Effects of the ionophore grisorixin on myocardial function and metabolism in isolated perfused working rat heart under normoxic and hypoxic conditions

1986 ◽  
Vol 64 (5) ◽  
pp. 631-640 ◽  
Author(s):  
Françoise Chollet-Debord ◽  
Nicole Moins ◽  
Monique Renoux ◽  
Pierre Gachon
Keyword(s):  
Heart Rate ◽  
Coronary Flow ◽  
Lactate Production ◽  
Creatine Phosphate ◽  
Aortic Flow ◽  
Control Series ◽  
Control Value ◽  
Beneficial Effects ◽  
Hypoxic Conditions ◽  
Rat Hearts

The effects of grisorixin, a monocarboxylic ionophore, were studied on isolated working rat hearts perfused with a suspension of washed pig erythrocytes (10% hematocrit). Grisorixin (2.5 μM) induced a transient stimulation of heart work, maximal at 5 min, expressed by an increase in heart rate (+21%) and aortic flow (+17%) and by an increase in coronary flow, maximal at 10 min (+47%). Concomitantly, myocardial [Formula: see text] was slightly enhanced and the myocardial creatine phosphate level dropped (2 min). The lactate production increased by 82% (5 min) then dropped to the control value (10 min) and increased again till the 45th min (+211%), indicating a cardiac metabolic drift towards anaerobic glycolysis due to partial inhibition of the oxidative metabolism. Owing to its properties as an ionophore, grisorixin also induced a strong and rapid increase of potassium concentration in the perfusate and a decrease of sodium. Grisorixin was tested on hearts submitted to 20 min of hypoxic conditions. The hypoxia was rather mild and induced only very slight modifications of the ultrastructure. In the control series, heart rate and aortic flow decreased regularly while coronary flow and lactate production increased. Upon reoxygenation, the heart performances were rapidly restored. Grisorixin was administered according to four different protocols. When injected at the onset of hypoxia or 5 min later, it was able to maintain the aortic flow during the first minutes and induce a higher coronary dilation. These beneficial effects were short-lasting and no deleterious effects were found on the ultrastructure of hearts subjected to grisorixin whether after hypoxia or after reoxygenation.

Atenolol and fentanyl effects upon the heart rate, myocardial contractility, and coronary flow in isolated rat hearts

2001 ◽  
Vol 33 (6) ◽  
pp. A75
Author(s):  
H.K. Maués ◽  
W.C. Pádua Filho ◽  
M. Faraj ◽  
H. Junqueira Neves ◽  
E.S. Gomes ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Contractility ◽  
Coronary Flow ◽  
Rat Hearts ◽  
Isolated Rat

Effect of tris(hydroxymethyl)aminomethane on ischemic myocardium

1978 ◽  
Vol 235 (2) ◽  
pp. H167-H174 ◽  
Author(s):  
M. B. Effron ◽  
T. Guarnieri ◽  
J. W. Frederiksen ◽  
H. L. Greene ◽  
M. L. Weisfeldt
Keyword(s):  
Oxygen Consumption ◽  
Left Ventricle ◽  
Coronary Flow ◽  
Energy Production ◽  
Myocardial Function ◽  
Lactate Production ◽  
Creatine Phosphate ◽  
Sodium Concentration ◽  
Inotropic Effect ◽  
Intracellular Acidosis

Intracellular acidosis may depress myocardial function and metabolism during ischemia. In the present study, the function and metabolism of a globally ischemic, isovolumic cat left ventricle preparation, perfused with oxygenated Krebs-Ringer biocarbonate solution, was examined. Addition of tris(hydroxymethyl)-aminomethane (Tris) (15 mM) to the perfusate at physiologic pH and PCO2 increased performance during ischemia to a greater extent and for a longer period than low PCO2 )15 mmHg), alkalotic (pH, 7.8) perfusate and a control sucrose perfusate. Under nonischemic conditions the inotropic effect of Tris was only briefly greater than sucrose perfusate. The inotropic effect of Tris during ischemia did not appear to depend on changes in coronary flow, oxygen consumption, sodium concentration, perfusate osmolality, or catecholamine release. During ischemia, lactate production was unchanged with Tris, but increased with low PCO2-alkalosis. Tissue levels of ATP and creatine phosphate for control ischemic hearts did not differ from Tris-perfused or low PCO2-alkalosis hearts. Thus, Tris appears to exert an inotropic effect that is more prominent in ischemic than nonischemic myocardium. The results are consistent with the possibility that Tris acts as an intracellular buffer to increase the efficiency of energy production and/or utilization during ischemia.

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.

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.

Role of Heart Rate Reduction in the Management of Myocarditis

2018 ◽  
Vol 24 (3) ◽  
pp. 365-378 ◽  
Author(s):  
Chen Guang-Yi ◽  
Ge Li-Sha ◽  
Li Yue-Chun
Keyword(s):  
Heart Rate ◽  
Nitrosative Stress ◽  
Ventricular Remodeling ◽  
Animal Experiments ◽  
Viral Myocarditis ◽  
Protective Effects ◽  
Heart Rate Reduction ◽  
Rate Reduction ◽  
Beneficial Effects ◽  
Biological Technique

The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease. Recent studies also show that the autonomic nervous system is involved in immunomodulatory myocarditis processes. Heart rate reduction treatment is recommended in myocarditis based on a number of animal experiments and clinical trials. It is possible that heart rate-lowering treatments can help to attenuate the inflammatory response and myocyte injury and reverse ventricular remodeling. However, how to execute the protective effects of heart rate reduction on myocarditis is still not clear. In this review, we discuss the pathogenesis and pathophysiological process of viral myocarditis and propose heart rate lowering as a therapeutic target for myocarditis, especially in light of the third-generation β-blockade carvedilol and funny channel blocker ivabradine. We also highlight some additional beneficial effects of such heart rate reduction agents, including anti-inflammatory, antioxidation, anti-nitrosative stress, anti-fibrosis and antiapoptosis properties.

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