TY - JOUR

T1 - Mortality and morbidity in different immunization protocols for experimental autoimmune myocarditis in rats

AU - Schmerler, P

AU - Jeuthe, S

AU - O h-Ici, D

AU - Wassilew, K

AU - Lauer, D

AU - Kaschina, E

AU - Kintscher, U

AU - Müller, S

AU - Muench, F

AU - Kuehne, T

AU - Berger, F

AU - Unger, T

AU - Steckelings, U M

AU - Paulis, L

AU - Messroghli, D

N1 - © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

PY - 2014/4

Y1 - 2014/4

N2 - AIM: We aimed to investigate the histological and clinical presentations of experimental autoimmune myocarditis (EAM) induced by different immunization schemes.METHODS: Male young Lewis rats were divided into five groups immunized by porcine myocardial myosin: subcutaneously (SC) 2 mg (in two 1-mg doses on day 0 and 7), 0 mg (sham group) subcutaneously into rear footpads (RF), 0.25 mg RF, 0.5 mg RF or 1 mg RF (all RF once on day 0). On day 21, left ventricular (LV) function was assessed by cardiac magnetic resonance imaging and cardiac catheterization. The type and degree of myocardial inflammatory infiltrates were determined by conventional histology and immunohistochemistry.RESULTS: In the SC immunized rats and in the RF sham group, we observed 0% mortality, while in the actively RF immunized rats, mortality was 20, 20 and 44% for the 0.25 mg, 0.5 mg and 1 mg myosin doses respectively. Morbidity as defined by inflammatory infiltrates on haematoxylin and eosin (HE) staining was 22% in the SC immunized rats, 0% in the RF sham group and 100% in all actively RF immunized groups. We observed augmented relative ventricle weight and spleen weight, increased LV end-diastolic pressure, reduced LV developed pressure and reduced LV ejection fraction in all with myosin-immunized RF groups without any systematic dose effect.CONCLUSION: Subcutaneous immunization to the neck and flanks did not induce a reproducible EAM, while RF myosin administration reliably led to EAM. Lower myosin doses seem to induce the complete histological and clinical picture of EAM while being associated with lower mortality, non-specific symptoms and animal distress.

AB - AIM: We aimed to investigate the histological and clinical presentations of experimental autoimmune myocarditis (EAM) induced by different immunization schemes.METHODS: Male young Lewis rats were divided into five groups immunized by porcine myocardial myosin: subcutaneously (SC) 2 mg (in two 1-mg doses on day 0 and 7), 0 mg (sham group) subcutaneously into rear footpads (RF), 0.25 mg RF, 0.5 mg RF or 1 mg RF (all RF once on day 0). On day 21, left ventricular (LV) function was assessed by cardiac magnetic resonance imaging and cardiac catheterization. The type and degree of myocardial inflammatory infiltrates were determined by conventional histology and immunohistochemistry.RESULTS: In the SC immunized rats and in the RF sham group, we observed 0% mortality, while in the actively RF immunized rats, mortality was 20, 20 and 44% for the 0.25 mg, 0.5 mg and 1 mg myosin doses respectively. Morbidity as defined by inflammatory infiltrates on haematoxylin and eosin (HE) staining was 22% in the SC immunized rats, 0% in the RF sham group and 100% in all actively RF immunized groups. We observed augmented relative ventricle weight and spleen weight, increased LV end-diastolic pressure, reduced LV developed pressure and reduced LV ejection fraction in all with myosin-immunized RF groups without any systematic dose effect.CONCLUSION: Subcutaneous immunization to the neck and flanks did not induce a reproducible EAM, while RF myosin administration reliably led to EAM. Lower myosin doses seem to induce the complete histological and clinical picture of EAM while being associated with lower mortality, non-specific symptoms and animal distress.

KW - Animals

KW - Autoimmune Diseases

KW - Immunization

KW - Male

KW - Myocarditis

KW - Myocardium

KW - Myosins

KW - Random Allocation

KW - Rats

KW - Rats, Inbred Lew

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/apha.12227

DO - 10.1111/apha.12227

M3 - Journal article

C2 - 24410878

VL - 210

SP - 889

EP - 898

JO - Acta Physiologica (Online)

JF - Acta Physiologica (Online)

SN - 1748-1716

IS - 4

ER -