Intestinal Fatty Acid-Binding Protein as a Potential Biomarker for Gastrointestinal Complications after Complex Endovascular Aortic Surgery.

BACKGROUND: This study aimed to investigate the association between intestinal fatty acid-binding protein (I-FABP), acute gastrointestinal injury (AGI) grade, and gastrointestinal (GI) complications after fenestrated or branched endovascular aortic aneurysm repair. METHODS: A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal, or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for I-FABP with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the AGI grade every day during postoperative intensive care. RESULTS: Higher concentrations of I-FABP at 24 hr and 48 hr correlated to higher AGI grade on postoperative days 1, 2, and 3 (P = 0.032 and P = 0.048, P = 0.040 and P = 0.018, and P = 0.012 and P = 0.016, respectively). Patients who developed a GI complication within 90 days postoperatively had a higher overall AGI grade than those who did not develop a GI complication (P < 0.001), as well as higher concentrations of I-FABP at 48 hrs (P = 0.019). Patients developing GI dysfunction (AGI grade ≥2) had a higher frequency of complications (P = 0.009) and longer length of stay in the intensive care unit (P = 0.008). CONCLUSIONS: In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma I-FABP concentrations and postoperative GI dysfunction, evaluated using the AGI grade, were associated with GI complications, indicating that these measures may be useful in the postoperative management of these patients.

A 12-year experience of endovascular repair for ruptured abdominal aortic aneurysms in all patients.

OBJECTIVE: Endovascular aneurysm repair (EVAR) has been increasingly performed for ruptured abdominal aortic aneurysms (rAAAs). However, multiple randomized trials have failed to demonstrate a survival benefit compared with open aortic surgery. During a 12-year period, 100% of patients without a history of aneurysm surgery had undergone EVAR for a rAAA at Örebro University Hospital, with no emergent open aortic surgery performed. In the present study, we evaluated the mortality and technical success during this "EVAR-only" period. METHODS: A single-center, retrospective observational study was conducted. We identified all patients who had presented to Örebro University Hospital with a rAAA between October 2009 and September 2021. Patients with isolated iliac artery, thoracic, and thoracoabdominal aortic ruptures were not included. Patients who had received previous aortic interventions (open or endovascular) and patients who had received palliative treatment instead of surgical intervention were also excluded. The patient characteristics, perioperative and postoperative data, and mortality rate were investigated. RESULTS: EVAR had been performed in 100 patients. Preoperative hemodynamic instability had been present in 54 patients (54%), and 18 (18%) had undergone aortic balloon occlusion. The aneurysm location was infrarenal in 89 patients (89%). Bifurcated stent grafts had been used in 97 patients (97%), and adjunct endovascular techniques had been used for 27 patients (27%). Of 98 patients, EVAR had been performed with the patient under local anesthesia for 62 patients (63%). Peri- and postoperative complications at 30 days had occurred in 20 of 100 patients (20%) and 22 of 79 patients (28%), respectively. The overall mortality at 30 days was 27% (27 of 100 patients), and the mortality for those with an isolated infrarenal rAAA was 24% (21 of 89 patients). The overall mortality at 1 year was 39% (39 of 100 patients) and for those with an isolated infrarenal rAAA was 37% (33 of 89 patients). The presence of preoperative hemodynamic instability and the use of ABO were statistically significantly and independently associated with increased 30-day mortality on multivariate logistic regression analysis. CONCLUSIONS: All 100 patients who had undergone surgery for a rAAA had been treated using EVAR and endovascular adjuncts, with a relatively low mortality rate, thus continuing the "EVAR-only" approach. A low proportion of rAAA patients were considered surgically unsuitable. These findings support the applicability of EVAR for the treatment of all rAAAs at suitable centers.

Early Onset of Postoperative Gastrointestinal Dysfunction Is Associated With Unfavorable Outcome in Cardiac Surgery: A Prospective Observational Study.

OBJECTIVE: The distribution of postoperative gastrointestinal (GI) dysfunction and its association with outcome were investigated in cardiac surgery patients. Gastrointestinal function was evaluated using the Acute Gastrointestinal Injury (AGI) grade proposed by the European Society of Intensive Care Medicine. DESIGN: Prospective observational study at a single center. SETTING: University hospital. PATIENTS: Consecutive patients presenting for elective cardiac surgery with extracorporeal circulation (ECC). INTERVENTIONS: None. RESULTS: Daily assessment using the AGI grade was performed on the first 3 postoperative days in addition to standard care. For analysis, 3 groups were formed based on the maximum AGI grade: AGI 0, AGI 1, and AGI ≥2. Five hundred and one patients completed the study; 32.7%, 65.1%, and 2.2% of the patients scored a maximum AGI 0, AGI 1, and AGI ≥2, respectively. Patients with AGI grade ≥2 had more frequently undergone thoracic aortic surgery and had longer surgery duration and time on ECC. Patients with AGI grade ≥2 had statistically significant higher frequency of GI complications within 30 days (63.6% vs 1.2% and 5.5% in patients with AGI 0 and AGI 1) and higher 30-day mortality (9.1% vs 0.0% and 1.8% in patients with AGI 0 and AGI 1). CONCLUSIONS: Early GI dysfunction following cardiac surgery was associated with an unfavorable outcome. Increased attention to GI dysfunction in cardiac surgery patients is warranted and the AGI grade could be a helpful adjunct to a structured approach.

Intestinal fatty acid-binding protein and acute gastrointestinal injury grade in postoperative cardiac surgery patients.

BACKGROUND AND AIM: Gastrointestinal complications post cardiac surgery are infrequent but difficult to diagnose and carry a high mortality. Plasma intestinal fatty acid-binding protein (I-FABP) concentrations and the relationship between I-FABP, gastrointestinal dysfunction, and postoperative outcomes were investigated in patients who developed gastrointestinal dysfunction (acute gastrointestinal injury [AGI] grade ≥2) and those with normal gastrointestinal function. METHODS: Patients with (AGI 2 group, n = 11) and without (matched controls, AGI 0 group, n = 22) early postoperative gastrointestinal dysfunction were extracted from a larger single-center prospective observational study, including adults undergoing elective cardiac surgery with extracorporeal circulation, and investigated in this nested case-control analysis. RESULTS: Both groups displayed variations in I-FABP concentrations with higher I-FABP on postoperative Day 1 compared to baseline and postoperative Days 2 and 3 (p < .001 and p = .005, respectively). The AGI 2 group had higher I-FABP concentrations on Day 2 compared to the AGI 0 group (p = .024). I-FABP on Day 2 correlated positively with AGI grade over the first 3 days (p = .036, p = .021 and p = .018, respectively). High I-FABP (defined as fourth quartile concentrations) on Day 1 was associated with more prolonged surgical procedures (p < .05). Furthermore, fourth quartile I-FABP on Day 1 and early gastrointestinal dysfunction were associated with higher frequencies of postoperative organ dysfunction (p < .05) and gastrointestinal complications (p < .05), and higher 365-day mortality. CONCLUSION: The present study indicates an association between intraoperative gastrointestinal injury, postoperative gastrointestinal dysfunction and gastrointestinal complications. A high-powered study is needed to further explore this relationship and the interpretation of I-FABP concentrations in individual cardiac surgery patients.

Total resuscitative endovascular balloon occlusion of the aorta causes inflammatory activation and organ damage within 30 minutes of occlusion in normovolemic pigs.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) causes physiological, metabolic, end-organ and inflammatory changes that need to be addressed for better management of severely injured patients. The aim of this study was to investigate occlusion time-dependent metabolic, end-organ and inflammatory effects of total REBOA in Zone I in a normovolemic animal model. METHODS: Twenty-four pigs (25-35 kg) were randomized to total occlusion REBOA in Zone I for either 15, 30, 60 min (REBOA15, REBOA30, and REBOA60, respectively) or to a control group, followed by 3-h reperfusion. Hemodynamic variables, metabolic and inflammatory response, intraperitoneal and intrahepatic microdialysis, and plasma markers of end-organ injuries were measured during intervention and reperfusion. Intestinal histopathology was performed. RESULTS: Mean arterial pressure and cardiac output increased significantly in all REBOA groups during occlusion and blood flow in the superior mesenteric artery and urinary production subsided during intervention. Metabolic acidosis with increased intraperitoneal and intrahepatic concentrations of lactate and glycerol was most pronounced in REBOA30 and REBOA60 during reperfusion and did not normalize at the end of reperfusion in REBOA60. Inflammatory response showed a significant and persistent increase of pro- and anti-inflammatory cytokines during reperfusion in REBOA30 and was most pronounced in REBOA60. Plasma concentrations of liver, kidney, pancreatic and skeletal muscle enzymes were significantly increased at the end of reperfusion in REBOA30 and REBOA60. Significant intestinal mucosal damage was present in REBOA30 and REBOA60. CONCLUSION: Total REBOA caused severe systemic and intra-abdominal metabolic disturbances, organ damage and inflammatory activation already at 30 min of occlusion.

Results of postoperative microdialysis intraperitoneal and at the anastomosis in patients developing anastomotic leakage after rectal cancer surgery.

Introduction: Anastomotic leakage postoperatively in patients operated with rectum resection and primary anastomosis is a common and feared complication. We have studied seven patients with an anastomotic leakage after surgery and compared them with 13 patients without complications.Methods: Metabolic measurements with microdialysis were done during the first seven postoperative days, with measurements of glucose, pyruvate, lactate and glycerol. The lactate/pyruvate ratio was calculated. Measurements were performed subcutaneously, intraperitoneally and at the anastomosis. The inflammatory cytokines, IL 6 and IL 10, were measured intravenously and intraperitoneally 48 hours postoperatively.Results: Intravenous and intraperitoneal IL 6 were higher in the leakage group. Around the small intestine (intraperitoneally), we found that patients developing anastomotic leakage had higher lactate and lactate/pyruvate ratio immediately after surgery. They also showed lower glycerol levels. At the anastomosis, we found higher lactate and lactate/pyruvate ratio in anastomotic leak patients after the fourth postoperative day.Conclusions: The results indicate that a possible mechanism behind an anastomotic leakage is an impaired circulation and thus insufficient saturation to the small intestine peroperatively. This develops into an inflammation both intraperitoneally and intravenously, which, if not reversed, spread within the gastrointestinal tract .The colorectal anastomosis is the most vulnerable part of the gastrointestinal tract postoperatively and hypoxia and inflammation may occur there, and an anastomosis leakage will be the consequence.

Metabolic Response to Claudication in Peripheral Arterial Disease: A Microdialysis Pilot Study.

OBJECTIVES: This is a pilot study, and the objective of the study was to investigate the possible uses of microdialysis in the calf muscle to assess the metabolic response to intermittent claudication (IC) and in addition evaluate the simultaneous systemic inflammatory reaction. METHODS: Dialysate and venous blood sampling was performed before, during and after walking on a treadmill to maximal tolerable claudication (controls 10 min) using 1 microdialysis catheter inserted in the gastrocnemius muscle, 1 subcutaneously in the pectoral region (as a reference), and a peripheral venous catheter. RESULTS: A total of 9 participants were recruited, 6 patients with IC and 3 healthy control subjects. At baseline, patients with IC and control subjects did not differ in metabolic findings (glucose, lactate, pyruvate, and glycerol) in the gastrocnemius muscle. Subcutaneous glucose concentration was higher in control subjects. After physical exertion, gastrocnemius and subcutaneous glycerol, lactate, and pyruvate concentrations increased in patients with IC. Plasma concentrations of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), hepatocyte growth factor, and vascular endothelial growth factor were higher in IC subjects at baseline, and TNF-α, IL-6, and IL-18 increased after walking as did IL-6 and IL-1ß in control subjects. The muscle catheters did not show any signs of harm. CONCLUSIONS: Microdialysis can be used to study the ongoing metabolic response during walking and claudication. Our results suggest both an acute local and a systemic inflammatory reaction during development of claudication.

Perioperative intraperitoneal metabolic markers in patients undergoing cardiac surgery with cardiopulmonary bypass: an exploratory pilot study.

BACKGROUND: Cardiopulmonary bypass and postoperative cardiac dysfunction cause splanchnic hypoperfusion resulting in intra-abdominal anaerobic metabolism and risk for gastrointestinal complications. The intra-abdominal metabolism can be monitored by intraperitoneal measurement of relevant metabolites using microdialysis. The aim of this study was to investigate the intraperitoneal metabolism using microdialysis during and after cardiopulmonary bypass at 34°C. METHODS: In six patients undergoing elective coronary artery bypass grafting or aortic valve replacement under cardiopulmonary bypass, microdialysis was used to measure intraperitoneal and subcutaneous glucose, lactate, pyruvate, glycerol and glutamate concentrations, intraoperatively and up to 36 hours postoperatively. Arterial and central venous blood gases were analysed as were haemodynamics and the development of complications. RESULTS: All patients had an ordinary perioperative course and did not develop gastrointestinal complications. The arterial, intraperitoneal and subcutaneous lactate concentrations changed during the perioperative course with differences between compartments. The highest median (interquartile range) concentration was recorded in the intraperitoneal compartment at 1 hour after the end of cardiopulmonary bypass (2.1 (1.9-2.5) mM compared to 1.3 (1.2-1.7) mM and 1.5 (1.0-2.2) mM in the arterial and subcutaneous compartments, respectively). In parallel with the peak increase in lactate concentration, the intraperitoneal lactate/pyruvate ratio was elevated to 33.4 (12.9-54.1). CONCLUSION: In cardiac surgery, intraperitoneal microdialysis detected changes in the abdominal metabolic state, which were more pronounced than could be shown by arterial blood gas analysis. Despite an uneventful perioperative course, patients undergoing low-risk surgery under cardiopulmonary bypass might be subjected to a limited and subclinical intra-abdominal anaerobic state.

Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium.

BACKGROUND: While studying a urothelium-derived inhibitory factor in guinea pig urinary bladders we observed considerable release of prostanoids, including PGD2-like activity. The present study was carried out to identify the prostanoids and to study their roles in modulating guinea pig urinary bladder motility. METHODS: Release of PGE2 and PGD2 in isolated guinea pig urinary bladder preparations was analyzed by high performance liquid chromatography (HPLC) combined with bioassay on bladder strips. Isolated urothelium-intact (UI) or -denuded (UD) bladder strips were subjected to electrical field stimulation (EFS) and applications of PGE2 and PGD2. RESULTS: A resting release of 95±9 (n=5) nggtissue(-1)h(-1) PGE2-like activity and 210±34 (n=4) nggtissue(-1)h(-1) PGD2-like activity was found, where PGD2-like was subject to marked spontaneous inactivation during isolation. Prostanoids release was decreased by 70-90% by the cyclo-oxygenase inhibitor diclofenac in UI preparations. Urothelium removal decreased prostanoids release by more than 90%. PGE2 increased basal tone and spontaneous contractions, whereas PGD2 had little or no effect on these. Exogenous PGE2 enhanced and PGD2 inhibited contractile responses to EFS, exogenous acetylcholine- and ATP, whereas PGD2 caused marked dose-dependent inhibition. PGE2 and PGD2 effects were more pronounced in diclofenac-treated UD tissues. CONCLUSIONS: PGD2 and PGE2 are released from guinea pig bladder urothelium and PGD2 has inhibitory effects on bladder motility, mainly through a postjunctional action on smooth muscle responsiveness. GENERAL SIGNIFICANCE: The release and inhibitory effects merit further studies in relation to normal biological function as well as overactive bladder syndrome.

Intra-abdominal hypertension--an experimental study of early effects on intra-abdominal metabolism.

BACKGROUND: The main aim of this experimental study was to investigate the early effects of intra-abdominal hypertension (IAH) on intra-abdominal metabolism and intestinal mucosal blood flow to evaluate whether metabolites can serve as markers for organ dysfunction during IAH. METHODS: A swine model was used, and the animals were anesthetized and ventilated. Fifteen animals were subjected to IAH of 30 mm Hg for 4 hr by carbon dioxide insufflation. Seven animals served as controls. Hemodynamic data, arterial blood samples, and urine output were analyzed. Intraluminal laser Doppler flowmetry measured intestinal mucosal blood flow. Glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (l/p) ratio were measured intraperitoneally and intramurally in the small intestine and rectum using microdialysis. RESULTS: IAH lowered the abdominal perfusion pressure by 12-18 mm Hg, reduced the intestinal mucosal blood flow by 45-63%, and decreased urine output by 50-80%. In the intervention group, glycerol concentrations increased at all locations, pyruvate concentrations decreased, and the l/p ratio increased intraperitoneally and intramurally in the small intestine. Control animals remained metabolically stable. Glucose and lactate concentrations were only slightly affected or unchanged in both the groups. CONCLUSIONS: IAH reduces intestinal blood flow and urinary output and causes early metabolic changes, indicating a discrete shift toward anaerobic metabolism. Intraperitoneal microdialysis may be useful in the early detection of impaired organ dysfunction with metabolic consequences in IAH and abdominal compartment syndrome.

Intraperitoneal metabolic consequences of supraceliac aortic balloon occlusion in an experimental animal study using microdialysis.

BACKGROUND: To investigate the effects of supraceliac aortic balloon occlusion (ABO) and superior mesenteric artery (SMA) occlusion on abdominal visceral metabolism in an animal model using intraperitoneal microdialysis (IPM) and laser Doppler flowmetry. METHODS: A total of 9 pigs were subjected to ABO and 7 animals were subjected to SMA occlusion for 1 hour followed by 3 hours of reperfusion. Seven animals served as controls. Hemodynamic data, arterial blood samples, urinary output, and intestinal mucosal blood flow (IBF) were followed hourly. Intraperitoneal (i.p) glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (l/p) ratio were measured using IPM. RESULTS: Compared with the baseline, ABO reduced IBF by 76% and decreased urinary output. SMA occlusion reduced IBF by 75% without affecting urinary output. ABO increased the i.p l/p ratio from 18 at baseline, peaking at 46 in early reperfusion. SMA occlusion and reperfusion tended to increase the i.p l/p ratio, peaking at 36 in early reperfusion. ABO increased the i.p glycerol concentration from 87 µM at baseline to 579 µM after 3 hours of reperfusion. SMA occlusion and reperfusion increased the i.p glycerol concentration but to a lesser degree. CONCLUSIONS: Supraceliac ABO caused severe hemodynamic, renal, and systemic metabolic disturbances compared with SMA occlusion, most likely because of the more extensive ischemia-reperfusion injury. The intra-abdominal metabolism, measured by microdialysis, was affected by both ABO and SMA occlusion but the most severe disturbances were caused by ABO. The i.p l/p ratios and the glycerol concentrations increased during ischemia and reperfusion and may serve as markers of these events and indicate anaerobic metabolism and cell damages respectively.

Induced Moderate Hypothermia in Aortic Rupture With Retroperitoneal Bleeding: A Randomized Porcine Study.

OBJECTIVE: Induced hypothermia improves outcome in aortic arch surgery, neonatal neurointensive care, and transplant surgery for example. In contrast, spontaneous hypothermia has been associated with worse outcomes in patients suffering from hemorrhagic shock, mostly explained by its adverse effects on the coagulation system. We investigated if induced hypothermia would impair short-term survival in experimental aortic rupture with retroperitoneal bleeding. METHODS: Anesthetized pigs were randomized into 2 groups: hypothermia by peritoneal lavage of ice-cold Ringer's acetate and external cooling (n = 10) and normothermia (n = 10). Aortic rupture with retroperitoneal bleeding was induced by endovascular means creating a 6 mm hole in the retroperitoneal portion of abdominal aorta. Survival (primary outcome), hemodynamics, and arterial blood gases including lactate were collected and analyzed up to 180 min after aortic rupture. RESULTS: The body temperature (mean ± standard deviation) in the hypothermic group was 31.5 ± 1.0 °C and 38.7 ± 0.4 °C in the normothermic group at the time for aortic rupture. Survival up to 180 min after the retroperitoneal bleeding was significantly higher in the hypothermic compared with the normothermic group (P = 0.023). CONCLUSIONS: Induced hypothermia did not impair survival in this experimental retroperitoneal aortic bleeding model in anesthetized pigs. This finding may indicate a minor role for the coagulation system in this type of bleeding.

The effect of an endovascular Heaney maneuver to achieve total hepatic isolation on survival, hemodynamic stability, retrohepatic bleeding, and collateral flow in a porcine model.

PURPOSE: Combining resuscitative endovascular balloon occlusion of the aorta (REBOA) and the inferior vena cava (REBOVC) with open surgery is a new hybrid approach for treating retrohepatic vena caval injuries. We compared endovascular total hepatic isolation with supraceliac REBOA ± suprahepatic REBOVC and no occlusion in experimental retrohepatic vena cava bleeding regarding survival, bleeding volume, hemodynamic stability, and arterial collateral blood flow. METHODS: Twenty-five anesthetized pigs (n = 6-7/group) were randomized to REBOA; REBOA + REBOVC; REBOA + infra and suprahepatic REBOVC + portal vein occlusion (endovascular Heaney maneuver, four-balloon-occlusion, 4BO) or no occlusion. After balloon inflation, free bleeding was initiated from an open sheath in the retrohepatic vena cava. Bleeding volume, right internal thoracic artery (RITA) blood flow, hemodynamics, and arterial blood variables were measured until death or up to 90 min. RESULTS: The REBOA group had a longer median survival time (63 min) compared with the 4BO (24 min, P = 0.02) and no occlusion (30 min, P = 0.02) groups, not versus the REBOA + REBOVC group (49 min, P > 0.05). The first 15 min accumulated bleeding was comparable in all groups (P > 0.05); Thereafter, bleeding volume was higher in the REBOA group versus the 4BO group (P < 0.05), not versus the other groups. RITA blood flow and MAP were higher in the REBOA group versus the other groups after 10 min of bleeding (P < 0.05). CONCLUSIONS: Endovascular Heaney maneuver was not beneficial for survival or hemodynamic stability in this porcine model, whereas supraceliac REBOA was. Anatomical differences in thoracoabdominal collaterals between pigs and humans must be considered when interpreting these results.

NO-Donation Increases Visceral Circulation in a Porcine Model of Abdominal Hypertension.

Intraabdominal hypertension (IAH) is negative for outcome after intensive care. Little research has focused on medical intervention to improve visceral circulation during IAH. A nitric oxide (NO)-donor was compared with placebo in 25 pigs; each pig was randomized into three groups: PDNO (NO-donor), Control (placebo), or Sham. IAH was induced by CO2 insufflation to 30 mmHg. Sham group had surgical preparation only. Blood gases, invasive venous and arterial blood pressure, intestinal microcirculation and superior mesenteric blood flow were measured. The PDNO group had significantly increased intestinal microcirculation compared with Controls during IAH (last hour, P = 0.009). The mean arterial pressure and abdominal perfusion pressures (APP) were decreased, and the cardiac index were increased in the PDNO group. Also, systemic and pulmonary vascular resistances were lower in the PDNO group compared with Controls. These experimental findings indicate that NO should be further explored with potential application to improve intestinal microcirculation in IAH patients.

Intra-aortic and Intra-caval Balloon Pump Devices in Experimental Non-traumatic Cardiac Arrest and Cardiopulmonary Resuscitation.

Intra-aortic balloon pump (IABP) use during CPR has been scarcely studied. Intra-caval balloon pump (ICBP) may decrease backward venous flow during CPR. Mechanical chest compressions (MCC) were initiated after 10 min of cardiac arrest in anesthetized pigs. After 5 min of MCC, IABP (n = 6) or ICBP (n = 6) was initiated. The MCC device and the IABP/ICBP had slightly different frequencies, inducing a progressive peak pressure phase shift. IABP inflation 0.15 s before MCC significantly increased mean arterial pressure (MAP) and carotid blood flow (CBF) compared to inflation 0.10 s after MCC and to MCC only. Coronary perfusion pressure significantly increased with IABP inflation 0.25 s before MCC compared to inflation at MCC. ICBP inflation before MCC significantly increased MAP and CBF compared to inflation after MCC but not compared to MCC only. This shows the potential of IABP in CPR when optimally synchronized with MCC. The effect of timing of intra-aortic balloon pump (IABP) inflation during mechanical chest compressions (MCC) on hemodynamics. Data from12 anesthetized pigs.

A porcine study of ultrasound-guided versus fluoroscopy-guided placement of endovascular balloons in the inferior vena cava (REBOVC) and the aorta (REBOA).

Objectives: In fluoroscopy-free settings, alternative safe and quick methods for placing resuscitative endovascular balloon occlusion of the aorta (REBOA) and resuscitative endovascular balloon occlusion of the inferior vena cava (REBOVC) are needed. Ultrasound is being increasingly used to guide the placement of REBOA in the absence of fluoroscopy. Our hypothesis was that ultrasound could be used to adequately visualize the suprahepatic vena cava and guide REBOVC positioning, without significant time-delay, when compared with fluoroscopic guidance, and compared with the corresponding REBOA placement. Methods: Nine anesthetized pigs were used to compare ultrasound-guided placement of supraceliac REBOA and suprahepatic REBOVC with corresponding fluoroscopic guidance, in terms of correct placement and speed. Accuracy was controlled by fluoroscopy. Four intervention groups: (1) fluoroscopy REBOA, (2) fluoroscopy REBOVC, (3) ultrasound REBOA and (4) ultrasound REBOVC. The aim was to carry out the four interventions in all animals. Randomization was performed to either fluoroscopic or ultrasound guidance being used first. The time required to position the balloons in the supraceliac aorta or in the suprahepatic inferior vena cava was recorded and compared between the four intervention groups. Results: Ultrasound-guided REBOA and REBOVC placement was completed in eight animals, respectively. All eight had correctly positioned REBOA and REBOVC on fluoroscopic verification. Fluoroscopy-guided REBOA placement was slightly faster (median 14 s, IQR 13-17 s) than ultrasound-guided REBOA (median 22 s, IQR 21-25 s, p=0.024). The corresponding comparisons of the REBOVC groups were not statistically significant, with fluoroscopy-guided REBOVC taking 19 s, median (IQR 11-22 s) and ultrasound-guided REBOVC taking 28 s, median (IQR 20-34 s, p=0.19). Conclusion: Ultrasound adequately and quickly guide the placement of supraceliac REBOA and suprahepatic REBOVC in a porcine laboratory model, however, safety issues must be considered before use in trauma patients. Level of evidence: Prospective, experimental, animal study. Basic science study.

Detection and isolation of intestinal muscle relaxant substances from the root of Taverniera abyssinica A. Rich.

ETHNOPHARMACOLOGICAL RELEVANCE: In Ethiopian traditional medicine the root of Taverniera abyssinica A.Rich is known as a remedy for sudden gastrointestinal cramping and fever. In this study we have isolated and identified the bioactive principle of Taverniera abyssinica that exerts effects on isolated smooth muscle tissues of the rabbit duodenum and guinea-pig ileum. AIM OF THE STUDY: To isolate and purify the bioactive principle from the root of Taverniera abyssinica A.Rich by bioassay-guided fractionation, HPLC purification and masspectrometry, with further investigation of its bioactivity on isolated smooth muscle strips. MATERIALS AND METHODS: Roots of Taverniera abyssinica A.Rich extracted in 75% methanol/water were fractioned with a reverse phase column and then subjected to HPLC purification. Each fraction collected from the HPLC was tested for its bioactivity using electric field stimulation-evoked contractions of the rabbit duodenum and guinea-pig ileum. Finally, detailed structural analysis of the fraction displaying significant bioactivity was made by mass spectrometry. RESULTS: Through bioassay-guided fractionation and HPLC purification the bioactive fractions were identified. These were tested for bioactivity on isolated smooth muscle strips which showed about 80% inhibition of contractions evoked by electric field stimulation. These compounds were identified as formononetin, afrormosin and tectorigenin by using masspectrometry applying relevant standards for detection. CONCLUSION: The traditionally claimed smooth muscle-relaxing effect of the roots of Taverniera abyssinica A.Rich is essentially due the three isolated and purified the two isoflavones formononetin, afrormosin as well as the metoxyisoflavone tectorigenin, along with possibly other not yet purified bioactive substances, however with similar smooth muscle-relaxing properties.

A randomized porcine study of hemorrhagic shock comparing end-tidal carbon dioxide targeted and proximal systolic blood pressure targeted partial resuscitative endovascular balloon occlusion of the aorta in the mitigation of metabolic injury.

BACKGROUND: The definition of partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is not yet determined and clinical markers of the degree of occlusion, metabolic effects and end-organ injury that are clinically monitored in real time are lacking. The aim of the study was to test the hypothesis that end-tidal carbon dioxide (ETCO2) targeted pREBOA causes less metabolic disturbance compared to proximal systolic blood pressure (SBP) targeted pREBOA in a porcine model of hemorrhagic shock. MATERIALS AND METHODS: Twenty anesthetized pigs (26-35 kg) were randomized to 45 min of either ETCO2 targeted pREBOA (pREBOAETCO2, ETCO2 90-110% of values before start of occlusion, n = 10) or proximal SBP targeted pREBOA (pREBOASBP, SBP 80-100 mmHg, n = 10), during controlled grade IV hemorrhagic shock. Autotransfusion and reperfusion over 3 h followed. Hemodynamic and respiratory parameters, blood samples and jejunal specimens were analyzed. RESULTS: ETCO2 was significantly higher in the pREBOAETCO2 group during the occlusion compared to the pREBOASBP group, whereas SBP, femoral arterial mean pressure and abdominal aortic blood flow were similar. During reperfusion, arterial and mesenteric lactate, plasma creatinine and plasma troponin concentrations were higher in the pREBOASBP group. CONCLUSIONS: In a porcine model of hemorrhagic shock, ETCO2 targeted pREBOA caused less metabolic disturbance and end-organ damage compared to proximal SBP targeted pREBOA, with no disadvantageous hemodynamic impact. End-tidal CO2 should be investigated in clinical studies as a complementary clinical tool for mitigating ischemic-reperfusion injury when using pREBOA.

Low profile REBOA device for increasing systolic blood pressure in hemodynamic instability: single-center 4-year experience of use of ER-REBOA.

BACKGROUND: Hemodynamic instability due to torso hemorrhage can be managed with the assistance of resuscitative endovascular balloon occlusion of the aorta (REBOA). This is a report of a single-center experience using the ER-REBOA™ catheter for traumatic and non-traumatic cases as an adjunct to hemorrhage control and as part of the EndoVascular resuscitation and Trauma Management (EVTM) concept. The objective of this report is to describe the clinical usage, technical success, results, complications and outcomes of the ER-REBOA™ catheter at Örebro University hospital, a middle-sized university hospital in Europe. METHODS: Data concerning patients receiving the ER-REBOA™ catheter for any type of hemorrhagic shock and hemodynamic instability at Örebro University hospital in Sweden were collected prospectively from October 2015 to May 2020. RESULTS: A total of 24 patients received the ER-REBOA™ catheter (with the intention to use) for traumatic and non-traumatic hemodynamic control; it was used in 22 patients. REBOA was performed or supervised by vascular surgeons using 7-8 Fr sheaths with an anatomic landmark or ultrasound guidance. Systolic blood pressure (SBP) increased significantly from 50 mmHg (0-63) to 95 mmHg (70-121) post REBOA. In this cohort, distal embolization and balloon rupture due to atherosclerosis were reported in one patient and two patients developed renal failure. There were no cases of balloon migration. Overall 30-day survival was 59%, with 45% for trauma patients and 73% for non-traumatic patients. Responders to REBOA had a significantly lower rate of mortality at both 24 h and 30 days. CONCLUSIONS: Our clinical data and experience show that the ER-REBOA™ catheter can be used for control of hemodynamic instability and to significantly increase SBP in both traumatic and non-traumatic cases, with relatively few complications. Responders to REBOA have a significantly lower rate of mortality.

Hemodynamic Effect of Resuscitative Endovascular Balloon Occlusion of the Aorta in Hemodynamic Instability Secondary to Acute Cardiac Tamponade in a Porcine Model.

BACKGROUND: The pre-hospital use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is increasing, although it remains controversial, in part because of suggested contraindications such as acute cardiac tamponade (ACT). As both the pre-hospital and in-hospital use of REBOA might potentially occur with concurrent ACT, knowledge of the hemodynamic effect of REBOA in this setting is crucial. This study, therefore, aimed at investigating the physiological effects of REBOA in hemodynamic instability secondary to ACT in a porcine model. We hypothesize that REBOA can temporarily increase systemic blood pressure and carotid blood flow, and prolong survival, in hemodynamic shock caused by ACT. METHODS: Fourteen pigs (24-38 kg) underwent ACT, through true cardiac injury and hemorrhage into the pericardial space, and were allowed to hemodynamically deteriorate. At a systolic blood pressure (SBP) of 50 mm Hg (SBP50) they were randomized to total occlusion REBOA in zone 1 or to a control group. Survival, hemodynamic parameters, carotid blood flow (CBF), femoral blood flow (FBF), cardiac output (CO), end-tidal CO2, and arterial blood gas parameters were analyzed. RESULTS: REBOA intervention was associated with a significant increase in SBP (50 mm Hg to 74 mm Hg, P = 0.016) and CBF (110 mL/min to 195 mL/min, P = 0.031), with no change in CO, compared to the control group. At 20 min after SBP50, the survival rate in the intervention group was 86% and in the control group 14%, with time to death being significantly longer in the intervention group. CONCLUSIONS: This randomized animal study demonstrates that REBOA can help provide hemodynamic stabilization and prolong survival in hemodynamic shock provoked by ACT. It is important to stress that our study does not change the fact that urgent pericardiocentesis or cardiac surgery is, and should remain, the standard optimal treatment for ACT.Level of evidence: Prospective, randomized, experimental animal study. Basic science study, therapeutic.