Influence of metabolic substrate on rat heart function and metabolism at different coronary flows

1991 ◽  
Vol 261 (3) ◽  
pp. H741-H750 ◽  
Author(s):  
D. Burkhoff ◽  
R. G. Weiss ◽  
S. P. Schulman ◽  
R. Kalil-Filho ◽  
T. Wannenburg ◽  
...  
Keyword(s):  
Heart Function ◽  
Ventricular Volume ◽  
High Energy ◽  
Left Ventricular ◽  
Low Flow ◽  
Coronary Perfusion ◽  
Metabolic Substrate ◽  
Work Related ◽  
The Difference ◽  
Developed Pressure

The influence of metabolic substrate on contractile strength, myocardial oxygen consumption (MVO2), high- and low-energy phosphate levels, and intracellular pH were determined in isovolumically contracting isolated rat hearts perfused with solutions containing either glucose or hexanoate at both high and low coronary perfusion pressures (CPP). Contractile strength was not significantly influenced by substrate at a CPP of 80 mmHg. As coronary flow was decreased, developed pressure measured at a fixed left ventricular volume (LVV) was lower during hexanoate than glucose perfusion. The relationship between MVO2 and mechanical work determined at a CPP of 80 mmHg over a range of LVVs was shifted upward in a parallel manner when substrate was switched from glucose to hexanoate. The MVO2-work relationship measured at a fixed LVV but over a range of coronary flows (7-20 ml/min) was also parallel shifted upward on switching from glucose to hexanoate. Basal MVO2 was greater during hexanoate than glucose perfusion by an amount that accounted for two-thirds the total increase in MVO2 observed between the substrates under unloaded beating conditions. The remainder of the difference was attributed to increased energy requirements for excitation-contraction coupling. Inorganic phosphate concentrations increased more and phosphocreatine concentrations decreased more during low-flow conditions (3 ml/min) when hearts were perfused with hexanoate compared with glucose. Thus hexanoate decreases myocardial efficiency compared with glucose in large part by increasing non-work-related oxygen demands. This inefficiency impacts adversely on contractile strength and high-energy phosphate concentrations at low coronary flows.

Diabetic type of cardiomyopathy in food-restricted rats

1992 ◽  
Vol 70 (7) ◽  
pp. 1040-1047 ◽  
Author(s):  
Fatemeh Savabi ◽  
Arlene Kirsch
Keyword(s):  
Molecular Mechanisms ◽  
Contractile Function ◽  
Fold Increase ◽  
Ventricular Volume ◽  
High Energy ◽  
Left Ventricular ◽  
Perfused Heart ◽  
Developed Pressure ◽  
Inotropic Responses ◽  
Better Than

We have demonstrated that food restriction that is associated with weight loss can produce a type of cardiac dysfunction similar to that produced by diabetes. As in diabetic atria, the food-restricted atria had a 2-fold increase in contraction force, rate of force development, and rate of force decline compared with controls. Both food-restricted and diabetic atria could tolerate anoxia better than controls. The contractile function of the whole perfused heart from the food-restricted rat was reduced, as in the case of the diabetic heart. As the left ventricular volume was increased, the left ventricular developed pressure and the rate of rise and fall in pressure were significantly reduced in both food-restricted and diabetic hearts, compared with those of age- and weight-matched controls. The positive inotropic responses of atria and whole perfused heart to increasing concentrations of extracellular calcium were similarly altered in food-restricted and diabetic hearts. The possible molecular mechanisms of these findings and some of the differences observed between food-restricted and diabetic hearts are discussed.Key words: diabetes, heart, cardiomyopathy, calorie restriction, high energy phosphate, creatine kinase.

Adenosine antagonism decreases metabolic but not functional recovery from ischemia

1991 ◽  
Vol 260 (1) ◽  
pp. H193-H200 ◽  
Author(s):  
D. A. Angello ◽  
J. P. Headrick ◽  
N. M. Coddington ◽  
R. M. Berne
Keyword(s):  
Functional Recovery ◽  
Left Ventricular ◽  
Low Flow ◽  
Ischemia And Reperfusion ◽  
Constant Flow ◽  
Hemodynamic Parameters ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Adenosine Antagonism ◽  
Developed Pressure

The effect of adenosine receptor antagonism on function and metabolism was examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic rat hearts perfused at constant flow were subjected to 30 min of ischemia followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8-phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic parameters or metabolism preischemia. During ischemia, left ventricular developed pressure declined to approximately 15% of preischemic values in control and 8-PT hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of preischemic values in control and 8-PT hearts, respectively. After reperfusion, function recovered to greater than 95% of preischemic levels in control and 8-PT hearts. Unlike control hearts, recovery of metabolites was significantly different during reperfusion in 8-PT hearts (P less than 0.05); ATP, phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of preischemic values, respectively. Venous purine washout was significantly greater (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to adversely affect metabolic but not functional recovery in the ischemic-reperfused myocardium.

Cardiac function in spontaneously hypertensive diabetic rats

1986 ◽  
Vol 251 (3) ◽  
pp. H571-H580 ◽  
Author(s):  
B. Rodrigues ◽  
J. H. McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Developed Pressure ◽  
Working Heart ◽  
Diabetes Induction

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.

Protective effects of adenosine in the perfused rat heart: changes in metabolism and intracellular ion homeostasis

1993 ◽  
Vol 264 (4) ◽  
pp. C986-C994 ◽  
Author(s):  
T. A. Fralix ◽  
E. Murphy ◽  
R. E. London ◽  
C. Steenbergen
Keyword(s):  
Cell Injury ◽  
Recovery Of Function ◽  
Ion Homeostasis ◽  
High Energy ◽  
Left Ventricular ◽  
Protective Effects ◽  
Intracellular Ca ◽  
Developed Pressure ◽  
High Energy Phosphate Metabolism ◽  
Glycolytic Rate

Increased concentrations of intracellular H+, Na+, and Ca2+ have been observed during ischemia, and these ionic alterations have been correlated with several indexes of cell injury in a number of studies. Recently, adenosine was proposed to play a role in ischemic preconditioning, since adenosine antagonists block the protective effects of these brief intermittent periods of ischemia and reflow. In this study we evaluated the protective effects of adenosine (20 microM) on high-energy phosphate metabolism, H+ and Ca2+ accumulation, and glycolytic rate during 30 min of no-flow ischemia. Adenosine was observed to slow the onset of contracture (7.0 +/- 0.9 min) and to improve left ventricular developed pressure (62 +/- 7% of initial) during reperfusion compared with untreated hearts (5.0 +/- 0.6 min and 18 +/- 5%, respectively). Intracellular Ca accumulation at the end of 30 min of ischemia was higher in the untreated (2,835 +/- 465 nM) than in the adenosine-treated (2,064 +/- 533 nM) hearts, while intracellular pH fell more in the untreated (5.85 +/- 0.17) than in the adenosine-treated hearts (6.27 +/- 0.16). Glycolytic rate and the rate of ATP decline were significantly attenuated in the adenosine-treated hearts during ischemia. Thus adenosine treatment slowed the rate of metabolism and delayed the accumulation of H+ and Ca2+ during ischemia, resulting in better recovery of function upon reflow.

Endogenous endothelin-1 impairs endothelium-dependent relaxation after myocardial ischemia and reperfusion

1994 ◽  
Vol 267 (5) ◽  
pp. H1833-H1841 ◽  
Author(s):  
J. M. Hagar
Keyword(s):  
Myocardial Ischemia ◽  
Control Release ◽  
Microvascular Dysfunction ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Developed Pressure ◽  
Eta Receptor Antagonist

Endothelin (ET)-1 is produced in response to myocardial ischemia and reperfusion. It is a potent constrictor of coronary resistance vessels and may therefore contribute to myocardial injury and postischemic microvascular dysfunction. Isolated buffer-perfused rabbit hearts, under conditions of constant flow and isovolumic contraction, underwent 60 min of global ischemia and 60 min of reperfusion after pretreatment with selective ETA receptor antagonist BQ-123 (10(-7) M) in perfusate, exogenous ET-1 (10(-11) M), or control. Release of ET increased significantly at 20 and 60 min of reperfusion. BQ-123 did not enhance the recovery of left ventricular developed pressure or coronary perfusion pressure, whereas exogenous ET tended to worsen them. Cumulative creatine kinase release over 20 min of reperfusion did not differ significantly between groups. Maximum endothelium-dependent dilation to acetylcholine (ACh) was initially 62 +/- 6, 71 +/- 6, and 63 +/- 8% (SE) of U-46619-induced preconstriction in control, BQ-123-, and ET-treated hearts. At 20 min of reperfusion it was 37 +/- 5, 73 +/- 9, and 22 +/- 5%, and at 60 min of reperfusion it was 35 +/- 7, 79 +/- 6, and 22 +/- 3% (P < 0.001 for BQ-123 vs. control at 20 min and P < 0.0001 at 60 min). Endothelium-independent dilation to nitroglycerin was unaltered by ischemia and reperfusion. Neither BQ-123 alone nor a 1-h infusion of ET (10(-10) M) altered the response to ACh in nonischemic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Static and dynamic operating characteristics of a pericardial balloon

2001 ◽  
Vol 90 (4) ◽  
pp. 1481-1488 ◽  
Author(s):  
Douglas R. Hamilton ◽  
Gwyneth Devries ◽  
John V. Tyberg
Keyword(s):  
Frequency Response ◽  
Diastolic Pressure ◽  
Ventricular Volume ◽  
Left Ventricular ◽  
Operating Characteristics ◽  
Minimum Diameter ◽  
Before And After ◽  
Unity Gain ◽  
Dynamic Operating ◽  
The Difference

Previously, we developed a balloon transducer to measure the constraint of the pericardium (i.e., pericardial pressure) on the surface of the heart. It was validated physiologically in that it was shown to measure a pressure equal to the difference between the left ventricular end-diastolic pressure measured before and after pericardiectomy at the same left ventricular volume. To define its static operating characteristics, we loaded the balloon nonuniformly with weights that covered fractions of the balloon surface and found that the balloon accurately recorded the average stress if the stress was applied over at least 23% of its surface. To test its performance when curved, we placed it in large and small cylinders (minimum diameter 31 mm) and found that the balloon accurately recorded the stress. To define its dynamic operating characteristics, we applied sinusoidal stresses and found that its frequency response was limited only by that of the connecting catheter. When better dynamic response is required, we introduce a micromanometer-tipped catheter to obtain a unity-gain frequency response that is flat to 200 Hz.

Influence of coronary perfusion and myocardial edema on pressure-volume diagram of left ventricle

1961 ◽  
Vol 201 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Cecil E. Cross ◽  
P. Andre Rieben ◽  
Peter F. Salisbury
Keyword(s):  
Diastolic Pressure ◽  
Myocardial Edema ◽  
Ventricular Volume ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Similar Degree ◽  
Coronary Perfusion ◽  
Fluid Accumulation ◽  
Tension Development ◽  
Isolated Hearts

Pressure-volume diagrams of paced, isolated hearts were derived from isovolumic contractions and auxotonic contractions (simultaneous changes of pressure and volume). Coronary perfusion, fluid accumulation in heart muscle, and left ventricular volume and pressure were measured and controlled. Pressure-volume diagrams from isovolumic and auxotonic contractions were virtually identical in the same heart and were influenced by the same factors to a similar degree. At equal diastolic volumes the magnitude of systolic, as well as of diastolic pressures, and the occurrence of a systolic descending limb were directly related to coronary perfusion pressure. At equal diastolic volumes, other factors being constant, myocardial edema did not influence the contractile strength (i.e., maximum contractile tension development) of a ventricle, but did decrease its distensibility (i.e., increase diastolic pressure) in proportion to fluid accumulation. Myocardial water content and coronary factors (coronary arterial and venous pressures, coronary blood volume and flow) therefore constitute intrinsic mechanisms which can regulate the performance of a ventricle by changing its contractile strength, its distensibility, or both. The effects of coronary factors and of myocardial edema on the distensibility of a ventricle are sufficient in magnitude to explain hemodynamic abnormalities which characterize certain types of congestive heart failure.

Cardioprotective Effects of Propofol and Sevoflurane in Ischemic and Reperfused Rat Hearts 

1999 ◽  
Vol 91 (5) ◽  
pp. 1349-1349 ◽  
Author(s):  
Sanjiv Mathur ◽  
Parviz Farhangkhgoee ◽  
Morris Karmazyn
Keyword(s):  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphates ◽  
Constant Flow Rate ◽  
Rat Hearts ◽  
Reperfusion Period ◽  
Coronary Syndromes ◽  
Cardioprotective Effects ◽  
Developed Pressure

Background Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane. Methods Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion. Results Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment. Conclusion HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.

Use of 2,3-butanedione monoxime to estimate nonmechanical VO2 in rabbit hearts

1993 ◽  
Vol 265 (3) ◽  
pp. H834-H842 ◽  
Author(s):  
H. Yaku ◽  
B. K. Slinker ◽  
T. Mochizuki ◽  
B. H. Lorell ◽  
M. M. LeWinter
Keyword(s):  
Ventricular Volume ◽  
Rabbit Heart ◽  
Contractile Proteins ◽  
Left Ventricular ◽  
Energy Utilization ◽  
Selective Effect ◽  
Low Concentration ◽  
Butanedione Monoxime ◽  
Developed Pressure ◽  
Whole Heart

The purpose of the present study was to evaluate the feasibility of partitioning myocardial O2 consumption (VO2) into mechanical and nonmechanical components in the whole heart preparation using a negative inotrope, 2,3-butanedione monoxime (BDM), which has been reported to have a selective effect on the contractile proteins in a low concentration range (< 6 mM). In six isolated bovine red blood cell-perfused rabbit hearts, VO2 and force-time integral (FTI) were measured during infusion of varying concentrations of BDM at a constant left ventricular volume chosen such that control left ventricular peak isovolumic pressure was approximately 100 mmHg. The VO2-FTI relation with BDM concentrations < or = 5 mM was highly linear (median r = 0.98). Its VO2-axis intercept at zero FTI had a positive value (mean 23% of control, 0.014 ml O2.beat-1 x 100 g-1). To confirm the selective effect of BDM on the contractile proteins, the intracellular free Ca2+ transient was measured with the fluorescent indicator indo 1 in three isolated buffer-perfused rabbit hearts. The amplitude of the Ca2+ transient was not altered by BDM at concentrations < or = 10 mM, although left ventricular developed pressure was markedly depressed. This finding indicates that BDM < or = 10 mM does not affect excitation-contraction coupling. We conclude that the VO2-axis intercept value of the VO2-FTI relation during BDM infusion in a low concentration range represents VO2 for nonmechanical energy utilization. The BDM method to partition VO2 into mechanical and nonmechanical components is thus feasible in the whole rabbit heart.

Chronically Administered Acetaminophen and the Ischemia/Reperfused Myocardium

2003 ◽  
Vol 228 (6) ◽  
pp. 674-682 ◽  
Author(s):  
R. Golfetti ◽  
T. Rork ◽  
G. Merrill
Keyword(s):  
Creatine Kinase ◽  
Tap Water ◽  
Chronic Administration ◽  
Left Ventricular ◽  
Low Flow ◽  
Control Group ◽  
Coronary Perfusion ◽  
In Vitro Production

Male and female Hartley strain guinea pigs weighing 280 ± 10 g were given acetaminophen-treated water ad libitum for 10 days. Sham-treated control animals were given similar quantities of untreated tap water (vehicle-treated control group). On Day 10, hearts were extracted, instrumented, and exposed to an ischemia (low-flow, 20 min)/reperfusion protocol. Our objective was to compare and contrast ventricular function, coronary circulation, and selected biochemical and histological indices in the two treatment groups. Left ventricular developed pressure in the early minutes of reperfusion was significantly greater in the presence of acetaminophen, e.g., at 1 min, 40 ± 4 vs 21 ± 3 mmHg ( P < 0.05). Coronary perfusion pressure was significantly less from 3 to 40 min of reperfusion in the presence of acetaminophen. Creatine kinase release in vehicle-treated hearts rose from 42 ± 14 (baseline) to 78 ± 25 units/liter by the end of ischemia. Corresponding values in acetaminophen-treated hearts were 36 ± 8 and 44 ± 14 units/liter. Acetaminophen significantly ( P < 0.05) attenuated release of creatine kinase. Chemiluminescence, an indicator of the in vitro production of peroxynitrite via the in vivo release of superoxide and nitric oxide, was also significantly attenuated by acetaminophen. Electron microscopy indicated a well-preserved myofibrillar ultrastructure in the postischemic myocardium of acetaminophen-treated hearts relative to vehicle-treated hearts (e.g., few signs of contraction bands, little or no evidence of swollen mitochondria, and well-defined light and dark bands in sarcomeres with acetaminophen; opposite with vehicle). We conclude that chronic administration of acetaminophen provides cardioprotection to the postischemic, reperfused rodent myocardium.

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