title: Is rate-pressure product of any use in the isolated rat heart? Assessing cardiac 'effort' and oxygen consumption in the Langendorff-perfused heart.
abstract: What is the central question of this study? Rate-pressure product (RPP) is commonly used as an index of cardiac 'effort'. 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. However, given that isolated rodent hearts demonstrate a negative force-frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac 'effort') in the Langendorff-perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β-adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate-pressure product (RPP); a rather ill-defined index of 'work' or, more correctly, 'effort'. Rate-pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV̇O2). 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. The aim of this study was to examine the relationship between RPP and MV̇O2 in Langendorff-perfused rat hearts. Paced hearts (300-750 beats min(-1)) were perfused either with Krebs-Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV̇O2) was recorded. Metabolic status was assessed using (31) P magnetic resonance spectroscopy and lactate efflux. Experiments were repeated in the presence of isoprenaline and in unpaced hearts where heart rate was increased by cumulative isoprenaline challenge. In KH buffer-perfused hearts, MV̇O2 increased with increasing heart rate, but given that left ventricular developed pressure decreased with increases in rate, RPP was not correlated with MV̇O2, lactate production or phosphocreatine/ATP ratio. Although the provision of substrates or β-adrenoceptor stimulation changed the shape of the RPP-MV̇O2 relationship, neither intervention resulted in a positive correlation between RPP and oxygen consumption. Rate-pressure product is therefore an unreliable index of oxygen consumption or 'cardiac effort' in the isolated rat heart.
authors.affiliation: British Heart Foundation Centre of Research Excellence, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: Dunja
authors.initials: D
authors.lastname: Aksentijević
authors.affiliation: British Heart Foundation Centre of Research Excellence, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Lewis
authors.affiliation: British Heart Foundation Centre of Research Excellence, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shattock
mesh_terms: D000818:Animals; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D000067268:Isolated Heart Preparation / Q000379:methods; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D010477:Perfusion / Q000379:methods; D010725:Phosphocreatine / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
chemical_list: D011943:Receptors, Adrenergic, beta; D010725:Phosphocreatine; D019344:Lactic Acid; D010100:Oxygen