Measurement of the activation time of oxidative phosphorylation in isolated mouse hearts

2000 ◽  
Vol 279 (6) ◽  
pp. H3118-H3123 ◽  
Author(s):  
Lori A. Gustafson ◽  
Johannes H. G. M. Van Beek
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Response Time ◽  
Myocardial Metabolism ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Rate Pressure Product ◽  
Activation Time ◽  
Dynamic Regulation

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.

Activation time of myocardial oxidative phosphorylation in creatine kinase and adenylate kinase knockout mice

2002 ◽  
Vol 282 (6) ◽  
pp. H2259-H2264 ◽  
Author(s):  
Lori A. Gustafson ◽  
Johannes H. G. M. Van Beek
Keyword(s):  
Heart Rate ◽  
Creatine Kinase ◽  
Oxygen Consumption ◽  
Response Time ◽  
Adenylate Kinase ◽  
Contractile Function ◽  
Left Ventricular ◽  
Wild Type ◽  
Dynamic Regulation ◽  
Developed Pressure

Our goal was to determine whether mice genetically altered to lack either creatine kinase (M/MtCK−/−) or adenylate kinase (AK−/−) show altered properties in the dynamic regulation of myocardial oxygen consumption (MV˙o 2). We measured contractile function, oxygen consumption, and the mean response time of oxygen consumption to a step increase in heart rate [i.e., mitochondrial response time ( t mito)] in isolated Langendorff-perfused hearts from wild-type ( n = 6), M/MtCK−/− ( n = 6), and AK−/− ( n = 4) mice. Left ventricular developed pressure was higher in M/MtCK−/− hearts (88.2 ± 6.8 mmHg) and lower in AK−/− hearts (46.7 ± 9.4 mmHg) compared with wild-type hearts (60.7 ± 10.1 mmHg) at the basal pacing rate. Developed pressure fell slightly when heart rate was increased in all three groups. Basal MV˙o 2 at 300 beats/min was 19.1 ± 2.4, 19.4 ± 1.5, and 16.3 ± 1.9 μmol · min−1 · g dry wt−1for M/MtCK−/−, AK−/−, and wild type, respectively, which increased to 25.5 ± 3.7, 25.4 ± 2.6, and 22.0 ± 2.6 μmol · min−1 · g−1, when heart rate was increased to 400 beats/min. The t mito was significantly faster in M/MtCK−/− hearts: 3.0 ± 0.3 versus 7.3 ± 0.6 and 8.0 ± 0.4 s for M/MtCK−/−, AK−/−, and wild-type hearts, respectively. Our results demonstrate that MV˙o 2 of M/MtCK−/− hearts adapts more quickly to an increase in heart rate and thereby support the hypothesis that creatine kinase acts as an energy buffer in the cytosol, which delays the energy-related signal between sites of ATP hydrolysis and mitochondria.

Consistent substrate utilization despite reduced flow in hearts with maintained work

1983 ◽  
Vol 244 (6) ◽  
pp. H799-H806 ◽  
Author(s):  
K. A. Fox ◽  
H. Nomura ◽  
B. E. Sobel ◽  
S. R. Bergmann
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Myocardial Oxygen Consumption ◽  
Myocardial Metabolism ◽  
Diastolic Pressure ◽  
Rabbit Heart ◽  
Substrate Utilization ◽  
Left Ventricular ◽  
Low Flow ◽  
Heart Preparation

Assessments of myocardial metabolism based on external detection of accumulation of radiolabeled substrates may be influenced, as a result of alterations in flow, by altered substrate delivery as well as altered work (with concomitant changes in metabolic requirements). To determine whether reduced delivery limits substrate utilization under defined conditions of reduced perfusion, an isolated rabbit heart preparation was employed in which flow was reduced but myocardial oxygen consumption (MVo2) and work were kept constant by adjustment of left ventricular end-diastolic pressure and heart rate. Flow was reduced from 1.5 to 0.5 ml . g-1 . min-1, while work was maintained constant in hearts functioning at either low or high levels of MVo2. Consumption of palmitate remained constant (48.8 +/- 11.6 and 68.8 +/- 23.3 nmol . g-1 . min-1), because the proportion of palmitate extracted increased (8.8 +/- 4 to 29.1 +/- 7.2% and 10.3 +/- 3.4 to 21.0 +/- 6.1%). The results indicate that, despite reduction of flow, hearts at constant work loads can extract increasing proportions of delivered substrates such that net utilization remains constant until flow is reduced below the level required to maintain cellular function. They suggest that, under conditions of low flow, impaired extraction of substrates reflects either primarily or secondarily depressed myocardial metabolism rather than simply decreased delivery of substrate.

Heart rate-independent energetics and systolic pressure-volume area in dog heart

1983 ◽  
Vol 244 (2) ◽  
pp. H206-H214 ◽  
Author(s):  
H. Suga ◽  
R. Hisano ◽  
S. Hirata ◽  
T. Hayashi ◽  
O. Yamada ◽  
...  
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Left Ventricle ◽  
Mechanical Energy ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Canine Heart ◽  
Heart Rates ◽  
Dog Heart ◽  
Total Mechanical Energy

Left ventricular (LV) systolic pressure-volume area (PVA), a new measure of total mechanical energy for the contraction, linearly correlates with its oxygen consumption per beat (VO2) regardless of contraction mode in a canine heart with stable chronotropism and inotropism. PVA is the area in the pressure-volume (PV) diagram circumscribed by the end-systolic and end-diastolic PV relation curves and the systolic segment of the PV loop and has dimensions of energy. We investigated whether primary changes in heart rate would affect the VO2-PVA relation. In the excised cross-circulated canine heart with left ventricular load controlled with a servo pump, we changed heart rate by pacing to compare the VO2-PVA relations at low [124 +/- 17 (SD) min-1] and high (193 +/- 23) heart rates. In 15 left ventricles, VO2 (ml O2 X beat-1 X 100 g LV-1) was (1.75 +/- 0.57) X 10(-5) PVA (mmHg X ml X beat-1 X 100 g LV-1) + 0.031 +/- 0.011 (ml O2 X beat-1 X 100 g LV-1). The VO2-PVA relation was virtually independent of heart rate in individual hearts. We conclude that the load-independent VO2-PVA relationship is not affected by chronotropism in a given canine left ventricle.

Dynamic adaptation of cardiac oxidative phosphorylation is not mediated by simple feedback control

1999 ◽  
Vol 277 (4) ◽  
pp. H1375-H1384 ◽  
Author(s):  
J. H. G. M. van Beek ◽  
M. H. van Wijhe ◽  
M. H. J. Eijgelshoven ◽  
J. B. Hak
Keyword(s):  
Heart Rate ◽  
Feedback Control ◽  
Oxidative Phosphorylation ◽  
Response Time ◽  
Immediate Feedback ◽  
Perfused Heart ◽  
Dynamic Regulation ◽  
Fast Phase ◽  
Before And After ◽  
Simple Feedback

The classic idea about regulation of cardiac oxidative phosphorylation (OxPhos) was that breakdown products of ATP (ADP and Pi) diffuse freely to the mitochondria to stimulate OxPhos. On the basis of this metabolic feedback control system, the response time of OxPhos ( t mito) is predicted to be inversely proportional to the mitochondrial aerobic capacity (MAC). We determined t mito during steps in heart rate in isolated perfused rabbit hearts ( n = 16) before and after reducing MAC with nonsaturating doses of oligomycin. The reduction of MAC was quantified in mitochondria isolated from each perfused heart, dividing oligomycin-sensitive, ADP-stimulated state 3 respiration by oligomycin-insensitive uncoupled respiration. The t mito to heart rate steps from 60 to 70 and 80 beats/min was 5.6 ± 0.6 and 7.2 ± 0.8 s (means ± SE) and increased an estimated 34 and 40% for a 50% decrease in MAC ( P < 0.05), respectively, which is much less than the 100% predicted by the feedback hypothesis. For steps to 100 or 120 beats/min, t mito was 8.3 ± 0.5 and 11.2 ± 0.6 s and was not reduced with decreases in MAC ( P > 0.05). We conclude that immediate feedback control by quickly diffusing ADP and Pi cannot explain the dynamic regulation of cardiac OxPhos. Because calcium entry into the mitochondria also cannot explain the first fast phase of OxPhos activation, we propose that delay of the energy-related signal in the cytoplasm dominates the response time of OxPhos.

CARDIORESPIRATORY SYSTEM UNDER BICYCLE ERGOMETER TEST IN SKIERS WITH DIFFERENT TRAINING STATUS (KOMI REPUBLIC)

2019 ◽  
pp. 76-84
Author(s):  
Yu.G. Solonin ◽  
T.P. Loginova ◽  
I.O. Garnov ◽  
A.L. Markov ◽  
A.A. Chernykh ◽  
...  
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Komi Republic ◽  
Rate Pressure Product ◽  
Training Status ◽  
Maximum Oxygen Consumption ◽  
Bicycle Ergometry ◽  
Cardiorespiratory System ◽  
Unit Pulse ◽  
Ski Racers

The aim of the study is to examine the impact of training status on ski racers (Komi Republic) at rest and under bicycle ergometry evaluating their cardiorespiratory system parameters. Materials and Methods. The authors examined male ski racers with different training status: 22 first-rank sportsmen, 22 candidates for Master of Sports and 22 Masters of Sports. Athletes underwent bicycle ergometry loads up to refusal. Oxycon Pro system (Germany) was used. Then authors studied the complex of cardiorespiratory parameters, calculating maximum oxygen consumption and unit physiological cost. Results. At rest and under standard physical load (200 W) Masters of Sports demonstrate significantly increased training status among ski racers in such cardiorespiratory system parameters as heart rate, rate pressure product and oxygen pulse. Under standard physical load (200 W) statistically significant differences between first-rank sportsmen and candidates for Master of Sports are detected by heart rate, rate pressure product, respiration rate, respiratory minute volume and oxygen utilization coefficient. Such deviations indicate differences in training status. Under maximum load, the highest training status is found in Masters of Sports: bicycle ergometry load power and duration; unit pulse, pressor and cardiac cost, bulk and unit values of maximum oxygen consumption. Heart rate values, unit pulse and heart-vent cost indicate a high training status in candidates for Master of Sports under load up to refusal, if compared with first-rank sportsmen. Athletes’ organism under load up to refusal works more efficiently than under moderate load (200 W). The training status in ski racers (Komi Republic) is manifested in the saving cardiorespiratory system functions, both at rest and under standard bicycle ergometry, as well as in parameters of unit physiological cost under loads up to refusal and increased values of maximum oxygen consumption. Keywords: ski racers, Komi Republic, training status, bicycle ergometry loads, cardiorespiratory system, maximum oxygen consumption.

alpha-Adrenergic control of oxygen delivery to myocardium during exercise in conscious dogs

1982 ◽  
Vol 242 (5) ◽  
pp. H805-H809 ◽  
Author(s):  
G. R. Heyndrickx ◽  
P. Muylaert ◽  
J. L. Pannier
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Oxygen Delivery ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Adrenergic Blockade ◽  
Adrenergic Control

alpha-Adrenergic control of the oxygen delivery to the myocardium during exercise was investigated in eight conscious dogs instrumented for chronic measurements of coronary blood flow, left ventricular (LV) pressure, aortic blood pressure, and heart rate and sampling of arterial and coronary sinus blood. After alpha-adrenergic receptor blockade a standard exercise load elicited a significantly greater increase in heart rate, rate of change of LV pressure (LV dP/dt), LV dP/dt/P, and coronary blood flow than was elicited in the unblocked state. In contrast to the response pattern during control exercise, there was no significant change in coronary sinus oxygen tension (PO2), myocardial arteriovenous oxygen difference, and myocardial oxygen delivery-to-oxygen consumption ratio. It is concluded that the normal relationship between myocardial oxygen supply and oxygen demand is modified during exercise after alpha-adrenergic blockade, whereby oxygen delivery is better matched to oxygen consumption. These results indicate that the increase in coronary blood flow and oxygen delivery to the myocardium during normal exercise is limited by alpha-adrenergic vasoconstriction.

Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs

1980 ◽  
Vol 49 (1) ◽  
pp. 28-33 ◽  
Author(s):  
G. R. Heyndrickx ◽  
J. L. Pannier ◽  
P. Muylaert ◽  
C. Mabilde ◽  
I. Leusen
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Myocardial Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Myocardial Oxygen Consumption ◽  
Left Ventricular ◽  
Adrenergic Blockade ◽  
Oxygen Balance

The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction.

Abstract 13421: Ventricular and Arterial Elastance During Isometric Handgrip Exercise and Post-exercise Circulatory Arrest in Heart Failure With and Without Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Naoki Fujimoto ◽  
Keishi Moriwaki ◽  
Issei Kameda ◽  
Masaki Ishiyama ◽  
Taku Omori ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Circulatory Arrest ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Isometric Handgrip ◽  
Arterial Elastance ◽  
Post Exercise

Introduction: Isometric handgrip (IHG) training at 30% maximal voluntary contraction (MVC) lowers blood pressure in hypertensive patients. Impacts of IHG exercise and post-exercise circulatory arrest (PECA), which isolates metaboreflex control, have been unclear in heart failure (HF). Purpose: To investigate the impacts of IHG exercise and PECA on ventricular-arterial stiffness and left ventricular (LV) relaxation in HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). Methods: We invasively obtained LV pressure-volume (PV) loops in 20 patients (10 HFpEF, 10 HFrEF) using conductance catheter with microtip-manometer during 3 minutes of IHG at 30%MVC and 3 minutes of PECA. Hemodynamics and LV-arterial function including LV end-systolic elastance (Ees) by the single-beat method, effective arterial elastance (Ea), and time constant of LV relaxation (Tau) were evaluated every minute. Results: At rest, HFpEF had higher LV end-systolic pressure (ESP) and lower heart rate than HFrEF with similar LV end-diastolic pressure (EDP). The coupling ratio (Ees/Ea) was greater in HFpEF than HFrEF (1.0±0.3 vs. 0.6±0.3, p<0.01). IHG for 3minutes similarly increased heart rate in HFpEF (by 10±8 bpm) and HFrEF (by 14±6 bpm). IHG also increased end-diastolic and LVESP (134±21 vs. 158±30 mmHg and 113±25 vs. 139±25 mmHg) in both groups (groupхtime effect p≥0.25). In HFpEF, Ees, Ea and Ees/Ea (1.0±0.3 vs. 1.1±0.4) were unaffected during IHG. In HFrEF, IHG induced variable increases in Ea. LV end-systolic volume and the ESPV volume-axis intercept were larger, and Ees at IHG 3 rd min was greater (1.30±0.7 vs. 3.1±2.1 mmHg/ml, p<0.01) than baseline, resulting in unchanged Ees/Ea at IHG 3 rd min (0.6±0.3 vs. 0.8±0.4, p≥0.37). Tau was prolonged only in HFrEF during IHG and was returned to the baseline value during PECA. During the first 2 minutes of PECA, LVESP was lower than that at IHG 3 rd min only in HFpEF, suggesting less metaboreflex control of blood pressure in HFpEF during IHG. Conclusions: IHG exercise at 30%MVC induced modest increases in LV end-systolic and end-diastolic pressures in HFpEF and HFrEF. Although the prolongation of LV relaxation was observed only in HFrEF, the ventricular and arterial coupling was maintained throughout the IHG exercise in both groups.

LV pressure-volume area and oxygen consumption: evaluation in intact dog by fast CT

1990 ◽  
Vol 258 (4) ◽  
pp. H1208-H1215
Author(s):  
N. Chung ◽  
X. Wu ◽  
K. R. Bailey ◽  
E. L. Ritman
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Myocardial Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Adrenergic Blockade ◽  
Ct Scanner ◽  
Beta Adrenergic ◽  
The Relationship

The relationship between left ventricular (LV) myocardial oxygen consumption (MVO2) and LV systolic pressure-volume area (PVA) was investigated in anesthetized closed-chest dogs with intact reflexes and subsequently with beta-adrenergic blockade, with or without simultaneous muscarinic blockade. LV chamber volumes were measured using a fast computerized tomography (CT) scanner (dynamic spatial reconstructor, DSR) at 33-ms intervals. Myocardial blood flow was measured from the DSR scans of aortic root angiograms. With intact reflexes, LV MVO2 (Y) related to PVA (X) values as Y = (4.28 +/- 1.81)X + (1.94 +/- 6.0) (n = 24) (mJ.g-1.cycle-1). With beta-adrenergic blockade, LV MVO2 (Y) related to PVA (X) value as Y = (4.24 +/- 1.03)X - (6.43 +/- 6.5), (n = 9) (mJ.g-1.cycle-1). With beta-adrenergic and muscarinic blockade, LV MVO2 (Y) related to PVA (X) value as Y = (2.84 +/- 1.72)X + (3.51 +/- 5.15), (n = 13) (mJ.g-1.cycle-1). The slopes of these regressions are higher than the slopes demonstrated by others in isolated ventricles but very similar to those demonstrated in open-chest dogs.

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