PhysioZoo: A Novel Open Access Platform for Heart Rate Variability Analysis of Mammalian Electrocardiographic Data.

Background: The time variation between consecutive heartbeats is commonly referred to as heart rate variability (HRV). Loss of complexity in HRV has been documented in several cardiovascular diseases and has been associated with an increase in morbidity and mortality. However, the mechanisms that control HRV are not well understood. Animal experiments are the key to investigating this question. However, to date, there are no standard open source tools for HRV analysis of mammalian electrocardiogram (ECG) data and no centralized public databases for researchers to access. Methods: We created an open source software solution specifically designed for HRV analysis from ECG data of multiple mammals, including humans. We also created a set of public databases of mammalian ECG signals (dog, rabbit and mouse) with manually corrected R-peaks (>170,000 annotations) and signal quality annotations. The platform (software and databases) is called PhysioZoo. Results: PhysioZoo makes it possible to load ECG data and perform very accurate R-peak detection (F 1 > 98%). It also allows the user to manually correct the R-peak locations and annotate low signal quality of the underlying ECG. PhysioZoo implements state of the art HRV measures adapted for different mammals (dogs, rabbits, and mice) and allows easy export of all computed measures together with standard data representation figures. PhysioZoo provides databases and standard ranges for all HRV measures computed on healthy, conscious humans, dogs, rabbits, and mice at rest. Study of these measures across different mammals can provide new insights into the complexity of heart rate dynamics across species. Conclusion: PhysioZoo enables the standardization and reproducibility of HRV analysis in mammalian models through its open source code, freely available software, and open access databases. PhysioZoo will support and enable new investigations in mammalian HRV research. The source code and software are available on www.physiozoo.com.

Early detection of deteriorating ventilation by monitoring bilateral chest wall dynamics in the rabbit.

PURPOSE: Mechanical complications during assisted ventilation can evolve due to worsening lung disease or problems in airway management. These complications affect lung compliance or airway resistance, which in turn affect the chest wall dynamics. The objective of this study was to explore the utility of continuous monitoring of the symmetry and dynamics of chest wall motion in the early detection of complications during mechanical ventilation. METHODS: The local tidal displacement (TDi) values of each side of the chest and epigastrium were measured by three miniature motion sensors in 18 rabbits. The TDi responses to changes in peak inspiratory pressure (n = 7), induction of one-lung intubation (n = 7), and slowly progressing pneumothorax (PTX) (n = 6) were monitored in parallel with conventional respiratory (SpO(2), EtCO(2), pressure and flow) and hemodynamic (HR and BP) indices. PTX was induced by injecting air into the pleural space at a rate of 1 mL/min. RESULTS: A strong correlation (R(2) = 0.99) with a slope close to unity (0.94) was observed between percent change in tidal volume and in TDi. One-lung ventilation was identified by conspicuous asymmetry development between left and right TDis. These indices provided significantly early detection of uneven ventilation during slowly developing PTX (within 12.9 ± 6.6 min of onset, p = 0.02) almost 1 h before the SpO(2) dropped (77.3 ± 27.4 min, p = 0.02). Decreases in TDi of the affected side paralleled the progression of PTX. CONCLUSIONS: Monitoring the local TDi is a sensitive method for detecting changes in tidal volume and enables early detection of developing asymmetric ventilation.

A new method for continuous monitoring of chest wall movement to characterize hypoxemic episodes during HFOV.

INTRODUCTION: Monitoring ventilated infants is difficult during high-frequency oscillatory ventilation (HFOV). This study tested the possible causes of hypoxemic episodes using a new method for monitoring chest wall movement during HFOV in newborn infants. METHODS: Three miniature motion sensors were attached to both sides of the chest and to the epigastrium to measure the local tidal displacement (TDi) at each site. A >20% change in TDi was defined as deviation from baseline. RESULTS: Eight premature infants (postmenstrual age 30.6 ± 2.6 weeks) were monitored during 10 sessions (32.6 h) that included 21 hypoxemic events. Three types of such events were recognized: decrease in TDi that preceded hypoxemia (n = 11), simultaneous decrease in TDi and SpO2 (n = 6), and decrease in SpO(2) without changes in TDi (n = 4). In the first group, decreases in TDi were detected 22.4 ± 18.7 min before hypoxemia, and were due to airway obstruction by secretions or decline in lung compliance. The second group resulted from apnea or severe abdominal contractions. In the third group, hypoxia appeared following a decrease in FiO2. CONCLUSIONS: Monitoring TDi may enable early recognition of deteriorating ventilation during HFOV that eventually leads to hypoxemia. In about half of cases, hypoxemia is not due to slowly deteriorating ventilation.

In vivo validation of a novel method for regional myocardial wall motion analysis based on echocardiographic tissue tracking.

The objective of this study was to validate a recently developed tissue tracking (TT) method for cardiac motion, by comparing it with precise invasive measurements of motion and to prove its capability to reflect moderate hemodynamic changes induced by asynchronous activation. In four open-chest sheep, sono-crystals measured the left ventricle(LV) equator's diameters simultaneously with 2D ultrasound acquisition. The LV was paced either from the posterior or from the lateral wall, just prior to the normal LV activation. Global functional indices were calculated based on the regional motions extracted by the TT method. The correlation coefficient between the shortening of the diameters and the global circumferential strain (GCS) was 0.99 +/- 0.004. The peak GCS differentiated between the pacing modes (paired t test, P < 0.05). The GCS, a measurement closely based on the TT method, followed the precise sono-crystals measurements and reflected moderate hemodynamic changes, thus providing a substantial proof of the TT method's accuracy and clinical value.

Detection of the cardiac activation sequence by novel echocardiographic tissue tracking method.

Asynchronous cardiac activation leads to decreased pumping efficiency. Quantifying the activation sequence may optimize both the selection of patients for cardiac resynchronization therapy (CRT) and its efficacy. The feasibility of assessing the directivity and the degree of synchronous activation with ultrasound was examined. A tissue tracking method (CEB, GE-Ultrasound, AFI, GE Healthcare Inc., Wauwatosa, WI, USA) provided the regional strain profiles. The first maxima in systole of the regional circumferential strains were considered as the activation times. An integrative vector (SDV) describes the activation synchrony and directivity. In six open-chest sheep, activation maps and SDV were calculated in short-axis planes of the left ventricle for normal activation and induced pacings from the anterior and lateral free walls. Both magnitude and angle of the SDV were statistically different (p < 0.05) for the different pacings. Localization of the pacing site was 3 degrees +/- 18 degrees from true position. Conclusions were that motion analysis in echocardiograms provides insightful information regarding the activation process and may enhance procedures such as CRT.

Effects of synchronized cardiac assist device on cardiac energetics.

A novel physiological cardiac assist device (PCAD), the LEV RAM assist device, which is synchronized with the failing heart ejection, was developed to improve the failing heart systolic and diastolic functions and cardiac energetics. The PCAD uses a single short cannula, which is inserted into the beating left ventricle (LV) by means of a specially designed device. Blood is ejected from the PCAD into the LV after the opening of the aortic valve and augments the cardiac stroke work. The same amount of blood is withdrawn from the LV into the PCAD, through the same cannula, during the diastole. The study aims to test the effects of the PCAD on cardiac energetics and coronary blood flow. Adult normal sheep were anesthetized and the heart was exposed by left thoracotomy. Pressures transducers (Millar Instruments, Inc., Houston, TX) were inserted into the LV and aorta. LV volume was measured by sonocrystals (Sonometrics Corp., London, Ontario, Canada) and impedance catheter (CD Lycom, Argonstrat 116 Zoetermeer, 2718 SP The Netherlands). Flowmeters (transonic) measured the cardiac output (CO) and the coronary arteries (left anterior descending (LAD) and circumflex) flows. A thin cannula was inserted into the coronary sinus and the oxygen content of the LV and the coronary sinus were determined (AVOXimeter-1000). Pressure-volume loops, myocardial energetics, and coronary flow were measured. The displaced PCAD volume was 11 mL. Four different levels of assist were studied by changing the frequency of the assist: (1) assist beat after three successive regular beats [1:4], (2) assist every third beat [1:3], (3) alternate assist and normal beat [1:2], and (4) continuous assist [1:1]. Cardiac output (CO) and stroke volume (SV) increased proportionally with increasing frequency of assist. Systolic mechanical efficiency of the PCAD was above 90%. Simultaneously, the PCAD decreased the end-diastolic volume (EDV; diastolic unloading). The PCAD increased coronary flow and decreased cardiac arterial-venous O(2) difference. We conclude that the PCAD efficiently augments CO and stroke work, decreases preload, and decreases the coronary arterial-venous O(2) difference; all these may expedite cardiac reverse remodeling, and promote recovery of function and eventual easy explanation of the device.

Augmentation of dilated failing left ventricular stroke work by a physiological cardiac assist device.

A novel physiological cardiac assist device (PCAD), otherwise known as the LEVRAM assist device, which is synchronized with the heartbeat, was developed to assist the left ventricle (LV) in chronic heart failure (CHF). The PCAD utilizes a single cannula, which is inserted in less than 15 s through the apex of the beating LV by means of a specially designed device. Blood is withdrawn from the LV into the PCAD in diastole and is injected back to the LV, through the same cannula, during the systolic ejection phase, thereby augmenting stroke volume (SV) and stroke work (SW). CHF with dilated LV was induced in sheep by successive intracoronary injections of 100-microm beads. The sheep (92.2 +/- 25.9 kg, n = 5) developed stable CHF with increased LV end-diastolic diameter (69.4 +/- 3.3 mm) and end-diastolic volume (LVEDV = 239 +/- 32 mL), with severely reduced ejection fraction (23.8 +/- 7.6%), as well as mild-to-moderate mitral regurgitation. The sheep were anesthetized, and the heart was exposed by left thoracotomy. Pressure was measured in the LV and aorta (Millar). The SV was measured by flow meters and the LV volume by sonocrystals. Assist was provided every 10 regular beats, and the assisted beats were compared with the preceding unassisted beats, at the same LVEDV. The PCAD displaced 13.6 +/- 3.4 mL, less than 8% of LVEDV. Added SW was calculated from the assisted and control pressure-volume loops. The efficiency, defined as an increase in SW divided by the mechanical work of the PCAD, was 85.4 +/- 16.9%. We conclude that the PCAD, working with a small displaced blood volume in synchrony with the heartbeat, efficiently augments the SW of the dilated failing LV. The PCAD is suggested for use as a permanent implantable device in CHF.

In vivo extracellular recording of sympathetic ganglion activity in a chronic animal model.

Surgery of the sympathetic system is performed for a variety of indications, hyperhidrosis being a major one. Despite excellent results, sympathectomy for hyperhidrosis bears a number of sequels, some of which may be devastating. Several surgical methods, empirically advocated to alleviate these problems, have only limited success. Chronic in vivo recording of the electrical activity from sympathetic ganglia may assist in understanding and clarifying complex problems of sympathetic surgery; however, no suitable method has been reported. An electrode device developed by our group was implanted on the stellate ganglion, in a chronic animal model (dog). The signals obtained were amplified, filtered, and transmitted via an A/D interface to be acquired and saved on a computer, using special software which we developed. Our method enabled the separate recording of neuroelectrical signals, ECG, and respiration waves. An additional software program, also developed by our group, was used to analyze the data. This chronic animal model allows investigation of surgical and pharmacological manipulations of the sympathetic system.