To identify amino acid residues involved in PDE3-selective inhibitor binding, we selected eight presumed interacting residues in the substrate-binding pocket of PDE3A using a model created on basis of homology to the PDE4B crystal structure. We changed the residues to alanine using site-directed mutagenesis technique, expressed the mutants in a baculovirus/Sf9 cell system, and analyzed the kine...

OBJECTIVES To investigate the value of targeted neonatal echocardiography (TnECHO) in predicting cardiorespiratory instability after patent ductus arteriosus (PDA) ligation, and to evaluate the impact of TnECHO-directed care. STUDY DESIGN We reviewed serial echocardiography evaluations of 62 preterm infants after PDA ligation to investigate the relationship between indices of myocardial perfo...

The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide contents in the guinea pig gall bladder were investigated. Various selective PDE inhibitors, vinpocetine (type 1), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, type 2), milrinone (type 3), Ro20-1724 (type 4), and zaprinast (type 5), inhibited CCh-induced contractions in a concentrati...

BACKGROUND Postoperative atrial fibrillation (AF), a frequent complication after cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF. METHODS AND RESULTS We evaluated perioperative risk factors in 23...

Milrinone, a new bipyridine compound related to amrinone, is a potent non-adrenergic inotrope in experimental preparations and also shows vasodilator activity. In the present study the haemodynamic and metabolic effects of milrinone were evaluated in 12 patients with congestive heart failure. Milrinone 5 mg given orally produced a sharp reduction in left ventricular end diastolic pressure witho...

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared w...

BACKGROUND Levosimendan was shown to increase calcium sensitivity by a novel mechanism and to inhibit phosphodiesterase III activity in animal myocardium. METHODS AND RESULTS We investigated the influence of levosimendan on isometric contractions and calcium transients (aequorin method) in muscle strips from human hearts with end-stage failing dilated or ischemic cardiomyopathy (n=27). Data w...

UNLABELLED Acute kidney injury (AKI) is a serious complication that occurs commonly following cardiopulmonary bypass (CPB) in infants and children. Underlying risk factors for AKI remain unclear, given changes in CPB practices during recent years. This retrospective, case-control study examined the relationships between patient, perioperative factors, AKI, and kidney failure in children who und...