatracurium. Heart rate, peak left ventricular pressures, and diaphragmatic force reduced dose-dependently with verapamil. Complete cardiovascular collapse was achieved at 100 μg/kg/min. Skeletal muscle transiently increased during 25 and 50 μg/kg/min and subsequently fell during the highest dose. Peripheral limb train-of-four was unaffected by verapamil.Taken together, these results and observations demonstrate an in vivo anesthetized and mechanically-ventilated non-human primates model is capable of detecting neuromuscular (diaphragmatic and skeletal) and cardiovascular alterations in situ. The non-human primate preparation was shown to be both stable and responsive to cardiovascular and neuromuscular changes triggered by either verapamil or cisatracurium.Hence, the utility of this model could be extended to confirm liabilities of both cardiovascular and respiratory systems in a species that is more similar to humans.

Chronic recordings of systemic arterial blood pressure in a conscious animal with concomitant blood draws to establish pharmacokinetic-pharmacodynamics (PK/PD) relationships is very common tool in safety pharmacology. Herein, we established a robust model that permits both in healthy rabbits. Twenty-one (21) rabbits (~3 kg) were anesthetized xylazine-ketamine and underwent instrumentation with M-10 telemetry (DSI) and an indwelling venous catheter attached to a catheter access button (CAB, SAI technologies). Isoflurane and fentanyl were used for surgical maintenance. Two approaches were compared, laparotomy approach (iliac vein/artery) and neck approach (jugular vein, carotid artery). Following surgery, animals were allowed to recover. Blood pressure signals and venous catheter patency were followed for up to 10 weeks. An initial pilot (n = 2) using a laparotomy approach proved doable but challenging. One of which recovered from surgery with hind limb paralysis. The remaining animals (n = 19) were successfully instrumented via a neck approach with the telemetry unit and CAB tunneled and secured subcutaneously in the intrascapular region. Two unexpectedly died several days after recovery (from unknown causes). Of the 17 implants, 15 had reliable/physiological arterial pressure curves and 15 had patent venous catheters for up to 10 weeks. Interestingly, the magnet in the CAB sporadically turned the telemetry unit on and off due to the close connection (~2–3 in.) in about 38 % of the first batch of instrumented animals. After further separation, ~4 in., only ~11 % had periodical turn offs in the second batch of implants. With proper telemetry instrumentation in the carotid artery and jugular vein catheterization, placement, and maintenance of a CAB, PK/PD relationships with systemic blood pressure can be reliably performed in rabbits.

Myxomatous mitral valve disease (MMVD) is the most common valvular heart disease in geriatric small-to medium-sized dogs. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), has shown promise in managing heart failure in human patients. This pilot study aimed to explore the short-term effects of dapagliflozin, when added to conventional therapy in symptomatic MMVD dogs. In a prospective, randomized, single-blind study, five dogs with stage C MMVD received dapagliflozin (0.31 mg/kg, PO, q24h) alongside pimobendan, furosemide, and ramipril. A control group (n = 7) received conventional therapy without dapagliflozin. Echocardiographic, electrocardiographic, blood pressure, blood glucose, NT-proBNP, and urinary glucose data were collected at baseline (D0) and follow-up (D28, D84, and D140). Compared to the control group, dogs receiving dapagliflozin showed significant reductions in the percent change from baseline for left atrial to aortic root ratio, left ventricular internal diameter in diastole normalized to body weight, end-diastolic volume, end-diastolic volume index, end-systolic volume, and end-systolic volume index (P < 0.05). Additionally, ejection fraction significantly increased in the dapagliflozin group (P < 0.05). Glucosuria was consistently present only in the dapagliflozin group. These findings suggest that dapagliflozin, when added to conventional therapy, may promote reverse remodeling and improve cardiac function in dogs with stage C MMVD. Further studies with larger sample sizes and longer follow-up are warranted to validate the cardioprotective effects of dapagliflozin in veterinary patients.

After spinal cord injury (SCI), cardiovascular remodeling occurs at multiple levels. Despite the high prevalence of cardiovascular disease following SCI, there are few studies that attempt to illustrate the interplay between cardiac structure and function following injury. This study aims to assess cardiovascular remodeling and its relationship to cardiovascular dysfunction following chronic cervical (C8) midline spinal contusion. Nineteen Sprague-Dawley rats either received C8 midline contusion (cSCI, n = 10; Infinite Horizon Impact Device; 250 kilodynes; 0 s dwell time) or laminectomy (LAM, n = 9) as sham control. Fifteen weeks post-surgery, echocardiography was performed to assess cardiac function and morphology. At week 16, rats were anesthetized by urethane and a blood pressure catheter was placed into the aortic arch via the left common carotid artery. Orthostatic stress testing was introduced to evaluate the cardiovascular responses during 3-minute 90 degrees head-up tilting, followed by pharmacological stress testing via norepinephrine (NE) infusion (i.v.) at low (1 µg/kg/min) and high (4 µg/kg/min) doses. After tissue collection, collagen content (Masson trichrome stain), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation (IC 100 stain), and sympathetic innervation (tyrosine hydroxylase stain) were next investigated in the cardiovascular tissues. Correlation analyses were also performed between cardiovascular structural and functional measures. Results demonstrated that cSCI rats became hypotensive at rest and 70% of cSCI rats experienced significant orthostatic hypotension with an inability to maintain heart rate (HR) during head-up tilting. HR and mean arterial pressure reactivity in response to high-dose NE infusion were also significantly decreased in cSCI rats ( p <0.05) compared to LAM rats. Echocardiographic results showed reduced left ventricular (LV) diameter and volume ( p <0.01). Additionally, histological results revealed increased LV collagen content ( p <0.001), number of ASC specks (p<0.05), and increased sympathetic nerve density and quantity, especially within the LV posterior wall ( p <0.01 and p <0.05, respectively). Moreover, a strong linear relationship between histopathological and cardiovascular functional measures was observed. Overall, this study demonstrates that cardiovascular dysfunction is strongly correlated with cardiac atrophy, myocardial fibrosis, cardiac inflammation that is in part mediated by the inflammasome in the form of ASC specks, and enhanced cardiac sympathetic activity following chronic C8 midline contusion. This study was supported by: NIH (R01 NS131493) and Florida Department of Health (COPBC). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Purpose The purpose of this qualitative study is to compare the perceptions of employed people in Mexico and Colombia about managerial and leadership behavioural effectiveness. Design/methodology/approach A qualitative multiple cross-case and cross-nation comparative analysis of findings obtained from the two past emic replication (Mexico and Colombia) studies was conducted. Findings The study suggests that people within Mexican and Colombian organizations perceive “managerial and leadership behavioural effectiveness” in very similar ways. The findings support those researchers whose studies indicate that culture may not, as previously thought, play a significant role in the way managers should manage and lead their subordinates. Research limitations/implications The authors acknowledge two main limitations related to the sample size and scope of the two compared sets of empirical source data. The number of critical incidents about perceived managerial behavioural effectiveness obtained from the two compared studies was unbalanced (318 from the Mexican study and 267 from the Colombian study). Thus, the authors suggest more indigenous replication managerial behaviour studies be carried out in both Mexico and Colombia with the objective of identifying (if possible) the existence of critical incidents that could lead to different findings. Furthermore, the authors suggest conducting replica studies focused on specific industries rather than a diverse range of organizations to test the generalizability of the findings. Practical implications The findings of the comparative study are relevant to those human resource development professionals in international companies with operations in Mexico and/or Colombia when preparing their executives for international assignments in these Latin American countries. Originality/value The comparative study attempts to generate new insights and better understanding within the context of “managerial and leadership behavioural effectiveness” research, which the authors hope will make a useful contribution to the existing small body of knowledge regarding similarities and differences in managerial practices across culturally diverse Latin American countries.

Background: Myocardial infarction (MI) is a leading cause of death in the United States. However, none of the therapies can regenerate the damaged heart muscle. Objective: The objective of this study was to assess the safety and engraftment of a nanofiber cardiac patch laden with human iPSC-derived cardiomyocytes (hiCMs) and transplanted in a preclinical porcine MI model. Methodology: MI was induced in pigs via advancing a balloon catheter from the femoral artery into the left anterior descending coronary artery (LAD) below the first diagonal branch (D1) and the balloon was inflated for 90-min to induce myocardial ischemia. Immunosuppressant drug Tacrolimus was given orally one-week before the cardiac patch transplantation and continued for up to 4-weeks post-cardiac patch transplantation. Epicardial transplantation of aligned nanofiber cardiac patch (2 layers) loaded with hiCMs was performed at one-week post MI. Magnetic resonance Imaging (MRI) was performed prior to the MI induction (Baseline), 1-week post-MI and at 4-weeks post cardiac patch transplantation to assess severity of MI and cardiac function. At 4-weeks post-MI, pigs were euthanized, and the heart tissues were processed for immunostaining to confirm the retention and engraftment (Human Nuclear Antibody staining) of the implanted cells in the host myocardium. Results: (a) A significant increase in ST-elevation following 90-min of MI, (b) Incidence of cardiac arrhythmias were not observed post cardiac patch transplantation, confirming the safety of cardiac patch, (c) No teratomas were observed at the transplanted site, indicating safety of terminally differentiated hiCMs and (d) Immunofluorescence staining of cardiac sections in the transplanted cardiac patch area confirmed engraftment of transplanted cells via anti-human nuclear antibody, which demonstrates the survival and engraftment of implanted cells. Conclusions: In summary, we have demonstrated for the first time that aligned nanofiber cardiac patch loaded with hiCMs is safe and can enhance retention of transplanted cells. Further studies are warranted to assess the long-term efficacy of cardiac patch transplantation in improving the cardiac function and to perform first-in-human clinical trials in the near future.

Pimobendan, diuretics, and an angiotensin-converting enzyme inhibitor (ACEi) are widely used for the management of chronic valvular heart disease in dogs; however, the effects of that combination on heart rate variability (HRV) are unknown. The purpose of this study was to assess the HRV of symptomatic myxomatous mitral valve degeneration (MMVD) dogs in response to therapy with a combination of pimobendan, diuretics, and ACEi. MMVD stage C (n = 17) dogs were enrolled and a 1-hour Holter recording together with echocardiography, blood pressure measurement, and blood chemistry profiles were obtained before and 1, 3, and 6 months after oral treatment with pimobendan (0.25 mg/kg), enalapril (0.5 mg/kg), and furosemide (2 mg/kg) twice daily. The results revealed that MMVD stage C dogs at the baseline had lower values of time-domain indices, low frequency (LF), high frequency (HF), and total power, as well as higher value of LF/HF. Triple therapy significantly increases these parameters in MMVD stage C dogs (P < 0.05). A positive moderate correlation was observed between time domain parameters and a left ventricular internal diastole diameter normalized to body weight (P < 0.05). It can be concluded that MMVD stage C dogs possess low HRV due to either the withdrawal of parasympathetic tone or enhanced sympathetic activation, and a combination therapy was shown to enhance cardiac autonomic modulation inferred from the increased heart rate variability. Therefore, a combination therapy may be useful for restoring normal autonomic nervous system activity in dogs with MMVD stage C.

Centell-S is a water-soluble extract of Centella asiatica containing more than 80% w/w triterpenoid glycosides. Madecassoside and asiaticoside are two major components of the extract and can be converted into active metabolites, triterpenic acids in large mammal species. In this study, the pharmacokinetic profiles and metabolomic changes generated by the bioactive triterpenoids of Centell-S alone, and in combination with the bioenhancers piperine and curcumin, were investigated in beagle dogs. The test substances were orally administered over multiple doses for 7 consecutive days. At day 1 and 7 after receiving the test compounds, the level of major bioactive triterpenoids and related metabolites were measured using triple quadrupole and high-resolution accurate mass orbitrap models of LCMS to determine pharmacokinetic and metabolomic profiles, respectively. Centell-S was well tolerated, alone and in all combination groups. The combination of Centell-S and piperine significantly increased ( p < 0.05) the systemic exposure of madecassoside on day 1 and asiatic acid on day 7, by approximately 1.5 to 3.0-fold of C max and AUC values as compared to the Centell-S alone, while the addition of curcumin did not provide a significant improvement. Several metabolomic changes were observed from pre-dose to 4 h post-dose, with some biomarkers of neurodegenerative diseases including l -glutamine, lysophosphatidylcholine (17:0), taurochenodeoxycholic acid, uric acid, stearic acid, palmitic acid, and lactic acid showing good correlation with the systemic exposure of the bioactive triterpenoids (asiatic acid). Thus, the combining of piperine to Centell-S exhibits the improvement of bioactive triterpenoids which are related to the biomarkers of neurodegenerative diseases. These promising results might be useful for the development of this standardised extract to become a more effective phytomedicine for neurodegenerative diseases.

Potentially damaging “heart stress” is reversed using reactive nerve stimulation controlled by artificial intelligence.

Echocardiograms were obtrained from 15 standing clinically normal cows using an ultrasonic recording device. The echo beam penetrated the right thoracic wall in the area of the fourth intercostal space with a frequency of 2.25 MH3. Left ventricular wall thickness measured 2.00 +/- .19 cm while the septal dimension was slightly higher at 2.24 +/- .26 cm. Velocity of circumferential fiber shortening (Vcf), and index of contractility, was .87 +/- .4 m/s and minor axis shortening fraction (% delta D), and indicator of pump frunction, was 43.5 +/- 5.8%.

Removal of excess fluid in acute decompensated heart failure (ADHF) targets the intravascular space, whereas most fluid resides in the interstitial space. The authors evaluated an approach to interstitial decongestion using a device to enhance lymph flow. The device was deployed in sheep with induced heart failure (HF) and acute volume overload to create a low-pressure zone at the thoracic duct outlet. Treatment decreased extravascular lung water (EVLW) volume (mL/kg) (-32% +/- 9%, P = 0.029) compared to controls (+46% +/- 9%, P = 0.003). Device-mediated thoracic duct decompression effectively reduced EVLW. Human studies may establish devicebased interstitial decongestion as a new ADHF treatment. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

This paper presents a coaching assignment decisionmaking framework to assist coaches, and others in related to roles, to evaluate and make an informed choice about whether or not to accept a coaching assignment. There are good reasons to say ‘no’ to a coaching assignment, and a failure to do so can exact a serious cost – psychosocial, career-related or both. This paper presents empirical data, addressing the consequences of saying ‘yes’ when ‘no’ would have been the best decision in the circumstances, and presents a series of questions to inform the pre-coaching assignment decision-making process. The empirical data consists of a short survey completed by 345 experienced coaches. The data was subsequently analysed using NVivo in order to identify themes and illustrative responses, as well as summarizing and synthesizing the data as a whole. The findings explore the circumstances and factors respondents take into account when considering a coaching assignment. The authors present a coaching assignment decisionmaking framework. We hope that practitioners engaged in coaching may be able to benefit from the approach through the application of a practical framework and series of questions designed to be sufficiently flexible to apply to different contextual settings and circumstances. Introduction Practitioner and academic studies predominantly focus on the coaching approach, coaching process and/or the impact of coaching on the coachee (Wageman, Nunes, Burruss & Hackman, 2008; Chin-Yun, Long-Sheng, Ing-Chuang & Kuo-Chin, 2010). The quality of the relationship between the coach, the client and key stakeholders is believed to be one of the most critical indicators of coaching effectiveness (Baron & Morin, 2009; Bluckert, 2005; de Haan, Duckworth, Birch & Jones, 2013) and, ‘the more you and your client can include the whole system, the more effective the coaching is likely to be’ (Rogers, 2008, p. 123). Despite the known importance and value placed on the quality of the relationship, few studies focus on the decision-making process and questions posed by the coach in any role or context to assist in the pre-coaching assignment phase, or as commonly known, the contracting phase which helps to steer and determine the quality of the relationship. Furthermore, the role of multi-stakeholder contracting is an area of growing importance as coaches find themselves working for multiple clients, where little guidance in the pre-assignment phase is currently provided in practitioner or academic studies. Against this backdrop, the authors aim to address the paucity of practice-based coaching studies in this area, presenting a coaching assignment decisionmaking framework, to assist coaches in any role, context or multi-party arrangement, to evaluate and make an informed choice about whether or not to accept a coaching assignment. The impetus for this paper is two-fold. First, the cause of saying ‘yes’ to a coaching assignment when the answer should be ‘no’ can be largely attributed to the absence of a thorough exploration and contracting phase.

Background: Pimobendan provides a significant survival benefit in dogs with cardiac disease, including degenerative mitral valve disease and dilated cardiomyopathy (DCM). Its positive inotropic effect is well-known, however, it has complex effects and the mechanisms behind the survival benefit are not fully characterized. Secondary hemodynamic effects may decrease mitral regurgitation (MR) in DCM, and the benefits of pimobendan may extend to improved cardiac relaxation and improved atrial function.Hypothesis/Objectives: Our objective was to investigate the acute cardiac effects of pimobendan in dogs with a DCM phenotype. We hypothesized that pimobendan would increase left atrial (LA) contractility, reduce mitral regurgitation, improve diastolic function, and lower circulating NT-ProBNP levels.Animals: Seven purpose-bred Beagles were studied from a research colony with tachycardia induced DCM phenotype.Methods: The effects of pimobendan were studied under a placebo-controlled single-blinded cross-over design. In short, dogs underwent baseline and 3 h post-dose examinations 7 days apart with echocardiography and a blood draw. Dogs were randomized to receive oral placebo or 0.25 mg/kg pimobendan after their baseline exam. Investigators were blinded to treatments until all measurements were compiled.Results: When treated with pimobendan, the dogs had significant increases in systolic function and decreases in MR, compared to when treated with placebo.There were no detectable differences in left atrial measures, including LA size, LA emptying fraction, LA functional index or mitral A wave velocity. Heart rate decreased significantly with pimobendan compared to placebo. There was also a decrease in isovolumetric relaxation time normalized to heart rate. NT-proBNP levels had a high degree of variability.Conclusions: Improved mitral regurgitation severity and improved lusitropic function may contribute to the reported survival benefit for dogs with cardiac disease administered pimobendan. Pimobendan did not overtly improve LA function as assessed by echocardiography, and NT-proBNP was not significantly changed with a single dose of this medication. Further studies are needed to better characterize LA effects with other imaging modalities, to better quantify the total improvement of MR severity, and to assess chronic use of pimobendan on diastolic function in DCM.

The accuracy with which preclinical studies performed on infrahuman mammals predict the efficacy and safety of potential new therapeutics intended for human use is a topic of interest and concern to preclinical scientists, physicians, veterinarians, regulators, and patients everywhere. Factors that impact the potential accuracy of preclinical assessments of safety and efficacy in surrogate species for humans include substantial differences in the mechanisms of cardiac repolarization and excitation–contraction coupling, as well as in the isoforms of the heart's contractile proteins. Some species are so similar to humans that they suffer the same spontaneous heart diseases — and yet so different that toxic doses of drugs or interventions that would be instantly fatal to a human have literally no effect on them. These differences are in part explained by the sometimes enormous differences in size and scale among species and in part by genetic and biochemical differences that we have only recently begun to understand. In reviewing some of the more striking species differences and similarities in cardiovascular physiology, this article hopes to stimulate interest in and inform the choices of scientists involved in surrogate model selection as they work to improve both the positive and negative predictive value of preclinical drug studies.

The term myocardial contractility is thought to have originated more than 125 years ago and has remained and enigma ever since. Although the term is frequently used in textbooks, editorials and contemporary manuscripts its definition remains illusive often being conflated with cardiac performance or inotropy. The absence of a universally accepted definition has led to confusion, disagreement and misconceptions among physiologists, cardiologists and safety pharmacologists regarding its definition particularly in light of new discoveries regarding the load dependent kinetics of cardiac contraction and their translation to cardiac force-velocity and ventricular pressure-volume measurements. Importantly, the Starling interpretation of force development is length-dependent while contractility is length independent. Most historical definitions employ an operational approach and define cardiac contractility in terms of the hearts mechanical properties independent of loading conditions. Literally defined the term contract infers that something has become smaller, shrunk or shortened. The addition of the suffix “ility” implies the quality of this process. The discovery and clinical investigation of small molecules that bind to sarcomeric proteins independently altering force or velocity requires that a modern definition of the term myocardial contractility be developed if the term is to persist. This review reconsiders the historical and contemporary interpretations of the terms cardiac performance and inotropy and recommends a modern definition of myocardial contractility as the preload, afterload and length-independent intrinsic kinetically controlled, chemo-mechanical processes responsible for the development of force and velocity.

BACKGROUND:Patients with refractory hypercholesterolemia, who have high low-density lipoprotein (LDL) cholesterol levels despite treatment with lipid-lowering therapies at maximum tolerated doses, have an increased risk of atherosclerosis. In such patients, the efficacy and safety of subcutaneous and intravenous evinacumab, a fully human monoclonal antibody against angiopoietin-like 3, are not known.METHODS:In this double-blind, placebo-controlled, phase 2 trial, we enrolled patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia, with a screening LDL cholesterol level of 70 mg per deciliter or higher with atherosclerosis or of 100 mg per deciliter or higher without atherosclerosis. Patients were randomly assigned to receive subcutaneous or intravenous evinacumab or placebo. The primary end point was the percent change from baseline in the LDL cholesterol level at week 16 with evinacumab as compared with placebo.RESULTS:In total, 272 patients were randomly assigned to the following groups: subcutaneous evinacumab at a dose of 450 mg weekly (40 patients), 300 mg weekly (43 patients), or 300 mg every 2 weeks (39 patients) or placebo (41 patients); or intravenous evinacumab at a dose of 15 mg per kilogram of body weight every 4 weeks (39 patients) or 5 mg per kilogram every 4 weeks (36 patients) or placebo (34 patients). At week 16, the differences in the least-squares mean change from baseline in the LDL cholesterol level between the groups assigned to receive subcutaneous evinacumab at a dose of 450 mg weekly, 300 mg weekly, and 300 mg every 2 weeks and the placebo group were -56.0, -52.9, and -38.5 percentage points, respectively (P<0.001 for all comparisons). The differences between the groups assigned to receive intravenous evinacumab at a dose of 15 mg per kilogram and 5 mg per kilogram and the placebo group were -50.5 percentage points (P<0.001) and -24.2 percentage points, respectively. The incidence of serious adverse events during the treatment period ranged from 3 to 16% across trial groups.CONCLUSIONS:In patients with refractory hypercholesterolemia, the use of evinacumab significantly reduced the LDL cholesterol level, by more than 50% at the maximum dose. (Funded by Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03175367.).

It is well established that adenosine induces arterial vasodilation in various vascular beds. However, its effect on the venous circulation is still largely unknown. The splanchnic system receives approximately 25% of cardiac output (CO) and contains approximately 20% of total blood volume. Mesenteric (part of splanchnic system, o. d. 150–250 μm) arteries (MA) and their adjacent veins (MV) from rats, dogs, mini‐pigs and humans were isolated and mounted on a myograph (DMT Technology, USA). Vessels were preconstricted with 1 μM phenylephrine (PE) for arteries and prostaglandin F2α (PGF2α) for veins. Cumulative concentrations of 5’‐N‐Ethylcarboxamidoadenosine (NECA, 10−11 – 10−5 M), a non‐specific adenosine agonist, were applied and evaluated. Tension development was normalized to the tension induced by PE/PGF2α as %. NECA induced a concentration dependent arterial vasodilation in all 3 animals and human MA (Fig. 1). The effects were very similar in all 3 animals (maximum of 91.09±10.94% to 93.88±1.93%), however human responses were less pronounced (maximum of 59.14±4.61%). Interestingly, veins from all species responded to NECA very differently (Fig. 2). MVs from rats were the only vessels that constricted strongly in response to NECA (182.94±17.52% of pre‐constriction), which has not been previously reported (Figs. 2– 3). NECA induced vasodilation in MV from the other species varied. NECA induced vasodilation in MV from dogs were similar to MA at high concentrations (Fig. 6, 10−8 M and above). However, MV from mini‐pig (Fig. 5) and human (Fig. 6) responses were minimal (Fig. 2, maximum of 24.56±14.67% in mini‐pig and 33.54±9.61% relaxation in human) compared to 92.93±2.26% relaxation in dogs. In conclusion, although mesenteric arterial vascular reactivity responds similarly to adenosine among species, mesenteric venous vascular reactivity responses varied greatly to adenosine among species. MVs from rats were the only vessel constricted strongly in response to NECA. Caution is advised when choosing animal models for studying vascular reactivity.Figure 1Figure 2Figure 3Figure 4Figure 5Figure 6