Malinowski Marcin, Deja Marek A, Gołba Krzysztof S, Roleder Tomasz, Biernat Jolanta, Woś Stanisław
2nd Department of Cardiac Surgery, Medical University of Silesia, Katowice, Poland.
Eur J Cardiothorac Surg. 2008 Feb;33(2):225-31. doi: 10.1016/j.ejcts.2007.11.007. Epub 2007 Dec 20.
It has been recently suggested that perivascular tissue (PVT) releases hypothetic adipocyte- or adventitia-derived relaxing factor. The aim of the study was to assess anticontractile properties of perivascular tissue of human internal thoracic artery (ITA) and to check if this activity is nitric oxide (NO)- or prostacyclin-dependent. We also analyzed the influence of pleural adipose tissue on ITA reactivity.
Human ITA rings were studied in vitro. First, skeletonized and pedicled ITA reactivity to serotonin and angiotensin II was compared. In subsequent experiments fragments of ITA were skeletonized and divided into two preparations. One was incubated alone, the other together with PVT or pleural adipose tissue floating freely in the bath. First, concentration-response curves to either serotonin or angiotensin II were constructed. Tissue was then transferred from one bath to the other and concentration-response curves were reconstructed. The same protocol was applied with the inhibition of NO synthase with L-NMMA (10(-4)M) and cyclooxygenase with indomethacin (10(-5)M).
Skeletonization augmented contractile response to serotonin (E(max) 16.6+/-1.85 mN vs 43.8+/-3.87 mN; pedicled vs skeletonized ITA, respectively; p<0.001) and angiotensin II (E(max) 10.9+/-1.07 mN vs 26.6+/-1.45 mN, respectively; p<0.001). PVT presence in the bath caused decrease of E(max) from 40.8+/-5.01 to 20.1+/-2.69 mN for serotonin; p<0.001 and from 31.4+/-3.75 to 13.0+/-1.60 mN for angiotensin II, p<0.001 (PVT(-) vs PVT(+), respectively). PVT did not change ITA sensitivity (EC(50)) to serotonin or angiotensin II. Pleural adipose tissue did not change the contractile response of ITA to serotonin (E(max) 37.2+/-4.95 mN vs 36.3+/-4.83 mN, pleural fat+and pleural fat-, respectively; p=0.9). NO and prostacyclin inhibition failed to abolish anticontractile properties of perivascular tissue. PVT with cyclooxygenase and NO synthase inhibition decreased E(max) of serotonin from 46.6+/-3.03 to 28.2+/-4.02 mN, p<0.001 and E(max) of angiotensin II from 27.2+/-2.00 to 16.4+/-2.10 mN, p<0.001.
Perivascular tissue of ITA releases potent, soluble, nitric oxide and prostacyclin-independent anticontractile factor. The pleural adipose tissue does not influence ITA reactivity to vasoconstrictors. Preservation of perivascular tissue may protect against vasospasm of ITA graft in clinical settings.
最近有研究表明血管周围组织（PVT）可释放假定的脂肪细胞或外膜衍生的舒张因子。本研究旨在评估人胸廓内动脉（ITA）血管周围组织的抗收缩特性，并检查该活性是否依赖于一氧化氮（NO）或前列环素。我们还分析了胸膜脂肪组织对ITA反应性的影响。
对人ITA环进行体外研究。首先，比较去神经化和带蒂ITA对5-羟色胺和血管紧张素II的反应性。在随后的实验中，将ITA片段去神经化并分为两份标本。一份单独孵育，另一份与自由漂浮在浴槽中的PVT或胸膜脂肪组织一起孵育。首先，构建对5-羟色胺或血管紧张素II的浓度-反应曲线。然后将组织从一个浴槽转移到另一个浴槽，并重建浓度-反应曲线。使用L-NMMA（10⁻⁴M）抑制NO合酶和吲哚美辛（10⁻⁵M）抑制环氧化酶时应用相同的方案。
去神经化增强了对5-羟色胺的收缩反应（E(max)分别为16.6±1.85 mN和43.8±3.87 mN；带蒂ITA与去神经化ITA相比，p<0.001）以及对血管紧张素II的收缩反应（E(max)分别为10.9±1.07 mN和26.6±1.45 mN，p<0.001）。浴槽中存在PVT导致5-羟色胺的E(max)从40.8±5.01 mN降至20.1±2.69 mN；p<0.001，血管紧张素II的E(max)从31.4±3.75 mN降至13.0±1.60 mN，p<0.001（分别为PVT(-)与PVT(+)）。PVT未改变ITA对5-羟色胺或血管紧张素II的敏感性（EC(50)）。胸膜脂肪组织未改变ITA对5-羟色胺的收缩反应（E(max)分别为37.2±4.95 mN和36.3±4.83 mN，分别为胸膜脂肪+和胸膜脂肪-；p = 0.9）。抑制NO和前列环素未能消除血管周围组织的抗收缩特性。抑制环氧化酶和NO合酶时，PVT使5-羟色胺的E(max)从46.6±3.03 mN降至28.2±4.02 mN，p<0.001，血管紧张素II的E(max)从27.2±2.00 mN降至16.4±2.10 mN，p<0.001。
ITA的血管周围组织释放一种强效、可溶性、不依赖于一氧化氮和前列环素的抗收缩因子。胸膜脂肪组织不影响ITA对血管收缩剂的反应性。在临床环境中，保留血管周围组织可能预防ITA移植物的血管痉挛。
