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Item Coronary CTA plaque volume severity stages according to invasive coronary angiography and FFR(Elsevier, 2022) Min, James K.; Chang, Hyuk-Jae; Andreini, Daniele; Pontone, Gianluca; Guglielmo, Marco; Bax, Jeroen J.; Knaapen, Paul; Raman, Subha V.; Chazal, Richard A.; Freeman, Andrew M.; Crabtree, Tami; Earls, James P.; Medicine, School of MedicineBackground: Atherosclerotic plaque characterization by coronary computed tomography angiography (CCTA) enables quantification of coronary artery disease (CAD) burden and type, which has been demonstrated as the strongest discriminant of future risk of major adverse cardiac events (MACE). To date, there are no clinically useful thresholds to assist with understanding a patient's disease burden and guide diagnosis and management, as there exists with coronary artery calcium (CAC) scoring. The purpose of this manuscript is to establish clinically relevant plaque stages and thresholds based on evidence from invasive angiographic stenosis (ICA) and fractional flow reserve (FFR) data. Methods: 303 patients underwent CCTA prior to ICA and FFR for an AHA/ACC clinical indication. Quantitative computed tomography (QCT) was performed for total plaque volume (TPV, mm3) and percent atheroma volume (PAV, %). We segmented atherosclerosis by composition for low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), and calcified plaque (CP). ICAs were evaluated by quantitative coronary angiography (QCA) for all coronary segments for % diameter stenosis. The relationship of atherosclerotic plaque burden and composition by QCT to ICA stenosis extent and severity by QCA and presence of ischemia by FFR was assessed to develop 4 distinct disease stages. Results: The mean age of the patients was 64.4 ± 10.2 years; 71% male. At the 50% QCA stenosis threshold, QCT revealed a mean PAV of 9.7 (±8.2)% and TPV of 436 (±444.9)mm3 for those with non-obstructive CAD; PAV of 11.7 (±8.0)% and TPV of 549.3 (±408.3) mm3 for 1 vessel disease (1VD), PAV of 17.8 (±9.8)% and TPV of 838.9 (±550.7) mm3 for 2VD, and PAV of 19.2 (±8.2)% and TPV of 799.9 (±357.4) mm3 for 3VD/left main disease (LMD). Non-ischemic patients (FFR >0.8) had a mean PAV of 9.2 (±7.3) % and TPV of 422.9 (±387.9 mm3) while patients with at least one vessel ischemia (FFR ≤0.8) had a PAV of 15.2 (±9.5)% and TPV of 694.6 (±485.1). Definition of plaque stage thresholds of 0, 250, 750 mm3 and 0, 5, and 15% PAV resulted in 4 clinically distinct stages in which patients with no, nonobstructive, single VD and multi-vessel disease were optimally distributed. Conclusion: Atherosclerotic plaque burden by QCT is related to stenosis severity and extent as well as ischemia. We propose staging of CAD atherosclerotic plaque burden using the following definitions: Stage 0 (Normal, 0% PAV, 0 mm3 TPV), Stage 1 (Mild, >0-5% PAV or >0-250 mm3 TPV), Stage 2 (Moderate, >5-15% PAV or >250-750 mm3 TPV) and Stage 3 (Severe, >15% PAV or >750 mm3 TPV).Item Impact of Opioid and Nonopioid Drugs on Postsurgical Pain Management in the Rat(Hindawi Publishing Corporation, 2016) Wilson, Natalie M.; Ripsch, Matthew S.; White, Fletcher A.; Department of Anesthesia, IU School of MedicineAim. Nonsteroidal anti-inflammatory drugs or opioids are commonly used to control surgical pain following veterinary and clinical procedures. This study evaluated the efficacy of postoperative ketorolac or buprenorphine following abdominal surgery. Main Methods. Mean arterial pressure (MAP), heart rate, animal activity, corticosterone levels, and a nociceptive sensitivity assay were used to evaluate 18 adult male Sprague-Dawley rats which underwent aortic artery occlusion for implantation of a radiotelemetry device. The animals were treated postoperatively with intraperitoneal injections of vehicle, ketorolac (10 mg/kg), or buprenorphine (0.06 mg/kg) every 8 hours for 3 days. Key Findings. There were no consistent significant changes in any of the telemetry parameters after treatment with ketorolac compared with no saline treatment with the exception of increased MAP in the buprenorphine group during the first 48 hours when compared with other treatment groups. There was a sustained increase in fecal corticosterone levels from baseline on days 2-7 with buprenorphine compared with vehicle- or ketorolac-treated animals. All treatment conditions displayed reduced paw withdrawal thresholds (PWTs) from day 1 to day 21 following surgery. Compared with the vehicle treatment group, buprenorphine-treated animals exhibited significantly lower PWT levels from day 4 to 14 days. Significance. Given the prolonged increase in fecal corticosterone levels and pronounced changes in tactile hyperalgesia behavior in rodents subjected to buprenorphine treatment, these data suggest that ketorolac may be superior to buprenorphine for the treatment of postprocedure pain behavior in rodents.Item KMT2D-NOTCH Mediates Coronary Abnormalities in Hypoplastic Left Heart Syndrome(American Heart Association, 2022) Yu, Zhiyun; Zhou, Xin; Liu, Ziyi; Pastrana-Gomez, Victor; Liu, Yu; Guo, Minzhe; Tian, Lei; Nelson, Timothy J.; Wang, Nian; Mital, Seema; Chitayat, David; Wu, Joseph C.; Rabinovitch, Marlene; Wu, Sean M.; Snyder, Michael P.; Miao, Yifei; Gu, Mingxia; Radiology and Imaging Sciences, School of MedicineItem Optimism and cardiovascular health: Longitudinal findings from the CARDIA Study(Wolters Kluwer, 2020) Boehm, Julia K.; Qureshi, Farah; Chen, Ying; Soo, Jackie; Umukoro, Peter; Hernandez, Rosalba; Lloyd-Jones, Donald; Kubzansky, Laura D.; Medicine, School of MedicineObjective: Favorable cardiovascular health is associated with greater longevity free of cardiovascular disease. Although the prevalence of cardiovascular health decreases with age, less is known about protective factors that promote and preserve it over time. We investigated whether optimism was associated with better cardiovascular health over a 10-year period. Methods: Participants included 3188 Black and White men and women from the Coronary Artery Risk Development in Young Adults study. Self-reported optimism was assessed in 2000 (this study's baseline) with the revised Life Orientation Test. Favorable cardiovascular health was defined by healthy status on five components of cardiovascular functioning that were repeatedly assessed through 2010 either clinically or via self-report (blood pressure, lipids, body mass index, diabetes, and smoking status). Linear mixed-effects models examined whether optimism predicted cardiovascular health over time, adjusting for covariates such as sociodemographic characteristics, health behaviors, health status, and depression diagnosis. Results: In models adjusting for sociodemographic characteristics, optimism was associated with better cardiovascular health across all time points (β = 0.08, 95% confidence interval = 0.04-0.11, p ≤ .001) but not with rate of change in cardiovascular health. Findings were similar when adjusting for additional covariates. Optimism did not interact significantly with race (p = .85) but did with sex, such that associations seemed stronger for women than for men (p = .03). Conclusions: Optimism may contribute to establishing future patterns of cardiovascular health in adulthood, but other factors may be more strongly related to how slowly or quickly cardiovascular health deteriorates over time.Item Regulation of Coronary Blood Flow(Wiley, 2017-03-16) Goodwill, Adam G.; Dick, Gregory M.; Kiel, Alexander M.; Tune, Johnathan D.; Cellular and Integrative Physiology, School of MedicineThe heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. © 2017 American Physiological Society. Compr Physiol 7:321-382, 2017.