Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function

Apstein, Carl S.; Dennis, Richard C.; Briggs, Laura E.; Vogel, Werner; Frazer, Jonathan; Valeri, C. R.

doi:10.1152/ajpheart.1985.248.4.h508

Cited by 31 publications

(32 citation statements)

References 16 publications

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“…The 40% increase in oxygen consumption due to altered extraction during CF-PS was much smaller than the 148% increase in oxygen consumption due to accelerated delivery during IF-PS. Furthermore, the current values for oxygen extraction fraction are comparable to those reported for other isolated blood perfused heart preparations in which myocardial oxygen extraction ranged from 0.20 to 0.45 (10,(12)(13)(14)19).…”

Section: Resultssupporting

confidence: 83%

“…1 are from experiments evaluating the functional and metabolic stability of the retrograde blood perfused rabbit heart during 60 min ofcontrol stimulation and perfusion. Oxygen consumption and extraction (a), lactate consumption and the lactate/pyruvate ratio (b), and developed pressure and the rate times pressure product (c) were all within the range previously reported by other investigators employing isolated blood perfused hearts (10,(12)(13)(14)19). Stability of the current preparation was indicated by statistical analysis ofthis data that did not reveal any significant time-related simple trends in any of the physiologic parameters assessed.…”

Section: Resultssupporting

confidence: 78%

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Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

Marshall¹,

Nash²,

Bersohn³

et al. 1987

J. Clin. Invest.

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The effect on myocardial energy balance of increasing oxygen demand without altering basal myocardial perfusion rate was assessed in isolated, isovolumic, retrograde blood perfused rabbit hearts. Myocardial energy requirements were increased with paired stimulation. The capacity of rapid paired stimulation to increase mechanical energy consumption was demonstrated in the presence of increased perfusion with the rate X pressure product and oxygen consumption increasing 86 and 148%, respectively, compared with control values. In contrast, rapid paired stimulation under constant, basal flow conditions did not alter the rate X pressure product, while oxygen extraction and consumption increased only 40% relative to control. Myocardial ATP, creatine-phosphate, and lactate content were identical under control and constant flow-paired stimulation conditions. The results of this study indicate that no detectable energy imbalance was produced by rapid paired stimulation with flow held constant at basal rates. These results suggest that the myocardium does not increase mechanical energy expenditure in response to inotropic or rate stimulation in the presence of restricted flow reserve and are inconsistent with the concept of "demand-induced" or "relative" myocardial ischemia.

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Section: Resultssupporting

confidence: 83%

Section: Resultssupporting

confidence: 78%

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

Marshall¹,

Nash²,

Bersohn³

et al. 1987

J. Clin. Invest.

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show abstract

“…Preparation of isovolumically beating, retrograde blood-perfused rabbit hearts was similar to that previously reported (14)(15)(16). Briefly, after administration of 10 mg of sodium heparin and 200 mg of sodium pentobarbital via an ear vein, hearts from nonfasted male New Zealand white rabbits (2.0-2.5 kg) were excised through a median sternotomy and arrested in ice-cold saline.…”

Section: Methodsmentioning

confidence: 89%

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Marshall¹

1988

J. Clin. Invest.

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The relationships between contractile function, myocardial oxygen consumption, and tissue high energy phosphate and lactate content were investigated during partial coronary flow disruption. The experimental preparation was an isolated, isovolumic retrograde blood-perfused rabbit heart. Both developed pressure (r = 0.94) and dp/dt (r = 0.95) exhibited strong linear correlations with myocardial oxygen consumption that were stable for up to 45 min after blood flow reduction. In contrast, tissue high energy phosphate content exhibited nonlinear relationships with both developed pressure and oxygen consumption such that systolic mechanical function and oxidative metabolism declined to 20 and 30% of control values, respectively, before significant abnormalities in myocardial high energy phosphate stores were observed. Similarly, developed pressure and oxygen consumption decreased to 36 and 48% of control, respectively, before abnormal tissue lactate content was detected. The results of this study indicate that: (a) mechanical function is closely related to the rate of oxidative energy production during partial coronary flow disruption, and (b) despite the development of significant contractile dysfunction, tissue high energy phosphate content remains at normal levels except under the most severely flow-deprived conditions. The preservation of tissue energy stores can be explained by the apparent coupling of contractile performance to oxidative energy production, which could function to maintain myocardial energy balance during partial coronary flow restriction.

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“…In contrast to high P 50 , low P 50 impaired tissue O 2 availability by limiting diffusion. Low P 50 blood was shown to reduce bile flow and Pv O 2 (3), increased mortality after hemorrhagic shock (28), and decreased myocardial contractility (2). Gastric intramucosal pH fell after transfusion of blood with low P 50 (29).…”

Section: Discussionmentioning

confidence: 99%

“…Right shifting the ODC, or increasing the O 2 tension at which Hb is 50% saturated (P 50 ), favors release of O 2 from hemoglobin at higher tissue PO 2 (4,13). As a consequence, the O 2 gradient between RBCs and the mitochondria is increased, and more of the O 2 transported in the blood is available for consumption in the tissues.…”

mentioning

confidence: 99%

Increasing P₅₀does not improve Do_2critor systemicV˙o₂in severe anemia

Eichelbrönner

D'Almeida

Sielenkämper

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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binding affinity facilitates O2 unloading from Hb, potentially increasing tissue mitochondrial O2 availability. We hypothesized that a reduction of Hb-O2 affinity would increase O2 extraction when tissues are O2 supply dependent, reducing the threshold of critical O2 delivery (DO2 CRIT). We investigated the effects of increased O2 tension at which Hb is 50% saturated (P50) on systemic O2 uptake (V O2 SYS), DO2 CRIT, lactate production, and acid-base balance during isovolemic hemodilution in conscious rats. After infusion of RSR13, an allosteric modifier of Hb, P 50 increased from 36.6 Ϯ 0.3 to 48.3 Ϯ 0.6 but remained unchanged at 35.4 Ϯ 0.8 mmHg after saline (control, CON). Arterial O 2 saturations were equivalent between RSR13 and saline groups, but venous PO 2 was higher and venous O2 saturation was lower after RSR13. Convective O2 delivery progressively declined during hemodilution reaching the DO2 CRIT at 3.4 Ϯ 0.8 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 (CON) and 3.6 Ϯ 0.6 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 (RSR13). At Hb of 8.1 g/l V O2 SYS started to decrease (CON: 1.9 Ϯ 0.1; RSR13: 1.8 Ϯ 0.2 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ) and fell to 0.8 Ϯ 0.2 (CON) and 0.7 Ϯ 0.2 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 (RSR13). Arterial lactate was lower in RSR13-treated than in control animals when animals were O 2 supply dependent. The decrease in base excess, arterial pH, and bicarbonate during O2 supply dependence was significantly less after RSR13 than after saline. These findings demonstrate that during O 2 supply dependence caused by severe anemia, reducing Hb-O2 binding affinity does not affect V O2 SYS Right shifting the ODC, or increasing the O 2 tension at which Hb is 50% saturated (P 50 ), favors release of O 2 from hemoglobin at higher tissue PO 2 (4, 13). As a consequence, the O 2 gradient between RBCs and the mitochondria is increased, and more of the O 2 transported in the blood is available for consumption in the tissues. This increased O 2 gradient between RBCs and mitochondria should allow O 2 to diffuse over longer distances or offering more O 2 for local mitochondrial metabolism.Recent research has led to the discovery of new allosteric modifiers of the Hb-O 2 affinity (1). RSR13, a 2- [4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methyl-proprionic acid monosodium salt, reliably reduces the Hb-O 2 affinity in vivo. Because RSR13 binds to a site distinct from that of 2,3-diphosphoglycerate, the naturally occurring allosteric modifier of Hb, RSR13 generates an additive rightward shift of the ODC, which should facilitate added O 2 release (1). Superfusion of tissues with or infusion of RSR13 reduced hypoxia-induced vasodilation (44), increased tissue PO 2 (21), and reduced brain infarct size (43). During maximal exercise, low P 50 diminished maximal O 2 consumption (V O 2 max ) (14), whereas an increased P 50 by RSR13 enhanced maximal O 2 uptake (33). These findings suggest that modifications of the strength of the Hb-O 2 bond can effectively alter tissue O 2 availability.Under normal conditions, tissue O 2 availability and systemic V O 2 (V ...

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Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function

Cited by 31 publications

References 16 publications

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Increasing P₅₀does not improve Do_2critor systemicV˙o₂in severe anemia

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Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function

Cited by 31 publications

References 16 publications

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Increasing P50does not improve Do2critor systemicV˙o2in severe anemia

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Increasing P₅₀does not improve Do_2critor systemicV˙o₂in severe anemia