Guillaume L. Hoareau’s research while affiliated with UT Dots and other places

Introduction/Background: Pulmonary vasodilators reduce pulmonary vascular resistance and may improve blood flow during CPR. However, most are not available outside of an ICU setting. Nitroglycerin is an inexpensive pulmonary vasodilator that EMS widely uses to treat chest pain. Research Questions/Hypothesis: We hypothesized that nebulized, inhaled nitroglycerin (NIN) would improve carotid blood flow (CBF) without reducing coronary perfusion (CPP) or arterial pressures. Goals/Aims: The principal aim of this investigation was to assess the hemodynamic effects of NIN administered during CPR in a swine model of cardiac arrest. Methods/Approach: N=17 Mixed breed Yorkshire swine (54 + 5 kg) were sedated, intubated, and placed under isoflurane general anesthesia. Following instrumentation with arterial and right atrial pressure catheters as well as a carotid flow probe, the fraction of inspired oxygen (FiO 2 ) was titrated to achieve a PaO 2 of 80-100 mmHg. Ventricular fibrillation (VF) was then induced with a pacing catheter, and the ventilator turned off. After 7 minutes of untreated VF, mechanical chest compressions with a LUCAS device were initiated. Three minutes later, mechanical ventilation was resumed at prearrest settings with 100% FiO 2 . Two minutes later, 5 mL of either nebulized normal saline (NNS controls, n=9) or 10 mg of nitroglycerin (NIN treatment, n=8) was delivered through a nebulizer placed in line with the endotracheal tube, by random allocation. After 4 minutes of nebulized treatment, IV epinephrine (0.15 mg/kg) was administered, followed 2 minutes later by defibrillation. NIN or nebulized NS was continued until the volume was fully delivered, while standard ALS resuscitation proceeded until ROSC or 40 min of arrest had elapsed. Data were analyzed using mixed effects models. Results/Data: Prearrest hemodynamic and blood gas variables were similar between groups. There were no statistically significant differences in systolic or diastolic arterial pressures or CPP. However, there was a statistically significant increase in CBF following NIN (Figure). After 4 minutes of treatment, CBF in NIN-treated animals was approximately double that of NNS controls: 85 mL/min (95% CI 63-108 mL/min) vs 41 mL/min (95% CI 21-61 mL/min), respectively. ROSC was achieved in 3/9 (33%) NNS controls and in 5/8 (63%) of NIN-treated animals (p=0.23). Conclusions: In this small study, early NIN treatment resulted in superior CBF without decreasing arterial pressures or CPP.

OBJECTIVE To utilize sidestream dark field video microscopic technology to evaluate the endothelium in a canine hemorrhagic shock and resuscitation model. METHODS 6 purpose-bred adult dogs were anesthetized, instrumented, and subjected to hemorrhagic shock from September 2021 through June 2022. Each dog was resuscitated with 5 resuscitation strategies in an experimental crossover design study: (1) lactated Ringer’s solution (LRS) and hydroxyethyl starch (HES) solution; (2) canine chilled whole blood (CWB); (3) canine fresh frozen plasma (FFP) and packed RBCs (pRBC); (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC); or (5) HBOC/FDP and canine lyophilized platelets. Sidestream dark field video microscopic evaluation was performed at 5 time points: commencement, after hemorrhage, after shock, after resuscitation (T135), and conclusion (T180). RESULTS There was a significant difference between the perfused boundary region (PBR) measurements when comparing the LRS/HES resuscitation arm to the CWB and FFP/pRBC resuscitation arms at T180. A significant difference in PBR was appreciated in the LRS/HES arm at T135 and T180 compared to its baseline. No other significant differences in PBR were appreciated when resuscitation arms were compared longitudinally or to each other. CONCLUSIONS Shelf-stable blood products preserved the endothelial glycocalyx similarly to CWB and pRBC/FFP as evaluated by sidestream dark field video microscopy. Lactated Ringer and HES solutions did not adequately preserve the endothelial glycocalyx compared to CWB and pRBC/FFP. CLINICAL RELEVANCE Shelf-stable blood products are a viable option to preserve the endothelial glycocalyx when used during hemorrhagic resuscitation in dogs.

Introduction Hemorrhage remains a leading cause of death in civilian and military trauma. Hemorrhages also extend to military working dogs, who can experience injuries similar to those of the humans they work alongside. Unfortunately, current physiological monitoring is often inadequate for early detection of hemorrhage. Here, we evaluate if features extracted from the arterial waveform can allow for early hemorrhage prediction and improved intervention in canines. Methods In this effort, we extracted more than 1,900 features from an arterial waveform in canine hemorrhage datasets prior to hemorrhage, during hemorrhage, and during a shock hold period. Different features were used as input to decision tree machine learning (ML) model architectures to track three model predictors—total blood loss volume, estimated percent blood loss, and area under the time versus hemorrhaged blood volume curve. Results ML models were successfully developed for total and estimated percent blood loss, with the total blood loss having a higher correlation coefficient. The area predictors were unsuccessful at being directly predicted by decision tree ML models but could be calculated indirectly from the ML prediction models for blood loss. Overall, the area under the hemorrhage curve had the highest sensitivity for detecting hemorrhage at approximately 4 min after hemorrhage onset, compared to more than 45 min before detection based on mean arterial pressure. Conclusion ML methods successfully tracked hemorrhage and provided earlier prediction in canines, potentially improving hemorrhage detection and objectifying triage for veterinary medicine. Further, its use can potentially be extended to human use with proper training datasets.

Introduction: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available. Methods: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (MAP <50 mmHg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product. Results: At the time when animals were determined to be out of shock as defined by a shock index <1, MAP (mm Hg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8. ± 2.1) as compared to WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared to LRS/heta and CWB (p < 0.01). Conclusion: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma. Level of evidence: This is a Therapeutic/Care management study with Level of Evidence IV.

Trauma is a common cause of morbidity and mortality in humans and companion animals. Recent efforts in procedural development, training, quality systems, data collection, and research have positively impacted patient outcomes; however, significant unmet need still exists. Coordinated efforts by collaborative, translational, multidisciplinary teams to advance trauma care and improve outcomes have the potential to benefit both human and veterinary patient populations. Strategic use of veterinary clinical trials informed by expertise along the research spectrum (i.e., benchtop discovery, applied science and engineering, large laboratory animal models, clinical veterinary studies, and human randomized trials) can lead to increased therapeutic options for animals while accelerating and enhancing translation by providing early data to reduce the cost and the risk of failed human clinical trials. Active topics of collaboration across the translational continuum include advancements in resuscitation (including austere environments), acute traumatic coagulopathy, trauma-induced coagulopathy, traumatic brain injury, systems biology, and trauma immunology. Mechanisms to improve funding and support innovative team science approaches to current problems in trauma care can accelerate needed, sustainable, and impactful progress in the field. This review article summarizes our current understanding of veterinary and human trauma, thereby identifying knowledge gaps and opportunities for collaborative, translational research to improve multispecies outcomes. This translational trauma group of MDs, PhDs, and DVMs posit that a common understanding of injury patterns and resulting cellular dysregulation in humans and companion animals has the potential to accelerate translation of research findings into clinical solutions.