Richard L. Donnerstein

Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.

Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal echocardiography. I. Normal anatomy as determined by real-time--directed M-mode ultrasound.

With current ultrasound technology, it is now possible to obtain accurate real-time and M-mode information from the fetal heart with the use of real-time--directed M-mode echocardiography. With this method, the M-mode cursor is directed to the fetal cardiac structures of interest while the image is obtained in the real-time mode. This enables M-mode echocardiograms to be obtained in an accurate, reproducible manner. The most useful imaging planes for cardiac evaluation are the long axis four-chamber plane, the short axis plane through the atrioventricular valves, and the short axis plane through the aortic and pulmonic outflow tracts. Once normal fetal cardiac anatomy is understood, structural defects and/or alterations of function can be evaluated accurately antenatally.

Fetal echocardiography: II. The diagnosis and significance of a pericardial effusion in the fetus using real-time-directed M-mode ultrasound☆☆☆

By means of real-time--directed M-mode ultrasound, the hearts of normal and abnormal fetuses were evaluated for evidence of a pericardial effusion. Because of its limited potential space, the pericardial sac appears to become distended with fluid prior to ultrasound evidence of ascites, pleural effusions, or soft tissue edema. Fetal echocardiography, therefore, appears to be useful in the assessment of fetuses at risk for developing hydrops.

Dobutamine infusions in stable, critically ill children: Pharmacokinetics and hemodynamic actions

ObjectiveTo delineate dobutamine pharmacokinetics and hemodynamic responses in children. DesignProspective, pharmacokinetic study using sequential, graded dosing of drug. InterventionsGraded intravenous dobutamine infusions of 0.5, 2.5, 5, 10, and 20 μg/kg/min were sequentially administered for 25 mins each. Plasma dobutamine concentrations and echocardiographically determined hemodynamic data were obtained at baseline and at 15 and 25 mins during each infusion rate. Hemodynamic responses were evaluated by paired t-test and by computerized evaluation of individual dose-response curves. SettingPediatric intensive care unit in a university setting. PatientsEleven stable, critically ill children previously requiring inotropic support with dobutamine. Seven patients were postcardiac surgical patients; four patients had acute cardiac dysfunction with septic shock and/or adult respiratory distress syndrome. Measurements and Main ResultsMean cardiac index increased from 3.8 to 5.2 L/min/m2 (p < .05). Increasing the infusion rate from 10 to 20 μg/kg/min increased cardiac index by 16% (p < .05). Cardiac index increased by >10% in four of seven patients at a dobutamine infusion rate of 0.5 μg/ kg/min (mean 21%).The relationship of plasma dobutamine concentration to cardiac index, systolic blood pressure, and heart rate fit a threshold model with a log-linear relationship after the threshold in seven of nine, seven of 11, and eight of 11 patients, respectively. As anticipated, in the patients who responded, there were linear increases in hemodynamic responses with exponential increases in plasma dobutamine concentrations.Mean plasma clearance rate was 82 ± 3 mL/ min/kg. First-order kinetics were demonstrated by the direct linear relationship of plasma dobutamine concentration to infusion rate (mean r2 = .95; p < .01 for each patient) and by independence of clearance from dose and duration of each infusion. ConclusionsDobutamine effectively improves systolic function in critically ill children. Hemodynamic responses to dobutamine generally follow a predicted log-linear dose-response model. Dobutamine clearance in this study was consistent with first-order kinetics. The wide variability in hemodynamic responses and clearance kinetics indicate that dobutamine infusions must be titrated individually. (Crit Care Med 1993; 21:678–686)

Acute effects of caffeine ingestion on signal-averaged electrocardiograms

BACKGROUND Although moderate caffeine ingestion has not been shown to be arrhythmogenic, caffeine toxicity can cause severe cardiac arrhythmias, including atrial fibrillation and ventricular tachycardia. Atrial fibrillation and ventricular tachycardia have been associated with prolongation of P-wave and QRS complex durations on signal-averaged electrocardiograms. This study investigated acute effects of caffeine ingestion on signal-averaged P-wave and QRS complexes. METHODS AND RESULTS Signal-averaged electrocardiograms were obtained from 12 normal subjects (6 men, 6 women; ages 21 to 26 years) before and after ingestion of caffeine (5 mg/kg body weight) or placebo in a randomized, double-blind, crossover fashion. Electrocardiograms for signal averaging were recorded from electrodes left in a constant location. After bandpass filtering (30 to 300 Hz) and amplification, signals were sampled over 7.2 minutes at 2000 Hz. Signal-averaged P-wave and QRS complex durations did not significantly change after placebo ingestion. After caffeine ingestion QRS duration prolonged in 9 of 11 subjects at 90 minutes (mean +/- SEM = 0.8+/-0.3 ms, P< .02) and in 8 of 9 after 3 hours (1.1+/-0.2 ms, P< .001). No significant change in P-wave duration or heart rate was found after caffeine ingestion at any test interval. Average caffeine level in saliva 90 minutes after ingestion was 6.6+/-1.6 (SD) microg/dL. CONCLUSIONS Although probably not arrhythmogenic in normal subjects, moderate caffeine ingestion does produce a small but statistically significant prolongation of signal-averaged QRS complexes. Further prolongation caused by excessive caffeine intake may be a factor in the genesis of arrhythmias associated with caffeine toxicity.

Accuracy of central venous pressure monitoring in the intraabdominal inferior vena cava: A canine study

STUDY OBJECTIVE To test the hypotheses that in multiple pathophysiologic settings (1) end-expiratory central venous pressure measurements in the intraabdominal inferior vena cava accurately reflect those in the superior vena cava and (2) mean central venous pressure monitoring is as reliable in the inferior vena cava as it is in the superior vena cava. DESIGN Simultaneous inferior vena caval and superior vena caval pressures were measured during five ventilatory phases: apnea, end-expiratory mechanical ventilation, maximal inspiratory mechanical ventilation, end-expiratory spontaneous ventilation, and maximal inspiratory spontaneous ventilation. Measurements were repeated after progressive intravascular volume depletion. SUBJECTS Eight puppies. MEASUREMENTS AND RESULTS Simultaneous inferior vena caval and superior vena caval end-expiratory pressures did not differ significantly (mean differences 0 to 0.1 mm Hg) and the limits of agreement of these measurements were within 2 mm Hg. Differences between mean maximal inspiratory pressures in the inferior vena cava and superior vena cava during mechanical and spontaneous ventilation were -0.7 and 3.6 mm Hg, respectively (p less than 0.01), and the limits of agreement extended beyond 2 mm Hg. Furthermore, mean maximal inspiratory pressures in the superior vena cava differed from end-expiratory pressures in the superior vena cava (1.1 and -3.6 mm Hg, p less than 0.01), whereas those in the inferior vena cava did not differ from end-expiratory superior vena caval pressures. CONCLUSIONS Under the experimental conditions studied (1) end-expiratory intraabdominal inferior vena caval pressures accurately reflected end-expiratory superior vena caval pressures and (2) mean central venous pressure monitoring was as reliable in the inferior vena cava as in the superior vena cava.

Continuous spectral analysis of heart murmurs for evaluating stenotic cardiac lesions

Severity of stenotic heart lesions affects timing, quality and pitch of associated heart murmurs. This quantitative study investigated the relation between instantaneous sound frequencies contained in heart murmurs and magnitudes of Doppler jet velocities measured distal to associated obstructions. Heart murmurs were recorded from 18 patients, ages 1 day to 23 years, with 21 separate murmurs resulting from abnormal valves (18 studies) or left-to-right shunts (3 studies). Recorded murmurs were digitized and divided into 12.3-ms time segments for computer frequency analysis using the maximum entropy method. Murmur spectra were plotted in gray scale against time. All murmurs contained dominant frequencies that varied with time. Dominant murmur frequencies and associated Doppler jet velocities at equivalent points in time were measured at 50-ms intervals. For 88 points analyzed, instantaneous dominant frequencies ranged from 130 to 410 Hz (mean +/- standard deviation 282 +/- 70 Hz) and instantaneous jet velocities ranged from 110 to 460 cm/s (290 +/- 80 cm/s). For the 21 murmurs studied, peak murmur frequencies ranged from 200 to 410 Hz (308 +/- 70 Hz) and peak jet velocities ranged from 165 to 460 cm/s (320 +/- 78 cm/s). Instantaneous dominant frequency correlated to instantaneous jet velocity (r = 0.85) and peak dominant frequency correlated to peak jet velocity (r = 0.89). This in vivo study demonstrates that dominant frequencies contained in heart murmurs are related to instantaneous jet velocities distal to associated obstructions.

Hemodynamic effects of acute caffeine ingestion in young adults

This study investigated hemodynamic effects of acute caffeine ingestion in young adults 21 to 26 years of age. Data showed an increase in heart rate corrected velocity of circumferential fiber shortening at an indexed afterload up to 4.5 hours following caffeine consumption.

The influence of myocardial substrate on ventricular fibrillation waveform: A swine model of acute and postmyocardial infarction

Objective:In cardiac arrest resulting from ventricular fibrillation, the ventricular fibrillation waveform may be a clue to its duration and predict the likelihood of shock success. However, ventricular fibrillation occurs in different myocardial substrates such as ischemia, heart failure, and structurally normal hearts. We hypothesized that ventricular fibrillation is altered by myocardial infarction and varies from the acute to postmyocardial infarction periods. Design:An animal intervention study was conducted with comparison to a control group. Setting:This study took place in a university animal laboratory. Subjects:Study subjects included 37 swine. Interventions:Myocardial infarction was induced by occlusion of the midleft anterior descending artery. Ventricular fibrillation was induced in control swine, acute myocardial infarction swine, and in postmyocardial infarction swine after a 2-wk recovery period. Measurements and Main Results:Ventricular fibrillation was recorded in 11 swine with acute myocardial infarction, ten postmyocardial infarction, and 16 controls. Frequency (mean, median, dominant, and bandwidth) and amplitude-related content (slope, slope-amp [slope divided by amplitude], and amplitude–spectrum area) were analyzed. Frequencies at 5 mins of ventricular fibrillation were altered in both acute myocardial infarction (p < .001 for all frequency characteristics) and postmyocardial infarction swine (p = .015 for mean, .002 for median, .002 for dominant frequency, and <.001 for bandwidth). At 5 mins, median frequency was highest in controls, 10.9 ± .4 Hz; lowest in acute myocardial infarction, 8.4 ± .5 Hz; and intermediate in postmyocardial infarction, 9.7 ± .5 Hz (p < .001 for acute myocardial infarction and p = .002 for postmyocardial infarction compared with control). Slope and amplitude–spectrum area were similar among the three groups with a shallow decline after minute 2, whereas slope-amp remained significantly altered for acute myocardial infarction swine at 5 mins (p = .003). Conclusions:Ventricular fibrillation frequencies depend on myocardial substrate and evolve from the acute through healing phases of myocardial infarction. Amplitude related measures, however, are similar among these groups. It is unknown how defibrillation may be affected by relying on the ventricular fibrillation waveform without considering myocardial substrate.

Complex atrial tachycardias and respiratory syncytial virus infections in infants.

Respiratory syncytial virus (RSV), a common cause of respiratory infections in children, has only rarely been associated with acquired heart disease. We reviewed hospital charts, rhythm strips, and electrocardiograms of 8 infants with abnormal supraventricular tachycardia (SVT), > 250 beats/min, associated with acute RSV infections. Cultures of nasopharyngeal specimens from six of eight infants grew RSV. Two infants with negative viral culture results had symptoms typical of an RSV infection during a documented RSV epidemic. Two infants had congenital heart defects. Seven of the eight infants had an ectopic atrial tachycardia, chaotic atrial tachycardia, or atrial flutter, and five of eight had episodes of nonsustained wide-complex SVT. One patient was initially treated with intravenously administered lidocaine for an incorrect diagnosis of ventricular tachycardia. SVT was unrelated to either beta-agonist therapy or hypoxic episodes. SVT did not recur after discharge in any infant with a structurally normal heart. Both patients with structural heart disease had recurrences of SVT. We conclude that RSV infections in infants may be associated with unusual atrial tachycardias and that the diagnosis may be complicated by episodes of nonsustained, wide-complex tachycardias. In patients with RSV and structurally normal hearts, chaotic and ectopic atrial tachycardias are self-limited and do not require prolonged drug therapy.