Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2006. / Introduction: Obesity, which is implicated in the development of the metabolic
syndrome (MS) is reaching epidemic proportions worldwide. MS significantly
increases the risk of developing cardiovascular disease, which includes
coronary artery disease. The current absence of animal models of diet induced
obesity and the MS makes the investigation of the cardiovascular
consequences of MS virtually impossible. As a result the effects of the MS on
cardiac function, morphology and susceptibility to ischaemia are not well
understood.
Aims: We set out to: 1) develop and characterize a rodent model of dietinduced
obesity and the MS, 2) investigate the susceptibility of hearts from
these animals to ischaemia/reperfusion induced injury and, 3) determine
whether angiotensin II (Ang II) and endothelin-1 (ET-1) plays a role in cardiac
remodelling and/or the severity of ischaemia and reperfusion injury in this
model.
Methods: Male Wistar rats were fed a standard rat chow diet or cafeteria diet
(CD) for 16 weeks. After the feeding period rats were sacrificed and blood and
myocardial tissue samples were collected to document biochemical changes in
these animals. Hearts were perfused on the isolated working rat heart perfusion
apparatus to assess myocardial mechanical function before and after
ischaemia. In a separate series of experiments, hearts underwent coronary
artery ligation to determine the incidence and duration of ventricular arrhythmias
during ischaemia and reperfusion, using electrocardiography. To assess a possible link between myocardial remodelling and ischaemia/reperfusion injury
and myocardial Ang II and ET-1 content, we also measured these peptides
under basal conditions and during ischaemia. Two-dimensional targeted Mmode
echocardiography was used to assess in vivo myocardial mechanical
function in control and obese rats.
Results: After 16 weeks on the CD, obese rats satisfied the World Health
Organization (WHO) criteria for the MS by having visceral obesity, insulin
resistance, dyslipidaemia and an elevated systolic blood pressure, compared to
control rats. Circulating Ang II levels, but not ET-1 levels, were elevated in CD
fed rats. Obese rats had cardiac hypertrophy and ex vivo basal myocardial
mechanical function was depressed in the CD fed rat hearts compared to
control rat hearts. CD fed rat hearts had poorer aortic output (AO) recoveries
compared to hearts from control rats. These hearts also had a higher incidence
and duration of reperfusion arrhythmias. No such functional differences were
seen in the in vivo experiments. No differences in basal or ischaemic
myocardial Ang II and ET-1 levels were seen in either group.
Conclusion: We have developed and characterized a model of diet-induced
obesity and the MS. Obesity is associated with cardiac hypertrophy and an
increased myocardial susceptibility to ischaemia and reperfusion injury in our
model. The hearts from obese rats were also more prone to reperfusion
ventricular arrhythmias. As myocardial function was only poorer in the ex vivo
obese animal experiments, our data suggests that the obesity associated
changes in function observed in the ex vivo studies may be related to the absence of circulating substrates or factors, which are essential for their normal
mechanical function.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/2446 |
| Date | 03 1900 |
| Creators | Smith, Wayne |
| Contributors | Du Toit, E. F., Moolman, J. A., University of Stellenbosch. Faculty of Health Sciences. Dept. of Biomedical Sciences. Medical Physiology. |
| Publisher | Stellenbosch : University of Stellenbosch |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | University of Stellenbosch |
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