The anomalous origin of coronary arteries has been extensively documented in the literature. Most of the anomalies are incidentally found either during coronary angiography or imaging studies and are usually benign; however, malignant outcomes have been reported in the literature. Here, we present the case of a 76-year-old male with non-ST segment elevation myocardial infarction who was found to have an asymptomatic anomalous origin left anterior descending artery from the right sinus of Valsalva.

Peripheral artery disease (PAD) is associated with increased risk for arterial thromboembolic events, and antithrombotic therapy is fundamental to its treatment. Females with PAD have unique characteristics that impact their disease experience, but data is lacking on the differential effects of antithrombotic regimens in females with PAD. We developed a protocol and conducted two systematic reviews and meta-analyses to 1) assess the impact of female sex on cardiovascular, limb, and bleeding events in antithrombotic trials enrolling PAD patients, and 2) evaluate the representation of female PAD patients in antithrombotic trials, as well as trial generalizability. Females did not confer any benefit from dual antiplatelet therapy, dual pathway inhibition, or therapeutic oral anticoagulation over mono-antiplatelet therapy alone, however trial generalizability was limited by poor female enrolment and insufficient sex-based analyses. A more tailored approach to secondary prevention in females with PAD (beginning with improved study design) may yield better outcomes.

No description available.

The current study evaluated the potentially detrimental effects of daily resistance training on cardiovascular health using a longitudinal study design. This study also addressed the effects of resistance training on vascular endothelial function. Recent cross-sectional studies have shown resistance trained individuals have reduced whole-body arterial compliance compared to sedentary controls and that the age-associated reduction of arterial compliance is augmented in resistance trained athletes. The effect of resistance training on vascular endothelial function has not been addressed to date in the literature. Twenty-eight young healthy males (age: 23±3.9 [mean±SD]) were whole body resistance trained five times a week for twelve weeks, using a split body design. Measurements of supine resting arterial blood pressure at the brachial artery, carotid, brachial and femoral cross-sectional compliance, and brachial vascular endothelial function (using flow-mediated dilation) were acquired prior to, halfway through and following the exercise training protocol. Strength of various body segments increased significantly following the resistance training program. Shoulder press one repetition maximum (1RM) lifts increased from 141.4±7.6 lbs. to 185.2±8.8 lbs. and double leg press 1RM from 483.0±29.0 lbs. to 859.8±52.1 lbs. Resting diastolic blood pressure increased significantly from Mid to Post training (61.8±1.3 mmHg to 65.4±1.2 mmHg) yet was not significantly changed from Pre values (62.9±1.2 mmHg). Pulse pressure was reduced significantly with exercise training by the Post training time-point (Pre 63.3±1.9 mmHg; Mid 59.0±2.4 mmHg; Post 53.7±2.8 mmHg). Mean arterial carotid and femoral artery diameters were not changed with resistance training; however, mean brachial artery diameter increased by the Mid training time-point and remained elevated at the Post training time-point (Pre 3.81±0.10 mm; Mid 4.03±0.1 0 mm; Post 4.04±0.11 mm). Cross-sectional compliance did not change at the carotid or the brachial arteries, however the femoral artery experienced a reduction of compliance by the Mid time-point that remained to the Post training time-point (Pre 0.162±0.012 mm²/mmHg; 0.125±0.013 mm²/mmHg; Post 0.129±0.015 mm²/mmHg). Brachial vascular endothelial function measured using flow-mediated dilation did not show a significant change with resistance training. When normalized for shear rate (which was also unaltered with resistance training) there were no changes in endothelial function. Peak and 1 0-s average brachial post-occlusion blood flow was enhanced with resistance training (Pre 247.5±14.0 ml/min; Mid 331.1±18.5 ml/min; Post 290.5±21.0 ml/min) possibly revealing enhanced resistance vessel function. In conclusion, resistance exercise training results decreased PP, reduced femoral compliance, an increase in mean brachial artery diameter and enhanced post-ischemic blood flow. The exact mechanisms responsible for such changes remain unknown and require further investigation. / Thesis / Master of Science (MS)

Coronary artery disease (CAD) remains the leading cause of death in both the United States and the world at large. This is primarily due to the extreme difficulty associated with preemptive diagnosis of CAD. Currently, only about 20% of all patients are diagnosed with CAD prior to the occurrence of a heart attack. This is the result of limitations in current techniques, which are either noninvasive, extremely expensive, or have very poor correlation with the actual disease state of the patient. Phonoangiography is an alternative approach to the diagnosis of CAD that relies upon detection of the sound generated by turbulent flow downstream from occlusions. Although the technique is commonly used for the carotid arteries, in the case of the coronary arteries the technique is hampered by signal-to-noise problems as well as uncertainty regarding the spectral characteristics associated with CAD. To date, these signal processing difficulties have prevented the use of the technique clinically. This research introduces an alternative approach to the processing of phonoangiographic data based upon knowledge of the acoustic transfer within the chest. The validity of the proposed approach was examined using transfer functions which were calculated for 14 physiologically relevant locations within the chest using a 2-D Finite Element Model (FEM) generated from physiologic data. These transfer functions were then used to demonstrate the technique using test cases generated with the FEM. Finally, the vulnerability of the technique to noise was quantified through calculation of matrix condition numbers for the chest acoustic transfer at each frequency. These results show that while in general the technique is susceptible to noise; noise tolerance is greatly improved within the frequency range most likely to correspond to an occlusion. Taken together, these results suggest that the proposed technique has the potential to make phonoangiography viable as a screening technique for CAD. Such a technique would greatly reduce the cost of CAD, measured in terms of both financial cost as well as lives. / Master of Science

Cardiovascular diseases (CVD) are the leading cause of death in the world. According to the World Health Organization (WHO) 17.3 million people died from cardiovascular disease in 2008, representing 30% of all global deaths. The most common modality of treatment of occluded arteries is the use of stents. Despite the widespread use of stents, the incidence of post-stent restenosis is still high. The study of stents in conditions that are similar to in-vivo conditions is limited. This work tries to address the behavior of stents in conditions similar to in-vivo conditions in a generalized framework, thus providing insights for stent design and deployment. Three dimensional, time accurate computational fluid dynamics (CFD) simulations in a pulsatile flow with fluid-structure interaction (FSI) were carried out in realistic coronary arteries, with physiologically relevant flow parameters and dynamics due to induced motion of the heart. In addition, the geometric effects of the stent on the artery were studied to point towards possible beneficial stent deployment strategies. The results suggest that discontinuities in compliance and dynamic geometry cause critical changes in local hemodynamics, namely altering the local pressure and velocity gradients. Increasing the stent length, reducing the transition length and increasing the overexpansion caused adverse flow conditions. From this work, detailed flow characteristics and hemodynamic characteristics due to the compliance mismatch and applied motion were obtained that gave insights towards better stent design and deployment. / Ph. D.

Coronary artery bypass graft (CABG) är en väl etablerad behandling för patienter med kranskärlssjukdom. Operationen är utmanande och påfrestande för patienten och upplevelserna efter genomgången operation är varierade. Att som sjuksköterska ha kännedom om patienters upplevelser tiden efter operationen är av betydelse för att möjliggöra god omvårdnad och återhämtning för patienten. Syftet var att belysa patienters upplevelser tiden efter en CABG. Studien grundades på 11 vetenskapliga artiklar och genomfördes som en litteraturstudie. Fyra teman framkom i resultatet; den relationella upplevelsen, den kroppsliga upplevelsen, den mentala skörheten och en ny syn på livet. Det framkom att patienterna upplevde stödet från omgivningen som det viktigaste för god återhämtning. Information från vårdpersonalen ansågs till viss del bristfällig av patienterna. Flera upplevde smärta efter operationen och hade delvis symtom kvar, men dessa avtog med tiden. Centralt efter operationen var även oro, men med tiden kom förbättrad livskvalitet och motivation. Det framkom att en CABG var en stor påfrestning för patienten och upplevelserna var både positiva och negativa. Kunskapsluckor avseende patientupplevelser efter operationen finns och ytterligare forskning bör fokusera på området för att ge sjuksköterskestudenter och sjuksköterskor ökad kunskap i mötet med denna patientgrupp. / Coronary artery bypass graft (CABG) is a well-established treatment for patients with coronary artery disease. The surgery is challenging and stressful for the patient and experiences varied after surgery. It’s important for the nurse to be aware of patients’ experiences after surgery to enable good care and recovery for the patient. The aim was to illuminate patients’ experiences during the time after a CABG. The study was based on 11 scientific articles and was conducted as a literature review. Four themes emerged; the relational experience, the bodily experience, the mental fragility and a new view on life. The result showed that patients' experienced the support from the surroundings as the most important for good recovery. Information given by caregivers were in some cases considered inadequate by the patients. Patients experienced pain after surgery and had partial symptoms left, which subsided with time. Concern was a central experience after surgery, but over time came improved quality of life and motivation. A CABG is a major strain for the patients and the experiences were both positive and negative. There are gaps in knowledge regarding patient experiences after the surgery and further research should focus on that area to give nursing students and nurses knowledge in the meeting with these patients.

Migraine is one of the most prevalent contributors to the global burden of mental and neurological disorders. It is a complex episodic condition that presents as intense recurrent unilateral headaches lasting hours to days that can be accompanied by nausea, photophobia, phonophobia and other neurological symptoms. The causes of migraine appear multifactorial and are not fully understood. However, activation of the trigeminovascular system and sphenopalatine parasympathetic neurons and the resulting vasodilation of meningeal arteries have been associated with the development of migraine pain. Recently, the neurotransmitter and neurotrophic peptide pituitary adenylate cyclase activating polypeptide (PACAP) has been implicated in this migraine headache pathway. The effects of PACAP parallel those of other migraine inducing agents and notably PACAP induces vasodilation of the MMA concurrent with the genesis of migraine headache when administered to human subjects. The mechanisms by which PACAP induces dilation are presently unclear. The objective of this present work was to elucidate the signaling pathways linking PACAP to MMA dilation. To achieve this objective, we developed an ex vivo approach to study isolated MMA at physiologically relevant intravascular pressure. Using this preparation we found that PACAP dilates MMA at picomolar concentrations via PAC1 receptors. Further, in MMA, PACAP-induced dilation is mediated exclusively though activation of KATP channels. While investigating the mechanisms of PACAP-induced dilation of MMA we discovered that basal KATP channel activity influences MMA diameter. Inhibition of KATP channels with glibenclamide or PNU37883 at physiological intravascular pressure resulted in a vasoconstriction of ≈ 20 %. Also consistent with basal KATP activity, glibenclamide induced a membrane potential depolarization of ≈ 14 mV. Further, in MMA loaded with the ratiometric Ca2+ indicator, Fura-2-AM, glibenclamide-induced MMA constriction was correlated with a simultaneous increase in the ratio of 340 nm/380 nm excited fura-2 fluorescence, consistent with an increase in intracellular Ca2+. Vascular smooth muscle KATP channels can be phosphorylated and activated by PKA, resulting in membrane potential hyperpolarization. KT5720, a PKA inhibitor, induced a constriction in MMA similar to that of glibenclamide (≈ 25 %). Additional treatment with glibenclamide did not induce further constriction suggesting that PKA activity may underlie tonic KATP channel activation. Together these results suggest that tonic PKA activity underlies basal KATP channel activity and together play a key role in regulation of MMA diameter. In summary, results presented in this dissertation suggest that picomolar PACAP-induced dilation of MMA is via activation of the PAC1-Hop1 receptor splice variant and KATP channel activation. Furthermore, KATP channels are also involved in tonic regulation of MMA diameter due to basal PKA activity. These unique features of the MMA provide additional insight into potential therapeutic targets in the development of treatments for migraine.

Cardiovascular diseases (CVD) remain the most common cause of death in the United States. Additionally, peripheral artery disease affects thousands of people each year. A major underlying cause of these diseases is the occlusion of the coronary or peripheral arteries due to arteriosclerosis. To overcome this, a number of vascular interventions have been developed including angioplasty, stenting, endarterectomies and bypass grafts. Although all of these methods are capable of restoring blood flow to the distal organ after occlusion, they are all plagued by unacceptably high restenosis rates. While the biological reactions that occur as a result of each of these methods differ, the initiating factor of both the primary atherosclerosis and subsequent failure of vascular interventions appears to be intimal hyperplasia (IH). Intimal hyperplasia is most simply defined as the expansion of multiple layers of cells internally to the internal elastic lamina of the blood vessel. This excessive cellular growth leads to arterial stenosis, plaque formation and inflammatory reactions. Despite extensive research the underlying factors that cause IH remain unclear. A quantity of research to date has implicated endothelial cell mechanosensation as the mechanism by which IH is initiated with evidence positively correlating wall shear stress with IH. Others, however, have demonstrated that changes in the stresses applied to the wall in vitro can modulate IH independent of hemodynamic shear stress. Thus, relations between wall tensile stress and IH in vivo may shed light on the underlying mechanisms of IH. Since noninvasive measurement of wall tensile stress in vivo is difficult, it is most feasible to measure oscillatory wall strain which is intimately related to wall tensile stress through the mechanical properties of the arterial wall. In this dissertation, we hypothesize that reductions in oscillatory wall strain precede the formation of intimal hyperplasia in a murine model. To test our hypothesis, we first developed a novel, high spatial and temporal resolution method to measure oscillatory wall strains in the murine common carotid artery. We validated this method both in vitro using an arterial phantom and in vivo using a murine model of abdominal aortic aneurysms. To assess relationships between strain and IH, we applied our strain measurement technique to a recently developed mouse model of IH. In this model, a suture is used to create a focal stenosis and reduce flow through the common carotid artery by 85%; resulting in proximal IH formation. Using this approach, we identified a relationship between oscillatory strain reductions and IH. Subsequent analysis demonstrated that early reductions in mechanical strain just 4 days after focal stenosis creation correlate with IH formation nearly 1 month later. Since IH is not expected to form by day 4 in this model, we went on to assess changes in gross vascular morphology at day 4. We discovered that, although strains are significantly reduced by day 4, no significant IH can be observed, suggesting that changes in wall structure are resulting in strain reductions. At day 4 post-op, we observed cellular proliferation and leukocyte recruitment to the wall without intimal hyperplasia. These studies suggest that early reductions in mechanical strain may be an important predictor of IH formation. Clinically, this relation could be important for the development of novel techniques for predicting IH formation before it becomes hemodynamically significant.

No description available.