Decreased Affinity of Blood for Oxygen in Patients with Low-Output Heart Failure

Metcalfe, James; Dhindsa, Dharam S.; Edwards, Miles J.; Mourdjinis, Athanasios

doi:10.1161/01.res.25.1.47

Cited by 66 publications

(11 citation statements)

References 21 publications

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“…Increased hemoglobin p50 is reported in patients during angina (7), after acute myocardial infarction (8)(9)(10), with congestive heart failure and cardiogenic shock (12,13,25), as well as in patients with congenital heart disease (26). Higher 2,3-diphosphoglycerate (DPG) levels contribute to the increased p50 in these clinical settings (11) and is typically on the order of ∼2-3 mmHg.…”

Section: Discussionmentioning

confidence: 99%

“…There are several naturally occurring modifiers of hemoglobin affinity, including 2,3-diphosphoglycerate (DPG), CO 2 , and H + . A rightward shift in the Hb-O 2 dissociation curve is observed in patients with angina, congestive heart failure with shock, and acute myocardial infarction, and is believed to be an adaptive response that increases myocardial oxygen delivery (7)(8)(9)(10)(11)(12)(13). Clofibrate and some other synthetic compounds also modestly alter the affinity of hemogloPreservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity bin for oxygen (14)(15)(16)(17)(18) (19,20).…”

Section: Introductionmentioning

confidence: 99%

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Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin–oxygen affinity

Weiss¹,

Mejia²,

Kass³

et al. 1999

J. Clin. Invest.

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Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2- [4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31 P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin–oxygen affinity

Weiss¹,

Mejia²,

Kass³

et al. 1999

J. Clin. Invest.

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“…But even if oxygen delivery decreases, oxygen uptake may be maintained by the fol lowing mechanisms: ( 1 ) the oxygen extraction ratio is accelerated in peripheral tissues [4]; (2) the distribution of regional blood flow is shifted to vital organs that have large oxygen demand [6.7]; (3) the oxygen-hemoglobin dis sociation curve shifts to the right and acceler ates the oxygen release from erythrocytes [8,9]. Under these conditions, the oxygen uptake is independent of the oxygen supply.…”

Section: Discussionmentioning

confidence: 99%

Oxygen Demand-Supply Relationship in Peripheral Tissues as a Therapeutic Indicator in Acute Myocardial Infarction with Advanced Heart Failure

Inoue¹,

Morooka²,

Sakai³

et al. 1993

Cardiology

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Oxygen demand-supply relationships in peripheral tissues were studied in 14 patients who had acute myocardial infarction with advanced pump failure. Seven patients with acute myocardial infarction but without pump failure were studied as a control. In all patients, a Swan-Ganz catheter and a radial arterial cannula were inserted for the purpose of hemodynamic monitoring, and arterial and mixed venous blood were sampled. Initially, oxygen delivery (DO₂) (p < 0.01) was lower, and oxygen extraction ratio (OER) (p < 0.001) and oxygen tension at 50% saturation (P₅₀) (p < 0.01) were higher in patients with pump failure than in the controls. During the therapeutic course, with an increase in the cardiac index and DO₂, oxygen uptake (VO₂) did not change but OER (p < 0.001) and P₅₀ (p < 0.01) significantly decreased in 6 survivors with pump failure. In contrast, an increased VO₂ (p < 0.01) and no change of OER and P₅₀ were observed in 8 non-survivors with pump failure. These results suggest that reversibility of oxygenokinetics might be an important factor for recovery from critical heart failure.

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“…Few studies have been made of red cell adaptive changes during low blood flow states. W~oodson, Torrance, Shappell, and Lenfant (7) and Metcalfe, Dhindsa, Edwards, and Mourdjinis (8), studying patients with chronic cardiac decompensation, have shown that reduced cardiac output is associated with elevated red cell 2,3-DPG (7) and decreased hemoglobin-oxygen affinity (7,8). Kostuk, Suwa, Bernstein, and Sobel observed decreased affinity after acute myocardial infarction (9).…”

Section: Introductionmentioning

confidence: 99%

The Relationships between Arterial Oxygen Flow Rate, Oxygen Binding by Hemoglobin, and Oxygen Utilization after Myocardial Infarction

Lichtman¹,

Cohen²,

Young³

et al. 1974

J. Clin. Invest.

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A B S T R A C T The interrelationships of arterial oxygen flow rate index, oxygen binding by hemoglobin, and oxygen consumption have been examined in patients with acute myocardial infarction. Proportional extraction of oxygen increased in close association with decreasing oxygen flow rate, and hence, whole body oxygen consumption was constant over nearly a threefold variation in arterial oxygen flow rate. A reduction in hemoglobin-oxygen affinity at in vivo conditions of pH, PCo2 and temperature also occurred in proportion to the reduction in arterial oxygen flow rate. Therefore, the increased proportional removal of oxygen from arterial blood at low oxygen flow rates, required to maintain oxygen consumption, may have been facilitated by the reduced affinity of hemoglobin for oxygen at in vivo conditions. However, the decrease in affinity did not appear to explain more than 30-40%0 of the increased extraction.Respiratory alkalosis was a frequent occurrence in these patients and 2,3-diphosphoglycerate was positively associated with blood pH as well as with the time-averaged proportion of deoxyhemoglobin in arterial and venous blood.Hemoglobin-oxygen affinity measured at standard conditions and the mixed venous oxygen saturation were equally good indicators of reduced arterial oxygen flow rate in patients without shock. However, Svro2 is more easily measured and is a more useful indicator of reduced oxygen flow rate, since its relationship to oxygen flow appears to be independent of affinity changes and time.

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Decreased Affinity of Blood for Oxygen in Patients with Low-Output Heart Failure

Cited by 66 publications

References 21 publications

Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin–oxygen affinity

Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin–oxygen affinity

Oxygen Demand-Supply Relationship in Peripheral Tissues as a Therapeutic Indicator in Acute Myocardial Infarction with Advanced Heart Failure

The Relationships between Arterial Oxygen Flow Rate, Oxygen Binding by Hemoglobin, and Oxygen Utilization after Myocardial Infarction

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