Diaspirin crosslinked hemoglobin enables extreme hemodilution beyond the critical hematocrit

Background: Normovolemic hemodilution is an effective strategy to limit per ioperative homologous blood transfusions. The reduction of hematocrit relat ed to hemodilution results in reduced arterial oxygen content, which initia lly is compensated for by an increase in cardiac output and oxygen extracti on ratio. To increase the efficacy of hemodilution, a low hematocrit should be aimed for; however, this implies the risk of myocardial ischemia and ti ssue hypoxia. Objective: To assess whether hemodilution can be extended to lower hematocr it values by the use of a hemoglobin-based artificial oxygen carrier soluti on. Design: Prospective, randomized, controlled. Setting: Animal laboratory of a university hospital. Subjects: Twelve anesthetized, mechanically ventilated pigs. Interventions: Isovolemic hemodilution was performed with either 10% diaspi rin crosslinked hemoglobin (DCLHb Baxter Healthcare, Boulder, GO; n = 6) or 8% human albumin solution (HSA, oncotically matched to DCLHb, Baxter Healt hcare; n = 6) to a hematocrit of 15%, 8%, 4%, 2%, and 1%. Measurements and Main Results: In both groups, measurements were performed at baseline at the previously mentioned preset hematocrit values and at the onset of myocardial ischemia characterized by critical hematocrit (signifi cant ST-segment depression >0.1 mV and/or arrhythmia). To determine periphe ral tissue oxygenation and myocardial perfusion and function, the following variables were evaluated: total body oxygen transport variables, tissue ox ygen partial pressure (tPo(2), MDO-Electrode, Eschweiler Kiel, Germany) on the surface of the skeletal muscle, coronary perfusion pressure, left ventr icular (LV) end-diastolic pressure, global and regional myocardial contract ility (maximal change in pressure over time, LV segmental shortening, micro sonometry method), LV myocardial blood flow (fluorescent microsphere techni que), LY oxygen delivery, and the ratio between LY subendocardial and subep icardial myocardial perfusion. In the HSA group, critical hematocrit was fo und at 6.1 (1.8)% (hemoglobin, 2 g.dL(-1)), whereas all DCLHb-treated anima ls survived hemodilution until hematocrit 1.2 (0.2)% (hemoglobin, 4.7 g.dL( -1)) was achieved without signs of hemodynamic instability. Although arteri al oxygen content was higher in the DCLHb group at 1.2% hematocrit than in the HSA group at critical hematocrit (i.e., hematocrit, 6.1%; hemoglobin, 2 g.dL(-1)) neither oxygen delivery and oxygen uptake nor median tPo(2) and hypoxic tPo(2) values on the skeletal muscle were different between groups. In contrast, subendocardial ischemia was absent in DCLHb-diluted animals u ntil 1.2% hematocrit was achieved. This was attributable to a higher corona ry perfusion pressure (65 (22) mm Hg vs. 19(8)mm Hg; p < .05), higher suben docardial perfusion (4.1 (2.6) mL.min(-1).g(-1) vs. 1.2 (0.4) mL.min(-1).g( -1)), and subendocardial oxygen delivery (5.7 (2) mL.min(-1).g(-1), p < .05 ) in DCLHb-diluted animals, resulting in superior myocardial contractility reflected by maximal change in pressure over time (3829 (1914) vs. 1678 (73 0); p < .05) and higher regional myocardial contractility (11 (8)% vs. 6 (2 )%; p < .05). An increased LV end-diastolic pressure reflected LV myocardia l pump failure in HSA-diluted animals but was unchanged in DCLHb-diluted an imals. in the DCLHb group, systemic vascular resistance index remained at b aseline values throughout the protocol, whereas coronary vascular resistanc e decreased. In contrast, both variables decreased in HSA-diluted animals. Conclusion:DCLHb as a diluent allowed for hemodilution beyond the hematocri t value, determined "critical" after hemodilution with HSA (6.1% (1.8)%). E ven at 1.2% hematocrit (hemoglobin, 4.7 g.dL(-1)) myocardial perfusion and function were maintained, although at the expense of peripheral tissue oxyg enation. This discrepancy in regional oxygenation might be caused by a redi stribution of blood flow favoring the heart, which is related to a dispropo rtionate decrease of coronary vascular resistance index during hemodilution with DCLHb.