Effect of maleimide-polyethylene glycol hemoglobin (MP4) on hemodynamics and acid-base status after uncontrolled hemorrhage in anesthetized swine: comparison with crystalloid and blood.
BACKGROUND
Maleimide-polyethylene glycol hemoglobin, 4.3 g/dL (MP4), is a hemoglobin-based oxygen carrier consisting of native human hemoglobin modified with maleimide polyethylene glycol. This study evaluated resuscitation with MP4 after uncontrolled hemorrhage in anesthetized swine, and compared the effects of MP4 alone with those of standard-of-care crystalloid or crystalloid + blood.


METHODS
Pigs were anesthetized with isoflurane and hemorrhaged 250 mL by controlled withdrawal, which was followed by a 5-mm tear in the abdominal aorta. Three groups of pigs (n = 7 each) were randomized after aortic tear to receive 500 mL of MP4, unlimited Ringer's acetate (RA), or 2 L of RA + 250 mL of autologous blood. Measurements included arterial and pulmonary artery pressures, central venous and pulmonary capillary wedge pressures, cardiac output, renal blood flow, urine output, arterial and venous blood gases, lactate concentration, and hemoglobin. Animals were monitored for 150 minutes after hemorrhage.


RESULTS
Average body weight (22-24 kg) and hemorrhage volume (28-34 mL/kg) were similar in the three groups. The nadir of mean arterial pressure (23-25 mm Hg) and base excess (-3 to -4 mEq/L) after hemorrhage were similar in all groups, indicating equivalent shock in the three groups. Two hours after administration of MP4, arterial pressure and base excess were significantly improved compared with those of animals administered RA or RA + blood, despite a significantly lower volume of infused fluids (MP4 = 36 +/- 2 mL/kg; RA = 224 +/- 28 mL/kg; RA + blood = 110 +/- 10 mL/kg), and a significantly lower total hemoglobin than achieved with RA + blood. Arterial pressure did not rise above baseline values, cardiac output was not diminished, and systemic vascular resistance was unchanged after administration of MP4, indicating the lack of cardiac effects or peripheral vasoconstriction.


CONCLUSIONS
These data demonstrate that resuscitation with a small volume of MP4 induces recovery from hemorrhage without vasoconstriction. Overall, the effects of MP4 alone on hemodynamic and acid-base indices appear to be of greater benefit than those observed with a large volume of RA alone or RA + blood.
Young
Mark A
MA
Sangart, Inc. San Diego, CA, USA. myoung@sangart.com
Riddez
Louis
L
Kjellström
B Thomas
BT
Winslow
Robert M
RM
D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000818:Animals; D001803:Blood Transfusion; D000077324:Crystalloid Solutions; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use*; D006470:Hemorrhage / Q000628:therapy*; D007552:Isotonic Solutions / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008301:Maleimides / Q000494:pharmacology / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012151:Resuscitation / Q000379:methods; D013552:Swine
D000077324:Crystalloid Solutions; D006454:Hemoglobins; D007552:Isotonic Solutions; D008301:Maleimides; C493836:maleimide-polyethylene glycol-modified hemoglobin, MP4; D011092:Polyethylene Glycols