??-Adrenoreceptor Antagonists Attenuate Brain Injury After Transient Focal Ischemia in Rats

Abstract

Beta-adrenoreceptor antagonists experimentally reduce cardiac and renal injury after ischemia and are also clinically useful for myocardial infarction and severe burns. In addition, beta-adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. We conducted the present study to compare the neuroprotective effects of several beta-adrenoreceptor antagonists in rat transient focal cerebral ischemia. Halothane-anesthetized normothermic adult male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received an IV infusion of saline 0.5 mL/h, propranolol 100 microg x kg(-1) x min(-1), carvedilol 4 microg x kg(-1) x min(-1), esmolol 200 microg x kg(-1) x min(-1), or landiolol 50 microg x kg(-1) x min(-1) (n = 6 in each group). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. Additional rats received esmolol 50 microg x kg(-1) x min(-1) or landiolol 10 microg x kg(-1) x min(-1) intrathecally (IT) via the cisterna magna (n = 5 in each group), according to the same experimental protocol. The neurological deficit score was evaluated at 22 h after reperfusion, and the brains were removed and stained with triphenyltetrazolium chloride for evaluation of infarct volume. Additional rats that received saline, esmolol, and landiolol IV (n = 6 in each group) were allowed to survive for 7 days followed by measurement of infarct size. Neurological deficit scores were smaller in rats treated with propranolol-IV, carvedilol-IV, esmolol-IV, landiolol-IV, esmolol-IT, and landiolol-IT compared with saline-treated rats (P < 0.05). Cortical and striatum infarct volumes were less in the rats receiving beta-adrenoreceptor antagonists via either IV or IT than in saline-treated rats (P < 0.05). We conclude that beta-adrenoreceptor antagonists improve neurological and histological outcomes after transient focal cerebral ischemia in rats independent of administration route.

β-adrenoceptor blockers protect against staurosporine-induced apoptosis in SH-SY5Y neuroblastoma cells

“…In the brain, β1-adrenoceptors are expressed mainly in neurons whereas β2-adrenoceptors are largely restricted to the glial cells (Nicholas et al, 1996). In the intact brain, both non-selective and β1-adrenoceptor selective blockers have been shown to decrease infarct volume and enhance functional recovery in a transient focal ischemia model (Goyagi et al, 2006; and references cited therein). However, the cellular mechanism responsible for such apparent neuro-protection by β-adrenoceptor blockers is not known.…”

Landiolol, an ultra short acting β1-blocker, improves pulmonary edema after cardiopulmonary resuscitation with epinephrine in rats

“…First, because this experiment was performed in young, healthy rats, the results of this study cannot be directly applied to a general human population. Second, because blood esterase activity is higher in rats than in humans, the blood level of landiolol could be different from that in humans [15]. Third, the PaO 2 /FiO 2 ratio showed a tendency of improvement even though the differences were not significant.…”

“…The antioxidative effect of landiolol has been described in some papers [14,15]. Kimura-Kurosawa et al [5] demonstrated that landiolol exhibited a lipid peroxidation-reducing effect in isolated guinea pig hearts subjected to ischemia-reperfusion.…”

“…Its rates of onset and elimination are faster, and it exhibits a less potent negative inotropic effect than esmolol [10]. Moreover, the antioxidative effect of landiolol has been described in some papers [5,14,15].…”

Possible indications of beta-blockers in the perioperative period other than prevention of cardiac ischemia

“…In contrast, Junker et al [80] showed that clenbuterol induces neuroprotective effects via an increase in nerve growth factor expression and that this beneficial effect is blocked by propranolol. Goyagi et al [81,82] recently examined the neuroprotective effects of several beta-blockers in rats with transient focal cerebral ischemia. The rats received an intravenous infusion of saline, propranolol, carvedilol, esmolol, and landiolol 30 min before MCA occlusion, and the infusion was continued for 42 h. Cerebral infarct volumes in the cortex were lower in rats treated with propranolol (72 ± 33 mm 3 ), carvedilol (64 ± 25 mm 3 ), esmolol (65 ± 18 mm 3 ), and landiolol (44 ± 18 mm 3 ) than in saline-treated rats (205 ± 28 mm 3 ).…”