Barbara J Buckley

Cardiac effects of esophageal stimulation: possible relationship between gastroesophageal reflux (GER) and sudden infant death syndrome (SIDS)

Twenty-six artificially ventilated newborn pigs were subjected to simulated gastroesophageal reflux; saline (10 cc) of varying pH was flushed through the esophagus from below. At a given pH threshold, reflex bradycardia, which could be blocked by atropine, was elicited. Transecting of the superior laryngeal nerves, the recurrent laryngeal nerves, and the pharyngeal plexus nerves did not block the reflex bradycardia. However, bypassing the regions superior to the esophagus with a shunt prevented the bradycardia. These results indicate that bradycardia caused by gastroesophageal reflux is independent of changes in ventilation and may be an important cause of sudden infant death.

Cardiac responses elicited by stimulation of loci within stellate ganglia of developing swine

Stimulation with bipolar electrodes of specific loci in stellate ganglia elicited in anesthetized piglets, 1-4 weeks of age, alterations in cardiac function and aortic pressure. Responses were also elicited by chemical stimulation in specific loci of these ganglia. The probability of eliciting a cardiovascular response by stimulating loci in a stellate ganglion increased with increasing postnatal age. For instance, no responses were elicited when loci in the left stellate ganglia of 1-week-old piglets were stimulated. Significant heart rate responses were obtained only when loci in right stellate ganglia were stimulated. The number of ganglionic loci from which cardiovascular responses were obtained increased with increasing postnatal age. It is concluded that the capacity of stellate ganglion neurons to modulate the cardiovascular system matures during the first four weeks of life, heart rate being modulated primarily by neurons in the right stellate ganglion and inotropism by neurons in both stellate ganglia.

Chest Pain, Dyspnea on Exertion, and Exercise Induced Asthma in Children and Adolescents

The contribution of maximal exercise tests to the evaluation of 180 patients with chest pain associated with exercise (n = 147) or dyspnea on exertion (DOE, n = 33) was examined. The ages ranged from 5 to 22 (mean 13.2) years, and 68 patients were females. All patients had a normal cardiovascular examination, electrocardiogram, chest x-ray, and 2D-echocardiogram. Maximal exercise tests were performed on a treadmill or bicycle ergometer, and flow volume loops were performed before and after exercise (n = 65). Exercise tests did not reveal any cardiovascular abnormalities, but 14 patients with chest pain (9.5%) and seven patients with DOE (21.2%) developed exercise-induced asthma. Postexercise decrease in peak expiratory flow rate was 26.2 ± 3.7 percent in patients with chest pain and 39.4 ± 8.9 percent in those with DOE. Only five patients had a personal history and four others had a family history of asthma. Seven patients had a personal or family history of allergies. Implications: 1) exercise-induced asthma should be considered in pediatric patients with symptoms of chest pain or dyspnea on exertion; 2) when exercise tests are performed, flow volume loops should be included before and after exercise; 3) maximal exercise tests are unlikely to unmask any cardiovascular abnormalities in such patients.

Age-Related Effects of Single Injections of Dopamine on Cardiovascular Function in Developing Swine

The cardiovascular effects of single intravenous injections of dopamine (DPA; 2, 5, 10 and 25 micrograms/kg) were evaluated in swine, less than or equal to 1 day to 2 months of age, anesthetized with halothane in 50% N2O-O2. Mean aortic pressure increased following all doses of DPA in swine less than or equal to 1 month of age. Renal vasoconstriction was obtained with 5-25 micrograms/kg in the younger animals and with 25 micrograms/kg in the oldest. After 2 micrograms/kg, renal vasodilation occurred in 2-month-old swine. Femoral and carotid vasoconstriction was elicited in day-old swine after 5-25 micrograms/kg DPA, but carotid vasodilation occurred in the oldest swine. Responses to 25 micrograms/kg DPA after combined alpha and beta adrenergic receptor blockade were generally vasodilator. Thus, dopaminergic receptors were unmasked and a postnatal maturation of these receptors was revealed.

Maturation-related differences in regional circulatory effects of dopamine infusion in swine.

The cardiovascular effects of dopamine (DPA) infusions were evaluated in developing swine, less than or equal to 1 day, 2 weeks, and 2 months of age, anesthetized with halothane in 50% N2O and O2. DPA was given by intravenous infusion in randomized doses of 2, 5, 10 and 20 micrograms/kg/min for 10 min. Depressor responses and bradycardia were observed during 2 micrograms/kg/min in 2-week-olds and during 2, 5 and 10 micrograms/kg/min in 2-month-olds. During infusion of 20 micrograms/kg/min, DPA pressor responses were observed in animals less than or equal to 2 weeks of age; in addition, tachycardia occurred in 1-day-old swine. Renal resistance decreased during infusion of 2 micrograms/kg/min in all swine. It increased during 10 and 20 micrograms/kg/min in the 1-day and 2-week groups, but not in the 2-month group. Mesenteric resistance decreased during infusion of 2, 5 and 10 micrograms/kg/min in less than or equal to 2-week-olds and at all doses in 2-month-olds. Following combined alpha- and beta-adrenergic receptor blockade, infusion of 20 micrograms/kg/min DPA inhibited renal vasoconstriction in most animals and elicited mesenteric vasodilation in all. The results indicate that dopaminergic responses undergo a postnatal maturation which has a different time course for different regional circulations.

Cardiovascular and respiratory responses to right atrial injections of phenyl diguanide in pentobarbital-anesthetized newborn piglets.

Summary: The present series of experiments was designed to determine whether the piglet has mature cardiorespiratory responses to the administration of phenyl diguanie (PDG) similar to those reported in adult mammals. A total of 26 acutely instrumented piglets aged 2–23 days were lightly anesthetized with sodium pentobarbital. After control conditions were established, PDG was injected into the right atrium. Each animal was its own control for determination of presence and magnitude of aortic pressure, heart rate, respiratory rate and volume, and blood flow responses to test doses of PDG. A fall in blood pressure was observed in all animals within 2–4 sec after right atrial injection of PDG. Bradycardia occurred and a transient cardiac arrhythmia, consisting of 2nd and 3rd degree heart block, was observed in most animals; the latter has not been previously reported. Apnea followed by rapid shallow breathing was observed in most animals. This respiratory effect was more pronounced in the younger animals. After atropine, PDG elicited a monophasic rise in aortic pressure; the cardiac rhythm and rate changes were abolished. However, the apneic response was retained. Subsequent bilateral vagotomy abolished the hypotensive effect on PDG. Such results suggest the possibility that the piglets cardiorespiratory response to the administration of PDG may be evoked by stimulation of type J pulmonary receptors. These have been postulated to be responsible for the triad of responses of hypotension, bradycardia, and apnea seen in other species after PDG administration.Speculation: At present, there is no explanation for the apnea and bradycardia observed in premature infants with Respiratory Distress Syndrome and/or a large patent ductus arteriosus. Mild interstitial pulmonary edema has been postulated to be the physiologic stimulus for the type J (juxtacapuiary) pulmonary receptor. The authors speculate that the piglets response to PDG which includes apnea, hypotension, and bradycardia may be mediated by artificial stimulation of the J receptor. It is possible that in the human neonate, an immaturely controlled or an inappropriately strong response to the pathophysiologic stimulation of pulmonary edema may be a mechanism for the clinical symptoms of apnea and bradycardia in the small neonate.

Comparative effects of bicarbonate and dichloroacetate in newborn swine with hypoxic lactic acidosis.

UNLABELLED Sodium bicarbonate (BC) and dichloroacetate (DCA) were studied in 7- to 14-day-old (n = 25) anesthetized swine with hypoxic acidosis. BC (base deficit X kg X 0.3, n = 10), DCA (300 mg/kg, n = 7) or saline (n = 8) was infused for 1 h. Blood lactic acid, dP/dtmax, heart rate and cardiac output increased and base excess and total arterial and carotid resistances (R) decreased with acidosis; aortic pressure, renal and mesenteric R did not change. BC induced higher pH, base excess and lactic acid. Heart rate in all and dP/dtmax with BC and DCA were restored; renal and mesenteric R and aortic pressure decreased in all. Cardiovascular responses to DCA and BC did not differ except for renal R. CONCLUSION BC is a more effective alkalizer than DCA, which induced a greater renal vasodilation; both restored contractility.

Increasing extracellular calcium concentration does not prevent hypotensive effects of verapamil in neonatal swine

Effects of CaCl2 on cardiac function and regional circulatory responses to verapamil (V) infusion were studied in pentobarbital-anesthetized 2-week-old swine. V 100 micrograms/kg (n = 15) or 300 micrograms/kg (n = 15), given as a 2-min intravenous infusion, was repeated after 30 min. Only V was given to 15 of these. The other 15 were given CaCl2 (15 mg/kg) over 2 min, pre-V (protocol A), and over 4 min, 2 min pre-V and during V (protocol B). Positive chronotropic and negative inotropic responses to V were attenuated by CaCl2; hypotensive effects were unaltered. Renal, but not mesenteric and femoral, vasodilation was augmented by CaCl2, CaCl2 alone produced marked positive inotropic and renal vasodilatory effects which contributed to maintenance of the hypotensive effect of V.

Age-Dependent Cardiovascular Effects of Verapamil in Newborn Swine

ABSTRACT. Since there are limited studies concerning the hemodynamic effects of verapamil in pediatric patients, cardiovascular effects of clinical doses (100 or 300 μ/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 %Δ ± 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 μ/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 μ/kg verapamil in 2 wk olds. After infusion of 300 μ/kg verapamil ended, heart rate decreased and reached the nadir (—10.0 ± 2.9) by 10 min in 2 wk olds. Decreases in renal resistance (—7.6 ± 1.7) were not dose dependent while superior mesenteric resistance decreased (—12.9 ± 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.

Resetting of the Baroreceptor-Heart Rate Reflex in Coarcted Neonates

The long-term effect of periductal aortic coarctation (COARCT) on baroreceptor (BARO) responses and renal hypertension have been reported [1–3]. However, the cardiovascular (CV) effects of COARCT in the neonatal period have not been investigated. We have established a model of COARCT in newborn swine to investigate the pathophysiology of CV regulation in this disease. This paper reports that resetting the BARO-heart rate (HR) reflex occurred along with changes in peripheral circulatory dynamics in the neonatal period.