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Somatostatin attenuates ischemic intestinal injury
J B Morris1, N H Guerrero, E E Furth
1Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104-4283.
Abstract:
Pancreatic-derived proteases play a central role in the pathogenesis of ischemic intestinal injury. We postulated that exocrine blockade by pretreatment with a long-acting somatostatin analogue, octreotide acetate, would attenuate ischemic mucosal injury. Sprague-Dawley rats received subcutaneous octreotide (10 micrograms/kg/d) for 6 days by means of surgically implanted infusion ports. In a group of sham control rats, splanchnic blood flow (portal vein Doppler measurement) and duodenal trypsin activity (p-toluene sulfonyl-L-arginine methyl ester assay) were determined. In a separate experiment, pretreated animals were subjected to 60 minutes of superior mesenteric artery ischemia alone or followed by 30 minutes of reperfusion. Gross extent of hemorrhagic necrosis and microscopic injury (rank analysis) were assessed by a blinded observer. Pretreatment with octreotide reduced intraluminal duodenal trypsin activity by 46% without affecting portal blood flow. However, octreotide pretreatment significantly attenuated the microscopic depth of injury during ischemia and the extent of gross injury during reperfusion. It appears that somatostatin may have an adjuvant role in the prevention or progression of intestinal ischemic injury.
Insights
Octreotide acetate, a somatostatin analogue, reduced pancreatic proteases in rats, significantly lessening intestinal injury from ischemia. This suggests somatostatin may aid in preventing or managing ischemic intestinal damage.
Area of Science:
- Gastroenterology
- Surgical Research
- Pathophysiology
Background:
- Pancreatic proteases contribute significantly to ischemic intestinal injury.
- Targeting exocrine function may offer a therapeutic strategy for this condition.
Purpose of the Study:
- To investigate the efficacy of octreotide acetate, a somatostatin analogue, in attenuating ischemic intestinal injury.
- To determine if blocking pancreatic exocrine function reduces mucosal damage.
Main Methods:
- Sprague-Dawley rats were pretreated with octreotide acetate for 6 days.
- Splanchnic blood flow and duodenal trypsin activity were measured.
- Animals underwent superior mesenteric artery ischemia and reperfusion, with injury assessed by a blinded observer.
Main Results:
- Octreotide acetate reduced intraluminal duodenal trypsin activity by 46% without altering portal blood flow.
- Pretreatment significantly attenuated microscopic injury depth during ischemia.
- Octreotide acetate lessened the extent of gross injury following reperfusion.
Conclusions:
- Octreotide acetate effectively reduces pancreatic protease activity in the intestine.
- Somatostatin analogues may play an adjuvant role in preventing or mitigating intestinal ischemic injury.