| Backgrounds:Hypothermic circulatory arrest (HCA) is often applied during treatment procedure of aortic arch surgery. Although great progress had been made on HCA in recent years, aortic arch surgery still have relatively high postoperative mortality and morbidity.Common complications include respiratory failure, liver and kidney dysfunction, spinal cord injury, gastrointestinal complications . Present studies suggest that multi-organ dysfunction is related to systemic inflammatory response syndrome (SIRS) after CPB. Gastrointestinal hypoperfusion and subsequent ischemia reperfusion injury lead to loss of gastrointestinal mucosal barrier function resulted in the toxins absorbed into the bloodstream, is the initial pathogenesis factor of SIRS. Protection of visceral organ function in major vascular surgery is of great importance.In aortic arch surgery, distal aortic perfusion from the femoral artery is ommonly used to protect internal organs during cardiopulmonary bypass. When celiac artery is involved in thoracoabdominal aortic aneurysm (TAAA) , bridge arterial perfusion is more likely to be used . However, the above methods has either complex operation procedure or ineffective protection results.Inferior vena cava and hepatic, kidney veins of human ,pigs and dogs have no obvious venous valves. It is theoretically feasible to protect viseral organs via retrograde perfusion through inferior vena cava . Literatured reviewed , there has not systemic research on retrograde perfusion through inferior vena cava to protect abdominal organs.Objective:The aim of this subject is to build model of deep hypothermia circulatory arrest with retrograde perfusion through inferior vena cava and to test it's protection results of visceral organ function during DHCA .Methods(1) Pigs were used as experimental animals model to simulate aortic arch surgery conditions of deep hypothermic circulatory arrest. Group A is under DHCA at 20℃for 90 min. Group B is under the same condition as DHCA and at the same time by retrograge perfusion through IVC with Autologous diluted blood. Both groups were declamped 90 minutes later. When the status were stable and body temperature were remarmed to 37℃, cardiopulmonary bypass was stopped and maintain anesthesia status for another 10 hours. During this progress, biochemical, blood gas, mesenteric microcirculation, pathology and other index were detected to evaluate the method of the protective effect of important abdominal organs.(2) Level of inflammatory factor serum TNF-α, IL-1, IL-6, IL-8, levels of serum,liver and kidney Malondialdehyde (MDA) content and superoxide dismutase (SOD) were detected.(3) Depending on the perfusion pressure, the subjects were divided into 4 groups. group A in under DHCA alone, Group B is under DHCA and 25 mmHg retrograde perfusion pressure. Group C is under 15mmHg pressure and Group D is under35 mmHg pressure. Serum liver and kidney function, mesenteric blood flow, pathological changes were tested in different groups to evacuate the protective effect complications of each group.(4)Kidneys, liver cell apoptosis index were measured by Tunel staining. The mRNA levels of apoptosis related genes Bax, Bcl-2 of liver and kidney tissue were tested by real-time quantitative PCR. Caspase-3 activity of liver and kidney tissue were detected by spectrophotometry .Results(1) Model of hypothermic circulatory arrest with retrograde perfusion through IVC was constructed successfully.(2) The level of alanine transarninase and aspartate aminotransferase were declined in group B compared with group A 10 hours after DHCA (P <0.05); blood urea nitrogen, creatinine have no Significant difference between these two groups(P> 0.05).β2-microglobulin were increased in group A since 1 hour after reperfusion compared with group B(P<0.05).(3) Blood gas analysis showed lactate clearance rate (LER) of liver, oxygen consumption of live and kidney were higher in group B compared with group A during retrograde perfusion period (P <0.01).(4) Blood flow velocity of mesentery microvessels were greatly increased in group B compared with group A 60 minutes after retrograde perfusion, 30 and 60minutes after reperfusion. Blood flow velocity in Group B during retrograde perfusion was about 25-36% of CPB level, while it was only about 1% of CPB in group A during DHCA.(5) The levels of malondialdehyde contents in Serum, liver and kidney tissue were decreased in group B after DHCA compared with group A(P<0.05), while the level of superoxide dismutase activity in Serum, liver and kidney tissue were increased in group B compared with group A(P<0.05).(6) The levels of serum IL-1, L-6, IL-8, TNF-αwere increased significantly (P <0.01) after DCHA . However , it can be reduced significantly by retrograde perfusion through IVC (P <0.01).(7) Blood flow velocity of mesenteric arteriole was faster in group B compared with group C, and slower compared with group D (P<0.05). Blood flow velocity of mesenteric veinule was faster in group B compared with group C(P<0.05), However ,there is no significant difference between group C and D(P>0.05).(8) Pathological examination show swelling of hepatocytes tubular epithelial cells in group D. No morphological abnormality has been observed in group A,B and C.(9) Apoptosis index in liver tissues by Tunel staining show group A (10.51±2.65)> group D (7.73±1.54)> group C (4.30±0.97)> group B (2.40±0.34). Apoptosis index in kidney tissues by Tunel staining group A (10.51±2.65)> group D (7.73±1.54)> group C (4.30±0.97)> group B (2.40±0.34).(10)The mRNA expression of Bcl-2 was lower in group A than group B,C,D (P <0.05). Group D was slower group B,C (P <0.05). Bax mRNA expression in group A was higher than group B,C and D (P <0.05 ). It was higher in group D than that in group B and group C (P <0.05). Caspase-3 activity was higher in group A than that in group B,C and D (30.08±5.16)(p <0.01). It was higher in group D than that in group B and group C.Conclusions:(1) The animal model of hypothermic circulatory arrest with retrograde perfusion through IVC was constructed successfully.(2) By applications of retrograde perfusion via IVC with Autologous diluted blood , the levels of serum ALT, AST andβ2-microglobulin can be decreased ,and blood flow velocity of mesentery microvessels , lactate clearance rate of liver, oxygen consumption of live and kidney can be improved .(3) The levels of malondialdehyde were increased and superoxide dismutase activity were decreased in Serum,liver and kidney tissues during DHCA procedure. Retrograde perfusion through IVC can reduce oxidative stress and ischemia reperfusion injury by decrease MDA contents and increase SOD activity in serum , liver and kidney tissues.(4) The level of plasmic TNF-a,IL-1,IL-6,IL-8 were increased during DHCA procedure. Retrograde perfusion through IVC can alleviate the inflammatory response by greatly reduce the level of TNF-a,IL-1,IL-6,IL-8 , and thus has anti-inflammatory effect .(5) Retrograde perfusion through IVC can decreased the apoptosis index in liver and kidney tissues , probably by enhancing Bcl- 2 mRNA expression , decreasing Bax gene expression and reducing the activity of Caspase-3.(6) Optimal retrograde perfusion pressure is 25 mmHg compared with 15mmHg and 35mmHg.
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