Tissue oxidative metabolism after extreme hemodilution with peg-conjugated hemoglobin

Pedro Cabrales, Fantao Meng, Seetharama A. Acharya

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

NADH-localized fluorometry was used as a noninvasive technique to monitor changes in the energy state of intact tissue (muscle and connective tissue), without anesthesia, as a function of blood plasma O2-carrying capacity in the hamster window chamber model. Acute moderate isovolemic hemodilution was induced by two isovolemic hemodilution steps: in the first step, 6% 70-kDa dextran (Dex70) was used to induce an acute anemic state (18% Hct); in the second step, exchange transfusion of polyethylene glycol (PEG) maleimide-conjugated Hb (4 g/dl, PEG-Hb) or Dex70 (6 g/dl) was used to reduce erythrocytes to 75% of baseline (11% Hct). PEG-Hb had six copies of PEG (5 kDa) conjugated to each human Hb (0.48 g PEG/g Hb) through extension arm-facilitated chemistry. Systemic parameters, microvascular perfusion, functional capillary density, intravascular and interstitial Po2, and intracellular NADH fluorescence were monitored. Mean arterial blood pressure after extreme hemodilution was statistically significantly reduced for Dex70 compared with PEG-Hb. The presence of PEG-Hb in the circulation maintained positive acid-base balance. While microvascular blood flows were not different, functional capillary density was significantly higher for PEG-Hb than Dex70. Arteriolar Po2 was higher in the presence of PEG-Hb than Dex70, but tissue and venular Po2 were not different. Cellular energy metabolism (intracellular O2) in the tissues was improved with PEG-Hb. Moderate hemodilution to 18% Hct (6.4 g Hb/dl) brings tissue O2 delivery to the verge of inadequacy. Extreme hemodilution to 11% Hct (3.7 g Hb/dl) produces tissue anoxia, and high-O2-affinity PEG-Hb (Po2 at which blood is 50% saturated with O2 = 4 Torr, 1.1 g Hb/dl) only partially decreases anaerobic metabolism without increasing tissue Po2.

Original languageEnglish (US)
Pages (from-to)1852-1859
Number of pages8
JournalJournal of Applied Physiology
Volume109
Issue number6
DOIs
StatePublished - Dec 2010

Fingerprint

Hemodilution
Hemoglobins
NAD
Arterial Pressure
Anaerobiosis
Fluorometry
Acid-Base Equilibrium
Conservation of Natural Resources
Dextrans
Cricetinae
Connective Tissue
Energy Metabolism
Anesthesia
Perfusion
Erythrocytes
Fluorescence

Keywords

  • Critical oxygen supply
  • Functional capillary density
  • Microcirculation
  • NADH fluorescence
  • Oxygen release
  • Polyethylene glycol maleimide-conjugated hemoglobin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Tissue oxidative metabolism after extreme hemodilution with peg-conjugated hemoglobin. / Cabrales, Pedro; Meng, Fantao; Acharya, Seetharama A.

In: Journal of Applied Physiology, Vol. 109, No. 6, 12.2010, p. 1852-1859.

Research output: Contribution to journalArticle

Cabrales, Pedro ; Meng, Fantao ; Acharya, Seetharama A. / Tissue oxidative metabolism after extreme hemodilution with peg-conjugated hemoglobin. In: Journal of Applied Physiology. 2010 ; Vol. 109, No. 6. pp. 1852-1859.
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abstract = "NADH-localized fluorometry was used as a noninvasive technique to monitor changes in the energy state of intact tissue (muscle and connective tissue), without anesthesia, as a function of blood plasma O2-carrying capacity in the hamster window chamber model. Acute moderate isovolemic hemodilution was induced by two isovolemic hemodilution steps: in the first step, 6{\%} 70-kDa dextran (Dex70) was used to induce an acute anemic state (18{\%} Hct); in the second step, exchange transfusion of polyethylene glycol (PEG) maleimide-conjugated Hb (4 g/dl, PEG-Hb) or Dex70 (6 g/dl) was used to reduce erythrocytes to 75{\%} of baseline (11{\%} Hct). PEG-Hb had six copies of PEG (5 kDa) conjugated to each human Hb (0.48 g PEG/g Hb) through extension arm-facilitated chemistry. Systemic parameters, microvascular perfusion, functional capillary density, intravascular and interstitial Po2, and intracellular NADH fluorescence were monitored. Mean arterial blood pressure after extreme hemodilution was statistically significantly reduced for Dex70 compared with PEG-Hb. The presence of PEG-Hb in the circulation maintained positive acid-base balance. While microvascular blood flows were not different, functional capillary density was significantly higher for PEG-Hb than Dex70. Arteriolar Po2 was higher in the presence of PEG-Hb than Dex70, but tissue and venular Po2 were not different. Cellular energy metabolism (intracellular O2) in the tissues was improved with PEG-Hb. Moderate hemodilution to 18{\%} Hct (6.4 g Hb/dl) brings tissue O2 delivery to the verge of inadequacy. Extreme hemodilution to 11{\%} Hct (3.7 g Hb/dl) produces tissue anoxia, and high-O2-affinity PEG-Hb (Po2 at which blood is 50{\%} saturated with O2 = 4 Torr, 1.1 g Hb/dl) only partially decreases anaerobic metabolism without increasing tissue Po2.",
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