Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain)

Madhulika Chandra, Herbert B. Tanowitz, Stefka B. Petkova, Huan Huang, Louis M. Weiss, Murray Wittner, Stephen M. Factor, Vitaliy Shtutin, Linda A. Jelicks, John Chan, Jamshid Shirani

Research output: Contribution to journalArticle

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Abstract

Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To assess the functional significance of NOS2 in murine Chagas' disease, we infected NOS2 knockout (NOS2-/-) and C57BL/6 × 129sv (wild type) mice with the Tulahuen strain of T. cruzi. Serial transthoracic echocardiography was performed to assess the progression of left and right ventricular dysfunction in infected mice. Uninfected wild type and NOS2-/- mice served as controls. At day 10 post-infection (p.i.), infected wild type mice had larger left ventricular end-diastolic diameter (2.52 ± 0.14-vs-2.11 ± 0.06 mm, P < 0.02) and right ventricle (0.6 ± 0.2-vs-0 visual grade, P < 0.02) as compared with uninfected wild type mice. At day 19 p.i., compared with uninfected controls, infected wild type mice had larger left ventricular end-diastolic diameter (3.30 ± 0.29-vs-2.11 ± 0.07 mm), left ventricular end-systolic diameter (1.86 ± 0.29-vs-0.88 ± 0.05 mm), right ventricle (1.6 ± 0.2-vs-0 visual grade), lower heart rate (413 ± 27-vs-557 ± 25 beats per min), left ventricular relative wall thickness (0.44 ± 0.05-vs-0.64 ± 0.03) and fractional shortening (45 ± 4-vs-57 ± 2%) [P < 0.05 for all]. In contrast, no differences in left ventricular end-diastolic diameter or fractional shortening were noted among infected and uninfected NOS2-/- mice at day 19 p.i. Compared with uninfected controls, infected NOS2-/- mice had significantly lower heart rate (272 ± 23-vs-512 ± 31 beats per min, P < 0.01) and larger right ventricle (0.6±0.2-vs-0, P < 0.05 visual grade). The magnitude of right ventricular dilation in NOS2-/- mice was less than that observed in infected wild type mice. At necropsy, the heart weight was greater (129 ± 16-vs-109 ± 7 mg, P = 0.02) and myocardial inflammation more severe in infected wild type compared with infected NOS2-/- mice. Myocardial interleukin (IL)-1β, IL-6, tumour necrosis factor-α, and interferon-γ were induced in all infected mice. These data indicate that nitric oxide derived from NOS2 plays an important role in the development and progression of ventricular dilation and systolic dysfunction in acute murine chagasic myocarditis caused by infection with the Tulahuen strain.

Original languageEnglish (US)
Pages (from-to)897-905
Number of pages9
JournalInternational Journal for Parasitology
Volume32
Issue number7
DOIs
StatePublished - 2002

Fingerprint

Trypanosoma cruzi
Myocarditis
Nitric Oxide Synthase Type II
Knockout Mice
Heart Ventricles
Chagas Disease
Infection
Dilatation
Heart Rate
Right Ventricular Dysfunction
Left Ventricular Dysfunction
Interleukin-1
Interferons
Echocardiography
Interleukin-6
Nitric Oxide
Tumor Necrosis Factor-alpha
Cytokines
Inflammation
Weights and Measures

Keywords

  • Chagas' disease
  • Echocardiography
  • Inducible nitric oxide synthase
  • Knockout mice
  • Nitric oxide
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain). / Chandra, Madhulika; Tanowitz, Herbert B.; Petkova, Stefka B.; Huang, Huan; Weiss, Louis M.; Wittner, Murray; Factor, Stephen M.; Shtutin, Vitaliy; Jelicks, Linda A.; Chan, John; Shirani, Jamshid.

In: International Journal for Parasitology, Vol. 32, No. 7, 2002, p. 897-905.

Research output: Contribution to journalArticle

Chandra, Madhulika ; Tanowitz, Herbert B. ; Petkova, Stefka B. ; Huang, Huan ; Weiss, Louis M. ; Wittner, Murray ; Factor, Stephen M. ; Shtutin, Vitaliy ; Jelicks, Linda A. ; Chan, John ; Shirani, Jamshid. / Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain). In: International Journal for Parasitology. 2002 ; Vol. 32, No. 7. pp. 897-905.
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abstract = "Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To assess the functional significance of NOS2 in murine Chagas' disease, we infected NOS2 knockout (NOS2-/-) and C57BL/6 × 129sv (wild type) mice with the Tulahuen strain of T. cruzi. Serial transthoracic echocardiography was performed to assess the progression of left and right ventricular dysfunction in infected mice. Uninfected wild type and NOS2-/- mice served as controls. At day 10 post-infection (p.i.), infected wild type mice had larger left ventricular end-diastolic diameter (2.52 ± 0.14-vs-2.11 ± 0.06 mm, P < 0.02) and right ventricle (0.6 ± 0.2-vs-0 visual grade, P < 0.02) as compared with uninfected wild type mice. At day 19 p.i., compared with uninfected controls, infected wild type mice had larger left ventricular end-diastolic diameter (3.30 ± 0.29-vs-2.11 ± 0.07 mm), left ventricular end-systolic diameter (1.86 ± 0.29-vs-0.88 ± 0.05 mm), right ventricle (1.6 ± 0.2-vs-0 visual grade), lower heart rate (413 ± 27-vs-557 ± 25 beats per min), left ventricular relative wall thickness (0.44 ± 0.05-vs-0.64 ± 0.03) and fractional shortening (45 ± 4-vs-57 ± 2{\%}) [P < 0.05 for all]. In contrast, no differences in left ventricular end-diastolic diameter or fractional shortening were noted among infected and uninfected NOS2-/- mice at day 19 p.i. Compared with uninfected controls, infected NOS2-/- mice had significantly lower heart rate (272 ± 23-vs-512 ± 31 beats per min, P < 0.01) and larger right ventricle (0.6±0.2-vs-0, P < 0.05 visual grade). The magnitude of right ventricular dilation in NOS2-/- mice was less than that observed in infected wild type mice. At necropsy, the heart weight was greater (129 ± 16-vs-109 ± 7 mg, P = 0.02) and myocardial inflammation more severe in infected wild type compared with infected NOS2-/- mice. Myocardial interleukin (IL)-1β, IL-6, tumour necrosis factor-α, and interferon-γ were induced in all infected mice. These data indicate that nitric oxide derived from NOS2 plays an important role in the development and progression of ventricular dilation and systolic dysfunction in acute murine chagasic myocarditis caused by infection with the Tulahuen strain.",
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T1 - Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain)

AU - Chandra, Madhulika

AU - Tanowitz, Herbert B.

AU - Petkova, Stefka B.

AU - Huang, Huan

AU - Weiss, Louis M.

AU - Wittner, Murray

AU - Factor, Stephen M.

AU - Shtutin, Vitaliy

AU - Jelicks, Linda A.

AU - Chan, John

AU - Shirani, Jamshid

PY - 2002

Y1 - 2002

N2 - Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To assess the functional significance of NOS2 in murine Chagas' disease, we infected NOS2 knockout (NOS2-/-) and C57BL/6 × 129sv (wild type) mice with the Tulahuen strain of T. cruzi. Serial transthoracic echocardiography was performed to assess the progression of left and right ventricular dysfunction in infected mice. Uninfected wild type and NOS2-/- mice served as controls. At day 10 post-infection (p.i.), infected wild type mice had larger left ventricular end-diastolic diameter (2.52 ± 0.14-vs-2.11 ± 0.06 mm, P < 0.02) and right ventricle (0.6 ± 0.2-vs-0 visual grade, P < 0.02) as compared with uninfected wild type mice. At day 19 p.i., compared with uninfected controls, infected wild type mice had larger left ventricular end-diastolic diameter (3.30 ± 0.29-vs-2.11 ± 0.07 mm), left ventricular end-systolic diameter (1.86 ± 0.29-vs-0.88 ± 0.05 mm), right ventricle (1.6 ± 0.2-vs-0 visual grade), lower heart rate (413 ± 27-vs-557 ± 25 beats per min), left ventricular relative wall thickness (0.44 ± 0.05-vs-0.64 ± 0.03) and fractional shortening (45 ± 4-vs-57 ± 2%) [P < 0.05 for all]. In contrast, no differences in left ventricular end-diastolic diameter or fractional shortening were noted among infected and uninfected NOS2-/- mice at day 19 p.i. Compared with uninfected controls, infected NOS2-/- mice had significantly lower heart rate (272 ± 23-vs-512 ± 31 beats per min, P < 0.01) and larger right ventricle (0.6±0.2-vs-0, P < 0.05 visual grade). The magnitude of right ventricular dilation in NOS2-/- mice was less than that observed in infected wild type mice. At necropsy, the heart weight was greater (129 ± 16-vs-109 ± 7 mg, P = 0.02) and myocardial inflammation more severe in infected wild type compared with infected NOS2-/- mice. Myocardial interleukin (IL)-1β, IL-6, tumour necrosis factor-α, and interferon-γ were induced in all infected mice. These data indicate that nitric oxide derived from NOS2 plays an important role in the development and progression of ventricular dilation and systolic dysfunction in acute murine chagasic myocarditis caused by infection with the Tulahuen strain.

AB - Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To assess the functional significance of NOS2 in murine Chagas' disease, we infected NOS2 knockout (NOS2-/-) and C57BL/6 × 129sv (wild type) mice with the Tulahuen strain of T. cruzi. Serial transthoracic echocardiography was performed to assess the progression of left and right ventricular dysfunction in infected mice. Uninfected wild type and NOS2-/- mice served as controls. At day 10 post-infection (p.i.), infected wild type mice had larger left ventricular end-diastolic diameter (2.52 ± 0.14-vs-2.11 ± 0.06 mm, P < 0.02) and right ventricle (0.6 ± 0.2-vs-0 visual grade, P < 0.02) as compared with uninfected wild type mice. At day 19 p.i., compared with uninfected controls, infected wild type mice had larger left ventricular end-diastolic diameter (3.30 ± 0.29-vs-2.11 ± 0.07 mm), left ventricular end-systolic diameter (1.86 ± 0.29-vs-0.88 ± 0.05 mm), right ventricle (1.6 ± 0.2-vs-0 visual grade), lower heart rate (413 ± 27-vs-557 ± 25 beats per min), left ventricular relative wall thickness (0.44 ± 0.05-vs-0.64 ± 0.03) and fractional shortening (45 ± 4-vs-57 ± 2%) [P < 0.05 for all]. In contrast, no differences in left ventricular end-diastolic diameter or fractional shortening were noted among infected and uninfected NOS2-/- mice at day 19 p.i. Compared with uninfected controls, infected NOS2-/- mice had significantly lower heart rate (272 ± 23-vs-512 ± 31 beats per min, P < 0.01) and larger right ventricle (0.6±0.2-vs-0, P < 0.05 visual grade). The magnitude of right ventricular dilation in NOS2-/- mice was less than that observed in infected wild type mice. At necropsy, the heart weight was greater (129 ± 16-vs-109 ± 7 mg, P = 0.02) and myocardial inflammation more severe in infected wild type compared with infected NOS2-/- mice. Myocardial interleukin (IL)-1β, IL-6, tumour necrosis factor-α, and interferon-γ were induced in all infected mice. These data indicate that nitric oxide derived from NOS2 plays an important role in the development and progression of ventricular dilation and systolic dysfunction in acute murine chagasic myocarditis caused by infection with the Tulahuen strain.

KW - Chagas' disease

KW - Echocardiography

KW - Inducible nitric oxide synthase

KW - Knockout mice

KW - Nitric oxide

KW - Trypanosoma cruzi

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