Lack of effect of dihydroergotamine on endothelial and smooth muscle cell proliferation and endothelial cell prostanoid production

The most important effect of dihydroergotamine is venoconstriction, but certain metabolic effects and changes in vessel prostanoid activity have also been suggested. In this study endothelial cell production of 6-keto PGF 1α and TxB 2 was quantitated in vitro. No evidence of altered prostanoid production was noted after incubation with dihydroergotamine (exposure ranging from 5×10 −3 to 5×10 −7 g/l). Similarly, no effect of dihydroergotamine on the growth rates of endothelial cells or smooth muscle cells in vitro was documented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42798/1/18_2005_Article_BF01941713.pd

Improved endothelial function after a modified harvesting technique of the internal thoracic artery

Objective: One of the most important factors in bypass surgery is the preservation of endothelial function in the arterial graft. It was of interest, therefore, whether a slightly modified preparation procedure during surgery could contribute to improved endothelial function of the graft. We compared the functional activity of internal thoracic arteries (ITA) prepared according to the traditional harvesting method with occlusion by a clip, dissection at the distal end and storage of the artery in papaverine until its implantation (CA) with the functional activity of arteries which were also prepared and wrapped in papaverine, but were left perfused and dissected immediately before their anastomoses (PA). Methods: Samples of ITA were obtained from a total number of 28 patients, undergoing bypass surgery, and randomly distributed into two groups. The arteries were cut into rings and suspended in organ baths, containing Krebs-Henseleit solution, for isometric tension recording. Cumulative concentration response curves were determined for the contractile agents endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), noradrenaline (NA) and potassium chloride (KCl) and the relaxant compounds acetylcholine (ACH) and sodium nitroprusside (SNP) during active tone induced by 30 mM KCl. Results: ET-1 and 5-HT stimulated rings from both groups within the same concentration ranges but elicited significantly (P<0.05) higher contractile responses in CA compared to PA. By contrast, concentration response curves for KCl and NA where nearly superimposable. On the other hand, maximal endothelium-dependent relaxant responses to ACH proved to be significantly stronger in PA (0.84±0.20 g) as compared to CA (0.31±0.05 g, P<0.05) while endothelium independent relaxant responses to SNP where similar in both groups. Conclusion: These data suggest that leaving the ITA perfused during harvesting might improve considerably the endothelial function of the graf

Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study

<p>Abstract</p> <p>Background</p> <p>Methylergonovine is an ergot alkaloid widely used in postpartum women. It is also an active metabolite of methysergide and previous studies suggest that it could be effective against refractory headache and cluster headache. The purpose of the present study was to assess the potential therapeutic effectiveness of methylergonovine in the emergency treatment of severe migraine.</p> <p>Methods</p> <p>One hundred and twenty five female patients with migraine attending the emergency department received 0.15 mg of methylergonovine intravenously. Pain intensity, heart rate, blood pressure, and methylergonovine side effects were checked 5, 10, 15, 30 and 60 minutes after drug administration. An additional 0.075 mg dose of methylergonovine was administered to those patients who did not experienced relevant pain relief 15 minutes after dosing. </p> <p>Results</p> <p>Pain intensity decreased markedly from the first minutes after dosing, the 74.4% of patients being pain free at 60 minutes. Only seven patients required an additional dose of methylergonovine. Nausea and vomiting were the most relevant side effects related with methylergonovine administration (84% of patients). A substantial decrease (10 to 25 mmHg) in systolic blood pressure values was observed in 56% of the patients. A significant correlation (p < 0.0001) was found between the decrease in pain intensity and the reduction of systolic blood pressure.</p> <p>Conclusion</p> <p>Although limited by the non-controlled design of the study, our data suggest that intravenous methylergonovine can be an effective and safe drug in the management of severe migraine attacks in the emergency room.</p

The mechanism of cryoinjury: In vitro studies on human internal mammary arteries

1. The mechanism of cryoinjury was investigated in human internal mammary arteries (IMA) by monitoring contractile responses to ET-1 and KCl. 2. For cryopreservation segments of IMA were equilibrated for 20 min with the cryomedium (RPMI 1640 culture medium containing 1.8 M DMSO and 0.1 M sucrose), frozen at a mean cooling rate of 1.3°C min(−1) to −70°C and stored in liquid nitrogen. Before use, samples were thawed slowly and the cryomedium removed by dilution. 3. Compared to unfrozen controls, ET-1 stimulated frozen/thawed IMA with similar efficacy but at 3 fold lower concentrations (P<0.001). Addition of ET-1 (100 nM) induced maximal contraction of unfrozen IMA within 10 min, declining thereafter to 25% after 90 min. In frozen/thawed IMA the ET-1-induced contraction was sustained but could be reversed if protein kinase C was blocked by staurosporine (100 nM). Responses to ET-1 of cryostored IMA were 5 fold more susceptible to blockade by nifedipine than those of controls. 4. After cryostorage the efficacy of KCl was diminished to 40% (P<0.05) and the KCl curve was shifted to the left (2 fold, P<0.001). In both unfrozen and cryostored IMA the KCl (60 mM) effect was sustained and equally susceptible to nifedipine. 5. It is suggested that the smooth muscle cell of IMA is receptive to physical forces which occur during cryopreservation. These forces modify transmembrane signal transduction and intracellular pathways, that are common to pharmacological agonists thereby changing vascular responses to several contractile agonists after thawing