Left ventricular function of isoproterenol-induced hypertrophied rat hearts perfused with blood: mechanical work and energetics

Abstract

Ϫ1 ⅐ day Ϫ1 for 3 days (Iso3) or 7 days (Iso7)]-induced hypertrophied rat heart preparation under isovolumic contractionrelaxation. We evaluated pressure-time curves per beat, end-systolic pressure-volume and end-diastolic pressure-volume relations, and myocardial O 2 consumption per beat (V O2)-systolic pressure-volume area (PVA; a total mechanical energy per beat) linear relations at 240 beats/min, because Iso-induced hypertrophied hearts failed to completely relax at 300 beats/min. The LV relaxation rate at 240 beats/min in Iso-induced hypertrophied hearts was significantly slower than that in control hearts [saline 24 l/day for 3 and 7 days (Sa)] with unchanged contraction rate. The V O2-intercepts (composed of basal metabolism and Ca 2ϩ cycling energy consumption in excitationcontraction coupling) of V O2-PVA linear relations were unchanged associated with their unchanged slopes in Sa, Iso3, and Iso7 groups. The oxygen costs of LV contractility were also unchanged in all three groups. The amounts of expression of sarcoplasmic reticulum Ca 2ϩ -ATPase, phospholamban (PLB), phosphorylated-Ser 16 PLB, phospholemman, and Na ϩ -K ϩ -ATPase are significantly decreased in Iso3 and Iso7 groups, although the amount of expression of NCX1 is unchanged in all three groups. Furthermore, the marked collagen production (types I and III) was observed in Iso3 and Iso7 groups. These results suggested the possibility that lowering the heart rate was beneficial to improve mechanical work and energetics in isoproterenol-induced hypertrophied rat hearts, although LV relaxation rate was slower than in normal hearts. cardiac function; excitation-contraction coupling; systolic pressurevolume area; oxygen consumption CARDIAC HYPERTROPHY IS A MAJOR risk factor for the development of heart failure and sudden cardiac death. Therefore, to reduce mortality from cardiovascular diseases, elucidation of the mechanisms involved in cardiac hypertrophy is pivotal. It is recognized that activation of the sympathetic nervous system is associated with cardiac hypertrophy and heart failure in humans (4, 11). In addition, chronic treatment of hearts with an ␣,␤-stimulant, norepinephrine, or a ␤-stimulant, isoproterenol, induces cardiac hypertrophy accompanied with enhanced fibrosis among cardiac interstitial cells in experimental animal models (3,21,25,26). So far, various mechanisms for this remodeling have been proposed (25,26,10,36).We have recently reported that 3-day and 7-day subcutaneous infusions of isoproterenol to rats induced cardiac hypertrophy with unchanged left ventricular (LV) systolic and diastolic functions compared with normal hearts that was reversible to the control levels after the cessation of infusion (8,30). In in vivo ejecting heart model, the significant decrease of mechanical work due to the decrease of LV volume (LVV) was observed. Furthermore, these short-term models did not show any marked differences in the LV mechanical work capability compared with that induced by a 2-wk isoproterenol infusion (30). The expression l...

Upregulation of TRPC1 Contributes to Contractile Function in Isoproterenol-induced Hypertrophic Myocardium of Rat

“…The Western blot analysis revealed that the expression of TRPC1 was upregulated in the CH group, while the levels of TRPC3, TRPC6 and NCX1 remained stationary. The data were consistent with previous reports [10,21], and were shown in Fig. 1.…”

Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia

“…Considered with the present experiments, these data imply a role for sympathetic dysregulation in the progression of cardiac disease in diabetic rats. Continuous β-adrenergic stimulation by infusion of isoproterenol generates cardiac hypertrophy, bradycardia, and slowed end-diastolic relaxation rates [43]. NET knockout mice display elevated cardiac NE, hypertension and tachycardia [44].…”

Changes to both cardiac metabolism and performance accompany acute reductions in functional capillary supply

“…Indeed, our evidence suggests that for the perfused heart as much as one-third of the ATP production is required to maintain viability of cardiomyocytes, even when not contributing to contractile work. When normalised ( moles metabolism/unit RPP) palmitate oxidation is tightly coupled to cardiac work, and for the current protocol this most likely represents the decline in ATP synthesis as a consequence of decreased O 2 delivery limiting the work done by the heart [40]. This suggests close coupling of oxidative phosphorylation, and a high degree of mitochondrial efficiency.…”