Download PDF
J Reconstr Microsurg 2007; 23(5): 257-262
DOI: 10.1055/s-2007-985206
© Thieme Medical Publishers

Efficacy of Ethyl Nitrite in Reversing Surgical Vasospasm

Alessio Baccarani1 , Koji Yasui1 , Kevin C. Olbrich1 , Ahmed El-Sabbagh1 , Stephen Kovach1 , Keith E. Follmar1 , Detlev Erdmann1 , L. Scott Levin1 , Jonathan S. Stamler2 , Bruce Klitzman1 , Michael R. Zenn1
  • 1Division of Plastic, Reconstructive, Maxillofacial, and Oral Surgery, Duke University Medical Center, Durham, North Carolina
  • 2Department of Medicine, Division of Cardiovascular Medicine, Duke University Medical Center, Durham, North Carolina
Further Information

Publication History

Publication Date:
18 September 2007 (online)

Also available at
    Permissions and Reprints

ABSTRACT

Vasospasm leading to thrombosis is a major cause of free flap failure. Flap blood flow may improve by application of vasodilating agents to the pedicle. The purpose of this study is to evaluate the effect of a novel S-nitrosylating agent, O-ethyl nitrite, on flap blood flow and pedicle vessels diameter in a rat model, after induction of vasospasm. Two hours after surgery, the arterial diameter was significantly (P < .05) dilated by treatment with O-ethyl nitrite, lidocaine, or lidocaine + O-ethyl nitrite. None of these treatments had a statistically significant effect on blood flow or venous diameter. Twenty-four hours following surgery, both O-ethyl nitrite- and lidocaine-treated groups had larger arteries than the control group (P < .05). The O-ethyl nitrite-treated animals also had significantly (P < .05) elevated blood flow compared with control animals, but lidocaine-treated animals did not demonstrate any improved flow at 24 hours. O-Ethyl nitrite may become clinically useful in microvascular surgery procedures.

KEYWORDS

Vasospasm - vasodilating agents - ethyl nitrite (ENO)

REFERENCES

  • 1 Lantieri L A, Carayon A, Maistre O et al.. Tissue and plasma levels of endothelin in free flaps.  Plast Reconstr Surg. 2003;  111 85-91
    PubMedGoogle Scholar
  • 2 Zhang J, Lipa J, Black C E et al.. Pharmacological characterization of vasomotor activity of human muscolocutaneous perforator artery and vein.  J Appl Physiol. 2000;  89 2268-2275
    CrossrefPubMedGoogle Scholar
  • 3 Siemionow M, Arslan E. Ischemia/reperfusion injury: a review in relation to free tissue transfers.  Microsurgery. 2004;  24 468-475
    CrossrefPubMedGoogle Scholar
  • 4 Kerrigan C L, Zelt G, Daniel R K. Secondary critical ischemia time of experimental skin flaps.  Plast Reconstr Surg. 1984;  74 522-524
    CrossrefPubMedGoogle Scholar
  • 5 Kerrigan C L, Daniel R. Critical ischemia time and the failing skin flap.  Plast Reconstr Surg. 1982;  69 986-989
    CrossrefPubMedGoogle Scholar
  • 6 Howell S T, Seaber A, Urbaniak J R. Microcirculatory responses to vascular washout following ischemia.  Microsurgery. 1989;  10 522-526
    PubMedGoogle Scholar
  • 7 Wettstein R, Wessendorf R, Sckell A, Leunig M, Banic A, Erni E. The effect of pedicle artery vasospasm on microhemodynamics in anatomically perfused and extended skin flap tissue.  Ann Plast Surg. 2000;  45 155-161
    CrossrefPubMedGoogle Scholar
  • 8 Seaber A. Experimental vasospasm.  Microsurgery. 1987;  8 234-241
    CrossrefPubMedGoogle Scholar
  • 9 Erni D, Sakai H, Banic A, Tshopp H M, Intaglietta M. Quantitative assessment of microhemodynamics in ischemia skin flap tissue by intervital microscopy.  Ann Plast Surg. 1999;  43 405-415
    CrossrefPubMedGoogle Scholar
  • 10 Bruch H P, Hörl M, Lanz U, Bauer B, Epping J. Vascular spasm in microsurgery.  Handchir Mikrochir Plast Chir. 1987;  19 186-190
    PubMedGoogle Scholar
  • 11 Hou S M, Seaber A, Urbaniak J R. Blood-induced arterial segmental spasm.  J Reconstr Microsurg. 1986;  3 29-32
    PubMedGoogle Scholar
  • 12 Bentz M L, Sheppeck R, Macpherson T et al.. Vasospasm and platelet deposition in human arteries: effects of topical methylene blue.  Plast Reconstr Surg. 1991;  88 851-859
    PubMedGoogle Scholar
  • 13 Jokuszies A, Jansen V, Lahoda L U, Steinau H U, Vogt P M. Plasma concentration of endothelin-1 after myocutaneous latissimus dorsi-transplantation: role in reperfusion injury.  Handchir Mikrochir Plast Chir. 2005;  37 193-201
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Joshua I. Endothelin-induced vasoconstriction of small resistance vessels in the microcirculation of the rat cremaster muscle.  Microvasc Res. 1990;  40 191-198
    CrossrefPubMedGoogle Scholar
  • 15 Perez del Villar C, Gracia Alonso C, Feldstein C A, Juncos L A, Romero J C. Role of endothelin in the pathogenesis of hypertension.  Mayo Clin Proc. 2005;  80 84-96
    PubMedGoogle Scholar
  • 16 Pang C Y, Xu H, Huang N, Forrest C R, Perreault T M, Neligan P C. Amplification effect and mechanism of action of ET-1 in U-46619-induced vasoconstriction in pig skin.  Am J Physiol Regulat Intergrat Comp Physiol. 2001;  280 R713-R720
    PubMedGoogle Scholar
  • 17 Samuelson U E, Heden P, Jembeck J, Wiklund N P. Endothelin reduces blood flow in experimental skin flaps.  Scand J Plast Reconstr Surg Hand Surg. 1992;  26 241-245
    PubMedGoogle Scholar
  • 18 Fyhrquist F, Saijonmaa O, Metsarinne K, Tikkanen I, Roseniof K, Tikkanen T. Raised plasma endothelin-1 concentration following cold pressor test.  Biochem Biophys Res Commun. 1990;  169 217-221
    CrossrefPubMedGoogle Scholar
  • 19 Evans G R, Gherardini G, Gurlek A et al.. Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardinpine, papaverine, and lidocaine on the rabbit carotid artery.  Plast Reconstr Surg. 1997;  100 1475-1481
    CrossrefPubMedGoogle Scholar
  • 20 Notodihardjo H W, Ogawa Y, Kusumoto K. The blood flow patterns of microsurgical procedures in rats with topical and systemic vasodilators.  Scand J Plast Reconstr Surg Hand Surg. 1998;  32 249-254
    CrossrefPubMedGoogle Scholar
  • 21 Gherardini G, Gurleka A, Cromeens D, Joly G A, Wang B G, Evans G R. Drug-induced vasodilation: in vitro and in vivo study on the effects of lidocaine and papvenne on rabbit carotid artery.  Microsurgery. 1998;  18 90-96
    CrossrefPubMedGoogle Scholar
  • 22 Kim D C, Chen D, Perrotta V J et al.. Porcine gastroepiploic artery as an in vitro experimental model to study vasodilators in microsurgery.  Ann Plast Surg. 1996;  36 502-507
    CrossrefPubMedGoogle Scholar
  • 23 Chafin J B, Wax M, Johnstone R, Bishop D. The use of lidocaine in microvascular reconstruction.  Otolaryngol Head Neck Surg. 1997;  117 93-98
    CrossrefPubMedGoogle Scholar
  • 24 Queen L, Ferro A. Beta-adrenergic receptors and nitric oxide generation in the cardiovascular system.  Cell Mol Life Sci. 2006;  63 1070-1083
    CrossrefPubMedGoogle Scholar
  • 25 Qi W N, Zhang L, Chen L E, Seaber A V, Urbaniak J R. Nitric oxide involvement in reperfusion injury of denervated muscle.  J Hand Surg. 2004;  29 638-645
    CrossrefPubMedGoogle Scholar
  • 26 Tesfamariam B. The effects of HMG-CoA reductase inhibitors on endothelial function.  Am J Cardiovasc Drugs. 2006;  6 115-120
    CrossrefPubMedGoogle Scholar
  • 27 Foster M W, McMahon T J, Stamler J S. S-Nitrosylation in health and disease.  Trends Mol Med. 2003;  9 160-168
    CrossrefPubMedGoogle Scholar
  • 28 Liu L, Yan Y, Zeng M et al.. Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock.  Cell Mol Life Sci. 2004;  116 617-628
    PubMedGoogle Scholar
  • 29 Chen L E, Seaber A, Urbaniak J R. Vasodilator action of prostaglandin E1 on microcirculation of rat cremaster muscle.  Microsurgery. 1990;  11 204-208
    CrossrefPubMedGoogle Scholar
  • 30 Hou S M, Seaber A, Urbaniak J R. Relief of blood-induced arterial vasospasm by pharmacologic solutions.  J Reconstr Microsurg. 1987;  3 147-151
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Bertelli J A, Mira J. Vascular freezing-a new method for immediate and permanent vasospasm relief: an experimental study in the rat.  Plast Reconstr Surg. 1994;  93 1041-1049
    CrossrefPubMedGoogle Scholar
  • 32 Puckett C L, Winter R, Geter R K, Goebel D. Studies of pathologic vasoconstriction (vasospasm) in microvascular surgery.  J hand Surg. 1985;  10 343-349
    PubMedGoogle Scholar
  • 33 Yang Z, Bauer E, von Segesser L, Stulz P, Turina M, Luscher T F. Different mobilization of calcium in endothelin-1-induced contraction in human artery and veins: effects of calcium antagonists.  J Cardiovasc Pharmacol. 1990;  16 654-660
    PubMedGoogle Scholar
  • 34 Tane N, Inoue H, Aihara M, Ishida H. The effect of endothelin-1 on flap necrosis.  Ann Plast Surg. 1995;  35 389-395
    CrossrefPubMedGoogle Scholar
  • 35 Blair W F, Greene E, Eldridge M, Cipoletti R. Hemodynamics after microsurgical anastomosis: the effects of topical lidocaine.  J Microsurg. 1981;  2 157-164
    CrossrefPubMedGoogle Scholar
  • 36 Vanhoutte P M, Auch-Schwelk W, Boulanger C et al.. Does endothelin-1 mediate endothelium-dependent contractions during anoxia.  J Cardiovasc Pharmacol. 1989;  13(suppl 5) S124-S128
    PubMedGoogle Scholar
  • 37 Lusher T F, Yang Z, Tschudi M et al.. Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins.  Circ Res. 1990;  66 1088-1094
    PubMedGoogle Scholar
  • 38 Beekman W H, Sluimers J, Kort W J, van der Meulen J C. Resolution of experimental microvascular vasoconstriction in rats by topical application of lidocaine hydrochloride in varying concentrations.  Ann Plast Surg. 1988;  21 570-575
    CrossrefPubMedGoogle Scholar
  • 39 Jernbeck J, Samuelson U E. Effects of lidocaine and calcitonin gene-related peptide (CGRP) on isolated human radial arteries.  J Reconstr Microsurg. 1993;  9 361-365
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Zelis R. Mechanisms of vasodilation.  Am J Med. 1983;  27 3-12
    PubMedGoogle Scholar
  • 41 Hata T, Matsuki H, Kaneshina S. Effect of local anesthetics on the bilayer membrane of dipalmitoylphosphatidylcholine: interdigitation of lipid bilayer and vesicle-micelle transition.  Biophys Chem. 2000;  87 25-36
    CrossrefPubMedGoogle Scholar
  • 42 Matsuzaki K. Effect of skin flap ischemia on plasma endothelin-1 levels.  Ann Plast Surg. 1993;  31 499-503
    CrossrefPubMedGoogle Scholar
  • 43 Gobeil Jr F, Zhu T, Brault S et al.. Nitric oxide signaling via nuclearized e-NOS modulates expression of the immediate early genes i-NOS and mPGES-1.  J Biol Chem. 2006;  281 16058-16067
    CrossrefPubMedGoogle Scholar
  • 44 Kuo Y R, Wang F S, Jeng S F, Lutz B S, Huang H C, Yang K D. Nitrosoglutathione improves blood perfusion and flap survival by suppressing iNOS but protecting eNOS expression in the flap vessels after ischemia/reperfusion injury.  Surgery. 2004;  135 437-446
    CrossrefPubMedGoogle Scholar
  • 45 Cary S P, Winger J A, Derbyshire E R, Marietta M A. Nitric oxide signaling: no longer simply on or off.  Trends Biochem Sci. 2006;  31 231-239
    CrossrefPubMedGoogle Scholar
  • 46 Barman S A. Effect of nitric oxide on mitogen-activated protein kinases in neonatal pulmonary vascular smooth muscle.  Lung. 2005;  183 325-335
    CrossrefPubMedGoogle Scholar

Michael R ZennM.D. 

Division of Plastic, Reconstructive, Maxillofacial, and Oral Surgery

Box 3358, Duke University Medical Center, Durham, NC 27710