The Cardioprotective and Gastro-Modulatory Effects of Verapamil on Streptozotocin-Induced Diabetic Rats

concentrated on determining whether HRV is affected in people with lowered eGFR and whether diabetes has an effect on HRV in mild/subclinical renal disease, that is 60 ml/min < eGFR < 90 ml/min but above 60 ml/min. Methods and Results: Fifty-five patients were included in this study. Patients were divided into two groups: Control (n = 45) and Diabetic (n = 10). A 20 min lead II ECG was recorded for each patient and analysed (Chart 5; ADInstruments). The control and diabetes group was further divided in to those with 60 ml/min < eGFR < 90 ml/min and those with an eGFR < 60 ml/min. No exclusion criteria were applied. Analysis of data was with ANCOVA (SPSS V17). Significance was set at p < 0.05. There was a significant (p = 0.0125) interaction between eGFR and diabetes status. Our results indicated that lowered eGFR did not affect HRV in nondiabetics but had an effect in people with diabetes. Discussion: Heart function was significantly related to diabetes and eGFR status even with clinically normal kidney function. This suggests that regular screening of kidney function and the presence of diabetic dysautonomia should be carried out from the time of diabetes diagnosis. http://dx.doi.org/10.1016/j.hlc.2012.05.179 170 The Cardioprotective and Gastro-Modulatory Effects of Verapamil on Streptozotocin-Induced Diabetic Rats S. Yesmine, D. Jackson, F. Coulson, A. Fenning ∗ CQ University, Rockhampton, Australia Calcium channel antagonists have been found to have positive effects on the course of cardiovascular dysfunction following diabetes. The aim of this study was to investigate the effects of chronic verapamil (V) administration 4 mg/kg/day (orally) on cardiovascular and gastrointestinal dysfunction following diabetes. Diabetes was induced in eight week-old, male Wistar rats by a single i.v. dose (65 mg/kg) of streptozotocin (S). Age-matched male Wistar rats were used as the control (C) with C + V, S and S + V treated groups with an eight-week treatment protocol. Tissue bath experiments included the isolated Langendorff heart, thoracic aortic ring preparations and sections of ileum. Diabetic rats showed a significant increase in blood glucose levels which was reduced by V treatment (C – 10.5 ± 1.6; S – 32.0 ± 1.0*; S + V – 27.8 ± 2.2** mmol/L). Verapamil treatment improved diabetes-induced decrease in left ventricular compliance as evidenced by an increased diastolic stiffness (C – 22.8 ± 0.7; S – 26.6 ± 0.9*, S + V – 24.1 ± 0.8) and a reduction in developed pressure (C – 107 ± 4.4; S – 76 ± 0.6*; S + V – 115 ± 1.8** mmHg) and end systolic pressure (C – 116 ± 4.4; S – 87 ± 7.3*; S + V – 127 ± 1.6** mmHg). Chronic V administration also improved both maximal contractile responses to NA and maximal endothelium-independent relaxation to SNP and endothelium dependent vasodilation to ACh. In isolated ileum, V improved the reduced contractile response to the muscarinic receptor agonist carbachol, however,

CSANZ 2012 Abstracts

S71

responses to pilocarpine and EFS in V-treated diabetic rats were significantly reduced. These results indicate that V does not improve altered neural M2 -muscarinic receptor function following diabetes. In conclusion, eight weeks of V dosing in diabetic rats significantly improved cardiovascular function together with a partial improvement in gastrointestinal responses following induced diabetes. http://dx.doi.org/10.1016/j.hlc.2012.05.180 171 The Effect of Long-Term Infusions of HDL Cholesterol in a Murine Model of Established Atherosclerotic Plaque J. Morton 1,2,∗ , C. Bursill 1 , D. Celermajer 1,2,3 , S. Bao 2 , M. Ng 1,2,3 1 The

Heart Research Institute, Australia of Sydney, Australia 3 Department of Cardiology, Royal Prince Alfred Hospital, Australia 2 University

Raising HDL cholesterol (HDL-C) has been shown to reduce the development of atherosclerosis in short-term animal studies targeting early-stage atherosclerosis. Two recent landmark studies of HDL raising in humans with established atherosclerosis have had neutral results. In this study we examine the effects of long-term ApoA-I intervention on established atherosclerosis in mice. Methods: At six weeks of age male ApoE knockout C57BL6 mice were placed on a high fat diet for 18 weeks. Mice (n = 25) then received ApoA-I infusions (40 mg/kg) three times/week for six weeks then two times/week for 10 weeks or saline (n = 28), whilst continuing on the high fat diet. At sacrifice: (1) Plaques in the descending thoracic aortas were examined for (i) atheroma size, (ii) smooth muscle cells, and (iii) macrophages using histology; and in a separate cohort, (2) Micro-CT scans of MicroFil infused aortas were assessed for (i) atheroma size and (ii) adventitial neovascularisation. Results: (1) There were no significant differences in ApoA-I mice and saline controls for (i) atheroma size (43.0 ± 3.6% vs. 38.8 ± 3.7%, p = 0.4), (ii) smooth muscle cell content (10.3 ± 2.1% vs. 7.8 ± 1.3%, p = 0.3), or (iii) macrophage content (36.2 ± 3.6% vs. 35.8 ± 3.3%, p = 0.9). (2) Similarly, micro-CT also revealed there were no significant differences in (i) atheroma size (69.6 ± 0.6% vs. 69.0 ± 0.5%, p = 0.4), or (ii) adventitial neovascularisation volume (0.26 ± 0.04 mm3 vs. 0.25 ± 0.02 mm3 , p = 0.95). Conclusion: Long-term delivery of high-dose ApoA-I had no effect on atherosclerotic lesion size or any markers of plaque stability (smooth muscle cell/macrophage content or neovascularisation) in a murine model of established atherosclerosis. http://dx.doi.org/10.1016/j.hlc.2012.05.181

ABSTRACTS

Heart, Lung and Circulation 2012;21:S1–S142