A H Chester1, M Misfeld, H H Sievers, M H Yacoub. 1. Department of Cardiothoracic Surgery, Heart Science Centre, Harefield Hospital, NHLI, Imperial College of Science Technology and Medicine, Middlesex, UK.
Abstract
BACKGROUND AND AIM OF THE STUDY: The contraction of cusp tissue has been implicated to play a role in aortic valve function. The effect of the contractile agent 5-hydroxytryptamine (5-HT) on the competence of isolated aortic roots has been assessed, and the vasomotor properties of 5-HT on aortic root tissue examined. METHODS: Isolated porcine aortic roots were pressurized with Kreb's solution through the aortic arch. 5-HT was added in increasing concentrations (10(-7) to 10(-5) M) and the degree of leakage measured over time. In additional experiments, portions of sinotubular junction, sinus, annular and cusp tissue were set up in organ baths, placed under tension, and challenged with 5-HT (10(-9) to 10(-5) M). Viability of each valve structure was assessed by addition of KCl (90 mM). RESULTS: The rate of leakage from intact aortic roots increased when 10(-6) and 10(-5) M 5-HT was added. The maximum effect, observed at 10(-5) M 5-HT, was equal to an increase of 61.8+/-23.0% above control (p <0.05). The perfusion pressure at each concentration of 5-HT was unchanged. This response was inhibited by the 5-HT2A receptor antagonist ketanserin. Addition of KCl to isolated valve structures gave a mean contractile response of 0.8+/-0.1mN for cusp, 19+/-11.0 mN for annular, 29+/-8.0 mN for sinus, and 23+/-8.0 mN for sinotubular junction tissue (each n = 4). Only cusp tissue contracted when treated with 5-HT, with a maximum 105.5+/-17.2% (n = 4) of the response to KCl. The response to 5-HT was blocked by the 5-HT2A-receptor antagonist ketanserin at 10(-6) M (n = 4). None of the other aortic root structures responded to 5-HT. CONCLUSION: These results show that 5-HT influences the competence of isolated porcine aortic valves. This effect is contributed by contraction of the cusp tissue, and is mediated by 5-HT2A receptors. These effects may contribute to the association between valve dysfunction, 5-HT and certain appetite suppressants.
BACKGROUND AND AIM OF THE STUDY: The contraction of cusp tissue has been implicated to play a role in aortic valve function. The effect of the contractile agent 5-hydroxytryptamine (5-HT) on the competence of isolated aortic roots has been assessed, and the vasomotor properties of 5-HT on aortic root tissue examined. METHODS: Isolated porcine aortic roots were pressurized with Kreb's solution through the aortic arch. 5-HT was added in increasing concentrations (10(-7) to 10(-5) M) and the degree of leakage measured over time. In additional experiments, portions of sinotubular junction, sinus, annular and cusp tissue were set up in organ baths, placed under tension, and challenged with 5-HT (10(-9) to 10(-5) M). Viability of each valve structure was assessed by addition of KCl (90 mM). RESULTS: The rate of leakage from intact aortic roots increased when 10(-6) and 10(-5) M 5-HT was added. The maximum effect, observed at 10(-5) M 5-HT, was equal to an increase of 61.8+/-23.0% above control (p <0.05). The perfusion pressure at each concentration of 5-HT was unchanged. This response was inhibited by the 5-HT2A receptor antagonist ketanserin. Addition of KCl to isolated valve structures gave a mean contractile response of 0.8+/-0.1mN for cusp, 19+/-11.0 mN for annular, 29+/-8.0 mN for sinus, and 23+/-8.0 mN for sinotubular junction tissue (each n = 4). Only cusp tissue contracted when treated with 5-HT, with a maximum 105.5+/-17.2% (n = 4) of the response to KCl. The response to 5-HT was blocked by the 5-HT2A-receptor antagonist ketanserin at 10(-6) M (n = 4). None of the other aortic root structures responded to 5-HT. CONCLUSION: These results show that 5-HT influences the competence of isolated porcine aortic valves. This effect is contributed by contraction of the cusp tissue, and is mediated by 5-HT2A receptors. These effects may contribute to the association between valve dysfunction, 5-HT and certain appetite suppressants.
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