The potential use of four radioiodinated fatty acids as myocardial imaging agents were evaluated. Preliminary distribution studies revealed that the terminal labeled fatty acids demonstrated higher myocardial uptake. Thus, 10-Iodocapric acid (10-iododecanoic) and 12-Iodolauric acid were subjected to further investigation. Comprehensive tissue distribution studies involving both radioiodinated fatty acids in mice indicated that the highest accumulation of the total injected activity occurred in the muscle and the blood. Other organs investigated included the heart, liver, lung, kidneys, spleen, stomach, intestines, bone and adrenals. The heart exhibited the highest concentration of the radioiodinated fatty acids for the relative accumulation of activity per unit weight. Erom the tissue distribution studies, the optimum scanning time was found to be immediately following injection of the radiopharmaceutical. Toxicity studies were performed in mice after intravenous administration of 10-Bromocapric acid and 12-Bromolauric acid. The LD₅₀ of Sodium Bromolaurate in 10% Human Serum Albumin was found to be 210 mg/kg (194 mg/kg - 228 mg/kg). The stability problem encountered with 10-Bromocapric acid necessitated the use of a different solvent system. The LD₅₀ obtained after intravenous injection was found to be 86.1 mg/kg (83.0 mg/kg - 89.3 mg/kg). However, this observed toxicity may not necessarily reflect the toxicity of the Bromocapric acid solely. Whole body excretion studies were performed in mice and revealed a triexponential excretion curve. For 10-Iodocapric acid, the effective half-lives were .90 hours (36.7%), 3.91 hours (61.6%) and 74.9 hours (14.5%). For 12-Iodolauric acid, the effective half-lives were 1.67 hours (46.6%), 7.68 hours (38.4%), and 71.6 hours (17.8%). For both 10-Iodocapric acid and 12-Iodolauric acid, the first as well as the second component of the excretion curve presumably represented a decrease in the whole body activity due mainly to urinary excretion. The third component appeared to represent activity which was tightly bound and slowly released. The third component presumably represented elimination by fecal excretion. The excretion of the injected activity was primarily in the urine, although some activity was recovered in the feces. For 10-Iodocapric acid, 82.4% of the injected activity had been recovered in the urine within the first 24 hours and 8.88% had been recovered in the feces. For 12-Iodolauric acid, 78.9% of the injected dose was recovered in the urine at 24 hours and 9.4% in the feces. From the urine results, the effective half-life of the radio-iodinated fatty acids in the kidneys was found to be 4.8 hours. Myocardial scans were done on rabbits using ¹³¹I-capric acid, ¹³¹I-lauric acid, NaI-131 (6% Human Serum Albumin), and Thallium-201 at specified time intervals after injection. Iodine-123, a radionuclide possessing more favorable imaging properties, was not readily available due to production problems at the time of scanning. The mean absorbed dose to the whole body, the liver, the kidneys, the muscle, and the heart were computed based on the results from the distribution and excretion studies. The dosimetry calculations were done using Iodine-123 as the radionuclide. For ¹³¹I-capric acid, the radiation doses were calculated as 34.76 mrads/2 mCi for the whole body, 136.3 mrads/2 mCi for the kidneys, 86.6 mrads/2 mCi for the liver, 38.5 mrads/2 mCi for the muscle, and 25.89 mrads/2 mCi for the heart. For ¹³¹I-lauric acid, the radiation doses were 41.73 mrads/2 mCi for the whole body, 199.8 mrads/2 mCi for the kidneys, 185.9 mrads/2 mCi for the liver, 52.07 mrads/2 mCi for the muscle, and 46.39 mrads/2 mCi for the heart. / Pharmaceutical Sciences, Faculty of / Unknown

This exploratory study examined the phenomenon of loss as expressed by the spouses of myocardial infarction patients. The purpose of the study was to describe the thoughts, feelings, actions and observable behaviours of the spouses from the initial impact of illness to six weeks post myocardial infarction and to develop a framework, based on the literature, which related the concept of loss to the experience of spouses of M.I. patients. The study was conducted with a convenience sample of 12 spouses, ten women and two men, whose partners had experienced their first myocardial infarction. Using a semi-structured interview guide with open-ended questions, the investigator interviewed each subject four times over a six week period; from the initial impact of illness to approximately six weeks post myocardial infarction. Each interview covered three content areas: thoughts, feelings and actions. Broad open-ended questions were used to elicit data on the spouses thoughts, feelings and actions. During the interview the investigator observed the verbal (type, quality, characteristics of speech, focus of conversation) and non-verbal (activity, eye contact, body language, appearance) behaviours of the spouses. An empirical inductive approach was used as the methodology for this study. Data coding and analysis were approached using the constant comparative method, an inductive method of discovering grounded theory developed by Glaser and Strauss (1967). The findings revealed that the spouses experienced behaviours in response to loss that were common and formed a pattern through time. Three distinct phases were identified: Phase I The Event and Initial Spousal Response; Phase II Reaction to the Event; Phase III Impact of the Event. The phases were described further in light of the constructs formulated from the literature review: (1) Reactions to Loss; (2) The Elements of Loss; (3) The Meaning of Loss. This study was designed to provide insight into understanding the event of a myocardial infarction within the context of the phenomenon of loss. The findings supported the use of a loss framework for assessing the reactions of spouses who are threatened with the death of their partner. Nurses are in a critical position to assist spouses experiencing loss. Implications and recommendations for nursing education, practice and research were delineated in light of the conclusions of the present study. / Applied Science, Faculty of / Nursing, School of / Graduate

Les nouvelles gamma-caméras à semi-conducteurs utilisant des détecteurs au CZT sont dédiées aux explorations cardiaques. Leurs sensibilité, résolution spatiale et en énergie nettement améliorées comparativement aux gamma-caméras conventionnelles sont une révolution en médecine nucléaire. Ces gamma-caméras utilisent de nouvelles géométries d’acquisition, de nouveaux algorithmes de reconstruction, et ouvrent de nouvelles perspectives dans les études simultanées en double-isotope de l’123I et du 99mTc, dont les pics énergétiques sont proches.Nous avons étudié l’impact de l’amélioration de la résolution en énergie en comparant deux modèles de gamma-caméras à détecteurs semi-conducteurs aux gamma-caméras conventionnelles. A l’aide d’études sur fantômes anthropomorphes et chez des patients porteurs d’insuffisance cardiaque, notre travail s’est concentré sur les acquisitions scintigraphiques (i) de la fonction ventriculaire gauche (99mTc) en présence d’123I, (ii) de la perfusion myocardique (99mTc) en présence d’123I (innervation), et (iii) du rapport cardiomédiastinal de la fixation d’123I- métaiodobenzylguanidine (123I-MIBG) lors d’acquisitions double-isotope (123I-MIBG/99mTc- tétrofosmine) chez les patients souffrant d’insuffisance cardiaque.Nos résultats montrent que la meilleure résolution en énergie des gamma-caméras CZT permet en étude double-isotope (i) une évaluation de la FEVG et du mouvement régional dans les différentes fenêtres d'énergie (123I ou 99mTc) et les types d'acquisition (simple- vs double-isotope), (ii) une évaluation simultanée et combinée de la perfusion (99mTc) et de l’innervation (123I) du myocarde, et (iii) l’évaluation du rapport cardiomédiastinal de la fixation d’123I-MIBG. Chacune de ces trois parties a fait l’objet d’une publication. / New dedicated-cardiac cameras using CZT detectors have dramatically transformed the routine of myocardial perfusion imaging. With a better count detection sensitivity, an improved spatial and energy resolution, they potentially enable combined assessment of myocardial innervation (123I) and perfusion (99mTc) within a single imaging session. These cameras images with different sharpness and contrast-to-noise ratios.Using two CZT cameras with anthropomorphic phantom, and clinical studies in heart failure patients, our work focused on (i) the left ventricular function assessment within the 99mTc window in presence of 123I, (ii) the evaluation of regional myocardial innervation (123I) and perfusion (99mTc) match and mismatch with single- (separate 123I and 99mTc acquisition) and simultaneous dual-isotope acquisitions, and (iii) the late heart-to-mediastinal ratio (HMR) of 123I-MIBG uptake determined using dual-isotope CZT acquisition with that determined using conventional planar imaging in patients with heart failure.Our results found no impact of the acquisition mode (single vs dual) or the type of CZT camera on 123I and 99mTc defect size and mismatch, LVEF, and HMR of 123I-MIBG uptake.This work provides a new step toward simultaneous dual-isotope acquisition for combined innervation, perfusion and ventricular function assessment.

Bakgrund: Hjärt- kärlsjukdom är i dag den främsta dödsorsaken i Sverige för både kvinnor och män. Hjärtinfarkt uppkommer när en åderförkalkning i hjärtats kranskärl brister och det bildas en propp. Kvinnors och mäns symtombild under den akuta fasen skiljer sig mycket åt och det kan även erfarenheterna efter hjärtinfarkten göra.   Syfte: Syftet med denna studie var att beskriva kvinnors erfarenheter efter att ha drabbats av en hjärtinfarkt.   Metod: En litteraturstudie baserad på elva kvalitativa studier. Artikelsökningen genomfördes i Cinahl, PubMed och APA PsycINFO. Därefter analyserades studierna med hjälp av Fribergs analysmodell.   Resultat: Resultatet visar att kvinnor kan uppleva olika erfarenheter efter en hjärtinfarkt. De upplevde fysiska-, psykiska-, sociala- och existentiella förändringar i vardagen och resultatet kunde delas in i tre kategorier och nio subkategorier. Kategorierna var: Påverkan på återhämtningen, Förändringar i det vardagliga livet och Förändrad syn på livet. Konklusion: Litteraturstudien visar att kvinnor upplevde hjärtinfarkten som en dramatisk omställning i livet. Flera olika symtom var vanligt förekommande och kunde hålla i sig i flera år. Kvinnorna lärde sig hantera och acceptera situationen efter en tid men var i behov av stöd från familj, vänner, vård och rehabiliteringsgrupper. / Background: Myocardial infarction is today the leading cause of death in Sweden for both women and men. Myocardial infarction occurs when atherosclerosis in the coronary arteries of the heart ruptures and a blockage forms. The symptoms of women and men during the acute phase are very different and so can the experiences after the myocardial infarction.  Aim: The purpose of this study was to describe women's experiences after suffering a myocardial infarction.  Methods: A litterature study based on eleven qualitative studies. The article search was conducted in Cinahl, PubMed and APA PsycINFO. The studies were then analyzed using Friberg’s analysis model.   Results: The results show that women can have different experiences after a myocardial infarction. They experienced physical, mental, social and existential changes in everyday life and the result could be divided into three categories and nine subcategories. The categories were; Impact on recovery, Changes in everyday life and Changed outlook on life. Conclusion: The literature study shows that women experienced the myocardial infarction as a dramatic change in life. Several different symptoms were common and could persist for years.  The women learned to handle and accept the situation after a while but were in need of support from family, friends, care and rehabilitationgroups.

Remodeling after myocardial infarction (MI) associates with left ventricular (LV) dilation, decreased cardiac function and increased mortality. The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play a significant role in myocardial remodeling post-MI. Expression of osteopontin (OPN) increases in the heart post-MI. Evidence has been provided that lack of OPN induces LV dilation which associates with decreased collagen synthesis and deposition. Inhibition of matrix metalloproteinases, key players in ECM remodeling process post-MI, increased ECM deposition (fibrosis) and improved LV function in mice lacking OPN after MI. This review summarizes — 1) signaling pathways leading to increased expression of OPN in the heart; 2) the alterations in the structure and function of the heart post-MI in mice lacking OPN; and 3) mechanisms involved in OPN-mediated ECM remodeling post-MI.

Background: Myocardial apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the myocardium from I/R injury. This study investigated the role of miR-214 in hypoxia/ reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R injury in vivo. Methods and Results: H9C2 cardiomyoblasts were transfected with lentivirus expressing miR-214 (LmiR-214) or lentivirus expressing scrambled miR-control (LmiR-control) respectively, to establish cell lines of LmiR-214 and LmiR-control. The cells were subjected to hypoxia for 4 h followed by reoxygenation for 24 h. Transfection of LmiR-214 suppresses PTEN expression, significantly increases the levels of Akt phosphorylation, markedly attenuates LDH release, and enhances the viability of the cells subjected to H/R. In vivo transfection of mouse hearts with LmiR-214 significantly attenuates I/R induced cardiac dysfunction and reduces I/Rinduced myocardial infarct size. LmiR-214 transfection significantly attenuates I/Rinduced myocardial apoptosis and caspase-3/7 and caspase-8 activity. Increased expression of miR-214 by transfection of LmiR-214 suppresses PTEN expression, increases the levels of phosphorylated Akt, represses Bim1 expression and induces Bad phosphorylation in the myocardium. In addition, in vitro data shows transfection of miR-214 mimics to H9C2 cells suppresses the expression and translocation of Bim1 from cytosol to mitochondria and induces Bad phosphorylation. Conclusions: Our in vitro and in vivo data suggests that miR-214 protects cells from H/R induced damage and attenuates I/R induced myocardial injury. The mechanisms involve activation of PI3K/Akt signaling by targeting PTEN expression, induction of Bad phosphorylation, and suppression of Bim1 expression, resulting in decreases in I/R-induced myocardial apoptosis.

Ataxia-telangiectasia mutated kinase (ATM) is a serine/threonine kinase. Mutations in the ATM gene cause a rare autosomal multisystemic disease known as Ataxia-telangiectasia (AT). Individuals with mutations in both copies of the ATM gene suffer from increased susceptibility to ionizing radiation, predisposition to cancer, insulin resistance, immune deficiency, and premature aging. Patients with one mutated allele make-up ~1.4 to 2% of the general population. These individuals are spared from most of the symptoms of the disease. However, they are predisposed to developing cancer or ischemic heart disease, and die 7-8 years earlier than the non-carriers. DNA double-strand breaks activate ATM, and active ATM is known to phosphorylate an extensive array of proteins involved in cell cycle arrest, DNA repair, and apoptosis. The importance of ATM in the regulation of DNA damage response signaling is fairly well-established. This review summarizes the role of ATM in the heart, specifically in cardiac remodeling following β-adrenergic receptor stimulation and myocardial infarction.

<p>Worldwide, more than 2 million patients die within 30 days after noncardiac surgery anually. Postoperative ischemic myocardial injury is frequent, however, no consensus exists about its definition.</p> <p><strong>Objective: </strong>to develop a term Myocardial Injury after Noncardiac Surgery (MINS) caused by myocardial ischemia, requiring at least, troponin T (TnT) elevation, and with prognostic relevance at 30 days after surgery.</p> <p><strong>Methods: </strong>we performed a prospective study including 15,167 patients ³45 years-old undergoing noncardiac surgery, who had fourth-generation TnT measurements during the first 3 postoperative days. We undertook Cox regression analyses with 30-day mortality after surgery as the dependent variable, using different TnT thresholds, clinical features and several perioperative variables. Non-ischemic etiologies were excluded. Furthermore, we developed a scoring system to predict risk in MINS patients.</p> <p><strong>Results:</strong> MINS was defined as TnT ≥0.03 ng/mL with or without clinical features, and it was an independent predictor of 30-day mortality (adjusted HR 3.82, CI 95% 2.84-5.10). We determined that MINS incidence was 8%, its population attributable risk 33.7%, and 30-days mortality rate 9.6%. Patients did not experience ischemic symptoms in 84% of MINS cases. Additionally, we developed a scoring system in patients suffering MINS with 3 independent predictors of death (age ≥75 years, new ST elevation or left bundle branch block, and anterior location of ECG changes),</p> <p><strong>Conclusion: </strong>Among patients undergoing noncardiac surgery, we defined MINS based on a TnT threshold ≥0.03 ng/mL. Mostly, MINS patients were asymptomatic. Therefore, this strongly suggests the importance of a troponin monitoring during the first few days after surgery.</p> / Master of Health Sciences (MSc)

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the degree of Master of Science in Medicine, 2014 / The earliest possible initiation of reperfusion therapy is necessary to reduce morbidity and mortality from acute STEMI. Therefore improving the time to thrombolysis where percutaneous coronary interventional facilities are limited or do not exist is critical. The most effective system would integrate three key components to deliver continuous patient care, including: 1) from time of call for help through to emergency response; 2) transportation to and admission to hospital; 3) assessment and initiation of thrombolytic therapy. The purpose of this prospective study is: to develop a chest pain awareness education programme appropriate for the South African context; to assess safe initiation of thrombolytic therapy by emergency care practitioners for STEMI; and to compare the performance of emergency care practitioner thrombolysis with historical control data.

Die kardiale Magnetresonanztomographie (MRT) ermöglicht nach einem akuten Myokardinfarkt (AMI) die Visualisierung und Quantifizierung der Myokardschädigung anhand verschiedener Parameter wie Ejektionsfraktion (EF), Infarktgröße, Mikrovaskuläre Obstruktion (MO) und „Myocardial Salvage Index“ (MSI). Anhand dieser MRT-Marker kann das Risiko für kardiovaskuläre Komplikationen eingeschätzt werden, was für die Weiterversorgung des Patienten sowie für die kardiologische Forschung von großem Interesse ist. In dieser Arbeit wurde die prognostische Relevanz der MRT-Parameter erstmals in einer großen, multizentrischen Studie untersucht. Zudem sollte unter den vier genannten MRT-Markern derjenige mit der größten prognostischen Aussagekraft ermittelt werden. Dazu wurden 795 Patienten aus der AIDA STEMI Studie einer MRT unterzogen und dann zwölf Monate lang im Hinblick auf den kombinierten Endpunkt „Major Adverse Cardiac Events“ (MACE; bestehend aus Tod, Reinfarkt und Klinikaufnahme wegen Herzinsuffizienz) nachbeobachtet. Die Ergebnisse belegen, dass die genannten MRT-Parameter prognostisch relevant sind und insbesondere die MO und die Infarktgröße einen Einfluss auf die Prognose ausüben, welcher über den Wert etablierter klinischer Risikomarker hinausgeht. Herausragende Bedeutung kommt dabei der MO zu, welche nach multivariater Analyse der potenteste MRT-Prädiktor für kardiovaskuläre Ereignisse ist. Somit sollten die MRT-Parameter in kommenden kardiologischen Studien als Surrogatmarker für klinische Endpunkte berücksichtigt werden. Zudem könnten sie für den klinischen Alltag die Möglichkeit bieten, die Patientenversorgung enger an die individuelle Prognose anzupassen.