Exercise Protects the Heart Against Subsequent Pressure Overload

between TRX/TXNIP by hyperglycaemia, consistent with TRX repression by TXNIP. Conclusion. The thioredoxin system plays a key role in angiogenesis. Hyperglycaemia, by stimulating TXNIP, inhibits TRX with accompanying impairment in vascular network formation. TXNIP may therefore play a critical role in the pathogenesis of impaired angiogenesis in diabetes mellitus and may represent a novel therapeutic target. doi:10.1016/j.hlc.2007.06.512 Poster Session 55 Role of ␤-Adrenergic Stimulated Oxidative Stress and Inflammation in Cardiac Hypertrophy and Failure Q. Xu ∗ , L. Fang, H. Kiriazis, X.M. Gao, R.H. Ritchie, A.M. Dart, X.J. Du Baker Heart Research Institute, Melbourne, Australia Sympathetic nervous system (SNS) and ␤-adrenergic receptors (␤-AR) are tonically activated in heart failure (HF). Effectiveness of ␤-blockade in this setting indicates the critical roles of SNS/␤-AR in HF progression. In this study, we examined the relationship of sympathoadrenergic activation, reactive oxygen species (ROS) and inflammation in HF. Mice that overexpress ␤2 -AR in cardiomyocytes (␤2 -TG) developed dilated cardiomyopathy, fibrosis and HF with aging. Compared with wild type (WT) littermates, hearts of ␤2 -TG mice had increased superoxide production (14.2 ± 1.8 vs. 9.3 ± 0.8 RLU/mg s on lucigenin chemiluminescence, P < 0.05), upregulated gene expression of both NADPH oxidase (gp91phox subunit, 2.4 ± 0.6-fold WT) and inflammatory cytokines (TNF-␣, IL-1␤ and IL-6; 1.7 ± 0.3, 3.4 ± 0.7 and 9.1 ± 2.5-fold WT, respectively), as well as elevated MMP-2 activity (6.7 ± 0.5-fold, all P < 0.05 vs. WT, n = 7–9 per strain). We also observed an enhanced systemic inflammation in ␤2 -TG mice, evidenced by enhanced TNF-␣ and MMP-9 gene expression in circulating neutrophils (4.0 ± 0.6 and 3.1 ± 1.1-fold, respectively, both P < 0.05 vs. WT). Chronic pressure overload-induced hypertrophy elevated gene expression of TNF-␣, IL-1␤ and IL-6 (1.4 ± 0.2, 1.8 ± 0.2 and 12.4 ± 2.6-fold, respectively, all P < 0.05 vs. WT sham). In sharp contrast, disruption of both ␤1 - and ␤2 -ARs abolished cytokine upregulation (all P < 0.05 vs. WTcounterparts, n = 7–9 per group), which was associated with blunted hypertrophy and fibrosis and preserved LV function following chronic pressure overload. Collectively, these findings indicate that ROS and inflammatory cytokines are induced by sympathoadrenergic activation and likely contribute to progression of hypertrophy and HF. doi:10.1016/j.hlc.2007.06.513

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70 Age-related Differences in Post-infarct Cardiac Rupture and LV Remodelling Associated with MMPs Activation Y.N. Yang 1 , W. Han 1 , J. Li 1 , Y. Xiang 1 , F. Liu 1 , X. Ma 1 , J.F. Zhang 1 , Z. FU 1 , Y.T. Ma 1 , X.J. Du 2 , X.M. Gao 2,∗ 1 Xinjinag 2 Baker

Cardiovascular Research Institute, Urumqi, China Heart Research Institute, Melbourne, Australia

Background. Older age (>65 years) is an important risk factor for post-infarct cardiac rupture (PICR). Currently, it is little known the mechanisms responsible for such agerelated cardiac disorder. Methods. Male C57BL mice, aging at 3- and 12-mo were subjected to MI and followed up to day-7 after surgery. Incidence of PICR, degree of LV remodelling, inflammatory response, collagen content and MMPs activity were studied. Results. A higher incidence of PICR (40.7% vs. 18.3%, P = 0.013) and more severe LV remodelling and dysfunction, indicated by a lower FS% (80% vs. 64%), LV wall thinning (posterior wall thickness%, 18% vs. 51%) and chamber dilatation (LVEDd, 5.2 ± 0.1 vs. 4.3 ± 0.2 mm, all P < 0.05), were observed in old than in young mice despite a similar infarct size between the two groups (47 ± 2 vs. 44 ± 4%). Collagen type I and III contents in the infarct zone were higher in old than in young mice at day-3 and day-7 after MI, In the infarct area at day-3, a 14-fold increase of MMP9 level was detected in old versus a 11fold elevation in young mice (P < 0.05). A higher level of MMP9 in old mice was associated with a greater inflammatory cell density in the border zone of the infarct area (5804 ± 173 vs. 4045 ± 298, P < 0.01). Conclusion. A greater inflammatory cell infiltration and enhanced MMP9 level are likely to lead to more collagen degradation, therefore may be responsible for a higher incidence of rupture in old mice despite more collagen in aged heart. doi:10.1016/j.hlc.2007.06.514 71 Exercise Protects the Heart Against Subsequent Pressure Overload J.R. McMullen ∗ , X.M. Gao, H. Kiriazis, Z. Ming, K.A. Hewitt, J.P. Mollica, X.J. Du Baker Heart Research Institute, Commercial Road, Melbourne, Victoria, Australia Background. Physiological cardiac hypertrophy induced by exercise is usually beneficial in marked contrast to pathological hypertrophy which is associated with disease. The aim of the study was to examine whether exercise-induced cardiac hypertrophy can provide protection against a subsequent pathological insult, despite cessation of exercise prior to the insult. Methods. Ten week old mice were divided into two groups: untrained (un) and exercise trained (ex). Mice assigned to exercise were subjected to swim training for

ABSTRACTS

Heart, Lung and Circulation 2007;16:S211–S217

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Heart, Lung and Circulation 2007;16:S211–S217

Abstract

ABSTRACTS

4 weeks. At completion of the protocol, exercise trained and untrained mice were subjected to either pressureoverload [ascending aortic-constriction (AAC) to induce pathological hypertrophy] or the sham operation for 1 week. Results. Exercise-induced cardiac hypertrophy had a favourable effect on cardiac function in the pressureoverload model (fractional shortening (%); un-AAC: 43 ± 3, n = 6; ex-AAC: 56 ± 2, n = 6; P < 0.05), attenuated pathological growth and inhibited fibrosis (P < 0.05). Furthermore, markers of pathological hypertrophy (e.g. atrial and B-type natriuretic peptides) were significantly lower in aortic-banded hearts from exercise-trained mice than untrained mice. Conclusion. Exercise-induced cardiac hypertrophy provided sustained protection in a setting of pressure overload via beneficial effects on cardiac function, growth, and fibrosis. Examination of the “preconditioning” capacity of regular physical activity and the molecular mechanisms responsible for this phenomenon could provide new strategies to protect the heart form pathological insults. doi:10.1016/j.hlc.2007.06.515 72 What’s Inside a Ventricular Trabecula? P. Joshi, Q. Dollie, G. Sands, D. Gerneke, I. LeGrice, D. Loiselle ∗ Department of Physiology and Bioengineering Institute, University of Auckland, New Zealand Isolated ventricular trabeculae carnae are extensively used as generic models of cardiac muscle tissue in studies of heart function. An understanding of their structure is essential for the interpretation of results arising from such studies. Our aim was to quantify the relative proportions of myocytes, connective tissue and blood vessels constituting right-ventricular trabeculae carnae from adult rats. Hearts were Langendorff-perfusion-fixed with 3% formalin in a high osmolarity phosphate buffer. A trabecula was dissected from the right-ventricular free wall and embedded in a resin block. The block was fixed onto the translation stage of an extended-volume imaging system and its surface milled to expose the preparation in cross-section. The exposed surface was etched, stained with toluidine blue (myocytes), followed by ponceau de xylidine and acid fuchsin (connective tissue), and photographed using a digital camera attached to a compound light microscope with a 20×, 0.7 NA, water-immersion lens. The samples were milled at 20 ␮m intervals to obtain a series of sequential cross-sectional images. Images were segmented, based upon colour and intensity differences. The relative areas (mean ± 95% confidence limits, n = 8) were: 0.77 ± 0.028 myocytes, 0.11 ± 0.030 collagen and 0.11 ± 0.018 blood vessels. With the exception of those in the peripheral layer, essentially every myocyte had at least one immediately adjacent capillary while, on average, each capillary serviced two myocytes. Three-dimensional

reconstruction (at 1 ␮m intervals) of a 50 ␮m segment revealed that most axially aligned capillaries are interconnected, forming a reticulated microvascular network within the trabecula. doi:10.1016/j.hlc.2007.06.516 295a A Single 4 mg Dose of Nicotine Decreases Heart Rate Variability in Healthy Non-smokers N. Sjoberg, D.A. Saint ∗ School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, Australia Objective. To assess the cardiovascular effects of nicotine using heart rate variability (HRV) in non-smoking, healthy young adults. Methods. Twenty males and 20 females aged between 18 and 25 received 4 mg oral nicotine or placebo. HRV was assessed in 15 min periods before, during and after ingestion. Results. Nicotine significantly increased LF (females 65.36 ± 2.61 to 69.95 ± 2.67, p = 0.016: males 65.63 ± 2.27 to 70.35 ± 2.04, p = 0.014) and decreased HF (males 28.51 ± 2.23 to 24.32 ± 1.82, p = 0.013: females 27.19 ± 2.30 to 23.90 ± 2.35, p = 0.025). LF/HF ratio significantly increased in males (from 2.67 ± 0.27 to 3.44 ± 0.40, p = 0.016) and females (from 3.09 ± 0.47 to 3.86 ± 0.54; p = 0.016). HR increased in both (females 80.51 ± 2.8 vs. 78.06 ± 2.69; p = 0.0008: males 75.42 ± 2.25 vs 72.65 ± 2.02; p = 0.006). Conclusions. A single dose of 4 mg oral nicotine produces a significant reduction in heart rate variability in healthy young non-smokers consistent with a reduced vagal tone. This has implications for nicotine replacement treatments aimed at cessation of smoking. doi:10.1016/j.hlc.2007.06.517 295b Comparison of the Anti-Arrhythmic Effects of Lidocaine and Riluzole Immediately Post-Coronary Artery Occlusion in Pigs S.M. Weiss ∗ , P.W. Gage, W.B. Cowden The John Curtin School of Medical Research, Acton, Australian Capital Territory, Australia Background. Ischaemic events, such as heart attacks, make affected myocardium hypoxic, which opens persistent sodium channels and contributes to cellular sodium overload and subsequent calcium overload. This can give rise to early lethal ventricular arrhythmias. This study compared the anti-arrhythmic efficacy of lidocaine and riluzole (putative blockers of persistent sodium channels) in the early stages of myocardial ischaemia. Methods. Twenty-seven pigs (M + F, 20–35 kg) were divided into control (n = 10), lidocaine (n = 11) and riluzole (n = 6) groups. Under isoflurane anaesthesia (0.5–2% in oxygen), lidocaine (2.5–12 mg/kg plus 0.05–0.24 mg/kg/min iv) and riluzole (8 mg/kg ip) were