The Slow Force Response to Stretch in Isolated RV Trabeculae from Rat Hearts

S316

Heart, Lung and Circulation 2009;18S:S299–S318

Abstracts

ABSTRACTS

sis, both important mechanisms of cardiac remodelling, suggesting a potential direct therapeutic role for sEHIs via attenuation of cardiac remodelling, additional to other CV effects. doi:10.1016/j.hlc.2009.05.486 695 THE SLOW FORCE RESPONSE TO STRETCH IN ISOLATED RV TRABECULAE FROM RAT HEARTS Xin Shen, Marie-Louise Ward Department of Physiology, The University of Auckland, New Zealand Stretching cardiac muscle yields a biphasic increase in the force of contraction. The increase in force immediately following the stretch is well understood, and attributed to effects on the myofilaments. The mechanism(s) associated with the secondary increase in force following stretch are still debated, but it is known that it is accompanied by an increase in the Ca2+ transient amplitude. The aim of this study was to further investigate the slow force response to stretch. Cardiac trabeculae (150–350 ␮m in diameter, 2–3 mm long), were excised from the right ventricle of rat hearts, and mounted in a muscle chamber between a hook attached to a force transducer and a snare so that trabeculae length could be easily adjusted. Preparations were continuously superfused with oxygenated physiological solution and subjected to a step increases in length while isometric force and intracellular Ca2+ (fura-2/AM) were recorded. Preliminary data show that increasing the stimulation frequency from 0.1 Hz to 0.5 Hz increased the magnitude of both the slow force response, and the Ca2+ transient, while reducing the time constant of decay of Ca2+ transients. These data suggest that the slow force response to stretch may therefore include a cellular mechanism that is enhanced by excitation–contraction coupling. doi:10.1016/j.hlc.2009.05.487 696 TOLERANCE OF ISOLATED CARDIAC MYOCYTES FROM MALE AND FEMALE RATS TO SIMULATED ISCHEMIA AND REPERFUSION J.R. Bell 1 , I.R. Wendt 2 , M. Vila Petroff 3,1 , C.L. Curl 1 , A. Mattiazzi 3 , L.M.D. Delbridge 1 1 Department of Physiology, The University of Melbourne, VIC

3010, Australia of Physiology, Monash University, VIC 3800, Australia 3 Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP, Argentina 2 Department

Cardiac-specific sex differences have the potential to impact on the cardiac response to stresses such as ischemia, as evidenced by depressed post-ischemic contractile function in ex vivo perfused hearts of male rats compared with female rats [1]. The goal of the present study was to examine whether sex differences in the sus-

ceptibility to ischemic damage are evident at the level of the single isolated cardiac myocyte. Fura-2 fluorescence and cell shortening were monitored in cardiac myocytes isolated from hearts of 12–14-week-old male and female Sprague–Dawley rats. Cells were paced at 4 Hz (37 ◦ C) and subjected to a protocol designed to mimic ischemia (20 min) and reperfusion. In some experiments, the cells were treated with the CaMKII inhibitor, KN-93. During simulated ischemia, cell shortening initially decreased substantially, coincident with diastolic cell lengthening. Upon ‘reperfusion’ with control solution, cells exhibited diastolic contracture and variable recovery of contractile function. There was a marked sex difference in cell mortality during ‘reperfusion’ with only a 33% survival rate in male cells (total 19 myocytes) as compared to 75% survival in female cells (total 20 myocytes). Diastolic Ca2+ at 20 min ischemia was significantly greater in non-surviving cells than surviving cells (fluorescence ratio 360/380: male non-survivor 1.88 ± 0.10 vs survivor 1.60 ± 0.03; female 1.85 ± 0.10 vs 1.68 ± 0.06, p < 0.05), though no differences were apparent in the contractile state or cellular Ca2+ handling immediately prior to reperfusion. CaMKII inhibition markedly enhanced cell viability during ‘reperfusion’ in male cells (70% survival), with a more modest effect in female cells (85% survival). These results suggest that reduced ischemic resilience in intact male hearts may be due to a greater susceptibility of myocytes to I/R-induced cell loss rather than impaired contractile recovery of surviving cells. Higher cellular steady-state Ca2+ levels in male cardiac myocytes may elevate CaMKII activity and contribute to a greater vulnerability to I/R damage.

Reference [1] Bell, et al. Am J Physiol 2008;294:H1514–22.

doi:10.1016/j.hlc.2009.05.488 Rehabilitation, Exercise and Prevention 697 ASSESSMENT OF CHANGES IN PLASMA MARKERS OF INFLAMMATION, OXIDATIVE STRESS AND NITRIC OXIDE FOLLOWING A RURAL TERTIARY OUTPATIENT CARDIAC REHABILITATION PROGRAM Andrew Fenning, Anna Voss, Len Knott, Fiona Coulson Central Queensland University, QLD, Australia and The Range Medical Practice Current models of secondary and tertiary cardiac rehabilitation programs in rural and remote areas have proven to be unsuccessful in terms of patient compliance and adherence and uptake of the activity. To combat these problems, a novel cardiac rehabilitation program was developed in the regional centre of Toowoomba. The 14week cardiac rehabilitation program caters for patients with significant coronary artery disease and/or myocardial infarction. While the program has been running since the mid to late 1990s, there has been no quantitative assessment of the effectiveness of the program