論文の公開元へEffects of adrenaline and vasopressin on cerebral microcirculation in the normal state and during global brain ischemia/reperfusion injury in rabbits
概要
Purpose: We aimed to investigate the direct effects of adrenaline and vasopressin on cerebral microvasculature in both normal and ischemia/reperfusion states.
Methods: The closed cranial window method was used to visualize cerebral microcirculation and changes in the pial arteriole diameter. First, various adrenaline and vasopressin concentrations were administered to evaluate the response. Subsequently, the effects of adrenaline and vasopressin on the brain during ischemic/reperfusion injury were investigated. Global brain ischemia/reperfusion was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Adrenaline, vasopressin, or artificial cerebrospinal fluid was infused 5 min after initiation of ischemia through 120 min after reperfusion. Pial arteriole diameter and hemodynamic and physiological parameters were recorded before ischemia, during ischemia, and after reperfusion.
Results: In the first experiment, adrenaline did not act directly on the cerebral pial arterioles in the normal state. At 10-11 and 10-7mol/L, vasopressin tended to produce pial arteriolar dilation and constriction, respectively; however, these changes were not significant. In the second experiment, the pial arterioles were constricted in the control and vasopressin groups. Topical administration of adrenaline counteracted the vasoconstriction during ischemia/reperfusion injury, with no significant differences in hemodynamic and physiological parameters among the control, adrenaline, and vasopressin groups.
Discussion: This study showed that adrenaline had no direct effects on the pial arterioles. While low concentrations of vasopressin tended to produce pial arteriolar dilation, at high concentrations tended to induce pial arteriolar constriction.
During the ischemia-reperfusion period, pial arterioles were slightly dilated and then constricted in the control group; adrenaline counteracted cerebral vasoconstriction during the global brain ischemia-reperfusion period. Conversely, vasopressin did not show any effect on pial arterioles during the global brain ischemia-reperfusion period.
In a previous global brain ischemia-reperfusion study, we had reported that pial arterioles temporarily dilated, subsequently constricting throughout the reperfusion period. Delayed hypoperfusion after brain ischemia has been reported to contribute to development of cerebral edema, concurrently, preventing cerebral vasoconstriction in the cerebral vasculature after ischemic stroke in female rats has been shown to improve long-term neurological outcomes. We assumed that cerebral vasodilation after brain ischemia may remove acidic metabolites from ischemic brain tissue. Additionally, cerebral vasodilation may provide sufficient oxygen and glucose to preserve normal neuronal function; thus, attenuation of cerebral vasoconstriction after brain ischemia is important. The current study demonstrated that adrenaline increased pial arteriolar diameter during the reperfusion period, and may counteract cerebral vasoconstriction during the global brain ischemia-reperfusion period, thus, adrenaline could be useful during a period of brain ischemia and reperfusion.
Vasopressin has been reported to constrict cerebral pial arterioles during the ischemia-reperfusion period. We observed that pial arterioles were constricted during the reperfusion period; however, pial arteriolar changes were similar between the control and vasopressin groups during the ischemia-reperfusion periods, suggesting that vasopressin did not exert its cerebrovascular-constricting effects during ischemia-reperfusion period. This result might coincide with Kumazawa’s study, which showed that the vasoconstrictor effect of vasopressin was reduced after cerebral ischemia. Ristagno et al. reported that cerebral cortical microcirculatory blood flow was preserved with vasopressin after the restoration of spontaneous circulation from the cardiac arrest; this effect lasted up to 6 min after the restoration of circulation. Cerebral microcirculatory blood flow after resuscitation was equivalent to that before cardiac arrest. In agreement with their findings, pial arteriolar diameters at 5 and 10 min after reperfusion were comparable to those before brain ischemia in the vasopressin group in the present study; thus, vasopressin might not deteriorate cerebral circulation during the brain ischemia-reperfusion period.
Ristagno et al. demonstrated that adrenaline markedly cerebral cortical microcirculatory blood flow up to 6 min after the restoration of circulation; by contrast, adrenaline did not constrict pial arterioles at 5 and 10 min after reperfusion in the present study. There are several differences between Ristagno’s study and our own; first, while brain ischemia was induced with cardiac arrest in their study, our study used arterial clamping. Second, adrenaline was injected into the right atrium in the Ristagno’s study and continuously injected into the cranial window in this study. Lats, pigs were used in Ristagno’s study, whereas rabbits were used in this study. These differences may have affected the results. Contrary to their report, our study suggested that adrenaline did not impair cerebral circulation during the reperfusion period.
Conclusions: Adrenaline did not act directly on the cerebral pial arterioles, while vasopressin may have dilator and constrictor effects on cerebral pial arterioles in the normal state. During ischemia-reperfusion, adrenaline increased cerebral pial arteriolar diameters, and may thus counteract cerebral vasoconstriction during the global brain ischemia-reperfusion period.
