title: Short-term cardiovascular effects of selective phosphodiesterase 3 inhibitor olprinone versus non-selective phosphodiesterase inhibitor aminophylline in a meconium-induced acute lung injury.
abstract: Various anti-inflammatory drugs have been used for treatment of neonatal meconium aspiration syndrome (MAS). As their adverse effects are poorly described, this study compared effects of selective phosphodiesterase (PDE) 3 inhibitor olprinone and non-selective PDE inhibitor aminophylline on cardiovascular parameters in animal model of MAS. Oxygen-ventilated rabbits were intratracheally instilled 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were intravenously given olprinone (0.2 mg/kg) at a single dose at 0.5 h after meconium instillation, or aminophylline (2.0 mg/kg) at two doses at 0.5 and 2.5 h after meconium instillation, or were left without treatment. Cardiovascular changes were evaluated within 5 min of administration and 5 min after finishing the administration. Furthermore, respiratory and cardiovascular parameters were measured within 5 hours following treatment delivery. Oxidation markers (thiobarbituric acid-reactive substances (TBARS), and total antioxidant status) and markers of cardiovascular injury (aldosterone, gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)) were determined in the plasma. Meconium instillation induced acute lung injury associated with oxidative stress, elevated aldosterone, and slightly increased GGT and AST levels. Both aminophylline and olprinone improved lung functions and reduced oxidation stress. However, the PDE inhibitors acutely increased blood pressure and heart rate, whereas heart rate variability remained higher till the end of experiment and correlated well with markers of cardiovascular injury. Considering that systemic administration of olprinone and aminophylline was accompanied by acute cardiovascular changes in the meconium-instilled animals, use of PDE inhibitors in the newborns with MAS should be carefully monitored.
authors.affiliation: Department of Physiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovakia. mokra@jfmed.uniba.sk.
authors.forename: D
authors.initials: D
authors.lastname: Mokra
authors.forename: I
authors.initials: I
authors.lastname: Tonhajzerova
authors.forename: H
authors.initials: H
authors.lastname: Pistekova
authors.forename: Z
authors.initials: Z
authors.lastname: Visnovcova
authors.forename: J
authors.initials: J
authors.lastname: Mokry
authors.forename: A
authors.initials: A
authors.lastname: Drgova
authors.forename: M
authors.initials: M
authors.lastname: Repcakova
authors.forename: A
authors.initials: A
authors.lastname: Calkovska
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D000410:Alanine Transaminase / Q000097:blood; D000450:Aldosterone / Q000097:blood; D000628:Aminophylline / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles; D008471:Meconium Aspiration Syndrome / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D018384:Oxidative Stress; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D011728:Pyridones; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D017392:Thiobarbituric Acid Reactive Substances; D000628:Aminophylline; D000450:Aldosterone; C059498:olprinone; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase