Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys
| Autor: | Nancy Winslow, Kim D. Vandegriff, Robert M. Winslow, Ashok Malavalli, Mark A. Young |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Mean arterial pressure medicine.medical_treatment Mean corpuscular hemoglobin Exchange transfusion Hemodynamics Blood Pressure Bone Marrow Cells Clinical Chemistry Tests Blood volume Body Temperature Polyethylene Glycols Maleimides Electrocardiography Hemoglobins Heart Rate Physiology (medical) Toxicity Tests medicine Animals Humans Aspartate Aminotransferases Infusions Intravenous Hematologic Tests L-Lactate Dehydrogenase medicine.diagnostic_test Mean corpuscular hemoglobin concentration business.industry Biochemistry (medical) Public Health Environmental and Occupational Health Alanine Transaminase Anemia General Medicine Macaca mulatta Anesthesia Toxicity Female Hemoglobin business Spleen Foam Cells |
| Zdroj: | Translational Research. 149:333-342 |
| ISSN: | 1931-5244 |
| DOI: | 10.1016/j.trsl.2006.09.007 |
| Popis: | Maleimide-polyethylene glycol-modified (MalPEG) hemoglobin, 4.3 g/dL (MP4; Hemospan), is a hemoglobin-based oxygen carrier consisting of human hemoglobin (Hb) modified with maleimide polyethylene glycol. This study evaluates the potential toxicity and hemodynamic actions of a single dose of MP4 administered by exchange transfusion to rhesus monkeys. Monkeys were administered MP4 (21 mL/kg, or approximately 30% of estimated blood volume) or an equivalent volume of lactated Ringer's solution (LR). In the toxicity study, blood samples were obtained predose and 3, 7, and 13 days after dosing for clinical chemistry and hematology. Animals were euthanized for complete necropsy and histopathology on day 3 or day 13. A separate group of animals was used for evaluation of arterial pressure, core temperature, and electrocardiogram, by telemetry, for 7 days after dosing with MP4. The results demonstrate no significant toxicity, with only modest, transient elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) on day 3. Mild anemia caused by hemodilution was observed at each time point in both groups, but to a slightly greater degree in the MP4-treated animals. Histologic observations included foamy or vacuolated macrophages in the spleen and marrow of the sternum, rib, and femur, representing the accumulation of test article or a metabolite. In the telemetry study, no changes occurred in arterial pressure, heart rate, or electrocardiogram attributable to administration of MP4 at any time for 7 days after administration. These results demonstrate that MP4 is safe and is without hemodynamic effects when administered as an exchange transfusion of 30% of estimated blood volume. |
| Databáze: | OpenAIRE |
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