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Background: It is reported that mast cells are involved in ischemia-reperfusion (I/R) injury of several organs such as intestine, heart, and brain in rats. However, the roles of mast cells are not known in rat hepatic I/R injury. We determined using genetically mast cell deficient (Ws/Ws) rats whether mast cells participate in the genesis of hepatic I/R injury., Methods: Isolated livers from male Ws/Ws rats (n = 6), their wild type +/+ rats (n = 6), and Sprague Dawely (SD) rats (n = 12) were perfused portally with diluted blood (Hct 8%) at a constant blood flow. Ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h, followed by 1-h reperfusion in a recirculating manner. The pre- and post-sinusoidal resistances were determined by measuring the portal venous pressure (Ppv), hepatic venous pressure, blood flow and the sinusoidal pressure, which was assessed by the double occlusion pressure (Pdo). Liver injury was assessed by blood alanine aminotransferase (ALT) levels, bile flow rate and histology of the livers., Results: In the +/+ group, liver injury occurred after reperfusion; blood ALT levels increased from 19 ± 4 (SD) to 71 ± 18 and 135 ± 30 (IU/L) at 30 and 60 min, respectively, and bile flow decreased to 51% ± 6% of the baseline at 60 min after reperfusion. Histologic examination revealed marked hepatic degeneration. Similar changes were observed in the Ws/Ws rats and the SD rats (n = 6), and there were no significant differences in the variables among the Ws/Ws, +/+, and SD groups. In any ischemia groups, immediately after reperfusion, Ppv substantially, but Pdo only slightly, increased, followed by a return towards the baseline, indicating a predominant increase in pre-sinusoidal resistance over post-sinusoidal resistance. Liver weight significantly increased at 60 min after reperfusion. In the control SD rats without I/R (n = 6), no significant changes were observed in the variables., Conclusions: I/R injury occurs in the absence of hepatic mast cells in the isolated perfused rat liver model of I/R injury., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Anaphylactic shock in rats is characterized by antigen-induced hepatic venoconstriction and the resultant portal hypertension. We determined the role of portal hypertension in anaphylactic hypotension by using the side-to-side portacaval shunt- and sham-operated rats sensitized with ovalbumin (1 mg). We measured the mean arterial blood pressure (MAP), portal venous pressure (PVP), and central venous pressure (CVP) under pentobarbital anesthesia and spontaneous breathing. Anaphylactic hypotension was induced by an intravenous injection of ovalbumin (0.6 mg). In sham rats, the antigen caused not only an increase in PVP from 11.3 cmH(2)O to the peak of 27.9 cmH(2)O but also a decrease in MAP from 103 mmHg to the lowest value of 41 mmHg. CVP also decreased significantly after the antigen. In the portacaval shunt rats, in response to the antigen, PVP increased slightly, but significantly, to the peak of 17.5 cmH(2)O, CVP did not decrease, and MAP decreased to a lesser degree with the lowest value being 60 mmHg. These results suggest that the portacaval shunt attenuated anaphylactic portal hypertension and venous return decrease, partially preventing anaphylactic hypotension. In conclusion, portal hypertension is involved in rat anaphylactic hypotension presumably via splanchnic congestion resulting in decreased venous return and thus systemic arterial hypotension.

Background: Patients treated with propranolol, a nonselective β-adrenoceptor antagonist, have increased incidence and severity of anaphylaxis. We determined whether β1- or β2-adrenoceptor antagonist modulated pulmonary vasoconstriction and bronchoconstriction in rat anaphylactic hypotension., Methods: Anesthetized ovalbumin-sensitized male Sprague-Dawley rats were randomly allocated to the following pretreatment groups (n = 7/group): (1) sensitized control (nonpretreatment), (2) propranolol, (3) the selective β2-adrenoceptor antagonist ICI 118,551, (4) the selective β1-adrenoceptor antagonist atenolol, and (5) adrenalectomy. Shock was induced by an intravenous injection of the antigen. Mean arterial pressure, pulmonary arterial pressure, left atrial pressure, central venous pressure, portal venous pressure, airway pressure, and aortic blood flow were continuously measured., Results: In either sensitized control or atenolol-pretreated rats, mean arterial pressure and aortic blood flow decreased substantially, whereas pulmonary arterial pressure and airway pressure did not increase soon after antigen injection. In contrast, in rats pretreated with either propranolol, ICI 118,551, or adrenalectomy, airway pressure significantly increased by 14 cm H2O, and pulmonary arterial pressure by 7.5 mmHg after antigen injection. At 2.5 min after antigen injection, the plasma concentration of epinephrine increased 14-fold in the sensitized rats except for the adrenalectomy group. Portal venous pressure after antigen injection increased by 16 mmHg similarly in all sensitized rats. All of the sensitized control group and two of the atenolol group were alive for 60 min after antigen injection, whereas all rats of the propranolol, ICI 118,551, and adrenalectomy groups died within 50 min after antigen injection., Conclusions: The pulmonary vasoconstrictive and bronchoconstrictive responses to systemic anaphylaxis were weakened via β2-adrenoceptor activation by epinephrine endogenously released from the adrenal gland in the anesthetized Sprague-Dawley rats.