Erythrocyte extracts enhance neurogenic vasoconstriction of dog cerebral arteries in vitro.

Cerebral blood vessels of the dog have been shown to receive vasodilator and constrictor nerves. In isolated ring arterial preparations, neurogenic vasodilation was blocked while neurogenic vasoconstriction was potentiated by hemolysates isolated from hemolyzed erythrocytes. These results suggest that an overall increase in cerebral neurogenic vasoconstriction may occur in vivo following subarachnoid hemorrhage. The significance of this finding in the pathogenesis of cerebral vasospasm is discussed.

In vivo characterization of vasocontractile activities in erythrocytes.

Partially purified protein from washed and artificially hemolyzed erythrocytes, known to cause significant contractions of isolated canine cerebral vessels in vitro, was injected into the cisterna magna of intact anesthetized dogs. Cerebral blood flow, measured by the xenon-133 washout technique, decreased from a control value of 49.5 +/- 1.17 ml/100 gm/min to an experimental value of 34.1 +/- 1.65 ml/100 gm/min at 2 hours. Cerebral vascular resistance rose from a control value of 2.05 +/- 0.17 PRU (peripheral resistance units) to an experimental value of 2.91 +/- 0.25 PRU at 2 hours. Mean arterial blood pressure, heart rate, intracranial pressure, and cerebral perfusion pressure remained stable. Cardiac output also fell significantly (in 2-hour control animals it was 2.89 +/- 0.37 liter/min, and in 2-hour experimental animals 1.43 +/- 0.13 liter/min) and peripheral vascular resistance rose. These changes were evident by 10 minutes after the cisternal injection of the hemolysate protein, and remained for the duration of the 2-hour monitoring period. Serial vertebrobasilar angiograms demonstrated marked narrowing of the intracranial basilar artery when compared to control values. The narrowing persisted for several days in most animals, and tended to increase with time. Relaxation occurred by the 10th through the 14th day. The authors conclude that this experimental preparation may be a useful model for both in vitro and in vivo investigation of chronic cerebral vasospasm.

Preliminary characterization of vasocontractile activities in erythrocytes.

The vasocontractile activities of washed red cell preparations hemolyzed by various methods were studied in vitro using isolated canine basilar arteries. Significant contractions were induced by each preparation. The maximum strength of contraction attained by the various preparations was similar. The contractile activity appeared to be dose-related, and molecular exclusion chromatography demonstrated that the activity migrated with the fraction of approximately 40,000 to 45,000 molecular weight. The vasocontractile effect of the active fraction was sustained in vitro when tested against basilar artery, but was inactive in peripheral arterial preparations. Preliminary biochemical characterization indicates that the contractile activity resides in a protein. Enzymatic digestion of the crude fraction appears to enhance the contractile activity significantly, and this observation suggests a possible mechanism for the delayed onset of ischemic symptoms encountered in the clinical situation.