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15. Abnormal plasma gut hormone levels in pathologic duodenogastric reflux and their response to surgery
15. AbnormalPlasma Gut Hormone Levels in Pathologic Duodenogastric Reflux and Their Response to Surgery
16.
Effect of Verapamilon Hepatic Ischemia-Reperfusion Injury
P. Wilson, N. T. Welch, M. A. Anselmino, R. A. Hinder, T. R. DeMeester, T. E. Adrian Departments of Surgery and Biomedical Sciences Creighton University Omaha, NE Department of Surgery University of Southern California Los Angeles, CA
H. J. Stein, M. M. J. Oosthuizen, R. A. Hinder Department of Surgery Creighton University School of Medicine Omaha, NE
Abnormal antroduodenal motility, producing pathologic duodenogastric reflux (DGR), may be related to specific abnormalities in gastrointestinal regulatory hormones. To examine this issue, the interprandial and postprandial plasma levels of the foregut hormones gastrin, motilin, secretin, cholecystokinin (CCK), pancreatic polypeptide, and gastric inhibitory peptide, and of the distal gut hormones neurotensin (NT) and peptide YY (PYY) were measured in 14 patients with primary pathologic DGR and 8 age-matched healthy control subjects. Plasma levels in response to a meal were remeasured after pancreatico-biliary diversion surgery. Patients with pathologic DGR had significantly elevated postprandial levels of CCK and the distal gut hormones NT and PYY (all p <0.05), which normalized after surgery (p <0.05). Patients also had elevated basal levels of NT, which normalized after surgery (p <0.05). Pancreatico-biliary diversion produced a significant reduction (p <0.05) in basal levels of PYY with respect to before surgery and with respect to normal control subjects. These hormones are known to profoundly affect antroduodenal motility. I
I
I
Pre-op DGR
NOma18
Bad CCK Nr PYV
1.6 z 0.2 8.0 r 2.0 13.9 t 1.1
Basal 1.6 + 0.2 10.5 * 2.3 ,4.8 t 1.4
op<0.&5 “BRL”8 M)mlB, andpost-opWA; nm
Fed
Fed 5.0 3 0.3 10.1 * 2.3 16.0 + 0.9
8.3 f 1.1’ 19.5 i 2.70L 31.6 * 6.9Q
Post-op DGR Basal
Fed
1.6 zo.1 6.8+0.9P 10.4 r o.gs
4.5 L 0.c 11.3*1.220.8 * 3.c
Bp
and pre-opDGR: ‘p < 0.05 wrsw ~m-op DGR (Mann-~finey U test).
There are specific abnormalities of foregut and distal gut hormones in patients with pathologic DGR that may be either primary or secondary adaptive changes to the disease process. Measurement of these hormones may be useful in the diagnosis of this condition.
630
INTRODUCTION: Uncontrolled cellular calcium influx is a critical factor in the pathogenesis of hepatic ischemic injury and may mediate the release of oxygen radicals in the reperfusion period. We investigated the effect of the calcium channel blocker verapamil (VER) on ischemia/reperfusion (I/R) injury in normal rats and rats sensitized to oxidative injury by depletion of the endogenous antioxidant glutathione (GSH). MATERIALS AND METHODS: Fifty rats were randomly assigned to one of three groups. One group was sham operated only (control). In the other two groups, the hepatic blood supply was clamped for 45 minutes followed by reperfusion. One of the these two groups was pretreated with VER (2.5 mg/kg), whereas the other received vehicle only. Half of the rats in each group were pretreated with the GSH-depleting agent diethylmaleate (DEM). Sixty minutes after clamp removal, serum glutamic pyruvic transaminase (SGPT) was measured, and the livers were removed and processed for determination of GSH and lipid peroxidation products (LP), an indicator of oxidative injury. RESULTS: I/R caused a drop in liver GSH (p
THE AMERICAN JOURNAL OF SURGERY
Groups Control I/R I/R + VER DEM control DEM I/R DEM I/R + VER
SGPT (U/L)
GSH Wol/g)
LP @mot/g)
ask 12 621 2 119 606 f 82
5.7 -+0.3 3.5 2 0.2 5.1 f 0.5
12129 109 * 7 119 -c10
86'11 1,741 + 230 581 + 113
1.4 + 0.2 0.4 f 0.1 1.3 2 0.3
125+13 168ItlO 129 + 15
*All values are mean 2 SEW There were seven to nine animals per group.
CONCLUSION: VER prevents the I/R-induced drop in liver GSH and reduces hepatocellular I/R injury (SGPT’, LP) in rats sensitized to oxidative injury, suggesting that VER may protect against oxygen radical attack.
VOLUME 163 JUNE 1992
16.
Effect of Verapamilon Hepatic Ischemia-Reperfusion Injury
P. Wilson, N. T. Welch, M. A. Anselmino, R. A. Hinder, T. R. DeMeester, T. E. Adrian Departments of Surgery and Biomedical Sciences Creighton University Omaha, NE Department of Surgery University of Southern California Los Angeles, CA
H. J. Stein, M. M. J. Oosthuizen, R. A. Hinder Department of Surgery Creighton University School of Medicine Omaha, NE
Abnormal antroduodenal motility, producing pathologic duodenogastric reflux (DGR), may be related to specific abnormalities in gastrointestinal regulatory hormones. To examine this issue, the interprandial and postprandial plasma levels of the foregut hormones gastrin, motilin, secretin, cholecystokinin (CCK), pancreatic polypeptide, and gastric inhibitory peptide, and of the distal gut hormones neurotensin (NT) and peptide YY (PYY) were measured in 14 patients with primary pathologic DGR and 8 age-matched healthy control subjects. Plasma levels in response to a meal were remeasured after pancreatico-biliary diversion surgery. Patients with pathologic DGR had significantly elevated postprandial levels of CCK and the distal gut hormones NT and PYY (all p <0.05), which normalized after surgery (p <0.05). Patients also had elevated basal levels of NT, which normalized after surgery (p <0.05). Pancreatico-biliary diversion produced a significant reduction (p <0.05) in basal levels of PYY with respect to before surgery and with respect to normal control subjects. These hormones are known to profoundly affect antroduodenal motility. I
I
I
Pre-op DGR
NOma18
Bad CCK Nr PYV
1.6 z 0.2 8.0 r 2.0 13.9 t 1.1
Basal 1.6 + 0.2 10.5 * 2.3 ,4.8 t 1.4
op<0.&5 “BRL”8 M)mlB, andpost-opWA; nm
Fed
Fed 5.0 3 0.3 10.1 * 2.3 16.0 + 0.9
8.3 f 1.1’ 19.5 i 2.70L 31.6 * 6.9Q
Post-op DGR Basal
Fed
1.6 zo.1 6.8+0.9P 10.4 r o.gs
4.5 L 0.c 11.3*1.220.8 * 3.c
Bp
and pre-opDGR: ‘p < 0.05 wrsw ~m-op DGR (Mann-~finey U test).
There are specific abnormalities of foregut and distal gut hormones in patients with pathologic DGR that may be either primary or secondary adaptive changes to the disease process. Measurement of these hormones may be useful in the diagnosis of this condition.
630
INTRODUCTION: Uncontrolled cellular calcium influx is a critical factor in the pathogenesis of hepatic ischemic injury and may mediate the release of oxygen radicals in the reperfusion period. We investigated the effect of the calcium channel blocker verapamil (VER) on ischemia/reperfusion (I/R) injury in normal rats and rats sensitized to oxidative injury by depletion of the endogenous antioxidant glutathione (GSH). MATERIALS AND METHODS: Fifty rats were randomly assigned to one of three groups. One group was sham operated only (control). In the other two groups, the hepatic blood supply was clamped for 45 minutes followed by reperfusion. One of the these two groups was pretreated with VER (2.5 mg/kg), whereas the other received vehicle only. Half of the rats in each group were pretreated with the GSH-depleting agent diethylmaleate (DEM). Sixty minutes after clamp removal, serum glutamic pyruvic transaminase (SGPT) was measured, and the livers were removed and processed for determination of GSH and lipid peroxidation products (LP), an indicator of oxidative injury. RESULTS: I/R caused a drop in liver GSH (p
THE AMERICAN JOURNAL OF SURGERY
Groups Control I/R I/R + VER DEM control DEM I/R DEM I/R + VER
SGPT (U/L)
GSH Wol/g)
LP @mot/g)
ask 12 621 2 119 606 f 82
5.7 -+0.3 3.5 2 0.2 5.1 f 0.5
12129 109 * 7 119 -c10
86'11 1,741 + 230 581 + 113
1.4 + 0.2 0.4 f 0.1 1.3 2 0.3
125+13 168ItlO 129 + 15
*All values are mean 2 SEW There were seven to nine animals per group.
CONCLUSION: VER prevents the I/R-induced drop in liver GSH and reduces hepatocellular I/R injury (SGPT’, LP) in rats sensitized to oxidative injury, suggesting that VER may protect against oxygen radical attack.
VOLUME 163 JUNE 1992