Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · May 2011
Randomized Controlled TrialEffect of olprinone, a phosphodiesterase III inhibitor, on balance of cerebral oxygen supply and demand during cardiopulmonary bypass.
Neuropsychological dysfunction with cardiopulmonary bypass (CPB) may be facilitated by inadequate cerebral oxygen balance during CPB. Olprinone, a phosphodiesterase III inhibitor, augments cerebral blood flow by a direct vasodilator effect on cerebral arteries. We conducted the present randomized study in patients undergoing cardiac surgery with CPB to investigate whether olprinone improved the balance of cerebral oxygen supply and demand during the rewarming period of CPB. ⋯ Furthermore, there was a minor reduction of the bilateral rSO2 at low doses of olprinone (0.2 μg·kg(-1)·min(-1)). We conclude that olprinone prevents the decrease of the SjO2 at the rewarming period and improves the balance of cerebral oxygen supply and demand during the rewarming period of CPB. In addition, a future extended study may be required to elucidate the effect of low dose of olprinone.
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J. Cardiovasc. Pharmacol. · Feb 2011
Comparative StudySimvastatin reduces lipoprotein-associated phospholipase A2 in lipopolysaccharide-stimulated human monocyte-derived macrophages through inhibition of the mevalonate-geranylgeranyl pyrophosphate-RhoA-p38 mitogen-activated protein kinase pathway.
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), which is produced primarily by macrophages and is predominately found in the blood and in atherosclerotic plaques, represents a potentially promising target for combating atherosclerosis. Although statins are known to decrease the levels and activity of circulating and plaque Lp-PLA(2) during atherosclerosis, little is known regarding the mechanisms underlying inhibition of Lp-PLA(2) by statins. Therefore, the aim of this study was to explore the molecular mechanisms responsible for inhibition of Lp-PLA(2) by statins. ⋯ Treatment of human monocyte–derived macrophages with either simvastatin or C3 exoenzyme prevented LPS-induced activation of p38 MAPK, which could be abolished by treatment with GGPP. Together, these results suggest that simvastatin reduces Lp-PLA(2) expression and secreted activity in LPS-stimulated human monocyte–derived macrophages through the inhibition of the mevalonate–GGPP–RhoA-p38 MAPK pathway. These observations provide novel evidence that statins have pleiotropic effects and suggest that inhibition of Lp-PLA(2) via this mechanism may account, at least in part, for the clinical benefit of statins in combating atherosclerosis.
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J. Cardiovasc. Pharmacol. · Dec 2010
ReviewEstrogens and development of pulmonary hypertension: interaction of estradiol metabolism and pulmonary vascular disease.
Severe pulmonary arterial hypertension (PAH) is characterized by clustered proliferation of endothelial cells (ECs) in the lumina of small size pulmonary arteries resulting in concentric obliteration of the lumina and formation of complex vascular structures known as plexiform lesions. This debilitating disease occurs more frequently in women, yet both animal studies in classical models of PAH and limited clinical data suggest protective effects of estrogens: the estrogen paradox in pulmonary hypertension. Little is known about the role of estrogens in PAH, but one line of evidence strongly suggests that the vascular protective effects of 17β-estradiol (estradiol; E2) are mediated largely by its downstream metabolites. ⋯ This review focuses on the effects of estrogens and their metabolites on pulmonary vascular pathobiology and the development of experimental PAH and offers potential explanation for the estrogen paradox in PAH. Furthermore, we propose that unbalanced estradiol metabolism may lead to the development of PAH. Recent animal data and studies in patients with PAH support this concept.
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J. Cardiovasc. Pharmacol. · Nov 2010
The influence of proton pump inhibitors on the antiplatelet potency of clopidogrel evaluated by 5 different platelet function tests.
Proton pump inhibitors (PPIs) are metabolized by the cytochrome P450 enzyme system to a variable degree and may therefore interact with the metabolism of clopidogrel to its active form. The conflicting data on this potential interaction may be due to the use of different PPIs and platelet function tests in recent studies. We therefore evaluated the influence of different PPIs on the antiplatelet effect of clopidogrel by 5 platelet function tests in the same population. ⋯ Furthermore, we observed no significant differences of ADP-inducible platelet reactivity between patients without PPIs and patients with pantoprazole (n = 95, 70.4%), esomeprazole (n = 22, 16.3%), omeprazole (n = 9, 6.65%), or lansoprazole (n = 9, 6.65%) (all P > 0.3). High on-treatment residual ADP-inducible platelet reactivity occurred to a similar extent in patients without and with PPI therapy in each assay (all P > 0.05). In conclusion, concomitant treatment with PPIs did not attenuate the antiplatelet effect of clopidogrel in patients on dual antiplatelet therapy irrespective of the type of PPI and the used test system.
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J. Cardiovasc. Pharmacol. · Oct 2010
Clinical TrialEfficacy of low-dose bepridil for prevention of ventricular fibrillation in patients with Brugada syndrome with and without SCN5A mutation.
It has been reported that bepridil prevents ventricular fibrillation (VF) in patients with Brugada syndrome, but the comparative efficacy with and without mutation in the SCN5A gene has not been elucidated. The purpose of this study was to assess the efficacy of low-dose bepridil (100 mg/day) for VF prevention in patients with Brugada syndrome with and without SCN5A mutation. Among 130 patients with Brugada-type electrocardiogram (ECG), low-dose bepridil was administered to seven patients because of repetitive VF episodes, including three with and four without SCN5A mutation. ⋯ Frequencies of VF episodes were reduced after treatment with low-dose bepridil in all three patients with the SCN5A mutation (before: 0.33 versus after: 0.02 episodes/month, P < 0.01), but not in all four patients without the SCN5A mutation (before: 0.43 versus after: 2.94 episodes/month, P = nonsignificant). Levels of ST-segment elevation at J points and duration of low-amplitude signals less than 40 µV in the terminal filtered QRS complex (LAS40) in signal-averaged ECG were improved exclusively in patients with the SCN5A mutation. Treatment with bepridil prevented recurrence of VF along with improvement of ST elevation and LAS40 in patients with Brugada syndrome with the SCN5A mutation.