The Effects Of Intra-abdominal Hypertension On Heart, Adrenal, Pancreatic Function In Canine And Its Mechanism

The damage of increased intra-abdominal pressure (IAP) to heart, adrenal andpancreatic function had been found150years ago. However, it was until2006whenintra-abdominal hypertension (IAH) was defined by World Society of the abdominalaompartment ayndrome (WSACS) as intra-abdominal pressure that rose to more than12mmHg and abdominal compartment syndrome (ACS) as elevated intra-abdominalpressure combined with or without abdominal perfusion pressure (APP)≤60mmHg aswell as organ disfuction and failure. Elevated IAP results in systematic organ disfuction ineither direct or indirect manners. Experiments on animals by Emerson in1911have proveddeath from cardiovascular event caused by elevated IAP. So far studies on the effects ofIAH on the cardiovascular system mainly focused on hemodynamics, and cardiacdysfunction related researches are few and prone to be one-sided. In addition, relativemechanism of cardiac dysfunction caused by IAH has not been reported. Dopplerechocardiography (Doppler UCG) is now widely used in the evaluation of hemodynamicsand regional wall motion. Speckle tracking imaging (STI) is employed in the evaluation ofsystolic and diastolic segmental endocardial motion, mainly in coronary artery disease. STIin the systematic evaluation of impact of early IAH to cardiac dysfunction shall bear greatclinical value due to its advantages of rapidity, invasiveness, cost effectiveness and bedsideoperation. Therefore, the search and establishment of early systematic evaluation method inIAH related cardiac function changes aimed at exploration into the possible mechanism ofcardiac dysfunction caused by IAH and corresponding intervention measures have greatsignificance in the improvement of curative rates and mortality reduction.IAH has impact on various body organs systems, but studies on the functional effectsof IAH on endocrine function are rare. While the adrenal gland and pancreas play importantrole in maintaining stability of the internal environment, so in this study, we also observedthe effect of IAH on the secretion of adrenal glands and pancreas. The main experimental methods:PartⅠThe effect and mechanism of intra-abdominal hypertension on the cardiacfunction in dogs.1. Impact of intra-abdominal hypertension on hemodynamics in dogs.IAH models were made from local hybrid dogs by slowly injecting air (5ml/s) intotheir abdomens with50ml syringes. Models were divided into the sham operation group(GroupⅠ,n=6), the IAH group (Group Ⅱ,n=24) and the Decompression group (GroupⅢ, n=24). The IAH group was subdivided into four groups due to differentintra-abdominal pressure ((15mmHg,20mmHg,25mmHg,30mmHg respectively) with6models in each group. The Decompression group was subdivided into four groups due todifferent intra-abdominal pressure (15mmHg,20mmHg,25mmHg,30mmHgrespectively, n=6). Models in Group Ⅲwere decompressed to0mmHg after4hours ofpressure maintenance and observed for2hours. Changes of HR, RR, SP, DP, MAP,CVP, IVCP, paCO2, paO2, SaCO2, pH, BE, HCO3-, Na+, K+, Ca2+were observedat different time intervals (before IAH,0.5hours after IAH,1hours after IAH,2hours afterIAH,4hours after IAH,0.5hours after decompression,1hours after decompression,2hours after decompression,4hours after decompression).2. Impact of IAH on the cardiac function in dogsSpeckle tracking imaging (STI) was employed to detect the impact of IAH on thelongitudinal strain and time to peak. Real-time myocardial contrast echocardiography(RT-MCE) was employed to observe the impact of IAH on myocardial perfusion in dogs.3. Mechanism of cardiac dysfunction caused by IAH in dogs1) DAS-ELISA was employed to detect CK-MB and cTnT in serum.2) Pathological changes of myocardial tissue, including gross pathology, microscopicpathology and ultrastructural pathology were observed.3) Immunohistochemistry method was employed to detect the impact of IAH on theexpression of ICAM-1in myocardial tissues.4) Colorimetry was employed to detect the impact of IAH on content of NO and NOSin myocardial tissues.Part Ⅱ Impact of intra-abdominal hypertension on adrenal secretion in dogs1. IAH models were made in the same method as in Part Ⅰ. Radioimmunoassay was employed to detect the concentration changes of cortisol, aldosterone, adrenaline andnoradrenaline at different time intervals.2. Enzyme-linked immuno sorbent assay (ELISA) was employed to detect contentchanges of IL-1, IL-6, and TNF-α in adrenal cortical tissues.3. Optical microscope was employed to detect the pathological changes in adrenalcortical tissues.Part Ⅲ Impact of intra-abdominal hypertension on pancreatic secretion in dogs1. IAH models were made in the same method as in Part Ⅰ. Radioimmunoassay wasemployed to detect the concentration changes of glucose, insulin, glucagon and amylase atdifferent time intervals.2. ELISA was employed to detect content changes of IL-1, IL-6, and TNF-α inpancreatic tissues.3. Optical microscope was employed to detect the pathological changes in pancreatictissues.The main research results:1. When IAH reached15mmHg, the heart rate and respiratory rate changed faster; thesystolic pressure, diastolic pressure, mean arterial pressure declined; central venouspressure increased and the inferior vena cava pressure was nearly equal to IAP. All aboveindexes returned to nomal after decompression. When IAP increased, values of paCO2、paO2、SaCO2、pH、BE、HCO3-decreased. The serum kalium was abnormal when IAPreached30mmHg. Left ventricle, basal ganglia, the middle section, apical and wholelongitudinal strain had no significant change, but the time to peak was significantlyprolonged after IAH. IAH in the4hours of observation time was difficult to causesignificant changes in markers of myocardial injury. However, it could cause cardiacmitochondrial swelling, muscle filaments dissolution, Z line breakage, neutrophilicexudation and other changes, as well as endothelial cell swelling of cardiac microvessles,increased expression of ICAM-1in myocardial tissue and abnormal NO.2. IAH resulted in the increased concentrations of cortisol, aldosterone, epinephrineand norepinephrine (P＜0.01) that changed more significantly with greater pressure andgradually returned to normal2hours after decompression. Compared with the sham operation group, IL-1, IL-6, TNF-α in adrenal tissue increased significantly in the IAHgroups(P＜0.01), and they increased more significantly if the pressure was greater anddecreased but still higher than that of the sham operation group2hours after decompression.Histopathology showed that adrenal tissue gradually developed congestion, extravasation oferythrocytes and neutrophilic exudation with the increase of IAP. The extent ofpathological changes was positively related to that of IAH.3. IAH resulted in the increased concentration of glucose, glucagon, amylase anddecreased insulin levels (P＜0.01) that changed more significantly with greater pressure.The above indexes could be changed but could not return to normal2hours afterdecompression. Compared with the sham operation group, the content of IL-1, IL-6andTNF-α in pancreatic tissue increased significantly in IAH groups(P＜0.01), and theyincreased more significantly if the pressure was greater and decreased but still higher thanthe that of the sham operation group2hours after decompression. Histopathology showedthat pancreatic tissue gradually developed congestion, extravasation of erythrocytes, andneutrophilic exudation with the increase of IAP. The extent of pathological changes waspositively related to that of IAH.Conclusion1. Abdominal decompression was effective in interventing instable hemodynamic,acidosis and abnormal serum kalium caused by IAH. It’s feasible to make use of STI toevalue the effect of IAH on cardiac function, which mainly reflected in the prolonged timeto peak and subclinical cardiac dysfunction.The vascular endothelial cell injury maybe thekey point in myocardial injury induced by IAH, and the possible mechanism may be theabnormal expression of caveolin-1in endothelial cells and accordingly abnormal signaltransduction pathway of PI3K/Akt/eNOS.2. The secretion of adrenal hormone and the extent of adrenal inflammatory damagewere positively related to the duration of IAH and IAP, and abdominal decompression waseffective to improve the adrenal function.3. IAP can cause pancreatic secretion dysfunction and inflammatory reaction, and its mechanism may be related to endothelial injury of pancreatic microvessles.