Control of myocardial oxygen consumption in transgenic mice overexpressing vascular eNOS

2004 ◽  
Vol 287 (5) ◽  
pp. H2115-H2121 ◽  
Author(s):  
E. K. Walsh ◽  
H. Huang ◽  
Z. Wang ◽  
J. Williams ◽  
R. de Crom ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Blood Vessels ◽  
Myocardial Oxygen Consumption ◽  
Cardiac Tissue ◽  
Peripheral Resistance ◽  
Systolic Pressure ◽  
Oxygen Electrode ◽  
Left Ventricular ◽  
Similar Degree ◽  
Coronary Blood Vessels

Our objective was to investigate the potential role of selective endothelial nitric oxide (NO) synthase (eNOS) overexpression in coronary blood vessels in the control of myocardial oxygen consumption (MVo2). Transgenic (Tg) eNOS-overexpressing mice (eNOS Tg) ( n = 22) and wild-type (WT) mice ( n = 24) were studied. Western blot analysis indicated greater than sixfold increase of eNOS in cardiac tissue. Echocardiography in awake mice indicated no difference in cardiac function between WT and eNOS Tg; however, systolic pressure in eNOS Tg mice decreased significantly (126 ± 2.3 to 109 ± 2.3 mmHg; P < 0.05), whereas heart rate (HR) was not different. Total peripheral resistance (TPR) was also decreased (9.8 ± 0.8 to 7.6 ± 0.4 4 mmHg·ml−1·min; P < 0.05) in eNOS Tg. Furthermore, female eNOS Tg mice showed even lower TPR (7.2 ± 0.4 mmHg·ml−1·min) compared with male eNOS mice (8.6 ± 0.5, mmHg·ml·min−1; P < 0.05). Left ventricular slices were isolated from WT and eNOS Tg mice. With the use of a Clark-type oxygen electrode in an airtight bath, MVo2 was determined as the percent decrease during increasing doses (10−10 to 10−4 mol/l) of bradykinin (BK), carbachol (CCh), forskolin (10−12 to 10−6 mol/l), or S-nitroso- N-acetyl penicillamine (SNAP; 10−7 to 10−4 mol/l). Baseline MVo2 was not different between WT (181 ± 13 nmol·g−1·min−1) and eNOS Tg (188 ± 14 nmol·g−1·min−1). BK decreased MVo2 (10−4 mol/l) in WT by 17% ± 1.1 and 33% ± 2.7 in eNOS Tg ( P < 0.05). CCh also decreased MVo2, 10−4 mol/l, in WT by 20% ± 1.7 and 31% ± 2.0 in eNOS Tg ( P < 0.05). Forskolin (10−6 mol/l) or SNAP (10−4 mol/l) also decreased MVo2 in WT by 24% ± 2.8 and 36% ± 1.8 versus eNOS 31% ± 1.8 and 37% ± 3.5, respectively. N-nitro-l-arginine methyl ester (10−3 mol/l) inhibited the MVo2 reduction to BK, CCh, and forskolin by a similar degree ( P < 0.05), but not to SNAP. Thus selective overexpression of eNOS in cardiac blood vessels in mice enhances the control of MVo2 by eNOS-derived NO.

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.

Comparative effects of levosimendan, OR-1896, OR-1855, dobutamine, and milrinone on vascular resistance, indexes of cardiac function, and O2 consumption in dogs

2008 ◽  
Vol 294 (1) ◽  
pp. H238-H248 ◽  
Author(s):  
Patricia N. Banfor ◽  
Lee C. Preusser ◽  
Thomas J. Campbell ◽  
Kennan C. Marsh ◽  
James S. Polakowski ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Pulse Pressure ◽  
Myocardial Oxygen Consumption ◽  
Plasma Concentrations ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Systemic Resistance ◽  
Dose Dependent

Levosimendan enhances cardiac contractility via Ca2+ sensitization and induces vasodilation through the activation of ATP-dependent K+ and large-conductance Ca2+-dependent K+ channels. However, the hemodynamic effects of levosimendan, as well as its metabolites, OR-1896 and OR-1855, relative to plasma concentrations achieved, are not well defined. Thus levosimendan, OR-1896, OR-1855, or vehicle was infused at 0.01, 0.03, 0.1, and 0.3 μmol·kg−1·30 min−1, targeting therapeutic to supratherapeutic concentrations of total levosimendan (62.6 ng/ml). Results were compared with those of the β1-agonist dobutamine and the phosphodiesterase 3 inhibitor milrinone. Peak concentrations of levosimendan, OR-1896, and OR-1855 were 455 ± 21, 126 ± 6, and 136 ± 6 ng/ml, respectively. Levosimendan and OR-1896 produced dose-dependent reductions in mean arterial pressure (−31 ± 2 and −42 ± 3 mmHg, respectively) and systemic resistance without affecting pulse pressure, effects paralleled by increases in heart rate; OR-1855 produced no effect at any dose tested. Dobutamine, but not milrinone, increased mean arterial pressure and pulse pressure (17 ± 2 and 23 ± 2 mmHg, respectively). Regarding potency to elicit reductions in time to peak pressure and time to systolic pressure recovery: OR-1896 > levosimendan > milrinone > dobutamine. Levosimendan and OR-1896 elicited dose-dependent increases in change in pressure over time (118 ± 10 and 133 ± 13%, respectively), concomitant with reductions in left ventricular end-diastolic pressure and ejection time. However, neither levosimendan nor OR-1896 produced increases in myocardial oxygen consumption at inotropic and vasodilatory concentrations, whereas dobutamine increased myocardial oxygen consumption (79% above baseline). Effects of the levosimendan and OR-1896 were limited to the systemic circulation; neither compound produced changes in pulmonary pressure, whereas dobutamine produced profound increases (74 ± 13%). Thus levosimendan and OR-1896 are hemodynamically active in the anesthetized dog at concentrations observed clinically and elicit cardiovascular effects consistent with activation of both K+ channels and Ca2+ sensitization, whereas OR-1855 is inactive on endpoints measured in this study.

Norepinephrine increases the economy of pressure development in isolated canine hearts

1992 ◽  
Vol 263 (3) ◽  
pp. H715-H721
Author(s):  
J. W. Allyn ◽  
R. Teplick ◽  
J. B. Steinberg ◽  
N. A. Munfakh ◽  
G. A. Geffin ◽  
...  
Keyword(s):  
Activation Energy ◽  
Oxygen Consumption ◽  
Linear Regression ◽  
Myocardial Oxygen Consumption ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Pressure Development ◽  
Measures Of Performance

To test for oxygen wasting by norepinephrine (NE) without relying on normalization by measures of performance such as the pressure-volume area, myocardial oxygen consumption (MVO2) was determined for isovolumic beats at five different left ventricular (LV) end-diastolic volumes (EDV) in nine isolated cross-perfused canine hearts in each of three states: a basal anesthetic state (B); after depression with halothane (H); and after adding NE to increase contractility back to the B state (H+NE). The end-diastolic and peak systolic pressure-volume lines were identical for B and H+NE. The R2 for a linear regression of MVO2 per beat for B vs. H+NE for beats originating at the same EDV and developing similar (within 10%) peak isovolumic pressures for all hearts was 0.85. The slope and intercept were 0.83 and 0.01, which are significantly less than one (P less than 0.001) and greater than zero (P less than 0.001), respectively. These data suggest that NE increases both the economy of pressure development as well as activation energy of an isovolumically contracting LV.

Mechanical determinants of myocardial oxygen consumption in conscious dogs

1995 ◽  
Vol 269 (2) ◽  
pp. H609-H620 ◽  
Author(s):  
J. R. Elbeery ◽  
J. C. Lucke ◽  
M. P. Feneley ◽  
G. W. Maier ◽  
C. H. Owen ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Myocardial Oxygen Consumption ◽  
Virtual Work ◽  
Mechanical Energy ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Stroke Work ◽  
External Energy ◽  
Work Model

A new practical descriptor of metabolic to mechanical myocardial energy transfer (MET), termed the virtual work model, was evaluated in 32 conscious dogs and in 8 isolated canine hearts. An index of total mechanical energy expenditure (TME) was calculated as the sum of external energy (stroke work) and an internal energy index of heat (left ventricular end-diastolic volume times left ventricular mean ejection pressure). Physiological comparison of TME (x-axis) and myocardial oxygen consumption (MVO2; y-axis) yielded highly linear MET relationships (mean r = 0.93 +/- 0.07), with an average slope of 0.86 +/- 0.39 (SD) and a y-intercept of 9.1 +/- 6.4 mW/ml myocardium. The linear MVO2-TME relationship did not vary under steady-state vs. dynamic vena caval occlusion, increased heart rate, increased afterload, or increased inotropic state with calcium infusion. Compared with five other indexes of myocardial energetics, the virtual work model of MET was the most linear, the most practical in not requiring determination of the end-systolic pressure-volume relationship, and the most accurate predictor of MVO2 under normal and altered hemodynamic conditions.

Clinical and Experimental Analysis of 201Thallium Uptake of the Heart

1978 ◽  
Vol 17 (04) ◽  
pp. 142-148
Author(s):  
U. Büll ◽  
S. Bürger ◽  
B. E. Strauer
Keyword(s):  
Oxygen Consumption ◽  
Left Ventricle ◽  
Muscle Mass ◽  
Myocardial Oxygen Consumption ◽  
Animal Experiments ◽  
Left Ventricular ◽  
Left Ventricular Wall ◽  
Ventricular Wall ◽  
Flow Measurements ◽  
Myocardial Flow

Studies were carried out in order to determine the factors influencing myocardial 201T1 uptake. A total of 158 patients was examined with regard to both 201T1 uptake and the assessment of left ventricular and coronary function (e. g. quantitative ventriculography, coronary arteriography, coronary blood flow measurements). Moreover, 42 animal experiments (closed chest cat) were performed. The results demonstrate that:1) 201T1 uptake in the normal and hypertrophied human heart is linearly correlated with the muscle mass of the left ventricle (LVMM);2) 201T1 uptake is enhanced in the inner (subendocardial) layer and is decreased in the outer (subepicardial) layer of the left ventricular wall. The 201T1 uptake of the right ventricle is 40% lower in comparison to the left ventricle;3) the basic correlation between 201T1 uptake and LVMM is influenced by alterations of both myocardial flow and myocardial oxygen consumption; and4) inotropic interventions (isoproterenol, calcium, norepinephrine) as well as coronary dilatation (dipyridamole) may considerably augment 201T1 uptake in accordance with changes in myocardial oxygen consumption and/or myocardial flow.It is concluded that myocardial 201T1 uptake is determined by multiple factors. The major determinants have been shown to include (i) muscle mass, (ii) myocardial flow and (iii) myocardial oxygen consumption. The clinical data obtained from patient groups with normal ventricular function, with coronary artery disease, with left ventricular wall motion abnormalities and with different degree of left ventricular hypertrophy are correlated with quantitated myocardial 201T1 uptake.

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.

Role of reflexes following myocardial necrobiosis

1965 ◽  
Vol 209 (6) ◽  
pp. 1081-1088 ◽  
Author(s):  
G. Ascanio ◽  
F. Barrera ◽  
E. V. Lautsch ◽  
M. J. Oppenheimer
Keyword(s):  
Peripheral Resistance ◽  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Hemodynamic Changes ◽  
Ventricular Systolic Pressure ◽  
Arterial Blood ◽  
Bilateral Vagotomy ◽  
Left Ventricular Systolic Pressure

Intracoronary administration of hexachlorotetrafluorobutane (Hexa) into non-thoracotomized dogs produced a statistically significant decrease in left ventricular systolic pressure (LVSP), mean femoral arterial blood pressure (MFAP), first derivative of left ventricular pressure pulse (dP/d t), total peripheral resistance (TPR), and cardiac output (C.O.) lasting up to 1 hr after injection. Femoral vascular resistance decreased during the first 3 min after production of necrobiosis. Fifty percent of the dogs died of ventricular fibrillation (VF) after Hexa infarction. Prereserpinized dogs did not show significant changes in the parameters which were significantly changed in normal dogs after Hexa necrobiosis except in the case of VF which was almost absent in this group. Bilateral vagotomy prior to Hexa administration prevented most hemodynamic changes after necrobiosis whereas atropine did not. Bilateral vagotomy and atropine 1 hr after necrobiosis increased MFAP, dP/d t, LVSP, C.O., and TPR. Apparently excitatory efferent sympathetic activity on heart and femoral arterial vessels is reflexly inhibited by the effects of intracoronary injection of Hexa. The afferent pathway is via the vagus nerve.

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