Nimodipine down-regulates CGRP expression in the rat trigeminal nucleus caudalis.

L-type calcium channel blockers like verapamil are used in the prophylaxis of migraine. However, their effect on the expression of CGRP in the trigeminal nucleus caudalis (TNC) is unknown. It is important because an earlier study had shown that olcegepant, a CGRP receptor antagonist, acts at the level of the trigeminal spinal nucleus rather than the trigeminal ganglia. Nimodipine was used in the present study as it crosses the blood-brain barrier. The objective of the study was to determine the pattern of expression of calcitonin gene-related peptide (CGRP) in the TNC after administration of nimodipine and/or morphine. Wistar rats were injected with saline, morphine, nimodipine or morphine + nimodipine for 14 days. Subsequently, the lowest part of the medulla oblongata containing the spinal nucleus was removed and processed for immunohistochemical localization of CGRP. The density of expression was quantified using Image J software. The results were statistically analyzed. CGRP expression was noted over the superficial part of the TNC, which decreased significantly after nimodipine administration. Conversely, morphine produced an up-regulation. The expression was unchanged with reference to saline in the morphine + nimodipine treated group. Decreased expression of CGRP in the trigeminal nucleus caudalis after nimodipine is being reported for the first time. Also, whether CGRP expression can be used as a marker for predicting the therapeutic efficacy of an anti-migraine drug is currently being investigated.

Levosimendan in patients with low-output heart failure: lessons from the LIDO trial.

The novel calcium sensitizer levosimendan improves myocardial contractility without causing an increase in intracellular calcium and cyclic adenosine monophosphate concentrations. It also has a vasodilator action due to an opening of the adenosine triphosphate-sensitive potassium channels. In a double-blind clinical trial levosimendan was compared with dobutamine in 203 patients with severe low-output congestive heart failure. A 24-hour infusion of these inotropic drugs was administered to increase the cardiac output by at least 30% together with a decrease in the pulmonary capillary wedge pressure by > or = 25%. The pre-defined hemodynamic improvement was achieved in 28% of patients receiving levosimendan compared to only 15% with dobutamine (p = 0.022). Levosimendan also reduced the 1- and 6-month mortality more than dobutamine (7.8 vs 17%, p = 0.045 and 26 vs 38%, p = 0.029, respectively). Levosimendan produced less myocardial ischemia and cardiac arrhythmias than dobutamine. Calcium sensitizers offer a new therapeutic possibility in patients with decompensated low-output heart failure.