Erik Kågström

Local Cerebral Blood Flow in the Recovery Period following Complete Cerebral Ischemia in the Rat

This study examines reflow patterns in the recirculation period following complete, global ischemia. Cerebrospinal fluid (CSF) compression ischemia was induced in ventilated rats for 5–30 min, and local cerebral blood flow (CBF) was measured autoradiographically after 5, 60, and 90 min of recirculation, Ischemia of 15 min duration was induced by four-vessel occlusion combined with arterial hypotension in two additional groups, with recovery periods of 5 or 60 min, In the immediate recirculation period (5 min), following 15 min of ischemia, local CBF was markedly heterogeneous, Thus, whereas most structures gave clear evidence of “reactive hyperemia,” others showed perfusion defects of the “no-reflow” type, Typically these defects affected the striatum, thalamus, and hippocampus, as well as the frontal, sensorimotor, and parietal cortices. Areas of no-reflow appeared after 10 min, were more extensive after 15 min, and occupied a major part of the brain after 30 min of ischemia. When recirculation was instituted for 60 or 90 min, following 15 min of ischemia, flow returned in previously unperfused areas. However, a delayed hypoperfusion developed, which differed widely between structures (range of CBF values, 20–80% of control). When the ischemic period was prolonged to 30 min, some perfusion defects remained, even after 90 min of recirculation.

Recirculation in the Rat Brain following Incomplete Ischemia

The objective of this study was to characterize local cerebral blood flow (CBF) in the recirculation period following incomplete forebrain ischemia. Specifically, 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, forebrain ischemia of 15 min duration was induced in fed and fasted ventilated rats under 70% N2O. 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 many forebrain structures, including the cerebral cortices, caudoputamen, and hippocampus. In spite of this, perfusion 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 recirculation, pronounced hypoperfusion developed. The magnitude 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 detrimental effect of feeding (or glucose infusion) is also reflected in lower perfusion rates.

Influence of Blood Glucose Concentration on Brain Lactate Accumulation During Severe Hypoxia and Subsequent Recovery of Brain Energy Metabolism

The effects of hypoxaemia on regional cerebral blood flow (CBF) and brain cortical metabolite concentrations were investigated at different blood glucose concentrations in rats under nitrous oxide anaesthesia. Tissue hypoxia of 15-min duration was induced by a combination of arterial hypoxaemia, hypotension, and clamping of the right carotid artery. Blood glucose concentrations were manipulated by varying the food intake in the 24 h before the experiment, and by glucose administration. Cortical CBF doubled during hypoxia on the intact side, but did not differ significantly from control values on the clamped side. In the clamped hemisphere there was a substantial decrease in adenylate energy charge. At brain tissue glucose concentrations of 1 μmol g−1 and above, there was an inverse correlation between adenylate energy charge and brain lactate concentration. In starved animals with mean brain glucose of 0.32 ± 0.00 μmol g−1, lactate concentration was significantly lower, in spite of equally severe disruption of energy state. Recovery of brain adenylate energy charge was worse in fed and glucose-infused groups than in the fasted group. These results demonstrate that limitation of substrate supply during severe hypoxia in the rat allows enhanced recovery of brain energy metabolism following the hypoxic episode.

Temporary clipping during early operation for ruptured aneurysm: preliminary report.

Temporary arterial occlusion was performed in 16 patients undergoing early aneurysm operation. Ten patients had a ruptured middle cerebral artery (MCA) aneurysm, and 6 had a ruptured anterior communicating artery aneurysm. Premature aneurysm rupture during operation necessitated temporary arterial occlusion in 10 patients. In 5 patients, temporary arterial occlusion was performed to facilitate dissection of the aneurysm. In 1 patient with a large MCA aneurysm, temporary occlusion was performed to provoke collapse of the completely exposed aneurysm sac, thus making clipping of the base possible. The results do not indicate that temporary occlusion by the standard aneurysm clips now in general use leads to angiographically detectable arterial wall changes or increased thromboembolic complications. Temporary clipping of the MCA proximal to the perforating arteries may be well tolerated for up to 20 minutes during early aneurysm operation. Temporary occlusion of one or both anterior cerebral arteries or temporary pericallosal clipping need not unconditionally lead to disastrous consequences if rendered necessary during aneurysm operations performed in the acute stage.

Effect of the Calcium Antagonist Nimodipine on the Delayed Hypoperfusion following Incomplete Ischemia in the Rat

Regional cerebral blood flow (CBF) was measured autoradiographically in the recovery period following 15 min of forebrain ischemia in rats pretreated with either nimodipine (0.1 mg kg−1) or vehicle. The results showed that although nimodipine increased postischemic CBF, the flow enhancement was regionally heterogeneous, sometimes resulting in zones of gross hypoperfusion and overt hyperemia within the same structures. This patchy improvement of delayed postischemic hypoperfusion was not accompanied by recovery of sensory evoked responses, and return of EEG activity was not enhanced.