Local cerebral blood flow response to locally infused 2-chloroadenosine during hypotension in piglets

Abstract

Brain interstitial adenosine increases during hypotension in piglets. If adenosine is to participate in the regulation of neonatal cerebral blood flow (CBF) during hypotension, it must retain its vasodilatory action under that condition. To examine this issue, we studied the effects of locally infused 2-chloroadenosine (2-CADO), a stable adenosine analog, on local CBF in the piglet frontal cortex during normotension and graded hemorrhagic hypotension. We used the modified brain microdialysis/hydrogen clearance technique to simultaneously infuse 2-CADO into the frontal cortex and measure local CBF from the same area. When 2-CADO from 10 −8 M to 10 −3 M was infused under control conditions ( n = 7), CBF increased 61% at 10 −5 M, 167% at 10 −4 M, and 210% at 10 −3 M. In hypotension experiments, local infusion of 10 −5 M 2-CADO ( n = 8) caused significant increases in CBF ( P < 0.05) under control conditions (MABP = 65 mmHg) and at hypotensive blood pressures of 55 mmHg and 44 mmHg, respectively. At a blood pressure of 33 mmHg, however, infusion of the analog failed to increase CBF. Local infusion of 10 −3 M 2-CADO also produced a similar change in CBF during graded hypotension. These results indicate that 2-CADO dilates intracerebral vessels during normotension, and mild and moderate hypotension, and support the hypothesis that endogenous adenosine mediates autoregulatory adjustments of CBF during hypotension in newborn piglets.