Age-Dependent Cardiovascular Effects of Verapamil in Newborn Swine

Abstract

ABSTRACT. Since there are limited studies concerning the hemodynamic effects of verapamil in pediatric patients, cardiovascular effects of clinical doses (100 or 300 pg/kg) of verapamil, given as a 2-min intravenous infusion, were examined in sodium pentobarbital anesthetized swine, aged 1 day (n = 15) and 2 wk (n = 18). Aortic and left ventricular pressures, index of left ventricular contractility, heart rate, and phasic superior mesenteric, renal, and femoral arterial flows were recorded; mean aortic pressure and vascular resistances were calculated. Maximum changes in cardiovascular function (mean %A -C SEM) occurred at the end of the infusion. Mean aortic pressure and index of left ventricular contractility decreased in all animals; responses were larger in magnitude with the higher dose. By 30 min after infusion of 300 pg/kg verapamil had ended, mean aortic pressure in both 1 day and 2 wk olds and index of left ventricular contractility and femoral flow in 1 day olds were still decreased. During infusion of verapamil, heart rate decreased (-11.6 + 2.9) to the high dose in 1 day olds but increased (+6.4 +. 2.7) to 100 and 300 pglkg verapamil in 2 wk olds. After infusion of 300 pglkg verapamil ended, heart rate decreased and reached the nadir (-10.0 f 2.9) by 10 min in 2 wk olds. Decreases in renal resistance (-7.6 f 1.7) were not dose dependent while superior mesenteric resistance decreased (-12.9 2 2.7) only to low dose verapamil in 2 wk olds. In 1 day olds decreases in renal and superior mesenteric resistance were not sustained throughout the infusion. The results indicate that verapamil has both age-and dose-dependent cardiovascular effects in newborn swine and suggest that verapamil be used with caution in infants. (Pediatr Res 20: 428-432, 1986) Abbreviations AoP, aortic pressure -AoP, mean aortic pressure ECG, electrocardiogram HR, heart rate LV, left ventricular LV dP/dt max, index of LV contractility R, resistance iv, intravenous While verapamil is widely used in children and infants for the treatment of supraventricular tachycardia (1-5), adverse effects such as profound hypotension and arterioventricular block have been reported (1, 4, 6, 7). In piglets (aged 18 a 6 days) with hypoxic pulmonary hypertension, verapamil infusion (150 pg/ kg over 2 min) decreased systemic and pulmonary artery pressures (8). In puppies a bolus injection of 400 pg/kg verapamil reduced stroke volume and blood flow velocities in aorta and carotid and femoral arteries (9); these effects were not observed in adult dogs.Since there is little information available concerning the cardiac and regional circulatory effects of verapamil in the newborn period (%-lo), we undertook to study the hemodynamic responses to verapamil in two ages of young swine to further the understanding of the pharmacology of verapamil in pediatrics as a function of postnatal development. MATERIALS AND METHODSAnimal preparation. Two age groups of neonatal swine were used in this study: 1 day (< 24 h old; n = 15) and 2 wk (12-16 days; n = 8). These t...

Increasing Extracellular Calcium Concentration Does Not Prevent Hypotensive Effects of Verapamil in Neonatal Swine

“…The results of these experiments confirmed our ear lier report that cardiovascular variables examined in this study returned to control levels by 30 min after a 2-min V infusion of 100 or 300 pg/kg in 2-week-old piglets [8]. In each animal, the designated V infusion dose was then repeated 30 min later.…”

“…Animal Preparation Thirty 2-week-old swine (mean age 14.3 ± 0.2 days; mean body weight 3.0 ± 0.2 kg) were anesthe tized with intraperitoneal sodium pentobarbital (25 mg/kg); supplemental doses were administered in travenously at one tenth the initial dose as needed throughout the experiment, as in our previous study [8]. Tracheostomy was performed and the animals were ventilated on a Palmer respirator.…”

“…The following procedures were carried out as in our previous study [8], The abdominal aorta was catheterized via the right femoral artery for measure ment of aortic pressure and for blood gas sampling. ECG, heart rate (HR), AoP, LVP, LV dP/dt and flows were recorded continuously on a SensorMedics R611 dynograph.…”

“…The animals were then treated randomly and received either 100 pg/kg (n = 15) or 300 pg/kg (n = 15) V (Isoptin, racemic mixture, Knoll Pharmaceutical) as a 2-min intravenous infu sion, as in our previous study [8]. Animals in each dose group were again randomly assigned to either control or CaCL protocols which are described be low.…”

“…Verapamil (V) is an effective agent for the treatment of supraventricular tachycardia in infants and children [1][2][3][4], but its use has resulted in significant adverse effects, in cluding hypotension and dysrhythmias [5][6][7], Maturation-related differences in the ac tion^) of V on the cardiovascular system in developing animals have been reported [8][9][10][11], in particular the findings from this labo ratory [8] that neonatal piglets displayed protracted hypotension and ventricular de pression without evidence of reflex accom modation.…”