Time Course of Anoxia-Induced Increase in Cerebral Blood Flow Rate in Turtles: Evidence for a Role of Adenosine

Abstract

Summary:The exceptional ability of the turtle brain to survive prolonged anoxia makes it a unique model for studying anoxic survival mechanisms. We have used epi illumination microscopy to record blood flow rate in ve nules on the cortical surface of turtles (Trachemys scripta). During anoxia, blood flow rate increased 1.7 times after 45-75 min, whereupon it fell back, reaching preanoxic values after 115 min of anoxia. Topical super fusion with adenosine (50 /-LM) during normoxia caused a 3.8-fold increase in flow rate. Superfusing the brain with Freshwater turtles of the genera Trachemys and Chrysemys possess the exceptional ability among vertebrates to tolerate prolonged anoxia, surviving days of anoxia at room temperature and several months at temperatures close to ooe (Ultsch, 1989).In vertebrates, from mammals (Hansen, 1985; Siesjo, 1992) to fish (Nilsson et aI., 1993), the brain is particularly sensitive to anoxia, rapidly losing ATP levels-the primary cause of neuronal death. To maintain brain ATP levels, turtles utilize two cooperating strategies. An initial enhancement of glycolytic ATP production is followed by deep hy pometabolism (Lutz, 1992).An increased glycolytic rate would probably de mand increased cerebral blood flow and/or an ele vated blood glucose level. Previous studies on tur tles using the microsphere technique have shown an approximately threefold increase in cerebral blood Received January 19, 1994; final revision received March 7, 1994; accepted March 8, 1994.Address correspondence and reprint requests to Dr. P.Hylland at Vertebrate Physiology and Behaviour Unit, Depart ment of Limnology, Norbyvagen 20, S-752 36 Uppsala, Sweden. 877the adenosine receptor blocker aminophylline (250 /-LM)totally inhibited the effects of both adenosine and anoxia, while aminophylline had no effect on normoxic flow rate. None of the treatments affected systemic blood pressure. These results indicate an initial adenosine-mediated in crease in cerebral blood flow rate during anoxia, probably representing an emergency response before deep meta bolic depression sets in.

α-Adrenergic regulation of systemic peripheral resistance and blood flow distribution in the turtleTrachemys scriptaduring anoxic submergence at 5°C and 21°C

“…Similarly, during hypoxia and underwater diving, endotherms redistribute blood flow towards cerebral, myocardial and adrenal vascular beds, while blood flow to visceral organs is reduced by a selective vasoconstriction which, in many cases, is mediated by α-adrenergic control (Johansen, 1964;Elsner et al, 1966;Chalmers et al, 1967;Krasney, 1971;Butler and Jones, 1971;Jones et al, 1979;Zapol et al, 1979). Consistent with these blood flow patterns, blood flow to various visceral organs is reduced during short-term anoxia in anaesthetized turtles, while brain blood flow is largely maintained (Davies, 1989(Davies, , 1991Bickler, 1992;Hylland et al, 1994Hylland et al, , 1996.…”

“…Changes in systemic blood flow distribution with anoxic exposure A redistribution of blood flow towards oxygen-sensitive tissues such as the brain and heart is critical to survival and is a commonly used survival strategy among vertebrates when exposed to hypoxia (Johansen, 1964;Elsner et al, 1966;Chalmers et al, 1967;Krasney, 1971;Butler and Jones, 1971;Jones et al, 1979;Zapol et al, 1979;Boutilier et al, 1986;Davies, 1989Davies, , 1991Bickler, 1992;Hylland et al, 1994Hylland et al, , 1996Nilsson et al, 1994;Yoshikawa et al, 1995;Söderström et al, 1999). Here, we provide a quantitative description of systemic blood flow distribution during the large depression in cardiac status occurring with anoxic submergence in the anoxia-tolerant freshwater turtle.…”

No oxygen? No problem! Intrinsic brain tolerance to hypoxia in vertebrates

“…In longer anoxic exposures, glutamate release is suppressed by adenosine and GABA (Thompson et al, 2007). Adenosine in turn affects channel arrest (Pék and Lutz, 1997;Pérez-Pinzón et al, 1993), dopamine release (Milton and Lutz, 2005;Milton et al, 2002), NMDAR currents (Buck and Bickler, 1998) and cerebral blood flow (Hylland et al, 1994). …”

Slow death in the leopard frogRana pipiens: neurotransmitters and anoxia tolerance

“…The turtle, on the other hand, appears to use the first hour of anoxia to actively shut down metabolic processes in preparation for long-term anoxia. The first hour of anoxia is marked by temporary increases in extracellular adenosine levels and blood flow (Hylland et al, 1994), the decreased release of dopamine and glutamate (S. L. Milton and P. L. Lutz, manuscript in preparation; Milton et al, 2002) and the active downregulation of ion channels (Bickler et al, 2002).…”