The role of COX 2 in acute cardiac remodeling secondary to pressure overload

Abstract

We hypothesized that pharmacologic blockade of Cyclooxygenase 2(COX 2) using Nimesulide (Nime) prevents maladaptive changes in the LV structure/function secondary to pressure overload. In vivo LV structure/function was assessed by pressure/volume catheter at 14 days post surgery in 3 groups(n ≥ 6 per group); Sham-operated (Sham), Untreated pressure overload (PO) and PO + Nime (10 mg/kg/d). Relative to sham, LV mass index was significantly increased in PO group(P≤0.05). End diastolic volume, an indicator of chamber size, was significantly decreased in the PO animals compared to sham (202 ± 17 vs. 143 ± 16 Sham vs. PO, Nime + PO: 226 ± 9). Hydroxyproline analysis demonstrated collagen levels in PO rats were significantly elevated relative to Sham. Nime treatment significantly prevented the increase in LV mass index, reduction in end diastolic volume and increase in collagen levels. In summary, COX 2 inhibition with Nime prevented the maladaptive changes in the LV after pressure overload. This suggests that acute cardiac remodeling during pathological stress occurs by COX 2 mediated inflammatory pathway and can be attenuated by COX 2 inhibitors. Acknowledging the clinical failure of chronic COX 2 inhibitor use, we propose that acute treatment with COX 2 inhibitors during the initial stages of cardiac remodeling can be beneficial in maintaining normal cardiac structure and function. AHA 09BGIA2090065