The effect of somatostatin 201-995 on the early course of porcine pancreaticoduodenal allotransplantation.

This study was undertaken to determine the effects of somatostatin 201-995 (SMS) on the maintenance dose of intravenous cyclosporine and on graft blood flow, exocrine secretion, and rejection after porcine pancreaticoduodenal allotransplantation (PDA). For seven days, 12 pigs (6 control, 6 SMS-treated) were studied to determine the effects of SMS on serum CsA concentrations. Twenty-six pigs (14 control, 12 SMS) with streptozocin-induced diabetes underwent PDA. Blood flow was measured through graft celiac and superior mesenteric arteries 15 and 60 min after reperfusion. SMS (75 micrograms s.c.) was given after the 15-min blood-flow measurement in the SMS group. Sixteen pigs (8 control, 8 SMS) were followed postoperatively with daily measurements of serum glucose and amylase concentrations, and urine amylase and trypsin activities. All pigs were immunosuppressed with azathioprine, prednisone, and i.v. CsA. SMS pigs also received SMS (75 micrograms s.c.) every 8 hr. SMS had no effect on maintenance dose of CsA or on serum amylase, urine amylase, or urine trypsin activities. Mean days to rejection were also not affected. Intraoperative graft blood flow was significantly decreased by SMS, but incidence of graft thrombosis was unchanged. These results suggest that in the porcine PDA model, SMS does not appear to inhibit exocrine secretion and potentially may adversely affect the early course of PDA by decreasing graft blood flow.

Different effects of protamine on canine coronary microvessel and conductance arteries: evidence of hyperpolarizing factor release.

BACKGROUND: Protamine administration may lead to systemic hypotension, perhaps because of vasodilatation produced by endothelial nitric oxide. This study compared release of vasoactive substances from canine coronary microvessels with that from paired conductance arteries. METHODS: Microvessels were mounted in a videoscopic no-flow system, and circumflex arteries were studied in organ chambers; both were induced to contract by endothelin-1. RESULTS: Protamine (10 to 160 micrograms/mL) produced concentration-dependent relaxation in both microvessel and conductance arteries (46% +/- 14% maximal relaxations in microvessel and 82% +/- 15% in conductance arteries, n = 10 each). Removal of the endothelium abolished this relaxation (P < .05, n = 6). Indomethacin (10(-5) mol/L) did not alter the relaxation in either group (51% +/- 10% in microvessel and 103% +/- 7% in conductance arteries, n = 6 each). NG-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L) attenuated relaxation in conductance arteries (38% +/- 12%, P = .04, n = 6) but had no effect on microvessel arteries (58% +/- 10%, n = 6). Tetraethylammonium chloride (10(-3) mol/L), an inhibitor of voltage-dependent potassium channels, had no effect on conductance arteries (103% +/- 9%, n = 6) but abolished relaxation in microvessels (-25% +/- 11%, P = .03, n = 6). CONCLUSIONS: Protamine sulfate causes endothelium-dependent relaxation in microvessel and conductance arteries in the heart by different mechanisms--that is, by nitric oxide release in conductance arteries and by endothelium-derived hyperpolarizing factor (EDHF) release in microvessels. This is the first description of the release of EDHF in response to protamine administration.

Pharmacological studies on internal mammary artery bypass grafts. Action of endogenous and exogenous vasodilators and vasoconstrictors.

BACKGROUND: The purpose of this experiment was four-fold: 1) to determine the effect of currently used cardiovascular drugs on internal mammary artery (IMA) vascular tone, 2) to examine IMA reactivity to autacoids and products released from aggregating platelets, 3) to compare the vascular reactivity of the right versus left IMA, and 4) to determine whether the canine IMA was an acceptable physiological model as regards its similarity to the human IMA, which is used routinely for coronary artery bypass grafting. METHODS: To study factors that modulate the tone of IMA, bypass grafts, right and left canine IMAs were studied in vitro in organ chambers (95% O(2)/5% CO(2), pH=7.4). RESULTS: Increasing concentrations (10(-9) to 10(-4M)) of the neurotransmitter acetylcholine (ACH) and the platelet-derived products adenosine diphosphate (ADP) or serotonin (5-HT) induced vasodilatation of contracted right and left IMAs. The vasodilation caused by ACH and ADP was endothelium-dependent while serotonin acted directly on the vascular smooth muscle. Histamine and bradykinin also induced IMA vasodilation, histamine via a direct action on the smooth muscle, and bradykinin through the release of nitric oxide (NO). In canine IMAs, the calcium ionophore A23187 produced endothelium-dependent vasodilation of contracted blood vessels; this vasodilation was blocked by N(G)-nitro-L-arginine (10(-4)M), a competitive inhibitor of nitric oxide synthesis from L-arginine, and by hemoglobin (10(-5)M). Dopamine, dobutamine, and papaverine induced vasodilation of the IMA regardless of the presence or absence of an intact intima, while norepinephrine induced profound IMA vasoconstriction, which was comparable to contraction to potassium ions or the constrictor peptide endothelin. CONCLUSIONS: These experiments establish a pharmacological profile of IMA and demonstrate that endogenous and exogenous compounds can significantly alter its vascular tone.