ABSTRACTS Heart, Lung and Circulation S87 2012;21:S1–S142 CSANZ 2012 Abstracts weight/body weight ratio was greater in STNx + MI com- pared to STNx + Sham animals (p < 0.05), despite no difference in blood pressure (204.9 ± 11.6 in STNx + MI vs 221.8 ± 9.1 mmHg in STNx + Sham). In the non- infarct zone of the LV, STNx+MI animals demonstrated greater cardiomyocyte cross-sectional area (840.0 ± 29.3 vs 700.7 ± 24.7 m 2 ) and increased cardiac interstitial fibrosis (13.3 ± 2.7% vs 7.4 ± 0.9%) compared to STNx + Sham ani- mals (p < 0.01 and p < 0.05 respectively). Despite no further deterioration in renal function, increased renal interstitial fibrosis in the non-infarct zone was observed in STNx + MI (8.4 ± 0.6%) compared to STNx + Sham (5.5 ± 0.8%) ani- mals (p < 0.05). Conclusions: Myocardial infarction accelerated subtotal nephrectomy–induced cardiac hypertrophy, fibrosis and dysfunction as well as renal fibrosis; all of these effects were BP-independent. This study demonstrates that STNx followed by MI is a potentially useful animal model to assess the pathophysiology and mechanisms underlying CRS. http://dx.doi.org/10.1016/j.hlc.2012.05.219 210 Nitroxyl (HNO), The Novel Redox Sibling of NO • , Enhances Left Ventricular (LV) Function and Coronary Flow via Thiol-Sensitive and cGMP-Dependent Actions: Impact of Diabetes R. Ritchie 1,3,∗ , K. Chin 1,2 , C. Qin 1 , N. Cao 1 , B. Kemp- Harper 3 , O. Woodman 2 1 Baker IDI Heart & Diabetes Institute, Australia 2 RMIT University, Australia 3 Monash University, Australia The cardioprotective actions of HNO include potent enhancement of LV function and vasodilatation; both cGMP and CGRP are putative mediators of HNO actions. In the diabetic heart, impaired LV function is accompa- nied by impaired inotropic responsiveness, but the impact of diabetes on cardiac HNO effects is unknown. In the present study, hearts from adult male Sprague-Dawley rats were Langendorff-perfused at constant pressure. Dose-response curves to the HNO donor Angeli’s salt were performed following preconstriction with U46619 to ∼50% of baseline coronary flow. In normal hearts, Angeli’s salt (10 pmol to 10 mol) elicited significant dose- dependent increases in LV systolic pressure, LV developed pressure, LV end-diastolic pressure, LV ± dP/dt, and coro- nary flow. These effects were significantly inhibited by co-administration of the HNO scavenger L-cysteine (4 mM) or the soluble guanylyl cyclase inhibitor ODQ (10 M), but were insensitive to the CGRP antago- nist CGRP 8–37 (0.1 M). The positive inotropic effects of Angeli’s salt remained evident in hearts isolated from rats subjected to eight weeks streptozotocin diabetes (albeit slightly blunted); whereas diabetes markedly impaired inotropic responsiveness to isoprenaline (0.1 nmol). The enhanced LV diastolic function elicited by Angeli’s salt was preserved in diabetic hearts, whilst the vasodilator actions were markedly attenuated. Our results demonstrate that the inotropic and vasodilator effects of Angeli’s salt are mediated by HNO and cGMP, but not CGRP. HNO donors may represent additional options for inotropic support for the diabetic heart. http://dx.doi.org/10.1016/j.hlc.2012.05.220 211 PDH Adaptation and Dysfunction in the Failing Human Heart F. Sheeran ∗ , S. Pepe Murdoch Childrens Research Institute, Australia Metabolic adaptation and remodelling in myocardial cells following low oxygen stress, in order to attain an increase in metabolic efficiency, often involves reversion to a foetal metabolic phenotype in adult heart. One major metabolic pathway regulator is pyruvate dehydrogenase (PDH) which acts as the gateway between the glycolytic and Krebs cycles and is crucial to NADH delivery to mitochondrial respiratory protein Complex I. Despite extensive studies of PDH activity in disease, PDH function in failing human heart is not well studied. Methods: Left ventricular samples from human non- failing (n = 20) and end-stage failing (n = 20) adult human hearts were assayed for PDH enzyme activity, PDH kinase, PDH phosphatase and expression of PDH component pro- tein subunits E1, E1, E2, E2/3, using enzymatic, ELISA and Western blotting methods. Results and conclusions: Protein expression of all PDH subunits was significantly increased relative to Com- plex V (ATP synthase) or VDAC1 in the failing heart (p < 0.01), despite unchanged enzyme activity, reflect- ing an increased reliance on glycolytic metabolism. In turn, levels of reduced pyridine nucleotides (NADH) and Complex I activity were significantly decreased (p < 0.01). Thus, despite early adaptation permitting maintenance of NADH, subsequent, end-stage failure is characterised by altered regulation of PDH by its phosphatase and kinases, post-oxidative modification and impedance of mitochon- drial enzymes, and reduced capacity for mitochondrial biogenesis and membrane turnover. http://dx.doi.org/10.1016/j.hlc.2012.05.221 212 Predictors of Therapeutic Dose Achievement in the Man- agement of Heart Failure A. Hickey 1,∗ , J. Suna 2 , L. Marquart 3 , C. Denaro 2 , G. Javorsky 1 , J. Atherton 2 1 The Prince Charles Hospital, Australia 2 Royal Brisbane and Women’s Hospital, Australia 3 Queensland Institute of Medical Research, Australia This study is part of a larger project that is testing approaches to ensure that patients with systolic heart failure attain optimal dosage of Ace Inhibitors and Beta Blockers post-hospital discharge. The aim of the current