Thesis (MScPhysio)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Aim: The aim of this study is to determine if the addition of a pre-extubation recruitment manoeuvre to standard care is safe and will improve lung compliance and subsequent PaO2/FiO2 (PF ratio) after extubation in postoperative coronary artery bypass graft surgery patients. Design: Prospective, triple blind, randomised, controlled trial. Method: This study was conducted in a private hospital in the Northern suburbs of Cape Town, South Africa. All patients admitted between 03/10/2010 and 22/11/2011, for uncomplicated elective coronary artery bypass graft (CABG) surgery were eligible for inclusion into the study. Patients were randomly allocated into either the intervention group or the control group. The intervention group received a gradual build-up lung recruitment manoeuvre (RM). The primary outcome was PaO2/FiO2 (PF ratio). The secondary outcomes were safety and static lung compliance. ICU length of stay (LOS) and hospital LOS were also recorded. The pre-RM hemodynamic stability of the patient was checked before the intervention and repeated at 5 minutes after the intervention by the nursing sister. Data to calculate static lung compliance was captured at the same time. Criteria for safety and discontinuation of the RM were monitored during the intervention by the principle investigator only. Results: Of the 69 patients eligible for the study 47 were randomly allocated into the intervention group (n=22) and control group (n=25) respectively. Groups were the same at baseline with regards to sex, pulmonary risk, sedation and surgical procedures. The RM could be completed in all patients. The prior defined criteria for discontinuation of the RM were not reached in any of the patients. No adverse effects were noted. The PaO2/FiO2 (PF ratio) decreased significantly in both groups from pre-surgery measurements compared to when measured before the RM (p<0.001). There was a tendency noted for the intervention group to return to pre-surgery measurements of PF ratio within 12 hours after extubation when compared to the control group. There was no significant difference between the groups from extubation to 24 hours (p = 0.6). The static compliance improved at 5 minutes following the RM (p<0.001) and remained improved until extubation (p<0.001) for the intervention group. No difference was noted in the static compliance of the control group over the same time period. The mean hospital length of stay for the intervention group was 8.61 (95% confidence interval 7.26 to 9.96 days) and 10.08 (95% confidence interval 8.52 – 11.63 days) for the control group. Conclusion: A gradual recruitment manoeuvre at 30cmH2O 30minutes before extubation significantly improved static lung compliance within 5 minutes with no adverse hemodynamic side effects. There was noted maintained improved PF ratio at extubation or immediately afterwards for the intervention group and no difference in the PF ratio between the intervention group and control group. / AFRIKAANSE OPSOMMING: Doel: Die doel van hierdie studie is om te bepaal of die toevoeging van ’n pre-ekstubasie herwinningstegniek tot standaard sorg veilig is, en of dit longvervormbaarheid en gevolglike PaO2/FiO2 (PF-verhouding) na ekstubasie in post-operatiewe kroonaaromleidingchirurgiepasiënte sal verbeter. Ontwerp: Prospektiewe, trippel-blinde, ewekansige, gekontroleerde proefneming. Metode: Hierdie studie is uitgevoer in ’n privaat hospitaal in die noordelike voorstede van Kaapstad, Suid-Afrika. Alle pasiënte wat tussen 03/10/2010 en 22/11/2011 gehospitaliseer is vir ongekompliseerde elektiewe kroonaaromleidingchirurgie, kon in aanmerking kom vir die studie. Pasiënte is op ewekansige wyse ingedeel in die intervensie- en kontrolegroepe. ’n Geleidelike-opbou-van-druk-longherwinningstegniek (HT) is op die intervensiegroep toegepas. Die primêre uitkoms was die PaO2 /FiO2 (PF-verhouding). Die sekondêre uitkoms was veiligheid en statiese longvervormbaarheid. ISE-verblyf en hospitaalverblyf is ook genoteer. Die navorsingsassistent het data van bestaande eenheiddokumentasie geneem. Die pre-HT-hemodinamiese stabiliteit van die pasiënte is gemonitor voor en weer 5 minute na die intervensie. Inligting om die statiese longvervormbaarheid te bereken is terselfdertyd genoteer. Kriteria vir veiligheid en vir die staking van die HT is gemonitor tydens uitvoering deur die primêre ondersoeker en die verpleegkundige. Resultate: Van die 69 pasiënte wat in aanmerking kon kom vir die studie is 47 op ewekansige wyse ingedeel in die intervensiegroep (n=22) en die kontrolegroep (n=25). Die groepe was dieselfde by die basislyn. Die herwinningstegniek kon volledig op alle pasiënte uitgevoer word. Die vooraf gedefinieerde kriteria vir staking van die HT is met geen pasiënte bereik nie. Geen nadelige uitwerking is genoteer nie. Die PaO2 /FiO2 (PF-verhouding) het beduidend verminder in beide groepe van pre-operatiewe metings in vergelyking met meting voor die HT (p<0.001). ‘n Neiging is genoteer dat die intervensiegroep binne 12 uur na ekstubasie tot pre-chirurgie PF-metings teruggekeer het. Daar was geen merkbare verskil tussen die groepe vanaf ekstubasie tot 24 uur (p=0.6) nie. Die statiese vervormbaarheid het verbeter teen 5 minute na HT (p<0.001) en het verbeter gebly tot ekstubasie (p<0.001) vir die intervensiegroep. Daar was geen verskil in die statiese vervormbaarheid van die kontrolegroep nie. Die gemiddelde hospitaalverblyf vir die intervensiegroep was 8.61 (95% betroubaarheidsinterval 7.26 tot 9.96 dae) en 10.08 (95% betroubaarheidsinterval 8.52 – 11.63 dae) vir die kontrolegroep. Gevolgtrekking: ’n Geleidelike herwinningstegniek teen 30cmH2O 30 minute voor ekstubasie het statiese longvervormbaarheid beduidend verbeter binne 5 minute, met geen nadelige hemodinamiese newe-effekte nie. Daar was geen verskil in die oksigenasie-indeks tussen die intervensie- en kontrolegroep na ekstubasie nie.

Thesis (MA)--University of Stellenbosch, 2000. / ENGLISH ABSTRACT: It is well known that coronary bypass graft surgery influences the psycho-social adjustment of the patient, but little is known about the effect of bypass surgery on the family members of the patient. The primary aim of this study was to assess the effect of coronary bypass graft surgery on certain aspects of the marital relationship and family functioning of the patient. The secondary aim was to determine which coping strategies families used during the two months after the operation. An experimental pre-test and post-test research design was used. Data during the first measure was collected by means of Biographical, Enriching and Nurturing Relationship Issues, Communication and Happiness (ENRICH)- and Family Adaptability and Cohesion Evaluation Scale-II (FACES II)-questionnaires, which were completed by the patient, the spouse of the patient and the eldest child still living with the parents. ENRICH-, FACES 11-and Family Crisis Oriented Personal Evaluation Scales (F-COPES)-questionnaires were used during the second measure which was conducted two months after the operation. The results indicated that bypass surgery affected the patients' marital satisfaction and communication negatively and changed their attitudes toward the division of new roles in the marriage and family. Bypass surgery had a further negative influence on the emotional bonding of the patients and their spouses with other members of the family. The patients' adaptability regarding new challenges facing the family was also negatively affected. The patients in the experimental group who were still working also showed a greater decline than the retired patients with regards to some of the measured variables. The coping strategies most often used by the families were the seeking of spiritual support and the reframing of the problem. Correlation coefficients between changes in the marital and family variables of the patient and the coping strategies used indicated that if passive appraisal was used, the patients' marital satisfaction would decrease and if reframing of the problem was used, the patients' adaptability regarding new challenges facing the family would increase. / AFRIKAANSE OPSOMMING: Alhoewel kroonaarsiektes die psigo-sosiale aanpassing van die pasiënt beïnvloed, bestaan daar min inligting oor die invloed wat kroonaarhartomleidingchirurgie op die huweliksverhouding en gesinsfunksionering van die pasiënt het. Die doel van hierdie ondersoek is om te bepaal hoe kroonaarhartomleidingchirurgie sekere aspekte van die pasiënt se huweliks- en gesinslewe beïnvloed. Verder het die ondersoek ten doelom te bepaal watter coping-strategieë die gesin post-operatief gebruik. Daar is van 'n eksperimentele voor- en na-metingnavorsingsontwerp gebruik gemaak. Data is ingesamel met Biografiese, Enriching and Nurturing Relationship Issues, Communication and Happiness (ENRICH)- en Family Adaptability and Cohesion Evaluation Scale-II (FACES II)-vraelyste wat gedurende 'n voormetingsgeleentheid deur die pasiënt, huweliksmaat van die pasiënt en oudste kind wat nog in die huis bly, voltooi is. Die na-meting, wat bestaan het uit die voltooing van ENRICH-, FACES 11-en Family Crisis Oriented Personal Evaluation Scales (F-COPES)-vraelyste, het twee maande na die operasie plaasgevind. Die resultate toon dat kroonaarhartomleidingchirurgie die pasiënte se huwelikstevredenheid en -kommunikasie nadelige beïnvloed het en 'n veranderinge in hul houding oor die rolverdeling in die huwelik en gesin teweeg gebring het. Verder het die operasie 'n nadelige effek op die pasiënte en hul huweliksmaats se gevoel van emosionele binding met ander gesinslede gehad. Die pasiënte se vermoë om by nuwe eise en uitdagings wat aan die gesin gestel word aan te pas, is ook nadelig beïnvloed. Verder is bevind dat die werkende pasiënte 'n groter verandering as die afgetrede pasiënte ten opsigte van sekere van die gemete veranderlikes getoon het. Die coping-strategieë wat die meeste deur die gesinne gebruik is, is die soeke na geestelike ondersteuning en die herdefiniëring van die probleem. Die resultate het ook aangedui dat as passiewe waardering as coping-strategie gebruik word, die pasiënte se tevredenheid met hul huwelik sal afneem. Verder sal gesinne se vermoë om by nuwe eise en uitdagings wat aan die gesin gestel word aan te pas, toeneem indien herdefiniëring van die probleem as coping-strategie gebruik word.

published_or_final_version / Community Medicine / Master / Master of Public Health

Cognitive impairment in coronary artery disease (CAD) patients can predict poorer quality of life, dementia, and increased mortality. This study aimed to determine the association between long-term cortisol elevations and cognitive function in CAD patients. Participants were recruited at the beginning of a 1 year cardiac rehabilitation program and followed forward. Composite Z-scores were computed from tests measuring memory and executive function at baseline and 1 year. Cortisol deposition (3 months) was measured from a 20 mg, 3 cm hair sample. Analyses of covariance showed less improvement in memory function (F1,50=4.721, p=0.035) but not executive function (F1,49=0.318, p=0.575) in patients dichotomized into a high cortisol group based on a previously established reference range. Prolonged cortisol elevation may be associated with cognitive changes in subjects with CAD.

Cognitive impairment in coronary artery disease (CAD) patients can predict poorer quality of life, dementia, and increased mortality. This study aimed to determine the association between long-term cortisol elevations and cognitive function in CAD patients. Participants were recruited at the beginning of a 1 year cardiac rehabilitation program and followed forward. Composite Z-scores were computed from tests measuring memory and executive function at baseline and 1 year. Cortisol deposition (3 months) was measured from a 20 mg, 3 cm hair sample. Analyses of covariance showed less improvement in memory function (F1,50=4.721, p=0.035) but not executive function (F1,49=0.318, p=0.575) in patients dichotomized into a high cortisol group based on a previously established reference range. Prolonged cortisol elevation may be associated with cognitive changes in subjects with CAD.

Angiogenic cell therapy is currently being developed as a treatment for coronary artery disease (CAD); however, endothelial dysfunction (ED), commonly found in patients with CAD, impairs the ability for revascularization to occur. We hypothesized that culture on a collagen matrix will improve survival and function of circulating progenitor cells (CPCs) isolated from a mouse model of ED. Overall, ED decreased the expression of endothelial markers in CPCs and impaired their function, compared to normal mice. Culture of CPCs from ED mice on collagen was able to increase cell marker expression, and improve migration and adhesion potential, compared to CPCs on fibronectin. Nitric oxide production was reduced for CPCs on collagen for the ED group; however, CPCs on collagen had better viability under conditions of serum deprivation and hypoxia, compared to fibronectin. This study suggests that a collagen matrix may improve the function of therapeutic CPCs that have been exposed to ED.

The endothelial nitric oxide synthase (eNOS) co-factor tetrahydrobiopterin (BH4) has been shown to play a pivotal role in maintaining endothelial function in experimental vascular disease models. In BH4-deficient states, eNOS becomes enzymatically ‘uncoupled’, generating reactive oxygen species instead of nitric oxide, thus promoting endothelial dysfunction. In humans with coronary artery disease (CAD), higher vascular BH4 levels have been shown to be associated with improved endothelial function, and genetic variation in endogenous BH4 synthesis has implicated a causal role. Accordingly, BH4 has been proposed as a potential therapeutic target in vascular disease states. The work in this thesis aims to further elucidate the roles of exogenous and endogenous BH4 in humans. In a randomised, placebo-controlled clinical trial of oral BH4 therapy in patients with CAD, exogenous BH4 had no effect on endothelial function or vascular oxidative stress. Subsequent pharmacokinetic and pharmacodynamic analysis revealed that oral BH4 significantly augmented BH4 levels in plasma and in venous tissue (but not in arterial tissue), but also increased levels of the oxidation product dihydrobiopterin (BH2), which lacks eNOS cofactor activity. Thus, there was a null effect on overall biopterin redox status. To further understand the mechanics of exogenous BH4 oxidation, ex vivo studies of human blood and vascular tissue demonstrated that exogenous BH4 is very rapidly oxidised to BH2; co-administration with an antioxidant had only a modest effect on preventing BH4 oxidation in blood, with no beneficial effect on biopterin redox state in the vasculature. Finally, using a “Mendelian randomisation” approach, I studied the effects of a haplotype of GCH1 (the gene encoding the rate limiting enzyme in BH4 synthesis) on endogenous BH4 bioavailability and vascular function in healthy individuals. In patients with CAD, this haplotype has been associated with decreased BH4 bioavailability and eNOS uncoupling, however in healthy individuals the haplotype exerted no significant effect, likely due to reduced inflammatory stimulation of GCH1.

No description available.

Heart disease is a major cause of morbidity and mortality in the United States with coronary artery disease (CAD) representing more than half of all cardiovascular events. Stable patients presenting with symptoms suggestive of CAD are likely to undergo either an exercise ECG and/or imaging study as a first line diagnostic assessment. A cardiopulmonary exercise test (CPX) is an ECG stress test plus ventilatory gas analysis. Recently CPX has been used to detect exercise-induced myocardial ischemia suggestive of underlying CAD. Currently there are a number of diagnostic tests available for the identification of CAD with the most widely used being exercise ECG, myocardial perfusion imaging (MPI) and cardiac catheterization. Exercise ECG, although inexpensive, has a number of well-recognized limitations, including low sensitivity resulting in false positive results. MPI and catheterization are more accurate but also more invasive and expensive. It appears that CPX may improve the diagnostic accuracy of exercise ECG in a cost effective manner.

Os pacientes portadores de afecções ateroscleróticas das artérias coronárias, que necessitam tratamento odontológico sob anestesia local com vasoconstritor, constituem um grupo especial de manejo por múltiplos aspectos. Trata-se de doença que pode apresentar, nestas circunstâncias, complicações com potencial de gravidade como: arritmias, angina instável e até mesmo infarto agudo do miocárdio. O cirurgião-dentista diante destes riscos deve conhecer as soluções anestésicas, bem como as interações medicamentosas e eventuais repercussões cardiovasculares. Objetivos: avaliar a ocorrência das seguintes variáveis detectoras de isquemia miocárdica durante ou após o tratamento odontológico:1) alterações do segmento ST avaliadas pelo sistema Holter; hipocontratilidade do ventrículo esquerdo pela Doppler-ecocardiografia e elevação dos marcadores bioquímicos; 2) precordialgia, arritmias e insuficiência mitral. Métodos: Os pacientes coronariopatas eram submetidos à exodontia sob anestesia local com ou sem vasoconstritor, divididos em dois grupos (sorteio por envelope). Em todos praticava-se monitoração eletrocardiográfica com Holter por 24 horas; Doppler-ecocardiograma antes e após intervenção odontológica e dosavam-se os marcadores bioquímicos antes e 24 horas após a exodontia (CKMB massa, CKMB atividade e troponina T). Aferia-se, também, a freqüência cardíaca e a pressão arterial nas fases pré, pós-anestesia e pós-exodontia. A Doppler-ecocardiografia avaliava a contratilidade segmentar do ventrículo esquerdo e a eventual ocorrência de insuficiência mitral. Resultados: 54 pacientes com doença coronária comprovada por cinecoronariografia e com indicação de extração dentária foram incluídos no estudo, no período de maio de 2004 a maio de 2005. Os casos foram divididos em dois grupos: grupo I com 27 pacientes tratados sob anestesia local com vasoconstritor e grupo II, 27 casos sem vasoconstritor. A média das idades no grupo I foi 58 (DP 7,98) anos e no grupo II de 55 anos (DP 8,57); 59,3 por cento eram do sexo masculino no grupo I e 66,7 por cento no grupo II; 66,6 por cento apresentaram infarto do miocárdio prévio com ou sem supradesnivelamento do segmento ST no grupo I e 77,7 por cento no grupo II. No grupo I a média de dentes extraídos foi de 1,6 dentes por paciente (DP 0,96) e 1,8 dentes por paciente (DP 1,21) no grupo II e a média de tubetes anestésicos por paciente no grupo I foi 1,5 tubetes (DP 0,87) e 1,8 tubetes (DP 0,79) no grupo II. Três pacientes do grupo I apresentaram depressão do segmento ST (1,0 mm), durante a aplicação da anestesia, e em nenhum deles verificou-se presença de isquemia avaliada pelos outros métodos; dois outros pacientes do mesmo grupo I tiveram elevação da CKMB massa. No estudo não se observou ocorrência ou agravamento de hipocontratilidade segmentar do ventrículo esquerdo, precordialgia, arritmias ou insuficiência mitral. Conclusão: Exodontia praticada sob uso de anestesia com epinefrina 1:100.000 não implica em riscos isquêmicos adicionais, uma vez que realizada com boa técnica anestésica e manutenção do tratamento farmacológico prescrito pelo cardiologista / Background: Patients with coronary artery disease, needing odontological treatment under local anesthesia with vasoconstrictor agents, comprised a special group to manage because of multiple aspects. In this situation, cardiovascular disease can be presented with serious complications, such as: arrhythmias, unstable angina and even acute myocardial infarction. The dental practioner facing these controversies must know the anesthesical solutions, drug interactions and possible cardiovascular repercussions. Objectives: To evaluate the occurrence of myocardial ischemic parameters during or after the odontological treatment such as: 1) ST-segment changes evaluated by Holter system, left ventricular hypocontractility by Doppler-echocardiography and serium biomarkers elevation; 2) angina pectoris, arrhythmias and mitral insufficiency. Methods: The coronary patients were submitted to dental extractions under local anesthesia with or without vasoconstrictor and were divided into two groups according to randomization. All patients were monitor with Holter throughout 24 hours; Doppler-echocardiograms were done before and after odontological interventions and the biochemical markers were measured before and 24 hours after the dental extractions (CKMB mass, CKMB activity and Troponin T). Besides that, cardiac rate and blood pressure were also measured pre and post-anesthesia and post-dental extractions. The Doppler-echocardiograms were done to evaluate the left ventricular contractility and possible mitral insufficiency. Results: Between May 2004 and May 2005, fifty-four patients with coronary artery disease and with indication for dental extraction were included in this study. Patients were equally divided into two groups: 27 patients treated with local anesthesia with vasoconstrictor (group I) and 27 patients without vasoconstrictor (group II). The mean age of group I was 58 years old (SD 7.98) and of group 2 was 55 years old (SD 8.57); male gender was 59.3 per cent in group I and 66.7 per cent in group II; 66.6 per cent had previous myocardial infarction with or without ST elevation in group I and 77.7 per cent in group II. In group I the mean dental extraction was 1.6 teeth per patient (SD 0.96) and 1.8 teeth per patient (SD 1.21) in group II. The mean number of anesthesic tubes per patient were 1.5 tubes (SD 0.87) and 1.8 tubes (SD 0.79) for groups I and II, respectively. Three patients from group I had ST-segment depression (1.0 mm) during the anesthesia application, and in none of these patients were observed any other ischemic method. Two other patients from group I had CKMB mass elevation. In none of the patients was observed left ventricular hypocontractility, angina pectoris, arrhythmias or mitral insufficiency. Conclusions: The dental extraction performed under the use of anesthesia with epinephrine 1:100,000 do not cause additional ischemical risks, since it is done with good anesthesical technique and maintenance of the pharmacological treatment prescribed by the cardiologist