Hydraulic Bench Testing of the TruCATHTM/TruCCOMTM Continuous Cardiac Output Monitor

The aim of this study was to test the truCATH^TM/ truCOMMS^TM continuous cardiac output catheter/monitor in a computer-controlled pulsatile mock loop system. The pulmonary artery catheter is equipped with two thermistors and a heating coil which maintains a 2°C temperature difference between the thermistors. The required electrical power is assumed to be an indicator of cardiac output. The catheter was tested under a variety of loading conditions including changes in heart rate (60, 75, 90, 120 beats/mm), filling pressures (0–15 mmHg), ventricular driving pressures (22–135 mmHg), and pulmonary resistance (0.08–1.47 mmHgs/mL) in random combinations, generating flows of 1.5–10 L/min. Fluid temperature was varied between 32 and 42°C. Our data demonstrate a good linear relation between the electrical power output of the TruCATH^TM/TruCOMMS^TM catheter and the actual flow as measured volumetrically. The system appeared to be sensitive to fluid temperature changes, but dimensionless analysis with Womersley and Reynolds numbers revealed that it is a direct consequence of the temperature-dependent water viscosity. We conclude that the TruCATH^TM/TruCOMMS^TM is a potentially useful clinical tool but the absolute correspondence between the catheter output and the patient's actual cardiac output remains to be assessed.     

Definition of pulmonary embolism‐related death and classification of the cause of death in venous thromboembolism studies: Communication from the SSC of the ISTH

Pulmonary embolism (PE)‐related death is often a component of the primary outcome in venous thromboembolism (VTE) clinical studies. Definitions for PE‐related death vary widely, which may lead to biased risk estimates of clinical outcomes, thereby affecting both internal and external validity of study results. We here provide a standardized definition of PE‐related death and propose guidance for classification and reporting of the cause of death for clinical studies in VTE. The proposal was developed in a four‐step process, including a systematic review of definitions used for PE‐related death in previous studies, two subsequent surveys with VTE experts, and meetings held within the Scientific and Standardization Committee (SSC) working group until consensus on the proposal was reached. The proposed classification comprises three categories: Category A: PE‐related death, category B: undetermined cause of death, and category C: cause of death other than PE. Category A includes A1: autopsy‐confirmed PE in the absence of another more likely cause of death; A2: objectively confirmed PE before death in the absence of another more likely cause of death; and A3: PE is not objectively confirmed, but is most likely the main cause of death. Category B includes B1: cause of death is undetermined, despite available information; and B2: insufficient clinical information available to determine the cause of death. The use of the proposed definition will hopefully improve the accuracy of study outcomes, between‐study comparisons, meta‐analyses, and validity of future clinical VTE studies.     

Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study

The authors describe 12 pregnancies in women with epilepsy using lamotrigine (LTG) monotherapy. A seizure increase in nine pregnancies was probably related to a gradual decline of LTG level-to-dose ratio to 40% of baseline. After delivery, LTG kinetics returned swiftly to baseline, causing toxic side effects in some women. Frequent LTG level monitoring and appropriate dose adjustments are advised in the period before and during pregnancy and after delivery, especially in women on LTG monotherapy.     

Qualitative and quantitative analysis of characteristic body surface potential map features in anterior and inferior myocardial infarction

Body surface potential maps were recorded from 120 electrode sites in 236 normal subjects and 258 patients with initial evidence of either anterior myocardial infarction (MI) or inferior MI to identify characteristic map patterns in both groups. After time normalization, averaged map distributions were displayed at 18 equal time intervals during both QRS and ST-T waveforms from the normal, anterior MI and inferior MI groups. At each time instant, the 120-point averaged normal map was subtracted in turn from the corresponding anterior and inferior MI maps; the resulting differences at each electrode site were divided by the pooled standard deviation and the obtained values (discriminant indexes), plotted as contour lines with 1 standard deviation increments, producing discriminant maps for each bi-group comparison. The most consistent discriminant patterns in 114 patients with anterior MI were observed in early QRS in the upper left anterior chest where abnormal negative voltages reflected loss of electric potentials while reciprocal changes were noticed in the lower back; by mid-QRS, both distributions had moved jointly and vertically, the former in the lower torso on the midsternal line, the latter in the upper back. In 144 patients with inferior MI, abnormal positive distributions were observed in early QRS in the upper back, followed later by excessive negative voltages in the inferior right anterior chest; at mid-QRS, both distributions had migrated horizontally, the former proceeding toward the upper anterior torso, the latter to the lower left dorsal area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial properties as determinants of time-varying myocardial stress in humans

Myocardial and arterial load are time-varying phenomena. Despite their importance in myocardial function, the arterial properties that determine time-resolved myocardial wall stress are unknown. We aimed to assess arterial properties as determinants of time-resolved myocardial stress among 1214 men and women enrolled in the Asklepios Study. Time-resolved central pressure, flow, and left ventricular geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography, respectively, for computation of arterial load and ejection-phase time-varying myocardial wall stress. For any given end-diastolic left ventricular geometry and cardiac output, peak myocardial stress correlated directly with systemic vascular resistance (standardized β=1.12; P<0.0001) and aortic characteristic impedance (standardized β=0.17; P<0.0001). The ejection-phase stress-time integral correlated with systemic vascular resistance (standardized β=1.06; P<0.0001), lower total arterial compliance (standardized β=-0.13; P=0.0008), and earlier return of wave reflections (standardized β=-0.10; P<0.0001) but not with reflection magnitude, whereas end-systolic wall stress correlated with systemic vascular resistance (standardized β=1.06; P<0.0001) and reflection magnitude (standardized β=0.12; P<0.0001). After adjustment for age, all of the measured arterial properties, end-diastolic left ventricular geometry, and cardiac output, women demonstrated greater peak (534 versus 507 kdyne/cm(2); P<0.0001), end-systolic (335 versus 320 kdyne/cm(2); P<0.0001), and ejection-phase stress-time integral (157 versus 142 kdyne · s · cm(-2); P<0.0001). In conclusion, different arterial properties have selective effects on time-resolved ejection-phase myocardial wall stress, which are not apparent from single-time point measurements. Women demonstrate less efficient myocardial-arterial coupling, with higher wall stress development for any given left ventricular geometry, arterial properties, and flow output. These observations may relate to the differential susceptibility of women to heart failure.     

Clinical usefulness and safety of bronchoalveolar lavage (BAL) in elderly patients

Little is known about the indications, safety and clinical usefulness of bronchoalveolar lavage (BAL) in elderly patients. In order to address these issues, we reviewed our last 200 consecutive BAL procedures, of which 23 (11.5%) were performed in patients older than 75 years (range 75-90, mean age 80.7 years, 13 men and 10 women). All procedures were well tolerated and no complications were observed. In 17 of the 23 patients (74%), BAL results were compatible with or diagnostic for infectious pneumonia (6 cases), idiopathic pulmonary fibrosis (5 cases), lung cancer (2 cases), hypereosinophilic syndrome (2 cases), chronic eosinophilic pneumonia (1 case) and lymphoma (1 case). In 6 of the 23 patients (26%), BAL yielded no specific diagnostic information. These data indicate that BAL is a safe procedure with a high diagnostic yield in an elderly population with pulmonary disease of unknown origin.     

Hemodynamic modes of ventricular assist with a rotary blood pump: continuous, pulsatile, and failure

Pulsatile operation of rotary blood pumps (RBPs) has received interest due to potential concern with nonphysiological hemodynamics. This study aimed to gain insight to the effects of various RBP modes on the heart-device interaction. A Deltastream diagonal pump (Medos Medizintechnik GmbH) was inserted in a cardiovascular simulator with apical-to-ascending aorta cannulation. The pump was run in continuous mode with incrementally increasing rotating speed (0-5000 rpm). This was repeated for three heart rates (50-100-150 bpm) and three levels of left ventricular (LV) contractility. Subsequently, the Deltastream was run in pulsatile mode to elucidate the effect of (de)synchronization between heart and pump. LV volume and pressure, arterial pressure, flows, and energetic parameters were used to evaluate the interaction. Pump failure (0 rpm) resulted in aortic pressure drops (17-46 mm Hg) from baseline. In continuous mode, pump flow compensated by diminished aortic flow, thus yielding constant total flow. High continuous rotating speed resulted in acute hypertension (mean aortic pressure up to 178 mm Hg). In pulsatile mode, unmatched heart and pulsatile pump rates yielded unphysiologic pressure and flow patterns and LV unloading was found to be highly dependent on synchronization phase. Optimal unloading was achieved when the minimum rotating speed occurred at end-systole. We conclude that, in continuous mode, a perfusion benefit can only be achieved if the continuous pump flow exceeds the preimplant (baseline) cardiac output. Pulsatile mode of support results in complex pressure and volume variations and requires accurate triggering to achieve optimal unloading.     

Central chemoreceptor modulation of breathing via multipath tuning in medullary ventrolateral respiratory column circuits

Ventrolateral respiratory column (VRC) circuits that modulate breathing in response to changes in central chemoreceptor drive are incompletely understood. We employed multielectrode arrays and spike train correlation methods to test predictions of the hypothesis that pre-B?tzinger complex (pre-B?tC) and retrotrapezoid nucleus/parafacial (RTN-pF) circuits cooperate in chemoreceptor-evoked tuning of ventral respiratory group (VRG) inspiratory neurons. Central chemoreceptors were selectively stimulated by injections of CO(2)-saturated saline into the vertebral artery in seven decerebrate, vagotomized, neuromuscularly blocked, and artificially ventilated cats. Among sampled neurons in the B?tzinger complex (B?tC)-to-VRG region, 70% (161 of 231) had a significant change in firing rate after chemoreceptor stimulation, as did 70% (101 of 144) of the RTN-pF neurons. Other responsive neurons (24 B?tC-VRG; 11 RTN-pF) had a change in the depth of respiratory modulation without a significant change in average firing rate. Seventy B?tC-VRG chemoresponsive neurons triggered 189 offset-feature correlograms (96 peaks; 93 troughs) with at least one responsive B?tC-VRG cell. Functional input from at least one RTN-pF cell could be inferred for 45 B?tC-VRG neurons (19%). Eleven RTN-pF cells were correlated with more than one B?tC-VRG target neuron, providing evidence for divergent connectivity. Thirty-seven RTN-pF neurons, 24 of which were chemoresponsive, were correlated with at least one chemoresponsive B?tC-VRG neuron. Correlation linkage maps and spike-triggered averages of phrenic nerve signals suggest transmission of chemoreceptor drive via a multipath network architecture: RTN-pF modulation of pre-B?tC-VRG rostral-to-caudal excitatory inspiratory neuron chains is tuned by feedforward and recurrent inhibition from other inspiratory neurons and from "tonic" expiratory neurons.     

Flip angle optimization for dynamic contrast-enhanced MRI-studies with spoiled gradient echo pulse sequences

Spoiled gradient echo pulse (SPGRE) sequences are commonly used in dynamic contrast-enhanced MRI (DCE-MRI) studies to measure the contrast agent concentration in a tissue of interest over time. However, due to improper tuning of the SPGRE parameters, concentration uncertainty can be very high, even at high signal-to-noise ratio in the MR measurement. In this work, an optimization procedure is proposed for selecting the optimal value of the SPGRE-flip angle FA(opt), given the expected concentration range. The optimization condition ensures that every concentration in the assumed range has the lowest possible uncertainty. By decoupling the R(1)- and R*(2)-effects caused by the presence of the contrast agent, a contour plot has been generated from which FA(opt) can be read off for any study design. Investigation of ten recent DCE-MRI studies showed that improper flip angle selection unnecessarily increases the concentration uncertainty, up to 742% and 72% on average for the typical physiological concentration ranges of 0-2 mM in tumour tissue and 0-10 mM in blood, respectively. Simulations show that the reduced noise levels on the concentration curves, observed at the optimal flip angle, effectively increase the precision of the kinetic parameters estimates (up to 82% for K(trans), 82% for ν(e) and 92% for ν(p) in the case of an individually measured arterial input function (AIF), up to 53% for K(trans), 59% for ν(e) and 67% for ν(p) in the case of a standard AIF). In vivo experiments confirm the potential of flip angle optimization to increase the reproducibility of the kinetic parameter estimates.