Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Dec 2004
Randomized Controlled Trial Clinical TrialLevosimendan in off-pump coronary artery bypass: a four-times masked controlled study.
We tested the hypothesis that levosimendan produced beneficial hemodynamic effects during and after off-pump coronary artery bypass grafting in patients with good preoperative left ventricular function. Levosimendan at low dose (12 microg/kg), high dose (24 microg/kg), or placebo were administered in thirty-one patients in a randomized and four-times masked controlled study. Heart rate was not significantly different between experimental groups. ⋯ Both doses of levosimendan produced significant increased stroke volume and decreased systemic vascular resistance. Mean arterial pressure, pulmonary capillary wedge pressure, and left ventricular end-systolic volume were not significantly different between groups. The low-dose levosimendan produced better hemodynamic response than high-dose and may be preferable in patients undergoing off-pump coronary artery bypass grafting.
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J. Cardiovasc. Pharmacol. · Nov 2004
Randomized Controlled Trial Multicenter StudySTRIDE 1: effects of the selective ET(A) receptor antagonist, sitaxsentan sodium, in a patient population with pulmonary arterial hypertension that meets traditional inclusion criteria of previous pulmonary arterial hypertension trials.
Sitaxsentan (SITAX; Thelin, Encysive Corporation, Bellaire, TX, U. S. A.) is a highly selective oral endothelin-A receptor antagonist. ⋯ The results were: change for placebo (mean +/- SE) vs change for sitaxsentan (mean +/- SE) vs treatment effect (mean), all statistically significant: 6-minute walk (m): -26 +/- 13, 39 +/- 10, 65; mean right atrial pressure (mmHg): 2.1 +/- 0.8, -1.2 +/- 0.5, -3.3; mean pulmonary arterial pressure (mmHg): 0.4 +/- 1.5, -4.7 +/- 1.5, -5.1; cardiac index (L/min per m): -0.09 +/- 0.09, 0.38 +/- 0.06, 0.47; pulmonary vascular resistance (dyne.s.cm): 85 +/- 60, -274 +/- 47, -359. A 45% improvement in functional class was seen in sitaxsentan-treated patients (P = 0.0005). Thus, in the STRIDE-1 subpopulation that met enrolment criteria of previous pulmonary arterial hypertension trials, improvement in efficacy parameters with sitaxsentan therapy was even greater than seen in the entire STRIDE-1 population.
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J. Cardiovasc. Pharmacol. · Nov 2004
A novel combination of opiates and endothelin antagonists to manage pain without any tolerance development.
Several neurotransmitter mechanisms have been proposed as playing a role in the development of morphine tolerance. We provide evidence for the first time that endothelin antagonists can restore morphine analgesia in morphine-tolerant rats and prevent the development of tolerance to morphine. Studies were carried out in rats and mice treated with implanted placebo or implanted morphine pellet. ⋯ Guanosine triphosphate binding was stimulated by morphine and endothelin-1 in non-tolerant mice and not in morphine-tolerant mice; however, guanosine triphosphate binding was stimulated by BQ123 in morphine-tolerant mice and was unaffected in non-tolerant mice. These results suggest that uncoupling of G-protein occurs in morphine tolerance and endothelin antagonist restores the coupling of G-protein to its receptors. A combination use of endothelin antagonist and opiates could provide a novel approach in improving analgesia and eliminating tolerance.
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J. Cardiovasc. Pharmacol. · Nov 2004
Comparative StudyInhibition of both neutral endopeptidase and endothelin-converting enzyme by SLV306 reduces proteinuria and urinary albumin excretion in diabetic rats.
Diabetic nephropathy is a serious complication of diabetes associated with a poor prognosis which deteriorates to end-stage renal disease. Increased urinary excretion of protein and albumin are early clinical markers for diabetic renal disease and increased risk of cardiovascular disease. Diabetes causes activation of the renal endothelin system inducing renal damage. ⋯ Computer-aided image analysis revealed that renal interstitial matrix content was significantly decreased in diabetic rats treated with either the angiotensin-converting enzyme inhibitor or the neutral endopeptidase/endothelin-converting enzyme inhibitor as compared to untreated diabetic rats. It was found that SLV306 decreases renal matrix protein content as well as protein and albumin excretion in diabetic rats independent of blood pressure. These effects are comparable to those of angiotensinconverting enzyme inhibition.
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J. Cardiovasc. Pharmacol. · Nov 2004
Comparative Study Clinical TrialNitric oxide inhalation modulates endothelin-1 plasma concentration gradients following left ventricular assist device implantation.
Inhaled nitric oxide (iNO) therapy is an effective treatment of pulmonary hypertension following left ventricular assist device (LVAD) implantation. As iNO may also modulate circulating endothelin-1 (ET-1) and big endothelin following LVAD implantation, we investigated the effects of iNO on ET-1 and big endothelin plasma concentration gradients. In order to assist weaning from cardiopulmonary bypass, iNO was administered to 15 consecutive patients with secondary pulmonary hypertension following implantation of a LVAD. ⋯ Big endothelin plasma concentration gradients were not altered significantly. The decrease in ET-1 plasma concentration gradients during and after iNO administration may reflect a restoration of the physiologic balance between the different vascular beds. This provides further evidence that intermittent iNO therapy may modulate ET-1 after LVAD implantation.