scholarly journals Effect of pyruvate, lactate and insulin on ATP supply and demand in unpaced perfused rat heart

2009 ◽  
Vol 423 (3) ◽  
pp. 421-428 ◽  
Author(s):  
Bernard Korzeniewski ◽  
Véronique Deschodt-Arsac ◽  
Guillaume Calmettes ◽  
Gilles Gouspillou ◽  
Jean-Michel Franconi ◽  
...  

Mitochondrial respiration/oxidative phosphorylation is the main source of energy, in the form of ATP, in the heart under physiological conditions. Different respiratory substrates were used in various experiments during heart perfusion: glucose, pyruvate, lactate, glucose+pyruvate, glucose+lactate, glucose+insulin etc. Also under physiological conditions, the concentration of respiratory substrates/hormones in blood can vary significantly. In the present study, we tested the effect of pyruvate, lactate and insulin (all in the presence of glucose) and glucose (in the presence of pyruvate) on the ATP-producing and -consuming blocks in perfused rat heart, in a system where HR (heart rate) was allowed to vary (no pacing). Changes in RPP (rate-pressure product) and PCr (phosphocreatine) concentration were measured. PAA (Proportional Activation Approach) was used to visualize and quantitatively analyse the data. It was demonstrated that addition of glucose (in the presence of pyruvate) exerted essentially no effect on the system. Insulin (in the presence of glucose) activated only the ATP producer. The most interesting finding is that, in our system, pyruvate and lactate (added in the presence or instead of glucose) activated ATP producer, but significantly inhibited ATP consumer (their effect was quantitatively identical).

1999 ◽  
Vol 277 (1) ◽  
pp. H308-H317 ◽  
Author(s):  
P. Mateo ◽  
V. Stepanov ◽  
B. Gillet ◽  
J.-C. Beloeil ◽  
J. A. Hoerter

To study the relation among mitochondrial energy supply, cardiac performance, and energy transfer through creatine kinase (CK), two acute models of inhibition of ATP synthesis were compared in the isovolumic acetate-perfused rat heart. Similar impairments of mechanical performance (rate-pressure product, RPP) were achieved by various stepwise decreases in O2 supply ([Formula: see text] down to 20% of control) or by infusing CN (0.15–0.25 mM). The forward CK flux measured by saturation-transfer 31P NMR spectroscopy was 6.1 ± 0.4 mM/s in control hearts. Only after severe hypoxia ([Formula: see text] < 40% of control) did CK flux drop (to 1.9 ± 0.2 mM/s at[Formula: see text] = 25% of control) together with impaired systolic activity and a rise in end-diastolic pressure. In contrast, in mild hypoxia CK flux remained constant and similar to control (5.3 ± 0.5 mM/s, not significant) despite a twofold reduction in systolic activity. Similarly in all CN groups, constant CK flux was maintained for a threefold reduction in RPP, showing the absence of a relation between cardiac performance and global NMR-measured CK flux during mild ATP synthesis inhibition.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 105-106
Author(s):  
Mia Y Kawaida ◽  
Oh-Sung Kwon ◽  
Ahram Anh ◽  
Amanda S Reiter ◽  
Nicole M Tillquist ◽  
...  

Abstract Mitochondria are critical for oxidative phosphorylation in skeletal muscle, especially in athletic species such as the horse. Mitochondrial respiration increases with physical exercise, but the relationship between mitochondrial respiration and cardiovascular functions are not well described in the horse. The objective of this study was to determine if there is a relationship between heart rate (HR) during and after submaximal exercise tests (SETs) and skeletal muscle mitochondrial respiration in polo ponies. We hypothesized that horses with greater maximum HR and average HR during the exercise tests would have greater mitochondrial respiration in skeletal muscle. Twelve fit polo ponies (14.8 ± 1.7 years old, 10 mares and 2 geldings) were equipped with Polar equine heart rate monitors (Polar Electro Inc., Lake Success, NY) and underwent 26-minute SETs designed to mimic a polo chukker followed by a 30-minute recovery period. Muscle biopsy samples from the semitendinosus muscle were taken 2 weeks prior to the SET to determine mitochondrial oxygen consumption using the Oroboros O2k high-resolution respirometer (Oroboros Instruments, Innsbruck, Austria). Data were analyzed using the PROC CORR procedure (SAS Inst. Inc., Cary, NC). Correlations were considered strong at r &gt; 0.6 and significant at P &lt; 0.05. Maximum HR during SET and state IV respiration were positively correlated (P = 0.02, r = 0.68). Average HR during SET and state IV respiration were also positively correlated (P = 0.01, r = 0.72). However, correlations between maximum and average HR and state III respiration were not as strong (P ≥ 0.05, r &lt; 0.6). These data suggest that state IV mitochondrial respiration (proton leak) in equine skeletal muscle may impact cardiac responses to high-intensity exercise. Horses with higher HR during exercise may have less efficient oxidative phosphorylation, resulting in earlier fatigue and/or greater formation of reactive oxygen species resulting from proton leak.


2014 ◽  
Vol 307 (2) ◽  
pp. H228-H235 ◽  
Author(s):  
Matthew D. Muller ◽  
Zhaohui Gao ◽  
Patrick M. McQuillan ◽  
Urs A. Leuenberger ◽  
Lawrence I. Sinoway

Cardiac ischemia and angina pectoris are commonly experienced during exertion in a cold environment. In the current study we tested the hypotheses that oropharyngeal afferent blockade (i.e., local anesthesia of the upper airway with lidocaine) as well as systemic β-adrenergic receptor blockade (i.e., intravenous propranolol) would improve the balance between myocardial oxygen supply and demand in response to the combined stimulus of cold air inhalation (−15 to −30°C) and isometric handgrip exercise (Cold + Grip). Young healthy subjects underwent Cold + Grip following lidocaine, propranolol, and control (no drug). Heart rate, blood pressure, and coronary blood flow velocity (CBV, from Doppler echocardiography) were continuously measured. Rate-pressure product (RPP) was calculated, and changes from baseline were compared between treatments. The change in RPP at the end of Cold + Grip was not different between lidocaine (2,441 ± 376) and control conditions (3,159 ± 626); CBV responses were also not different between treatments. With propranolol, heart rate (8 ± 1 vs. 14 ± 3 beats/min) and RPP responses to Cold + Grip were significantly attenuated. However, at peak exercise propranolol also resulted in a smaller ΔCBV (1.4 ± 0.8 vs. 5.3 ± 1.4 cm/s, P = 0.035), such that the relationship between coronary flow and cardiac metabolism was impaired under propranolol (0.43 ± 0.37 vs. 2.1 ± 0.63 arbitrary units). These data suggest that cold air breathing and isometric exercise significantly influence efferent control of coronary blood flow. Additionally, β-adrenergic vasodilation may play a significant role in coronary regulation during exercise.


1985 ◽  
Vol 17 (1) ◽  
pp. 71-81 ◽  
Author(s):  
E.O. Fuller ◽  
D.I. Goldberg ◽  
J.W. Starnes ◽  
L.M. Sacks ◽  
M. Delivoria-Papadopoulos

Several metabolites and intracellular pH in intact organs can be studied in a nondestructive manner by phosphorus nuclear magnetic resonance ( 31 P n.m.r.). This possibility was demonstrated by us nearly five years ago. Since then we have developed the appropriate physiological techniques and improved the n.m.r. method for the study of animal hearts and kidneys. Here we describe measurements aimed at clarifying three problems. (1) Having measured the enzyme-catalysed fluxes between phosphocreatine and ATP by the method of saturation transfer n.m.r., we examine the relation between energy supply and heart rate in the isolated perfused rat heart. (2) We describe experiments to establish the validity of the perfusion model. For the first time, we report 31 P n.m.r. measurements of an in vivo rat heart and compare the results with those obtained for the perfused rat heart. (3) Ischaemia and metabolism in rabbit kidneys is investigated to establish the relation between functional and metabolic recovery after a renal transplant operation.


2007 ◽  
Vol 293 (6) ◽  
pp. E1828-E1835 ◽  
Author(s):  
Patrick McConville ◽  
Edward G. Lakatta ◽  
Richard G. Spencer

Differences in energy metabolism during β1- and β2-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during β1- compared with β2-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved 13C- and 31P-NMR spectroscopy was used during β1- and β2-AR stimulation at matched peak workload (2.5 times baseline) in the isolated perfused rat heart to monitor glycogen levels, phosphorylation potential, and intracellular pH. Simultaneous measurements of left ventricular (LV) function [LV developed pressure (LVDP)], heart rate (HR), and rate-pressure product (RPP = LVDP × HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during β1- than β2-AR stimulation with G (54% vs. 38% reduction, P = 0.006) and SF (92% vs. 79% reduction, P = 0.04) perfusions. The greater β1-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However, with SF perfusion, the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during β1- than β2-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, despite a slightly weaker overall inotropic response, during β1- than β2-AR stimulation. These findings are consistent with β1-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.


2000 ◽  
Vol 279 (6) ◽  
pp. H3118-H3123 ◽  
Author(s):  
Lori A. Gustafson ◽  
Johannes H. G. M. Van Beek

The purpose of this study was to develop a technique for determination of the dynamic regulation of oxidative myocardial metabolism in the mouse. The response time of myocardial oxygen consumption (MV˙o 2) to a step in heart rate was determined in Langendorff-perfused mouse hearts. We examined the effect of glucose-only perfusate and glucose combined with 1, 3, or 6 mM pyruvate. Left ventricular systolic pressure (LVSP) decreased, yet the rate-pressure product (RPP) and MV˙o 2 increased with upward steps in heart rate. Pyruvate increased LVSP, RPP, and MV˙o 2 at the lower concentrations; however, when 6 mM pyruvate was added, LVSP and RPP became depressed while MV˙o 2 remained elevated. The mean response time of oxygen consumption to a step in heart rate from 270 to 350 beats/min was 9.8 s ( n = 7) in the glucose-only perfused hearts. Perfusion with glucose plus 6 mM pyruvate decreased the response time to 5.3 s. These results are similar to those found in the rabbit heart and lay the groundwork for further examination of the dynamic regulation of oxidative myocardial metabolism in genetically altered mice. We concluded that the activation time of oxidative phosphorylation in the mouse is similar to that in larger species, despite the high mitochondrial content and natural heart rate of the mouse.


1972 ◽  
Vol 50 (9) ◽  
pp. 853-859 ◽  
Author(s):  
Charles W. Tomlinson ◽  
Naranjan S. Dhalla

The effects of changes in heart rate and contractile force due to electrical stimulation, alteration of the temperature of the perfusion medium, and varying degrees of stretch tension on the subcellular distribution of calcium in the isolated perfused rat heart were studied. Increasing the frequency of stimulation from 80 to 320 pulses/min decreased myocardial contractility without appreciable changes in the levels of calcium in the tissue homogenate and heavy microsomal (8000 – 40 000 × g) fraction. On the other hand, mitochondrial (800–8000 × g) calcium content was greater in hearts stimulated at 120 pulses/min than in hearts stimulated at 80 pulses/min; further increase in the frequency of stimulation resulted in a decrease in the level of mitochondrial calcium. Increasing the temperature of the perfusion medium from 25 to 37 °C increased the heart rate and decreased the contractile force without any changes in the levels of calcium in the homogenate or subcellular fractions. Increasing the stretch tension on the hearts from 0 to 5 g increased the developed contractile force and the level of heavy microsomal calcium without changing the heart rate or the levels of calcium in the homogenate and mitochondria. The results do not reveal any cause–effect relationship between changes in heart function and subcellular distribution of calcium.


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