Can we continue research in splenectomized dogs? Mycoplasma haemocanis: Old problem - New insight

We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n=12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs. Copyright (C) 2004 S. Karger AG, Basel

Involvement of nitric oxide in the smooth muscle tone of the isolated canine spleen and the responses to acetylcholine and substance P

1 The canine isolated spleen was perfused at constant flow with warmed (37 degrees C) Krebs solution while the splenic arterial perfusion pressure (SAPP) and spleen weight were recorded continuously. An augmented smooth muscle tone was maintained by a continuous intra-arterial infusion of noradrenaline (0.01-0.1 mu mol min(-1)) throughout the experiment. 2 Intra-arterial infusion of indomethacin (5.6 mu M) significantly elevated (P < 0.05) the augmented vascular tone and the subsequent infusion of L-NAME (10 mu M) further raised this vascular tone significantly (P < 0.01), 3 The splenic vasoconstrictor response to L-NAME was significantly (P < 0.05) reduced by the subsequent infusion of L-arginine (300 mu M) but not of D-arginine (300 mu M). 4 Neither L-NAME nor D-NAME had any effect on the basal vascular tone or the spleen weight in conditions of either basal or augmented tone. 5 Bolus injection of acetylcholine, substance P, sodium nitroprusside and isoprenaline caused short-lasting reductions in the SAPP. 6 The splenic vasodilator responses to ACh and SP, but not those to SNP and ISO, were significantly (P < 0.05) reduced by the infusion of L-NAME (10 mu M), methylene blue (30 mu M) but not of D-NAME (10 mu M). 7 The reductions in the vasodilator responses to ACh and SP caused by L-NAME were partially reversed by L-arginine (300 mu M), but not by D-arginine (300 mu M). 8 The results demonstrate the contribution of nitric oxide (NO) release to the maintenance of the augmented splenic vascular tone and also the contribution of NO to the splenic vasodilator responses to ACh and SP.161354

CHARACTERIZATION OF FUNCTIONAL ENDOTHELIN RECEPTORS IN THE CANINE ISOLATED-PERFUSED SPLEEN

The endothelin receptor subtypes involved in the vasoconstriction, capsular smooth muscle contraction, prostaglandin E(2) and prostacyclin release induced by endothelin-l have been investigated in the canine isolated perfused spleen using both the endothelin ET(A) receptor antagonist FR 139317 and the endothelin ET(B) receptor agonist IRL 1620. The isolated canine spleen was perfused with warmed (37 degrees C) and oxygenated (95% O-2/5% CO2) Krebs solution at constant now with continuous recording of splenic arterial perfusion pressure and spleen weight, Samples of splenic venous effluent were collected to determine the amounts of prostaglandin E(2) and prostacyclin, measured by radioimmunoassay. Endothelin-1 (4-200 mu mol) and IRL 1620 (20-1000 pmol) dose-dependently increased splenic arterial perfusion pressure but the former was more potent on a molar basis (the molar dose ratio IRL/endothelin-1 required to increase splenic arterial vascular resistance by 25% was approximately 33). The infusion of the nitric oxide inibitor N-omega-nitro-L-arginine methyl ester (10 mu M), but not of the enantiomer N-omega-nitro-D-arginine methyl ester, significantly potentiated the increase in splenic arterial vascular resistance induced by endothelin-1. The infusion of FR 139317 (1 mu M) markedly attenuated the increased splenic arterial perfusion pressure induced by endothelin-1 without affecting that evoked by IRL 1620. At the highest dose (200 pmol, endothelin-1 induced a small but significant capsule contraction as reflected by the reduction in the spleen weight. The infusion of FR 139317 (1 mu M) abolished this contractile effect. IRL 1620 (in doses up to 1000 pmol) did not significantly affect the capsule tone. The administration of either endothelin-1 (20-200 pmol) or IRL 1620 (20-1000 pmol) caused the release of 6-oxo-prostaglandin F-1 alpha (breakdown product of prostacyclin) and prostaglandin E(2) into the splenic venous effluent. The amount of both prostanoids released by endothelin-1 was significantly greater than that induced by IRL 1620. FR 139317 (1 mu M) significantly reduced (P < 0.05) the release of both 6-oxo-prostaglandin F-1 alpha and prostaglandin E(2) by endothelin-1 without affecting that released by IRL 1620. The results demonstrate that the release of prostaglandins and nitric oxide modulates the vasoconstrictor activity of endothelin-1 in the splenic circulation. Furthermore, the vasoconstriction and eicosanoids (prostacyclin and prostaglandin E(2)) release by endothelin-1 are due to activation of both endothelin ET(A) and ET(B) receptors, although the former seems to be the predominant form. The splenic capsule contraction is mediated by activation of endothelin ET(A) receptors only.28241699576