Cardiorenal syndrome (CRS) is the acute (type1) or chronic (type2) worsening of renal function due to heart failure (HF) and to the activation of renin angiotensin system and the consequent renal vasoconstriction. Heme oxygenase 1 (HO-1) is the enzyme responsible for heme degradation to bilirubin, carbon monoxide and iron. Previous studies have shown that upregulation of HO-1 exerts a cardio protective effect in animal models of HF by reducing infarct size and post ischemic ventricular pathological remodeling. HO-1 exerts also a renoprotective effect against angiotensin II induced renal damage. Thus HO-1 induction could be a therapy for HF and CRS. High resolution EcoDoppler technique can be used to evaluate cardiac function and renal perfusion in small animals. There are no animal models that reproduce the physiopathology of CRS type 1 and 2. Aims of this study were: 1) the echocardiographic and renal echoDoppler characterization of a mice model of post ischemic HF and CRS with an high resolution echo machine 2) to evaluate the effect of HO-1 induction on renal vasoconstriction due to CRS. CD1 mice underwent left anterior descending coronary ligation (LAD). Mice were divided in 4 groups: 1) 5 control mice; 2) 5 mice with myocardial infarction without treatment (MI); 3) 5 mice with myocardial infarction treated daily with the HO-1 inducer Sodium Nitroprusside (SNP, 30µg/Kg); 4) 5 mice with myocardial infarction treated daily with SNP and three times a week with a new imidazolic HO-1 inhibitor named inhibitor-11 (10 mg/kg). Mice were treated from day 15 after LAD, until sacrifice (30 days after LAD). Mice underwent high resolution echocardiography and renal ecoDoppler performed with VEVO2100 high resolution echomachine 15 and 30 days after LAD. Renal vasoconstriction was quantified by renal pulsatility index (kPI) evaluation. Mice with LAD developed left ventricle dilatation (end diastolic area: p<0.01 vs controls) with reduction of ejection fraction (EF: p<0.05 vs controls) and diastolic dysfunction (myocardial performance index: p< 0.01 vs controls). Renal vasoconstriction was also significantly increased (kPI p<0.01 vs controls). HF and renal vasoconstriction were evident 15 days after LAD. In mice treated with SNP there was a significant improvement of cardiac contractile function (ejection fraction and fractional shortening: p <0.05 vs MI) and of renal vasoconstriction (k PI p<0.01 vs MI). HO-1 inhibitor administration reversed inductor effects. Conclusions: 15 days after LAD mice have significant cardiac and renal alterations detectable by high resolution echocardiography and renal ecoDoppler . Thus LAD can be used as model of HF and CRS. HO-1 induction improves cardiac function and renal vasoconstriction in mice with echographically detectable HF and CRS.

Echocardiographic and renal ecodoppler characterization of a mice model of cardiorenal syndrome and evaluation of heme oxygenase-1 induction therapeutic effect

VANELLA, LUCA;SORRENTI, Valeria;
2013

Abstract

Cardiorenal syndrome (CRS) is the acute (type1) or chronic (type2) worsening of renal function due to heart failure (HF) and to the activation of renin angiotensin system and the consequent renal vasoconstriction. Heme oxygenase 1 (HO-1) is the enzyme responsible for heme degradation to bilirubin, carbon monoxide and iron. Previous studies have shown that upregulation of HO-1 exerts a cardio protective effect in animal models of HF by reducing infarct size and post ischemic ventricular pathological remodeling. HO-1 exerts also a renoprotective effect against angiotensin II induced renal damage. Thus HO-1 induction could be a therapy for HF and CRS. High resolution EcoDoppler technique can be used to evaluate cardiac function and renal perfusion in small animals. There are no animal models that reproduce the physiopathology of CRS type 1 and 2. Aims of this study were: 1) the echocardiographic and renal echoDoppler characterization of a mice model of post ischemic HF and CRS with an high resolution echo machine 2) to evaluate the effect of HO-1 induction on renal vasoconstriction due to CRS. CD1 mice underwent left anterior descending coronary ligation (LAD). Mice were divided in 4 groups: 1) 5 control mice; 2) 5 mice with myocardial infarction without treatment (MI); 3) 5 mice with myocardial infarction treated daily with the HO-1 inducer Sodium Nitroprusside (SNP, 30µg/Kg); 4) 5 mice with myocardial infarction treated daily with SNP and three times a week with a new imidazolic HO-1 inhibitor named inhibitor-11 (10 mg/kg). Mice were treated from day 15 after LAD, until sacrifice (30 days after LAD). Mice underwent high resolution echocardiography and renal ecoDoppler performed with VEVO2100 high resolution echomachine 15 and 30 days after LAD. Renal vasoconstriction was quantified by renal pulsatility index (kPI) evaluation. Mice with LAD developed left ventricle dilatation (end diastolic area: p<0.01 vs controls) with reduction of ejection fraction (EF: p<0.05 vs controls) and diastolic dysfunction (myocardial performance index: p< 0.01 vs controls). Renal vasoconstriction was also significantly increased (kPI p<0.01 vs controls). HF and renal vasoconstriction were evident 15 days after LAD. In mice treated with SNP there was a significant improvement of cardiac contractile function (ejection fraction and fractional shortening: p <0.05 vs MI) and of renal vasoconstriction (k PI p<0.01 vs MI). HO-1 inhibitor administration reversed inductor effects. Conclusions: 15 days after LAD mice have significant cardiac and renal alterations detectable by high resolution echocardiography and renal ecoDoppler . Thus LAD can be used as model of HF and CRS. HO-1 induction improves cardiac function and renal vasoconstriction in mice with echographically detectable HF and CRS.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/110967
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