Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Jan 1995
Randomized Controlled Trial Comparative Study Clinical TrialHemodynamic and humoral effects at rest and after head-up tilt tests during 24-hour infusion of a new nitrate ester, ITF 296, compared with ISDN and placebo in healthy volunteers: a double-blind, randomized, within-subject study.
A double-blind, randomized, three-way complete crossover study was carried out to compare pharmacodynamic effects and tolerability during a 24-h intravenous infusion of ITF 296, isosorbide dinitrate (ISDN), and placebo, in the supine position and during 70 degrees head-up tilt. Ten healthy men aged 21-34 years participated in the study to obtain complete data in nine. Dosing started at 1 microgram/kg/min and was titrated up during the first 30 min of infusion, to produce a 10% reduction in diastolic blood pressure (DBP). ⋯ ISDN caused significantly greater neurohumoral counter-regulation than ITF 296. Hemodynamic response to tilt was attenuated, as judged by the fact that hypotension occurred only during the early hours of the infusion, but the variability in the response of BP to tilt does not allow any firm conclusions to be drawn about possible development of tolerance. Tolerability of ISDN was poor and that of ITF 296 was better.
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J. Cardiovasc. Pharmacol. · Jan 1995
Randomized Controlled Trial Clinical TrialDose-range study of a new calcium sensitizer, levosimendan, in patients with left ventricular dysfunction.
Levosimendan, a new drug that sensitizes troponin-C to calcium and selectively inhibits phosphodiesterase III, was administered to 24 patients with ischemic heart disease and ejection fraction below 40%. In a placebo-controlled, crossover, double-blind study, each patient received two intravenous doses of levosimendan on 2 consecutive study days. The doses were 0.25 mg (n = 6), 0.5 mg (n = 11), 1 mg (n = 12), 2 mg (n = 12), and 4 mg (n = 5). ⋯ Total peripheral resistance decreased significantly only after 2 and 4 mg, by 13 and 21%, respectively. However, there were no statistically significant changes in pulmonary vascular resistance. It is concluded that levosimendan has a hemodynamically favorable action after 0.25 and 0.5 mg but that decreases in filling pressures probably prevented the increase in stroke volume and caused a reflex increase in heart rate after 2 and 4 mg.
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J. Cardiovasc. Pharmacol. · Jan 1995
Pentoxifylline and lung ischemia-reperfusion injury: application to lung transplantation. Université Paris-Sud Lung Transplant Group.
Pentoxifylline (PTX) attenuates neutrophil-mediated lung injury in several models of acute lung inflammation. Because pulmonary neutrophil sequestration is the main determinant of ischemia-reperfusion (IR) injury in lung transplantation, we sought to determine whether or not PTX prevented IR injury in isolated perfused rat and rabbit lungs submitted to IR, and in pigs after left lung allotransplantation. In rat lungs after IR, the coefficient of lung endothelial permeability (Kfc) increased by 112 +/- 12% in controls and by 27 +/- 8% (p < 0.001) in PTX-treated lungs. ⋯ In pigs ventilated with pure oxygen, the PaO2 was greater in the PTX group than in the control group (423 +/- 49 vs. 265 +/- 43 mm Hg; p < 0.05), whereas the total pulmonary vascular resistance was lower (15 +/- 1 vs. 30 +/- 9 mm Hg/L/min; p < 0.02). After reperfusion, the decrease in circulating leukocyte count fell by 35 +/- 3% in the control group and remained unchanged in the PTX group, and the leukocyte count per microscopic field in the transplanted lung was lower in the PTX group than in the control group (p < 0.02). In conclusion, PTX prevented IR lung endothelium injury and improved post-IR lung function by decreasing neutrophil lung sequestration, and this agent might be useful in clinical lung transplantation.