The effect of a new calcium antagonist, TA3090 (clentiazem), on experimental transient focal cerebral ischemia in cats.

Abstract

Background and Purpose: TA3090 (Clentiazem) has been shown to have cerebrovascular protective properties in three experimental studies. An in vivo investigation was undertaken to determine its effects on pial arteries and cerebral blood flow and its therapeutic value in transient focal cerebral ischemia.Methods: This experiment was divided into two protocols. In the first, 200 or 400 ug/kg per hour TA3090 was administered continuously for 3 hours in cats without ischemic insult (n=6 for each group). The effects on pial arteries and cerebral blood flow were estimated. In the second protocol, 400 ,ug/kg per hour TA3090 (treated group, n=14) or physiological saline (control group, n=10) was administered 5 minutes before 1 hour of middle cerebral aretery occlusion in cats. The effects on the pial arteries and cerebral blood flow were observed continuously, followed by autoradiography for a quantitative measurement of cerebral blood flow 5 hours after middle cerebral artery recirculation. The volumes of the cerebral edema and infarct were estimated by planimetry from cerebral preparations made for histological examination.Results: Pial arteries dilated by up to approximately 10%v in the 400-,ug group and 3% in the 200-p£g group 30 minutes after administration of TA3090. Increases in cerebral blood flow of about 10%o in the

Secondary Reduction in the Apparent Diffusion Coefficient of Water, Increase in Cerebral Blood Volume, and Delayed Neuronal Death after Middle Cerebral Artery Occlusion and Early Reperfusion in the Rat

“…On reperfusion, there is a period of cerebral hyperemia in which the blood flow to the affected tissue exceeds the metabolic demand and is considered a period of “luxury perfusion” (Dijkhuizen et al, 1998; Marchal et al, 1996; Steiger et al, 1996). This transient hyperemia is often followed by a period of hypoperfusion, but both these events occur within the first few hours after return of blood flow to the ischemic territory (Sakaki et al, 1993). Increased CBV has been reported in several articles to occur shortly after reperfusion (Busch et al, 1998; Dirnagl et al, 1989), but only few studies report changes in cerebral hemodynamics later than 12 hours after reperfusion (Dijkhuizen et al, 1998; Marchal et al, 1996), as observed in our study.…”

Genes and Cerebral Ischemia Therapeutic Perspectives

“…In retrospect, the premise underly ing the research during these phases would seem to be that elaborate harmful mechanisms exist within the brain from which it needs to be protected. To some extent this has been a useful approach, since a num ber o f treatm ents are now known to reduce infarct volume by 50% [9][10][11][12][13][14] and clinical trials that may bring these therapies to stroke patients are now ongoing. More recently, molecular biolo gy has brought to the field an improved appreciation at two levels.…”

Neuroproteção hipotérmica pré, intra e pós-isquêmica na isquemia cerebral focal temporária em ratos: análise morfométrica

“…Detalhe da área de trabalho do programa KS400, no qual após a seleção do hemisfério esquerdo, a seleção do hemisfério direito é feita (SAKAKI et al, 1993, SWEENEY et al, 1995 Possivelmente a causa do fenômeno de lesão da reperfusão é a persistência da alteração na homeostasia iônica, principalmente na distribuição do cálcio, e o processo peroxidativo (FOLBERGROVÁ et al, 1993). Quando na reperfusão a cadeia mitocondrial de transporte de elétrons mantém seu comprometimento em razão da intensidade e duração da isquemia, não retornando a operar em níveis considerados normais, ocorre a aceleração na glicólise e na produção de lactato.…”