UBC Theses and Dissertations
MIBG uptake in the hypertensive-diabetic rat heart Herman, Lynda Michelle
Failure of the cardiovascular system, which is further exacerbated in the presence of hypertension, is considered the leading cause of death in diabetic individuals. Our aim in this study was to investigate the cardiac adrenergic neuronal changes induced by diabetes and hypertension, and then to correlate these changes with the contractile state of the myocardium. By using the radioactive agent, I-123 meta-iodobenzylguanidine (MIBG), which has the same uptake, storage and release mechanism as norepinephrine (NE), a non-invasive measurement of the integrity of the adrenergic nerve endings in heart and spleen was investigated. One week following streptozotocin (STZ) injection (55 mg/kg), male Sprague-Dawley rats were divided into two groups. They were given subcutaneous injections of either deoxycorticosterone-acetate (DOCA, 25 mg/kg) or DOCA vehicle twice weekly for 3, 6, 9, or 12 weeks, and received 0.9% saline with 0.5% KCl to drink. Rats were designated by their respective treatments for each time period: CON, DOCA, STZ, and STZ-DOCA. After 3, 6, 9, or 12 weeks of commencing DOCA or DOCA-vehicle treatment, MIBG was injected intravenously (15 mCi/mg). Five hours later the heart and spleen were dissected and counted with a gamma counter. Results were expressed as % Kg Dose and % Kg Dose/g. In similarly treated animals, after 12 weeks, the contractile function of the myocardium was studied using left ventricular papillary muscle preparations. Cardiac NE concentration was determined using HPLC with electrochemical detection. Although cardiac NE stores in STZ and STZ-DOCA were significantly increased from CON, results showed decreased MIBG uptake into the diabetic hearts at all time points compared to CON . There were no differences in MIBG values at any time point between STZ and STZ-DOCA. DOCA, STZ, and STZ-DOCA demonstrated significant reduction in MIBG accumulation in their left ventricles from 3 to 12 weeks. Length-tension studies revealed that with increasing preload tension the contractile performance in the STZ group was significantly diminished from CON between 4.5 g and 5.5 g. There were no significant differences between any of the other groups with increasing muscle length. None of the muscles responded well to the addition of either isoproterenol (1x10⁻¹⁰ to 1x10⁻⁴M) or tyramine (1x10⁻⁴ to 1x10⁻²M). From these results we concluded that either: 1) MIBG does not provide an accurate indication of adrenergic integrity; or 2) there is no correlation between sympathetic function and myocardial function after 12 weeks of DOCA or DOCA-vehicle treatment in diabetic rats. We also concluded that DOCA-induced hypertension does not significantly affect the sympathetic nervous activity or negatively affect myocardial functioning in diabetic animals.
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