Protease inhibitor infusion improves survival rate and hemodynamics in experimental pancreatic shock.
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Biomedical subjects
Publications and source records attributed to J O Stadaas.
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During the years 1981-85, 163 patients were treated with gastric banding for morbid obesity. Mean preoperative body weight (+/- s.e.m.) was 121.3 kg +/- 1.4, and mean overweight was 71.5% +/- 1.6 according to Broca's formula. Twenty-four patients had postoperative complications during the first 30 days, mostly minor. Four required reoperation and one of these died. Seventeen patients had late complications, six persistent vomiting necessitating reoperation, eight incisional hernia and three penetration of gastric wall by band. The weight loss was rapid during the first 6 months, and thereafter levelled off. After 2 years the weight loss was 33.4 kg +/- 2.4, corresponding to a mean weight loss of 27.6 percent +/- 1.9 of preoperative weight. There was no significant difference in weight loss expressed as a percentage of preoperative weight between patients operated with an outlet of 12 mm (45 patients) or 15 mm (118 patients), nor between males (37 patients) or females (126 patients). We conclude that our technique of gastric banding seems to be a relatively safe and reliable surgical treatment for morbid obesity. But our follow-up period has been limited to 2 years or less, and a longer follow-up is necessary before the method can be fully evaluated.
Acute pancreatitis was induced in anesthetized pigs by injection of Na-taurocholate into the pancreatic duct. The pigs were allocated to 4 groups. One group remained untreated while the other groups received either C1-inhibitor, aprotinin or methyl-prednisolone intravenously as pretreatment. Extensive necroses of the pancreatic parenchyma, peripancreatic oedema and accumulation of large amounts of fluid in the abdominal cavity developed within a few hours in all experimental groups. Pretreatment significantly improved hemodynamics and increased the survival rate at 6 hours. It is concluded that the most essential effect of the pretreatments were reduction of proteolytic activities which are secondary to the pancreatic lesions.
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Acute pancreatitis was induced in pigs by retrograde injection of Na-taurocholate into the pancreatic duct. Chromogenic peptide substrate assays showed increased trypsin (TRY) and plasma kallikrein activity (KK), parallel with a reduction of plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) values, in the peritoneal exudate in untreated animals. Intravenous high-dose pretreatment or therapy with aprotinin starting 3 h after the induction of acute pancreatitis resulted in significantly increased KKI capacity and unchanged KK and TRY activities in the peritoneal exudate. In test animals receiving aprotinin intravenously a significantly increased survival rate and improved cardiac output and arterial blood pressure were found during the 6-h observation period. All animals treated with aprotinin survived the observation period, whereas 63% of the untreated animals died. The study emphasizes the pathophysiological importance of the plasma kallikrein-kinin system in acute pancreatitis.
Acute pancreatitis was induced in pigs by manual retrograde injection of Na-taurocholate into the pancreatic duct. Chromogenic peptide substrate assays showed increased trypsin (TRY) and plasma kallikrein activities (KK), parallel with a reduction of prekallikrein (PKK) levels and functional plasma kallikrein inhibition (KKI), in the peritoneal exudate in untreated animals. Pretreatment with C1 inhibitor (C1 INH) concentrate significantly increased the KKI capacity, parallel with unchanged KK and TRY activities in the peritoneal exudate. Furthermore, C1 INH pretreatment significantly improved the hemodynamic performance and the survival rate during a 6-h observation period. The study underlines the pathophysiological importance of trypsin and the plasma kallikrein-kinin system during acute pancreatitis. C1 INH concentrates given intravenously prevent activation of this system locally in the peritoneal exudate during experimental acute pancreatitis.
The haemodynamic effects of intravenous injection into the test animals themselves of peritoneal exudate obtained during experimental acute pancreatitis in pigs were studied. The exudate had a distinct but moderate vasodilating effect when injected into the test animal. This decrease in afterload and a slight compensatory increase in heart rate led to a small increase in cardiac output. The profound hypotensive effect of intravenous injection of peritoneal pancreatic exudate observed by others when injecting the exudate into healthy animals could not be reproduced. In an organism severely affected by pancreatitis, the added pharmacological insult of peritoneal exudate intravenously seems to be of little haemodynamic consequence. Some of the effects previously reported may be caused by trypsin added to the fluid injected intraductally to produce the ailment.
Acute pancreatitis was induced in 15 anesthetized pigs by injection of Na-taurocholate into the pancreatic duct. Seven animals were pretreated with methyl-prednisolone sodium succinate 30 mg/kg intravenously. Using chromogenic peptide substrate assays, values of trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and arterial pressure (AP) were regularly monitored before and during a six hour observation period. In acute untreated pancreatitis a 40% reduction of PKK levels was found paralleled by an increased KK activity and a reduction of KKI capacity. High TRY levels were found in several animals. The mortality rate was 63%. The pretreated animals all survived. CO and AP were significantly less reduced than in the untreated animals. Components of the plasma kallikrein-kinin system and TRY in the exudate remained mainly unchanged. Methyl-prednisolone given as pretreatment significantly improves hemodynamic parameters and increases the survival rate. Methyl-prednisolone suppresses generation of trypsin activity and activation of the plasma kallikrein-kinin system in the peritoneal exudate which may be of significant importance to the outcome.
Using chromogenic peptide substrate assays the severity and clinical course were evaluated in 37 patients with acute pancreatitis. Retrospective clinical evaluation revealed that 20 patients had a severe disease, whereas 17 patients had mild acute pancreatitis. Seven of the patients with severe acute pancreatitis died. The proenzyme functional inhibition index (PFI index) is defined as the sum of deviations from the normal plasma pool values of plasma prekallikrein, functional kallikrein inhibition, plasminogen, antiplasmin, prothrombin and antithrombin III. Increased values are counted as positive, whereas reductions compared with the normal plasma pool values are recognized as negative. During the second day after admission the PFI index revealed significantly more negative values in severe cases than in patients with mild acute pancreatitis, -159 in severe case, -74 in mild cases (median values, P less than 0.05). The PFI index values were maintained strongly negative for the following 3 days in severe cases whereas the index was brought to positive values during the same period in patients with mild acute pancreatitis. The fatal cases revealed strongly negative PFI index values for the whole observation period. The patients with severe acute pancreatitis were earlier identified by means of the PFI index than by individual parameters also used for calculating the index. The results show that by means of the PFI index severity of acute pancreatitis can be recognized during early stages of the disease.
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Abdominal trauma has a high priority in the diagnosis and treatment of a patient with multiple injuries. Both blunt and penetrating injuries may be isolated or multiple and they are often combined with extraabdominal trauma. A close cooperation between surgical and other specialties is often needed. Transport from a smaller hospital to a center with full diagnostic and therapeutic facilities may be advantageous.
The intragastric pressure/volume relationship was recorded in six patients with duodenal ulcer to study gastric motility before and after proximal gastric vagotomy (PGV). Recordings were done preoperatively and 6 weeks and 1 year after surgery by means of a flaccid plastic bag in the stomach connected to a low-pressure transducer. The bag was filled and emptied stepwise with defined volumes to study responses in gastric basal pressure or tone and contractions. Significant increase in basal pressure and reduced strength of rhythmic contractions were found 6 weeks after the operation, indicating disturbance of the gastric reservoir in the corpus and fundus. These changes were still present 1 year later, but some reduction of the pressure/volume relation was seen. The study indicates that a small tendency to adaptation or a revere towards normal occurs with gastric motility responses to volume loads simulating a meal 1 year after PGV, but the changes are still significantly different from the preoperative recordings.
Ten patients were examined before and after proximal gastric vagotomy with videotape recordings of barium passage in esophagus, esophageal pressure recordings, and the insulin test. Four of the patients complained of dysphagia after the operation. The dysphagia subsided spontaneously after 1--2 months. Patients with dysphagia showed dilatation of the body of the esophagus and a tapered narrowing in the distal segment. The pressure recordings showed increased frequency and strength of rhythmic pressure waves compared with the preoperative findings. Our results support the theory of a neuromuscular dysfunction.
The intragastric pressure/volume relationship has been measured in six healthy volunteers. Increased gastric motility was achieved by gastric distension, by stepwise increasing the volume from 0--600 ml. When thyrotropin-releasing hormone (TRH), 0.04 mg/h, was infused concomitantly in the individuals, gastric motility was significantly inhibited (p less than 0.05) and, with 1 mh/h of TRH, nearly abolished compared with the saline control test. The basal pressure was unaffected at 0.04 mg/h, whereas a significant rise was seen after 1 mg/h of TRH (p less than 0.05) compared with the control test. In three of the subjects the effect of rapid injection of TRH (0.2 mg), followed by infusion of TRH (0.6 mg/h), on the stimulated gastric motility was analysed. After the injection of TRH, almost no motor activity was observed during the 15-min observation period. It is concluded that TRH has a potent inhibiting effect on gastric motility, and the possible physiological role of TRH in the gastric regulation in man is discussed.