Acute hemodynamic effects of piroximone (MDL 19,205) in patients with moderate congestive heart failure: comparison with sodium nitroprusside

Piroximone (MDL 19,205), a new imidazolone derivative, was given intravenously to 14 patients with congestive heart failure (NYHA class II-III), while under constant daily doses of digitalis and diuretics. In the first 3 patients, we determined the dose safely eliciting a favorable hemodynamic response. The subsequent 11 patients received 1 mg/kg of piroximone intravenously, and the hemodynamic effects were compared with those of sodium nitroprusside (SN) at a dose-lowering mean blood pressure by 10-20 mm Hg. Piroximone increased heart rate (13.2 +/- 2.0 beats/min, mean +/- SEM) and lowered mean arterial pressure (9 +/- 2.3 mm Hg). Both agents reduced similarly wedge pressure (6.5 +/- 2.9 and 9 +/- 2.9 mm Hg, respectively, for SN and piroximone) and total peripheral resistance. Cardiac index was increased less by SN (15%) than piroximone (48%) (p less than 0.001), and stroke work index significantly enhanced only by piroximone (p less than 0.001). The changes in loading conditions induced by the two agents being similar, it is likely that piroximone not only acts by peripheral vasodilation, but also possesses positive inotropic properties. Myocardial oxygen demand, assessed indirectly by tension-time index, was not affected by piroximone. Thus, piroximone appears to combine well-balanced vasodilator and inotropic properties which make this new agent potentially very useful for the management of congestive heart failure.     

Immunohistochemical characterization of extracellular matrix in the developing human cornea

Collagen, fibronectin and laminin are important components of the extracellular matrix of the human cornea. We used the immunofluorescence technique with polyclonal antibodies directed against these proteins and to bullous pemphigoid antigen (BPA), in order to study their distribution in human corneas from 8 weeks of gestation to term and in adult corneas. Immunoreactivity was observed with antibodies to type I collagen in the limbus and the corneal stroma at 8 weeks of gestation. At 11 weeks of gestation it was found in epithelial basement membrane (EBM) and Descemet's membrane (DM) and continued thus throughout fetal and adult life. Type II collagen was not detected in fetal or adult cornea. Type III collagen was detected during 8-20th weeks of gestation in the EBM, DM and stroma. After 27th weeks of gestation, type III collagen could no longer be detected in the central cornea. Type IV collagen was detected in the EBM as early as 8 weeks of gestation and remained positive throughout fetal and adult life. Descemet's membrane was negative for type IV collagen at 8 weeks of gestation and became positive thereafter. Immunostaining for fibronectin in DM was negative at 8 weeks of gestation, followed by patchy staining of corneal stroma and EBM up to the age of 37 weeks of gestation. Staining in the EBM was negative or variable up to 70 years of age, and then became positive again in a 77 year old individual. Staining for LN was positive in the EBM after 8 weeks of gestation. Staining was negative in DM at that age, but became positive after 9 weeks of gestation. Staining for BPA was negative at 8-9 weeks of gestation, then gradually became positive.