46 Potential Anti-Arrhythmic and Cardio-Protective Properties of the Novel B-Blocker Nebivolol C. Pullen ∗ , A. Fenning CQ University, Australia Nebivolol has been shown to display a unique pharmacological profile antagonising 1 -adrenodeptors whilst also increasing nitric oxide bioavailability. Much of the research on nebivolol has focused on its ability to decrease blood pressure in a range of subjects including humans, as well as various animal models of hypertension. The aim of this study was to examine the cardio-protective effects of nebivolol, independent of its haemodynamic properties in rodent models of hypertension and diabetes. Male Wistar rats were randomly divided into either control (C), hypertensive (L-NAME-induced (L)) or diabetic (streptozotocin-induced (S)) groups. A subset of these groups were treated with 0.5 mg/mg/day (oral gavage) of nebivolol commenced at eight weeks of age and continuing until the animals reached sixteen weeks of age. Blood pressure and heart rate were monitored at four-weekly intervals throughout the study. Terminal experiments included vascular organ bath studies in thoracic aorta rings and mesenteric vessels and electrophysiological studies on the left ventricular papillary muscles. Nebivolol did not attenuate the elevated blood pressure seen in L-NAME treated animals (C− 123.12 ± 2.80 mmHg; L− 224.15 ± 7.76 mmHg*; L+N− 187.19 ± 7.21 mmHg**), however reductions in action potential duration were observed in nebivolol treated hypertensive rats (APD20: C− 13.63 ± 0.53 ms; L− 19.52 ± 2.16 ms; L+N− 14.75 ± 0.75 ms). Vascular tissues from animals treatment with nebivolol demonstrated an increased sensitivity to noradrenaline. This indicates that nebivolol may be acting through nitric oxide to provide some anti-arrhythmic and vascular protective effects. http://dx.doi.org/10.1016/j.hlc.2012.05.056 47 Prenatal Psychological Stress Modulates Offspring’s Long-Term Cardiovascular Activity and Reactivity to Stress F. Fan 1,∗ , H. Tian 2 , J. Zhang 2 , Y. Liu 2 , Y. Meng 2 , Z. Hu 2 , Y. Zou 2 , X. Du 1,3 , A. Dart 1,2,3 1 BakerIDI
Heart & Diabetes Institute, Melbourne, VIC, Australia 2 1st Hospital of Medical College, Xi’an Jiaotong University, Xi’an, China 3 Heart Center, Alfred Hospital, Melbourne, VIC, Australia Introduction: Increased cardiovascular activity (CVA) and reactivity (CVR) to psychological stress have been identified as possible new markers for future cardiovascular risk. Animal studies showed psychological stress of pregnant mother, defined as prenatal psychological stress (PPS), modulates offspring’ CVA and CVR. How-
CSANZ 2012 Abstracts
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ever, the underlying mechanism is unclear and few studies have examined such possible influences in the human. We investigated the long-term effects and mechanism of PPS on CVA and CVR in seven to nine year-old children. Methods and results: we measured BP and HR at rest (rBP, rHR) and during video game stress (sBP, sHR) in 287 children whose mothers previously had thorough psychological assessment for PPS during pregnancy. rBP and rHR were used for CVA evaluation. CVR was defined as the maximum change in BP (BP) and HR (HR) in response to video game stress. Serum cortisol was serially measured before and during video game by radioimmunoassay to calculate absolute increment (cortisol). The results showed rBP and rHR, baseline cortisol (mean ± SD, 353 ± 37 nmol/L vs. 297 ± 36 nmol/L), BP (21 ± 2/12 ± 1 mmHg vs. 15 ± 1/10 ± 1 mmHg) and HR (18 ± 1 bpm vs. 13 ± 1 bpm), cortisol were all higher in children who experienced PPS than those without (all P < 0.01). Maternal effects on children’s CVA and CVR were most marked for combined maternal anxiety and depression, and least for depression alone. Conclusion: Our study confirms animal findings by demonstrating long lasting effects of PPS on offspring’s CVA and CVR in the human with likely effects on the subsequent risk of cardiovascular disease. http://dx.doi.org/10.1016/j.hlc.2012.05.057 48 Prevalence and Resolution of Pulmonary Hypertension (PHT) in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI) S. Jaijee 1,∗ , J. Yiannikis 2 , M. Wilson 1 , M. Vallely 1 , M. Ng 1 , D. Celermajer 1 1 Royal
Prince Alfred Hospital, Australia Repatriation Hospital, Australia
2 Concord
Background and aim: Left heart disease (LHD) is the most common cause of PHT but its pathogenesis is poorly understood. Severe aortic stenosis (AS) is a cause of LHD related PHT. Our aim was to assess the prevalence and time course of resolution of PHT when AS was relieved by transcatheter aortic valve implantation. Methods: We assessed 60 consecutively treated patients who underwent TAVI with serial echocardiography. PHT was defined as RV-RA pressure gradient ≥40 mmHg and a significant fall in pulmonary arterial pressure (PAP) was defined as >20% reduction in the RV-RA gradient. Results: Of 60 patients, 20/60 (33%) had PHT. From those 20 patients, six had an immediate reduction in PASP based on early echocardiography (<10 days). From the 14 patients who have reached >2 month follow up, six patients had a reduction in PAP, three had persistent PHT, one was lost to follow up and four did not have data available. Significance: In patients with PHT prior to TAVI, PAP falls in the majority but with an unpredictable time course. We have identified three patterns of response; early regression which could be related to relief of subendocardial ischaemia, late regression which may be explained
ABSTRACTS
Heart, Lung and Circulation 2012;21:S1–S142