Ischemia Triggered by Red Blood Cell Products in the Subarachnoid Space Is Inhibited by Nimodipine Administration or Moderate Volume Expansion/Hemodilution in Rats

Abstract

It has been proposed that delayed ischemic neurological deficits are induced by red blood cell (RBC) products after subarachnoid hemorrhage. Prophylactic treatment with the Ca2+ antagonist nimodipine or prevention of systemic volume contraction reduces the occurrence of delayed ischemic neurological deficits. To gain insight into the underlying mechanism, we studied the effects of nimodipine or volume expansion on ischemic events induced by RBC products in rats. A cranial window was implanted in 52 rats. At the window, cerebral blood flow (measured with laser Doppler flowmetry) and the subarachnoid direct current potential were recorded; the cortical surface was superfused with artificial cerebrospinal fluid. A spreading neuronal/astroglial depolarization wave was triggered at a remote site, from which it traveled to the cranial window. In 16 rats, the depolarization wave triggered an ischemic event at the cranial window when artificial cerebrospinal fluid containing the RBC product hemoglobin and elevated K+ levels was superfused. In contrast, in animals receiving intravenously administered nimodipine (n = 12) or moderate volume expansion/hemodilution with hydroxyethyl starch (6% hydroxyethyl starch 200/0.5) (n = 10), the depolarization wave triggered brief initial hypoperfusion, followed by brief hyperemia, in the cortical area exposed to the RBC products. Under physiological conditions, the depolarization wave triggered brief hyperemia (n = 14). Spreading ischemia induced by RBC products is antagonized by measures known to be beneficial in the prophylaxis of delayed ischemic neurological deficits. Our findings suggest that a mechanism involving the cortical microcirculation might underlie the therapeutic effects of nimodipine and volume expansion.