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Differentiating Spontaneous from Drug-Induced Vascular Injury in the Dog

Pfizer Global Research and Development, Sandwich, United Kingdom, frances_clemo{at}sandwich.pfizer.com

Winston E. Evering

Pfizer Global Research and Development, La Jolla, California

Paul W. Snyder

DepartmentofPathobiology, Purdue University, West Lafayette, Indiana

Mudher A. Albassam

Pfizer Global Research and Development, Ann Arbor, Michigan

When vascular injury is observed in dogs used in preclinical toxicology studies, careful evaluation of the lesions is warranted, especially when differentiating drug-induced vascular changes from spontaneous findings, such as idiopathic canine polyarteritis. The clinical signs as well as the nature and distribution of lesions can often be distinguishing, as is the case with vasoactive drugs, including vasodilators and/or positive inotropes (hydralazine, minoxidil, endothelin receptor antagonists, and phosphodiesterase III inhibitors). For most types of vasodilator-induced vascular injury, the lesion is often restricted to coronary arteries, whereas in idiopathic canine polyarteritis, arterial lesions not only involve coronary arteries, but also medium to small arteries of other organs. In addition, the nature of the changes in vessels yields important clues. Medial and adventitial hemorrhage is generally associated with vasodilator-induced arterial lesion, whereas hemorrhage is generally absent in idiopathic polyarteritis. Although idiopathic canine polyarteritis can generally be differentiated from vasoactive-induced vascular injury in dogs, there are increasing incidences of this type of polyarteritis in dogs receiving any 1 of a number of unrelated classes of compounds, suggestive of an exacerbation of the spontaneous disease. Therefore, in order to differentiate drug-induced injury from idiopathic canine polyarteritis, it is critical that examination of the vascular pathology be conducted with good understanding of clinical, pharmacological, and mechanistic data associated with the drug.

Key Words: Dog • vasculitis • drugs • vasoactive • polyarteritis • artery • arteriopathy • phosphodiesterase inhibitors.

References

• Albassam MA, Houston BJ, Greaves P., Barsoum N. (1989). Polyarteritis in a beagle. J Amer Vet Med Assos 194(11): 1595—1597.
• Albassam MA, Metz AL, Potoczak RE, Gallagher KP, Haleen S., Hallak H., McGuire EJ (2001). Studies on coronary arteriopathy in dogs following adminstration of CI-1020, an endothelin A receptor antagonist. Toxciol Pathol 29(3): 277—284.[CrossRef]
• Bishop SP (1990). Animal models of vasculitis. Toxicol Pathol 17: 109—117.[Web of Science]
• Boor PJ, Gothlieb AI, Joseph EC, Kerns WD, Roth RA, Tomaszewki KI (1995). Chemical-induced vasculature injury. Toxicol Appl Pharmacol 132: 177—195.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Boor PJ, Hysmith RM (1987). Allylamine cardiovascular toxicity. Toxicology 44: 129—145.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Bourdois PS, Dancla JL, Faccini JM, Nachbaur J., Monro AM (1982). The subacute toxicology of digoxin in dogs; clinical chemistry and histopathology of heart and kidneys. Arch Toxicol 51: 273—283.[CrossRef][Web of Science]
• Brooks PN (1984). Necrotizing vasculitis in a group of beagles. Lab Anim 18: 285—290.[Abstract/Free Full Text]
• Calabrese LH, Duna GF (1996). Drug-induced vasculitis. Curr Opin Rheumatol 8: 34—40.[Medline] [Order article via Infotrieve]
• Chelly JE, Doursout MF, Begaud B., Tsao CC, Hartley CJ (1986). Effects of hydralazine on regional blood flow in conscious dogs. J Pharmacol Exp Ther 238: 665—669.[Abstract/Free Full Text]
• Conrad LL, Gonzalez IE, Joel L., Furman RH (1956). Histochemical evaluation of canine coronary artery and arotic lesions induced by intravenous allylamine. Circ Res 4: 263—267.[Abstract/Free Full Text]
• Gans JH, Korson R., Cater MR, Ackerly CC (1980). Effects of short-term and long-term theobromine administration to male dogs. Toxicol Appl Pharmacol 53: 481—496.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Greaves P. (1998). Patterns of drug-induced cardiovascular pathology in the beagle dog: Relevance for humans. Exp Toxic Pathol 50: 283— 293.[Web of Science][Medline] [Order article via Infotrieve]
• Greaves P. (2000). Patterns of cardiovascular pathology induced by diverse cardioactive drugs. Toxicol Lett 112—113: 547—552.[CrossRef]
• Griffith RW, Grauwiler J., Hodel CH, Leist KH, Matter B. (1978). Toxicologic considerations. Ergot alkaloids and related compounds (1978). In: Handbook of Experimental Pharmacology, Vol. 49, Springer Verlag, Berlin. pp 805—851.
• Gristwood RW, Comer MB, Eden RJ, Taylor EM, Turner JA, Wallduck M., Owen DAA (1988). In vivo pharmacological studies with SK&F 94836, a potent intrope/vasodilator with sustained duration of action. Br J Pharmacol 93: 893—901.[Web of Science][Medline] [Order article via Infotrieve]
• Harcourt RA (1978). Polyarteritis in a colony of beagles. Vet Rec 102: 519— 522.[Abstract]
• Harleman HJ, Joseph EC, Eden RJ, Walker TF, Major IR, Lamb MS (1986). Cardiotoxicity of a new inotrope/vasodilator drug (SK&F 94120) in the dog. Arch Toxicol 59: 51—55.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Hartman HA (1987). Idiopathic extramural coronary arteritis in beagle and mongrel dogs. Vet Pathol 24: 537—544.[Abstract]
• Hayes TJ, Roberts GKS, Halliwell WH (1989). An idiopathic febrile necrotizing arteritis syndrome in the dog: Beagle pain syndrome. Toxicol Pathol 17(1): 129—137.[Web of Science][Medline] [Order article via Infotrieve]
• HogenEsch H., Snyder PW, Scott-Moncrieff CR, Glickman LT, Felsburg PJ (1995). Interleukin-6 activity in dogs with juvenile polyarteritis syndrome: Effects of corticosteroids. Clin Immunol Immunopathol 77(1): 107—110.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Humphery SJ, Zins GR (1984). Whole body and regional hemodynamic effects of minoxidil in the conscious dog. J Cardiovasc Pharmacol 6(6): 979—988.[Web of Science][Medline] [Order article via Infotrieve]
• Isaacs KR, Joseph EC, Betton GR (1989). Coronary vascular lesions in dogs treated with phosphodiesterase III inhibitors. Toxicol Pathol 17(1): 153—163.[Web of Science][Medline] [Order article via Infotrieve]
• Joseph EC (2000). Arterial lesions induced by phosphodiesterase III (PDE III) inhibitors and DA1 agonist. Toxicol Let 112—113: 537—546.[CrossRef]
• Joseph EC, Jones HB, Kerns WD (1996). Characterization of coronary arterial lesions in dog following administration of SK&F 95654, a phosphodiesterase III inhibitor. Toxicol Pathol 24(4): 429—435.[Abstract/Free Full Text]
• Joseph EC, Mesfin G., Kerns WD (1997). Pathogenesis of arterial lesions caused by vasoactive compounds in laboratory animals. In: Cardiovascular Toxicology, Bishop SP, Kerns WD (eds). Pergamon, New York, pp 279—307.
• Kelly DK (1989). Classification of naturally occurring arterial disease in the dog. Toxicol Pathol 17(1): 77—93.[Web of Science][Medline] [Order article via Infotrieve]
• Kelly DK, Grunsell CSG, Kenyon CJ (1973). Polyarteritis in the dog: A case report. Vet Rec 92: 363—366.[Web of Science][Medline] [Order article via Infotrieve]
• Kemi M., Usui T., Narama I., Takahasji R. (1990). Histopathology of spontanoeus panarteritis in beagle dogs. Jpn J Vet Sci 52(1): 55—61.[Web of Science]
• Kerns WD, Roth L., Hosokawa S. (2001). Idiopathic canine polyarteritis. In: Pathology of the Ageing Dog, Vol 2, Mohr U, Carlton WW, Dungworth DL, Benjamin SA, Capen CC, Hahn FF (eds). Iowa State University Press, Ames, IA, pp 118—126.
• Legendre AM (1995). Antimycotic drug therapy. In: Kirk's Current VeterinaryTherapyXIII, SmallAnimal Practice, Bonagura JD (ed). WB Saunders, Philadelphia, pp 327—331.
• Louden C., Nambi P., Branch C., Gossett K., Pullen M., Eustis S., Solleveld HA (1998). Coronary arterial lesions in dogs treated with an endothelin receptor antagonist. J Cardiovasc Pharmacol 31(Suppl 1): S384—S385.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Louden S., Nambi P., Pullen MA, Thomas RA, Tierney LA, Solleveld HA, Schwartz LW (2000). Endothelin receptor subtype distribution predisposes coronary arteries to damage. Am J Pathol 157: 123—134.[Abstract/Free Full Text]
• Mesfin GM, Piper RC, DuCharme DW, Carlson RG, Humphrey SJ, Zins GR ( 1989). Pathogenesis of cardiovascular alterations in dogs treated with minoxidil. Toxicol Pathol 17(1): 164—181.[Web of Science][Medline] [Order article via Infotrieve]
• Mesfin GM, Robinson FG, Higgins MJ, Zhong WZ, DuCharme DW (1995). The pharmacology basis of the cardiovascular toxicity of minodoxil in the dog. Toxicol Pathol 23(4): 498—506.[Abstract/Free Full Text]
• Mesfin GM, Shawaryn GG, Higgins MJ (1987). Cardiovascular alterations in dogs treated with hydralazine. Toxicol Pathol 15(1): 409—416.[Web of Science][Medline] [Order article via Infotrieve]
• Metz AL, Dominick MA, Suchanek G., Gough AW (1991). Acute cardiovascular toxicity induced by an adenosine agonist-antihypertensive in Beagles. Toxicol Pathol 19(2): 98—107.[Web of Science][Medline] [Order article via Infotrieve]
• Morishima H., Nonoyama T., Sasaki S., Miyajima H. (1990). Spontaneous lesions in beagle dogs used in toxicity studies. Exp Anim 39(2): 239—248.[Web of Science]
• Morris DO, Beale KM, Cutaneous vasculitis and vasculopathy (1999). Vet Clin North Amer: Small Anim Pract 29(6): 1325—1335.
• Randall MG, Hurvitz AI (1983). Immune-mediated vasculitis in five dogs. J Amer Vet Med Assoc 183(2): 207—211.
• Ruben Z., Deslex P., Nash G., Redmond NI, Poncet M., Dodd DC ( 1989). Spontaneous disseminated panarteritis in laboratory beagle dogs in atoxicity study: A possible genetic predilection. Toxicol Pathol 17(1): 145—152.[Web of Science][Medline] [Order article via Infotrieve]
• Sandusky GE, Means JR, Todd GC ( 1990). Comparative cardiovascular toxicity in dogs given inotropic agents by continuous intravenous infusion. Toxicol Pathol 18(2): 268—278.[Web of Science][Medline] [Order article via Infotrieve]
• Schlaeppi B., Roncari G., Zahm P. ( 1991). Vasculartoxicity in dogs associated with overdoses of a novel benzodiazepine receptor partial agonist. Arch Toxicol 65(1): 73—80.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Scott-Moncrieff JCR, Snyder PW, Glickman LT, Davis EL, Felsburg PJ (1992). Systemic necrotizing vasculitis in nine young beagles. J Amer Vet Med Assoc 201(10): 1553—1558.
• Snyder PW, Kazacos EA, Scott-Moncrieff JC, HogenEsch H., Carlton WW, Glickman LT, Felsburg PJ (1995). Pathologic features of naturally occurring juvenile polyarteritis in Beagle dogs. Vet Pathol 32: 337—345.[Abstract]
• Spencer A., Greaves P. (1987) Periarteritis in a beagle colony. J Comp Path 97: 121—128.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Stejskal V., Havu N., Malmfors T. (1982). Necrotizing vasculitis as an immunological complication in toxicity study. Arch Toxicol Suppl 5: 283—286.[Medline] [Order article via Infotrieve]
• Stephen-Gueldne M., Inomata A., Coronary arterial lesions induced by endothelin antagonists (2000). Toxicol Lett 112—113: 531—535.[CrossRef]
• Teske RH, Bishop SP, Righter HF, Detweiler DK (1976). Subacute digoxin toxicosis in the beagle dog. Toxicol Appl Pharmacol 35: 283—301.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Uprichard ACG, Metz AL, Hallak H., Haleen SJ (1998). PD 156707: A selective endothelin-A receptor antagonist. Cardiovas Drug Rev 16(2): 89— 104.[CrossRef]
• Van Vleet JF, Ferrans VJ, Herman E. (1991). Cardiovascular and skeletal muscle systems. In: Handbook of Toxicology Pathology, Haschek WM, Rousseaux CG (eds). Academic Press, Inc, San Diego, pp 539—624.
• Waters Ll, DeSuto-Nagy GI (1950). Lesions of the coronary arteries and great vessels of the dog following injection of adrenalin. Their prevention by dibenamine. Science 111: 634—635.[Free Full Text]
• Will JA, Bisgard GE (1972). Haemodynamic effects of oral aminorex and amphetamine in unanesthetized beagle dogs. Thorax 27: 120—126.[Abstract/Free Full Text]

Toxicologic Pathology, Vol. 31, No. 1 suppl, 25-31 (2003)
DOI: 10.1080/01926230390174904


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