Mesenteric Artery Injury Research Articles

Emergency rescue of a patient with hemorrhagic shock caused by superior mesenteric artery rupture: A case report

BACKGROUND Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient’s condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient’s condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient’s successful recovery.

Abstract 101: Similar Cd28 + Delta T Effector Memory Cell Subpopulations Are Present In Murine Perivascular Tissues Of Angiotensin II-infused Male Mice And Subcutaneous White Adipose Tissue Of Obese Women

Introduction: The innate-like γδ T cells play a role in angiotensin II (AngII)-induced hypertension, mesenteric artery injury and T cell activation in mesenteric vessels/perivascular adipose tissue (MV/PVAT) in mice. Blood γδ T cells frequency is associated with systolic blood pressure in humans. Obesity was associated with small artery injury in subcutaneous white adipose tissue (WAT) and is a risk factor for hypertension in humans. We hypothesized that single cell RNA sequencing (scRNA-seq) in MV/PVAT of AngII-infused vs control mice and in subcutaneous WAT of obese vs lean humans will reveal γδ T cell subpopulations involved in hypertension, vascular injury and T cell activation. Methods: Male C57BL/6J mice were infused SC or not with 490 ng/kg/min AngII for 14 days (n=3). Hypertension was confirmed by tail cuff blood pressure measurement. MV/PVAT were collected, and T cells were isolated and used for scRNA-seq. γδ T cell subpopulations were studied by subclustering T cells expressing the T cell receptor δ constant chain. Cell subpopulations were validated by flow cytometry. Subcutaneous WAT CD45 + cell ScRNA-seq data of 3 lean and 3 obese women were obtained from GEO NCBI database (GSE155960) and γδ T cell subpopulations analyzed as above. Results: ScRNA-seq identified 6 murine and 9 human δ T cell subclusters. AngII increased Cd28 high (% of T cells: 3.6±0.9 vs 1.4±0.2) and Trdv4 + δ T effector memory (EM) cells (7.3±1.3 vs 3.4±1.7) and lowered resting δ T cells (1.0±0.2 vs 4.2±1.5) in mice. Cd28 high δ T EM and resting δ T cell study by flow cytometry using unique marker pairs, CD28 + SELL - and CD28 - SELL + , showed that AngII increased CD28 + SELL - (cell number: 376±48 vs 220±40) and decreased CD28 - SELL + δ T cells (23±4 vs 45±4) in MV/PVAT. Cd28 / CD28 subclustering of δ T cells identified 4 human and murine cell populations and showed that AngII increased Cd28 + γδ natural killer T EM (% of T cells: 1.9±0.3 vs 0.5±0.2) and Cd28 high δ T EM cell subpopulations (1.6±0.5 vs 0.2±0.1) in mice, and that CD28 + δ T EM-1 cell subpopulation tended to be increased in obese vs lean women. Conclusion: ScRNA-seq revealed similar δ T EM cell subpopulations expressing CD28 in murine MV/PVAT and human subcutaneous WAT that could play a role in hypertension, vascular injury and T cell activation.

Superior Mesenteric Artery Injury during Robotic Radical Nephrectomy: Scenarios and Management Strategies.

Injury to the superior mesenteric artery (SMA) is a rare, underreported, and potentially devastating complication. This study aims to propose a systematic workup to describe how to prevent and manage SMA injury in a standardized stepwise manner. Three different instances of intraoperative injury to the SMA are described in an accompanying video. All three occurred when the SMA was misidentified as the left renal artery during left robotic radical nephrectomy. In the first case, the SMA was mistakenly identified as the renal artery, but after further dissection, the real renal artery was identified and SMA injury was prevented. In the second case, the SMA was clipped and the real left renal artery was subsequently identified, requiring clip removal. In the third case, the SMA was clipped and completely transected, requiring prompt repair by vascular surgery with a successful outcome. This study aims to propose a systematic workup to describe how to prevent and manage SMA injury in a standardized stepwise manner. The proper anatomic recognition of the SMA may prevent its injury. Intraoperative SMA injury should be promptly identified and repaired to avoid its devastating consequences.

Complications and Technical Consideration of Ultrasound-Guided Rectus Sheath Blocks: A Retrospective Analysis of 4033 Patients.

Although the ultrasound-guided rectus sheath block (RSB) is usually regarded as an easy and safe procedure in clinical settings, there is currently no report on complications incidence. Therefore, the present study investigated complications in a large cohort and described the technical considerations to minimize complications of real-time ultrasound-guided RSBs. This was a retrospective cohort study of patients who underwent real-time ultrasound-guided RSBs for perioperative pain control in laparoscopic surgery with an umbilical port between February 1, 2017, and February 28, 2021, at the Asan Medical Center in South Korea. All RSBs were performed bilaterally using a 23-gauge Quincke needle, and a bilateral 2-block placement was regarded as 1 RSB. Patient data, including demographics, preoperative laboratory data, preoperative antiplatelet or anticoagulant medication with the duration of discontinuation, and type of surgery, were collected to show the study population characteristics and explore potential factors associated with adverse events such as hematoma. Ultrasound images of patients and adverse events of RSBs, including extrarectus sheath injections, vascular injuries, bowel injury, or local anesthetic systemic toxicity, were also analyzed accordingly. A total of 4033 procedures were analyzed. The mean body mass index of the patients was 24.1 (21.8-26.5) kg/m2. The preoperative laboratory data were within normal range in 4028 (99.9%) patients. Preoperative antiplatelets or anticoagulants were administered in 17.3% of the patients. Overall, 96 complications (2.4%) were observed. Among them, extrarectus sheath injection occurred in 88 cases (2.2%), which included preperitoneal injection (0.9%) and intraperitoneal injection (1.3%). Vascular injuries constituted 8 cases (0.2%) and all vascular injuries resulted in hematoma: 7 cases of inferior epigastric artery injury with rectus sheath hematoma and 1 of inferior mesenteric artery injury with retroperitoneal hematoma. Bowel injury or local anesthetic systemic toxicity was not reported. In this study of RSBs performed on 4033 patients using a 23-gauge Quincke needle in patients with low body mass index, there were 8 cases (0.2%) of vascular injury, all of which accompanied hematoma.

H12‐(ADP)‐liposomes for hemorrhagic shock in thrombocytopenia: Mesenteric artery injury model in rabbits

BackgroundDamage control resuscitation improves patient outcomes after severe hemorrhage and coagulopathy. However, effective hemostasis methods for these critical situations are lacking. ObjectiveWe evaluated the hemostatic efficacy of fibrinogen γ‐chain (HHLGGAKQAGDV, H12)‐coated, adenosine‐diphosphate (ADP)‐encapsulated liposomes (H12‐[ADP]‐liposomes) in thrombocytopenic rabbits with hemorrhagic shock. MethodsAcute thrombocytopenia (80%) was induced in rabbits that also received mesenteric vessel injury, leading to hemorrhagic shock. Five minutes after injury, subjects received intravenous bolus injection with H12‐(ADP)‐liposomes (20 mg/kg), followed by isovolemic transfusion with stored red blood cells (RBCs)/platelet poor plasma (PPP) (RBC:PPP = 1:1 [vol/vol]), or lactated Ringer solution every 5 min to compensate blood loss. One group received H12‐(phosphate buffered saline [PBS]) liposomes followed by RBC/PPP. Additional groups were received isovolemic transfusion with RBC/platelet rich plasma (PRP) (RBC:PRP = 1:1 [vol/vol]), RBC/PPP, PPP alone, or lactated Ringer solution. ResultsTreatment with H12‐(ADP)‐liposomes followed by RBC/PPP transfusion and RBC/PRP transfusion effectively stopped bleeding in all thrombocytopenic rabbits. In contrast, three of 10 rabbits treated with RBC/PPP failed hemostasis, and no rabbits receiving lactated Ringer solution stopped bleeding or survived. Twenty‐four hours after hemorrhage, 80% of rabbits receiving H12‐(ADP)‐liposome followed by RBC/PPP transfusion survived and 70% of rabbits receiving RBC/PRP transfusion also survived, although RBC/PPP‐transfused rabbits showed 40% survival. Rabbits receiving H12‐(ADP)‐liposomes followed by lactated Ringer solution showed a transient hemostatic potential but failed to survive. H12‐(PBS)‐liposomes showed no beneficial effect on hemostasis. Neither the PPP group nor the lactated Ringer group survived. ConclusionH12‐(ADP)‐liposome treatment followed by RBC/PPP may be effective in lethal hemorrhage after mesenteric vessel injury in coagulopathic rabbits.

Superior Mesenteric Artery and Vein Injuries: Operative Strategies and Outcomes.

Traumatic injuries to the mesenteric vessels are rare and often lethal. Visceral vessels, such as the superior mesenteric artery (SMA) and vein (SMV), supply blood to the small and large bowel by a rich system of collaterals. Because fewer than 100 such injuries have been described in the literature, they pose challenges in both diagnosis and management and can unfortunately result in high mortality rates. Prompt diagnosis, surgical intervention, and resuscitation can lead to improved outcomes. Here, we review the literature surrounding traumatic injuries of the SMA/SMV and discuss management strategies.

A Novel Approach for Repairing Superior Mesenteric Artery Injury During Left Nephrectomy—6-year Follow-up

To describe a novel approach for reconstructing the superior mesenteric artery (SMA) during left nephrectomy and review the literature. The patient was a 57-year-old man with left back pain from an unknown cause for more than 3 hours. A computed tomography scan showed a 12-×15-cm firm mass and a subcapsular hematoma in the left kidney. It was considered to be bleeding and rupture of the solid renal mass, and because of persistent pain and no documented distant metastatic disease, a transperitoneal laparoscopic nephrectomy was elected, but the procedure was converted to open surgery for SMA injury. We reconstructed the SMA with end-to-end anastomosis between the SMA and the left renal artery stump. At the 6-year follow-up, the patient had no intestine-related sequelae. Our novel approach of an end-to-end anastomosis between the SMA and the left renal artery stump is an option for SMA injury, especially when orthotopic anastomosis or repair of the SMA is not indicated.

FJVIS 13. Endovascular Management of Blunt Celiac and Mesenteric Artery Injuries: Midterm Outcomes

FJVIS 13. Endovascular Management of Blunt Celiac and Mesenteric Artery Injuries: Midterm Outcomes

The effects of Xiaotan Huayu Liqiao formula on mesenteric artery function in rats exposed to chronic intermittent hypoxia

To investigate the effects of Xiaotan Huayu Liqiao formula (the Chinese Medicine) on mesenteric artery function in rats exposed to chronic intermittent hypoxia (CIH), and to explore the related mechanism. Forty-eight male SD rats were randomly divided into four groups as Normoxia, CIH, Formula+CIH and formula group. Rats were exposed to normoxia in the Normoxia and Formula group, or intermittent hypoxia in CIH or Formula+CIH group. Xiaotan Huayu Liqiao formula was given at 24g/kg by intragastric administration before intermittent hypoxia exposure. The pathological changes of mesenteric artery were determined by HE staining, and the relaxation of mesenteric artery (induced by acetylcholine(ACh) and L-arginine(L-Arg)) was recorded by microvascular ring technique. Serums of all rats were collected (0 d and 21 d) and the content of NO was detected by ELISA. The levels of endothelial nitric oxide synthase (eNOS) and p-eNOS were measured by Western blot. Compared with Normoxia group, the mesenteric arterial endothelial injury and media thickening were observed and the relaxation of mesenteric artery was significantly reduced in rats exposed to CIH. The level of NO in serum and the ratio of p-eNOS/eNOS were also decreased in the CIH group. Xiaotan Huayu Liqiao formula administration improved the pathologic changes and dilatation function of mesenteric artery, increased the levels of NO and p-eNOS. Compared with Normoxia group,all the results were not observed significant difference in Formula group. Xiaotan Huayu Liqiao formula increased the bioavailability of NO, and ameliorated the CIH induced mesenteric artery function injury.

Blunt Abdominal Aorta, Celiac Artery, and Superior Mesenteric Artery Injuries Treated Endovascularly

Blunt Abdominal Aorta, Celiac Artery, and Superior Mesenteric Artery Injuries Treated Endovascularly

The transmembrane protein disulfide isomerase TMX1 negatively regulates platelet responses

AbstractSecreted platelet protein disulfide isomerases, PDI, ERp57, ERp5, and ERp72, have important roles as positive regulators of platelet function and thrombosis. Thioredoxin-related transmembrane protein 1 (TMX1) was the first described transmembrane member of the protein disulfide isomerase family of enzymes. Using a specific antibody, the recombinant extracellular domain of TMX1 (rTMX1) protein, a knockout mouse model, and a thiol-labeling approach, we examined the role of TMX1 in platelet function and thrombosis. Expression of TMX1 on the platelet surface increased with thrombin stimulation. The anti-TMX1 antibody increased platelet aggregation induced by convulxin and thrombin, as well as potentiated platelet ATP release. In contrast, rTMX1 inhibited platelet aggregation and ATP release. TMX1-deficient platelets had increased aggregation, ATP release, αIIbβ3 activation, and P-selectin expression, which were reversed by addition of rTMX1. TMX1-knockout mice had increased incorporation of platelets into a growing thrombus in an FeCl3-induced mesenteric arterial injury model, as well as shortened tail-bleeding times. rTMX1 oxidized thiols in the αIIbβ3 integrin and TMX1-deficient platelets had increased thiols in the β3 subunit of αIIbβ3, consistent with oxidase activity of rTMX1 against αIIbβ3. Thus, TMX1 is the first identified extracellular inhibitor of platelet function and the first disulfide isomerase that negatively regulates platelet function.

Superior mesenteric artery injury during laparoscopic radical nephrectomy

The authors present to your a en on a rare clinical case of complete intersec on of the superior mesenteric artery in laparoscopic radical nephrectomy. This complica on emerged in the process of learning the technique of laparoscopic radical nephrectomy, before reaching the “plateau” of the learning curve, in condi ons of poor vision and in the interposi on of tissues due to paratumorous infitiltra on. This type of injury has a high risk of total necrosis of the small intestine. However, due to the concerted ac ons of the surgical service and the readiness of surgeons to complete the vascular suture of the main vessels, a successful reimplanta on of the superior mesenteric artery into the aorta was performed. This is confi rmed by postopera ve observa on and examina on, which included CT angiography. It should be noted that descrip ons of cases of aor c reimplanta on of the superior mesenteric artery are extremely rare in the world and national literature, except for cases of mesenteric ischemia. This case contributes to the description of rare cases of aor c reimplanta on of the superior mesenteric artery and shows the correctness of the selected surgical tactics.

The disulfide isomerase ERp72 supports arterial thrombosis in mice

AbstractSeveral CGHC motif–containing disulfide isomerases support thrombosis. We here report that endoplasmic reticulum protein 72 (ERp72), with 3 CGHC redox-active sites (ao, a, and a′), supports thrombosis. We generated a new conditional knockout mouse model and found that Tie2-Cre/ERp72fl/fl mice with blood and endothelial cells lacking ERp72 had prolonged tail bleeding times and decreased platelet accumulation in laser-induced cremaster arteriole injury and FeCl3-induced mesenteric arterial injury. Fibrin deposition was decreased in the laser injury model. Both platelet and fibrin accumulation defects were fully rescued by infusion of recombinant ERp72 containing functional a and a′ CGHC motifs (ERp72(oo-ss-ss)). Infusion of ERp72 containing inactivated a and a′ CGHC motifs (ERp72(ss-oo-oo)) inhibited platelet accumulation and fibrin deposition in wild-type mice. Infusion of ERp72(oo-ss-ss) into β3-null mice increased fibrin deposition in the absence of platelets. ERp72-null platelets had defective aggregation, JON/A binding, P-selectin expression, and adenosine triphosphate (ATP) secretion. The aggregation and ATP secretion defects were fully rescued by ERp72(oo-ss-ss) but partially rescued by ERp72(ss-oo-ss) and ERp72(ss-ss-oo). Aggregation and ATP secretion of human platelets was potentiated by ERp72(oo-ss-ss) but inhibited by ERp72(ss-oo-ss) and ERp72(ss-ss-oo). These data suggest that both the a and a′ active sites are required for platelet function. ERp72 bound poorly to β3-null mouse platelets, and the addition of ERp72(oo-ss-ss) to human platelets generated thiols in αIIbβ3, suggesting a direct interaction of ERp72 with αIIbβ3. Defective aggregation of ERp72-null platelets was recovered by ERp72, but not other thiol isomerases. In summary, ERp72 plays a critical role in platelet function and coagulation through the a and a′ CGHC motifs.

SMA Balloon OcclusionとDamage Control Surgeryが奏効した外傷性SMA損傷の1救命例

SMA Balloon OcclusionとDamage Control Surgeryが奏効した外傷性SMA損傷の1救命例

The Second CGHC Motif of Protein Disulfide Isomerase Mediates Thrombosis

Protein disulfide isomerase (PDI) catalyzes thiol-disulfide exchange reactions that are critical for protein function. PDI has two distinct CGHC redox-active sites, but nothing is known about which site is important in physiologic reactions including thrombosis. To study the role of PDI and its active sites in thrombosis we used two genetically-modified models, Mx1-Cre/PDIfl/fl mice with blood cells and vessel wall cells lacking PDI, and transgenic PDI(ss-oo) mice with PDI lacking the second CGHC active site. Using laser-induced cremaster arteriole injury fibrin deposition was decreased in both mouse models. Both mouse models showed attenuation of platelet accumulation using laser arterial injury and FeCl3-induced mesenteric artery injury. The defects in fibrin deposition and platelet accumulation were rescued by infusion of recombinant PDI(oo-ss) containing only a functional second active site, confirming the second active site of PDI was critical for both fibrin formation and platelet accumulation. In vitro studies showed that platelet aggregation depended on the second CGHC motif of PDI, and that binding of PDI protein to platelets depended on the presence of the αIIbβ3 integrin. Studies on platelet secretion revealed that P-selectin expression and ATP release were dependent on a functional second active site of PDI. Treatment of the platelets with eptifibatide did not affect P-selectin expression. Together these findings suggest the second active of PDI catalyzes a reaction in αIIbβ3 supporting platelet aggregation and a reaction in a non-αIIbβ3 substrate supporting secretion. In vivo studies on coagulation showed that PDI infusion rescued fibrin formation in eptifibatide-treated mice in which platelet accumulation was completely blocked, suggesting that PDI directly contributes to activation of coagulation. In summary, our results indicate that the second CGHC active site of PDI has a role in platelet function and coagulation. Targeting this site may have a dual inhibitory effect on thrombosis by decreasing both platelet and fibrin accumulation. DisclosuresNo relevant conflicts of interest to declare.

Endovascular Treatment of Proximal Superior Mesenteric Artery Pseudoaneurysm after Stab Injury

Superior mesenteric artery (SMA) injuries remain a challenge to most trauma surgeons and continue to result in significant mortality despite aggressive management. We report successful management of a proximal SMA injury through endovascular treatment in a 56-year-old man. The patient presented with hypotension due to a stab wound after the epigastrium. He underwent emergency laparotomy and repair of the penetrated wall of the stomach. Right retroperitoneal hematoma at the initial laparotomy expanded and ruptured, requiring a massive transfusion. At the second laparotomy, we performed lateral arteriorrhaphy of the proximal SMA. Follow-up abdominal computed tomography angiography on post-injury day 7 showed a pseudoaneurysm on the left side of the SMA trunk. The patient was treated successfully with an endovascular stent graft.

The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis.

Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown. Here, we evaluated the role of PDI and redox-active sites of PDI in thrombosis by generating mice with blood cells and vessel wall cells lacking PDI (Mx1-Cre Pdifl/fl mice) and transgenic mice harboring PDI that lacks a functional C-terminal CGHC motif [PDI(ss-oo) mice]. Both mouse models showed decreased fibrin deposition and platelet accumulation in laser-induced cremaster arteriole injury, and PDI(ss-oo) mice had attenuated platelet accumulation in FeCl3-induced mesenteric arterial injury. These defects were rescued by infusion of recombinant PDI containing only a functional C-terminal CGHC motif [PDI(oo-ss)]. PDI infusion restored fibrin formation, but not platelet accumulation, in eptifibatide-treated wild-type mice, suggesting a direct role of PDI in coagulation. In vitro aggregation of platelets from PDI(ss-oo) mice and PDI-null platelets was reduced; however, this defect was rescued by recombinant PDI(oo-ss). In human platelets, recombinant PDI(ss-oo) inhibited aggregation, while recombinant PDI(oo-ss) potentiated aggregation. Platelet secretion assays demonstrated that the C-terminal CGHC motif of PDI is important for P-selectin expression and ATP secretion through a non-αIIbβ3 substrate. In summary, our results indicate that the C-terminal CGHC motif of PDI is important for platelet function and coagulation.

Damage control surgery after severe superior mesenteric artery injury

Objective To determine the effect of different surgical modalities on hemodynamics,systemic major organ injury and survival rate following superior mesenteric artery (SMA) injury in an attempt to search a modality that conforms to principles of damage control surgery (DCS).Methods SMA was exposed in 30 domestic hybrid pigs,leaving the blood flow blocked using non-invasive vessel forceps.The animals were divided into control group,primary anastomosis group (anastomosis group) and temporary intravascular shunt (TIVS) group according to random number table.TIVS group was further divided into three subgroups:shunting for 6 hours group (TIVS-6 h group),9 hours group (TIVS-9 h group) and 12 hours group (TIVS-12 h group).At each time point,the angiography was performed for evaluation of shunt patency; hemodynamic parameters were detected,terminal ileum and SMA samples were harvested for pathological analysis.Results All groups suffered extreme physiological conditions including hypothermia,severe acidosis,hypotension,low cardiac output and low oxygen supply.Less requirement of resuscitation fluid,faster restoration of SMA blood flow,earlier clearance of lactate,milder intestinal ischemia-reperfusion injury and higher survival rate were observed in TIVS-6 h and TIVS-9 h groups,compared with anastomosis group.Patency rate in TIVS-6 h,9 h and 12 h groups was 100％,50％ and 0％ respectively.Pathologic outcome of intestine revealed diffuse intestinal necrosis in TIVS-12 h group and reversible intestinal ischemia-reperfusion injury in TIVS-6 h and 9 h groups.Conclusion For SMA injury in severe hemodynamic disarrangement and jeopardized condition,TIVS shortens intestinal ischemia time,maintains systemic hemodynamic stability,relieves intestinal injury,improves early survival rate and keeps long-term intestine patency when compared with primary vascular anastomosis. Key words: Shock; Mesenteric artery, superior; Damage control surgery

Evidence for the Nitric Oxide Pathway as a Potential Mode of Action in Fenoldopam-induced Vascular Injury

Fenoldopam, a dopaminergic DA1 agonist, induces vasodilatation via nitric oxide (NO), and this may be associated with mesenteric arterial injury. NO is produced from the enzymatic action of nitric oxide synthase (NOS), which is regulated by the shear-stress mediating protein caveolin-1. Profound vasodilatation and accompanied decreased shear are early events that could initiate vascular injury. Therefore, it is of interest to determine the role of caveolin-1 and the NO pathway in fenoldopam-induced vascular injury. At sites of fenoldopam-induced mesenteric arterial injury, decreased caveolin-1 expression and apoptosis were prominent immunohistochemical findings. An additional finding at these sites of injury were loss and/or reduced expression of caveolin-1 regulated structural proteins, connexin-43, (gap junction) ZO-1, and claudin (tight junctions). Because functional loss of caveolin-1 is associated with increased NOS activity and vasodilatation via NO, studies were conducted to show a NO donor produced vascular lesions in the mesenteric arteries morphologically similar to those induced by fenoldopam. Moreover, the incidence and severity of fenoldopam-induced vascular injury were reduced when an NOS inhibitor or a scavenger of NO-generated free radicals were coadministered with fenoldopam. Collectively, these data suggest that caveolin-1 and its regulated NO pathway may play an important role in vasodilatory drug-induced vascular injury.

Prolonged Indwelling Time of Temporary Vascular Shunts Is Associated With Increased Endothelial Injury in the Porcine Mesenteric Artery

Temporary intravascular shunts (TIVS) have been used as a damage control surgery (DCS) adjuncts in superior mesenteric artery (SMA) injuries, both experimentally and clinically. However, no study to date has evaluated the relationship between shunt indwelling time and resultant endothelial cell (EC) injury. We hypothesized that prolonged use of TIVS in SMA injuries would jeopardize EC integrity. After laparotomy, the SMA was clamped and transected while pigs were hemorrhaged to 40 mm Hg for 30 minutes. A TIVS was inserted between transected ends of the SMA without systemic anticoagulation. Totally, 24 animals were resuscitated and randomized to different shunt indwelling time groups: A, 3 hours; B, 6 hours; C, 9 hours; and D, 12 hours. Patency of shunts was monitored and recorded. Continuous wave Doppler was used as a determinant of adequacy of flow through the shunts. Transmural SMA biopsies from areas of TIVS placement were examined with electron microscopy for histopathologic injury after staining with hematoxylin and eosin and immunofluorescence using a validated histopathologic injury score (minimum-maximum score: 0-4). Severity of endothelial injury was observed to be directly related to shunt indwell time. SMA transmural biopsies harvested from group D animals showed the most profound injury, demonstrating extensive EC denudations and marked intimal rupture (injury grade, 3.4 ± 0.2). Sections from group A animals revealed the mildest EC injury (1.3 ± 0.3 vs. group D p < 0.01). No significant difference was detected between group A and B. EC injury grade in group C (2.7 ± 0.6) was higher than that in group B (1.8 ± 0.6) but did not reach statistical significance (p = 0.58). When possible, vascular reconstruction following use of shunts should include an interposition graft after debridement of the arterial edges having interfaced with the shunt. Finally, to minimize intimal injury to the native vessel, this model suggests that indwell times of shunts should be <9 hours.