AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum...AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 h were subjected to 35% total body surface area fullthickness burns, and were divided into three groups: no fluid resuscitation (NR, n = 10), in which animals did not receive fluid by any means in the first 24 h postburn; oral fluid resuscitation (OR, n = 8), in which dogs were gavaged with glucose-electrolyte solution (GES) with volume and rate consistent with the Parkland formula; and oral fluid with carbachol group (OR/CAR, n = 8), in which dogs were gavaged with GES containing carbachol (20 μg/kg), with the same volume and rate as the OR group. Twenty-four hours after burns, all animals were given intravenous fluid replacement, and 72 h after injury, they received nutritional support. Hemodynamicand gastrointestinal parameters were measured serially with animals in conscious and cooperative state. RESULTS: The mean arterial pressure, cardiac output and plasma volume dropped markedly, and gastrointestinal tissue perfusion was reduced obviously after the burn injury in all the three groups. Hemodynamic parameters and gastrointestinal tissue perfusion in the OR and OR/CAR groups were promoted to pre-injury level at 48 and 72 h, respectively, while hemodynamic parameters in the NR group did not return to pre-injury level till 72 h, and gastrointestinal tissue perfusion remained lower than pre-injury level until 120 h post-burn. CO 2 of the gastric mucosa and intestinal mucosa blood flow of OR/CAR groups were 56.4 ± 4.7 mmHg and 157.7 ± 17.7 blood perfusion units (BPU) at 24 h postburn, respectively, which were significantly superior to those in the OR group (65.8 ± 5.8 mmHg and 127.7 ± 11.9 BPU, respectively, all P < 0.05). Gastric emptying and intestinal absorption rates of GES were significantly reduced to the lowest level (52.8% and 23.7% of pre-injury levels) in the OR group at about 2 and 4 h post-burn, and did not return to 80% of pre-injury level until 24 h. In the first 24 h postburn, the rate of gastric emptying and intestinal water absorption were elevated by a mean 15.7% and 11.5%, respectively, in the OR/CAR group compared with the OR group. At 5 days, the mortality in the NR group was 30% (3/10), 12.5% in the OR group (1/8), and none in the OR/CAR group. CONCLUSION: Carbachol had a beneficial effect on oral resuscitation of burn shock by promoting gastric emptying and intestinal absorption in our canine model.展开更多
Lipid-based formulations(LBFs)have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.However,construction of in vitro and in vivo correlations(IVIVCs)for LBFs is quite chall...Lipid-based formulations(LBFs)have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.However,construction of in vitro and in vivo correlations(IVIVCs)for LBFs is quite challenging,owing to a complex in vivo processing of these formulations.In this paper,we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption;based on the concept of IVIVCs,the current status of in vitro models to establish IVIVCs for LBFs is reviewed,while future perspectives in this field are discussed.In vitro tests,which facilitate the understanding and prediction of the in vivo performance of solid dosage forms,frequently fail to mimic the in vivo processing of LBFs,leading to inconsistent results.In vitro digestion models,which more closely simulate gastrointestinal physiology,are a more promising option.Despite some successes in IVIVC modeling,the accuracy and consistency of these models are yet to be validated,particularly for human data.A reliable IVIVC model can not only reduce the risk,time,and cost of formulation development but can also contribute to the formulation design and optimization,thus promoting the clinical translation of LBFs.展开更多
基金Supported by The Special Foundation of the 11th five-yearPlan for Military Medical Projects, No. 06Z055
文摘AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 h were subjected to 35% total body surface area fullthickness burns, and were divided into three groups: no fluid resuscitation (NR, n = 10), in which animals did not receive fluid by any means in the first 24 h postburn; oral fluid resuscitation (OR, n = 8), in which dogs were gavaged with glucose-electrolyte solution (GES) with volume and rate consistent with the Parkland formula; and oral fluid with carbachol group (OR/CAR, n = 8), in which dogs were gavaged with GES containing carbachol (20 μg/kg), with the same volume and rate as the OR group. Twenty-four hours after burns, all animals were given intravenous fluid replacement, and 72 h after injury, they received nutritional support. Hemodynamicand gastrointestinal parameters were measured serially with animals in conscious and cooperative state. RESULTS: The mean arterial pressure, cardiac output and plasma volume dropped markedly, and gastrointestinal tissue perfusion was reduced obviously after the burn injury in all the three groups. Hemodynamic parameters and gastrointestinal tissue perfusion in the OR and OR/CAR groups were promoted to pre-injury level at 48 and 72 h, respectively, while hemodynamic parameters in the NR group did not return to pre-injury level till 72 h, and gastrointestinal tissue perfusion remained lower than pre-injury level until 120 h post-burn. CO 2 of the gastric mucosa and intestinal mucosa blood flow of OR/CAR groups were 56.4 ± 4.7 mmHg and 157.7 ± 17.7 blood perfusion units (BPU) at 24 h postburn, respectively, which were significantly superior to those in the OR group (65.8 ± 5.8 mmHg and 127.7 ± 11.9 BPU, respectively, all P < 0.05). Gastric emptying and intestinal absorption rates of GES were significantly reduced to the lowest level (52.8% and 23.7% of pre-injury levels) in the OR group at about 2 and 4 h post-burn, and did not return to 80% of pre-injury level until 24 h. In the first 24 h postburn, the rate of gastric emptying and intestinal water absorption were elevated by a mean 15.7% and 11.5%, respectively, in the OR/CAR group compared with the OR group. At 5 days, the mortality in the NR group was 30% (3/10), 12.5% in the OR group (1/8), and none in the OR/CAR group. CONCLUSION: Carbachol had a beneficial effect on oral resuscitation of burn shock by promoting gastric emptying and intestinal absorption in our canine model.
基金supported by Science and Technology Commission of Shanghai Municipality(Nos.19430741400 and 19410761200,China)National Natural Science Foundation of China(Nos.81973247 and 81703434)
文摘Lipid-based formulations(LBFs)have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs.However,construction of in vitro and in vivo correlations(IVIVCs)for LBFs is quite challenging,owing to a complex in vivo processing of these formulations.In this paper,we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption;based on the concept of IVIVCs,the current status of in vitro models to establish IVIVCs for LBFs is reviewed,while future perspectives in this field are discussed.In vitro tests,which facilitate the understanding and prediction of the in vivo performance of solid dosage forms,frequently fail to mimic the in vivo processing of LBFs,leading to inconsistent results.In vitro digestion models,which more closely simulate gastrointestinal physiology,are a more promising option.Despite some successes in IVIVC modeling,the accuracy and consistency of these models are yet to be validated,particularly for human data.A reliable IVIVC model can not only reduce the risk,time,and cost of formulation development but can also contribute to the formulation design and optimization,thus promoting the clinical translation of LBFs.
