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Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs.

Muir WW, Del Rio CL, Ueyama Y, Youngblood BL, George RS, Rausch CW, Lau BS, Hamlin RL - Crit Care Res Pract (2014)

Bottom Line: The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of 0.63 ± 0.01 and 1.11 ± 0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99.The administration of 0.65 g/kg OC99 significantly elevated pulmonary artery pressure.Plasma hemoglobin concentrations of OC99 ranging from 0.3 to 1.1 g/dL, in conjunction with colloid based fluid resuscitation, normalized clinical surrogates of tissue oxygen debt, improved tPO2, and avoided clinically relevant increases in pulmonary artery pressure.

View Article: PubMed Central - PubMed

Affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.

ABSTRACT
We determined the dose-dependent effects of OC99, a novel, stabilized hemoglobin-based oxygen-carrier, on hemodynamics, systemic and pulmonary artery pressures, surrogates of tissue oxygen debt (arterial lactate 7.2 ± 0.1 mM/L and arterial base excess -17.9 ± 0.5 mM/L), and tissue oxygen tension (tPO2) in a dog model of controlled severe oxygen-debt from hemorrhagic shock. The dose/rate for OC99 was established from a pilot study conducted in six bled dogs. Subsequently twenty-four dogs were randomly assigned to one of four groups (n = 6 per group) and administered: 0.0, 0.065, 0.325, or 0.65 g/kg of OC99 combined with 10 mL/kg lactated Ringers solution administered in conjunction with 20 mL/kg Hextend IV over 60 minutes. The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of 0.63 ± 0.01 and 1.11 ± 0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99. The administration of 0.65 g/kg OC99 significantly elevated pulmonary artery pressure. Plasma hemoglobin concentrations of OC99 ranging from 0.3 to 1.1 g/dL, in conjunction with colloid based fluid resuscitation, normalized clinical surrogates of tissue oxygen debt, improved tPO2, and avoided clinically relevant increases in pulmonary artery pressure.

No MeSH data available.


Related in: MedlinePlus

(a) OC99 plasma hemoglobin (Hbp) concentration versus tissue oxygen tension (tPO2). (b) OC99 Hbp concentration versus mean pulmonary artery (PAP) pressure. (c) Change in PAP when 0.65 g/kg OC99 is administered at 30 ml/kg/hr or 10 ml/kg/hr; each symbol represents a different dog. Solid circles: Hextend without OC99; open circles: repeat doses of Hextend with increasing concentrations of OC99 administered over 10 minutes. Solid triangle: Hextend with OC99 administered over 30 minutes.
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fig1: (a) OC99 plasma hemoglobin (Hbp) concentration versus tissue oxygen tension (tPO2). (b) OC99 Hbp concentration versus mean pulmonary artery (PAP) pressure. (c) Change in PAP when 0.65 g/kg OC99 is administered at 30 ml/kg/hr or 10 ml/kg/hr; each symbol represents a different dog. Solid circles: Hextend without OC99; open circles: repeat doses of Hextend with increasing concentrations of OC99 administered over 10 minutes. Solid triangle: Hextend with OC99 administered over 30 minutes.

Mentions: Infusion of OC99 produced dose and rate of administration dependent increases in Hbp. The Hbp concentrations after the first and second infusions for the three doses of OC99 (0.325, 0.1, and 0.05 g/kg) administered over 10 minutes were 0.84, 0.34, and 0.20 g/dL and 1.26, 0.48, and 0.27 g/dL, respectively. The infusion of OC99 produced Hbp concentration dependent increases in tPO2 in the intestinal mucosa. The greatest increases in tPO2 occurred at a Hbp concentration averaging 0.84 ± 0.13 g/dL. The administration of HEX infusions containing OC99 produced Hbp concentrations below 0.3 g/dL resulting in little or no change in PAP or tPO2 (tPO2 < 10 mm Hg; Figure 1). Infusion of HEX (0.0 g/kg) and the first dose (0.05 g/kg) of OC99 failed to attain this plasma concentration. The administration of repeat doses of OC99 resulting in Hbp values greater than 0.3 g/dL increased pulmonary artery pressure; Hbp concentration was an independent predictor of the mean pulmonary artery pressure (Figure 1). Pulmonary artery pressures exceeded 25 mm Hg when repeat dosages of 0.325 g/kg OC99 were administered over 10 minutes. We considered, a priori, a mean pulmonary artery pressure >25 mm Hg to be hypertensive [16]. The slower infusion of OC99 (0.325 g/kg over 30 min) prevented the increase in PAP. Based upon these results we hypothesized that the slow administration of OC99 to hemorrhaged dogs would increase tPO2 without producing pulmonary hypertension (i.e., mean PAP > 25 mm Hg) and when Hbp concentration was less than 1.1 g/dL. Subsequent dose response experiments were designed to encompass OC99 Hbp concentrations (0.3–1.1 gm/dL) that improved tPO2 without producing pulmonary hypertension.


Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs.

Muir WW, Del Rio CL, Ueyama Y, Youngblood BL, George RS, Rausch CW, Lau BS, Hamlin RL - Crit Care Res Pract (2014)

(a) OC99 plasma hemoglobin (Hbp) concentration versus tissue oxygen tension (tPO2). (b) OC99 Hbp concentration versus mean pulmonary artery (PAP) pressure. (c) Change in PAP when 0.65 g/kg OC99 is administered at 30 ml/kg/hr or 10 ml/kg/hr; each symbol represents a different dog. Solid circles: Hextend without OC99; open circles: repeat doses of Hextend with increasing concentrations of OC99 administered over 10 minutes. Solid triangle: Hextend with OC99 administered over 30 minutes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227330&req=5

fig1: (a) OC99 plasma hemoglobin (Hbp) concentration versus tissue oxygen tension (tPO2). (b) OC99 Hbp concentration versus mean pulmonary artery (PAP) pressure. (c) Change in PAP when 0.65 g/kg OC99 is administered at 30 ml/kg/hr or 10 ml/kg/hr; each symbol represents a different dog. Solid circles: Hextend without OC99; open circles: repeat doses of Hextend with increasing concentrations of OC99 administered over 10 minutes. Solid triangle: Hextend with OC99 administered over 30 minutes.
Mentions: Infusion of OC99 produced dose and rate of administration dependent increases in Hbp. The Hbp concentrations after the first and second infusions for the three doses of OC99 (0.325, 0.1, and 0.05 g/kg) administered over 10 minutes were 0.84, 0.34, and 0.20 g/dL and 1.26, 0.48, and 0.27 g/dL, respectively. The infusion of OC99 produced Hbp concentration dependent increases in tPO2 in the intestinal mucosa. The greatest increases in tPO2 occurred at a Hbp concentration averaging 0.84 ± 0.13 g/dL. The administration of HEX infusions containing OC99 produced Hbp concentrations below 0.3 g/dL resulting in little or no change in PAP or tPO2 (tPO2 < 10 mm Hg; Figure 1). Infusion of HEX (0.0 g/kg) and the first dose (0.05 g/kg) of OC99 failed to attain this plasma concentration. The administration of repeat doses of OC99 resulting in Hbp values greater than 0.3 g/dL increased pulmonary artery pressure; Hbp concentration was an independent predictor of the mean pulmonary artery pressure (Figure 1). Pulmonary artery pressures exceeded 25 mm Hg when repeat dosages of 0.325 g/kg OC99 were administered over 10 minutes. We considered, a priori, a mean pulmonary artery pressure >25 mm Hg to be hypertensive [16]. The slower infusion of OC99 (0.325 g/kg over 30 min) prevented the increase in PAP. Based upon these results we hypothesized that the slow administration of OC99 to hemorrhaged dogs would increase tPO2 without producing pulmonary hypertension (i.e., mean PAP > 25 mm Hg) and when Hbp concentration was less than 1.1 g/dL. Subsequent dose response experiments were designed to encompass OC99 Hbp concentrations (0.3–1.1 gm/dL) that improved tPO2 without producing pulmonary hypertension.

Bottom Line: The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of 0.63 ± 0.01 and 1.11 ± 0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99.The administration of 0.65 g/kg OC99 significantly elevated pulmonary artery pressure.Plasma hemoglobin concentrations of OC99 ranging from 0.3 to 1.1 g/dL, in conjunction with colloid based fluid resuscitation, normalized clinical surrogates of tissue oxygen debt, improved tPO2, and avoided clinically relevant increases in pulmonary artery pressure.

View Article: PubMed Central - PubMed

Affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.

ABSTRACT
We determined the dose-dependent effects of OC99, a novel, stabilized hemoglobin-based oxygen-carrier, on hemodynamics, systemic and pulmonary artery pressures, surrogates of tissue oxygen debt (arterial lactate 7.2 ± 0.1 mM/L and arterial base excess -17.9 ± 0.5 mM/L), and tissue oxygen tension (tPO2) in a dog model of controlled severe oxygen-debt from hemorrhagic shock. The dose/rate for OC99 was established from a pilot study conducted in six bled dogs. Subsequently twenty-four dogs were randomly assigned to one of four groups (n = 6 per group) and administered: 0.0, 0.065, 0.325, or 0.65 g/kg of OC99 combined with 10 mL/kg lactated Ringers solution administered in conjunction with 20 mL/kg Hextend IV over 60 minutes. The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of 0.63 ± 0.01 and 1.11 ± 0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99. The administration of 0.65 g/kg OC99 significantly elevated pulmonary artery pressure. Plasma hemoglobin concentrations of OC99 ranging from 0.3 to 1.1 g/dL, in conjunction with colloid based fluid resuscitation, normalized clinical surrogates of tissue oxygen debt, improved tPO2, and avoided clinically relevant increases in pulmonary artery pressure.

No MeSH data available.


Related in: MedlinePlus