Avoiding Glenoid Baseplate Fixation Failure by Altering Surgical Technique for Varying Bone Densities.

Glenoid baseplate failure is one of the causes of revision and poor outcomes in reverse shoulder arthroplasty (RSA). The objective of this study was to determine whether alterations in surgical technique can improve time-zero fixation of the baseplate in varying bone densities. A secondary objective was to identify whether preoperative radiographic glenoid sclerosis width was associated with the implementation of these techniques. Methods: This study included a biomechanical analysis and a retrospective radiographic review. The biomechanical portion describes 2 alterations to the standard surgical technique (under-preparation [A1] or over-preparation [A2] of the central screw pilot hole) and determined their torque-compression relationship via bone-substitute blocks with varying densities. Patients who underwent the described technical alterations were identified from a registry database of primary RSAs performed between 2007 and 2020. These patients were matched to patients who underwent the standard surgical technique, and preoperative radiographs were compared. Interrater reliability testing was performed to determine reproducibility. Results: With respect to the biomechanical arm, the average compressive force of the baseplate in the low-density block model when using the standard technique was 112 N compared with 300 N for the A1 technique (p = 0.01). In the high-density bone model, the standard technique resulted in failure to seat the baseplate, or screw breakage. Performing the A2 technique, the baseplate was seated without failure, with an average compressive force of 450 N. In the clinical arm, retrospective intraoperative video review for use of the alternative techniques found 20 shoulders in the "low-density" cohort and 21 in the "high-density" cohort. There was a significant difference in the glenoid sclerosis thickness between the experimental and matched control groups in our "high-density" cohort (p = 0.0014). The interrater reliability coefficient was found to be 0.69 for the "low-density" glenoid sclerosis thickness measurement and 0.92 for the "high-density" measurement. Conclusions: In low- and high-density bone models, alterations in surgical technique significantly improved compression and improved the ability to successfully seat the glenoid baseplate. Preoperative radiographs can assist in indicating the alternative technique in the sclerotic glenoid. Clinical Relevance: Utilization of these techniques intraoperatively will improve time-zero fixation of the glenoid baseplate and potentially avoid failure of fixation.

Predicting Success for Student Physical Therapists on the National Physical Therapy Examination: Systematic Review and Meta-Analysis.

BACKGROUND: In physical therapist education, the National Physical Therapy Examination (NPTE) is the predominant measure of student success. Because the NPTE is a high-stakes examination, predicting NPTE performance is important for physical therapist students and programs. PURPOSE: The purpose of this study was to determine the relationships between first attempt NPTE performance, physical therapist applicant variables, and physical therapist student variables. The 4 identified physical therapist applicant variables were undergraduate cumulative grade point average (GPA), undergraduate GPA for prerequisite courses, Graduate Record Examination verbal and quantitative subscale scores, and admission scores. The 4 identified physical therapist student variables were first- and third-year physical therapist student GPA, clinical performance scores (first and final clinical experiences), noncognitive student variables, and comprehensive examination scores. DATA SOURCES: A systematic search was performed using the databases PubMed and EBSCO (1966-2018). STUDY SELECTION: Studies included in the review met the following criteria: the physical therapist education program offered an entry-level master's or doctorate degree, pertinent data were available for each independent variable, the relationship between the independent variable and the NPTE was investigated, the NPTE was a continuous variable, the program was a US entry-level therapist education program, and the study was peer reviewed. DATA EXTRACTION: Two independent reviewers completed data extraction and quality appraisal using the McMaster Appraisal Tool. DATA SYNTHESIS: Random-effects meta-analyses using the Pearson product-moment correlation coefficient as the measure of effect size was used. LIMITATIONS: Limitations of the review included a lack of homogeneity, high NPTE pass rates, modifications to the McMaster Appraisal Tool, small sample sizes, and publication bias. CONCLUSIONS: No one physical therapist applicant variable should be used as an independent predictor of first attempt NPTE performance. For physical therapist students, first- and third-year physical therapist student GPA had a strong relationship with first attempt NPTE performance; clinical performance had a weak and nonsignificant relationship with first attempt NPTE performance.

17ß-estradiol reduces Cav 1.2 channel abundance and attenuates Ca2+ -dependent contractions in coronary arteries.

One mechanism by which the female sex may protect against elevated coronary vascular tone is inhibition of Ca2+ entry into arterial smooth muscle cells (ASMCs). In vitro findings confirm that high estrogen concentrations directly inhibit voltage-dependent Cav 1.2 channels in coronary ASMCs. For this study, we hypothesized that the nonacute, in vitro exposure of coronary arteries to a low concentration of 17ß-estradiol (17ßE) reduces the expression of Cav 1.2 channel proteins in coronary ASMCs. Segments of the right coronary artery obtained from sexually mature female pigs were mounted for isometric tension recording. As expected, our results indicate that high concentrations (≥10 µmol/L) of 17ßE acutely attenuated Ca2+ -dependent contractions to depolarizing KCl stimuli. Interestingly, culturing coronary arteries for 24 h in a 10,000-fold lower concentration (1 nmol/L) of 17ßE also attenuated KCl-induced contractions and reduced the contractile response to the Cav 1.2 agonist, FPL64176, by 50%. Western blots revealed that 1 nmol/L 17ßE decreased protein expression of the pore-forming α1C subunit (Cav α) of the Cav 1.2 channel by 35%; this response did not depend on an intact endothelium. The 17ßE-induced loss of Cav α protein in coronary arteries was prevented by the estrogen ERα/ERß antagonist, ICI 182,780, whereas the GPER antagonist, G15, did not prevent it. There was no effect of 1 nmol/L 17ßE on Cav α transcript expression. We conclude that 17ßE reduces Cav 1.2 channel abundance in isolated coronary arteries by a posttranscriptional process. This unrecognized effect of estrogen may confer physiological protection against the development of abnormal Ca2+ -dependent coronary vascular tone.

Using three-point bending to evaluate tibia bone strength in ovariectomized young mice.

It is well known that estrogen deficiency induces a deterioration of bone strength in aged females. The aim of this study is to determine the effect of estrogen depletion on tibia bone strength in sexually mature mice that are still undergoing skeletal maturation. At 8 weeks of age, C57BL/6 female mice underwent an ovariectomy (OVX) or sham (SHAM) surgery. Mice were killed at 2, 4, or 8 weeks post-surgery. Tibia length and cross-sectional area continued to increase in both treatment groups until 4 weeks post-surgery. Compared to SHAM mice, OVX mice demonstrated a significant reduction in uterine weight and plasma estrogen levels. Three-point bending was used to quantify the mechanical properties (breaking point, stress, stiffness, and elasticity) of the tibia. The tibias from the SHAM mice had a higher breaking point than all the age-matched OVX mice. At 8 weeks post-surgery, the tibias from the SHAM mice demonstrated higher elasticity, stress, and stiffness than the younger SHAM mice and the age-matched OVX mice. Compared to the SHAM mice, our study suggests that (1) there is a reduction in the mechanical strength of tibias from young OVX mice, and (2) the greatest decline in tibia strength of the OVX mice was once they reached skeletal maturity.

An Evolving Ecosystem for Natural Language Processing in Department of Veterans Affairs.

In an ideal clinical Natural Language Processing (NLP) ecosystem, researchers and developers would be able to collaborate with others, undertake validation of NLP systems, components, and related resources, and disseminate them. We captured requirements and formative evaluation data from the Veterans Affairs (VA) Clinical NLP Ecosystem stakeholders using semi-structured interviews and meeting discussions. We developed a coding rubric to code interviews. We assessed inter-coder reliability using percent agreement and the kappa statistic. We undertook 15 interviews and held two workshop discussions. The main areas of requirements related to; design and functionality, resources, and information. Stakeholders also confirmed the vision of the second generation of the Ecosystem and recommendations included; adding mechanisms to better understand terms, measuring collaboration to demonstrate value, and datasets/tools to navigate spelling errors with consumer language, among others. Stakeholders also recommended capability to: communicate with developers working on the next version of the VA electronic health record (VistA Evolution), provide a mechanism to automatically monitor download of tools and to automatically provide a summary of the downloads to Ecosystem contributors and funders. After three rounds of coding and discussion, we determined the percent agreement of two coders to be 97.2% and the kappa to be 0.7851. The vision of the VA Clinical NLP Ecosystem met stakeholder needs. Interviews and discussion provided key requirements that inform the design of the VA Clinical NLP Ecosystem.

The effect of simulated narratives that leverage EMR data on shared decision-making: a pilot study.

BACKGROUND: Shared decision-making can improve patient satisfaction and outcomes. To participate in shared decision-making, patients need information about the potential risks and benefits of treatment options. Our team has developed a novel prototype tool for shared decision-making called hearts like mine (HLM) that leverages EHR data to provide personalized information to patients regarding potential outcomes of different treatments. These potential outcomes are presented through an Icon array and/or simulated narratives for each "person" in the display. In this pilot project we sought to determine whether the inclusion of simulated narratives in the display affects individuals' decision-making. Thirty subjects participated in this block-randomized study in which they used a version of HLM with simulated narratives and a version without (or in the opposite order) to make a hypothetical therapeutic decision. After each decision, participants completed a questionnaire that measured decisional confidence. We used Chi square tests to compare decisions across conditions and Mann-Whitney U tests to examine the effects of narratives on decisional confidence. Finally, we calculated the mean of subjects' post-experiment rating of whether narratives were helpful in their decision-making. RESULTS: In this study, there was no effect of simulated narratives on treatment decisions (decision 1: Chi squared = 0, p = 1.0; decision 2: Chi squared = 0.574, p = 0.44) or Decisional confidence (decision 1, w = 105.5, p = 0.78; decision 2, w = 86.5, p = 0.28). Post-experiment, participants reported that narratives helped them to make decisions (mean = 3.3/4). CONCLUSIONS: We found that simulated narratives had no measurable effect on decisional confidence or decisions and most participants felt that the narratives were helpful to them in making therapeutic decisions. The use of simulated stories holds promise for promoting shared decision-making while minimizing their potential biasing effect.

Automated pictographic illustration of discharge instructions with Glyph: impact on patient recall and satisfaction.

OBJECTIVES: First, to evaluate the effect of standard vs pictograph-enhanced discharge instructions on patients' immediate and delayed recall of and satisfaction with their discharge instructions. Second, to evaluate the effect of automated pictograph enhancement on patient satisfaction with their discharge instructions. MATERIALS AND METHODS: Glyph, an automated healthcare informatics system, was used to automatically enhance patient discharge instructions with pictographs. Glyph was developed at the University of Utah by our research team. Patients in a cardiovascular medical unit were randomized to receive pictograph-enhanced or standard discharge instructions. Measures of immediate and delayed recall and satisfaction with discharge instructions were compared between two randomized groups: pictograph (n = 71) and standard (n = 73). RESULTS: Study participants who received pictograph-enhanced discharge instructions recalled 35% more of their instructions at discharge than those who received standard discharge instructions. The ratio of instructions at discharge was: standard = 0.04 ± 0.03 and pictograph-enhanced = 0.06 ± 0.03. The ratio of instructions at 1 week post discharge was: standard = 0.04 ± 0.02 and pictograph-enhanced 0.04 ± 0.02. Additionally, study participants who received pictograph-enhanced discharge instructions were more satisfied with the understandability of their instructions at 1 week post-discharge than those who received standard discharge instructions. DISCUSSION: Pictograph-enhanced discharge instructions have the potential to increase patient understanding of and satisfaction with discharge instructions. CONCLUSION: It is feasible to automatically illustrate discharge instructions and provide them to patients in a timely manner without interfering with clinical work. Illustrations in discharge instructions were found to improve patients' short-term recall of discharge instructions and delayed satisfaction (1-week post hospitalization) with the instructions. Therefore, it is likely that patients' understanding of and interaction with their discharge instructions is improved by the addition of illustrations.

Automated alerts and reminders targeting patients: A review of the literature.

OBJECTIVE: Information technology supporting patient self-management has the potential to foster shared accountability for healthcare outcomes by improving patient adherence. There is growing interest in providing alerts and reminders to patients to improve healthcare self-management. This paper describes a literature review of automated alerts and reminders directed to patients, the technology used, and their efficacy. METHODS: An electronic literature search was conducted in PubMed to identify relevant studies. The search produced 2418 abstracts; 175 articles underwent full-text review, of which 124 were rejected. 51 publications were included in the final analysis and coding. RESULTS: The articles are partitioned into alerts and reminders. A summary of the analysis for the 51 included articles is provided. CONCLUSION: Reminders and alerts are advantageous in many ways; they can be used to reach patients outside of regular clinic settings, be personalized, and there is a minimal age barrier in the efficacy of automated reminders sent to patients. As technologies and patients' proficiencies evolve, the use and dissemination of patient reminders and alerts will also change. PRACTICE IMPLICATIONS: Automated technology may reliably assist patients to adhere to their health regimen, increase attendance rates, supplement discharge instructions, decrease readmission rates, and potentially reduce clinic costs.

Evaluation of a pictograph enhancement system for patient instruction: a recall study.

OBJECTIVE: We developed a novel computer application called Glyph that automatically converts text to sets of illustrations using natural language processing and computer graphics techniques to provide high quality pictographs for health communication. In this study, we evaluated the ability of the Glyph system to illustrate a set of actual patient instructions, and tested patient recall of the original and Glyph illustrated instructions. METHODS: We used Glyph to illustrate 49 patient instructions representing 10 different discharge templates from the University of Utah Cardiology Service. 84 participants were recruited through convenience sampling. To test the recall of illustrated versus non-illustrated instructions, participants were asked to review and then recall a set questionnaires that contained five pictograph-enhanced and five non-pictograph-enhanced items. RESULTS: The mean score without pictographs was 0.47 (SD 0.23), or 47% recall. With pictographs, this mean score increased to 0.52 (SD 0.22), or 52% recall. In a multivariable mixed effects linear regression model, this 0.05 mean increase was statistically significant (95% CI 0.03 to 0.06, p<0.001). DISCUSSION: In our study, the presence of Glyph pictographs improved discharge instruction recall (p<0.001). Education, age, and English as first language were associated with better instruction recall and transcription. CONCLUSIONS: Automated illustration is a novel approach to improve the comprehension and recall of discharge instructions. Our results showed a statistically significant in recall with automated illustrations. Subjects with no-colleague education and younger subjects appeared to benefit more from the illustrations than others.

Oestrogen upregulates the sarcoplasmic reticulum Ca(2+) ATPase pump in coronary arteries.

The presence of circulating plasma 17ß-oestradiol (E2) is beneficial in women against abnormal vascular tone development, such as coronary arterial vasospasms. Several vascular diseases have demonstrated that increased expression of the sarcoplasmic reticulum Ca(2+) -ATPase pump (SERCA2b) serves to limit the excessive accumulation of intracellular Ca(2+) . Therefore, the hypothesis of the present study was that E2 would increase SERCA2b expression in the coronary vasculature. Coronary arteries were dissected from hearts obtained from mature female pigs. Artery segments were cultured for 24 h in E2 (1 pmol/L or 1 nmol/L) and homogenized for western blot analysis. At 1 nmol/L, E2 induced an approximate 50% increase in immunoreactivity for SERCA2b. In addition, E2 increased the protein expression of the known SERCA regulatory proteins, protein kinase A (PKA) and protein kinase G (PKG). The E2-induced increase in SERCA2b was attenuated when the culture medium was supplemented with the oestrogen receptor (ER) α/ß antagonist ICI 182,780 and the PKG antagonist KT5823 (10 µmol/L, 24 h for both). The PKA antagonist (KT5720; 10 µmol/L, 24 h) had no effect on SERCA2b expression. Removal of the endothelium (using a wooden toothpick) from artery segments prior to culture decreased the E2-mediated increase in SERCA2b and PKG expression by 45% and 47%, respectively. Overall, the findings suggest that one of the potential cardiovascular benefits of E2 in women is upregulation of SERCA2b, via activation of the classic ERα and ERß pathway.

Exploring the use of large clinical data to inform patients for shared decision making.

Barriers to patient participation in the shared decision making process prevent patients from fully participating in evaluating treatment options and treatment selection. Patients who use a decision aid are more informed and engaged in the shared decision making process. Patient decision aids do not use real clinical data for patient information and may not represent the data well. We designed an interface, for a shared decision making aid, that leverages clinical data to inform risk ratios and create patient stories, or vignettes, and present a visual representation of quantified treatment outcomes data. Usability testing was conducted with experts to evaluate the interface and the utility of using real clinical information that patients can explore. The experts' comments were transcribed and coded for themes. Themes were quantified and comments were interpreted for refinement and modification to the patient decision aid interface and data visualization.

Use of topic modeling for recommending relevant education material to diabetic patients.

The need for and challenges of educating and informing patients are well known and these are even greater for patients with low levels of literacy. Furthermore, as the population ages and with the increase in prevalence of chronic diseases where patient self-management is essential to holding disease in abeyance, patient education becomes increasingly important. With the advent of electronic medical records, there is an opportunity for automated tools to assist in addressing these challenges. In this paper we report on one approach to recommending relevant educational articles to patients. We attempt to infer the patient's information needs from his/her electronic medical records and use topic modeling to identify and match topics. A manual evaluation of the articles recommended by the proposed method showed that these articles are significantly more relevant (p < 0.01) to the patient's disease state than articles selected at random from within the same disease domain.

The Men's Program: does it impact college men's self-reported bystander efficacy and willingness to intervene?

This study considered whether a rape prevention program could reduce men's rape myth acceptance, enhance the perceived effectiveness of college men's bystander behavior, and increase men's willingness to intervene as bystanders in potentially dangerous situations. As predicted, college men who experienced The Men's Program significantly increased their self-reported willingness to help as a bystander and their perceived bystander efficacy in comparison to college men who experienced the comparison condition. Men's Program participants also significantly decreased their self-reported rape myth acceptance in comparison with comparison condition participants. The college policy and rape prevention program planning implications of these findings are discussed.

Nongenomic inhibition of coronary constriction by 17ß-estradiol, 2-hydroxyestradiol, and 2-methoxyestradiol.

The cardioprotective effects of 17beta-estradiol (E2) in women are hypothesized to be partially mediated by the E2 metabolites 2-hydroxyestradiol (2-HOE) and 2-methoxyestradiol (2-MeOH). Therefore, the purpose of our study was to determine the acute effects of E2, 2-HOE, and 2-MeOH on inhibition of coronary arterial constriction. Right coronary arteries obtained from breeding sows were cut into 4 mm rings and suspended in organ baths. Incubation of the rings with E2, 2-HOE, and 2-MeOH (10 micromol/L) for 60 min attenuated a subsequent KCl-induced contraction by approximately 50%. The protein synthesis inhibitor cycloheximide and the estrogen receptor antagonists ICI 182780 and tamoxifen did not affect the attenuation. Moreover, E2, 2-HOE, and 2-MeOH antagonized the contraction induced by the vasospasm agonist endothelin-1 (0.1 micromol/L) by approximately 36%. When the L-type Ca2+ channel blocker nifedipine was added at the conclusion of the experiment, no additional contractile attenuation was present. Our results suggest that E2, 2-HOE, and 2-MeOH demonstrate a similar nongenomic inhibition of agonist-induced extracellular Ca2+-dependent contractions.

Relation of daytime bradyarrhythmias with high risk features of sleep apnea.

Bradyarrhythmias (BA) have been reported in patients with sleep apnea (SA), but the incidence of SA in patients with BA remains unclear. A case-control study was conducted to assess the prevalence of high-risk features of SA in patients with documented BA on 24-hour Holter monitoring compared with patients without BA. Controls were age-matched patients selected from those with no evidence of BA on 24-hour Holter monitoring. BA were defined as the presence of pauses of >3 seconds, regardless of the mechanism, and/or heart rate <40 beats/min during presumed waking hours (8 a.m. to 8 p.m.). High-risk features of SA were determined by the Berlin Questionnaire, with positive results defined as having '2 of 3 positive high-risk categories. Body mass index (BMI), hypertension, beta-blocker use, and other underlying characteristics were cataloged. Nineteen patients with documented BA and 47 with no BA were identified. The mean ages and BMIs in the active and control groups were not statistically significant. High-risk features for SA were present in 57.8% of patients in the BA group compared with 21.3% in the control group (p = 0.003). After controlling for age, BMI, hypertension, and beta-blocker use, patients with BA were 6 times more likely to have high-risk features of SA compared with those without BA (logistic regression odds ratio 6.1, 95% confidence interval 1.5 to 24, p = 0.012). In conclusion, irrespective of BMI, age, and other underlying risk factors, the presence of daytime BA was highly associated with high-risk features of SA.

The enhanced endothelin-1-induced contraction in cultured coronary arteries from mature female pigs is not antagonized by 17beta-estradiol.

We have previously reported that organ cultured coronary arteries from market-age pigs (6-9 months of age) exhibit an enhanced contraction to the atherosclerotic-associated peptide, endothelin-1 (ET-1). The objective of this study was to investigate the interaction of 17beta-estradiol with ET-1 in organ cultured coronary arteries from older female pigs (3-4 years old). A cumulative concentration-response relationship (1 x 10(-9) M to 3 x 10(-7) M) was generated to ET-1, and the isometric tension measured in fresh and organ cultured (4 days at 37 degrees C) arterial rings that were each pre-incubated for 50 min in different concentrations (1 x 10(-9) M to 1 x 10(-5) M) of 17beta-estradiol. Compared to freshly used arteries, culturing induced a 2-fold increase in tension development to ET-1 (3 x 10(-7) M). Although 17beta-estradiol previously relaxed pre-constricted (with a 60 mM KCl solution) arteries, it did not affect the constrictive response to ET-1. Also, using an ET-1 ELISA we found that 17beta-estradiol did not effect ET-1 production in intact arteries. Our results indicate that 17beta-estradiol does not attenuate the production and constrictive properties of ET-1 in coronary arteries demonstrating a dedifferentiated cell phenotype.

A simple classroom teaching technique to help students understand Michaelis-Menten kinetics.

A new, simple classroom technique helps cell biology students understand principles of Michaelis-Menten enzyme kinetics. A student mimics the enzyme and the student's hand represents the enzyme's active site. The catalytic event is the transfer of marbles (substrate molecules) by hand from one plastic container to another. As predicted, increases in marble concentration increase the number of marbles transferred per unit time (initial rate, V(0)) until the turnover number becomes rate limiting and V(0) approaches the maximum velocity (V(max)), as described by the Michaelis-Menten equation. With this demonstration, students visualize an important concept: the turnover number is constant and independent of marble concentration. A student assessment of this exercise showed that it helped students visualize the turnover number and V(max) but not K(m), the marble concentration at which V(0) is one-half V(max). To address the concept of K(m), we use supplemental laboratory and lecture exercises. This exercise with plastic containers and marbles is equally suited to demonstrate the kinetics of carrier-mediated membrane transport. We conclude that this exercise helps students visualize the turnover number and V(max) and gives students important insights into the kinetic parameters used to characterize the catalytic activity of enzymes and membrane transporters.

Increased calcium buffering in coronary smooth muscle cells from diabetic dyslipidemic pigs.

No studies exist concerning the ability of the plasma membrane Ca(2+) pump (PMCA), sarcoplasmic reticulum Ca(2+) pump (SERCA) and Na(+)-Ca(2+) exchanger (NCX) to regulate myoplasmic Ca(2+) (Ca(m)) in vascular smooth muscle cells from diabetic individuals with dyslipidemia. We tested the hypothesis that diabetic dyslipidemia would increase vascular smooth muscle cells to buffer Ca(m). Cells were isolated from the coronary artery of male Yucatan pigs treated for 20 weeks with: (1) a low fat diet (control group); (2) a high fat/cholesterol diet (F group); or (3) alloxan-induced diabetic pigs fed the high fat diet (DF group). The maximum Ca(m) response to a depolarizing 80 mM KCl (80 K) solution was evaluated in the absence and presence of thapsigargin (TSG; inhibits SERCA) and low Na (inhibits NCX). In response to 80 K alone, there was no difference in the Ca(m) response between groups. In the presence of TSG, the 80 K response decreased by 43% in the DF group; TSG did not affect the 80 K response in the control and F groups. When exposed to both TSG and low Na, the 80 K response also decreased by 55% in the DF group. This suggests increased Ca(m) buffering by the PMCA and/or mitochondria in the DF group when SERCA and NCX are inhibited. Compared to the control and F groups, low Na alone elicited a 50% lower Ca(m) amplitude in the DF group, which was reversed with TSG treatment; this suggests that SERCA activity is increased in DF pigs. Western blots also indicated a 7-fold increase in the approximately 115 kDa band density of an anti-SERCA2 antibody in DF compared to control pigs. This is the first report to demonstrate increased Ca(2+) buffering, specifically by SERCA, in vascular smooth muscle cells from diabetic individuals with dyslipidemia.

Pharmacological characterization of a UTP-sensitive P2Y nucleotide receptor in organ cultured coronary arteries.

Our lab has previously demonstrated that organ cultured coronary smooth muscle cells express a nucleotide receptor that is dramatically more responsive to UTP than non-organ cultured cells. Thus, the purpose of this study was to pharmacologically characterize this UTP-sensitive nucleotide receptor. Porcine coronary arteries were organ cultured (serum-free media, 37 degrees C) for 4 days, and fura-2 imaging of single cells was used to measure myoplasmic Ca2+ (Cam) in response to several nucleotide agonists. A concentration-response relationship (0.01-100 microM) was generated to the nucleotide receptor agonists, UTP, UDP, ATP, ADP, and 2-MeSATP. The potency order was UTP >> UDP = ATP = ADP = 2-MeSATP, thus, this nucleotide receptor is predominantly UTP-sensitive. The Cam response to 10 microM UTP was attenuated approximately 50% by the nucleotide receptor antagonists (10 and 100 microM), suramin, reactive blue 2, and pyridoxalphosphate-6-azophenyl-2',4'-disulphonoic acid (PPADS). Depletion of the sarcoplasmic reticulum Ca2+ store with thapsigargin completely abolished the UTP-induced Cam response. In addition, the peak UTP-induced Cam increase was almost two-fold higher in a 2-mM Ca2+ solution than a 0-mM Ca2+ solution. This suggests that the UTP-induced Cam response is comprised of both Ca2+ influx and the mobilization of intracellular Ca2+ stores. Pertussis toxin reduced the UTP-induced Cam response 50%, thus, the UTP-induced increase in Cam is mediated, in part, via Gi/o. These data suggest this UTP-sensitive receptor belongs to the P2Y nucleotide receptor family; however, it does not possess pharmacological characteristics associated with any known P2Y receptor subtype.