AIM: To determine if anisodamine is able to augment mucosal perfusion during gut I/R ischemia-reperfusion. METHODS: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted i...AIM: To determine if anisodamine is able to augment mucosal perfusion during gut I/R ischemia-reperfusion. METHODS: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted into the sac which was filled with saline. The superior mesenteric artery was occluded (SMAO)for 60 minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO, either 0.2 mg/kg of anisodmine or dobutamine was injected into the jejunal sac. Laser Doppler mucosal blood flow and regional PCO2 (PrCO2)measurements were made. RESULTS: Mucosal blood flow was significantly increased at 30,60 and 90 minutes of reperfusion (R30, R60, R90) when intraluminal anisodamine or dobutamine was present compared to intraluminal saline only(44+/-3.3% or 48+/-4.1% vs 37+/-2.6% at R30, 57+/-5.0% or 56+/-4.7% vs 45+/-2.7% at R60, 64+/-3.3% or 56+/-4.2% vs 48+/-3.4% at R90,respectively P【0.05). Blood flow changes were also reflected by lowering of jejunal PrCO2 measurements after intraluminal anisodamine or dobutamine compared with that of the saline controls (41+/-3.1 mmHg or 44+/-3.0 mmHg vs 49+/-3.7 mmHg at R30,38+/-3.7 mmHg or 40+/-2.1 mmHg vs 47+/-3.8 mmHg at R60,34+/-2.1 mmHg or 39+/-3.0 mmHg vs 46+/-3.4 mmHg at R90, respectively, P【0.05). Most interesting finding was that there were significantly higher mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in dobutamine group at 90 minutes of reperfusion(64+/-3.3% vs 56+/-4.2% for blood flow or 34+/-2.1 mmHg vs 39+/-3.0 mmHg for PrCO2, respectively, P【0.05), suggesting that anisodamine had a more lasting effect on mucosal perfusion than dobutamine. CONCLUSION: Intraluminal anisodamine and dobutamine can augment mucosal blood flow during gut I/R and alleviate mucosal acidosis. The results provided beneficial effects on the treatment of splanchnic hypoperfusion following traumatic or burn shock.展开更多
AIM:To investigate the effect of local intestinal perfusion with hypertonic saline(HTS) on intestinal ischemia-reperfusion injury(IRI) in bothex vivo andin vivo rat models.METHODS:All experiments were performed on mal...AIM:To investigate the effect of local intestinal perfusion with hypertonic saline(HTS) on intestinal ischemia-reperfusion injury(IRI) in bothex vivo andin vivo rat models.METHODS:All experiments were performed on male Wistar rats anesthetized with pentobarbital sodium given intraperitoneally at a dose of 60 mg/kg.Ex vivo vascularly perfused rat intestine was subjected to 60-min ischemia and either 30-min reperfusion with isotonic buffer(controls),or 5 min with HTS of 365 or 415 mOsm/L osmolarity(HTS 365mOsm or HTS 415mOsm,respectively) followed by 25-min reperfusion with isotonic buffer.The vascular intestinal perfusate flow(IPF) rate was determined by collection of the effluent from the portal vein in a calibrated tube.Spontaneous intestinal contraction rate was monitored throughout.Irreversible intestinal injury or area of necrosis(AN) was evaluated histochemically using 2.3.5-triphenyltetrazolium chloride staining.In vivo,30-min ischemia was followed by either 30-min blood perfusion or 5-min reperfusion with HTS 365mOsm through the superior mesenteric artery(SMA) followed by 25-min blood perfusion.Arterial blood pressure(BP) was measured in the common carotid artery using a miniature pressure transducer.Histological injury was evaluated in both preparations using the Chui score.RESULTS:Ex vivo,intestinal IRI resulted in a reduction in the IPF rate during reperfusion(P < 0.05 vs sham).The postischemic recovery of the IPF rate did not differ between the controls and the HTS 365mOsm group.In the HTS 415mOsm group,postischemic IPF rates were lower than in the controls and the HTS 365mOsm group(P < 0.05).The intestinal contraction rate was similar at baseline in all groups.An increase in this parameter was observed during the first 10 min of reperfusion in the control group as compared to the sham-treated group,but no such increase was seen in the HTS 365mOsm group.In controls,AN averaged 14.8% ± 5.07% of the total tissue volume.Administration of HTS 365mOsm for 5 min after 60-min ischemia resulted in decrease in AN(5.1% ± 1.20% vs controls,P < 0.01).However,perfusion of the intestine with the HTS of greater osmolarity(HTS 415mOsm) failed to protect the intestine from irreversible injury.The Chiu score was lower in the HTS 365mOsm group in comparison with controls(2.4 ± 0.54 vs 3.2 ± 0.44,P = 0.042),while intestinal perfusion with HTS 415mOsm failed to improve the Chiu score.Intestinal reperfusion with HTS 365mOsm in the in vivo series secured rapid recovery of BP after its transient fall,whereas in the controls no recovery was seen.The Chiu score was lower in the HTS 365mOsm group vs controls(3.1 ± 0.26 and 3.8 ± 0.22,P = 0.0079 respectively,),although the magnitude of the effect was lower than in the ex vivo series.CONCLUSION:Brief intestinal postischemic perfusion with HTS 365mOsm through the SMA followed by blood flow restoration is a protective procedure that could be used for the prevention of intestinal IRI.展开更多
Intestinal ischemia occurs in a wide variety of clinical manifestations. The gut barrier is broken down by bacterial translocation after small intestinal ischemia reperfusion injury （IIRI）, which can result in many ...Intestinal ischemia occurs in a wide variety of clinical manifestations. The gut barrier is broken down by bacterial translocation after small intestinal ischemia reperfusion injury （IIRI）, which can result in many clinical consequences, even death. The intestinal mucosal mast cells （IMMCs） serve as a unique cellular source of large amounts of vasoactive mediators, and they can influence local tissue reactions. We and others have previously shown that IIRI could activate IMMCs, make them degranulate and release a mass of inflammatory mediators, which in turn aggravate IIRI.展开更多
基金the Tenth Five-Year Key Project of PLA,No.01L081
文摘AIM: To determine if anisodamine is able to augment mucosal perfusion during gut I/R ischemia-reperfusion. METHODS: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted into the sac which was filled with saline. The superior mesenteric artery was occluded (SMAO)for 60 minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO, either 0.2 mg/kg of anisodmine or dobutamine was injected into the jejunal sac. Laser Doppler mucosal blood flow and regional PCO2 (PrCO2)measurements were made. RESULTS: Mucosal blood flow was significantly increased at 30,60 and 90 minutes of reperfusion (R30, R60, R90) when intraluminal anisodamine or dobutamine was present compared to intraluminal saline only(44+/-3.3% or 48+/-4.1% vs 37+/-2.6% at R30, 57+/-5.0% or 56+/-4.7% vs 45+/-2.7% at R60, 64+/-3.3% or 56+/-4.2% vs 48+/-3.4% at R90,respectively P【0.05). Blood flow changes were also reflected by lowering of jejunal PrCO2 measurements after intraluminal anisodamine or dobutamine compared with that of the saline controls (41+/-3.1 mmHg or 44+/-3.0 mmHg vs 49+/-3.7 mmHg at R30,38+/-3.7 mmHg or 40+/-2.1 mmHg vs 47+/-3.8 mmHg at R60,34+/-2.1 mmHg or 39+/-3.0 mmHg vs 46+/-3.4 mmHg at R90, respectively, P【0.05). Most interesting finding was that there were significantly higher mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in dobutamine group at 90 minutes of reperfusion(64+/-3.3% vs 56+/-4.2% for blood flow or 34+/-2.1 mmHg vs 39+/-3.0 mmHg for PrCO2, respectively, P【0.05), suggesting that anisodamine had a more lasting effect on mucosal perfusion than dobutamine. CONCLUSION: Intraluminal anisodamine and dobutamine can augment mucosal blood flow during gut I/R and alleviate mucosal acidosis. The results provided beneficial effects on the treatment of splanchnic hypoperfusion following traumatic or burn shock.
基金Supported by Grant 2359.2012.7 of the President of the Russian Federation for the Support of Leading Scientific Groups
文摘AIM:To investigate the effect of local intestinal perfusion with hypertonic saline(HTS) on intestinal ischemia-reperfusion injury(IRI) in bothex vivo andin vivo rat models.METHODS:All experiments were performed on male Wistar rats anesthetized with pentobarbital sodium given intraperitoneally at a dose of 60 mg/kg.Ex vivo vascularly perfused rat intestine was subjected to 60-min ischemia and either 30-min reperfusion with isotonic buffer(controls),or 5 min with HTS of 365 or 415 mOsm/L osmolarity(HTS 365mOsm or HTS 415mOsm,respectively) followed by 25-min reperfusion with isotonic buffer.The vascular intestinal perfusate flow(IPF) rate was determined by collection of the effluent from the portal vein in a calibrated tube.Spontaneous intestinal contraction rate was monitored throughout.Irreversible intestinal injury or area of necrosis(AN) was evaluated histochemically using 2.3.5-triphenyltetrazolium chloride staining.In vivo,30-min ischemia was followed by either 30-min blood perfusion or 5-min reperfusion with HTS 365mOsm through the superior mesenteric artery(SMA) followed by 25-min blood perfusion.Arterial blood pressure(BP) was measured in the common carotid artery using a miniature pressure transducer.Histological injury was evaluated in both preparations using the Chui score.RESULTS:Ex vivo,intestinal IRI resulted in a reduction in the IPF rate during reperfusion(P < 0.05 vs sham).The postischemic recovery of the IPF rate did not differ between the controls and the HTS 365mOsm group.In the HTS 415mOsm group,postischemic IPF rates were lower than in the controls and the HTS 365mOsm group(P < 0.05).The intestinal contraction rate was similar at baseline in all groups.An increase in this parameter was observed during the first 10 min of reperfusion in the control group as compared to the sham-treated group,but no such increase was seen in the HTS 365mOsm group.In controls,AN averaged 14.8% ± 5.07% of the total tissue volume.Administration of HTS 365mOsm for 5 min after 60-min ischemia resulted in decrease in AN(5.1% ± 1.20% vs controls,P < 0.01).However,perfusion of the intestine with the HTS of greater osmolarity(HTS 415mOsm) failed to protect the intestine from irreversible injury.The Chiu score was lower in the HTS 365mOsm group in comparison with controls(2.4 ± 0.54 vs 3.2 ± 0.44,P = 0.042),while intestinal perfusion with HTS 415mOsm failed to improve the Chiu score.Intestinal reperfusion with HTS 365mOsm in the in vivo series secured rapid recovery of BP after its transient fall,whereas in the controls no recovery was seen.The Chiu score was lower in the HTS 365mOsm group vs controls(3.1 ± 0.26 and 3.8 ± 0.22,P = 0.0079 respectively,),although the magnitude of the effect was lower than in the ex vivo series.CONCLUSION:Brief intestinal postischemic perfusion with HTS 365mOsm through the SMA followed by blood flow restoration is a protective procedure that could be used for the prevention of intestinal IRI.
文摘Intestinal ischemia occurs in a wide variety of clinical manifestations. The gut barrier is broken down by bacterial translocation after small intestinal ischemia reperfusion injury （IIRI）, which can result in many clinical consequences, even death. The intestinal mucosal mast cells （IMMCs） serve as a unique cellular source of large amounts of vasoactive mediators, and they can influence local tissue reactions. We and others have previously shown that IIRI could activate IMMCs, make them degranulate and release a mass of inflammatory mediators, which in turn aggravate IIRI.
