Cardiorenal syndrome (CRS) is the acute (type-1) worsening of renal function in heart failure (HF), due to the activation of renin-angiotensin system. Heme-oxygenase-1 (HO-1), responsible for heme degradation to bilirubin, carbon-monoxide and iron, exerts a cardio protective effect in animal models of HF, and prevents angiotensin-II-induced renal damage. Thus, HO-1 induction could be a therapy for HF and CRS. There are no animal models of type-1-CRS.
Aims of this study were: 1) the echocardiographic and renal echoDoppler characterization of a mice model of post ischemic HF and CRS, 2) the evaluation of the effect of HO-1 induction on renal vasoconstriction due to CRS.
CD1 mice were divided in 4 groups: 1) 5 controls; 2) 5 with myocardial infarction (left anterior descending coronary ligation) (MI); 3) 5 with MI treated with the HO-1 inducer Sodium Nitroprusside (SNP,30µg/Kg); 4) 5 with MI treated with SNP and with a new imidazolic HO-1 inhibitor (inhibitor-11,10mg/kg). Mice were treated from day 15 after LAD, until sacrifice (30 days after LAD). Echocardiography and renal ecoDoppler were performed with VEVO2100 (Visualsonics,Canada) 15 and 30 days after LAD. Renal vasoconstriction was quantified by renal pulsatility index (kPI). Mice with MI developed left ventricle dilatation (EDA ctrl 0.154±0.02 MI 0.216±0.02cm2, p<0.05), reduction of ejection fraction (EF ctr 0.60±0.07; MI 0.45±0.04,p<0.05), diastolic dysfunction, renal vasoconstriction (kPI: ctr 0.87±0.1, MI 1.33±0.2, p<0.01), associated with an increase in creatinine (ctr 0.5±0.1mg/dl, MI 1.1±0.2mg/dl, p<0.05) and renin (ctr 15.2±3.5ng/ml, MI 31.7±5.2ng/ml, p<0.05), 15 days after LAD. In mice treated with SNP there was a significant improvement of cardiac contractile function and of renal vasoconstriction (PI: MI 1.33±0.2, MI+SNP 0.66±0.03, p<0.01). HO-1 inhibition reversed the improvement.
Conclusions: LAD can be used as model of HF and CRS, detectable by high resolution Doppler sonography. HO-1 induction improves cardiac function and renal vasoconstriction in mice with HF and CRS.
