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Effects of long-term corticosteroids and vitamin a on the healing of intestinal anastomoses in rabbits
19, Somatostatin Stimulates the Normal Esophagus
20. Effects of Long-TermCorticosteroids and Vitamin A on the Healing of Intestinal Anastomoses ia Rabbits
Linda Gunshefski, MD, William Rifley, MD, David W. Slattery, BS, Joseph J. Schifini, BS, Mary Hartsuck, BS, Alex G. Little, MD, FACS, Dept. of Surgery, University of Nevada School of Medicine, Las Vegas, NV
J. D. Phillips, C. S. Kim, E. W. Fonkalsrud,
H. Zeng, H. Dindar, Dept. of Surgery, UCLA School of Medicine, Los Angeles, CA
The inhibitory effects of somatostatin, a naturally occurring polypeptide, on the stomach and jejenum are well documented. However, its influence on esophageal body motility and the lower esophageal sphincter (LES) has not been thoroughly investigated. To study these effects and to consider therapeutic possibilities, we infused octreotide, a somatostatin analogue, in 15 healthy volunteers while manometrically measuring intraesophageal contraction pressure, velocity, and duration and LES pressure and length. Manometry was performed with a Konigsberg pressure catheter and Sandhill waveform analyzer. After initial baseline manometry was completed, an initial dose of octreotide 100 rg was administered intravenously followed by an 8.3 pg/minute infusion. Manometry was repeated at 30 and 60 minutes after bolus. Results: The effects on esophageal body contractions and LES pressure (P) and length (L) are shown in the Table as mean values f SEM. LES P
L
(mm Hs)
(cm)
Contractions Vel Prox (cm/s) (mm He) Amp Dis
4.0 f 0.1
119.8 f 11.4
3.lzkO.l
4.3f0.3
Time 30 28.7 f 3.1
3.3 & 0.1’
4.2 f 0.4’
5.1 f 0.9.
Time
3.7 ZIZ 0.1
134.5 & 12.8’ 130.2 f 12.8’
3.9 f 0.2’
4.8 k 0.3
80 29.2 f 2.8’
C (n = 7)
Vel Dis (cm/s)
25.0 f 2.0
Time 0
The ability of vitamin A to reverse the effects of corticosteroids on cutaneous wound healing is well established. To investigate this ability in the unique lowcollagen environment of the intestinal anastomosis, 35 rabbits received twice-daily injections of either saline (controls: C), dexamethasone (50 fig/kg: Dex), or dexamethasone plus low-dose (5,000 U/kg: VA-Pre-Lo) or high-dose vitamin A (50,000 U/kg: VA-Pre-Hi). Two weeks later, animals underwent small and large intestine (SI and LI) anastomoses. Postoperatively, injections were continued: five animals in the Dex group received, in addition, high-dose vitamin A (VA-Post). One week later, animals underwent in situ assessment of anastomotic bursting pressure (ABP, mm Hg) and histologic examination using a modified Ehrlich/Hunt scale (0 = none, 4 = many) for inflammatory cell infiltrate (WBC), fibroblast (Fib), and blood vessel (BV) ingrowth, and collagen deposition (Coll) (Table).
* p < 0.05 vs. Time 0.
SI ABP WBC Fib BV Colt LI ABP WBC Flb BV Coil
LES pressure, distal esophageal body contraction amplitude, and contraction velocity in both the proximal and distal esophagus were increased at 30 and 60 minutes. Conclusion: In contrast to gastric and jejunal inhibition, somatostatin has a previously undocumented positive inotropic effect on esophageal smooth muscle. This may have therapeutic implications in the treatment of certain esophageal motility disorders.
7 12
THE AMERICAN JOURNAL OF SURGERY
278 3.7 3.2 3.0 2.5 157 3.8 3.7 3.1 2.8
f 27 f 0.2 f 0.3 i 0.3 f 0.8 f 15 f 0.2 i 0.2 f 0.3 f 0.7
IhX (ll = 8) 149 f 1.8 1.8 1.8 1.0 87 2.0 2.4 2.2 3.4
i f f f f f f f f
14’ 0.3’ 0.3’ 0.3’ 0.7’ 20’ 0.3’ 0.2’ 0.4’ 0.2
VA-Pre-Lo (n = 7)
VA&e-HI (n = 8)
158 f
179 i
18
202 f
17
2.8 3.0 3.0 2.2 135 3.2 2.4 2.8 3.8
0.3 0.3 0.7 0.7 7 0.8 0.4 0.7 0.2
3.8 2.8 3.2 3.4 140 2.4 3.0 2.4 3.8
0.2 0.4 0.2 0.4 12 0.5 0.4 0.7 0.2
2.2f 2.5 1.3 1.7f 128 1.8f 2.5 2.0 2.3
f f i f f f
Mean f SEM. * p < 0.05 vs. C, ANOVA
14’ 0.5’ 0.4’ 0.4’ 0.5’ 14’ 0.8’ 0.5 0.4’ 0.9
f k i i f f & f i
and Fischer’s
VA-Post (n = 5)
f f f f f f f & f
Pi_.%
We conclude: (1) corticosteroids significantly impaired the healing of intestinal anastomoses, with decreased bursting pressures and histologic parameters at 1 week; (2) high-dose vitamin A significantly reversed this inhibitory effect, whether given preoperatively or only postoperatively; (3) patients receiving corticosteroids may benefit from perioperative vitamin A therapy when having intestinal surgery.
VOLUME 161 JUNE 1991
20. Effects of Long-TermCorticosteroids and Vitamin A on the Healing of Intestinal Anastomoses ia Rabbits
Linda Gunshefski, MD, William Rifley, MD, David W. Slattery, BS, Joseph J. Schifini, BS, Mary Hartsuck, BS, Alex G. Little, MD, FACS, Dept. of Surgery, University of Nevada School of Medicine, Las Vegas, NV
J. D. Phillips, C. S. Kim, E. W. Fonkalsrud,
H. Zeng, H. Dindar, Dept. of Surgery, UCLA School of Medicine, Los Angeles, CA
The inhibitory effects of somatostatin, a naturally occurring polypeptide, on the stomach and jejenum are well documented. However, its influence on esophageal body motility and the lower esophageal sphincter (LES) has not been thoroughly investigated. To study these effects and to consider therapeutic possibilities, we infused octreotide, a somatostatin analogue, in 15 healthy volunteers while manometrically measuring intraesophageal contraction pressure, velocity, and duration and LES pressure and length. Manometry was performed with a Konigsberg pressure catheter and Sandhill waveform analyzer. After initial baseline manometry was completed, an initial dose of octreotide 100 rg was administered intravenously followed by an 8.3 pg/minute infusion. Manometry was repeated at 30 and 60 minutes after bolus. Results: The effects on esophageal body contractions and LES pressure (P) and length (L) are shown in the Table as mean values f SEM. LES P
L
(mm Hs)
(cm)
Contractions Vel Prox (cm/s) (mm He) Amp Dis
4.0 f 0.1
119.8 f 11.4
3.lzkO.l
4.3f0.3
Time 30 28.7 f 3.1
3.3 & 0.1’
4.2 f 0.4’
5.1 f 0.9.
Time
3.7 ZIZ 0.1
134.5 & 12.8’ 130.2 f 12.8’
3.9 f 0.2’
4.8 k 0.3
80 29.2 f 2.8’
C (n = 7)
Vel Dis (cm/s)
25.0 f 2.0
Time 0
The ability of vitamin A to reverse the effects of corticosteroids on cutaneous wound healing is well established. To investigate this ability in the unique lowcollagen environment of the intestinal anastomosis, 35 rabbits received twice-daily injections of either saline (controls: C), dexamethasone (50 fig/kg: Dex), or dexamethasone plus low-dose (5,000 U/kg: VA-Pre-Lo) or high-dose vitamin A (50,000 U/kg: VA-Pre-Hi). Two weeks later, animals underwent small and large intestine (SI and LI) anastomoses. Postoperatively, injections were continued: five animals in the Dex group received, in addition, high-dose vitamin A (VA-Post). One week later, animals underwent in situ assessment of anastomotic bursting pressure (ABP, mm Hg) and histologic examination using a modified Ehrlich/Hunt scale (0 = none, 4 = many) for inflammatory cell infiltrate (WBC), fibroblast (Fib), and blood vessel (BV) ingrowth, and collagen deposition (Coll) (Table).
* p < 0.05 vs. Time 0.
SI ABP WBC Fib BV Colt LI ABP WBC Flb BV Coil
LES pressure, distal esophageal body contraction amplitude, and contraction velocity in both the proximal and distal esophagus were increased at 30 and 60 minutes. Conclusion: In contrast to gastric and jejunal inhibition, somatostatin has a previously undocumented positive inotropic effect on esophageal smooth muscle. This may have therapeutic implications in the treatment of certain esophageal motility disorders.
7 12
THE AMERICAN JOURNAL OF SURGERY
278 3.7 3.2 3.0 2.5 157 3.8 3.7 3.1 2.8
f 27 f 0.2 f 0.3 i 0.3 f 0.8 f 15 f 0.2 i 0.2 f 0.3 f 0.7
IhX (ll = 8) 149 f 1.8 1.8 1.8 1.0 87 2.0 2.4 2.2 3.4
i f f f f f f f f
14’ 0.3’ 0.3’ 0.3’ 0.7’ 20’ 0.3’ 0.2’ 0.4’ 0.2
VA-Pre-Lo (n = 7)
VA&e-HI (n = 8)
158 f
179 i
18
202 f
17
2.8 3.0 3.0 2.2 135 3.2 2.4 2.8 3.8
0.3 0.3 0.7 0.7 7 0.8 0.4 0.7 0.2
3.8 2.8 3.2 3.4 140 2.4 3.0 2.4 3.8
0.2 0.4 0.2 0.4 12 0.5 0.4 0.7 0.2
2.2f 2.5 1.3 1.7f 128 1.8f 2.5 2.0 2.3
f f i f f f
Mean f SEM. * p < 0.05 vs. C, ANOVA
14’ 0.5’ 0.4’ 0.4’ 0.5’ 14’ 0.8’ 0.5 0.4’ 0.9
f k i i f f & f i
and Fischer’s
VA-Post (n = 5)
f f f f f f f & f
Pi_.%
We conclude: (1) corticosteroids significantly impaired the healing of intestinal anastomoses, with decreased bursting pressures and histologic parameters at 1 week; (2) high-dose vitamin A significantly reversed this inhibitory effect, whether given preoperatively or only postoperatively; (3) patients receiving corticosteroids may benefit from perioperative vitamin A therapy when having intestinal surgery.
VOLUME 161 JUNE 1991