Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage.

Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom models and a strong correlation coefficient with blood loss averaged across subjects (>0.9) in a large animal model, with superior performance to vital sign metrics.

Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage.

Postpartum hemorrhage (PPH) is both the leading and most preventable cause of maternal mortality. PPH is currently diagnosed through visual estimation of blood loss or vital sign analysis of shock index (ratio of heart rate to systolic blood pressure). Visual assessment underestimates blood loss, particularly in the setting of internal bleeding, and compensatory mechanisms stabilize hemodynamics until hemorrhage is massive, beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels to shunt blood to the central organs, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The device was first tested using flow phantoms across a range of physiologically relevant flow rates and demonstrated a linear response. Subsequent testing occurred in swine hemorrhage studies (n=6) by placing the device on the posterior side of the swine's front hock and withdrawing blood from the femoral vein at a constant rate. Resuscitation with intravenous crystalloids followed the induced hemorrhage. The mean LSFI vs. percent estimated blood volume loss had an average correlation coefficient of -0.95 during the hemorrhage phase and 0.79 during resuscitation, both of which were superior to the performance of the shock index. With continued development, this noninvasive, low-cost, and reusable device has global potential to provide an early alert of PPH when low-cost and accessible management strategies are most effective, helping to reduce maternal morbidity and mortality from this largely preventable problem.

Comparison of Nociceptive Effects of Buprenorphine, Firocoxib, and Meloxicam in a Plantar Incision Model in Sprague-Dawley Rats.

Due to their reduced frequency of dosing and ease of availability, NSAIDs are generally preferred over opioids for rodent analgesia. We evaluated the efficacy of the highly COX2-selective NSAID firocoxib as compared with meloxicam and buprenorphine for reducing allodynia and hyperalgesia in rats in a plantar incision model of surgical pain. After a preliminary pharmacokinetic study using firocoxib, Sprague-Dawley rats (n = 12 per group, 6 of each sex) were divided into 6 groups: no surgery (anesthesia only), saline (surgery but no analgesia), buprenorphine (0.05 mg/kg SC every 8 h), meloxicam (2 mg/kg SC every 24 h), and 2 dosages of firocoxib (10 and 20 mg/kg SC every 24 h). The nociception assays were performed by using von Frey and Hargreaves methodology to test mechanical allodynia and thermal hyperalgesia. These assays were performed at 24 h before and at 20, 28, 44, and 52 h after start of surgery. None of the analgesics used in this study produced significantly different responses in allodynia or hyperalgesia from those of saline-treated rats. In the Hargreaves assay, female saline-treated rats experienced significantly greater hyperalgesia than did males. These findings add to a growing body of literature suggesting that commonly used dosages of analgesics may not provide sufficient analgesia in rats experiencing incisional pain.

Safety of Strontium Chloride as a Skeletal Marking Agent for Pacific Salmon.

The purpose of this study was to evaluate the biological effects associated with administering strontium chloride as a marking agent to age-0 Chinook Salmon Oncorhynchus tshawytscha fry. Fish were held in a 0× (0 mg/L), 1× (3,000 mg/L; current standard dosage), 3× (9,000 mg/L), or 5× (15,000 mg/L) solution of strontium chloride for 72 h (three times the standard duration of 24 h). The mortality among fish in the 5× strontium chloride exposure group was significantly higher than that observed in the other groups. A dose-related effect on general fish behavior and on feeding behavior was observed. Fish in all test tanks appeared to feed to satiation, except for fish in the 5× tanks during days 2 and 3. Fish in all other test tanks behaved normally. No dose-related effect on fish growth was detected. Histopathological evaluations showed that fish in the 5× exposure group had a significantly higher number of gill lesions than the 0× group. Our mortality, behavioral, and histological assessments suggested that juvenile Chinook Salmon could be safely immersed for three consecutive days in a 9,000-mg/L solution of strontium chloride. This finding potentially expands the present 1,000-3,000-mg/L dosage and 24-h holding period that can be used to mark juvenile fish with strontium chloride solutions. The research also provides necessary target animal safety data for U.S. Food and Drug Administration approval of strontium chloride as an alternative marking method that is suitable for fish with a short holding time. Received February 19, 2017; accepted July 16, 2017.

Analgesic Efficacy of Firocoxib, a Selective Inhibitor of Cyclooxygenase 2, in a Mouse Model of Incisional Pain.

Pain management in laboratory animals is generally accomplished by using opioids and NSAIDs. However, opioid use is hindered by controlled substance requirements and a relatively short duration of action. In this study, we compared the analgesic efficacy of firocoxib (a cyclooxygenase-2-selective NSAID) with that of buprenorphine in the mouse model of plantar incisional pain by objective measurement of mechanical allodynia and thermal hyperalgesia using von Frey and Hargreaves equipment, respectively. Our experimental design included 5 treatment groups: firocoxib at 10 mg/kg IP every 24 h (F10 group); firocoxib at 20 mg/kg IP every 24 h (F20); buprenorphine at 0.2 mg/kg SC every 8 h; intraperitoneal normal saline every 24 h; and sham group (anesthesia, no incision) treated with firocoxib at 20 mg/kg IP every 24 h (sham+F20). All mice underwent nociceptive assays at 24 h before and 4, 24, 48, and 72 h after surgery. Buprenorphine alleviated allodynia at all time points after incision. The F10 treatment alleviated allodynia at 4, 24, and 48 h, whereas F20 alleviated allodynia at 24, 48, and 72 h. None of the treatments alleviated thermal hyperalgesia at 4h. Except for F10 and buprenorphine at 24 h, all treatments alleviated thermal hyperalgesia at 24, 48, and 72 h. No significant differences were noted between the 2 doses of firocoxib and buprenorphine regarding mechanical allodynia and thermal hyperalgesia at all time points. In conclusion, the analgesic efficacy of firocoxib is comparable to that of buprenorphine in this mouse pain model.

Chronic performance of a subcutaneous hemodynamic sensor.

BACKGROUND: A subcutaneous photoplethysmography (PPG) sensor uses light to detect changes in vascular volume from a location outside the bloodstream. Incorporation into a chronically implanted device, such as a pacemaker or an implantable cardioverter defibrillator, may facilitate therapy optimization and disease monitoring by providing continuous assessment of hemodynamic function and arterial oxygen saturation. However, performance of a chronically placed subcutaneous sensor has not been established. METHODS: Six dogs were implanted with 2-4 PPG sensors subcutaneously in the neck or posterior thorax. Half of the sensors were directed toward deep tissue and half toward overlying cutaneous tissue. Each sensor contained a red and an infrared light emitting diode, a photodetector, and supporting electronics, which were encapsulated in epoxy and attached to a transcutaneous connector. Data were collected at implant and every 3 ± 1 days for 4-9 months starting 3 weeks postimplant. At explant, the fibrous encapsulation was histologically analyzed. RESULTS: A minimally to moderately neovascularized encapsulation formed over all sensors, consisting of fibrous and granulation tissue. Higher cardiac pulse amplitudes and direct current (DC) components were recorded in sensors oriented toward deep tissue, but no significant difference between orientations was found in respiratory wave amplitude. Cardiac pulse amplitude, respiratory wave amplitude, and DC component amplitude, as recorded by the sensor, did not significantly change over time. CONCLUSIONS: Despite fibrous encapsulation of PPG sensors, cardiac pulses and respiratory waves could easily be measured throughout the study and remained constant over time. These results suggest suitability of subcutaneous PPG technology for chronic applications.

Operation of an air filtration device results in morbidity and mortality in growing chickens (Gallus gallus domesticus).

Environmental conditions may influence experimental outcomes in laboratory animals. In this study, we measured the effects of a vortex air-filtration device (AFD) on growth rate, morbidity, mortality, behavior, and gross pathology in P2a Leghorn chickens (Gallus gallus domesticus) raised from hatchlings to 6 wk of age. Growth rate was reduced in the group exposed to the operating AFD ('AFD on' group) compared with the 2 control groups ('AFD off' and 'Historical' groups). Similarly, 6-wk survival probability and body weight were decreased in the AFD-on group compared with controls. Splenic and cardiac weight indices were lower in the AFD-on and AFD-off groups compared with the Historical group. A progressive increase in the ambient sound level (Historical, 53.5 ± 1.7 dBA; AFD off, 63.6 ± 0.5 dBA; AFD on, 71.8 ± 0.8 dBA) was the only variable found to correlate with the physiologic differences observed across the 3 groups of growing chickens. These findings indicate that experimental outcomes with growing chickens are negatively affected by vortex air-filtration devices.

Identification of hemodynamically unstable arrhythmias using subcutaneous photoplethysmography.

INTRODUCTION: Determination of hemodynamic status is central to arrhythmia management in the inpatient setting. In contrast, therapy decisions in implantable cardioverter defibrillators (ICDs) are based exclusively on the arrhythmia's electrical signature. Hemodynamic sensing in ICDs would allow tailoring of therapy according to perfusion status. Subcutaneous photoplethysmography (PPG) is an attractive technology for this application because it responds to changes in arterial pressure and can be readily incorporated into the housing of implanted devices. This study evaluated the accuracy of PPG in identifying hemodynamically unstable simulated arrhythmias in an animal model. METHODS AND RESULTS: Rapid atrial and ventricular pacing was used to simulate arrhythmias in an acute preparation of 7 healthy dogs. Aortic pressure and subcutaneous PPG were simultaneously recorded. Simulated arrhythmias were defined as hemodynamically unstable if aortic pressure decreased by >or=15 mmHg, marginally unstable if pressure decreased by 5-15 mmHg, and hemodynamically stable if pressure either increased or decreased by no more than 5 mmHg. An average of 56 arrhythmias were simulated in each animal. Changes in pressure and PPG output were highly correlated, with correlation coefficient of 0.7-0.9. Subcutaneous PPG identified hemodynamically unstable episodes with a sensitivity of 100% for 6 subjects and 80% for 1 subject. Specificity was more than 90% for 6 subjects and was 50% for 1 subject. CONCLUSIONS: Subcutaneous PPG detects hemodynamically unstable simulated arrhythmias in an acute canine preparation. If successfully validated in humans, this technology may allow ICD therapy to be specifically tailored according to the hemodynamic status of the arrhythmia.

Hemodynamic sensing using subcutaneous photoplethysmography.

Pacemakers and implantable defibrillators presently operate without access to hemodynamic information. If available, such data would allow tailoring of delivered therapy according to perfusion status, optimization of device function, and enhancement of disease monitoring and management. A candidate method for hemodynamic sensing in these devices is photoplethysmography (PPG), which uses light to noninvasively detect changes in blood volume. The present study tested the hypotheses that PPG can function in a subcutaneous location, that the acute changes in blood volume it detects are directly proportional to changes in arterial pressure, and that optimum pacing intervals identified by it are concordant with those determined by arterial pressure. Aortic pressure and PPG were simultaneously recorded in 10 dogs under general anesthesia during changes in atrioventricular (AV) delay and bursts of rapid pacing to simulate tachyarrhythmias. Direct proportionality between transient changes in pressure and PPG waveforms was tested using regression analysis. Scatter plots had a linear appearance, with correlation coefficients of 0.95 (SD 0.03) and 0.72 (SD 0.24) for rapid-pacing and AV delay protocols, respectively. The data were well described by a directly proportional relationship. Optimum AV delays estimated from the induced changes in aortic pressure and PPG waveforms were concordant. This preliminary canine study demonstrates that PPG can function subcutaneously and that it may serve as a surrogate for acute changes in arterial pressure.