BACKGROUND: Infants may be more sensitive than adults to myocardial depression by potent inhalation anesthetics. Most studies of cardiovascular effects of inhalation agents in infants are performed in vivo with multiple factors producing the observed effects. The purpose of this study was to determine if newborns are more sensitive than adults to the direct actions of halothane and isoflurane on global electrophysiologic, contractile and metabolic functions of the heart. METHODS: Direct myocardial effects of the agents were determined using isolated rabbit hearts perfused at constant pressure. Three doses of halothane and isoflurane were administered to 37 infant (3-8 days old) and 36 adult rabbit hearts. Heart rate and rhythm, atrioventricular conduction time, left ventricular function (systolic, diastolic, and developed pressures; maximum and minimum values of the differential wave (dP/dt); and time constant of isovolumic LV relaxation), coronary flow and O2 consumption, and fractional O2 extraction were measured and compared between age and anesthetic groups. RESULTS: Halothane was a more potent depressant of cardiac function than isoflurane and developmental differences were more evident with this agent. The most striking developmental differences in anesthetic effects were the significantly greater prolongation of atrioventricular conduction time and the time constant of isovolumic LV relaxation by halothane in infant compared with adult hearts. Infant hearts were also more sensitive to depression of left ventricular developed pressure and maximum value of the differential wave and to elevation of diastolic pressure by halothane. For both agents heart rate was less depressed in infants than in adults. There were no developmental differences in anesthetic effects on coronary flow and O2 metabolism. CONCLUSIONS: Developmental changes in myocardial physiology make the newborn less sensitive to direct depression of heart rate by halothane and isoflurane, but more sensitive to depression of contraction-relaxation and atrioventricular conduction by halothane.
BACKGROUND:Infants may be more sensitive than adults to myocardial depression by potent inhalation anesthetics. Most studies of cardiovascular effects of inhalation agents in infants are performed in vivo with multiple factors producing the observed effects. The purpose of this study was to determine if newborns are more sensitive than adults to the direct actions of halothane and isoflurane on global electrophysiologic, contractile and metabolic functions of the heart. METHODS: Direct myocardial effects of the agents were determined using isolated rabbit hearts perfused at constant pressure. Three doses of halothane and isoflurane were administered to 37 infant (3-8 days old) and 36 adult rabbit hearts. Heart rate and rhythm, atrioventricular conduction time, left ventricular function (systolic, diastolic, and developed pressures; maximum and minimum values of the differential wave (dP/dt); and time constant of isovolumic LV relaxation), coronary flow and O2 consumption, and fractional O2 extraction were measured and compared between age and anesthetic groups. RESULTS:Halothane was a more potent depressant of cardiac function than isoflurane and developmental differences were more evident with this agent. The most striking developmental differences in anesthetic effects were the significantly greater prolongation of atrioventricular conduction time and the time constant of isovolumic LV relaxation by halothane in infant compared with adult hearts. Infant hearts were also more sensitive to depression of left ventricular developed pressure and maximum value of the differential wave and to elevation of diastolic pressure by halothane. For both agents heart rate was less depressed in infants than in adults. There were no developmental differences in anesthetic effects on coronary flow and O2 metabolism. CONCLUSIONS: Developmental changes in myocardial physiology make the newborn less sensitive to direct depression of heart rate by halothane and isoflurane, but more sensitive to depression of contraction-relaxation and atrioventricular conduction by halothane.
Authors: Leslie C Thompson; Allen D Ledbetter; Najwa Haykal-Coates; Wayne E Cascio; Mehdi S Hazari; Aimen K Farraj Journal: Cardiovasc Toxicol Date: 2017-04 Impact factor: 3.231