ABSTRACT
The possibility that the ability of bezafibrate to lower the oxygen affinity of haemoglobin might lead to an increased oxygen delivery to ischaemic cerebral tissue was explored in preliminary studies in two animal models. The combined morbidity and mortality of unilateral carotid ligation in the gerbil appeared to be reduced at two hours in bezafibrate treated animals. By four hours and thereafter the outcome was unaffected. Two hours after MCA occlusion bezafibrate-treated rats showed a significantly reduced rise in tissue lactate concentration (p less than 0.01) suggesting less anaerobic metabolism had occurred in the ischaemic tissue.
Subject(s)
Bezafibrate/pharmacology , Brain Ischemia/metabolism , Acute Disease , Animals , Disease Models, Animal , Gerbillinae , Hemoglobins/physiology , Lactates/blood , Male , Oxygen/metabolism , Rats , Rats, Inbred StrainsABSTRACT
The effects of induced hypertension, hemodilution, and osmotherapy (mannitol) have been assessed singly and in combination on the metabolic sequelae 2 hr after middle cerebral artery (MCA) occlusion in the anesthetized rat. All regimes that included hypertension and monotherapy with mannitol significantly reduced the rise in hemispheric lactate produced by vessel occlusion. No treatment caused increase cerebral edema, and mannitol produced a slight reduction in the hemisphere water content. The significance of the results is discussed.
Subject(s)
Brain Ischemia/metabolism , Brain/metabolism , Hemodilution , Hypertension/metabolism , Lactates/metabolism , Animals , Brain Edema/etiology , Brain Edema/metabolism , Brain Ischemia/complications , Brain Ischemia/therapy , Disease Models, Animal , Hypertension/complications , Hypertension/therapy , Male , Mannitol/therapeutic use , Rats , Rats, Inbred Strains , Reference Values , Water-Electrolyte BalanceABSTRACT
Infusions of metaraminol and angiotensin were used to test the effect of increased perfusion pressure on tissue metabolism and oedema after induction of regional cerebral ischaemia in the rat and the gerbil. An increase of mean arterial blood pressure of 30-40 mm Hg in the rat over the first 2 hours after diathermy of the middle cerebral artery prevented the 100% rise in hemisphere lactate seen in normotensive control animals. Angiotensin infusion also prevented early hemispheric oedema in this model. In the gerbil, 4 hours after placing a clip on one carotid artery, metaraminol-induced increases in blood pressure had no such protective effect on the metabolic changes or on oedema. When the clip was removed after 3 hours to permit 1 hour of reperfusion, lactate levels returned to normal but the degree of oedema was unchanged. Hypertension in this reperfusion model caused a slight but not statistically significant increase in oedema. The evidence suggests that moderate increases in blood pressure may be protective against the early metabolic sequelae of focal cerebral ischaemia, but there are potential problems with oedema formation. It is argued that a clinical trial should study the potentially beneficial effects of a brief early increase in blood pressure in the acute aftermath of ischaemic stroke.
