Browsing by Author "Huisamen, B."
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- ItemA statement of intent on the formation of the NCRP on Cardiovascular and Metabolic Disease: A new initiative to fight heart disease, stroke, diabetes and obesity in South Africa(2007) Mayosi, B.; Bryer, A.; Lambert, V.; Levitt, N.; Noakes, T.; Ntsekhe, M.; Opie, L.; Rayner, B.; Zilla, P.; Abrahams, Z.; Abram, M.; Bhagwandin, N.; Bradshaw, D.; Dhansay, A.; Mbewu, A.; Madela-Mntla, N.; Parker, W-A.; Sifunda, S.; Skepu, A.; Steyn, N.; Brown, S.; Mollentze, W.; Brink, P.; Doubell, A.; Hough, S.; Huisamen, B.; Lochner, A.; Moolman-Smook, J.; Reuter, H.; Green-Thompson, W.; Horrocks, J.; Manga, P.; Norris, S.; Norton, G.; Raal, D.; Sliwa, K.; Woodiwiss, A.; Mntla, P.; Motala, A.; Naidoo, D.; Seedat, Y.; Ntutela, S.; Puoane, T.; Schwartz, P.[No abstract available]
- ItemMyocardial susceptibility to ischaemia/reperfusion in obesity : a re-evaluation of the effects of age(BioMed Central, 2017-03-17) Webster, I.; Salie, R.; Marais, E.; Fan, W. J.; Maarman, G.; Huisamen, B.; Lochner, A.Background Reports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory. The aim of this study was to re-evaluate the effects of age and diet-induced obesity (DIO) on myocardial I/R injury and preconditioning potential. Methods Four groups of Wistar male rats were used: age-matched controls (AMC) receiving standard rat chow for (i) 16 weeks and (ii) 16 months respectively; DIO rats receiving a sucrose-supplemented diet for (iii) 16 weeks and (iv) 16 months respectively. The ages of groups (i) and (iii) were 22 weeks (“young”) and groups (ii) and (iv) 17 months (“middle-aged”) at time of experimentation. Isolated perfused working hearts were subjected to 35 min regional ischaemia/1 h reperfusion. Endpoints were infarct size (tetrazolium staining) and functional recovery. Hearts were preconditioned by 3 × 5 min ischaemia/5 min reperfusion. Results were processed using GraphPad Prism statistical software. Results Age did not affect baseline heart function before induction of ischaemia and I/R damage as indicated by infarct size and similar values were obtained in hearts from both age groups. Age also had no effect on functional recovery of hearts during reperfusion after regional ischaemia in AMC rats, but cardiac output during reperfusion was better in hearts from middle-aged than young DIO rats. The diet reduced infarct size in hearts from young rats (% of area at risk: AMC: 32.4 ± 3.6; DIO: 20.7 ± 2.9, p < 0.05), with no differences in hearts from middle-aged rats (AMC: 24.6 ± 4.6; DIO: 28.3 ± 13.5, p = NS). Compared to their respective AMC, diet-induced obesity had no significant effect on functional recovery of hearts from both age groups after exposure to regional ischaemia. When exposed to the more severe stress of global ischaemia, the functional recovery potential of middle-aged DIO rats appeared to be impeded compared to hearts of young DIO rats, while age had no effect on the functional recovery of AMC hearts. Preconditioning reduced infarct size in hearts from young control rats and both middle-aged groups, but not from young DIO rats. Age had a significant effect on functional recovery in preconditioning: it was improved in hearts from young control and DIO rats, but depressed in both middle-aged groups. Conclusions The data showed that middle-age and obesity had no effect on baseline myocardial function and did not increase susceptibility to I/R damage upon exposure to regional ischaemia. On the contrary, obesity reduced I/R damage in young rats. Preconditioned aging hearts showed a decreased infarct size, but a reduction in functional recovery.
- ItemProtection of the ischaemic heart : investigations into the phenomenon of ischaemic preconditioning(Clinics Cardiv Publishing, 2009-02) Lochner, A.; Marais, E.; Genade, S.; Huisamen, B.; Du Toit, E. F.; Moolman, J. A.Exposure of the heart to one or more short episodes of ischaemia/reperfusion protects the heart against a subsequent prolonged period of ischaemia, as evidenced by a reduction in infarct size and an improvement in functional recovery during reperfusion. Elucidation of the mechanism of this endogenous protection could lead to the development of pharmacological mimetics to be used in the clinical setting. The aim of our studies was therefore to gain more information regarding the mechanism of ischaemic preconditioning, using the isolated perfused working rat heart as model. A preconditioning protocol of 1 × 5 or 3 × 5 min of ischaemia, interspersed with 5 min of reperfusion was found to protect hearts exposed to 25 min of global ischaemia or 35–45 min of regional ischaemia. These models were used throughout our studies. In view of the release of catecholamines by ischaemic tissue, our first aim was to evaluate the role of the alphaadrenergic receptor in ischaemic preconditioning. However, using a multi-cycle ischaemic preconditioning protocol, we could not find any evidence for alpha-1 adrenergic or PKC activation in the mechanism of preconditioning. Cyclic increases in the tissue cyclic nucleotides, cAMP and cGMP were found, however, to occur during a multi-cycle preconditioning protocol, suggesting roles for the beta-adrenergic signalling pathway and nitric oxide (NO) as triggers of cardioprotection. This was substantiated by the findings that (1) administration of the beta-adrenergic agonist, isoproterenol, or the NO donors SNAP or SNP before sustained ischaemia also elicited cardioprotection similar to ischaemic preconditioning; (2) beta-adrenergic blockade or nitric oxide synthase inhibition during an ischaemic preconditioning protocol abolished protection. Effectors downstream of cAMP, such as p38MAPK and CREB, were also demonstrated to be involved in the triggering process. Our next step was to evaluate intracellular signalling during sustained ischaemia and reperfusion. Our results showed that ischaemic preconditioned-induced cardioprotection was associated with a significant reduction in tissue cAMP, attenuation of p38MAPK activation and increased tissue cGMP levels and HSP27 activation, compared to non-preconditioned hearts. The role of the stress kinase p38MAPK was further investigated by using the inhibitor SB203580. Our results suggested that injury by necrosis and apoptosis share activation of p38MAPK as a common signal transduction pathway and that pharmacological targeting of this kinase offers a tenable option to manipulate both these processes during ischaemia/reperfusion injury.