Reliability and precision of a new thoracic electrical bioimpedance monitor in a lower body negative pressure model.

OBJECTIVE: To evaluate the reliability and precision of measurement in a new thoracic electrical bioimpedance (TEB) monitor. DESIGN: Prospective clinical trial using healthy volunteers. SETTING: Military tertiary care teaching hospital. SUBJECTS: Seventy-five healthy adult volunteers taking no medications. INTERVENTIONS: Induction of severe preload reduction using a standardized lower-body negative pressure protocol. Measurement of hemodynamic variables using a TEB monitor before, during, and immediately after application of negative pressure. MEASUREMENTS AND RESULTS: Seventy-five subjects were enrolled and completed the study. Pulse, blood pressure, stroke index, cardiac index, systolic time ratios (STR), and index of contractility were obtained on all subjects undergoing monitoring with the lower body negative pressure (LBNP) device. Hemodynamic measurements were recorded at 15-sec intervals during incremental application of 0, -10, -20, -40, and -60 mm Hg pressure for 10 mins at each pressure. Maximal tolerated LBNP produced reductions in cardiac, stroke, and contractility indices of 50%, 65%, and 45%, respectively. Pulse and STRs increased 44% and 113%, respectively. The precision of measurement (mean +/- 2 SD) for TEB-derived cardiac and stroke index was 16% and 10%, respectively. Repeatability of measurement was assessed by measuring hemodynamic changes after the abrupt cessation of maximal LBNP. There were significant increases in stroke index (p < .001) and decreases in STRs (p < .001) and pulse (p < .001) 3 mins after LBNP. There was no significant difference between initial and post-LBNP cardiac index (p > .05). Regression equations were applied to scattergram plots of stroke index vs. STRs and index of contractility vs. body mass. The use of these plots allowed elimination of values that appeared to be spurious (stroke index vs. STRs) and also raised the question whether the Sramek-Bemstein equation (stroke volume = left ventricular ejection time x volume of electrically participating tissue x dZ/dt/Zo) fully explained all the factors affecting the TEB waveform. CONCLUSIONS: This new monitor appears to overcome many of the signal processing problems encountered with previous devices. The results clearly demonstrate that accurate and reliable measurement of bioimpedance waveforms is possible and suggest that the monitor is capable of generating precise hemodynamic data across a wide spectrum of hemodynamic alterations. However, the evidence also indicates that new algorithms may be needed to more fully explain the multiple factors affecting this waveform.

Lack of agreement between measurement of ejection fraction by impedance cardiography versus radionuclide ventriculography.

OBJECTIVE: To determine the limits of agreement between left ventricular ejection fraction estimated using systolic time intervals from impedance cardiography and left ventricular ejection fraction estimated by radionuclide ventriculography. DESIGN: A prospective study for diagnostic tests using radionuclide ventriculography as the criterion standard. SETTING: A large military teaching hospital. PATIENTS: Twenty ambulatory adults scheduled for radionuclide ventriculography. MEASUREMENTS AND MAIN RESULTS: A regression equation to estimate ejection fraction from systolic time intervals is available in a widely used impedance-based cardiac monitoring device. The estimated ejection fraction is then used in an equation with stroke volume estimated by the same device to calculate an end-diastolic volume. We studied the agreement of the ejection fraction as estimated by this device with the ejection fraction estimated by radionuclide ventriculography by obtaining simultaneous estimates of ejection fraction over a broad range of adult patients. Twenty ejection fraction pairs were analyzed. The correlation of ejection fraction by impedance cardiography to ejection fraction by radionuclide ventriculography was significant (r2 = .55; p < .002). However, the mean difference between the technologies was -8.85%, with a standard deviation of the differences of 7.15%, resulting in a 95% confidence range for agreement of -23.2% to +5.5%. CONCLUSIONS: The 95% confidence range defining the limits of agreement between ejection fraction by impedance cardiography and ejection fraction by radionuclide ventriculography is not clinically acceptable. In the opinion of the authors impedance cardiography should not be used in place of radionuclide ventriculography for the assessment of ejection fraction at this time.

Thoracic electrical bioimpedance measurement of cardiac output in postaortocoronary bypass patients.

OBJECTIVE: To assess the degree of correlation and agreement between cardiac output by thermodilution and bioimpedance using the BoMed NCCOM3-R7 monitor in postaortocoronary bypass patients. DESIGN: Prospective, randomized sampling. SETTING: Military teaching hospital intensive care unit. PATIENTS: Fifty patients undergoing coronary artery bypass surgery with thermodilution pulmonary artery catheters in place. Simultaneous determination of cardiac output by thermodilution and thoracic bioimpedance was performed. Readings were taken between 8 and 24 hrs after surgery. Forty patients were intubated; 19 patients had left-sided tube thoracotomy in addition to two mediastinal tubes, and 19 patients were obese. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall degree of correlation between the two measures was fair (r2 = .24). The bias and precision measurements were inaccurate as well (-0.33 +/- 3.14). Patients with normal body habitus or who were not receiving mechanical ventilation showed the best correlation (r2 = .40 and r2 = .45, respectively). Only 62% (31/50) of all patients had simultaneous measurements fall within 20% of each other, and there were no clinical features that made identification of those patients possible. CONCLUSIONS: Use of the BoMed NCCOM3-R7 bioimpedance monitor as a replacement for thermodilution-derived cardiac output cannot be recommended in postaortocoronary bypass patients. The distortions of patients' normal anatomy and physiology, coupled with the presence of endotracheal tubes and mechanical ventilation, mediastinal tubes and chest tubes, result in only fair correlation, significant bias, and poor precision between the two measures of cardiac output.

Intrathoracic osteosarcoma diagnosed by CT scan and pleural biopsy.

Osteosarcoma rarely presents as a primary lesion in the chest, whereas pulmonary metastases are common. The diagnosis of primary intrathoracic osteosarcoma has invariably been by thoracotomy or autopsy. We present a case of a densely calcified, primary intrathoracic osteosarcoma where diagnosis was made antemortem by pleural biopsies and computed tomography scan.

Mediation of subacute anthracycline cardiotoxicity in rabbits by cardiac histamine release.

We tested the hypothesis that cardiac histamine release mediates subacute doxorubicin (DXR) cardiotoxicity in rabbits. New Zealand white rabbits given DXR 20 mg/kg i.v. over 30 min developed myocardial damage 24 h later that was similar to that observed in humans. In isolated heart preparations, DXR produced dose-related cardiac histamine release at DXR concentrations of 1, 5, and 25 micrograms/ml given as 1-min exposures. Prior exposure of isolated hearts to 10 microM cromolyn sodium completely prevented histamine release from 5 micrograms/ml DXR. Pretreatment of animals with cromolyn produced significant protection against DXR-mediated subacute cardiotoxicity. We conclude that the release of cardiac histamine may be involved in the pathogenesis of anthracycline cardiotoxicity.

Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts.

To identify the role of the myocardial beta-adrenergic pathway in congestive heart failure, we examined beta-adrenergic-receptor density, adenylate cyclase and creatine kinase activities, muscle contraction in vitro, and myocardial contractile protein levels in the left ventricles of failing and normally functioning hearts from cardiac-transplant recipients or prospective donors. Eleven failing left ventricles had a 50 to 56 per cent reduction in beta-receptor density, a 45 per cent reduction in maximal isoproterenol-mediated adenylate cyclase stimulation, and a 54 to 73 per cent reduction in maximal isoproterenol-stimulated muscle contraction, as compared with six normally functioning ventricles (P less than 0.05 for each comparison). In contrast, cytoplasmic creatine kinase activity, adenylate cyclase activities stimulated by fluoride ion and by histamine, histamine-stimulated muscle contraction, and levels of contractile protein were not different in the two groups (P less than 0.05). We conclude that in failing human hearts a decrease in beta-receptor density leads to subsensitivity of the beta-adrenergic pathway and decreased beta-agonist-stimulated muscle contraction. Regulation of beta-adrenergic receptors may be an important variable in cardiac failure.

Anthracycline-associated cardiac and renal damage in rabbits. Evidence for mediation by vasoactive substances.

We tested the hypothesis that anthracycline-induced cardiac and renal damage is mediated by vasoactive substances. A 1-minute exposure to 5 micrograms per ml. of doxorubicin (DXR, Adriamycin) produced cardiac histamine release in isolated rabbit hearts. Under conditions in which histamine uptake and metabolism were impaired, the administration of DXR, 2 mg. per kg., over 1 minute was associated with elevations in arterial histamine and catecholamines. The chronic weekly administration of DXR produced severe cardiac and renal damage. The administration of combined histaminic and adrenergic blockade with diphenhydramine, cimetidine, phentolamine, and propranolol (DCPP) pre- and immediately post-DXR resulted in near total protection against DXR-mediated cardiac damage and prevented the majority of the renal lesions. The combined administration of diphenhydramine, cimetidine, phentolamine, and propranolol did not appear to be acting by mechanisms other than blockade of vasoactive amine receptors as cardiac uptake of DXR and the DXR antitumor response were not altered by diphenhydramine, cimetidine, phentolamine, and propranolol. This study demonstrates that anthracycline-associated cardiac and renal toxicity may be mediated by vasoactive substances and that anthracycline cardiomyopathy is potentially preventable.

Acute and chronic cardiovascular effects of doxorubicin in the dog: the cardiovascular pharmacology of drug-induced histamine release.

We evaluated the acute hemodynamic effects of doxorubicin in the open-chest dog. Doxorubicin at doses of 1-4 mg/kg administered over 2 min produced profound hemodynamic changes that were similar to those produced by histamine. These changes persisted despite administering the drug as a slow infusion. Histamine release in peripheral tissues was documented by a marked increase in venous histamine levels following doxorubicin administration. The heart extracted histamine during a period when arterial levels were increased, as indicated by consistently low coronary sinus/aortic ratios. Secondary catecholamine release occurred in response to histamine and histamine-mediated hemodynamic effects. Immunoreactive prostaglandins E and F were increased in coronary sinus blood beginning 30 min after the initiation of a continuous infusion of doxorubicin, and increased slowly thereafter. H1- and H2-receptor blockade with diphenhydramine and cimetidine prevented the early (2-30 min postinfusion) effects of doxorubicin, and combined histaminergic and adrenergic blockade prevented the late effects. A dose of doxorubicin (1 mg/kg) that released histamine and catecholamines produced primary cardiac effects acutely and a cardiomyopathy when administered chronically. The release of vasoactive substances could be part of the pathogenetic mechanism of anthracycline cardiomyopathy.

Development of insulin resistance in normal dogs following alloxan-induced insulin deficiency.

Insulin resistance was measured in 16 normal dogs by a method involving the continuous intravenous infusion of epinephrine, propranolol, glucose and insulin. With this approach, endogenous insulin secretin is inhibited, similar steady state levels of exogenous insulin are achieved in all doags, and the resultant steady state plasma glucose level provides a direct estimate of the ability of insulin to dispose of the infused glucose load. Thus, the higher the steady state plasma glucose level, the more the insulin resistance. Different amounts of alloxan were then administered to these dogs in order to produce insulin deficiency of varying degrees. Insulin resistance was then measured again in each dog. The results indicated that insulin resistance did not develop in dogs with only a moderate degree of insulin deficiency (fasting plasma glucose levels less than 150 mg/100 ml). On the other hand, a significant degree of insulin resistance developed in dogs with severe insulin deficiency (fasting plasma glucose greater than 150 mg/100 ml). Furthermore, the insulin resistance that developed in dogs with severe insulin deficiency could be returned to normal with insulin replacement for one week. These results indicate that insulin resistance can occur as a secondary manifestation of insulin deficiency.