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ABSTRACT: Advanced aging is associated with hemodynamic dysfunction in rats as in humans. The aim of this study was to assess the mechanisms of development of left ventricular (LV) dysfunction in the rat model of aging. In vivo hemodynamics and ex vivo LV papillary muscle mechanics, myofilaments sensitivity to calcium in skinned fibers and pressure/volume curves in isolated perfused hearts were performed in 3, 24 and 28 month old (mo) male Wistar rats. Hemodynamic dysfunction occurs in 28 mo rats and is characterized by both a systolic and diastolic dysfunction and a LV hypertrophy (+34.7% of LV weight). In papillary muscle, normalized active developed force and myofilament sensitivity to calcium were unchanged between 24 and 28 months of age. In contrast, both resting force/total force ratio in papillary muscle and the slope of the pressure/volume curves in isolated heart are increased between 3 and 24 mo but also between 24 and 28 mo, indicating a progression of the impairment of both papillary muscle stiffness and LV compliance in advanced aging. Hemodynamic dysfunction occurring at advanced age, i.e. 28 mo in rats mainly results from impairment of ventricular compliance resulting from fibrosis.
Experimental Gerontology 04/2006; 41(3):289-95. · 3.74 Impact Factor
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ABSTRACT: This study investigated the effects of cariporide, an inhibitor of sodium-proton exchanger (NHE), during myocardial ischemia and reperfusion in senescence. Isolated Langendorff perfused hearts from 4 (adult) and 24 (senescent) month old male Wistar rats were submitted to prolonged low-flow ischemia (LFI) at 15% of initial coronary flow (180 min) or to 45 min of LFI (15% of initial coronary flow) followed by 30 min of reperfusion, without or with cariporide (10(-6)M). In senescent hearts, but not in adults, treatment with cariporide during prolonged LFI attenuated the elevation of coronary resistances (578 +/- 84 vs 1020 +/- 129% of baseline value after 180 min, P < 0.05) and delayed the decrease in active tension (35.6 +/- 5.1 vs 22.2 +/- 3.4% of baseline value after 60 min; P < 0.05). During reperfusion following LFI, the coronary flow impairment was more pronounced in senescents than in adults (48.4 +/- 9.4 and 75.3 +/- 4.9% of baseline value, respectively; P < 0.05) but was fully prevented in senescent hearts by cariporide treatment (95.6 +/- 17.0% of baseline value; P < 0.05 vs untreated group). This beneficial effect of cariporide on coronary tone was associated with an improvement of active and resting tensions and lower LDH release. Such functional protective effects of cariporide suggest an operative NHE during LFI at both coronary and myocardial levels in senescent heart. In addition, cariporide-associated improvement of post-ischemic recovery of coronary and contractile function as well as the limitation of cellular injury suggests a major role of calcium overload via NHE activation during reperfusion of senescent ischemic heart.
Experimental Gerontology 10/2004; 39(9):1307-14. · 3.74 Impact Factor
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ABSTRACT: This study investigated the effects of bosentan, a dual endothelin ETA and ETB receptor antagonist, during hypoxia–reoxygenation of senescent aorta and during ischemia–reperfusion of senescent heart. Isolated aortic rings and isolated hearts from adult and senescent rats were submitted, respectively, to hypoxia/reoxygenation (20/30 min) and to low-flow ischemia/reperfusion (45/30 min), without or with bosentan (10−5 M). In the aorta, bosentan treatment prevented the impairment of relaxation in response to acetylcholine after hypoxia–reoxygenation at both ages. In the heart, coronary flow recovery during reperfusion, which is lower in senescents than in adults (48% vs. 76% of baseline value, respectively; P<0.05) was fully prevented by bosentan. Prevention of endothelial dysfunction during reoxygenation of hypoxic aorta and of coronary vasoconstriction during reperfusion of ischemic heart with a dual endothelin ETA and ETB receptor antagonist suggests a role of endothelin in the vulnerability of aorta to hypoxia–reoxygenation, and of coronary arteries to ischemia–reperfusion, especially during aging.
European Journal of Pharmacology. 01/2001;
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ABSTRACT: The incidence of ischemic cardiac diseases increases with age and elderly subjects are more vulnerable to myocardial infarction. Endurance exercise (e.g. treadmill training) provides cardioprotection against an ischemia and reperfusion (IR) event in adult heart but such a potential beneficial effect of regular exercise has never been evaluated during aging. Therefore, this study investigated the effects of moderate running training on post-ischemic recovery of contractile function and coronary perfusion in senescent myocardium. Isolated hearts of sedentary (24 mo-sedentary; n = 10) and trained senescent (24 mo-trained; n = 11; moderate running: 1 h/day, 5 days/week for 12 weeks) rats were submitted to 45 min low-flow ischemia (15% of initial coronary flow (CF)) followed by 30 min reperfusion. Active tension (AT) and CF were recorded at baseline and after 1, 3, 5, 10, 15, 20, 25 and 30 min of reperfusion. Left ventricular protein carbonylation, and both heat-shock-protein 70 (HSP70) and endothelial nitric oxide synthase (eNOS) contents were determined by Oxyblotting and Western blotting, respectively. Regular physical exercise improves impairment of functional post-ischemic recovery (AT and CF) of aged hearts during reperfusion and this cardioprotection is associated to limited protein oxidation and increased HSP70 and eNOS myocardial contents.
Experimental Gerontology.
