Alteration in myocardial prostaglandin D synthase expression in pressure overload-induced left ventricular remodeling in rats

Abstract

We hypothesized that acute pharmacological blockade of cyclooxygenase-2 (COX-2) using nimesulide (Nime) would prevent maladaptive changes in left ventricular (LV) structure and function secondary to abdominal aortic coarctation-induced pressure overload (PO). In vivo LV chamber dimension and function were assessed by pressure/volume admittance catheter at 14 days' postsurgery in three groups (n ≥ 6/group): sham-operated (Sham); untreated PO; and selective COX-2 inhibitor nimesulide-treated PO (PO + Nime; 25 mg/kg/d). Treatment was initiated 24 h prior to surgical induction of PO. Relative to Sham, there was a marked increase in LV mass index in the PO groups (2.2 ± 0.01 mg/g versus 2.9 ± 0.10 mg/g Sham versus PO, PO+Nime: 2.5 ± 0.03 mg/g). End diastolic volume, an indicator of chamber size, was significantly decreased in the PO animals compared with Sham (202 ± 17μL versus 143 ± 16 μL Sham versus PO, PO + Nime: 226 ± 9 μL). Collagen levels in PO rats assessed by hydroxyproline analysis were significantly elevated relative to Sham values. Nimesulide treatment attenuated: (1) the increase in LV mass index; (2) the reduction in end diastolic volume; and (3) the PO-induced increase in myocardial collagen. In summary, acute COX-2 inhibition with nimesulide attenuated the maladaptive changes in the LV after PO. Acknowledging the clinical failure of chronic COX-2 inhibitor use, we propose that acute treatment with COX-2 inhibition during the initial stages of cardiac remodeling can be beneficial in maintaining the normal cardiac structure and function during PO.

A novel experimental model of erectile dysfunction in rats with heart failure using volume overload

“…Lower ejection fraction by the ventricle is an important feature of HF [ 28 ]. Previous studies have shown similar cardiovascular changes using the ACF model in rats after 4, 8 and 12 weeks [ 12 , 26 ].…”

“…HF experimental models in mammals have provided additional support for understanding HF pathophysiological alterations [ 11 ]. The aortocaval fistula (ACF) model has been extensively used for studying the pathophysiology of volume-overload HF in rats [ 11 , 12 ]. The ACF procedure leads to an instant and constant hemodynamic change due to a reduction in arterial pressure along with a considerable enhancement in venous blood circulation to the right ventricle, resulting in an offsetting stimulation of numerous neurohormonal factors and structural modifications in the vasculature and cardiac muscle [ 11 ].…”

Chronic Ethanol Administration Prevents Compensatory Cardiac Hypertrophy in Pressure Overload

“…Blunt dissection was used to reveal the right and left renal arteries branching from the abdominal aorta. The abdominal aorta was partially constricted with a size-0 silk suture tied around a 21-gauge needle at the site between the branching of the left and right renal arteries (Nagalla et al, 2012). The needle was withdrawn leaving a patent, but constricted aorta.…”

Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction

“…LV Chamber Volume and Contractile Function-Mice anesthetized with isoflurane were subjected to in vivo LV chamber volume and function analysis using a Scisense ADVantage TM pressure volume conductance catheter (FTS-1912B; Scisense Inc.) inserted into the LV via the right carotid artery (55). Data were analyzed using iWorx© Labscribe Instrument software (Dover, NH, USA) (16).…”