The role of beta-adrenoreceptor stimulation and contractile state in the preterm lamb's response to altered ductus arteriosus patency.
A model of patent ductus arteriosus in premature lambs was created to study the relative importance of beta-adrenoreceptor stimulation and increased myocardial contractility. In 39 fetal lambs (133 +/- 2, +/- SD days gestation, term 145 days), the ductus arteriosus was infiltrated with formalin, and a snare was placed around it to regulate its patency. One day later, the lambs were delivered, given sheep surfactant, paralyzed, and mechanically ventilated. Microsphere measurements of left ventricular output were made between 4 and 6 h after delivery. When the ductus was opened, there was no change in heart rate, but there were significant increases in left ventricular output, stroke volume, left ventricular end-diastolic pressure, and peak dP/dt. The increase in peak dP/dt due to opening the ductus was greater than that due to an increase in left ventricular end-diastolic pressure alone and was accompanied by an increase in norepinephrine secretion from the left ventricle. Propranolol (1 mg/kg) was used to evaluate the effect of beta-adrenergic tone on left ventricular output and contractility. The left atrium was paced in both control and propranolol-treated lambs. When the ductus was closed, propranolol significantly decreased stroke volume and peak dP/dt without changing left ventricular end-diastolic pressure or systemic vascular resistance. During a saline volume load (50 ml/kg over a 3-min period), propranolol-treated lambs had a reduced stroke volume and peak dP/dt despite similar values of left ventricular end-diastolic pressure and resistance as those of control lambs.(ABSTRACT TRUNCATED AT 250 WORDS)
Clyman
R I
RI
Cardiovascular Research Institute, University of California, San Francisco 94143.
Teitel
D
D
Padbury
J
J
Roman
C
C
Mauray
F
F
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004374:Ductus Arteriosus, Patent / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects*; D011247:Pregnancy; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D011433:Propranolol