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    Smooth Muscle Contraction Is Regulated by Chloride Channels: Functional Evidence for TMEM16A in Porcine Coronary Arteries
    (2021) Dick, Gregory; Tune, Johnathan
    Purpose: Contraction of coronary smooth muscle is influenced by ion channels controlling membrane potential (Em) and Ca2+ influx. A great deal of attention has been focused on K+ channels, as their opening makes Em more negative, reduces Ca2+, and causes relaxation. We investigated ion channels whose opening would depolarize Em, increase Ca2+, and promote contraction. A candidate for study is TMEM16A, a Ca2+-activated Cl- channel expressed in a variety of smooth muscles. We tested the hypothesis that drugs which influence TMEM16A would alter contraction. We predicted that contraction would be enhanced by a TMEM16A activator (Eact), whereas it would be attenuated by a TMEM16A inhibitor (T16Ainh-A01). Methods: We used isometric tension recording methods on epicardial coronary artery segments from domestic swine. Contractions to K+ were recorded before and after treatment with 5 µM Eact or 5 µM T16Ainh-01. Extracellular K+ was varied by adding K-gluconate, rather than KCl, to keep Cl- constant. Results: K+ contracted rings with an EC50 of 19.1 ± 0.6 mM and a maximum of 11.8 ± 1.4 g. Drug vehicle had no effect on EC50 or maximum. Eact shifted contraction to the left (17.8 ± 0.9 mM; P < 0.05) but did not affect the maximum (105 ± 3% of control). T16Ainh-A01 shifted contraction to the right (20.4 ± 0.6 mM; P < 0.05) but did not affect the maximum (90 ± 1% of control). Conclusions: These data suggest that TMEM16A is expressed in porcine coronary arteries and influences electromechanical coupling.
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    Tai Chi and Cardiovascular Conditions
    (2021) Kolenovic, Mersida; Liu, Howe; Salem, Yasser; Janssen, Allison; Logsdon, Liana
    Introduction: Tai Chi is a meditative and low intensity exercise that includes deep diaphragmatic breathing which promotes positive physiologic changes in the cardiovascular system. The purpose of this systematic review is to analyze evidence related to the benefits of Tai Chi pertaining to cardiovascular conditions and recognize the similarities of this intervention in research. Methods: This study includes twelve randomized control trial articles that encompass a variety of cardiovascular conditions. The electronic database utilized includes PubMed. Keywords used include Tai Chi intervention, hypertension, chronic heart failure, coronary artery disease, coronary heart disease, atherosclerosis, and myocardial infarction. Results: These articles discuss hypertension, myocardial infarction, atherosclerosis, coronary heart disease, coronary artery disease, heart failure, and cerebrovascular accidents related to a Tai Chi intervention. Significant improvements were observed in the following outcomes measured: TUG, VO2peak, 6MWT, endurance tests, blood pressure, arterial stiffness, blood lipid levels, BMI, blood sugar, cognition, Cardiac Health Behavior scale, quality of life scales, and psychosocial self-reports. The most common intervention protocol used in these articles was a 1-hour session of 24-form Yang style Tai Chi for three times a week over a 12-week period. On the other hand, two articles used a similar protocol but implemented these exercises twice a week over a 12 week period and were still able to see significant improvements in cardiovascular function. Conclusion: Overall, this systematic review reveals the significance of Tai Chi as an exercise that will improve cardiovascular function in a population with cardiovascular disease.
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    An Atypical Presentation of Takotsubo Cardiomyopathy
    (2021) Reynolds, Holli; Avila, Juan; Smith, Michael
    Background: Takotsubo cardiomyopathy is a reversible heart failure syndrome characterized by regional systolic dysfunction of the left ventricle. The syndrome mimics the presentation of myocardial infarction, yet it lacks evidence of obstructive coronary artery disease or plaque rupture. Case presentation: A 73-year-old Caucasian female presented to the Emergency Department with complaints of back pain following a non-syncopal fall after standing up too quickly and becoming dizzy the day previously. In addition, the patient complained of difficulty urinating and stooling for the past week. Her past medical history consisted of hypertension, hyperlipidemia, osteoporosis, and major depressive disorder. The patient was admitted, and a full workup was started. She was noted to have leukocytosis with blood cultures negative x2. Troponin I was also elevated at 5.42 and an ECG was performed which showed significant T wave inversions in V4 and V5 with a left axis deviation. CT Head, Cervical Spine, and Thoracic Spine without contrast showed no significant findings. An MRI of the lumbar spine was ordered to look for possible causes for her bladder and bowel retention but did not show spinal compression. In order to further evaluate the heart, an echocardiogram was performed and found global apical, septal, anterior akinesis with an estimated ejection fraction of 25-30%. Cardiology also performed a left heart catheterization (LHC), which found non-obstructive coronary artery disease. Conclusion: This case illustrates an atypical presentation of Takotsubo Cardiomyopathy due to the unique presentation and the unrelated symptoms that confused the clinical picture.
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    A Systematic Review on the Effects and Implications of Kratom Use on Cardiotoxicity
    (2021) Saxena, Raina; Sankar, Aparna; Demoss, Dustin; Briggs, Jeff
    Purpose: Mitragyna speciosa, referred to as kratom, is a plant native to Asia known for its opiate- and psychostimulant-like effects. Kratom use in the US has increased in the last fifteen years. Mitragynine, a kratom-derived alkaloid, has been shown to interfere with cardiac ion channels, leading to QTc prolongation and Torsades de Pointes. These findings are clinically relevant in the psychiatric population, where medications affecting QTc interval are commonly prescribed. This systematic review aims to bring awareness to the cardiac effects of kratom use and highlight the clinical significance for patients who are prescribed psychiatric medications. Methods: This systematic review was conducted using PubMed as the primary database. The query was specified as "All fields" with search terms: Kratom OR mitragynine OR mitragyna speciosa AND cardiac. This search yielded thirteen articles. Inclusion criteria included ability to access articles through the UNTHSC portal. Exclusion criteria included absence of search terms in the article title, abstract, and keywords. The final synthesis included five articles. Results: Two of the articles discussed the side effects of kratom, highlighting QTc prolongation. Three articles discussed the mechanism and interaction of kratom with other psychiatric medications. Conclusion: As kratom usage increases in the US, it is important to understand the mechanisms of kratom-induced cardiotoxicity. This is particularly relevant to the psychiatric population, where the use of medications known to affect QTc interval is prevalent. This systematic review highlights the need for increased awareness and research on the interactions between mitragynine and other psychiatric medications.
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    Point of Care Ultrasound Abdominal Aortic Aneurysm Screening: A Quality Improvement Project
    (2021) Philip, Timothy; Hughes, Jonathan; Adams, Ana; Pierce, Victoria; Carson, Madeline; McClellan, Elijah; Johnson, Jordyn; Walsh, Emerald; Miller, Dallas; Archer, Jennifer; Gibson, John
    The USPSTF recommends 1-time screening for abdominal aortic aneurysm (AAA) with ultrasonography (US) in men above 65 who have ever smoked. AAA screening has reduced rupture rates; however, the rates of screening are lower in rural areas. The Rural Osteopathic Medical Education program at Texas College of Osteopathic Medicine (TCOM) initiated a quality improvement project to increase rates of AAA screenings by means of medical students equipped with hand-held US devices. Methods: Consenting men above 65 who have ever smoked received an outpatient, point of care ultrasound (POCUS) AAA screening via Butterfly iQ. Screenings of the proximal, middle, and distal portions of the abdominal aorta in both longitudinal and transverse views were conducted. Patients were then referred to radiological services to receive a one-time ultrasound screening for AAA. The outcomes compared the variability between the students' and radiologists' measurements and radiology referral compliance. Results: 35 patients were screened in the clinic using the handheld ultrasound device. 3 patients screened positive for AAA at the radiology department, while 2 screened positive in the clinic. The average difference between the measurements by the students and the radiologists was -0.30 cm (95% CI, -0.45 to -0.15; P=0.0002). Results suggested that there was not a clinically significant difference between measurements obtained by the medical students and the radiology department. The patient follow-up compliance rate was only 51%. Based on these data, medical student performed POCUS AAA screening may provide better compliance with similar accuracy compared to traditional AAA screening.
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    White Mountain Expedition 2019: The Impact of Sustained Hypoxia on Cerebral Blood Flow Responses and Tolerance to Simulated Hemorrhage
    (2021) Rosenberg, Alexander; Anderson, Garen K.; Barnes, Haley J.; Bird, Jordan D.; Pentz, Brandon; Byman, Britta; Jendzjowsky, Nicholas; Wilson, Richard; Day, Trevor; Rickards, Caroline
    Trauma-induced hemorrhage can occur at high altitude (HA) from a variety of causes, including battlefield injuries, vehicle/air accidents, and major falls. As the partial pressure of oxygen decreases with ascent to altitude, compensatory increases in cerebral blood flow (CBF) and oxygen delivery occur to preserve cerebral tissue oxygenation (ScO2). Accordingly, we hypothesized that tolerance to simulated hemorrhage (via lower body negative pressure, LBNP) following sustained exposure to HA would be similar compared to low altitude (LA) due to compensatory increases in CBF and oxygen delivery, and the subsequent preservation of ScO2. Healthy adults (N=8;4F/4M) participated in LBNP protocols to presyncope at LA (1045m) and at HA (3800m) following 5-7 days of acclimatization. Arterial pressure, heart rate (HR), stroke volume (SV), internal carotid artery blood flow (ICA BF), and ScO2 were measured continuously. Time to presyncope was similar between conditions (LA:1276±304s vs. HA:1208±306s;P=0.58). Similar maximal responses to LBNP were observed at LA and HA in mean arterial pressure (LA:-16±6% vs. HA:-16±6%;P=0.85), SV (LA:-57±14% vs. HA:-60±13%;P=0.39), and HR (LA:+69±33% vs. HA:+65±23%;P=0.71). ICA BF was elevated at baseline at HA vs. LA (P=0.04) and decreased with LBNP under both conditions (P< 0.0001). There was no effect of altitude (P=0.59) on ScO2, which decreased with LBNP under both conditions (P=0.09). Sustained exposure to hypoxia at an altitude of 3800m does not affect tolerance to simulated hemorrhage in adults, which may be due to 1) similar cardiovascular reflex responses, and 2) compensatory increases in CBF and subsequent preservation of ScO2.
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    Preoperative factors for early mortality in patients with HLHS undergoing the Norwood procedure
    (2021) Karnkowska, Barbara; Kuo, James; Hamby, Tyler
    Hypoplastic left heart syndrome (HLHS) is characterized by hypoplasia of the left heart and outflow tract. The three-stage surgical reconstruction of heart consists of circumventing the underdeveloped left ventricle by connecting right ventricle to systemic circulation and grafting a passive flow conduit which shunts venous blood into pulmonary artery. First stage surgery (Norwood) has the highest mortality among common congenital surgeries (7-19%) followed by a high risk interstage (IS) phase where additional 4-15% of infants die. A retrospective chart review of HLHS patients was conducted at Cook Children's hospital between January 2007 through January 2017. The objective of the study was to identify preoperative risk factors that may lead to premature death during IS. Univariate logistic regression analyses were used to determine whether feeding, intubation, and ECMO predicted mortality. IS was defined as time following Norwood procedure until Glenn, the second stage of reconstruction. Analysis revealed that receiving preoperative Norwood feeding intubated prior to surgery was associated with lower mortality (OR=0.42, CI=0.20-0.90, p= 0.025). Furthermore, intubation prior to surgery (OR=1.73, CI=1.05-2.85, p= 0.03) and pre-operative extracorporeal membrane oxygenation (ECMO) procedures (OR=2.83, CI=1.12-7.19, p=0.028) were associated with a higher IS mortality. Findings suggest a positive relationship between pre-operative respiratory interventions and increased rate of mortality during IS. Elucidation of this relationship suggests that pre-operative pulmonary status of the patient may be a leading prognostic factor on infant death between Norwood and Glenn. Consequently, a closer look at HLHS palliative protocol is warranted.
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    The wall stress hypothesis for myogenic responses in the coronary circulation
    (2021) Bale, Alexander; Dick, Gregory; Tune, Johnathan
    Purpose: Coronary arterioles demonstrate myogenic reactivity, as the caliber of the arteriole is actively adjusted in response to the intraluminal distending pressure. The teleological purpose of myogenic reactivity remains unclear, but it has been proposed that myogenic responses act to mitigate pressure-induced changes in circumferential wall stress (σ). We investigated pressure-induced variations in σ with and without myogenic reactivity. Methods: Using previously published data, we calculated σ in coronary arterioles in both the longitudinal (branch order) and transmural (epicardial vs endocardial) directions with and without myogenic tone. Results: Active constriction from the myogenic response reduced σ in all arterioles examined. Arteriolar σ was higher in the endocardium in both the passive and active state, but the percent change from passive σ to active σ was similar when compared to epicardial arterioles of the same branch order. There was no major change in active arteriole σ in the longitudinal direction, except for branch order 5 epicardial arterioles, which had a larger reduction in σ and a larger change from passive when compared to other epicardial branch orders. Conclusions: The results indicate that the myogenic response reduces arteriole wall stress. The greater passive and active σ seen in endocardial arterioles compared to epicardial arterioles is due to transmural differences in wall thickness. Yet, the fact that the thinner endocardial arterioles were able to produce the same degree of reduction in active σ may indicate that these vessels have more myogenic activity.
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    Symptomatic Bradycardia in a KCNQ1 Patient
    (2021) Warner, James; Checketts, Rees; Aston, James
    Background: This case report is about a female that presented with severe weakness due to episodic bradycardia. The patient has a history of familial atrial fibrillation (FAF) from a KCNQ1 mutation treated with ablation in 2008. Is this presentation secondary to known FAF, a result of the ablation, or another unrelated disease process? Case Information: A 38-year-old Caucasian female presented to a standalone ED reporting sudden weakness and fatigue. She was at home when the symptoms caused her to sit on the kitchen floor. During the episode she had no syncope, chest pain, or shortness of breath. The patient's FAF has caused her no symptoms since 2008, when ablation through pulmonary vein isolation occurred. At the ED, ECG revealed sinus bradycardia. All other vitals were normal and chest x-ray was insignificant. CBC, CMP, and troponins were within normal limits, except for low Vitamin D. Cardiology placed a cardiac loop recorder which recorded symptomatic episodes of bradycardia and intermittent pauses. A pacemaker is scheduled for placement. Conclusions: Atrial fibrillation commonly presents with symptomatic tachycardia rather than bradycardia. The KCNQ1 mutation is not known to cause bradycardia. Additionally, bradycardia after a cardiac ablation is more likely to present acutely after the procedure. Evidence of post ablation bradycardia presenting years after the procedure is sparse. Perhaps this presentation is a separate undiagnosed disease entity that may or may not be related to prior treatment and/or as a result of this patient's cardiac history.
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    Investigating the Use of Resistance Breathing for the Detection of Acute Hypovolemia
    (2021) Rusy, Ryan; Anderson, Garen K.; Kay, Victoria; Rickards, Caroline
    Introduction: Standard vital signs (e.g., heart rate and blood pressure) lack sensitivity and specificity to detect blood volume status following hemorrhage. Inspiratory resistance breathing has therapeutic potential to increase blood pressure and cardiac output following blood loss. We hypothesize that resistance breathing will elicit greater increases in absolute and breath-to-breath amplitude of stroke volume and arterial pressure under hypovolemic vs. normovolemic conditions. Methods: Data were retrospectively analyzed from 23 healthy human subjects aged 18-45 years. Subjects underwent lower body negative pressure (LBNP) protocols to simulate hemorrhage with and without resistance breathing. Continuous mean arterial pressure (MAP) and stroke volume were measured via finger photoplethysmography. Comparisons of absolute and changes in the breath-to-breath amplitude of MAP and stroke volume were made under 4 conditions: 1) normovolemia; 2) normovolemia + resistance breathing; 3) hypovolemia, and; 4) hypovolemia + resistance breathing. Results: Preliminary findings show an average change in MAP of -3.1% in response to resistance breathing during normovolemia, and +8.2% during hypovolemia. MAP amplitude during normovolemia decreased by -1.5% and increased by 22.4% during hypovolemia. Stroke volume maximum increased by 3.8% during normovolemia and 20.0% during hypovolemia, while stroke volume amplitude during normovolemia increased by 52.4% % and 19.0% during hypovolemia. Conclusions: These data indicate that there may be differences in the hemodynamic response to resistance breathing that could aid in the diagnosis of acute hypovolemia.
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    Sex Differences in the Oxidative Stress and Inflammation Response During and After Simulated Hemorrhage in Humans
    (2021) Barnes, Haley J.; Rosenberg, Alexander; Anderson, Garen K.; Luu, My-Loan; Rickards, Caroline
    Introduction: Hemorrhage (i.e., massive blood loss) induces an oxidative stress and inflammatory response that can persist even following hemostasis and resuscitation. In this study, we hypothesized that young males would elicit a greater oxidative stress and inflammatory response compared to young females, both during and after simulated hemorrhage. Methods: Healthy human subjects (10F; 10M) participated in a presyncopal lower body negative pressure (LBNP) protocol (simulating hemorrhage). Stroke volume was estimated as a marker of central hypovolemia (indexed to body surface area). Venous blood samples were collected at baseline, at the onset of presyncope, and 60-min into recovery ("resuscitation"). The oxidative stress and inflammation response were assessed via measurement of circulating F2-Isoprostanes (F2-IsoP) and interleukin (IL)-6 and IL-10. Results: LBNP tolerance time was similar between male and female subjects (Males, 1592±124 s vs. Females, 1437±113 s; P=0.37), and stroke volume index decreased by a similar magnitude at presyncope (Males, -50.2±6.3% vs. Females, -49.4±3.2%; P = 0.87). There was no effect of time or sex on the %Δ [F2-IsoP] during or after LBNP (P≥0.12). However, male subjects exhibited a greater increase in both the %Δ [IL-6] and %Δ [IL-10] compared to female subjects at the 60-min recovery time point (IL-6: Males, 101.4±138.9% vs. Females, 12.3±34.0%; P=0.06. IL-10: Males, 71.1±133.3% vs. Females, -2.2±11.8%; P=0.06). Conclusion: These data suggest there may be a sex difference in the inflammatory response to blood loss and subsequent fluid resuscitation.