Recirculation in the Rat Brain following Incomplete Ischemia

Abstract

Summary: The objective of this study was to charac terize local cerebral blood flow (CBF) in the recirculation period following incomplete forebrain ischemia. Specifi cally, we wished to determine whether perfusion defects developed in the immediate recirculation period, to study how initial hyperemia and delayed hypoperfusion at the local level were related to the severity of the preceding ischemia, and to find out whether reflow was influenced by the nutritional state of the animals. To that end, fore brain ischemia of 15 min duration was induced in fed and fasted ventilated rats under 70% N20. Local CBF was measured with an autoradiographic technique at the end of ischemia, as well as at 5 and 60 min following the start of recirculation. Control experiments were performed to examine the influence of ischemia on cerebral metabolic state in fed and fasted animals. The ischemia reduced CBF to excessively low values «5% of control) in manyIn the accompanying article (Kl:1gstrom et aI., 1983) we reviewed previous results demonstrating that transient ischemia is usually followed by an initial hyperemia, later to be succeeded by a sec ondary decrease in cerebral blood flow (CBF) ("delayed hypoperfusion" ). In that article we re ported on experiments designed to characterize local cerebral blood flow (lCBF) in the recovery period following complete brain ischemia of 5 -30 min duration, as induced in lightly anaesthetized, artificially ventilated rats. The results obtained with 15 min of ischemia confirmed that a delayed hypoperfusion occurs. However, the autoradio graphic techniques used made it possible to reveal the appearance of a true "no-reflow" phenomenon, i.e., an initial hindrance to recirculation in centrally located brain structures. Thus, circulatory events following complete ischemia do not conform to the Address correspondence and reprint requests to Dr. Kiigstrom at Department of Neurosurgery, University Hospital, S-22185 Lund, Sweden .Abbreviations used: PCr, Phosphocreatine; EC, energy charge. 183forebrain structures, including the cerebral cortices, caudoputamen, and hippocampus. In spite of this, perfu sion defects failed to appear after 5 min of recirculation. Instead, moderate to marked hyperemia was present in all previously ischemic structures. After 60 min of recircula tion, pronounced hypoperfusion developed. The mag nitude of the initial hyperemia was poorly related to the severity of the preceding ischemia, but the latter partly determined the degree of delayed hypoperfusion. Thus, little or no hypoperfusion developed in structures whose flow rates exceeded 30-40% of control during ischemia. Fasted animals had a better preserved flow to many structures than did fed animals, indicating that the detri mental effect of feeding (or glucose infusion) is also re flected in lower perfusion rates. Key Words: Acidosis Cerebral blood flow-Delayed hypoperfusion-Incom plete forebrain ischemia-Rat-Reflow patterns.simple sequence, ischemia-initial hyperemia delayed hypoperfusion.

Deterioration of baroreflex by transient global cerebral ischemia: Its correlation with the degree of ischemia or post-ischemic hypoperfusion in the medulla oblongata.

“…These results are consistent with the previous literature (6,7,(15)(16)(17)(18), in which many investigators have failed to find the correlation between the degree of hypoperfusion and the degree of metabolic or histological changes in several models of transient cerebral ischemia. It has also been suggested that the post-ischemic hypoperfusion may occur secondarily to the primary cellular damage by ischemia itself (14,18,19).…”

Acute Functional Recovery of Cerebral Blood Flow after Forebrain Ischemia in Rat

“…Cerebral blood flow measured in the cortex was found to be less than 10% of the preischemic level after 10 to 15 mins of incomplete ischemia (Kagstrom et al, 1983;Inamura et al, 1988;Dirnagl et al, 1993), which is in agreement with our observations. After 5 mins reperfusion, a 250% to 300% hyperemia was usually seen (Kagstrom et al, 1983;Dirnagl et al, 1993), which is lower than the peak value observed 9 to 10 mins after the end of the ischemia in our study (538%±35%). These differences might be related to differences in anesthesia or duration of ischemia between the studies.…”

“…The phenomenon of hypoperfusion and postischemic hyperperfusion has been investigated extensively after severe incomplete ischemia in rat (Kagstrom et al, 1983;Inamura et al, 1988;Dirnagl et al, 1993). Cerebral blood flow measured in the cortex was found to be less than 10% of the preischemic level after 10 to 15 mins of incomplete ischemia (Kagstrom et al, 1983;Inamura et al, 1988;Dirnagl et al, 1993), which is in agreement with our observations.…”

Protective Preconditioning by Transient Global Ischemia in the Rat: Components of Delayed Injury Progression and Lasting Protection Distinguished by Comparisons of Depolarization Thresholds for Cell Loss at Long Survival Times

“…Recent results have associated increased expression of uncoupling protein-2 (UCP-2) with neuroprotection (Diano et al, 2003;Mattiasson et al, 2003), but its potential impact on ischemic depolarization per se is unclear. Established global ischemia models are characterized by very low residual flow during occlusion (Kågströ m et al, 1983;Pulsinelli et al, 1982), but perfusion effects of preconditioning are also possible. Better preservation of CBF and ATP levels during global ischemia has been shown in rat cortex after several days of ipsilateral carotid artery occlusion (Bronner et al, 1998).…”