gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Reduction of cardiac inflammation after treatment with cytokine-inhibitors improves LV function in diabetic cardiopathy

Die Reduktion der kardialen EntzŘndung nach Behandlung mit Zytokin-Hemmern verbessert die LV Funktion bei diabetischer Kardiopathie

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker S. Dhayat - Dep. of Cardiology, CharitÚ-University, UKBF (Berlin, D)
  • F. Spillmann - Dep. of Cardiology, CharitÚ-University, UKBF (Berlin, D)
  • N. Dhayat - Dep. of Cardiology, CharitÚ-University, UKBF (Berlin, D)
  • A. Riad - Dep. of Cardiology, CharitÚ-University, UKBF (Berlin, D)
  • M. Noutsias - Dep. of Cardiology, CharitÚ-University, UKBF (Berlin, D)
  • H.P. Schultheiss - Dep. of Cardiology, CharitÚ-University, UKBF (Berlin, D)
  • C. Tsch÷pe - Dep. of Cardiology, CharitÚ-University, UKBF (Berlin, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. DŘsseldorf, K÷ln: German Medical Science; 2004. Doc03hochP70

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch170.shtml

Published: November 11, 2004

© 2004 Dhayat et al.
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Outline

Text

Background

Oxidative stress-induced activation of the adhesion molecules ICAM and VCAM on endothelia is pivotal for the tissue migration of CD68+ macrophages, which can further process this inflammatory response via the synthesis of cytokines like TNFa, IL1b, IL2 and IL18. This study evaluated the role of this pathway for the development of streptozotocin (STZ)-induced diabetic cardiopathy as well after treatment with the interleukin-1b (IL1b)-converting enzyme inhibitor (ICEI) HMR3480 as TNFa antibody (TNFa-Ab) C432A.

Methods

ICAM-1, VCAM-1, macrophages (ED1), TNFa, IL1b, IL2 and IL18 infiltrates were visualized immunohistochemically and quantified by digtal image analysis in 5Ám-thick cardiac cryosections in male Sprague Dawley (SD) rats, STZ-induced diabetic rats (SD-STZ; 6 weeks after STZ injection 70mg/kg i.p.), SD-STZ rats treated with ICEI (50mg/kg/12h; p.o.) and in SD-STZ rats treated with TNFα-Ab (5mg/kg/60h; i.p.) (n=8/group). Hemodynamics represented by LVP, dP/dt max and dP/dt min were measured in anesthesized open-chest animals by a Millar tip catheter.

Results

In comparison to normoglycemic SD, LVP (61.3▒1.1 vs. 90.4▒2.0 mmHg), dP/dtmax (4300▒100 vs. 5500▒150 mmHg/s) and dP/dtmin (-2166▒400 vs. -4000▒300 mmHg/s) were significantly impaired by 32% in SD-STZ animals. LV function of ICEI and TNFa-Ab treated SD-STZ rats was improved by more than 25% compared to SD-STZ animals. Intramyocardial cytokine expression was significantly higher in SD-STZ animals than in the other animal groups [Tab.á1].

Conclusion

Cell adhesion molecule activation, immunocompetent infiltration and cytokines are involved in the pathophysiology of experimental diabetic cardiopathy. Both ICE-inhibition and TNFa antagonism minimize the intramyocardial inflammatory response and thus the cytokine-mediated negative inotropism.