Cardiovascular
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Item Ruptured Giant Abdominal Aortic Aneurysm(2022) Mahasamudram, Prathyusha; Jafferji, Fatema; Heckart, Logan; George, Kevin; Luka, Stacy; Fisher, Cara L.Abstract Background: An aneurysm is commonly defined as permanent and irreversible localized dilation of a vessel. Any aneurysm located in the infradiaphragmatic aorta could be clinically known as an abdominal aortic aneurysm (AAA), but this classification is typically limited to aneurysms of the infrarenal aorta rather than suprarenal aorta. Literature varies on the exact definition of AAA, but common definitions include vessel dilation of at least 150% compared to relative normal diameter of the artery, as well when the infrarenal aortic diameter is expanded greater than 3.0 cm. The infrarenal aortic aneurysm is the most common type of AAA with a frequency of 65%, but aneurysms do occur at other locations along the aorta. AAA's are also classified by their shape as either fusiform, which are expanded circumferentially, or as saccular, which are expanded in a spherical, but more localized manner. The greater the diameter of the AAA is versus the normal diameter at the level of the renal arteries, which is approximately 2.0 cm, the greater the risk of rupture. An AAA that is greater than 8.0 cm is estimated to have a 30%-50% chance of rupture according to the Joint Council of the American Association for Vascular Surgery. Case Information: During a routine cadaveric dissection, a AAA was identified in an 86-year-old Caucasian male, whose cause of death was documented as senile degeneration of the brain. The donor was 6'0" and 186 lbs (BMI = 25.2). He had a history of heart disease and chest pains. The aneurysm was discovered after noting evidence of significant bleeding in the retroperitoneum in the form of a blood clot. The blood clot itself measured 37.55 cm in transverse diameter and 22.35 cm in height. Removal of the blood clot revealed the aneurysm, which measured 10.82 cm in transverse diameter and 11.28 cm height. Conclusion: Documentation of this case adds to the current literature and understanding of AAA's of this size. With a transverse diameter greater than 10-13 cm, the identified AAA would be classified as a giant AAA. Bleeding from the rupture of this large aneurysm involved foregut, midgut, and hindgut structures. The inferior mesenteric artery, a branch of the abdominal aorta, which supplies the distal ⅓ of the transverse colon, descending colon, sigmoid colon, and the superior rectum was the most impacted. Other nearby arteries were also affected and damaged. Furthermore, we are able to note associations between the patient's medical history and the likelihood of development and rupture of an abnormal AAA. Increased risk for AAA is associated with ethnicity, age, sex, renal cysts, smoking history, CHD, and more. Our findings indicate that close follow-up with patients with increased risk-factors for AAA would be beneficial.Item Impaired cardiovascular function in obese Ossabaw swine model of heart failure with preserved ejection fraction(2022) Weber, Theodore Van; Dick, Gregory; Gerlt, Deitrich; Bale, Alexander; Warne, CooperPresenter: Ted Weber Authors: Ted Weber, OMS-II; Deitrich Gerlt, Alex Bale, Cooper Warne, Gregory Dick PhD, Johnathan Tune, PhD Title: Impaired cardiovascular function in obese Ossabaw swine model of heart failure with preserved ejection fraction Background: The lack of pre-clinical large animal models of heart failure with preserved ejection fraction (HFpEF) remains a growing, yet unmet obstacle to improving understanding of this complex condition. Objective: The goal of this study was to examine cardiovascular responses to acute reductions in blood pressure in lean-control vs. obese Ossabaw swine with HFpEF (obese HF). Heart failure was induced by chronic tachycardia at 180 beats/min for ~4 weeks. We tested the hypothesis that rapid ventricular pacing would augment left ventricular end diastolic pressure, impair cardiac contractile function, and diminish regional myocardial perfusion. Methods: Following completion of pacing protocol, swine were anesthetized and instrumented for continuous measurements of hemodynamic parameters, left ventricular pressure, volume, and coronary blood flow. After measurements were obtained under baseline conditions, blood was serially removed to lower blood pressure in ~10 mmHg increments down to a mean arterial pressure of ~40 mmHg. Arterial and coronary venous blood samples were obtained at rest and during each reduction in blood pressure. Results: Chronic tachycardia significantly increased left ventricular end diastolic pressure (P < 0.001) but did not affect ejection fraction (P = 0.79) in obese HF (n = 5) vs. lean-control (n = 7) swine. Hemorrhage reduced blood pressure from 106 ± 5 mmHg to 40 ± 1 mmHg vs. 102 ± 4 mmHg to 41 ± 1 mmHg in lean-control and obese HF swine, respectively. Reductions in arterial pressure robustly increased heart rate from 73 ± 8 to 136 ± 19 beats/min in lean swine. In contrast, the reflexive heart rate response was significantly attenuated in obese HF, as evidenced by a 4-fold reduction in the slope of the relationship between heart rate and blood pressure in obese HF vs. lean-control swine (P < 0.01). These changes were associated with significant reductions in the relationship between cardiac index (cardiac output/body weight) and end diastolic volume (P < 0.01), while the ratio of subendocardial to subepicardial blood flow to the left ventricle remained consistent as blood pressure was diminished in lean-control and obese HF (P = 0.53). Conclusions: These findings support that chronic high-rate ventricular pacing of obese Ossabaw swine induces key phenotypic features of HFpEF, including elevated left ventricular end diastolic pressure with normal ejection fraction, chronotropic incompetence, and impaired ventricular contractility.Item Phenotype of Pacing-Induced Heart Failure in Lean and Obese Ossabaw Swine(2022) Reagor, Caleb; Sweeney, Jonathan; Biggerstaff, Matthew; Tune, JohnathanCaleb Reagor*, Jonathan Sweeney*, Matthew Biggerstaff*, and Johnathan D. Tune *Authors contributed equally Purpose: There are numerous preclinical models of heart failure in large animals; however, almost all reflect heart failure with reduced ejection fraction (HFrEF). There are currently no suitable large animal models of heart failure with preserved ejection fraction (HFpEF). The lack of HFpEF models represents a significant gap in translational studies to understand pathophysiological mechanisms and elucidate potential treatments for approximately 50% of all heart failure cases. Obesity and its related comorbidities are more strongly associated with risk of future HFpEF versus HFrEF. We hypothesized that obese animals would develop HFpEF in response to 4 weeks of tachypacing, whereas lean animals would develop HFrEF in response to the same stimulus. Methods: Three groups of Ossabaw swine were studied, including lean swine without pacing (n = 9; control), lean swine with pacing (n = 5), and obese swine with pacing (n = 5). Ossabaw swine are an ideal model for these studies, as they demonstrate a human-like response to a high calorie, high fat diet (e.g., obesity, insulin resistance, and dyslipidemia). Swine were anesthetized and pacemakers were implanted to drive the right ventricle at 180 beats/min. After recovery and 4 weeks of pacing, animals were anesthetized, and a pressure-volume catheter was inserted into the left ventricle to assess the type and degree of heart failure. Results: Paced animals had grossly enlarged heart chambers and significant abdominal ascites. Tachypacing increased heart weight (176 ± 11, 229 ± 13, and 234 ± 14 g in control, lean, and obese swine, respectively; p < 0.01). Ejection fraction was not different between groups (58 ± 6, 53 ± 6, and 59 ± 6% in control, lean, and obese swine, respectively; p = 0.86). Tachypacing increased left ventricular end diastolic pressure (LVEDP), a hallmark of heart failure (12 ± 1, 28 ± 4, and 26 ± 1 mmHg in control, lean, and obese swine, respectively; p < 0.001). Conclusions: The data indicate that we have created a tachypacing-induced model of HFpEF in Ossabaw swine. However, in direct contrast to our prediction, tachypacing produced HFpEF in both lean and obese Ossabaw swine. Tachypacing significantly elevated filling pressure (LVEDP) to pathophysiological levels, but ventricular performance (ejection fraction) was maintained. Our findings support the idea that Ossabaw swine subjected to tachypacing represent a clinically relevant large animal model of HFpEF.Item Innate immune system stimulation during pregnancy induces upregulation of thromboxane synthesis in rat maternal heart(2022) Tucker, Selina; Cushen, Spencer; Bradshaw, Jessica L.; Gardner, Jennifer; Ricci, Contessa; Dick, Gregory; Tune, Johnathan; Goulopoulou, StylianiPurpose: Infections during pregnancy are associated with adverse clinical outcomes. We previously showed that exposure to immunostimulatory ODN2395 (synthetic Toll-like receptor 9 agonist) during pregnancy induces maternal vascular inflammation and enhances vascular tone in pregnant rats. These outcomes were mediated in part by activation of the cyclooxygenase/thromboxane A2 (COX/TxA2) pathway. The objective of this study was to investigate the impact of ODN2395-induced immune system stimulation on maternal hearts during pregnancy. We hypothesize that exposure to TLR9-mediated immune system activation during pregnancy upregulates the COX/TxA2 signaling pathway in maternal cardiac tissues in rats. Methods: Rats were treated with a synthetic CpG DNA (ODN2395, 1 mg/kg, intraperitoneal injection) or vehicle (saline) in late pregnancy. Fetoplacental biometrics were recorded after euthanasia on gestational day 20 and maternal hearts were collected to assess COX-1 and COX-2 expression and 6-keto PGF1α (PGI2 metabolic byproduct) and TxB2 (TxA2 metabolic byproduct) production. Results: Left ventricular tissues from dams treated with ODN2395 released higher concentrations of TxB2 compared to tissues from vehicle-treated dams (ODN2395: 0.56 ± 0.06 ng/mg protein vs. Vehicle: 0.31 ± 0.04 ng/mg protein, n5, p=0.0041) but there were no differences in cardiac 6-keto PGF1α release between groups (p=0.16). COX-2 expression was lower in left ventricles from ODN2395-treated rats compared to vehicle-treated rats (p=0.009). There were no differences in cardiac COX-1 expression between groups (p=0.27). Exposure to ODN2395 during pregnancy increased fetal-placental weight ratio (ODN2395: 5.3 ± 0.22 vs. Vehicle: 4.7 ± 0.15, p = 0.04). COX-2 expression was greater in placental tissues from ODN2395-treated rats (p=0.004) but there were no differences in placental 6-keto PGF1α (p=0.51) and TxB2 release (p=0.32). Conclusion: TLR9 activation during pregnancy induces upregulation of TxB2 synthesis in maternal cardiac tissues coupled with a reduction in COX-2 expression. Maternal heart may have enhanced sensitivity to bacterial infections during pregnancy.Item The Hypertrophic Septal Papillary Muscle(2022) Ntekim, Nedeke; Nazzal, Alex; Oad, Shayrin; Palapati, Tarun; Fisher, Cara L.Background: The septal papillary muscle (SPM) is one of three papillary muscles found in the right ventricle of the heart (the others are the anterior and posterior papillary muscles). Typically, the SPM arises from the interventricular septum and attaches to the chordae tendineae of the anterior and septal cusps of the tricuspid valve, although it can differ greatly in its location and morphology. The SPM has been found anterior to the septum, posterior to the septum, and laying centrally in the septum. One study also showed that a typical SPM originates from the upper one-third of the ventricle (81.25%) and attaches to chordae tendineae. In another study, it was found that the SPM was absent in around 22% of the hearts that were examined. The SPM has also been found to come off the top third of the wall of the ventricle and has a shape that resembles a cone. The average SPM in the aforementioned study had a mean measurement of 0.95 cm in length and 0.59 cm in width. Along with the other papillary muscles, the SPM functions to keep the tricuspid valve in position and closes the tricuspid valve to prevent the regurgitation of blood from the right ventricle back into the right atrium. In surgeries designed to correct ventricular septal defects, the SPM serves as a landmark for the right bundle branch within the right ventricle. Case Information: During a cadaver dissection in the anatomy lab for first-year medical students, a hypertrophic SPM was found in the right ventricle of a 67-year-old male. The SPM arose from the interventricular septum, attaching to the chordae tendineae and atypically to the anterior wall of the right ventricle. Using digital calipers, the width of the donor's SPM was measured to be 0.456 cm, while the length was measured to be 3.246 cm. Conclusion: Although the morphology of the SPM is quite variable, the one found in our donor is a unique variant because of its length and location. One study found the mean length of the SPM to be 0.51, 0.65, and 0.81 cm in three groups of adults at progressively older ages, adding to the conclusion that the SPM enlarges with age. The length of the donor's SPM in this case is approximately 340% longer than the average SPM. The attachment of the SPM to the anterior ventricular wall in this case is also unusual, even among common variants. Information on these variants of the SPM could prove useful in the identification of diseases and surgical operation within the right ventricle.Item Hydrodissection for Treatment of Vascular Thoracic Outlet Syndrome(2022) Ver Hoef, John M.The following case explores the effectiveness of a new treatment modality in the case of vascular thoracic outlet syndrome (vTOS). Few conservative treatments exist for use in alleviating symptoms of vTOS. In this case, a 25 year old male was diagnosed with vTOS 4 months prior to presentation. A combination of poor posture, inactivity, and protruding screws from a previous clavicle fracture repair were compromising the subclavicular vasculature. Symptoms of claudication and a cold right arm/hand led to the patient seeking medical treatment. He had failed physical therapy and pharmacotherapy, was told by a vascular surgeon that he was a surgical candidate. He sought non-surgical options for treatment, and after exploring possible remedies, hydrodissection was chosen for its potential merit in this case. After utilizing the treatment and decompressing the subclavicular neurovascular bundle, the patient reported immediate alleviation of his symptoms. After a 2 week and 3 month follow up, the patient still reports 100% reduction in symptoms with no recurrence. Though there is a lack of literature to support the use of hydrodissection to treat vTOS, this was a specific case in which hydrodissection demonstrated to be an effective treatment modality. The specific utilization of hydrodissection should be studied more in order to increase the literature base and increase awareness of its potential effectiveness for this and similar conditions.Item Effect of Acute Heat Exposure on the Pressor Response to a Voluntary Hypoxic Apnea: A Cross-tolerance Study.(2022) Saul, Benjamin; Hemingway, Holden; Richey, Rauchelle; Moore, Amy; Shokraeifard, Austin; Cope, Heidi; Yurvati, Albert; Cunningham, Rebecca; Smith, Michael; Romero, StevenThe pressor response induced by a voluntary hypoxic apnea is exaggerated in individuals with obstructive sleep apnea and is strongly correlated to sympathetic overactivity. Acute heat exposure alters neural control of blood pressure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. Therefore, we tested the hypothesis that acute heat exposure would attenuate the pressor response to a voluntary hypoxic apnea, and thereby manifest as a form of physiological cross-tolerance. Eight adults (3 females, 26 +/- 2 yrs) were subjected to passive heat stress (water perfused suit) sufficient to increase body core temperature by 1.2°C. Voluntary hypoxic apneas were performed in duplicate before acute heat exposure (pre-heat) and in recovery when body core temperature returned to ≤ 0.3°C of baseline. Participants breathed gas mixtures varying FiO2 (21%, 16%, and 12%; randomized) for 1 min followed immediately by a 15 s end-expiratory apnea. Beat-by-beat arterial blood pressure (Finometer) and arterial oxygen saturation (finger pulse oximetry) were measured throughout. The pressor response was calculated as a difference between baseline mean arterial pressure and the peak response following each apnea. The change in arterial oxygen saturation during each apnea did not differ from pre-heat to recovery (FiO2 21%, pre-heat 0 +/- 1 % vs. recovery 0 +/- 2 %; FiO2 16%, pre-heat -4 +/- 1 % vs. recovery -4 +/- 2 %; FiO2 12%, pre-heat -8 +/- 3 % vs. recovery -10 +/- 4 %; P = 0.3 for interaction). The pressor response to a voluntary apnea was attenuated in recovery from acute heat exposure across all concentrations of FiO2 (FiO2 21%, pre-heat 19 +/- 8 mmHg vs. recovery 16 +/- 8 mmHg; FiO2 16%, pre-heat 27 +/- 8 mmHg vs. recovery 20 +/- 8 mmHg; FiO2 12%, pre-heat 33 +/- 11 mmHg vs. recovery 27 +/- 13 mmHg; P = 0.02 for main effect of time). These data suggest that acute heat exposure induces a cross-tolerance effect such that the pressor response to a voluntary hypoxic apnea is reduced. Acute heat exposure could improve hypertension in adults with obstructive sleep apnea, secondary to altered chemoreflex function and sympathetic neural control, and provide additional therapeutic options for this population to improve cardiovascular health.Item Acute Heat Exposure Improves Microvascular Function in Skeletal Muscle of Aged Humans(2022) Richey, Rauchelle; Hemingway, Holden; Moore, Amy; Yurvati, Albert; Romero, StevenAcute heat exposure improves microvascular function in the leg of aged adults as assessed using post-occlusive reactive hyperemia. However, reactive hyperemia measures whole-limb blood flow and cannot isolate perfusion among various tissues. Thus, it is unclear if the skeletal muscle circulation contributes to the improvement in microvascular function observed following acute heat exposure. We tested the hypothesis that acute hot water immersion would improve microvascular function in the vastus lateralis of aged adults. Seven aged adults (1 man, 71 ± 4 yrs) were immersed to the umbilicus for 60 min in thermoneutral (36 °C) or hot (40 °C) water. Body core temperature was measured via a telemetric pill. Two microdialysis probes were placed in the vastus lateralis ~30 min after immersion. Microdialysis was utilized to bypass the cutaneous circulation and directly assess endothelial-dependent and endothelial-independent microvascular function in skeletal muscle by measuring the local blood flow response to a graded infusion of acetylcholine (ACh, 27.5 and 55.0 mM) and sodium nitroprusside (SNP, 21 and 42 mM), respectively. Local blood flow was measured using the ethanol washout technique. Body core temperature increased by Δ1.1 ± 0.3 °C during hot water immersion but was relatively unchanged during thermoneutral immersion (Δ0.1 ± 0.3 °C). Baseline skeletal muscle blood flow did not differ between thermal conditions for the ACh probe (P = 0.9), nor the SNP probe (P = 0.7). The hyperemic response to 27.5 mM ACh did not differ between thermal conditions (thermoneutral immersion, Δ11.3 ± 11.5 ml/min/100g vs. hot water immersion, Δ18.6 ± 16.8 ml/min/100g; P = 0.7). However, the hyperemic response to 55.0 mM ACh was increased with prior hot water immersion (thermoneutral immersion, Δ30.7 ± 16.9 ml/min/100g vs. hot water immersion, Δ56.2 ± 19.7 ml/min/100g; P < 0.01). Similarly, the hyperemic response to 21 mM SNP did not differ between thermal conditions (thermoneutral immersion, Δ16.9 ± 16.8 ml/min/100g vs. hot water immersion, Δ18.2 ± 18.8 ml/min/100g; P = 0.9), but was increased with prior hot water immersion during the infusion of 42 mM SNP (thermoneutral immersion, Δ29.3 ± 14.4 ml/min/100g vs. hot water immersion, Δ58.5 ± 31.2 ml/min/100g; P = 0.02). These data suggest that acute heat exposure improves endothelial-dependent and endothelial-independent microvasculature function in skeletal muscle of aged humans. Furthermore, these data highlight the therapeutic potential of heat therapy to attenuate the hypoperfusion of skeletal muscle that occurs in aged adults during conditions that require an elevated blood supply such as exercise.Item Acute Heat Exposure Protects Against Endothelial Ischemia-reperfusion Injury in Aged Humans(2022) Hemingway, Holden W.; Richey, Rauchelle; Moore, Amy; Yurvati, Albert; Romero, StevenNon-pharmacological therapies that protect against endothelial ischemia-reperfusion injury (I/R) remain limited in aged adults. Acute heat exposure protects against endothelial I/R injury in young adults, but its efficacy has never been explored in aged adults. Therefore, we tested the hypothesis that acute heat exposure would protect endothelial-dependent vasodilation following I/R injury in aged adults. Nine (2 men, 69 ± 8 yrs) aged adults were exposed to a thermoneutral control condition or whole-body passive heating (water-perfused suit) sufficient to increase body core temperature by 1.2 °C. Experiments were separated by at least 7 days. Heat exposure was always performed first in order to time-match the thermoneutral control condition. Endothelium-dependent vasodilation was assessed via flow-mediated dilation of the brachial artery before (pre-I/R) and after I/R injury (post-I/R), which was induced by 20 min of arm ischemia followed by 20 min of reperfusion. Ischemia-reperfusion injury reduced flow-mediated dilation following the thermoneutral control condition (pre-I/R, 4.5 ± 2.9 % vs. post-I/R, 0.9 ± 2.8 %, P < 0.01), but was well maintained with prior heat exposure (pre-I/R, 4.4 ± 2.8 % vs. post-I/R, 3.5 ± 2.8 %, P = 0.5). Taken together, acute heat exposure protects against endothelial I/R injury in aged adults. These results highlight the therapeutic potential of heat therapy to prevent endothelial dysfunction associated with I/R injury in aged adults who are most at risk for an ischemic event.Item Renal TLR7 expression is associated with renal injury in female mouse model of systemic lupus erythematosus(2022) Chaudhari, Sarika; D'Souza, Bradley; Morales, Jessica; Shimoura, Caroline; Young-Stubbs, Cassandra; Ma, Rong; Mathis, Keisa W.Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with exaggerated immune activation, autoantibody production, and immune complex formation. SLE patients are predominantly women of reproductive age that often present with end organ damage, specifically in the kidneys, and hypertension. This detrimental sequelae is likely due to deposition of the immune complexes and the resulting inflammation, but the exact mechanisms are unknown. It is known however that immune complexes activate toll like receptors (TLRs) on immune cells and TLR7 particularly is known to promote the pathogenesis of SLE. Therefore, we hypothesized that renal TLR7 impairs renal function and drives renal injury and hypertension in female SLE mice. Double-stranded DNA (dsDNA) autoantibodies, a hallmark of SLE, and albuminuria, a marker of renal injury, were monitored at 30 and 35 weeks of age in female and male SLE (NZBWF1) and control (NZW) mice. Glomerular filtration rate (GFR) was measured by sinistrin clearance and renal TLR7 and tumor necrosis factor (TNF)-α expression were measured via Western blot to assess renal function and renal inflammation at the end of 35 weeks. Mean arterial pressure was measured in conscious mice at 35 weeks of age using indwelling arterial catheters. At 30 weeks, female SLE mice had elevated plasma dsDNA autoantibodies (U/ml) compared to female controls (4.6e5 ± 1.3e5 vs 8.9e4 ± 3.3e4; n=3-5; all p< 0.05), male SLE mice (6.3e4 ± 2.7e4), and male controls (4.8e4 ± 9.3e3). At 30 weeks, 32% (7 out of 22) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 20) of male SLE, and no male controls. At 35 weeks, 63% (10 out of 16) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 19) of male SLE, and no male controls. GFR (µL/min/100 g body weight) was lower in female SLE mice compared to males at this same time point (865 ± 77 vs. 1066 ±60; p=0.029). Female SLE mice expressed a significantly higher renal cortical expression of TLR7 than both female control (p < 0.001) and male SLE mice (p < 0.001). Renal cortical expression of TNF-α, a downstream effector of TLR7, was increased in female SLE mice when compared to both female control mice (p < 0.001) and male SLE mice (p < 0.001). Both female and male SLE mice were hypertensive at 35 weeks: mean arterial pressure (mmHg) was higher in female SLE than female controls (152 ± 5 vs. 126 ± 3; n=6-8; p=0.003) and in male SLE compared to male controls (152 ± 4 vs. 136 ± 4 mmHg; n=6-11; p=0.041). These data indicate that increased expression of renal TLR7 and TNF-α is associated with renal injury and hypertension in female SLE mice. These data also suggest a potential sex difference in the pathogenesis of SLE in males. Therapeutic strategies targeting the TLR7 molecular pathway should be further investigated in both female and male lupus nephritis.Item Hypoxemia Augments the Local Metabolic Error Signal and Improves Coronary Pressure-Flow Autoregulation(2022) Warne, Cooper M.; Essajee, Sal; Dick, Gregory; Tune, JohnathanThe local metabolic hypothesis proposes that myocardial oxygen tension, indexed by coronary venous PO2 (CvPO2), determines the degree of coronary pressure-flow autoregulation by increasing the production of vasodilator metabolites as coronary perfusion pressure (CPP) is reduced. We tested this hypothesis by examining the extent to which exaggeration of the metabolic error signal influences coronary autoregulatory capability. Experiments were performed in anesthetized, open chest swine (n = 8) in which the left anterior descending coronary artery was cannulated and connected to a servo-controlled roller pump system. This allowed CPP to be reduced from 140 to 40 mmHg in increments of 10 mmHg before and during hypoxemia (PaO2 from 138 ± 5 to 34 ± 1 mmHg). Under control-normoxic conditions, CvPO2 decreased from 33 ± 1 to 20 ± 1 mmHg and coronary blood flow fell from 0.81 ± 0.09 to 0.35 ± 0.04 ml/min/g as CPP was reduced from 140 to 40 mmHg. Hypoxemia augmented myocardial oxygen consumption (P < 0.01), increased coronary blood flow (P < 0.0001), and reduced CvPO2 (22 ± 1 to 14 ± 1 mmHg; P < 0.0001) over the same range of CPPs. Increases in coronary blood flow during hypoxemia were sufficient to maintain myocardial oxygen delivery at values equivalent to normoxic conditions (P = 0.20). Calculation of closed-loop autoregulatory gain (Gc) over a CPP range of 120 to 60 mmHg (value of 1 represents perfect autoregulation) demonstrated that Gc was improved from 0.18 ± 0.05 to 0.45 ± 0.14 under normoxic vs. hypoxemic conditions respectively (P = 0.02). Gc was also inversely related to CvPO2 and the slope increased ~4-fold by hypoxemia. These findings support that coronary pressure-flow autoregulatory capability is augmented by hypoxemia-induced increases in the local metabolic error signal.Item PKD1 Variants of Uncertain Significance Found in a 64 year-old Male With Simple Renal Cysts and Thoracic Aortic Disease(2022) Tatapudi, Suhas V.V.Introduction: Thoracic aortic disease (TAD) - aneurysms and dissections, is a clinically silent disorder caused by weakening of major blood vessels which may lead to rupture and imminent mortality. Simple renal cysts are relatively common and are associated with numerous etiologies. Case presentation: Here we present the case of a 64 year-old male with a history of smoking, hypertension, and stroke due to cerebral aneurysm. He presented with substernal chest pain and was diagnosed with a type B aortic dissection extending from the left subclavian artery to the left iliac artery. An aortic endograft was placed to prevent rupture, covering the ostium of the left subclavian artery. Immediate post-operative bilateral lower extremity paraplegia developed, ultimately necessitating a subclavian artery bypass for resolution. Despite clinical improvement, two weeks post-operatively an aortic rupture occurred, leading to cardiac arrest and demise. Pathologic and Ancillary findings: Notable findings on autopsy included aortic dissection and rupture, left hemothorax, multicystic kidneys, and prior evidence of craniotomy. The dissection extended anterograde to left internal iliac artery and retrograde to the sinotubular junction with rupture just distal to the distal aspect of the endograft. No abnormalities were reported in aortopathy panels. Polycystic kidney disease panels revealed three variants of uncertain significance (VUS) within the PKD1 gene: p.Val2905Ile, p.Lys3232Glu, p.Leu3477Ile. Congophilic (amyloid) angiopathy was discovered within several vessels in the brain which may be associated with the history of a cerebral aneurysm. Discussion: Hypertension and smoking are significant risk factors for systemic vascular disease. While PKD1 and PKD2 mutations can be seen associated with autosomal dominant polycystic kidney disease, heterozygous mutations may result in milder cystic disease. Through retrospective case reports and series, Ziganshin et al proposed an association between simple renal cysts and TAD. As more evidence is established, a diagnosis of simple renal cysts may prompt the need for screening for TAD. Our clinical and molecular picture may further substantiate a potential relationship between TAD, cystic renal disease, and mutations in PKD1 and PKD2 genes. Furthermore, genetic counseling may also be necessary for surviving family members. This case exemplifies the importance of postmortem autopsies and the discovery of genetic variants with potential clinical implication.Item Characterization of arterial pressure and carotid blood flow responses to pulsatile perfusion therapy in a rat model of hemorrhage(2022) Bhuiyan, Nasrul; Farmer, George; Anderson, Garen K.; Davis, Kenneth; Cunningham, Joseph; Rickards, CarolineIntroduction: In a human model of simulated blood loss, oscillatory patterns of arterial pressure and blood flow, or "pulsatile perfusion", can protect cerebral and peripheral tissue oxygenation, and prolong tolerance to this stress. In this pilot study, we investigate whether pulsatile perfusion therapy can protect arterial pressure and cerebral blood flow in a rat model of actual blood loss. We hypothesized that pulsatile perfusion therapy (PPT), applied via repeated thigh cuff inflations, would attenuate the reduction in arterial pressure and cerebral blood flow following hemorrhage. Methods: Sprague Dawley rats underwent the following protocols: hemorrhage alone (control: N=4; 2 male, 2 female), or hemorrhage plus PPT (N=3; 1 male, 2 female). PPT was applied via rapid 1 s inflations and deflations of a thigh cuff (0.5 Hz). A catheter was inserted in the femoral artery for continuous measurement of arterial pressure, and a perivascular flow probe was placed around the common carotid artery (CCA) for measurement of blood flow. Following instrumentation, each animal completed a baseline period (15 min), followed by a ~55% hemorrhage (25 min), PPT or control (30 min), and a recovery period (155 min or until death). Results: Decreases in mean arterial pressure (MAP) and CCA blood flow were observed in response to hemorrhage (P≤0.002). At the end of the PPT period, no differences were observed between the PPT and control groups for MAP (PPT: 46.7±27.3 mmHg vs. control: 30.2±13.5 mmHg; P=0.44) or CCA peak blood flow (PPT: 2.7±1.5 ml/min vs. control: 1.9±1.3 ml/min; P=0.92). Similarly, no differences were observed in the relative change from baseline to the end of the PPT period for MAP (PPT: -45±38% vs. control: -55±14%; P=0.65) or CCA peak blood flow (PPT: -65±21% vs. control: -66±12%; P=0.70). Conclusion: These results suggest that following a 55% hemorrhage in rats, PPT did not protect arterial pressure or carotid blood flow. However, the sample size was low in this pilot study, resulting in high variability in the observed responses. Accordingly, additional experiments are needed with an increased sample size to accurately determine the potential beneficial effects of PPT following hemorrhage.Item Blood Pressure Responses to Exercise in Females: Impact of race(2022) Fletcher, Andrew; Martin, Zachary; Skow, Rachel; Merlau, Emily; Aldaas, Iman; Cardenas, Natalia; Campbell, Jeremiah; Fadel, Paul; Brothers, MatthewPurpose: A primary risk factor for cardiovascular disease (CVD) is hypertension, which impacts ~50% of individuals in the United States >18 years of age. Although resting blood pressure (BP) measures are informative, an exaggerated BP response to exercise, termed exercise-induced hypertension, has emerged as a strong predictor of future hypertension and subsequent CVD risk. In the United States, race/ethnicity-related health disparities persist. For example, Black females (BF) have an ~20% higher prevalence of hypertension and CVD relative to White females (WF). However, whether there are differences in the BP response during exercise between these populations remains unclear. Accordingly, in this preliminary study, we tested the hypothesis that BF have an exaggerated BP response during exercise relative to WF. Methods: 14 females (7 Black and 7 White, age 18-27 yrs, BMI 21.3-30.1 kg/m2), free from CVD or other health conditions, participated. All participants underwent a staged maximal exercise test on a cycle ergometer. Each stage was 2 min in duration and were based on individualized predicted maximal oxygen consumption (VO2peak). BP (Tango stress monitor), heart rate (3 lead EKG), and VO2 (Parvo metabolic cart) were collected during the final minute of each stage of the exercise protocol. The BP increase during exercise was evaluated as change in mean arterial pressure (delta MAP) and change in systolic BP (delta SBP) from rest to peak exertion. The SBP response for any given increase in workload was further analyzed as the slope of the relationship between SBP and metabolic equivalents (MET; SBP/MET). Results: Blood pressure responses during exercise were not different between groups; delta MAP (BF: 10 +/- 3 mmHg and WF: 20 +/- 3 mmHg; p=0.06) delta SBP (BF: 42 +/- 7 and WF: 48 +/- 6; p=0.49). Likewise, the SBP/MET slope (BF: 7.8 +/- 5.9 mmHg/MET and WF: 6.5 +/- 1.8 mmHg/MET; p=0.66) and exercise capacity as identified by VO2peak were not different between groups (BF: 2 +/- 0.1 L/min and WF: 2.2 +/- 0.2 L/min; p=0.46). Conclusions: These preliminary data suggest that the BP response during peak exercise is similar between relatively young and healthy Black and White females. Further investigation with more participants is warranted.