Thesis (MCur)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: A heart attack is a medical emergency and a life threatening disease. Patients with chest pain and a possible diagnosis of myocardial infarction require a detailed assessment and prompt medical management. The aim of the study was to determine the in-hospital delay in administrating thrombolytic therapy to patients with acute myocardial infarction (AMI) A mixed method with convergent parallel design was applied to the study. The population consisted of N=63 case notes of adult patients diagnosed with acute myocardial infarction and who had received thrombolytic therapy. The other population included (n=8) registered professional nurses working in the coronary care unit (CCU) of a tertiary hospital in the Western Cape. A record review was done using a data extraction form and semi-structured interview guide was used for data collection purposes. Reliability and validity was tested by the use of a nurse expert and a statistician. The nurse expert evaluated the data extraction form to ensure that all variables are included. A pilot study was done to test the data extraction form for errors. Ethical approval was obtained from the Health Research Ethics Committee of Stellenbosch University and permission to conduct the study was obtained from the management where the study was conducted. Informed consent was obtained from the participants. Data analysis was done by the researcher and a qualified statistician. Data was presented in the form of tables, histograms and frequencies. Analysis for the qualitative data was done by the researcher and the following themes were identified: cardiovascular nursing care, roles and responsibilities of nurses, scope of practice, perceptions of nurses on DNT and factors influencing DNT. Themes were presented in a form of a table and thereafter discussed extensively. Results: A total of 63 case notes of patients diagnosed with AMI were identified. The case notes were identified from the register kept in the CCU of the tertiary hospital. The case notes were of patients diagnosed with AMI and received thrombolytic therapy between the period of January 2009 to January 2014. A list of identified case notes was sent to Medical Records department for the retrieval of files. Once the files were retrieved, notes were obtained and used for data collection and analysis purposes (record review). Eleven (11) case notes could not be recovered, ten other case notes had incomplete data, two patients were thrombolysed at remote hospitals and one had a negative value after analysis. A total of 24 patients were excluded from the study. Only 39 patients were eligible for the study. The median door-to-needle time (DNT) of 30 minutes with a range between five to eighty five minutes was achieved. A door-to-needle time of 30 minutes or less was achieved in 23 (59.0%) of the patients; 56.25% of the patients arrived by ambulance and 43.75% used private transport. Of all the patients diagnosed, 24.5% had a pre-hospital ECG; more than 50% (n=30, 76.9%) of the population were smokers and 53.8% of the population had a risk factor of hypertension. The predominant infarct was inferior (61.5%), followed by anterior (38.5%). More than 70% of the patients were assessed by a junior registrar and only (23.1%) by the senior. Furthermore, (n=10, 25.6%) of the population was assessed by the junior registered professional nurse (RPN) and (n=29, 74.4%) by the senior RPN. Population had a median length in hospital of four days. Three patients died due to complications. The researcher read through all the transcriptions to achieve an overview of the interview. The aim was for the researcher to become immersed with the data. From the data, the researcher created codes and themes qualitatively and counted the number of times they occurred. Similar themes were grouped together and subthemes that emerged from the main themes were identified. The main themes identified were: cardiovascular nursing care, roles and responsibilities, scope of practice, perceptions of nurses on door-to-needle time (DNT) and factors influencing DNT. Conclusions: The majority of patients (74.4%) were assessed by a senior registered professional nurse (RPN) on presentation, yet (n=16) of the patients were not thrombolysed within 30 minutes. Patient, doctor, personnel, hospital and ECG factors influenced door-toneedle time in this study. Few nurses working in the CCU showed insight into DNT. The majority of the nurses reported that they have never seen a delay in DNT yet not all patients achieved a DNT of 30 minutes or less. No significant relationship was found between DNT and factors associated with DNT. There was no significant relationship between door-toneedle time and length of hospital stay p=0.40. Recommendations were made to improve patient care and management. / AFRIKAANSE OPSOMMING: ’n Hartaanval is ’n mediese noodgeval en ’n lewensgevaarlike siekte. Pasiënte met borspyn en ’n moontlike diagnose van miokardiale infarksie benodig ’n gedetailleerde assessering en vinnige mediese bestuur. Die doel van die studie was om die in-hospitaal vertraging in pasiënte met akute miokardiale infarksie (AMI) wat trombolitiese terapie benodig, te bepaal. ’n Gemengde metode is gebruik in die studie. Die populasie het bestaan uit N=63 gevalnotas van volwasse pasiënte wat gediagnoseer is met akute miokardiale infarksie en wat trombolitiese terapie ontvang het. Die ander populasie het bestaan uit (n=8) geregistreerde, professionele verpleegkundiges wat in die koronêre sorgeenheid van ’n tersiêre hospital in die Wes-Kaap werk. ’n Data-ontginningsvorm en semi-gestruktureerde onderhoude is gebruik vir data insamelingsdoeleindes. Betroubaarheid en geldigheid is getoets deur ’n verpleegkundige deskundige en statistikus. Die verpleegkundige deskundige het die dataontginningsvorm geëvalueer om te verseker dat alle veranderlikes ingesluit is. ’n Loodsstudie is onderneem om die data-ontginningsvorm vir foute te toets. Etiese toestemming is verkry van die Gesondheidsnavorsing-etiekkomitee van Stellenbosch Universiteit en toestemming om die studie uit te voer is van die bestuuur van die instansie waar die navorsing uitgevoer is, verkry. Ingeligte toestemming is van die deelnemers verkry. Data-analise is gedoen deur die navorser en ’n gekwalifiseerde statistikus. Data is aangebied in die vorm van tabelle, histogramme en frekwensies. Resultate: ’n Totaal van 63 gevalnotas van pasiënte gediagnoseer met AMI is geïdentifiseer. Elf (11) gevalnotas kon nie verkry word nie en tien ander gevalnotas het onvolledige inligting bevat, twee pasiënte is getrombolitiseer by afgeleë hospitale en een het ’n negatiewe waarde na analise gehad. ’n Totaal van 24 pasiënte is uitgesluit uit die studie. Slegs 39 pasiënte was in aanmerking vir die studie. Die median deur-tot-naald (DTN) tyd van 30 minute is bereik wat strek tussen vyf tot vyf-en-tagtig minute. ’n DTN tyd van 30 minute of minder is bereik in 23 (59.0%) van die pasiënte, 56.25% van die pasiënte het per ambulans aangekom en 43.75% het privaatvervoer gebruik. Van al die pasiënte gediagnoseer het 24.5% ’n prehospitaal EKG gehad, meer as 50% (n=30, 76.9%) van die populasie was rokers en 53.8% van die populasie het ’n risikofaktor vir hipertensie gehad. Die oorhersende infark was minderwaardig (61.5%), gevolg deur anterior (38.5%). Meer as 70% van die pasiënte is deur ’n junior registratrateur geassesser en slegs 23.1% deur die senior registrateur. Verder is 25.6% (n=10) van die populasie deur die junior professionele geregistreerde verpleegkundige geassesseer, en 74.4% (n=29) deur die senior geregistreerde verpleegkundige. Die populasie het ’n median lengte van verblyf van vier dae in die hospitaal gehad. Drie pasiënte is dood as gevolg van komplikasies. Konklusie: Die meerderheid van pasiënte (74.4%) is geassesseer deur ’n senior geregistreerde professionele verpleegkundige tydens aanbieding, alhoewel (n=16) pasiënte nie binne die eerste 30 minute getrombolitiseer nie. Pasiënt, dokter, personeel, hospitaal EKG was faktore wat deur-tot-naald tyd in die studie beïnvloed het. Min verpleegkundiges wat in die koronêre versorginseenheid gewerk het, het insig in DTN getoon. Die meerderheid van die verpleegkundiges het gerapporteer dat hulle nog nooit ’n vertraging in DTN gesien hiet nie, tog het nie alle pasiënte DTN in 30 minute of minder behaal nie. Geen beduidende verhouding is tussen deur-tot-naald tyd en lengte van verblyf in die hospital gevind nie (p=40). Aanbevelings is gemaak om pasiënt-behandeling en –bestuur te verbeter.

published_or_final_version / abstract / Medicine / Master / Master of Philosophy

published_or_final_version / abstract / Diagnostic Radiology / Master / Master of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

This exploratory study used Diagnostic Content Validity (DCV) and the Clinical Diagnostic Validation (CDV) models proposed by Fehring (1986) to clinically identify and validate the defining characteristics for Alteration in Tissue Perfusion: Cardiac. The literature based Kelly Cardiac Assessment Tool (KCAT) was designed as the data collection tool. The diagnostic content validity of the KCAT was 0.70. Twenty subjects, 18 years old and older were selected from a population who were admitted as inpatients in a southwestern university affiliated hospital. Data were collected through patient interviews, independent nurse assessment, and review of laboratory data. Using the steps described in Fehring's CDV model (1986) one major defining characteristic and 13 minor defining characteristics were clinically validated. The tool CDV score was 0.62. The nursing diagnosis Alteration in Tissue Perfusion: Cardiac was clinically validated and one major and 13 minor defining characteristics were identified.

Myocardial infarction activates the renin-angiotensin system, consequently upregulating aldosterone production that may stimulate pathological cardiac fibrosis via mineralocorticoid receptor (MR) activation. Results presented in this thesis were derived from an in vitro experimental model using cultures of human cardiac fibroblasts to study the effect of aldosterone on elastin production. They first confirmed that treatment with 1-50 nM of aldosterone leads to a significant increase in collagen type I production via MR activation. Most importantly, we discovered that treatment with 1-50 nM of aldosterone also increases elastin mRNA levels, tropoelastin synthesis, and elastic fiber deposition. Strikingly, pretreatment with MR antagonist spironolactone did not eliminate aldosterone-induced increases in elastin production. Interestingly, while cultures treated with elevated aldosterone concentrations (100 nM and 1 µM) showed a further increase (~3.5-fold) in collagen and (~3-fold) in elastin mRNA levels, they demonstrated subsequent increases only in the net deposition of collagen but not elastin. In fact, cultures treated with elevated aldosterone concentrations displayed a striking decrease in the net deposition of insoluble elastin, which could be reversed with spironolactone or with MMP inhibitors doxycycline or GM6001. Most importantly, we discovered that the pro-elastogenic effect of aldosterone involves a rapid increase in tyrosine phosphorylation of the insulin-like growth factor-I receptor (IGF-IR) and that the IGF-IR kinase inhibitor AG1024 or an anti-IGF-IR neutralizing antibody inhibits both IGF-I- and aldosterone-induced elastogenesis (Bunda et al., Am J Pathol. 171:809-819, 2007). Furthermore, we showed that the PI3 kinase signaling pathway propagates the elastogenic signal following IGF-IR activation and that activation of c-Src is an important prerequisite for aldosterone-dependent facilitation of the IGF-IR/PI3 kinase signaling. Results of explorative microarray analysis of 1 hour aldosterone-treated cultures revealed that aldosterone treatment upregulated expression of a heterotrimeric G protein, Gα13, that activates the PI3 kinase signaling pathway. We additionally demonstrated that aldosterone treatment transiently increases the interaction between Gα13 and c-Src and that siRNA-dependent elimination of Gα13 inhibited the pro-elastogenic effect of aldosterone. In summary, aldosterone, which stimulates collagen production in cardiac fibroblasts through the MR-dependent pathway, also increases elastogenesis via a parallel MR-independent pathway involving the activation of Gα13, c-Src, and IGF-IR/PI3 kinase signaling.

Glucocorticoids can reduce infarct size when given immediately after myocardial infarction (MI) but are detrimental when administration is continued into the post-infarct healing phase. A number of experimental studies have shown that reduction of infarct expansion by enhancing blood supply to the infarct border reduces remodelling and improves heart function post-MI. Previous experiments from this laboratory have shown that mice unable to locally regenerate corticosterone due to deficiency in 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) have an enhanced angiogenic response during myocardial infarct healing that is associated with improved cardiac function. We hypothesized that the enhanced angiogenic response in 11HSD1 knock out (-/-) mice would be preceded by augmented inflammation. Moreover this would be associated with improved cardiac function. This thesis aimed firstly to establish that murine cardiac phenotype was not influenced by 11HSD1 deficiency. 11HSD1-/- and C57Bl6 control mice had comparable cardiac structure and function. 11HSD1 expression was localised to fibroblasts and vascular smooth muscle cells in the myocardium. The second aim of this thesis was to characterise the healing response after MI in 11HSD1-/- mice compared to C57Bl6 mice. Neutrophil infiltration peaked 2 days after MI and was significantly enhanced in the 11HSD1-/- mice relative to C57Bl6 mice, despite comparable infarct size in both groups. This was followed by increased macrophage accumulation in the infarct border. Furthermore, in the 11HSD1-/- mice a greater proportion of macrophages were of the alternatively activated phenotype. Left ventricular expression of pro-angiogenic IL-8, but not VEGF, was increased. Cellular proliferation and vessel density at 7 days were greater in 11HSD1-/- compared to C57Bl6 hearts. This was associated with improved cardiac function 7 days post-MI. The third aim of this thesis was to determine whether the enhancement in vessel density and cardiac function was maintained beyond the initial wound healing phase. 11HSD1-/- mice retained the increased vessel density compared to C57Bl6 mice and these vessels were smooth muscle coated suggesting vessel maturation. This was associated with sustained improvement in cardiac function and modification of the scar characteristics. The final aim of this thesis was to establish whether the effect of the knock out could be recapitulated by administration of a small molecule inhibitor of 11HSD1 after MI. Oral administration of the 11HSD1 inhibitor had no effect on inflammation, angiogenesis and heart function as determined at 7 days post-MI relative to vehicle treated animals. In conclusion, the data confirm the enhancement in vessel density and cardiac function in 11HSD1-/- mice and demonstrate that this was preceded by enhanced inflammation. This was not due to an underlying cardiac phenotype or modification of the infarct size. Increased infiltration of alternatively activated macrophages may have been the source of pro-angiogenic factor, IL-8, which was also increased at the time of angiogenesis. Importantly the enhanced vessel density was retained 4 weeks after MI, these vessels were mature suggesting longevity and the improvement in cardiac function was retained. While pharmacological inhibition did not recapitulate the effect of the knock out this may have been due to route of administration. The data provides compelling evidence that further development and use of small molecule inhibitors of 11HSD1 may be of benefit post-MI.

Bakgrund Hjärtinfarkt är en vanligt förekommande sjukdom där livsstil påverkar risken att drabbas. Med livsstilsförändring inom områdena tobaksbruk, kostvanor, motion och alkoholkonsumtion kan en stor del av insjuknande i hjärtinfarkt förebyggas. Patientens attityd kan vara avgörande i arbetet med livsstilsförändringen. Syfte Syftet med litteraturstudien var att beskriva vilka faktorer som påverkar patienters attityder till eventuell livsstilsförändring efter hjärtinfarkt. Metod Studien är gjord som en litteraturöversikt baserad på 14 vetenskapliga artiklar med kvalitativ, kvantitativ och blandad ansats. Resultat Det framkom tio kategorier som enskilt eller tillsammans påverkade patientens attityd till livsstilsförändring. Faktorerna var rädsla, medvetenhet, stöd, självdisciplin, egna prioriteringar, fysiska hinder, tidsperspektiv, erfarenheter hämtade från omgivningen, vilja att återgå till tidigare fysisk kapacitet och livsåskådning. Slutsats Deltagarnas attityder påverkades tydligt av de framkomna faktorerna. En deltagare som fick stöd, hade medvetenhet om sitt tillstånd, viljan att återgå till tidigare fysisk kapacitet och hade god självdisciplin hade ökad motivation till att genomföra en livsstilsförändring efter hjärtinfarkten. I motsats till detta fanns fysiska hinder och tidsperspektiv som påverkade attityden negativt till att genomföra livsstilsförändring. Rädsla, egna prioriteringar och livsåskådning kunde påverka attityden till livsstilsförändring i både positiv och negativ riktning. / Background Myocardial infarction is a common disorder in which lifestyle affects risk. With lifestyle changes within physical activity, diets, tobacco use and alcohol consumption a great amount of myocardial infarction can be prevented. Patients´ attitudes can be crucial in the process of lifestyle change. Aim The aim of the study was to describe the factors that influence patients´ attitudes to potential lifestyle change after myocardial infarction. Method The study is designed as a literature review based on 14 scientific articles with qualitative, quantitative and mixed methods. Results Ten factors emerged that separately or together affected patients´ attitudes to lifestyle change. The factors were fear, awareness, support, self-discipline, own priorities, physical obstacles, perspective of time, experience collected from the entourage, desire to return to past physical capacity and conception of life. Conclusion The participants’ attitudes were clearly affected by the emerged factors. A participant who had support, awareness, desire to return to past physical capacity and had self-discipline had increased motivation to implement lifestyle change after myocardial infarction. In contrast physical obstacles and perspective of time affected the attitude negatively to implement lifestyle change. Fear, own priorities and conception of life could affect attitudes to lifestyle change in both positive and negative direction.

This report examines differences in risk of myocardial infarction and stroke (cardiovascular events) between the cyclooxygenase-2 (COX-2) inhibitors Rofecoxib, Celecoxib, and Valdecoxib, and the traditional nonsteroidal anti-inflammatory agents (NSAIDs) Naproxen and Ibuprofen, as well as Meloxicam, a preferential COX-2 inhibitor. The population studied was the DoD TRICARE beneficiary population greater than age 40 during the study period. In September of 2004, Rofecoxib was removed from the market due to an increased risk of cardiovascular events. In February of 2005, the Food and Drug Administration (FDA) examined the entire class of COX-2 inhibitors and recommended that Valdecoxib also be withdrawn from the market. According to Department of Defense TRICARE prescription records, COX-2 inhibitor prescription numbers were increasing rapidly and more than $7 million was spent on these agents alone in July of 2004. Logistic regression was used to analyze TRICARE prescription and diagnosis data from calendar years 2002, 2003, and 2004 for cardiovascular event risk comparisons among various NSAIDs. Rofecoxib was found to have a significantly increased risk of cardiovascular events when compared with all other medications in the study, including Valdecoxib. Odds ratios for comparison with Valdecoxib, Celecoxib, Meloxicam, Ibuprofen, and Naproxen were 1.09, 1.14, 1.15, 1.28, and 1.23. Valdecoxib showed a significant increase compared to Ibuprofen, Naproxen, and Celecoxib (odds ratios 1.21, 1.16, and 1.06). Ibuprofen showed a significantly decreased risk relative to all medications except Naproxen. When considering only cardiovascular risk, this study suggests prescribers should consider Ibuprofen or Naproxen as the primary agent of choice, with Meloxicam, and Celecoxib as reasonable second choices. Ultimately, the decision must also weigh the patient's risk of gastrointestinal side effects and cost of therapy.

Bakgrund : Vid hjärt- och kärlsjukdomar är kvinnor degraderade, de får sämre behandling jämfört med män, mindre forskning sker på kvinnor och de får oftare fel eller ingen diagnos. I och med att mannen varit normen och referensramen, behandlas även kvinnor efter samma kriterier. Kvinnors symtom på hjärtinfarkt skiljer sig från mannens. Syftet : Syftet med litteraturöversikten var att belysa kvinnors upplevelse av att drabbas av hjärtinfarkt. Metod : Studien genomfördes som en litteraturöversikt. Artiklarna söktes i databaserna Cinahl och PubMed vilket resulterade i elva kvalitativa artiklar. Resultat : Kvinnor upplevde fysiska symtom från olika delar av kroppen, det kan vara från mag-tarmkanalen, extremiteter och bröstregionen. De förnekar symtomen och försöker komma på orsaker till varför de uppstår. Vården ger bristfällig information och tar dem inte på allvar vilket leder till osäkerhet. Kvinnor mår fortfarande dåligt flera månader efter infarkten och har svårt att klara vardagen. De behöver stöd från familjen som kan stötta och finnas till, även om de inte alltid berättar hur de mår. Slutsats : Kvinnor upplever en rad olika symtom när de drabbas av hjärtinfarkt och symtom kan uppstå från olika delar på kroppen, inte bara i bröstregionen. De upplever också att vårdpersonalen ger bristfällig information och inte tar dem på allvar när de söker för sina symtom. Många kvinnor har kvarvarande symtom flera månader efter infarkten. / Background : When it comes to heart disease, women are degraded. Women get worse treatment, more often wrong or no diagnosis and research is less in women. As the man is the norm and reference the women also get treated after the same criteria. Women’s symptoms are different compered to men. Aim : The aim of this study was to explore women’s experiences of suffering from a myocardial infarction. Methods : The design is a literature review. Data collection occurred in the databases Cinahl and PubMed which resulted in eleven qualitative articles. Result s: Women experienced symptoms from different parts of the body, which may be from the gastrointestinal area, extremities and breast region. They deny the symptoms and try to find reasons why they occur. Care provides give lack of information and does not take them seriously, which causes women to feel insecure. Women still feel bad several months after the infarction and have difficulty coping with everyday life. They need support from the family that can give them support and help, although they do not always tell family how they feel. Conclusion : Women experience a variety of symptoms when they suffer from myocardial infarction, and symptoms may start from different parts of the body, not just in the breast region. They also experience that the caregiver provides inadequate information and do not take them seriously when they seek medical care. Many women have remaining symptoms several months after the infarction.