- Poster presentation
- Open Access
Pharmacological CCR1 blockade limits infarct size and preserves cardiac function in a chronic model of myocardial ischemia/reperfusion
© Van de Sandt et al. 2011
- Published: 1 March 2011
- Infarct Size
- Diastolic Function
- Chemokine Receptor CCR1
- CCR1 Antagonist
- Promising Therapeutic Approach
This study sought to determine the chronic effects of pharmacological blockade of the chemokine receptor CCR1 via application of the potent, selective antagonist BX471 in a murine model of myocardial ischemia/reperfusion (I/R). CCR1 is a prominent receptor in mediating inflammatory leukocyte recruitment. The intense inflammatory response is considered to be a key component of cardiac remodelling. Thus, limiting the post-reperfusion inflammatory pattern seems to be a promising therapeutic approach in limiting reperfusion injury. Previously, we demonstrated that CCR1-/- mice exhibit attenuated infarct expansion and preserved LV function in a chronic model of myocardial no-reflow infarction due to an abrogated inflammatory response.
C57/B6 mice underwent a 60-minute coronary occlusion in a closed-chest model of myocardial I/R. Mice were treated with the specific CCR1 antagonist, BX471 (50 mg/kg BW, s.c.), or placebo, for 96 hours at 8-hour intervals starting 15 minutes prior to reperfusion. At 21 days of reperfusion, cardiac function was assessed using a pressure- volume catheter (Millar) inserted in the left ventricle. Infarct size was analysed and cardiac content for collagen was elucidated.
Infarct size was significantly smaller in the BX471-treated group (placebo: 20.7 ± 2.8% vs. BX471: 11.6 ± 4.2%, P < 0.05; area at risk did no differ between the groups). At 21 days of reperfusion BX471-treated mice exhibited a tendency towards improved cardiac function. Significantly improved diastolic function was documented in BX471-treated mice (dP/dtmin placebo: -7,635 ± 1,090 vs. BX471: -9,845 ± 657, P < 0.01). In histochemical analysis, collagen content was elevated in the hearts of BX471-treated mice.
Pharmacological CCR1 antagonism leads to improved diastolic function and attenuated infarct size in a chronic model of ischemia/reperfusion, suggesting that CCR1 antagonism might provide a promising therapeutic approach in myocardial infarction. The increased cardiac collagen documented in the treated group of our study might point towards a beneficial effect in the restructuring of the extracellular collagen matrix. Further studies of the underlying mechanisms and a detailed analysis of structural remodelling after pharmacological CCR1 blockade are warranted.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.