Effect of pressure development on oxygen consumption by isolated rat heart

Neely,; Liebermeister, H.; Battersby, E. F.; Morgan, H. E.

doi:10.1152/ajplegacy.1967.212.4.804

Cited by 1,043 publications

(350 citation statements)

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“…Insulin degradation is not responsible for the low sensitivity of the heart to the hormone. These data, as well as others [20,21] indicate that insulin is not the main regulator of glucose metabolism in normal hearts, in contrast to work load which is a potent stimulator of glucose metabolism. When data are expressed in absolute values, basal and insulin-stimulated glucose metabolism in heart of 15-week-old genetically obese rats is decreased compared to that of lean controls.…”

Section: Discussionsupporting

confidence: 71%

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Dysregulation of glucose transport in hearts of genetically obese (fa/fa) Rats

1983

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Summary. Overall D-glucose metabolism and 3-0-methylglucose transport were measured in the perfused heart preparation of lean and genetically obese (fa/fa) rats. Absolute values of basal and insulin-stimulated glucose metabolism were decreased in hearts of 15-week-old obese rats when compared to lean age-matched controls. Basal and maximally stimulated (i. e., by the combined addition of insulin and increasing perfusion pressure) 3-0-methylglucose transport was normal in hearts from young obese rats (5-week-old). However, when only one stimulus was used (insulin or increasing perfusion pressure alone), 3-0-methylglucose transport was stimulated to values that were lower than those of lean rats. Basal 3-0-methylglucose transport was four times lower in hearts from older obese rats (15-week-old) than in lean ones of the same age. At this age, stimulation of 3-0-methylglucose transport by insulin alone, by increasing perfusion pressure alone or by the combination of both stimuli, reached values in obese rats that were only half those of lean animals. It is concluded that: (a) in the early phase of the syndrome, the basal glucose transport system in hearts of obese rats is normal, but its response to stimulation becomes abnormal and; (b) at a later phase of obesity, the glucose transport system becomes abnormal even under basal conditions and its responsiveness to various stimuli is markedly impaired.Key words: Perfused heart; genetically obese rats; glucose transport; insulin; perfusion pressure.Obesity in man and laboratory animals is usually associated with hyperinsulinaemia and insulin resistance [1]. It was initially thought that the major cause of insulin resistance in obese hyperinsulinaemic animals was the decreased ability of plasma membranes of liver [2][3][4][5], adipose tissue [6] and muscle [4,7] to bind insulin, an abnormality that could be accounted for by a decrease in specific insulin receptor number [8]. Subsequent studies have suggested that additional defects unrelated to the insulin receptors (i.e. post-receptor defects) also contributed to insulin resistance [% 9, 10]. In insulinresistant muscles, several such post-receptor defects have been described [4,7,[10][11][12][13][14]. In isolated soleus muscles of the genetically obese Zucker (fa/fa) rat the following post-receptor abnormalities have been shown: (a) increased utilization of endogenous fatty acids inhibitory to glycolysis [7]; (b) decreased uptake of the D-glucose analogue, 2-deoxy-D-glucose (2-DG) [4,7,12]. In the perfused hindquarter of obese hyperglycaemic (db/db) mice the existence of a post-receptor defect at the level of glucose transport (again measured with 2-DG) has been proposed to be the major cause of insulin resistance [15]. Thus the evidence that insulin resistance could be partly attributed to defectual glucose handling has been indirect, based either on overall glucose metabolism or on 2-DG glucose uptake.Studies carried out with 2-DG have two major drawbacks: (a) 2-DG is not only taken up but phosphorylated [16]; (b) t...

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Section: Discussionsupporting

confidence: 71%

“…The heart was rapidly removed, placed in ice-cold 0.9% NaC1 for 10 s, cannulated via the aorta and perfused, according to the Langendorff technique [20,21] in which the perfusion medium is pumped into the left ventricle via the aorta just above the coronary arteries.…”

Section: Heart Perfusionmentioning

confidence: 99%

Dysregulation of glucose transport in hearts of genetically obese (fa/fa) Rats

1983

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“…THE ISOLATED working rat heart apparatus was originally developed by Neely et al 1 to study cardiac metabolism in a heart performing external work. Performance could be assessed from measurements of left ventricular (LV) and aortic pressures and cardiac output.…”

mentioning

confidence: 99%

“…Performance could be assessed from measurements of left ventricular (LV) and aortic pressures and cardiac output. 1 and from these approximate values for external work could be obtained. However, more precise measurement of the pumping characteristics of the heart (instantaneous flow as well as pressure) was not possible, and the inability to measure ventricular volume precluded making extrapolations to muscle function.…”

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confidence: 99%

Effects of physical training on end-diastolic volume and myocardial performance of isolated rat hearts.

Bersohn¹,

Scheuer²

1977

Circulation Research

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SUMMARY We studied the performance of ventricular muscle and cardiac function of hearts from rats conditioned by swimming (CH) and from sedentary rats (SH) in an isolated working heart apparatus modified to measure end-diastolic volume by dye dilution. Instantaneous aortic flow, left ventricular (LV) pressure and oxygen consumption were measured. Heart rate and mean aortic pressure were kept constant, and atrial filling pressure was varied from 5 to 20 cm H 2 O. Heart weights of SH and CH were equal and end-diastolic pressures and volumes were similar at all atrial pressures. However, ejection fraction, calculated circumferential fiber velocity, peak systolic pressure, peak aortic flow, cardiac output, and stroke work were all greater in CH than in SH, and the differences increased as atrial pressure was increased. Maximal negative dP/dt was greater in CH than SH at all preloads (P < 0.001). Oxygen consumption of CH was increased in proportion to the increase in work. These results indicate that the improved pumping performance of CH is due to a change in ventricular muscle function. Faster relaxation is a prominent effect of physical training on the rat heart and may foster more complete filling at high heart rates.THE ISOLATED working rat heart apparatus was originally developed by Neely et al. 1 to study cardiac metabolism in a heart performing external work. Performance could be assessed from measurements of left ventricular (LV) and aortic pressures and cardiac output. 1 and from these approximate values for external work could be obtained. However, more precise measurement of the pumping characteristics of the heart (instantaneous flow as well as pressure) was not possible, and the inability to measure ventricular volume precluded making extrapolations to muscle function.The contractile performance of the heart is determined in part by the amount of stretch applied prior to contraction, as governed by the end-diastolic volume. Although end-diastolic pressure could be measured in the isolated working rat heart apparatus, the relation between enddiastolic pressure and volume might vary in different experimental conditions, and a change in this relationship would make alterations in cardiac performance impossible to interpret in terms of muscle function. For instance. Penpargkul and Scheuer 2 showed that cardiac performance was enhanced in hearts from rats subjected to moderate physical conditioning but. in the absence of information about ventricular volumes, it was not known whether the enhanced pumping performance resulted from greater muscle fiber-shortening from the same end-diastolic volume (increased contractility) or from an increased enddiastolic volume due to a change in compliance.This paper reports modifications of the rat heart apparatus so that end-diastolic volume can be determined by a dye-dilution technique and aortic flow can be measured with an electromagnetic flowmeter. From these data, ejection fraction, ventricular volume, peak values and first derivatives of pressure and flow, external ...

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“…11 This served as an experimental model for many studies on heart function and metabolism in the twentieth century.…”

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confidence: 99%