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

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.

Nandrolone-pretreatment enhances cardiac β2-adrenoceptor expression and reverses heart contractile down-regulation in the post-stress period of acute-stressed rats

“…The degree of increase in contractility indices during adrenergic stimulation observed in the heart of unstressed + vehicle rats is consistent with previous reports in buffer-perfused hearts [11,19]. We also observed a similar response in unstressed + ND animals, despite ␤ 2 -AR overexpression.…”

“…Coronary flow (CF) and CPP oscillations were limited using the 314 four roller pump-heads of the Watson-Marlow pump and by inserting a 50-ml Windkessel device into the perfusion line. Constant CF was used to minimize alterations in contractility caused by the Gregg phenomenon [11,15,16]. A small aperture in the left ventricular wall allowed the drainage of the thebesian flow.…”

“…Many of the above reported parameters that can affect inotropic response can be precisely separated and controlled in the isolated rat heart preparation [11]. Moreover, we know that short-term (2 weeks) ND-treatment may be effective as it alters heart response to cocaine without inducing cardiac hypertrophy in rats [12].…”

Myocardial protection from ischemic preconditioning is not blocked by sub-chronic inhibition of carnitine palmitoyltransferase I

“…We previously showed that in the isolated rat heart, the Frank-Starling mechanism and Gregg effect are sensitive to the type of metabolic substrate used after acute CPT-I inhibition. Fatty acid oxidation was necessary for an adequate contractile response of the isolated heart to myocardial stretch by increasing VV (Frank-Starling mechanism) or CF (Gregg effect), but not to h-receptor stimulation (Pagliaro et al, 2002). In these experiments of acute CPT-inhibition, however, the basal function of the heart was not altered.…”

“…In fact, compared with fat oxidation, carbohydrate utilization increases the ratio between adenosine triphosphate (ATP) synthesis and consumed oxygen (Starnes et al, 1985). We recently demonstrated that inhibition of LCFA oxidation by inhibition of carnitine palmitoyltransferase I (CPT-I), a key enzyme for transport of LCFA into the mitochondria, impedes an adequate contractile response of the isolated heart to increased pre-load or flow, whereas the inotropic response to adrenergic h-receptor stimulation is insensitive to changes in substrate availability (Pagliaro et al, 2002).…”