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Letters to the Editor Vein graft neointimal hyperplasia: Prevention is better than cure To the Editor: We read with interest the article by Thomas Schachner. 1 This review was an excellent description of the multiple factors involved in the initiation and progression of neoin- timal hyperplasia in vein grafts during cor- onary bypass surgery. Clearly much has been learned in recent years about the type and origin of the cells composing the hyper- plastic tissue and other various factors in- volved in the hyperplastic process. Schachner has proposed multiple pharmacologic strate- gies to reduce this hyperplastic process. However, we contend that this approach is similar to closing the stable door after the horse has bolted. Surely it is better to pre- vent the damage to the vein in the first place than to try to reverse the results in terms of neointimal hyperplasia after the damage has been done. There is a wealth of literature showing the adverse effects of surgical trauma, especially high pressure distension during vein graft harvesting, on the subsequent fate to the vein graft. 2 However, surgeons know instinctively that before they can implant a vein graft it must have an adequate lumen and be free of spasm. If vein spasm is present then the sur- geon invariably uses sufficient pressure to remove the spasm. We and others have shown that this procedure of distending the vein can generate extremely high intralu- minal pressures and lead to widespread loss of endothelial coverage. 2,3 We have also shown that this loss of endothelium can be prevented by pharmacologic relaxation of the vein with appropriate vasodilator agents. 4 We have shown in an extensive series of organ bath studies and clinical trials that a mixture of glyceryl trinitrate and vera- pamil is a highly effective means of reduc- ing vein graft spasm. This combination ret laxes the saphenous vein by 2 mechanisms. It has a rapid onset of effect and a long duration of action. 5 A more commonly used pharmacologic agent is papaverine. How- ever, we have shown that this agent results in inferior preservation of the endothelium. 4 Papaverine also has a number of other undesirable effects, especially endothelial damage from the acidity of its solution, particularly if it is undiluted. 6 Recent stud- ies have shown other adverse effects of papaverine on the endothelium. 6 Papaver- ine, however, continues to be used because it is readily available in the operating room. Although pharmacologic inhibition of vein graft neointimal hyperplasia is possi- ble, it is more important to prevent it in the first place by using pharmacologic relaxation of the vein graft conduit during harvesting. Franklin Rosenfeldt, FRACS a Guo Wei He, MD, DSc b Nick Roubos, MB, BS, BMedSci c Department of Cardiothoracic Surgery a Monash University Department of Surgery Alfred Hospital and the Baker Heart Research Institute Melbourne, Australia Department of Surgery b The Chinese University of Hong Kong Department of Cardiothoracic Surgery c Alfred Hospital Melbourne Melbourne, Australia References 1. Schachner T. Pharmacological inhibition of vein graft neointimal hyperplasia.J Thorac Cardiovasc Surg. 2006;131:1065-72. 2. Ramos JR, Berger K, Mansfield PB, Sauvage LR. Histologic fate and endothelial changes of distended and nondistended vein grafts. Ann Surg. 1976;183:205-28. 3. Angelini GD, Passani SL, Breckenridge IM, Newby AC. Nature and pressure dependence of damage induced by distension of human saphenous vein coronary artery bypass grafts. Cardiovasc Res. 1987;21:902-7. 4. Roubos N, Rosenfeldt FL, Richards SM, Conyers RA, Davis BB. Improved preserva- tion of saphenous vein grafts by the use of glyceryl trinitrate-verapamil solution during harvesting. Circulation. 1995;92(9 Suppl): II31-6. 5. He GW, Rosenfeldt FL, Angus JA. Pharma- cological relaxation of the saphenous vein during harvesting for coronary artery bypass grafting. Ann Thorac Surg. 1993;55:1210-7. 6. Rubens FD, Labow RS, Meek E, Bedard E, Gill IS, Dudani AK, et al. Papaverine solu- tions cause loss of viability of endothelial cells. J Cardiovasc Surg (Torino). 1998;39:193-9. doi:10.1016/j.jtcvs.2006.09.082 The Editor welcomes submissions for possible publication in the Letters to the Editor section that consist of commen- tary on an article published in the Jour- nal or other relevant issues. Authors should: Include no more than 500 words of text, three authors, and five references Type with double-spacing See http://jtcs.ctsnetjournals.org/misc/ ifora.shtml for detailed submission instructions. Submit the letter electronically via jtcvs.editorialmanager.com. Letters commenting on an article pub- lished in the JTCVS will be considered if they are received within 6 weeks of the time the article was published. Authors of the article being commented on will be given an opportunity to offer a timely response (2 weeks) to the letter. Authors of letters will be notified that the letter has been received. Unpublished letters cannot be returned. 1118 The Journal of Thoracic and Cardiovascular Surgery April 2007

Vein graft neointimal hyperplasia: Prevention is better than cure

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Letters to theEditor

Vein graft neointimal hyperplasia:Prevention is better than cureTo the Editor:We read with interest the article by ThomasSchachner.1 This review was an excellentdescription of the multiple factors involvedin the initiation and progression of neoin-timal hyperplasia in vein grafts during cor-onary bypass surgery. Clearly much hasbeen learned in recent years about the typeand origin of the cells composing the hyper-plastic tissue and other various factors in-volved in the hyperplastic process. Schachnerhas proposed multiple pharmacologic strate-gies to reduce this hyperplastic process.

However, we contend that this approachis similar to closing the stable door after thehorse has bolted. Surely it is better to pre-vent the damage to the vein in the firstplace than to try to reverse the results interms of neointimal hyperplasia after thedamage has been done. There is a wealth ofliterature showing the adverse effects ofsurgical trauma, especially high pressuredistension during vein graft harvesting, onthe subsequent fate to the vein graft.2

However, surgeons know instinctivelythat before they can implant a vein graft itmust have an adequate lumen and be free ofspasm. If vein spasm is present then the sur-geon invariably uses sufficient pressure toremove the spasm. We and others haveshown that this procedure of distending thevein can generate extremely high intralu-minal pressures and lead to widespread lossof endothelial coverage.2,3 We have alsoshown that this loss of endothelium can beprevented by pharmacologic relaxation ofthe vein with appropriate vasodilator agents.4

We have shown in an extensive seriesof organ bath studies and clinical trials thata mixture of glyceryl trinitrate and vera-pamil is a highly effective means of reduc-ing vein graft spasm. This combination retlaxes the saphenous vein by 2 mechanisms.It has a rapid onset of effect and a longduration of action.5 A more commonly usedpharmacologic agent is papaverine. How-ever, we have shown that this agent results ininferior preservation of the endothelium.4

Papaverine also has a number of otherundesirable effects, especially endothelialdamage from the acidity of its solution,particularly if it is undiluted.6 Recent stud-ies have shown other adverse effects ofpapaverine on the endothelium.6 Papaver-ine, however, continues to be used becauseit is readily available in the operating room.

Although pharmacologic inhibition ofvein graft neointimal hyperplasia is possi-ble, it is more important to prevent it in thefirst place by using pharmacologic relaxationof the vein graft conduit during harvesting.

Franklin Rosenfeldt, FRACSa

Guo Wei He, MD, DScb

Nick Roubos, MB, BS, BMedScic

Department of Cardiothoracic Surgerya

Monash University Department of SurgeryAlfred Hospital and the Baker Heart

Research InstituteMelbourne, Australia

Department of Surgeryb

The Chinese University of Hong KongDepartment of Cardiothoracic Surgeryc

Alfred Hospital MelbourneMelbourne, Australia

References

1. Schachner T. Pharmacological inhibition ofvein graft neointimal hyperplasia.J ThoracCardiovasc Surg. 2006;131:1065-72.

2. Ramos JR, Berger K, Mansfield PB, SauvageLR. Histologic fate and endothelial changesof distended and nondistended vein grafts.Ann Surg. 1976;183:205-28.

3. Angelini GD, Passani SL, Breckenridge IM,Newby AC. Nature and pressure dependenceof damage induced by distension of humansaphenous vein coronary artery bypass grafts.Cardiovasc Res. 1987;21:902-7.

4. Roubos N, Rosenfeldt FL, Richards SM,Conyers RA, Davis BB. Improved preserva-tion of saphenous vein grafts by the use ofglyceryl trinitrate-verapamil solution duringharvesting. Circulation. 1995;92(9 Suppl):II31-6.

5. He GW, Rosenfeldt FL, Angus JA. Pharma-cological relaxation of the saphenous veinduring harvesting for coronary artery bypassgrafting. Ann Thorac Surg. 1993;55:1210-7.

6. Rubens FD, Labow RS, Meek E, Bedard E,Gill IS, Dudani AK, et al. Papaverine solu-tions cause loss of viability of endothelial cells.J Cardiovasc Surg (Torino). 1998;39:193-9.

doi:10.1016/j.jtcvs.2006.09.082

The Editor welcomes submissions forpossible publication in the Letters to theEditor section that consist of commen-tary on an article published in the Jour-nal or other relevant issues. Authorsshould:● Include no more than 500 words of text,

three authors, and five references● Type with double-spacing● See http://jtcs.ctsnetjournals.org/misc/

ifora.shtml for detailed submissioninstructions.

● Submit the letter electronically viajtcvs.editorialmanager.com.

Letters commenting on an article pub-lished in the JTCVS will be considered ifthey are received within 6 weeks of thetime the article was published. Authorsof the article being commented on will begiven an opportunity to offer a timelyresponse (2 weeks) to the letter. Authorsof letters will be notified that the letterhas been received. Unpublished letterscannot be returned.

1118 The Journal of Thoracic and Cardiovascular Surgery ● April 2007