Robert F. Reder

Does Triggered Activity Have a Role in the Genesis of Cardiac Arrhythmias

Whether triggered activity plays a role in the genesis of cardiac arrhythmias is considered in this review. The characteristics of triggered activity are compared with those of automaticity and re-entry at the cellular electrophysiologic level, and these observations then are related to cardiac arrhythmias. We stress, however, that the relation between triggered activity and clinical arrhythmias still is largely speculative and that further experimental and clinical study is needed before the presence (or absence) of a role for triggered activity is verified.

Developmental changes in alpha adrenergic effects on canine Purkinje fiber automaticity.

Canine cardiac Purkinje fiber automaticity is modified by adrenergic agonists. Alpha adrenergic agonists slow and beta agonists increase the rate of automatic discharge. These effects vary with maturation and development. We used standard microelectrode techniques to study the effects of the alpha agonist, phenylephrine, on automaticity in isolated neonatal (less than 10 days) and adult canine cardiac Purkinje fibers. Fibers were superfused with 5 X 10(-8) M phenylephrine dissolved in Tyrodes solution. 75% (24/32) of adult and 52% (12/23) of neonatal fibers showed a decrease in rate. The magnitude of the decrease was similar at both ages and the effect was blocked during superfusion with 1 X 10(-9) M phentolamine. The remaining adult and neonatal fibers demonstrated a significant increase in rate in response to 5 X 10(-8) M phenylephrine. This effect was blocked by 5 X 10(-7) M propranolol in the adult group but not in the neonates. However, the increase in rate of fibers from 0- to 2-day neonates was blocked by phentolamine. As an indicator of adrenergic innervation of neonatal hearts, we assayed the myocardial norepinephrine concentration. There was a 6- to 8-fold increase in concentration during the first 10 days of neonatal life, suggesting that innervation was rapidly increasing during this time. In summary, neonatal Purkinje fibers can show an alpha adrenergic-induced acceleration of automatic rate. This alpha adrenergic acceleration is not seen in adults. The change in response from neonate to adult may be effected by growth and development of autonomic nerves and associated changes in receptor function.

Sphygmomanometry in the pediatric patient

The indirect measurement of blood pressure in the pediatric population is often difficult or impossible to perform and when values are obtained, they are often unreliable or inaccurate. An accurate measurement of arterial systolic pressure in the upper extremity is obtainable with a properly designed and sized occluding cuff and an ultrasonic device to detect the first Korotoff sound. For the detection of the first Korotkoff sound ultrasonic Doppler devices are superior to the stethoscope. When wider occluding cuffs than usual are applied to the upper extremity, the error of measurement is minimized. A method for accurately measuring end diastolic pressure has yet to be described despite assertions to the contrary.

Developmental Changes in the Interactions of Cholinergic and |[beta]|-Adrenergic Agonists on Electrophysiologic Properties of Canine Cardiac Purkinje Fibers

ABSTRACT. The parasympathetic nervous system attenuates the effects of sympathetic interventions on the hearts of mature animals. Whereas the vagal mediator, acetylcholine (ACh), alone has minor effects on electrophysiologic properties of the ventricular conducting system, in the presence of sympathetic amines, it induces an accentuated antagonism. Because there are developmental changes in both sympathetic and parasympathetic effects on the heart we studied the parasympathetic and sympathetic interaction in isolated neonatal canine Purkinje fibers (PF), and compared the results to those in adult PF. PF were exposed to isoproterenol (Iso) alone (1 x 10-9, 1 x 10-7 and 1 x 10-5 M) to ACh alone (1 x 10-7 or 1 x 10-5 M) and to Iso in the presence of ACh. In adult PF, supervision with Iso, 10-5 M, alone shortened action potential duration to 50% repolarization from a control value of 215 ± 9 to 200 ± 9. ms (p < 0.01). Simultaneous superfusion of adult PF with Iso 10-5 M and Ach 10-5 M decreased the extent of action potential shortening produced by Iso, so that action potential duration to 50% repolarization shortened from a control value of 221 ± 8 to only 214 ± 12 ms (p < 0.01). The response to superfusion with Iso and Ach (10-5 M) differed significantly from that with Iso alone (p < 0.01). In contrast, exposure of neonatal PF to Iso (10-5 M) prolonged action potential duration to 50% repolarization from a control value of 157 ± 7 to 180 ± 5 ms (p < 0.01). No inhibition of the effect of Iso by Ach (10-7 or 10-5 M) was observed in neonatal PF. At neither age did ACh, alone, exert a significant effect. Our data suggest that accentuated antagonism is not present in young animals having an immature autonomic nervous system, but that it occurs subsequent to maturation.

Left Ventricle to Aorta Valved Conduit for Relief of Diffuse Left Ventricular Outflow Tract Obstruction

Operative relief of congenital tunnel subaortic stenosis by means of local incision or excision, or both, has generally been unsatisfactory. The use of a valve-bearing conduit between the left ventricular apex and thoracic aorta offers a predictable means of bypassing the left ventricular outflow obstruction. The procedure was used in a 17 year old girl with an excellent hemodynamic result. The history of operative management with diverting plantation of valved conduits in this position have not been defined, but use of these prostheses appears advisable in severe subvalvular, valvular and supravalvular obstructions that are not readily amenable to predictable and safe surgical palliation. The operation may prove useful in selected cases of idiopathic hypertrophic obstructive cardiomyopathy.

Preparation and electrophysiological characterization of cardiac cell cultures derived from the fetal canine ventricle

We have developed a primary cardiac cell culture preparation using the fetal canine ventricle. These cultures exhibited widespread and synchronous spontaneous contractile activity, were sensitive to isoproterenol and had the following transmembrane action potential characteristics (means +/- SE): maximum diastolic potential (MDP) -70.9 +/- 0.9 mV; maximum velocity of phase 0 (Vmax) 84 +/- 4 V/s (and tetrodotoxin sensitive); amplitude (AMP) 98.9 +/- 1.1 mV; duration at half amplitude (APD50) 244 +/- 10 ms at a spontaneous cycle length of 1,600 +/- 100 ms. APD50 was linearly dependent on spontaneous cycle length (CL) (slope = 67 ms/s). The action potential of the intact fetal canine ventricle of comparable gestational age had MDP = -67.0 +/- 1.1 mV, Vmax = 127 +/- 6 V/s, AMP = 92.2 +/- 1.6 mV and APD50 = 153 +/- 2 ms at a paced CL of 500 ms. We conclude that myocardial cultures derived from the fetal dog ventricle exhibit electrophysiological characteristics similar to those of the intact canine ventricle, thereby making them a possible alternative to avian and rodent cardiac cultures.

CARDIOVASCULAR EFFECTS OF MATERNAL METHADONE ADDICTION IN THE NEWBORN

Systemic hypertension has been observed in a number of infants born to methadone-addicted mothers. A study was designed to determine the characteristics of this hypertensive state. Fifty newboms of mothers participating in the methadone program were selected. Blood pressures were obtained in both a sleeping and in a quiet, wakeful state. In 24 patients (48%) an abnormal elevation in the systolic blood pressure was documented (range: 90 to 120 mmHg.). The majority were normotensive at birth; hypertension usually developed during the third and fourth days of life. The average duration of hypertension was two weeks (range: 3 to 60 days). The following observations concerning the hypertensive state were noted: (1) hypertension was demonstrated both in the presence and absence of withdrawal symptoms. Normal blood pressures were observed in several patients with obvious withdrawal, (2) elevated blood pressure persisted several weeks after withdrawal symptoms ceased and was unaffected by usual treatment for withdrawal, (3) hypertension was unrelated to serum electrolytes, serum catecholamines, or maternal blood pressure. Electrocardiograms of 18 patients (36%) displayed abnormalities of the ST segments, T waves, and/or QT intervals. Congenital heart disease was documented in three patients (6%). Transient hypertension seems the most common cardiovascular abnormality in infants born to methadone-addicted mothers.

Autonomic Effects in the Developing Heart

Embryonic and fetal hearts have been studied for over 300 yr. Initially, the effects on the rate of impulse generation of various physical factors (e.g., temperature) and chemicals were observed. Later, cardiac electrophysiologic properties, including the characteristics of transmembrane action potentials, were investigated. Changes related to age and development were observed in these studies, the vast majority of which utilized the chick embryo and, to a lesser extent, the rat embryo. Although the heart of the human embryo or fetus has been studied, it has not been possible to perform detailed electrophysiological studies over the entire gestational period.

EVALUATING INDIRECT BLOOD PRESSURE TECHNIQUES|[ndash]|A COMPARATIVE STUDY

An accurate systolic blood pressure (SBP) can now be measured indirectly in all infants & children with an ultrasonic flow detector (UFD) and an inflatable cuff of appropriate size & design. Two semi-automatic blood pressure devices, Arteriosonde 1010 (A) & Infrasonde (I), are purported to accurately measure both SBP and diastolic blood pressure (DBP). A two-Pronged study was designed to evaluate the accuracy of indirect blood pressure obtained with A, I, & a new plastic (Pedisphyg) cuff (PC). In part one, with the cuff of either A, I, or PC systems applied to the upper arm in random and sequential fashion & with a catheter in the ipsilateral subclavian artery, simultaneous direct & indirect pressures were recorded & compared. In part two, A, I, & PC systolic BP values alone were compared by performing simultaneous measurements on both upper arms of selected infants previously shown to have identical SPP in both arms. Comparisons were made hy random application of A, I, & PC to each arm. In this two-pronged study, 125 comparisons revealed that (1) with a properly sized plastic cuff and an ultrasonic flow detector, systolic BP can be measured accurately but not diastolic BP, (2) A & I frequently fail to sound a distinct signal to mark SBP accurately, & even with a relatively good signal the plastic cuff & UFD system is more accurate than A or I, (3) neither A nor I accurately marks DBF and should not he relied upon for this measurement.