Adverse Effect of Therapeutic Vasoconstrictors in Experimental Acute Pancreatitis

Abstract

Alpha-adrenergic drugs commonly are used to treat hypotension resulting from severe acute pancreatitis. It was shown previously that although systemic arterial pressure is increased by phenylephrine, pancreatic microcirculatory perfusion is decreased. Because inadequate tissue perfusion may be critical in the progression of edematous pancreatitis to parenchymal necrosis, it was hypothesized that vasoconstrictors might be harmful in pancreatitis. Therefore the effect of phenylephrine on cerulein-induced mild pancreatitis were studied. Sprague-Dawley rats (n = 54) were randomly allocated to 6 experimental groups and subjected to the following infusion regimens: (1) cerulein (cae) + phenylephrine (phe), (2) cae + saline (NS), (3) NS + phe, (4) cae + phenoxybenzamine (pbz) + phe, (5) NS + pbz + phe, and (6) NS. Initial and terminal hematocrit, serum amylase activity, and blood ionized calcium concentration were determined. The animals were killed 9 hours after starting the infusion. Macroscopic and histologic changes were scored by a 'blinded' pathologist. Phenylephrine increased the severity of cerulein-induced pancreatitis as manifested by statistically significant adverse changes in serum amylase, hematocrit, ionized calcium, peripancreatitic soap formation, and acinar cell vacuolization. These changes were antagonized by alpha-adrenergic receptor blockade with phenoxybenzamine. It is concluded that phenylephrine is deleterious in acute experimental pancreatitis, the first demonstration of such an effect by a pharmacologic vasoconstrictor, and suggested that microcirculatory changes may be important in the transition of mild to severe pancreatitis. Caution in the use of vasoconstrictor drugs in patients with acute pancreatitis is recommended.

Epidural anaesthesia restores pancreatic microcirculation and decreases the severity of acute pancreatitis

“…Thus, a decrease in pancreatic blood flow occurs early in the course of AP and has been sug gested to play a role in the conversion of edematous to necrotizing AP [3][4][5][6][7] . The microcirculatory dysfunction includes arterial vasoconstriction with hypoperfusion, ischemia-re perfusion injur y, and obstruction of the venous outflow [8][9][10][11] . Other factors that participate in the development of microcirculatory dysfunction are hemoconcentration, hypercoagulability, and increase in microvascular permeability [8][9][10][11] .…”

“…The microcirculatory dysfunction includes arterial vasoconstriction with hypoperfusion, ischemia-re perfusion injur y, and obstruction of the venous outflow [8][9][10][11] . Other factors that participate in the development of microcirculatory dysfunction are hemoconcentration, hypercoagulability, and increase in microvascular permeability [8][9][10][11] . Besides perfusion abnormalities, AP is also characterized by local and systemic inflammatory responses, including leukocyte activation as well as release of free radicals and cytokines [12][13][14] .…”

Concentration of tissue angiotensin II increases with severity of experimental pancreatitis

“…In experimental models, pancreatic vascular perfusion failure has been implicated in the development of pancreatitis. Spormann et al (15) demonstrated that temporary ischemia significantly augmented the severity of pathology and Klar et al (16) revealed that vasoconstrictor administration has adverse effects in experimental acute pancreatitis. Intravascular thromboses have been indicated to represent a significant factor (17).…”

Pancreatic capillary blood flow during caerulein-induced pancreatitis evaluated by a laser-doppler flowmeter in rats

“…Pancreatic blood flow impairment is an important mechanism in the transition of edematous to necrohemorrhagic pancreatitis 4 . Although changes in the pancreatic blood flow during AP are well reported 4,5,6,7 , the initial mechanisms involving its pathogenesis remains poorly understood 8 . Besides, it is unclear whether the pancreatic capillary blood flow (PCBF) changes are cause or consequence of the AP 5 .…”