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.

Mechanisms of antifibrillatory effect of acidic reperfusion: role of perfusate bicarbonate concentration

1993 ◽  
Vol 264 (3) ◽  
pp. H783-H790 ◽  
Author(s):  
C. Ibuki ◽  
D. J. Hearse ◽  
M. Avkiran
Keyword(s):  
Heart Rate ◽  
Ventricular Fibrillation ◽  
Rat Heart ◽  
Coronary Flow ◽  
Isolated Rat Heart ◽  
Acidic Ph ◽  
Bicarbonate Concentration ◽  
Left And Right ◽  
Isolated Rat

Transient (2 min) acidic (pH 6.6) reperfusion with low [HCO3-] solution suppresses reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart. Using this preparation, we tested whether the effect was mediated by the high [H+] or the low [HCO3-] of perfusate. Left and right coronary beds were independently perfused with HCO3(-)-containing (25.0 mmol/l) solution at pH 7.4. Regional ischemia was then induced by stopping flow to the left coronary bed for 10 min. Hearts were subsequently assigned to four groups (n = 12 hearts/group), and the left coronary bed was reperfused with either HCO3(-)-containing (25.0 or 4.0 mmol/l) or HCO3(-)-free (5.0 mmol/l HEPES) solution, at pH 7.4 throughout (control reperfusion) or at pH 6.6 for the first 2 min and at pH 7.4 from 2 to 5 min (acidic reperfusion). Regardless of the buffer, controls exhibited a high (92 and 100%) incidence of VF; this was reduced to 42% in both of the acidic reperfusion groups (P < 0.05). There were no intergroup differences in heart rate, coronary flow, or size of ischemic zone. Thus high [H+], rather than low [HCO3-], appears to mediate the antifibrillatory effect of transient acidic reperfusion.

A model of graded ischemia in the isolated perfused rat heart

1976 ◽  
Vol 40 (6) ◽  
pp. 1004-1008 ◽  
Author(s):  
P. Kligfield ◽  
H. Horner ◽  
N. Brachfeld
Keyword(s):  
Coronary Flow ◽  
Metabolic Response ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphate ◽  
Ventricular Tissue ◽  
Perfusion Apparatus ◽  
Catheter Tip ◽  
Stabilization Period ◽  
Flow Pump

Insertion of a flow pump into the Langendorff retrograde perfusion apparatus has permitted the production of stable, graded ischemia in hearts whose hemodynamic and metabolic response may be evaluated. Ventricular pressures were monitored with a modified balloon and catheter-tip manometer system, and oxygen consumption , lactate and glucose metabolism, and tissue high-energy phosphate stores measured. A 15-min stabilization period in 56 paced hearts was followed by 15 min of either full, 40, 30, 20, or 10% coronary flow, after which the ventricular tissue was freeze-clamped for tissue assay. Tissue creatine phosphate fell progressively from 23.7 in full flow hearts to 9.9 mumol/g dry wt after 90% reduction in flow. This was accompanied by a graded reduction in ATP from 20.3 to 14.0 mumol/g dry wt and a rise in AMP from 1.1 to 2.6 mumol/g dry wt. Tissue lactate rose progressively from 22.3 to 60.1 mumol/g dry wt. Hemodynamic function correlated with coronary flow. This preparation offers an opportunity to study pharmacological and metabolic interventions in ischemic heart disease.

Metabolic responses to varying restrictions of coronary blood flow in swine

1975 ◽  
Vol 228 (2) ◽  
pp. 655-662 ◽  
Author(s):  
AJ Liedtke ◽  
HC Hughes ◽  
Neely
Keyword(s):  
Fatty Acid ◽  
Coronary Flow ◽  
Mechanical Performance ◽  
Glucose Consumption ◽  
Creatine Phosphate ◽  
High Energy ◽  
Coronary Perfusion ◽  
Acid Extraction ◽  
High Energy Phosphates ◽  
Tissue Levels

An in situ working swine heart preparation is described in which total coronary perfusion was controlled. At normal rates of coronary flow, oxygen, glucose, and fatty acid utilization were stable for at least a 60-min perfusion period. With a 50% reduction in coronary flow, oxygen and glucose consumption were reduced during 30 min of perfusion and fatty acid extraction was lower at the end of 30 min. Glycogen utilization was increased, but tissue levels of creatine phosphate, ATP, and lactate were similar to those in hearts receiving normal flow. With a 60% reduction in coronary flow, uptake of oxygen, glucose, and fatty acids were further decreased. Tissue levels of high-energy phosphates and glycogen were decreased and ADP, AMP, and lactate increased. Mechanical performance progressively deteriorated in these hearts, and ventricular fibrillation developed after about 20 min (19.8 plus or minus 3.0 min). The data indicate that this preparation is suitable for the study of myocardial metabolism during mild and severe ischemia and may be useful for the evaluation of pharmacological interventions designed for the treatment of myocardial ischemia.

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.

scholarly journals The dose-dependent effect of chronic Verapamil treatment on cardiac function in isolated rat heart with Hypertension

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
S Simovic ◽  
J Jeremic ◽  
G Davidovic ◽  
I Srejovic ◽  
V Zivkovic ◽  
...  
Keyword(s):  
Heart Rate ◽  
Rat Heart ◽  
Coronary Flow ◽  
Chronic Treatment ◽  
Low Dose ◽  
Isolated Rat Heart ◽  
High Dose ◽  
Chronotropic Effects ◽  
Dose Dependent ◽  
Isolated Rat

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Verapamil, a calcium channel blocker, is used for treatment of hypertension, paroxysmal supraventricular tachycardia  and angina pectoris. It primarily blocks L-type calcium channels preventing excessive influx of calcium into cardiomyocytes, leading to negative inotropic effect, and smooth muscle cells resulting in reduced relaxation of vasculature. With calcium antagonism it also causes negative chronotropic effect. However, there is no data on it’s dose-dependent effects on cardiac dynamic parameters and heart rate on isolated rat heart with hypertension. Purpose To investigate chronic, dose-dependent effects of Verapamil on cardiodynamic parameters in isolated rat heart with hypertension. Methods The present 4-week study was carried out on 24 spontaneously hypertensive Wistar Kyoto male rats  (6 weeks old): Control (n = 6), rats treated with 0.5 mg/kg/day of Verapamil (n = 6), rats treated with 5 mg/kg/day of Verapamil (n = 6) and rats treated with 50 mg/kg/day of Verapamil (n = 6). Isolated rat hearts were perfused on Langendorff perfusion apparatus. Results Chronic, low-dose Verapamil treatment significantly depressed function of all cardiodynamic parameters of the hypertensive heart when compared to the rats treated with higher doses of Verapamil (p &lt; 0.001), except on the coronary flow and heart rate when compared to the Control (p= 0.137; p = 1.000, respectively). There was no significant differences between Verapamil in middle dose (5 mg/kg/day) and the Control group in inotropic (p = 0.415) and lusitropic (p = 1.000) effects, while it significantly lowered values of coronary flow (p = 0.002). It achieved significantly lower inotropic, lusitropic and chronotropic effects (p &lt; 0.001) than high Verapamil dose and significantly better inotropic (p = 0.017), lusitropic (p &lt; 0.001), but not chronotropic effects than low-dose Verapamil treatment (p = 0.179). High-dose, chronic treatment with Verapamil significantly intensified function of  the isolated rat heart with hypertension when compared to Control and lower doses of Verapamil (p &lt; 0.001), without significant effects on coronary flow (p = 0.363). Conclusions Chronic treatment with Verapamil in high dose achieved better inotropic, chronotropic and lusitropic effects than treatment in low and middle doses of Verapamil, without significant effects on coronary flow. There is dose-depended effect of chronic Verapamil treatment on cardiac function of isolated rat heart with hypertension.

Performance of hypothermic isolated rat heart at various levels of blood acid-base status

1984 ◽  
Vol 56 (6) ◽  
pp. 1526-1532 ◽  
Author(s):  
M. Sinet ◽  
M. Muffat-Joly ◽  
D. Henzel ◽  
G. Renault ◽  
J. J. Pocidalo
Keyword(s):  
Heart Rate ◽  
Rat Heart ◽  
Coronary Flow ◽  
Myocardial Function ◽  
Isolated Rat Heart ◽  
Acid Base ◽  
External Work ◽  
Myocardial Oxygenation ◽  
Acid Base Status ◽  
Isolated Rat

The effects of respiratory-induced pH variation on mechanical function and myocardial oxygenation of isolated, blood-perfused working rat hearts were studied in hypothermia (26 degrees C) and compared with control values (37 degrees C). In these experiments, the change of plasma pH during hypothermia was parallel to the change in pH of neutral water. At 37 degrees C, pH was varied from 7.15 to 7.62; heart rate increased with pH, both cardiac output and external work remaining unaltered. An increase in pH induced a decrease in coronary flow and an increase in the O2 arteriovenous difference. In hypothermia, hemodynamic performance and myocardial O2 consumption decreased proportionately with no change in cardiac efficiency. At 26 degrees C, the cardiac capacity to react to acid-base variations (pH from 7.34 to 7.86) was preserved, i.e., heart rate increased with pH. As at 37 degrees C, regulation of both coronary flow and myocardial oxygenation was maintained. The present data suggest that the myocardial function of a working isolated rat heart undergoing hypothermia was also preserved. Moderate variations in extracellular acid-base status during hypothermia did not impair either myocardial function or the O2 supply-to-demand ratio.

Role of creatine phosphokinase in cellular function and metabolism

1978 ◽  
Vol 56 (5) ◽  
pp. 691-706 ◽  
Author(s):  
V. A. Saks ◽  
L. V. Rosenshtraukh ◽  
V. N. Smirnov ◽  
E. I. Chazov
Keyword(s):  
Energy Transport ◽  
Creatine Phosphokinase ◽  
Surface Membrane ◽  
Creatine Phosphate ◽  
Contractile Force ◽  
Energy Utilization ◽  
Regulatory Factor ◽  
Main Attention ◽  
Intracellular Energy

This paper summarizes the data concerning the role of the creatine phosphokinase system in muscle cells with main attention to the cardiac muscle. Creatine phosphokinase isoenzymes play a key role in the intracellular energy transport from mitochondria to myofibrils and other sites of energy utilization. Due to the existence of the creatine phosphate pathway for energy transport, intracellular creatine phosphate concentration is apparently an important regulatory factor for muscle contraction which influences the contractile force by determining the rate of regeneration of ATP directly available for myosin ATPase, and at the same time controls the activator calcium entry into the myoplasm across the surface membrane of the cells.

Glibenclamide decelerates the responses of coronary regulation in the goat

1994 ◽  
Vol 266 (5) ◽  
pp. H1715-H1721 ◽  
Author(s):  
J. Dankelman ◽  
C. P. Van der Ploeg ◽  
J. A. Spaan
Keyword(s):  
Heart Rate ◽  
Coronary Flow ◽  
Resistance Index ◽  
Katp Channels ◽  
Complete Response ◽  
Rate Of Change ◽  
Dynamic Responses ◽  
Minor Effect ◽  
Coronary Resistance ◽  
Before And After

The role of blocking ATP-sensitive potassium (KATP) channels by glibenclamide on the dynamic responses of coronary resistance to abrupt changes in perfusion pressure and heart rate was investigated. The left main coronary artery of the open-chest anesthetized goat was perfused with constant pressure (Pp). Pp and arterial flow were averaged per beat, and their ratio was calculated as index of coronary resistance. Responses of resistance index after heart rate (HR) and Pp changes before and after administration of glibenclamide were compared. Their rate of change was quantified by t50, the required time to obtain half of the complete response. During control, t50 for the dilating response induced by a decrease in Pp or increase in HR was 3.8 +/- 0.2 and 6.2 +/- 0.5 (SE) s, respectively. With glibenclamide these values were 24.4 +/- 1.6 and 14.9 +/- 2.1 s. For the constricting response, the numbers for control were 5.8 +/- 0.3 (increase Pp) and 7.2 +/- 0.8 (decrease HR) s. With glibenclamide these values were 22.1 +/- 1.5 and 16.0 +/- 2.9 s. The steady-state adjustment of coronary flow was not altered by glibenclamide. It was concluded that glibenclamide has a minor effect on coronary flow control but reduces the rate of change of coronary resistance index up to a factor of four. Because glibenclamide is supposed to act on KATP channels, it may be concluded that these channels play a major role in the dynamics of coronary blood flow regulation.

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.

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