Whole Blood Selective Aortic Arch Perfusion for Exsanguination Cardiac Arrest: Assessing Myocardial Tolerance to the Duration of Cardiac Arrest.

INTRODUCTION: Selective aortic arch perfusion (SAAP) is an endovascular technique that consists of aortic occlusion with perfusion of the coronary and cerebral circulation. It been shown to facilitate return of spontaneous circulation (ROSC) after exanguination cardiac arrest (ECA), but it is not known how long arrest may last before the myocardium can no longer be durably recovered. The aim of this study is to assess the myocardial tolerance to exsanguination cardiac arrest before successful ROSC with SAAP. METHODS: Male adult swine (n = 24) were anesthetized, instrumented, and hemorrhaged to arrest. Animals were randomized into three groups: 5, 10, and 15 min of cardiac arrest before resuscitation with SAAP. Following ROSC, animals were observed for 60 min in a critical care environment. Primary outcomes were ROSC, and survival at 1-h post-ROSC. RESULTS: Shorter cardiac arrest time was associated with higher ROSC rate and better 1-h survival. ROSC was obtained for 100% (8/8) of the 5-min ECA group, 75% (6/8) of the 10-min group, 43% (3/7) of the 15-min group (P = 0.04). One-hour post-ROSC survival was 75%, 50%, and 14% in 5-, 10-, and 15-min groups, respectively (P = 0.02). One-hour survivors in the 5-min group required less norepinephrine (1.31 mg ±â€Š0.83 mg) compared with 10-SAAP (0.76 mg ±â€Š0.24 mg), P = 0.008. CONCLUSION: Whole blood SAAP can accomplish ROSC at high rates even after 10 min of unsupported cardiac arrest secondary to hemorrhage, with some viability beyond to 15 min. This is promising as a tool for ECA, but requires additional optimization and clinical trials.Animal Use Protocol, IACUC: 0919015.

Characterizing Brain Perfusion in a Swine Model of Raised Intracranial Pressure.

INTRODUCTION: Perfusion of the brain is critical, but this can be compromised due to focal space occupying lesions (SOL). SOLs can raise intracranial pressure (ICP), resulting in reduced cerebral blood flow (CBF). Most gyrencephalic models of brain injury focus on parenchymal injury, with few models of acutely elevated ICP. We hypothesized that we could employ a SOL technique to develop a titratable ICP model and sought to quantitate the resulting decrease in brain perfusion. METHODS: Six swine were anesthetized and instrumented. A Fogarty balloon catheter was inserted intracranially. Blood CO2 partial pressure was maintained between 35 and 45 mmHg. The Fogarty balloon was infused with normal saline at 1 mL/min to ICP targets of 10, 20, 30, and 40 mmHg. CBF (mL/100 g/min) were assessed at each ICP level using computed tomography perfusion (CTP). Data are presented as the mean ± standard deviation with all pressures measured in mmHg. CBF values were compared between baseline and each ICP level using analysis of variance. RESULTS: Baseline ICP was 5 ± 2 and systolic blood pressure was 106 ± 7. Balloon volumes (mL) required to achieve each incremental ICP level were 2.4 ± 0.5, 4.9 ± 1.7, 7.6 ± 1.6, and 9.9 ± 1.7. CBF decreased with each raised ICP level, with CBF being significantly less than baseline at ICP values of 30 (56.1 ± 34.7 versus 20.6 ± 11.0, P < 0.05) and 40 (56.1 ± 34.7 versus 6.5 ± 10.6, P < 0.05). CONCLUSIONS: An intracranial balloon catheter can be used to increase ICP, delivering a proportionate reduction in CBF. This model can be used in the future studies to examine adjuncts that manipulate intracranial pressure and their effect on brain perfusion.

Open chest selective aortic arch perfusion vs open cardiac massage as a means of perfusion during in exsanguination cardiac arrest: a comparison of coronary hemodynamics in swine.

AIM: To describe and compare the aortic-right atrial pressure (AoP-RAP) gradients and mean coronary perfusion pressures (CPPs) generated during open chest selective aortic arch perfusion (OCSAAP) with those generated during open cardiac massage (OCM) in hypovolemic swine. METHODS: Ten male Hanford swine utilized in a prior poly-trauma study were included in the study. Animals were rendered hypovolemic via a 30% volume bleed. Upon confirmation of death, animals underwent immediate clamshell thoracotomy and aortic cross-clamping followed by 5 min of OCM. A catheter suitable for OCSAAP was then inserted into the aorta and animals underwent 1 min of OCSAAP at a rate of 10 mL/kg/min. Aortic and right atrial pressures were recorded continuously using solid-state blood pressure catheters. Representative 10-s intervals from each resuscitation method were extracted. Hemodynamic parameters including AoP-RAP gradients and CPPs were calculated and compared. RESULTS: At baseline, time from death to intervention was significantly shorter for OCM. However, mean CPPs and AoP-RAP gradients were significantly higher in animals undergoing OCSAAP. 98% of OCSAAP segments had a mean CPP > 15, compared to 35% of OCM intervals. While OCM had a significant negative correlation between time to intervention and maximum CPP, this correlation was not significant for OCSAAP. CONCLUSION: OCSAAP generates favorable and potentially time-resistant pressure gradients when compared to those generated by OCM. Further investigation of the technique of OCSAAP is warranted, as it may have potential utility as a therapy during resuscitative thoracotomy (RT).

The functional vascular anatomy of the swine for research.

OBJECTIVES: Swine (Sus Scrofa) are utilized broadly in research settings, given similarities to human vessel size and function; however, there are some important differences for clinicians to understand in order to interpret and perform translational research. This review article uses angiograms acquired in the course of a translational research program to present a description of the functional anatomy of the swine. METHODS: Digital subtraction angiography and computed tomography angiography were obtained throughout the course of multiple studies utilizing power injection with iodinated contrast. Subtracted two-dimensional images and three-dimensional multiplanar reformations were utilized post image acquisition to create maximal intensity projections and three-dimensional renderings of using open-source software (OsiriX). These imaging data are presented along with vessel measurements for reference. RESULTS: An atlas highlighting swine vascular anatomy, with an emphasis on inter-species differences that may influence how studies are conducted and interpreted, was compiled. CONCLUSIONS: Swine are utilized in broad-reaching fields for preclinical research. While many similarities between human and swine vasculature exist, there are important differences to consider when conducting and interpreting research. This review article highlights these differences and presents accompanying images to inform clinicians gaining experience in swine research.

An estrogen (17α-ethinyl estradiol-3-sulfate) reduces mortality in a swine model of multiple injuries and hemorrhagic shock.

BACKGROUND: Although 17α-ethinyl estradiol-3-sulfate (EES) reduces mortality in animal models of controlled hemorrhage, its role in a clinically relevant injury model is unknown. We assessed the impact of EES in a swine model of multiple injuries and hemorrhage. METHODS: The study was performed under Good Laboratory Practice, with 30 male uncastrated swine (25-50 kg) subjected to tibial fracture, pulmonary contusion, and 30% controlled hemorrhage for an hour. Animals were randomized to one of five EES doses: 0 (control), 0.3, 1, 3, and 5 mg/kg, administered postinjury. Subjects received no resuscitation and were observed for 6 hours or until death. Survival data were analyzed using Cox-proportional hazard regression. Left ventricular pressure-volume loops were used to derive preload recruitable stroke work as a measure of cardiac inotropy. Immediate postinjury preload recruitable stroke work values were compared with values at 1 hour post-drug administration. RESULTS: Six-hour survival for the 0, 0.3, 1, 3, and 5 mg/kg groups was 0%, 50%, 33.3%, 16.7%, and 0%, respectively. Following Cox regression, the hazard (95% confidence interval) of death was significantly reduced in the 0.3 (0.22 [0.05-0.93]) and 1 (0.24 [0.06-0.89]) mg/kg groups but not the 3 (0.49 [0.15-1.64]) and 5 (0.46 [0.14-1.47]) mg/kg groups. Mean survival time was significantly extended in the 1 mg/kg group (246 minutes) versus the 0 mg/kg group (96 minutes) (p = 0.04, t test). At 1 hour post-drug administration, inotropy was significantly higher than postinjury values in the 0.3 and 1 mg/kg groups (p = 0.003 and p < 0.001, respectively). Inotropy was unchanged in the 3 and 5 mg/kg groups but significantly depressed in the control (p = 0.022). CONCLUSION: Administration of EES even in the absence of fluid resuscitation reduces mortality and improves cardiac inotropy in a clinically relevant swine model of multiple injuries and hemorrhage. These findings support the need for a clinical trial in human trauma patients.

Development of a Swine Polytrauma Model in the Absence of Fluid Resuscitation.

BACKGROUND: In locations in which access to resuscitative therapy may be limited, treating polytraumatized patients present a challenge. There is a pressing need for adjuncts that can be delivered in these settings. To assess these adjuncts, a model representative of this clinical scenario is necessary. We aimed to develop a hemorrhage and polytrauma model in the absence of fluid resuscitation. MATERIALS AND METHODS: This study consisted of two parts: pulmonary contusion dose-finding (n = 6) and polytrauma with evaluation of varying hemorrhage volumes (n = 6). We applied three, six, or nine nonpenetrating captive bolt-gun discharges to the dose-finding group and obtained computed tomography (CT) images. We segmented images to assess contusion volumes. We subjected the second group to tibial fracture, pulmonary contusion, and controlled hemorrhage of 20%, 30%, or 40% and observed for 3 hours or until death. We used Kaplan-Meier analysis to assess survival. We also assessed hemodynamic and metabolic parameters. RESULTS: Contusion volumes for three, six, and nine nonpenetrating captive bolt-gun discharges were 24 ± 28, 50 ± 31, and 63 ± 77 cm3, respectively (p = .679). Animals receiving at least six discharges suffered concomitant parenchymal laceration, whereas one of two swine subjected to three discharges had lacerations. Mortality was 100% at 12 and 115 minutes in the 40% and 30% hemorrhage groups, respectively, and 50% at 3 hours in the 20% group. CONCLUSION: This study characterizes a titratable hemorrhage and polytrauma model in the absence of fluid resuscitation. This model can be useful in evaluating resuscitative adjuncts that can be delivered in areas remote to healthcare access.

Measuring Cardiac Output in a Swine Model.

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume and cardiac output are essential in this type of research. Contrast ventriculography, thermodilution, and pressure-volume loop (PV-loop) catheters can be used to accurately obtain cardiac performance data depending on which resources and expertise are available. For this study,five Yorkshire swine were anesthetized and intubated. Central venous and arterial access was obtained to place the necessary measurement instruments.A temperature probe was placed in the aortic root. A cold saline bolus was delivered to the right atrium and temperature deflection curve was recorded. Integration of the area under the curve allowed for the calculation of the current cardiac output.A pigtail catheter was percutaneously placed in the left ventricle and 30 mL of iodinated contrast was power injected over 2 seconds. Digital subtraction angiography images were uploaded to volumetric analysis software to calculate the stroke volume and cardiac output. A pressure volume-loop catheter was placed into the left ventricle (LV) and provided continuous pressure and volume data of the LV, which allowed the calculation of both stroke volume and cardiac output.All three methods demonstrated good correlation with each other. The PV-loop catheter and thermodilution exhibited the best correlation with a 3% error and a Pearson coefficient of 0.99, with 95% CI=0.97 to 1.1, (p=0.002). The PV-loop catheter against ventriculography also showed good correlation with a 6% error and a Pearson coefficient of 0.95, 95% CI=0.96 to 1.1 (p=0.01). Finally, thermodilution against ventriculography had a 2% error with r=0.95, 95% CI=0.93 to 1.11, (p=0.01). In conclusion, we state that the PV-loop catheter, contrast ventriculography, and thermodilution each offer certain advantages depending on the researcher's requirements. Each method is reliable and accurate for measuring various cardiac parameters in swine such as the stroke volume and cardiac output.

Selective aortic arch perfusion versus open cardiac massage in exsanguination cardiac arrest: A comparison of coronary pressure dynamics in swine.

AIM: To evaluate the mean aortic-right atrial pressure (AoP-RAP) gradients and mean coronary perfusion pressures (CPPs) observed during open cardiac massage (OCM) versus those obtained with selective aortic arch perfusion (SAAP) in post-mortem hypovolemic swine. METHODS: Post-mortum, male swine, utilized in prior studies of hemorrhage, were included in the study. Animals were bled ∼25-50% of circulating volume prior to death. Animals either underwent clamshell thoracotomy and OCM immediately after death was confirmed (n = 6) or underwent SAAP within 5-15 min of death (n = 6). Aortic root and right atrial pressures were recorded continuously during each method of resuscitation using solid state blood pressure catheters. Representative five beat samples were extracted; short, similarly timed segments of SAAP were also extracted. Mean AoP-RAP gradient and CPPs were calculated and compared. RESULTS: Mean AoP-RAP gradient and CPP were significantly higher in SAAP animals compared to OCM animals (mean ±â€¯SD; 29.1 ±â€¯8.4 vs. 24.5 ±â€¯5.0, p < 0.001; 28.9 ±â€¯8.5 vs. 9.9 ±â€¯6.0, p < 0.001). Mean CPP was not significantly different from mean AoP-RAP gradient in SAAP animals (p = 0.92); mean CPP was significantly lower than mean AoP-RAP gradient in OCM animals (p < 0.001). While 97% of SAAP segments had a CPP > 15 mmHg, only 17% of OCM segments had a CPP > 15 mmHg (p < 0.001). CONCLUSION: SAAP appears to create a more favorable and efficient hemodynamic profile for obtaining ROSC when compared to OCM in this preclinical porcine study.

The Cardiac Physiology Underpinning Exsanguination Cardiac Arrest: Targets for Endovascular Resuscitation.

ABSTRACT: Exsanguination leading to cardiac arrest is the terminal phase of uncontrolled hemorrhage. Resuscitative interventions have focused on preload and afterload support. Outcomes remain poor due to several factors but poor coronary perfusion undoubtedly plays a role. The aim of this study is to characterize the relationship between arterial pressure and flow during hemorrhage in an effort to better describe the terminal phases of exsanguination.Male swine weighing 60 kg to 80 kg underwent splenectomy and instrumentation followed by a logarithmic exsanguination until asystole. Changes in hemodynamic parameters over time were compared using one-way, repeated measures analysis of variance.Nine animals weighing 69 ±â€Š15 kg were studied. Asystole occurred at 53 ±â€Š13 min when 52 ±â€Š11% of total blood volume has been shed. The greatest fall in mean hemodynamic indices were noted in the first 15 min: SBP (80-42 mm Hg, P = 0.02), left ventricular end-diastolic volume (94-52 mL, P = 0.04), cardiac output (4.8-2.4 L/min, P = 0.03), coronary perfusion pressure (57-30 mm Hg, P = 0.01), and stroke volume (60-25 mL, P = 0.02). This corresponds to the greatest rate of exsanguination. Organized cardiac activity was observed until asystole without arrythmias. Coronary flow was relatively preserved throughout the study, with a precipitous decline once mean arterial pressure was less than 20 mm Hg, leading to asystole.In this model, initial hemodynamic instability was due to preload failure, with asystole occurring relatively late, secondary to failure of coronary perfusion. Future resuscitative therapies need to directly address coronary perfusion failure if effective attempts are to be made to salvage these patients.

Development of a Selective Aortic Arch Perfusion System in a Porcine Model of Exsanguination Cardiac Arrest.

Hemorrhage constitutes the majority of potentially preventable deaths from trauma. There is growing interest in endovascular resuscitation techniques such as selective aortic arch perfusion (SAAP) for patients in cardiac arrest. This involves active perfusion of the coronary circulation via a thoracic aortic balloon catheter and is approaching clinical application. However, the technique is complex and requires refinement in animal models before human use can be considered. This paper describes a large animal model of exsanguination cardiac arrest treated with a bespoke SAAP system. Swine were anesthetized, instrumented and a splenectomy was performed before a controlled, logarithmic exsanguination was initiated. Animals were heparinized and the shed blood collected in a reservoir. Once cardiac arrest was observed, the blood was pumped through an extra-corporeal circuit into an oxygenator and then delivered through a 10 Fr balloon catheter placed in the thoracic aorta. This resulted in the return of a spontaneous circulation (ROSC) as demonstrated by ECG and aortic root pressure waveform. This model and accompanying SAAP system allow for standardized and reproducible recovery from exsanguination cardiac arrest.