Conference Publication Details
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Lainis, F, Buckley, M and Johns, E.;
Physiological Society Meeting
Thyroxine induced heart hypertrophy: impact on cardiac function
2009
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()
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Dublin
01-JUL-09
04-JUL-09
Cardiac hypertrophy occurs when there is increased workload on the heart and is recognised as the first stage in the progression into heart failure. Recently, this laboratory reported that cardiac function parameters were elevated in a rat model of hypertrophy induced using isoprenaline and caffeine and by chronic thyroxine administration (Flanagan et al. 2008). The aim of this study was to determine how different exposure times to thyroxine impacted on basal cardiac function parameters and on the ability of the heart to respond to a β-adrenergic challenge. Groups of male Wister rats (250-270g) were given normal diet tap water to drink (n=9) or received daily i.p. injections of thyroxine (1mg/kg) for 7 (n=9) or 14 (n=9) days. On the day of study, anaesthesia was induced using 1ml ip chloralose/urethane (16.5/250 mg/ml) and cannulae were inserted into a femoral artery and vein to measure mean arterial pressure (MAP) and heart rate (HR) and to infuse saline (0.9g/l NaCl) at 3ml/h, respectively. A micro-tip pressure transducer catheter was introduced into the left ventricle via the right carotid artery (Flanagan et al 2008) to allow computation of cardiac index (CI) and dP/dtmax. Following 1-2 h recovery, basal measurements were taken over a 3 min period; thereafter, isoprenaline, 0.75mg was given i.v over 40s, and further recordings of the haemodynamic variables were taken as MAP recovered from its nadir. Data, means ± S.E.M. were considered significant when P<0.05 (one way ANOVA). In the control group, basal levels of MAP, HR, CI and dP/dtmax were 123±5mHg, 351±8 s-1 and 11.10 ±0.90 mmHg s-1 10-3 and these values were comparable to the basal values recorded in rats treated with thyroxine for 7 days. In rats treated with thyroxine for fourteen days, MAP was comparable at 131±10 mmHg, but HR, CI and dP/dtmax were higher (all P<0.05) at 408 ± 18 b/min, 167±7 s-1 and 13.75±0.67 mmHg s-1 10-3, respectively. Administration of isoprenaline i.v. in the control rats transiently decreased MAP, increased HR by 14% and CI by 15% (both P<0.05), but minimally changed dP/dtmax. In the group given thyroxine for 14 days, isoprenaline i.v. caused significant reductions (both P<0.05) in CI and dP/dtmax of some 9 and 15% respectively. Together, these data demonstrated that as the exposure to thyroxine was prolonged, heart size was increased and baseline cardiac function in terms of CI and dP/dtmax was raised. By contrast, a stimulatory challenge with isoprenaline, which enhanced cardiac function in normal rats, was blunted following the two weeks of thyroxine treatment and these parameters were decreased. The findings would suggest that in cardiac hypertrophy that although basal heart function was enhanced, the ability to respond to physiological challenges was impaired.
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