2990 Microsurgery.qxd - O'Brien Institute

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Scientific Research Bernard O’Brien Institute of Microsurgery Inhibition of blood vessel wall thickening by L-arginine L-arginine is an amino acid in the body which is converted into the important chemical known as nitric oxide (NO). NO has many useful properties in blood vessels. Notably it is responsible for dilating blood vessels and inhibiting the formation of blood clots. Arterial and vein grafts are commonly used to repair damaged blood vessels. In some traumatic accidents with a large amount of tissue loss, there is an insufficient length of blood vessel to perform this type of repair. At BOBIM we have found that blood vessels from different individuals of the same species, stored in the cold for a month, are convenient substitutes for the individual’s own blood vessels. However, one disadvantage of microsurgically repairing a blood vessel with that of another individual (allografting) is the thickening of the blood vessel wall (intimal hyperplasia) during the following month. This narrowing of the size of the blood vessel lumen increases the likelihood of vascular obstruction and failure of the graft. In this experimental study we administered L-arginine daily for 4 weeks from the time of microvascular repair of allografted blood vessels to see whether the NO generated could inhibit the blood vessel wall thickening. After 4 weeks the patency rate (those which had normal blood flow) of saline-treated controls was 57% compared with 83% in L-arginine-treated arterial allografts. Importantly, the intimal cross sectional area of the blood vessels decreased significantly from 678 m 2 in saline-treated controls to 277 m 2 for L-arginine-treated allografts. The mean blood pressure was not altered by L-arginine treatment. It is concluded that L-arginine (and therefore NO) treatment is very beneficial in reducing blood vessel thickening in arterial allografts, thus ensuring that this type of graft has a better chance of success. 4 week cold storage allograft, L-arginine treated. Shows less neointima thickening than saline-treated allograft. 4 week cold storage allograft, saline treated. 21
Scientific Research Bernard O’Brien Institute of Microsurgery Vascular smooth muscle cell proliferation Smooth muscle cells (SMC) are a normal component of blood vessels. However, damage to blood vessels can lead to their proliferation, and this can ultimately lead to blockage of the vessels. We are currently investigating the complex effects of NO on SMC proliferation. It is known that NO inhibits SMC proliferation. However, we have found that this effect depends upon the concentration and type of NO donor, as well as the concentration and type of mitogen. Under some circumstances we have found that NO may in fact enhance SMC proliferation. These observations may explain some of the apparently contradictory functions of NO reported in the literature. We aim to further characterise the apparent dual roles of NO on SMC proliferation. Ms Claire Ravenhall BSc (Hons) with her AMRAD Young Investigator’s Award 1997. Role of nitric oxide in tumour angiogenesis Our previous studies suggest that nitric oxide (NO) has complex regulatory effects on the growth of new blood vessels. Tumours require new blood vessels to grow beyond a microscopic size. We have used genetically modified mice lacking one of the genes for an enzyme that produces NO (iNOS KO mice) to investigate how this molecule influences tumour growth. In normal mice skin tumours (melanoma cells) grow to approximately 1g within 2 weeks of subcutaneous injection. In contrast, in iNOS KO mice the average tumour size was less than half that of normal mice. We are currently investigating the relationship between NO and the gene message for vascular endothelial cell growth factor (VEGF) which is a powerful stimulant of new vessel growth. Regulation of NO production may provide a new method for reducing the growth and spread of tumours. 22
Page 1 and 2: Bernard O’Brien Institute of Micr
Page 3 and 4: Patrons PATRON-IN-CHIEF His Excelle
Page 5 and 6: Chairman’s Report Microsurgery Fo
Page 7 and 8: Overview of Research Bernard O’Br
Page 9 and 10: Director’s Report Bernard O’Bri
Page 11 and 12: Director’s Report Bernard O’Bri
Page 13 and 14: Scientific Research Bernard O’Bri
Page 21: Scientific Research Bernard O’Bri
Page 27 and 28: Full and Part-Time Staff Bernard O
Page 29 and 30: Publications Bernard O’Brien Inst
Page 31 and 32: Collaborations Bernard O’Brien In
Page 33 and 34: Presentations Bernard O’Brien Ins
Page 35 and 36: Visiting Lecturers Bernard O’Brie
Page 37 and 38: Named Fellowships Bernard O’Brien
Page 39 and 40: Financial Statements PROFIT AND LOS
Page 41: Donations Bernard O’Brien Institu

2990 Microsurgery.qxd - O'Brien Institute

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