β-Adrenergic stimulation will phosphorylate key players in the pathway of excitation–contraction coupling, such as L-type Ca 2+ channels, phospholamban, phospholemman, troponin I and the ryanodine receptor changes that will modulate contractility and hence oxygen consumption (Lindemann et al. Despite this, many studies use electrical pacing to elevate rate in the absence of β-agonists (Sutherland et al.
This relationship is further complicated by the fact that the heart in vivo rarely, if ever, encounters a substantial rise in heart rate without β-adrenoceptors being occupied. Thus, although RPP may increase with heart rate and be correlated with myocardial O 2 consumption ( ) in the human heart, what happens in the isolated rat or mouse heart has never been defined. However, despite its widespread use, the application of this index to rat and mouse hearts, has a problem namely, whereas dogs, humans and most other large mammals show a positive force–frequency relationship (FFR) (Bers, 2000) (that is, as heart rate increases so does force development), this relationship is flat or even negative in the electrically paced isolated rat or mouse heart (Sutherland et al. This correlation with oxygen consumption was confirmed in human hearts by Kitamura et al. Rate–pressure product was originally described by Katz & Feinberg ( 1958) as an index of ‘cardiac effort’ in dog hearts and shown to be linearly correlated with oxygen consumption. One of the commonly used indices of function is rate–pressure product (RPP), which is frequently adopted as some rather ill-defined index of ‘work’ or, more correctly, ‘effort’. The ability to modify mice genetically has further enhanced the utility of this technique and the ability to phenotype these hearts reliably has become essential. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological, biochemical and molecular studies for many years. Rate–pressure product is therefore an unreliable index of oxygen consumption or ‘cardiac effort’ in the isolated rat heart. Although the provision of substrates or β-adrenoceptor stimulation changed the shape of the RPP– relationship, neither intervention resulted in a positive correlation between RPP and oxygen consumption. In KH buffer-perfused hearts, increased with increasing heart rate, but given that left ventricular developed pressure decreased with increases in rate, RPP was not correlated with, lactate production or phosphocreatine/ATP ratio. Experiments were repeated in the presence of isoprenaline and in unpaced hearts where heart rate was increased by cumulative isoprenaline challenge.
Metabolic status was assessed using 31P magnetic resonance spectroscopy and lactate efflux. The arteriovenous oxygen consumption ( ) was recorded. Paced hearts (300–750 beats min −1) were perfused either with Krebs–Henseleit (KH) buffer (11 m m glucose) or with buffer supplemented with metabolic substrates and insulin. The aim of this study was to examine the relationship between RPP and in Langendorff-perfused rat hearts. Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force–frequency relationship) has not been characterized. Rate–pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption ( ). One of the commonly used indices of function is rate–pressure product (RPP) a rather ill-defined index of ‘work’ or, more correctly, ‘effort’. The ability to phenotype these hearts reliably is, therefore, essential. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β-adrenoceptor stimulation. What is the main finding and its importance?ĭespite its widespread use, RPP is not correlated with oxygen consumption (or cardiac ‘effort’) in the Langendorff-perfused isolated rat heart. However, given that isolated rodent hearts demonstrate a negative force–frequency relationship, its use in this model requires validation. In canine and human hearts (which have a positive force–frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species-independent index of cardiac work. Rate–pressure product (RPP) is commonly used as an index of cardiac ‘effort’.
What is the central question of this study?
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