The GRF Glue Gelatin ResorcinolFormaldehyde Glue

A new tissue adhesive which was an elastic glue formed by cross-linking gelatin resorcine mixture with formaldehyde, was tested by Cooper and Falb9 and Koehnlein et al..10 It was found to have a better bond strength than other systems tested, viz. isocyanates, Eastman 910 monomer, and gelatin formaldehyde. In 1966, Braunwald and Tatooles11 conducted an experimental study on mongrel dogs and evaluated the usefulness of this modified G/R/F in controlling bleeding from standardised surgical injuries on their liver and kidneys. A solution was made with gelatin and resorcinol in 3:1 ratio and total solid content of 60 to 70%. The mongrel dogs were divided into two sets. In the first set of 25 dogs, a 3 by 2 cm portion of liver was excised in 12 animals, and a portion of the lower pole of the kidney was amputated in 13 animals. After ligating the large arteries on the cut surface of organs, a few drops of 37% formaldehyde U.S.P. were applied to the tissue surface, followed by the application of semi-liquid G-R mixture, which had been converted from the gel state to the sol state by warming to 40°C. One or two additional drops of formaldehyde were, then, added to the mixture. In the second set of animals, after a similar surgical procedure, a mixture of acidified G/R solution and formalin (5 ml of semi-liquid G/R acidified to a pH of 4 with 0.1 HCl and three drops of 37% formaldehyde) was applied onto the injured surface of liver and kidney, instead of a direct application of concentrated formalin on the tissue surface. This was followed by a fine spray of sodium bicarbonate powder, blown over the tacky adhesive from an atomizer bottle to raise the pH in situ and trigger the cross-linking reaction. All the animals were sacrificed at one- to six-month intervals and autopsied, excepting the two dogs of the first group that died of wound infection in the immediate postoperative period. On autopsy, a few filmy adhesions were seen about the operative site and surface of the liver and the kidney had healed well. Some residual gelatin was still visible on the surface for a few months and by six months only scar was visible. Microscopic examination revealed the presence of a small amount of residual glue up to six months and the removal of fragments of gelatin by macrophages and subsequent fibrosis. Initial polymorphonuclear leukocytes were replaced by a chronic inflammatory response with passage of time. While the tensile strength of the bond was comparable in both groups of animals, haemostasis was quick in the second group (two to three minutes). In the first group, several millimetres deep area of focal necrosis was often present at the site of application of formaldehyde, which was not the case in the second group. In addition, in the second group the total amount of formaldehyde used was considerably less, and the risk of accidental spillage of formalin on the tissues was averted.

Bonchek et al..12,13 later modified the glue by replacing formaldehyde by the better bonding formaldeyde-glutaraldehyde mixture. This was used in the repair of dissection of aorta in 1979 by Guilmet et al..14 and was called GRFG or G/R/A.

GRF has been extensively used as a haemostatic adjunct for vascular and cardiac operations.

Dapper et al..61 have used argon beam coagulator for bonding cross-linked gelatin fibres to heart muscles, lung pleura, and parenchyma. Rittoo et al..62 used GRF glue as a sealant of PTFE patch suture line with good results and no compromise of the characterisation of the patch.

Unlu et al..63 compared the use of fibrin glue, GRF, and collagen on a rabbit vascular graft model, for preventing suture hole bleeding. All were found to reduce blood loss, but fibrin-containing factor XIII was the most effective. Hata et al..64 have used GRF to aid operations for type-A aortic dissection with reasonable early and late mortality rates. There was no histological evidence of adverse tissue reaction. Nakajima et al.65 concluded in their study that the cause of re-dissection after surgery for type-A aortic dissection using GRF glue, is not too much formalin.

Suehiro et al66 found a high incidence of redissections of aortic root and false aneurysms and aortic insufficiency subsequent to surgery for acute aortic dissection using GRF glue. Tsukui et al..67 found coronary ostial stenosis between interposition graft and coronary artery attributable to inappropriate use of GRF glue. Kazui et al.68 concluded that GRF was associated with a certain risk of aortic wall necrosis when used for re-approximation of layers of dissected aortic root and suggested proper use of these glues. Bingley et al..69 undertook a study in their institution over a 5.5-year period with the intention of picking up complications of GRF glue used in cardiotho-racic cases, especially acute type-A dissections and paediatric cardiac cases. They found unsatisfactory, long-term complications related to the glue, and they discontinued its use in these groups.

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