The Physiological and Histopathological Response of Dogs to Exchange Transfusion with Polyethylene Glycol-Modified Bovine Hemoglobin (PEG-Hb)

Abstract

The performance of polyethylene glycol-modified bovine hemoglobin (PEG-Hb) was evaluated in dogs following the replacement of 30% or 50% of their blood volume with PEG-Hb or lactated Ringer's solution (LRS). Dogs fully instrumented with catheters and blood pressure probes were transfused by simultaneous bleeding from the jugular vein and infusion of PEG-Hb or LRS via the cephalic vein. Animals were monitored for abnormal behavior and clinical signs for fourteen days. No mortalities, overt toxicity, changes in body weight, food consumption or ophthalmology, or discernable trends in hematology, blood chemistry coagulation, urinalysis or hemodynamic parameters that could be attributed to PEG-Hb were noted. Blood gas analyses were steady and within physiological ranges. Dose-related histopathological findings of vacuolated histiocytes in the femoral bone marrow, splenic parenchyma, the medulla of the mesenteric and mandibular lymph nodes, and vacuolated sinusoidal cells in the liver and the renal tubular epithelial cells were believed to be related to the phagocytosis and degradation of PEG-Hb by the reticulo-endothelial system. The maintenance of high oxygen levels in the circulation for the two-week treatment period, as well as the insignificant physiological and histopathological findings indicate that PEG-Hb could be a successful blood substitute.

The safety profile of Hemospan®: a new oxygen therapeutic designed using maleimide poly(ethylene) glycol conjugation to human hemoglobin

“…In rats, Hemospan showed only minor, transient effects on hepatic enzymes and no effect on lipase or amylase 64 . Vacuolated spleen and bone marrow cells that were observed are believed to be a normal response in the clearance of PEGylated hemoglobin 65,66 …”

Highly Loaded Hemoglobin Spheres as Promising Artificial Oxygen Carriers

“…1,5À9 The first generation is the glutaraldehyde (GA) crosslinked polyhemoglobin that has been tested clinically in patients. 10,11 The second generation are the conjugates of Hb with polymers (such as dextran, 12 polyethylene glycol, 13 or polyoxyethylene 14 ), intramolecularly cross-linked Hb and recombinant Hb. The PolyHb and conjugated Hb are useful at clinical conditions where only oxygen carriers are requested.…”

“…However, cell-free Hb is too toxic to serve as a blood substitute. , Therefore, it is challenging to modify cell-free hemoglobin purposefully. Several types of Hb modification approaches were developed in the last few decades. ,− The first generation is the glutaraldehyde (GA) cross-linked polyhemoglobin that has been tested clinically in patients. , The second generation are the conjugates of Hb with polymers (such as dextran, polyethylene glycol, or polyoxyethylene), intramolecularly cross-linked Hb and recombinant Hb. The PolyHb and conjugated Hb are useful at clinical conditions where only oxygen carriers are requested.…”