Octreotide Pretreatment Research Articles

Time mode of growth hormone (GH) entry into the bloodstream and steady-state plasma GH concentrations, rather than sex, estradiol, or menstrual cycle stage, primarily determine the GH elimination rate in healthy young women and men.

We have investigated whether a reduced MCR of GH in women will account for their higher serum GH concentrations premenopausally compared with those in men. To this end, we directly compared the half-life (t 1/2) of GH and its volume of distribution (Vo) in 13 young men and 6 comparably aged women, each evaluated at three stages of the normal menstrual cycle (viz. the early follicular, late follicular, and midluteal phases). To estimate nonequilibrium GH kinetics, each subject received octreotide pretreatment to suppress endogenous GH release and then 3 randomly ordered iv bolus doses of recombinant human GH (1, 2, and 4 microg/kg). The resultant peak serum GH concentrations were 18 +/- 4, 36+/-8, and 70+/-9 microg/L in six women and 17+/-2, 30+/-4, and 84+/-25 microg/L in six men (P = NS, gender contrast). Corresponding Vo values were 66+/-1, 71+/-1, and 60+/-1 mL/kg in women and 69+/-1, 78+/-1, and 73+/-1 mL/kg in men (P = NS). Matching monoexponential GH t1/2 values were 7.6+/-0.3, 8.2+/-0.4, and 8.8+/-0.7 min in women and 9.8+/-0.8, 10+/-1, and 9.5+/-1 min in men (average 1.7 min longer in men). Regression analysis disclosed no relationship between serum estradiol concentrations and peak serum GH levels, GH t 1/2, or Vo. GH t 1/2 values were also invariant of menstrual cycle stage, e.g. t 1/2 values of 8.1+/-0.5, 9.1+/-1.0, and 8.1+/-0.4 min for the early follicular, late follicular, and midluteal phases, respectively. Corresponding normalized MCRs were 319+/-39 (early follicular), 340+/-48 (late follicular), and 340+/-71 (midluteal) L/m2 x day in women and 336+/-50 L/m2 x day in men (P = NS). In parallel equilibrium infusion studies in men, we administered GH by constant iv infusions for 240 min during octreotide suppression. At doses of 0.5, 1.5, and 4.5 microg/kg x min, steady state GH t 1/2 values were 9+/-1, 12+/-1, and 15+/-1 min (at respective steady state serum GH concentrations of 0.5+/-0.05, 2.1+/-0.2, and 7.5+/-0.5 microg/L). In a third analysis in the same volunteers, stopping the constant iv infusions revealed t 1/2 values of GH decay from equilibrium of 26+/-5 and 23+/-2.3 min for the two higher GH infusion rates. In a fourth paradigm, endogenous GH t 1/2 values, as assessed in the same individuals by deconvolution analysis of overnight (10-min sampled) serum GH concentration profiles, averaged 18+/-1.3 min. This value was intermediate between that of poststeady state decay and iv bolus elimination of GH. In summary, the foregoing clinical experiments in healthy men and women indicate that 1) the nonequilibrium GH t 1/2, (body surface area-normalized) Vo, and MCR are independent of GH dose, sex, menstrual cycle stage, and serum estradiol concentrations; 2) the GH t 1/2 calculated after iv bolus injection is significantly (50%) shorter than that assessed during or after steady-state GH infusions or endogenously (overnight) by deconvolution analysis; and 3) the descending rank order of GH t 1/2 values in healthy volunteers is approximately: decay from steady state (23+/-2.3 min) > endogenously secreted GH (18+/-1.3 min) > during equilibrium infusion (15+/-1 min) > after bolus infusion (9.8+/-0.8 min). We thus conclude that for any given body surface area, the elimination properties of GH in men and women reflect predominantly the time mode of hormone entry into the circulation, rather than gender, menstrual cycle stage, or prevailing serum estradiol concentration. Accordingly, differences in serum GH concentrations in premenopausal women compared to those in young men and across the normal menstrual cycle reflect commensurate differences in pituitary GH secretion rates.

Effects of Octreotide Pretreatment on Surgical Outcome in Acromegaly

Effects of Octreotide Pretreatment on Surgical Outcome in Acromegaly

Effect of Octreotide Pretreatment on Surgical Outcome in Acromegaly

Effect of Octreotide Pretreatment on Surgical Outcome in Acromegaly

Effect of Octreotide, A Somatostatin Analogue, on Release of Inflammatory Mediators from Isolated Guinea Pig Bladder

Objective Somatostatin has been demonstrated to inhibit inflammation under certain circumstances. We hypothesized that in vivo treatment with octreotide, a long-acting analogue of somatostatin analogue, would diminish the capacity of inflammatory peptides to stimulate in vitro release of inflammatory mediators by the bladder. Methods Female guinea pigs were injected with octreotide (20 mg./kg. i.m.) prior to euthanasia. Control guinea pigs received no treatment prior to euthanasia. Urinary bladder were removed and incubated with substance P (SP, 10 micro M), neurokinin A (NKA, 10 micro M), or bradykinin (BK, 10 micro M) in the presence or absence of indomethacin (50 micro M), and release of histamine, prostaglandins (PGE 2 and PGF 2 alpha), and leukotriene (LTB 4) was determined. Results Sensory peptides and BK induced time-dependent release of histamine and eicosanoids from isolated urinary bladder. Blockade of cyclooxygenase with indomethacin (50 micro M) abolished peptide-induced prostaglandin release but enhanced LTB 4 release. In vivo octreotide pretreatment decreased peptide-induced histamine release, had no effect on PGE 2 or PGF 2 alpha release, and LTB4 release. However, octreotide prevented the increase in LTB 4 release in tissues incubated with indomethacin. Conclusions These results indicate that somatostatin has the capacity to suppress the release of histamine and prevents potentiation of LTB4 release by indomethacin by the guinea pig bladder in response to pro-inflammatory peptides, indicating that somatostatin may be useful in preventing or treating some forms of cystitis.

Rat Liver Injury Induced by Hypoxic Ischemia and Reperfusion: Protective Action by Somatostatins is Independent from Changes in Glucose Metabolism

Changes in glucose metabolism mediated by natural somatostatin and two derivatives (octreotide, 008) were studied in hypoxic ischemic cell injury of the isolated perfused rat liver. The tested somatostatin and its analogues were previously shown to exert protective actions in liver damage induced by hypoxic ischemia and reperfusion. In isolated perfused livers of rats starved for 24 hours and unstarved rats flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. Glucose and lactate concentration, as well as LDH and GLDH activity, were determined in the effluent. In starved and unstarved rat livers hypoxic ischemia resulted in a substantial enzyme release. In livers harvested from unstarved rats hepatic glucose release was noticed which ceased towards prolonged low flow ischemia. In livers harvested from starved rats containing low hepatic glycogen concentration only minimal hepatic glucose release was present. In starved and unstarved rats pretreatment with somatostatin, octreotide, and 008 significantly reduced LDH and GLDH release (p < 0.001). In unstarved rats natural somatostatin and octreotide pretreatment resulted in a substantial output of glucose during the hypoxic ischemic perfusion period (p < 0.001), whereas livers with 008 pretreatment did not show any difference in glucose release compared to controls. In livers harvested from starved rats neither somatostatin nor octreotide nor 008 pretreatment led to a difference in glucose output observed in controls. Natural somatostatin and octreotide cause a strong hepatic glucose release even under hypoxic ischemic conditions in rat livers with filled glycogen stores. The protective action of natural somatostatin, octreotide, and 008 is not mediated by changes in glucose metabolism, and is not related to endocrine activity.

Somatostatin attenuates ischemic intestinal injury

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.

Somatostatin Analogs in the Treatment of Acromegaly

Medical therapy of acromegaly with the somatostatin analog octreotide is very successful. Both clinical symptomatology and hormonal hypersecretion by the growth hormone-secreting pituitary adenomas are controlled, and peripheral IGF-I levels also return to near normal levels. Tumor shrinkage is observed in most patients. Somatostatin analogs can be used after noncurative surgery and for a limited period after radiotherapy, and octreotide pretreatment might improve the outcome of surgery.

Does Somatostatin Analogue Prevent Experimental Acute Pancreatitis?

Because somatostatin is a potent inhibitor of pancreatic secretion, we hypothesized that pretreatment with somatostatin analogue octreotide (SMS 201-995) might prevent cerulein-induced edematous pancreatitis. We studied 18 rats prepared with jugular vein catheters. The following agents were administered intravenously to groups of four rats for 6 hours: 1 mL/h (control) crystalloid solution; 1-microgram/kg bolus then 1 microgram/kg per hour of octreotide; and 5 micrograms/kg per hour of cerulein; also, in a fourth group of six rats, octreotide and cerulein were administered simultaneously. At the end of experiments, blood was drawn for plasma amylase determinations; rats were killed and pancreata were examined. Supramaximal cerulein administration to conscious rats induced hyperamylasemia and edematous pancreatitis, confirming previous observations; in both groups of rats receiving cerulein, there was prominent interstitial edema, acinar vacuolization, and mild-to-moderate acute inflammation. While octreotide pretreatment of rats with cerulein-induced acute pancreatitis was associated with a lesser increase of wet pancreas weight and plasma amylase concentration, there was little overall benefit of octreotide pretreatment in this form of experimental acute pancreatitis.