Cerebrovascular response to decreased hematocrit: effect of cell-free hemoglobin, plasma viscosity, and CO₂

Abstract

The effect of transfusing a nonextravasating, zero-link polymer of cell-free hemoglobin on pial arteriolar diameter, cerebral blood flow (CBF), and O2 transport (CBF x arterial O2 content) was compared with that of transfusing an albumin solution at equivalent reductions in hematocrit (approximately 19%) in anesthetized cats. The influence of viscosity was assessed by coinfusion of a high-viscosity solution of polyvinylpyrrolidone (PVP), which increased plasma viscosity two- to threefold. Exchange transfusion of a 5% albumin solution resulted in pial arteriolar dilation, increased CBF, and unchanged O2 transport, whereas there were no significant changes over time in a control group. Exchange transfusion of a 12% polymeric hemoglobin solution resulted in pial arteriolar constriction and unchanged CBF and O2 transport. Coinfusion of PVP with albumin produced pial arteriolar dilation that was similar to that obtained with transfusion of albumin alone. In contrast, coinfusion of PVP with hemoglobin converted the constrictor response to a dilator response that prevented a decrease in CBF. Pial arteriolar dilation to hypercapnia was unimpaired in groups transfused with albumin or hemoglobin alone but was attenuated in the largest vessels in albumin and hemoglobin groups coinfused with PVP. Unexpectedly, hypocapnic vasoconstriction was blunted in all groups after transfusion of albumin or hemoglobin alone or with PVP. We conclude that 1) the increase in arteriolar diameter after albumin transfusion represents a compensatory response that prevents decreased O2 transport at reduced O2-carrying capacity, 2) the decrease in diameter associated with near-normal O2-carrying capacity after cell-free polymeric hemoglobin transfusion represents a compensatory mechanism that prevents increased O2 transport at reduced blood viscosity, 3) pial arterioles are capable of dilating to an increase in plasma viscosity when hemoglobin is present in the plasma, 4) decreasing hematocrit does not impair pial arteriolar dilation to hypercapnia unless plasma viscosity is increased, and 5) pial arteriolar constriction to hypocapnia is impaired at reduced hematocrit independently of O2-carrying capacity.

Insensitivity of cerebral oxygen transport to oxygen affinity of hemoglobin-based oxygen carriers

“…Pial arteriolar diameter was measured by intravital microscopy through closed cranial windows in anesthetized cats and rats [14]. Focal cerebral ischemia was produced in mice by occlusion of the middle cerebral artery, as described [8].…”

“…In subsequent sets of experiments [14,15], CBF was measured in anesthetized cats after isovolemic exchange transfusion of 7% sebacyl crosslinked tetrameric Hb (P 50 =34 Torr, n=2.1) and 12% polymeric Hb-Zerolink (P 50 =4 Torr). As mentioned, Hb-Zerolink is a large polymer (average MW∼25 MDa) that does not extravasate into renal lymph and does not produce arterial hypertension [1].…”

“…5C). When coinfusion with polyvinylpyrrolidone (PVP) was used to increase plasma viscosity, the vasodilation produced by albumin solutions was only marginally increased [14], whereas the constriction seen with Hb-Zerolink was reversed and the pial arterioles markedly dilated (Fig. 5C).…”

“…Values are means±SE. Adapted from [14,15]. Cerebral metabolic rate of oxygen (CMRO 2 ) (A) and cerebral fractional oxygen extraction (B) in 6 fetal lambs undergoing an exchange transfusion with adult sheep blood to increase the P 50 of red blood cell (RBC) hemoglobin (Hb) from 17 to 32 Torr (adapted from [17]), in 9 newborn lambs who underwent an exchange transfusion with adult sheep blood to increase the P 50 of RBC Hb from 26 to 37 Torr (adapted from [16]), in 8 cats after exchange transfusion with a 7% solution of fumaryl crosslinked tetrameric hemoglobin with a P 50 of 18 Torr (adapted from [11]), and in 12 cats after exchange transfusion with a 7% solution of sebacyl crosslinked tetrameric hemoglobin (adapted from [15]) with a P 50 of 34 Torr, which is close to cat blood (P 50 of 37 Torr).…”

“…(C) Exchange transfusion with albumin solution (N = 10) produced dilation, and exchange transfusion with Hb-Zerolink polymer (HbZL; N = 9) with a P 50 of 4 Torr produced constriction comparable to that of the low-affinity HbSebacyl (P 50 of 34 Torr). Increasing plasma viscosity by cotransfusion of polyvinylpyrrolidone (PVP) with HbZL (N = 6) converted the constrictor response to a dilator response in cats (adapted from [14]). (D) Exchange transfusion with albumin (N = 6) and HbZL (N = 6) in rats produced responses similar to those in cats.…”