A Comparative Study of Endothelium-Derived Relaxing Factor-Mediated Relaxation and Smooth Muscle Cell Function in Arterial and Venous Vein Bypass Grafts

Abstract

The development of intimal hyperplasia in reversed vein grafts is associated with altered endothelial and vasomotor function. This study examines the effect of surgery on the morphology and vasomotor function of experimental arterial and venous vein bypass grafts. Twelve reversed vein grafts, 12 in situ vein grafts and 12 venovenous grafts were placed in 24 New Zealand White rabbits. All grafts remained patent and were harvested after 28 days. Isometric contraction to norepinephrine, histamine, bradykinin, serotonin and relaxation to acetylcholine and sodium nitroprusside following pre-contraction with prostaglandin F_2α were determined on the grafts and on contralateral jugular veins. Compared to the contralateral jugular veins, norepinephrine supersensitivity was induced in the reversed vein grafts and venovenous vein grafts but not in the in situ vein grafts. Decrease in histamine sensitivity occurred in all grafted vessels. Bradykinin responses were significantly reduced in the in situ vein grafts and reversed vein grafts. Contractile responses to serotonin developed in the in situ vein grafts and reversed vein grafts only. Acetylcholine-induced endothelium-derived relaxing factor-mediated relaxation of the contralateral jugular veins was preserved in both venovenous grafts and in situ vein grafts but was lost in reversed vein grafts. All tissues relaxed to sodium nitroprusside in dose-dependent manner. The data suggest that norepinephrine supersensitivity in reversed vein grafts results from excision of the vessel. Attenuation of bradykinin responses and the enhanced contractile responses to serotonin appear predominantly to result from arterialization. Decreases in histamine sensitivity appear related both to excision and to arterialization. Neither the excision of the vein nor arterialization individually influences the alterations in endothelium-derived relaxing factor-mediated relaxation. However, a combination of excision and arterialization results in the altered endothelium-derived relaxing factor-mediated relaxation. This study suggests that the surgical preparation of the vein and the surgical procedure used have significantly different effects on endothelium-derived relaxing factor-mediated relaxation and smooth muscle contractility in vein grafts.

Keywords

vein grafts endothelial and smooth muscle cell intimal hyperplasia rabbit

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References

Fuster

Badimon

Taubman

Chesebro

. Syndromes of accelerated atherosclerosis: The role of vascular injury and smooth muscle cell proliferation. J Am Coll Cardiol 1990; 15: 1667–87.

Fuchs

JCA

Mitchener

Hagen

P-O

. Postoperative changes in autologous vein grafts. Ann Surg 1978; 188: 1–15.

Dobrin

Littooy

Endean

. Mechanical factors predisposing to intimal hyperplasia and medial thickening in autogenous vein grafts. Surgery 1989: 105: 393–400.

Makhoul

Davis

Mikat

McCann

Hagen

P-O

. Responsiveness of vein grafts to stimulation with norepinephrine and 5-hydroxytryptamine. J Vasc Surg 1987; 6: 32–8.

Cross

EI-Sanadiki

Murray

Mikat

McCann

Hagen

P-O

. Functional abnormalities of experimental autogenous vein graft neoendothelium. Ann Surg 1988; 208: 631–8.

Radic

O'Donohoe

Schwartz

. Alterations in serotonergic receptor expression in experimental vein grafts. J Vasc Surg 1991; 14: 40–7.

Towne

. The role of fibrointimal hyperplasia in vein graft failure. J Vasc Surg 1989; 10: 583–5.

Szilagyi

Hageman

Smith

Elliott

Brown

Dietz

. Autogenous vein grafting in femoropopliteal atherosclerosis: The limits of its effectiveness. Surgery 1979; 86: 536–51.

Bourassa

Fischer

Campeau

Gillespie

McConney

Lesperance

. Long-term fate of bypass grafts: The coronary artery surgery study (CASS) and the Montreal Heart Institute experience. Circulation 1985; 72 (suppl V): 71–8.

10.

Campeau

Enjalbert

Lesperance

Vaislic

Grondin

Bourassa

. Atherosclerosis and late closure of aorto-coronary saphenous vein grafts: Sequential angiographic studies at 2 weeks, 1 year, 5 to 7 years and 10 to 12 years after surgery. Circulation 1983; 68 (suppl II): 1–7.

11.

Ramos

Berger

Mansfield

Sauvage

. Histologic fate and endothelial changes of distended and non-distended vein grafts. Ann Surg 1976; 183: 205–28.

12.

Adcock

GLD

Adcock

Jr Wheeler

. Arterialization of reversed autogenous vein grafts: Quantitative light and electron microscopy of canine jugular vein grafts harvested and implanted using standard or improved techniques. J Vasc Surg 1987; 6: 283–95.

13.

Svendsen

Dalen

Moland

Engedal

. A quantitative study of endothelial cell injury in aorto-coronary vein grafts. J Cardiovasc Surg (Torino) 1986; 27: 65–7.

14.

Brody

Kosek

Angell

. Changes in vein grafts following aorto-coronary bypass induced by pressure and ischemia. J Thorac Cardiovasc Surg 1972; 64: 847–54.

15.

Kohler

Kirkman

Clowes

. The effect of rigid external support on vein graft adaptation to the arterial circulation. J Vasc Surg 1989; 9: 277–85.

16.

Schwartz

O'Donohoe

Purut

Mikat

Hagen

P-O

McCann

. Myointimal thickening in experimental vein grafts is dependent on wall tension. J Vasc Surg 1992; 15: 176–86.

17.

Dobrin

Littooy

Golan

. Mechanical and histologic changes in canine vein grafts. J Surg Res 1988; 14: 259–60.

18.

Rubanyi

, ed. Cardiovascular Significance of Endothelium-Derived Vasoactive Factors. 1st ed. Mount Kisco, New York: Futura Publishing Company, 1991.

19.

Dries

Mohammad

Woodward

Nelson

. The influence of harvesting technique on endothelial preservation in saphenous veins. J Surg Res 1992; 52: 219–25.

20.

Sayers

Watt

PAC

Muller

Bell

PRF

Thurston

. Structural and functional muscle injury after surgical preparation of reversed and non-reversed (in situ) saphenous vein bypass grafts. Br J Surg 1991; 78: 1256–8.

21.

Sayers

Watt

PAC

Muller

Bell

PRF

Thurston

. Endothelial cell injury secondary to surgical preparation of reversed and in situ saphenous vein bypass grafts. Eur J Vasc Surg 1992; 6: 354–61.

22.

Schwartz

Radic

O'Donohoe

McCann

Mikat

Hagen

P-O

. Functional and morphological endothelial damage in rabbit external jugular veins stored in heparinized normal saline. Blood Vessels 1991; 28: 511–19.

23.

Schwartz

Massey

Davies

Klyachkin

Hagen

P-O

McCann

. Effect of in vitro pressurization on human saphenous vein vasoreactivity (abstract) FASEB J 1992; 6: A1041.

24.

Quist

LoGerfo

. Prevention of smooth muscle cell phenotypic modulation in vein grafts: A histomorphometric study. J Vasc Surg 1992; 16: 225–31.

25.

Bush

Jakubowski

Curl

Deykin

Nabseth

. The natural history of endothelial structure and function in arterialized vein grafts. J Vasc Surg 1986; 3: 204–15.

26.

Cambria

Megerman

Abbott

. Endothelial preservation in reversed and in situ autogenous vein grafts. A quantitative experimental study. Ann Surg 1985; 202: 50–5.

27.

Magnant

Walsh

Schneider

James

Wagner

Cronenwett

. Differences in vasoreactivity of in situ and reversed vein grafts (abstract). J Vasc Surg 1992; 15: 1068.

28.

O'Donohoe

Murchan

Marks

Feely

Feeley

. Endothelium derived relaxing factor is absent in experimental in situ vein grafts. Eur J Vasc Surg 1993; 7: 144–50.

29.

Miller

Bower

McCullough

Gloviczki

Vanhoutte

. Endothelium-dependent responses in nonreversed (in situ) vein grafts. J Vasc Med Biol 1990; 2: 155–62.

30.

Goodfellow

Mikat

. Simultaneous demonstration of collagen muscle and elastin elements in mammalian tissue. Lab Med 1988; 19: 243–4.

31.

Finney

. Quantal responses and the tolerance distribution. In: Finney

, ed. Statistical Method in Biological Assay. London: Charles Griffin, 1978: 349–69.

32.

Seidel

Lewis

Bowers

. Adaptation of canine saphenous veins to grafting. Correlation of contractility and contractile protein content. Circ Res 1984; 55: 102–9.

33.

Soliman

Tackett

. Early alterations in vascular reactivity of autogenous saphenous vein grafts. Coronary Artery Disease 1992; 3: 523–7.

34.

Soliman

Tackett

. Altered responsiveness of saphenous vein grafts to norepinephrine and tyramine: Relation to tissue catecholamine stores. J Cardiovasc Pharmacol 1991; 17: 154–7.

35.

Waris

Loefstedt

Partanen

Smitten

. Innervation of synergeic vein grafts in the rat: The regeneration of adrenergic nerves. J Surg Res 1984; 37: 472–8.

36.

Massey

Davies

Svendsen

. Ketanserin inhibits experimental vein graft intimal hyperplasia. J Surg Res 1993; 54: 530–8.

37.

Robert

. Bradykinin receptor characterization, distribution and mechanisms of signal transduction. Prog Growth Factor 1989; 1: 237–52.

38.

Schwartz

Pence

Kerns

Inglehart

McCann

Hagen

P-O

. Kinetics of vein graft cell division and function. Surgical Forum 1991; XLVII: 362–5.

39.

Massey

Davies

Klyachkin

. Bradykinin responses in experimental vein grafts. J Vasc Med Biol 1993; 4: 122–7.

40.

Linz

Schoelkens

. Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 1992; 20: (suppl 9): S83–90.

41.

O'Donohoe

Davies

Radic

Mikat

Hagen

P-O

. Increased concentrations of angiotensin converting enzyme in the intimal hyperplasia of experimental vein grafts. J Cardiovasc Pharmacol 1994; 23: 594–601.

42.

O'Donohoe

Schwartz

Radic

Mikat

McCann

Hagen

P-O

. Chronic ACE inhibition reduces intimal hyperplasia in experimental vein grafts. Ann Surg 1991; 214: 727–32.

43.

Cross

Sanadiki

Murray

Mikat

McCann

Hagen

P-O

. Mast cell infiltration: A possible mechanism for vein graft vasospasm. Surgery 1988; 104: 171–7.

44.

Ardissino

Barberis

De Servis

. Abnormal coronary vasoconstriction as a predictor of restenosis after successful coronary angioplasty in patients with unstable angina pectoris. N Engl J Med 1991; 325: 1053–7.