Calcium-linked changes in myocardial metabolism in the isolated perfused rat heart

1977 ◽  
Vol 55 (4) ◽  
pp. 925-933 ◽  
Author(s):  
N. S. Dhalla ◽  
J. C. Yates ◽  
V. Proveda
Keyword(s):  
Cyclic Amp ◽  
Myocardial Metabolism ◽  
Contractile Activity ◽  
Control Level ◽  
Creatine Phosphate ◽  
High Energy ◽  
Contractile Force ◽  
Increase Glucose Uptake ◽  
Rat Hearts ◽  
External Calcium

Rat hearts were perfused for 40 min with aerobic medium containing different concentrations of calcium (0–5 mM) and their abilities to take up and oxidize glucose, and to produce lactate and glycerol were examined in addition to measuring glycogen, lipids, cyclic AMP, and high energy phosphate stores. Increasing the concentration of calcium was found to decrease myocardial glycogen but increase glucose uptake, glucose oxidation, and lactate release. A decrease in myocardial triglycerides and an increase in free fatty acid contents as well as glycerol release without any changes in cholesterol and phospholipid contents were observed upon increasing the concentration of external calcium. In comparison with the hearts perfused with Ca2+-free medium, the levels of creatine phosphate and ATP were lower and that of ADP higher in hearts perfused with medium containing 5 mM calcium. No differences in AMP and cyclic AMP contents were seen among hearts perfused with different concentrations of calcium. The contractile activity initially increased upon increasing the concentration of calcium from 1.25 to 5 mM and then declined towards the control level. The hearts were unable to generate contractile force in the absence of calcium, whereas the contractile force decreased and then began to recover upon perfusing the hearts with 0.31 mM calcium. These results indicate that elevated levels of intracellular calcium stimulate glycogenolytic, glycolytic, and lipolytic processes in myocardium directly.

Ischemic preconditioning-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contraction-induced myocardial injury

2004 ◽  
Vol 287 (1) ◽  
pp. H81-H90 ◽  
Author(s):  
Masakuni Kido ◽  
Hajime Otani ◽  
Shiori Kyoi ◽  
Tomohiko Sumida ◽  
Hiroyoshi Fujiwara ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Myocardial Injury ◽  
Contractile Activity ◽  
Integral Membrane Protein ◽  
Contractile Force ◽  
Global Ischemia ◽  
Blue Dye ◽  
Perfused Heart ◽  
Complete Restoration ◽  
Rat Hearts

Dystrophin is an integral membrane protein involved in the stabilization of the sarcolemmal membrane in cardiac muscle. We hypothesized that the loss of membrane dystrophin during ischemia and reperfusion is responsible for contractile force-induced myocardial injury and that cardioprotection afforded by ischemic preconditioning (IPC) is related to the preservation of membrane dystrophin. Isolated and perfused rat hearts were subjected to 30 min of global ischemia, followed by reperfusion with or without the contractile blocker 2,3-butanedione monoxime (BDM). IPC was introduced by three cycles of 5-min ischemia and 5-min reperfusion before the global ischemia. Dystrophin was distributed exclusively in the membrane of myocytes in the normally perfused heart but was redistributed to the myofibril fraction after 30 min of ischemia and was lost from both of these compartments during reperfusion in the presence or absence of BDM. The loss of dystrophin preceded uptake of the membrane-impermeable Evans blue dye by myocytes that occurred after the withdrawal of BDM and was associated with creatine kinase release and the development of contracture. Although IPC did not alter the redistribution of membrane dystrophin induced by 30 min of ischemia, it facilitated the restoration of membrane dystrophin during reperfusion. Also, myocyte necrosis was not observed when BDM was withdrawn after complete restoration of membrane dystrophin. These results demonstrate that IPC-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contractile force-induced myocardial injury and suggest that the cardioprotection conferred by IPC can be enhanced by the temporary blockade of contractile activity until restoration of membrane dystrophin during reperfusion.

Complete inhibition of creatine kinase in isolated perfused rat hearts

1987 ◽  
Vol 252 (1) ◽  
pp. E124-E129 ◽  
Author(s):  
E. T. Fossel ◽  
H. Hoefeler
Keyword(s):  
Creatine Kinase ◽  
Systolic Pressure ◽  
Creatine Phosphate ◽  
High Energy ◽  
Complete Inhibition ◽  
High Energy Phosphates ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Low Levels ◽  
Developed Pressure

Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure.

Substrate dependence of metabolic state and coronary flow in perfused rat heart

1985 ◽  
Vol 249 (4) ◽  
pp. H799-H806 ◽  
Author(s):  
J. W. Starnes ◽  
D. F. Wilson ◽  
M. Erecinska
Keyword(s):  
Energy Metabolism ◽  
Coronary Flow ◽  
Work Load ◽  
Creatine Phosphate ◽  
High Energy ◽  
Cardiac Cells ◽  
O2 Consumption ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Perfused Hearts

The effect of substrate source on the regulation of energy metabolism and coronary flow was studied in isolated perfused rat hearts. Compared with glucose-perfused hearts, those perfused at the same work load with palmitate or acetate demonstrated increases (P less than 0.01) in O2 consumption of 16 and 18%, respectively, and increases (P less than 0.01) in coronary flow of 30 and 32%, respectively. Parallel substrate-related changes occurred in the levels of high-energy phosphate compounds: tissue creatine, ADP free, and inorganic phosphate (Pi) were significantly decreased, leading to increases (P less than 0.01) in [creatine phosphate]/[creatine] and [ATP]free/[ADP]free[Pi]. These changes were accompanied by increased reduction of intramitochondrial pyridine nucleotides. Omitting orthophosphate from perfusate lowered intracellular Pi and modified cardiac function, but substrate-related differences were similar to those in Pi containing media. Differences in intracellular pH among substrates were observed, which may contribute in some instances to differences in energy metabolism and coronary flow. When work load was altered in glucose- and acetate-perfused hearts, both O2 consumption and coronary flow were linearly related to cytosolic [ATP]free/[ADP]free[Pi], and slopes of regression lines were similar for both substrates. These correlations support the view that [ATP]free/[ADP]free[Pi] is a major determinant of O2 consumption by cardiac cells and of coronary flow.

The effect of calcium on cardiac phosphorylase activation, contractile force and cyclic AMP in euthyroid and hyperthyroid rat hearts

1976 ◽  
Vol 54 (4) ◽  
pp. 590-595 ◽  
Author(s):  
Elizabeth J. Hartley ◽  
John H. McNeill
Keyword(s):  
Enzyme Activity ◽  
Thyroid Hormone ◽  
Cyclic Amp ◽  
Positive Inotropic Effect ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Chronotropic Effect ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Isolated Perfused Rat Hearts

Calcium chloride injected into isolated perfused rat hearts produced a positive inotropic effect and increased the levels of phosphorylase a (EC 2.4.1.1). The increase in enzyme activity lagged behind the inotropic effect. Pretreatment of animals with thyroid hormone enhanced the ability of noradrenaline to activate phosphorylase but did not affect the inotropic or phosphorylase activating effect of calcium. Thyroid hormone pretreatment did enhance the chronotropic effect of calcium. Calcium did not affect the cardiac levels of cyclic AMP. It is concluded that calcium can activate phosphorylase by a mechanism other than cyclic AMP and that the enhancement of adrenergic amine-induced phosphorylase activation by thyroid hormone is not a calcium mediated event.

Correlation Between Changes in the Endogenous Energy Stores and Myocardial Function due to Hypoxia in the Isolated Perfused Rat Heart

1972 ◽  
Vol 50 (4) ◽  
pp. 333-345 ◽  
Author(s):  
N. S. Dhalla ◽  
J. C. Yates ◽  
D. A. Walz ◽  
V. A. McDonald ◽  
R. E. Olson
Keyword(s):  
Heart Rate ◽  
Rat Heart ◽  
Coronary Flow ◽  
Creatine Phosphate ◽  
High Energy ◽  
Contractile Force ◽  
Rate Of Change ◽  
Energy Utilization ◽  
Phosphate Potential ◽  
Hypoxic Heart

On perfusing the isolated rat heart for 7 min with substrate-free hypoxic medium, the contractile force, rate of change of contractile force, time to peak tension, and heart rate declined whereas resting tension increased. The coronary flow and the pH of the perfusate reached maximum and minimum values, respectively, within 2 min of hypoxia whereas the optical density of the perfusate at 260 mμ increased progressively over the 7 min of perfusion with hypoxic medium. The levels of glycogen, creatine phosphate, and ATP declined whereas the concentrations of lactate, ADP, AMP, creatine, and Pi increased during the 1st min of hypoxia at which time the contractile force and heart rate decreased by about 20% of the control values. During the 1st min of hypoxia the diminution in phosphate potential and creatine phosphate/Pi ratio was found to be of greater magnitude than that in the contractile force. Between 2 and 7 min of perfusion with hypoxic medium a marked reduction in contractile force occurred without appreciable changes in the coronary flow, the phosphate potential, the levels of ADP and AMP, and creatine phosphate/Pi ratio. No change in myocardial lipids occurred under the present experimental conditions whereas changes in the electrical activity, time for half relaxation, norepinephrine stores, and mitochondrial structure lagged behind the changes in the high energy phosphate stores due to hypoxia. Although a clear relation between changes in the cardiac function and any one biochemical parameter throughout the period of hypoxia is not apparent from this study, the onset of failure of the hypoxic heart to generate contractility may be considered due to an insufficiency in the process of energy generation. The complete inability of the hypoxic heart to develop contractile force may be due to abnormalities in the processes of energy utilization subserving the mechanisms for the maintenance of ionic gradient and excitation–contraction coupling.

Responses of beta-adrenoceptor in rat soleus to phosphorus compound levels and/or unloading

1994 ◽  
Vol 266 (5) ◽  
pp. C1257-C1262 ◽  
Author(s):  
Y. Ohira ◽  
K. Saito ◽  
T. Wakatsuki ◽  
W. Yasui ◽  
T. Suetsugu ◽  
...  
Keyword(s):  
Contractile Activity ◽  
Creatine Supplementation ◽  
High Energy ◽  
Hindlimb Suspension ◽  
Phosphorus Compounds ◽  
High Energy Phosphates ◽  
High Energy Phosphate ◽  
Gravitational Unloading ◽  
Beta Adrenoceptor ◽  
Muscle Contractile

Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity.

Independent dual perfusion of left and right coronary arteries in isolated rat hearts

1991 ◽  
Vol 261 (6) ◽  
pp. H2082-H2090 ◽  
Author(s):  
M. Avkiran ◽  
M. J. Curtis
Keyword(s):  
High Energy ◽  
Low Flow ◽  
Blue Dye ◽  
Ischemia And Reperfusion ◽  
Langendorff Preparation ◽  
Rat Hearts ◽  
Left And Right ◽  
Conventional Models ◽  
Aortic Cannula ◽  
Isolated Rat

A novel dual lumen aortic cannula was designed and constructed to permit independent perfusion of left and right coronary beds in isolated rat hearts without necessitating the cannulation of individual arteries. Stability of the dual-perfusion preparation was shown to be similar to that of the conventional Langendorff preparation, in terms of coronary flow, heart rate, and high-energy phosphate content. The independence of left and right perfusion beds was confirmed by unilateral infusion of disulfine blue dye and spectrophotometric detection of the dye in ventricular homogenates. Transient cessation of flow to the left coronary bed resulted in severe ventricular arrhythmias upon reperfusion, as in conventional models of regional ischemia and reperfusion. The dual-perfusion model is technically undemanding, reproducible, inexpensive, and can be used in several species. It enables studies with 1) regional low flow ischemia, 2) regional zero-flow ischemia without coronary ligation (with attendant damage to vasculature), 3) selective application of drugs or interventions to the ischemic-reperfused zone, and 4) selective application of components of ischemia and reperfusion to a site anatomically relevant to ischemic heart disease.

scholarly journals Myocardial metabolism and function in acutely ischemic and hypoxemic isolated rat hearts

1995 ◽  
Vol 27 (5) ◽  
pp. 1213-1218 ◽  
Author(s):  
M SAMAJA ◽  
R MOTTERLINI ◽  
S ALLIBARDI ◽  
S CASALINI ◽  
G MERATI ◽  
...  
Keyword(s):  
Myocardial Metabolism ◽  
Rat Hearts ◽  
And Function ◽  
Isolated Rat
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