Benefits of various dextrans after delayed therapy in necrotizing pancreatitis of the rat.
OBJECTIVE
Ultrahigh-molecular dextran (500,000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline?


METHODS
Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n = 10 per group) receiving either Ringer solution or different dextrans (10%) including 70,000 Da (DEX-70), 160,000 Da (DEX-160), 300,000 Da (DEX-300) or 500,000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg.


RESULTS
Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significantly lower in DEX-70 and DEX-160 compared to Ringer controls (p < 0.05, t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p < 0.01, t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p < 0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70.


CONCLUSIONS
Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects.
Schmidt
J
J
Department of Surgery, University of Heidelberg, Germany.
Huch
K
K
Mithöfer
K
K
Hotz
H G
HG
Sinn
H P
HP
Buhr
H J
HJ
Warshaw
A L
AL
Herfarth
C
C
Klar
E
E
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D003102:Colloids; D003911:Dextrans / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006982:Hypertonic Solutions; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014362:Trypsinogen / Q000378:metabolism
D000925:Anticoagulants; D003102:Colloids; D003911:Dextrans; D006982:Hypertonic Solutions; D014362:Trypsinogen