In some pathophysiological conditions myocardial metabolism can switch from mainly long chain fatty acid (LCFA) oxidation to mainly glucose oxidation. Whether the predominant fatty acid or glucose oxidation affects cardiac performance has not been defined. In a buffer perfused isovolumetrically contracting rat heart, oxidation of endogenous pool LCFA was avoided by inhibiting carnitine-palmitoyl-transferase I (CPT-I) with oxfenicine (2 mM). In order to restore fatty acid oxidation, hexanoate (1 mM), which bypasses CPT-I inhibition, was added to the perfusate. Three groups of hearts were subjected to either an increase in left ventricular volume (VV, +25%) or an increase in coronary flow (CF, +50%), or inotropic stimulation with isoproterenol (10(-8) and 10(-6) m). The increase in VV (the Frank-Starling mechanism) increased rate-pressure product (RPP) by 21 +/- 2% under control conditions, but only by 6 +/- 2% during oxfenicine-induced CPT-I inhibition. The contractile response to changes in VV recovered after the addition of hexanoate. Similar results were obtained in hearts, in which an increase in CF was elicited (the Gregg phenomenon). Isoproterenol caused a similar increase in contractility regardless of the presence of oxfenicine or hexanoate. In all groups, a commensurate increase in oxygen consumption accompanied the increase in contractility. The fatty acid oxidation is necessary for an adequate contractile response of the isolated heart to increased pre-load or flow, whereas the inotropic response to adrenergic beta-receptor stimulation is insensitive to changes in substrate availability.

Fatty acids are important for the Frank-Starling mechanism and Gregg effect but not for catecholamine response in isolated rat hearts.

PAGLIARO, Pasquale;MACERAUDI, Donatella;PENNA, Claudia;RASTALDO, Raffaella;
2002

Abstract

In some pathophysiological conditions myocardial metabolism can switch from mainly long chain fatty acid (LCFA) oxidation to mainly glucose oxidation. Whether the predominant fatty acid or glucose oxidation affects cardiac performance has not been defined. In a buffer perfused isovolumetrically contracting rat heart, oxidation of endogenous pool LCFA was avoided by inhibiting carnitine-palmitoyl-transferase I (CPT-I) with oxfenicine (2 mM). In order to restore fatty acid oxidation, hexanoate (1 mM), which bypasses CPT-I inhibition, was added to the perfusate. Three groups of hearts were subjected to either an increase in left ventricular volume (VV, +25%) or an increase in coronary flow (CF, +50%), or inotropic stimulation with isoproterenol (10(-8) and 10(-6) m). The increase in VV (the Frank-Starling mechanism) increased rate-pressure product (RPP) by 21 +/- 2% under control conditions, but only by 6 +/- 2% during oxfenicine-induced CPT-I inhibition. The contractile response to changes in VV recovered after the addition of hexanoate. Similar results were obtained in hearts, in which an increase in CF was elicited (the Gregg phenomenon). Isoproterenol caused a similar increase in contractility regardless of the presence of oxfenicine or hexanoate. In all groups, a commensurate increase in oxygen consumption accompanied the increase in contractility. The fatty acid oxidation is necessary for an adequate contractile response of the isolated heart to increased pre-load or flow, whereas the inotropic response to adrenergic beta-receptor stimulation is insensitive to changes in substrate availability.
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PAGLIARO P; CHIRIBIRI A; D. MACERAUDI; PENNA C; RASTALDO R; RECCHIA FA.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/109226
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