RESUMO
Hemorrhage secondary to rupture of a brain arteriovenous malformations (AVM) is one of the initial manifestations, and the main cause of, morbidity and mortality in patients with this condition. Current treatment strategies include endovascular embolization with the goal of AVM obliteration and neurological preservation. In the transvenous endovascular embolization procedure, adenosine is the preferred agent to induce temporary hypotension and allow adequate AVM embolization. We describe the intraoperative management of an adenosine-resistant 38 year-old male who underwent a successful intracranial AVM embolization after concomitant administration of gradually increasing doses of nitroglycerin. This report suggests that nitroglycerin infusion can be combined with adenosine boluses to create a pronounced and dose-dependent hypotension in patients partially unresponsive to adenosine alone.
RESUMO
INTRODUCTION: A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature and the primary cause of morbidity and mortality following a subarachnoid hemorrhage. The middle cerebral artery (MCA) is commonly affected by CVSPs. Concomitant administration of dantrolene and nimodipine synergistically reduces vasospasms in aortic rings from Sprague Dawley rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effect of intravenous administration of dantrolene (2.5 mg/kg) and nimodipine (1 mg/kg and 2 mg/kg) on MCA blood flow velocity (BFV) 7 days after the induction of CVSPs. METHODS: Vasospasms were induced by bathing the left common carotid artery with autologous whole blood. Age-matched sham rats were used as controls. BFV, mean arterial pressure (MAP), and heart rate (HR) were measured with a PeriFlux 5000 Laser Doppler System, and a CODA non-invasive blood pressure system, before and after administering the drugs. Morphometric evaluations were also performed to assess vascular alterations. RESULTS: BFV was reduced by 37% with dantrolene alone (n = 6, p ≤ 0.05) and by 27% with 2 mg/kg nimodipine (n = 6, p < 0.05), while it was not affected by 1 mg/kg nimodipine. The combination of 1 mg/kg nimodipine with dantrolene, however, decreased BFV by 35% (from 435.70 ± 21.53 to 284.30 ± 23.13 perfusion units, n = 7, p ≤ 0.05). A similar reduction (31%) was obtained with dantrolene and 2 mg/kg nimodipine (from 536.00 ± 32.61 to 367.80 ± 40.93 perfusion units, n = 6, p ≤ 0.05). Neither MAP nor HR was affected by dantrolene or nimodipine alone. The combination of dantrolene with 2 mg/kg nimodipine, however, decreased MAP and increased HR. Furthermore, 7 days after the induction of vasospasms, lumen area of the left common carotid artery decreased, whereas media thickness and the wall-to-lumen ratio increased when compared to contralateral controls. The latter finding suggests that vascular remodeling was present at this stage. CONCLUSION: Altogether, our results indicate that 2.5 mg/kg dantrolene significantly reduces BFV in the MCA without altering systemic hemodynamic parameters to a similar extent than the highest dose of nimodipine or the combination of dantrolene and the lowest dose of nimodipine. Therefore, dantrolene may provide a promising alternative to lower the risk, or partially revert, CVSP.
Assuntos
Nimodipina , Hemorragia Subaracnóidea , Ratos , Animais , Nimodipina/farmacologia , Nimodipina/uso terapêutico , Dantroleno/farmacologia , Dantroleno/uso terapêutico , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Circulação CerebrovascularRESUMO
BACKGROUND: Diabetics have a higher risk of developing cerebral vasospasms (CVSPs) than non-diabetics. Current therapies are ineffective in reducing CVSPs, but a a combination of dantrolene and nimodipine may be a viable treatment. Considering the potentially harmful secondary effects of dantrolene, however, we evaluated the efficacy of 10 µM dantrolene compared to 50 µM dantrolene alone or in combination with 50 nM nimodipine. METHODS: Dose-response curves for the phenylephrine (PHE)-induced contraction and acetylcholine (ACh)-induced relaxation were performed on aortic rings from diabetic and non-diabetic rats, before and after a 30-min incubation period with dantrolene (50 µM and 10 µM), alone or in combination with 50 nM nimodipine. RESULTS: Whereas 50 µM dantrolene reduced PHE-induced contraction by 47% in diabetic rats and 29% in controls, 10 µM dantrolene failed to reduce this parameter in either group. Furthermore, 50 µM dantrolene reduced PHE-induced contraction by about 80% in both diabetic and controls when combined with nimodipine (N = 9, P < 0.05). The combination of 10 µM dantrolene and 50 nM nimodipine, however, was ineffective. Only 50 µM dantrolene improved endothelial dysfunction. CONCLUSIONS: Improved endothelial-dependent relaxation and reduced vascular contractility with dantrolene are dose dependent. Thus, although dantrolene appears to be a promising alternative for the treatment of CVSPs when added to conventional therapies, careful titration should be performed to achieve a significant reduction in vascular hyperreactivity. Moreover, if our findings with rats are applicable to humans, the combined use of dantrolene and nimodipine at optimal doses may reduce CVSPs, especially in the diabetic population.