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The ineffectiveness of magnesium sulphate and heparin in preventing thrombosis following microvascular anastomoses
THE INEFFECTIVENESS OF MAGNESIUM SULPHATE AND HEPARIN IN PREVENTING THROMBOSIS FOLLOWING MICROVASCULAR ANASTOMOSES By P. C. LEUNG,F.R.C.S.(Edin.), F.R.A.C.S.* and P. C. B.Sc.(Pharm.), M.Phil.(Pharm.)t
CHUNG,
* Plastic and Reconstructive Surgery Unit, Medical and Health Department of Hong Kong, and t Department of Pharmacology, University of Hong Kong HEPARINsolution has been used as a local agent to keep the operative field clear of clots ever since surgery on small blood vessels began (Buncke and Schulz, 1965; Cobbett, 1967). Some believe that it diffuses across the vessel walls, thus preventing thrombus Magnesium sulphate was introduced by Acland (1972) as an extremely formation. effective local agent in preventing thrombosis at the anastomosis. We have tested these 2 agents in the following experimental model. Wistar rats weighing either 200 g or 400 g were used. They were anaesthetised with intraperitoneal urethrane and the common carotid arteries were exposed through a midline incision in the neck. The common carotid artery was chosen as the vessel for anastomosis because it was of the desirable size: 0.7 to 0.8 mm in diameter in the 200 g rat and 0.9 to 1.0 mm in the 400 g rat. What made it even more suitable for our A type B experiments included its easy exposure and anastomosis after division. microvascular clamp1 was used and the anastomosis carried out with IO/O Nylon interrupted sutures. One of us (I’. C. L.) performed all the surgery and found that, after much experience of microsurgery, the thrombosis rate stabilised at about 30 per cent. Observations made for up to 24 hours showed that if a thrombus did form it invariably did so within the first hour after the anastomosis. As soon as blood flow was re-established in the artery when the clamp was removed, an isotonic solution of magnesium sulphate or a heparin solution of 10,000 units per litre was dripped from an overhead pipette onto the vessel which was then kept constantly bathed in a pool of either solution. Patency was tested at I hour. Control experiments using normal saline were carried out under exactly similar conditions. The results are shown in Tables I and 2. In neither instance was there any evidence of a beneficial effect in preventing thrombosis. TABLE I Results of the magnesium sulphate trial Patent at I hour 200 g rat 400 g rat
r MgSO,
I5 I7
7 Control (N-saline)
1I
16 16
MgSO,
Control (N-saline)
Thrombosed I hour
at
Total
5
20
:
20
4
20
Address for reprints: Dr P. C. Leung, Chief Surgeon, Plastic and Reconstructive Princess Margaret Hospital, Lai King Hill Road, Lai Chi Kok, Kowloon, Hong Kong. 1 Tokyo Hospital Supply. 22
Surgery
Unit,
PREVENTION
OF
THROMBOSIS
FOLLOWING
TABLE
MICROVASCULAR
ANASTOMOSES
‘3
2
Results of the heparin trial Pdtent at T hour zoo g rat _+oo g rar
Heparin Control Heparin Control
19 1X 15 17
(N-salicc (N-saline
Thrombosed I hour
at ‘I‘otal
1
20
2
20
5 3
20 20
Acland (1972), in his experiments with rat femoral arteries, observed that thrombosis, if occurring, will take place in the first IO minutes after completion of the anastomosis. In our experimental model, thrombosis invariably happened within the first hour. This delay in thrombosis may be explained by the high blood flow in the carotid arteries which could significantly prevent or delay the occurrence of thrombosis. Although Acland reported 90 per cent patency when using magnesium sulphate locally, as against 30 per cent in the controls, we have not been able to demonstrate a similar antitbrombotic effect. However, our experimental model is not comparable to that of Acland since he administered systemic heparin to all the rats while we did not heparinise any animals. Others have questioned the value of magnesium sulphate; thus Engrav ef al. (1975) reported the results of replantation of the hind legs of 44 rats. Magnesium sulphate was used and tested against controls; no benefit could be demonstrated. Heparin, while used as a systemic agent, has a well-known anti-coagulating effect. However, when used as a local agent, its antithrombotic effect becomes doubtful and could not be demonstrated in our models. SUMMARY
Neither magnesium sulphate nor heparin was found to have a significant local antithrombotic effect on microvascular anastomoses. The authors wish to give their heuq thanks to Professor Roberts of the Pharmacolog_v Department, University of Hong Kong, for the advice and encouragement he has given towards the They also wish to thank Mr Wai, the laboratory technician, for planning of the experiment. his assistance. REFERENCES Prevention of thrombosis in microvascular surgery by the use of ACKLAND, R. D. (1972). British Jotrrnal of Plastic Surgery, 25, 292. magnesium sulphate. BUNCKE, H. J. and SCHULZ, W. D. (1965). Experimental amputation and reimplantation. Plastic a,ld Reconstructive Surgery, 36, 62. BritishJournal of Plastic Surgery, 20, 16. COBBETT, J. R. (1967). Small vessel anastomosis. ENGRAV, L. H., BENJAMIN, C. I., CRANDALL, H. and PERRY, J. F. (1975). Experimental effects Plastic of heparin or magnesium sulphate on the patency of microvascular anastomoses. and Reconstructive Surgery, 55, 6 f 8.
CHUNG,
* Plastic and Reconstructive Surgery Unit, Medical and Health Department of Hong Kong, and t Department of Pharmacology, University of Hong Kong HEPARINsolution has been used as a local agent to keep the operative field clear of clots ever since surgery on small blood vessels began (Buncke and Schulz, 1965; Cobbett, 1967). Some believe that it diffuses across the vessel walls, thus preventing thrombus Magnesium sulphate was introduced by Acland (1972) as an extremely formation. effective local agent in preventing thrombosis at the anastomosis. We have tested these 2 agents in the following experimental model. Wistar rats weighing either 200 g or 400 g were used. They were anaesthetised with intraperitoneal urethrane and the common carotid arteries were exposed through a midline incision in the neck. The common carotid artery was chosen as the vessel for anastomosis because it was of the desirable size: 0.7 to 0.8 mm in diameter in the 200 g rat and 0.9 to 1.0 mm in the 400 g rat. What made it even more suitable for our A type B experiments included its easy exposure and anastomosis after division. microvascular clamp1 was used and the anastomosis carried out with IO/O Nylon interrupted sutures. One of us (I’. C. L.) performed all the surgery and found that, after much experience of microsurgery, the thrombosis rate stabilised at about 30 per cent. Observations made for up to 24 hours showed that if a thrombus did form it invariably did so within the first hour after the anastomosis. As soon as blood flow was re-established in the artery when the clamp was removed, an isotonic solution of magnesium sulphate or a heparin solution of 10,000 units per litre was dripped from an overhead pipette onto the vessel which was then kept constantly bathed in a pool of either solution. Patency was tested at I hour. Control experiments using normal saline were carried out under exactly similar conditions. The results are shown in Tables I and 2. In neither instance was there any evidence of a beneficial effect in preventing thrombosis. TABLE I Results of the magnesium sulphate trial Patent at I hour 200 g rat 400 g rat
r MgSO,
I5 I7
7 Control (N-saline)
1I
16 16
MgSO,
Control (N-saline)
Thrombosed I hour
at
Total
5
20
:
20
4
20
Address for reprints: Dr P. C. Leung, Chief Surgeon, Plastic and Reconstructive Princess Margaret Hospital, Lai King Hill Road, Lai Chi Kok, Kowloon, Hong Kong. 1 Tokyo Hospital Supply. 22
Surgery
Unit,
PREVENTION
OF
THROMBOSIS
FOLLOWING
TABLE
MICROVASCULAR
ANASTOMOSES
‘3
2
Results of the heparin trial Pdtent at T hour zoo g rat _+oo g rar
Heparin Control Heparin Control
19 1X 15 17
(N-salicc (N-saline
Thrombosed I hour
at ‘I‘otal
1
20
2
20
5 3
20 20
Acland (1972), in his experiments with rat femoral arteries, observed that thrombosis, if occurring, will take place in the first IO minutes after completion of the anastomosis. In our experimental model, thrombosis invariably happened within the first hour. This delay in thrombosis may be explained by the high blood flow in the carotid arteries which could significantly prevent or delay the occurrence of thrombosis. Although Acland reported 90 per cent patency when using magnesium sulphate locally, as against 30 per cent in the controls, we have not been able to demonstrate a similar antitbrombotic effect. However, our experimental model is not comparable to that of Acland since he administered systemic heparin to all the rats while we did not heparinise any animals. Others have questioned the value of magnesium sulphate; thus Engrav ef al. (1975) reported the results of replantation of the hind legs of 44 rats. Magnesium sulphate was used and tested against controls; no benefit could be demonstrated. Heparin, while used as a systemic agent, has a well-known anti-coagulating effect. However, when used as a local agent, its antithrombotic effect becomes doubtful and could not be demonstrated in our models. SUMMARY
Neither magnesium sulphate nor heparin was found to have a significant local antithrombotic effect on microvascular anastomoses. The authors wish to give their heuq thanks to Professor Roberts of the Pharmacolog_v Department, University of Hong Kong, for the advice and encouragement he has given towards the They also wish to thank Mr Wai, the laboratory technician, for planning of the experiment. his assistance. REFERENCES Prevention of thrombosis in microvascular surgery by the use of ACKLAND, R. D. (1972). British Jotrrnal of Plastic Surgery, 25, 292. magnesium sulphate. BUNCKE, H. J. and SCHULZ, W. D. (1965). Experimental amputation and reimplantation. Plastic a,ld Reconstructive Surgery, 36, 62. BritishJournal of Plastic Surgery, 20, 16. COBBETT, J. R. (1967). Small vessel anastomosis. ENGRAV, L. H., BENJAMIN, C. I., CRANDALL, H. and PERRY, J. F. (1975). Experimental effects Plastic of heparin or magnesium sulphate on the patency of microvascular anastomoses. and Reconstructive Surgery, 55, 6 f 8.