Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage.

BACKGROUND: Vasospasm is a prolonged constriction of a cerebral artery that is induced by hemoglobin after subarachnoid hemorrhage (SAH). The subarachnoid blood clot also contains the protein haptoglobin, which acts to neutralize hemoglobin. Because the haptoglobin alpha gene is dimorphic, a person can expresses only one of three types of haptoglobin (alpha1-alpha1, alpha1-alpha2, or alpha2-alpha2) depending on the alpha subunit genes he or she inherits. Each of these three haptoglobin types has different antihemoglobin activities; therefore, haptoglobin may influence the development of vasospasm differently in various patients with SAH. OBJECTIVE: To determine whether SAH patients who have haptoglobin containing the alpha2 subunit would be more likely to develop vasospasm than would be SAH patients who have haptoglobin alpha1-alpha1. METHODS AND RESULTS: A total of 32 patients with Fisher Grade 3 SAH were enrolled in this study. Haptoglobin type was determined by polyacrylamide gel electrophoresis. The primary measure for vasospasm was increased blood flow velocities as detected by daily transcranial Doppler ultrasonography (TCD). The authors found that only 2 of 9 patients with haptoglobin alpha1-alpha1 (22%) had development of "possible" vasospasm as measured by TCD, whereas 20 of 23 patients with the haptoglobin alpha2 subunit (either the alpha1-alpha2 or alpha2-alpha2 haptoglobin types) had development of "possible" vasospasm (87%). The secondary measure for vasospasm was cerebral angiography performed between 3 and 14 days after SAH. Similar results (17% vs 56%) were seen between these groups in those patients who underwent cerebral angiography, although its inconsistent use limited the strength of the statistical comparison. CONCLUSIONS: Haptoglobins containing the alpha2 subunit seem to be associated with a higher rate of vasospasm than is haptoglobin alpha1-alpha1.

Ultrastructural changes in mitochondria of the adrenal cortex of iron-deficient rats.

Male Sprague-Dawley rats aged 3 weeks that were maintained on an iron-deficient diet for 4-5 weeks developed severe anemia with markedly reduced hemoglobin levels (4.11 +/- 0.20 Hb g% versus controls 12.74 +/- 0.15 Hb g%). On sacrifice, the adrenal glands were removed and processed for light and transmission electron microscopy and enzyme cytochemistry. The major histological and ultrastructural changes in the adrenal cortex in response to the iron deficiency were seen in cells of the zona fasciculata, especially in its outer region, and to a lesser degree in cells of the zona reticularis. Structural changes were seen in the mitochondria of these cells, which often became grossly enlarged and developed unusual electron-dense inclusions. In addition, the lipid droplets in the iron-deficient cells of these regions were much less developed and less prominent compared with controls. Quantitative cytochemical localization of succinic dehydrogenase (SDH) activity in the adrenal glands showed that in iron-deficient rats there was an increase in SDH activity in the zona fasciculata (46%) and in the zona reticularis (74%), whereas there was a reduction of approximately 41% in SDH activity in the zona glomerulosa. Serum corticosterone levels were significantly raised in the iron-deficient rats compared with the control rats. Our results indicate that severe nutritional iron deficiency in rats causes ultrastructural and cytochemical changes in the mitochondria of the adrenal cortex accompanied by increased secretion of corticosterone.