Curative effect of an almitrine-raubasine combination in the postischemic syndrome following transient cerebral ischemia in dogs.
Cerebral hemodynamic and metabolic changes, occurring during delayed hypoperfusion following transient cerebral ischemia, and the influence of treatment with almitrine plus raubasine were studied in mongrel dogs. 10 min of transient cerebral ischemia was induced by bilateral clamping of both carotid and vertebral arteries. After declamping, the mean time necessary until cerebral venous PO2 (cvPO2) reached a value of 3.6 kPa, threshold for tissue hypoxia, was 80 min. At this time (T0), venous cerebral blood flow (vCBF) and cerebral perfusion pressure (Perf P) were below (60 and 20%, respectively) preischemic values, while cerebral vascular resistance (CVR) and oxygen and glucose extraction rates increased despite a normal cerebral oxygen consumption (CMRO2). At T0 ventilatory assistance without (control group) or with (treated group) intravenous infusion of almitrine plus raubasine was applied for 110 min. Between T0 and T110 min, 2 dogs died in the control group. During this period vCBF decreased by more than 60% in the control group while it slightly increased in the treated group. A strong decrease in Perf P (40%) and increase in CVR (140%) was observed in the control group while in the treated group Perf P and CVR slightly decreased (14 and 35%, respectively). CMRO2 decreased by 60% in the control group but remained within the normal range in the treated group. The fact that cvPO2 remained constantly below the initial value of 3.6 kPa in the control group and, on contrary, above this value in the group infused with raubasine plus almitrine indicates that the vCBF improvement leads to an increase in oxygen supply and is involved in the keeping of the adequacy between flow and metabolism. Our results support the hypothesis that the post-ischemic syndrome may play an important role in the acute prognosis of stroke. They clearly indicate that early cerebral resuscitation by infusion of almitrine plus raubasine, maintaining oxygen availability and CBF above initial thresholds, should improve the long-term neurological outcome.
Cahn
R
R
SIR international, Department of Experimental Therapy, Montrouge, France.
Cahn
J
J
D015765:Almitrine; D000818:Animals; D001783:Blood Flow Velocity; D002536:Cerebral Arteries; D002560:Cerebrovascular Circulation; D004285:Dogs; D004338:Drug Combinations; D002534:Hypoxia, Brain / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000627:therapeutic use*; D046948:Secologanin Tryptamine Alkaloids; D013997:Time Factors; D015016:Yohimbine / Q000627:therapeutic use*
D004338:Drug Combinations; D010879:Piperazines; D046948:Secologanin Tryptamine Alkaloids; D015016:Yohimbine; C005709:raubasine; D015765:Almitrine