Premium
Polymerized Hemoglobin Maintains Cardiac Function After Extreme Anemia
Author(s) -
Williams Alexander T.,
Muller Cynthia R.,
Eaker Allyn M.,
Bolden-Rush Crystal,
Palmer Andre F.,
Cabrales Pedro
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06291
Subject(s) - hemoglobin , anemia , cardiac function curve , economic shortage , blood volume , blood substitute , chemistry , oxygenation , medicine , hematocrit , heart failure , linguistics , philosophy , government (linguistics)
Background Blood transfusion as a treatment for anemia is vital in ensuring oxygen (O 2 ) carrying capacity. However, fears of blood shortages and adverse reactions to stored blood transfusion have driven the development of oxygen carrying alternatives to blood. One class of alternatives to blood for transfusion medicine are hemoglobin (Hb) based oxygen carriers (HBOCs), which have been in development for decades. A recent advancement in the development of HBOCs is the discovery that their O 2 affinity can be tightly regulated by locking Hb in the T state (low O 2 affinity), or R state (high O 2 affinity). By regulating O 2 affinity, O 2 extraction by tissues can be controlled, and targeted O 2 delivery to hypoxic tissues is made possible. As the heart is one of the most sensitive organs to changes in oxygenation due to its high metabolic rate, the objective of this study was to test the efficacy of high and low O 2 affinity HBOCs in maintaining cardiac function and systemic O 2 delivery during severe anemia. Methods Polymerized hemoglobin (PolyHb), the most scalable method of producing HBOCs, was synthesized in the high and low O 2 affinity state (R and T, respectively) with glutaraldehyde and then subjected to 8–9 cycles of diafiltration as previously described. This resulted in a PolyHb solution containing only polymerized Hb molecules > 500kDa suspended in Lactated Ringers solution. Rats were instrumented with a pressure‐volume catheter to monitor cardiac function. Severe anemia was induced via a 50% isovolumic hemodilution with 5% human serum albumin. Rats were then resuscitated by a 40% isovolumic infusion of a 10 g/dL solution of R PolyHb, T PolyHb, or fresh blood (drawn from the animal during the first exchange). Results Severe anemia resulted in impaired cardiac function and O 2 delivery. Transfusion of fresh blood, T PolyHb, and R PolyHb restored vascular resistance, blood pressure, and cardiac contractility. T PolyHb also promoted increased O 2 extraction and myocardial energy utilization. Severe anemia did not cause significant changes in blood electrolytes relative to baseline. Severe anemia resulted in blood acidification that only recovered for animals resuscitated with T PolyHb. Furthermore, resuscitation with T PolyHb resulted in higher arterial pO 2 and lower pCO 2 than other groups. R PolyHb increased lactate and glucose, suggesting that the high O 2 affinity prevented proper O 2 release to some tissues, despite maintaining cardiac function. Conclusions Both T and R PolyHb maintain myocardial O 2 extraction compared to fresh blood. T PolyHb appears to be the optimal molecule for increasing O 2 delivery during anemic conditions. Although R PolyHb apparently decreased systemic O 2 extraction during anemia, it can be potentially useful to increase O 2 uptake in the lungs during hypoxic‐hypoxia. This study indicates that PolyHb is as efficacious as fresh blood in restoring cardiac function and oxygenation in rats during severe anemia. Support or Funding Information This work was supported by the NIH Heart Lung and Blood Institute under Grants T32‐HL105373, R01‐HL126945, and R01‐HL138116.