Hong-Gang Wang

The effects of sevoflurane, enflurane, and isoflurane on baroreceptor-sympathetic reflex in rabbits

This study was designed to determine the effects of sevoflurane, enflurane, and isoflurane ranging from 0.5 to 1.25 minimum alveolar anesthetic concentration (MAC) on spontaneous efferent renal sympathetic nerve activity (RNA) and the baroreceptor-sympathetic reflex in rabbits. Enflurane produced significant decreases in spontaneous RNA by 22.5% +/- 6.6% at 1.0 MAC, while sevoflurane and isoflurane, at the equivalent MAC, did not. All of the anesthetics attenuated the baroreflex gain similarly when mean blood pressure (MBP) was changed by sodium nitroprusside or phenylephrine intravenously. However, the sensitivity of baroreceptors at the aortic wall was not changed by any anesthetic, because no changes in the relationship between aortic nerve activity and MBP were obtained in anesthetic concentration even at 1.25 MAC. Furthermore, these anesthetics suppressed the sympathoinhibitory response to aortic nerve stimulation above 1.0 MAC. In conclusion, enflurane inhibits RNA to a greater degree than sevoflurane or isoflurane. However, all three anesthetics depress the reflex regulation of RNA to the same degree. The suppression on the baroreceptor-sympathetic reflex does not appear to be related to a change in the receptor sensitivity on the aorta, but is mediated by suppression of the central or peripheral sympathetic integrating system. (Anesth Analg 1996;82:342-8)

Endothelin-1 selectively contracts portal vein through both ETA and ETB receptors in isolated rabbit liver.

We determined the constrictive effects of endothelin (ET)-1 on the hepatic vascular resistance distribution and the receptor subtype responsible for the effect in isolated rabbit livers perfused via the portal vein with 5% albumin-Krebs solution. The sinusoidal pressure was estimated using the double vascular occlusion pressure. The basal portal venous resistance comprised 59% of the total portal-hepatic venous resistance. In response to a bolus injection of ET-1 (0.05-5 micrograms), which led to a final concentration of 0.1-10 nM in the recirculating perfusate, the portal venous resistance increased in a dose-dependent manner, whereas the hepatic venous resistance did not change significantly at any concentration. This hepatic vasoconstriction was associated with liver weight loss. The selective portal venous constriction induced by ET-1 was confirmed in livers perfused retrogradely from the hepatic vein to the portal vein. The ET-1-induced hepatic vasoconstriction was significantly attenuated by the selective ETA receptor antagonist BQ-123 (1 microM). The ETB receptor antagonist BQ-788 (1 microM) also attenuated the constriction at ET-1 concentrations less than 10 nM. The combination of BQ-123 and BQ-788 tended to inhibit the hepatic vasoconstriction more effectively than BQ-123 alone. These results suggest that ET-1 selectively constricts the portal vein via both ETA and ETB receptors, with predominance of ETA receptor in isolated albumin-Krebs-perfused rabbit livers.We determined the constrictive effects of endothelin (ET)-1 on the hepatic vascular resistance distribution and the receptor subtype responsible for the effect in isolated rabbit livers perfused via the portal vein with 5% albumin-Krebs solution. The sinusoidal pressure was estimated using the double vascular occlusion pressure. The basal portal venous resistance comprised 59% of the total portal-hepatic venous resistance. In response to a bolus injection of ET-1 (0.05-5 μg), which led to a final concentration of 0.1-10 nM in the recirculating perfusate, the portal venous resistance increased in a dose-dependent manner, whereas the hepatic venous resistance did not change significantly at any concentration. This hepatic vasoconstriction was associated with liver weight loss. The selective portal venous constriction induced by ET-1 was confirmed in livers perfused retrogradely from the hepatic vein to the portal vein. The ET-1-induced hepatic vasoconstriction was significantly attenuated by the selective ETA receptor antagonist BQ-123 (1 μM). The ETB receptor antagonist BQ-788 (1 μM) also attenuated the constriction at ET-1 concentrations less than 10 nM. The combination of BQ-123 and BQ-788 tended to inhibit the hepatic vasoconstriction more effectively than BQ-123 alone. These results suggest that ET-1 selectively constricts the portal vein via both ETA and ETB receptors, with predominance of ETA receptor in isolated albumin-Krebs-perfused rabbit livers.

Thromboxane A2 analogue contracts predominantly the hepatic veins in isolated canine liver.

Thromboxane A2 (TxA2) is a potent vasoconstrictor and has been implicated as a mediator of liver diseases such as ischemic-reperfusion injury. We determined the effects of TxA2 and the well-known hepatic venoconstrictor histamine, on the vascular resistance distribution and liver weight in isolated canine livers perfused with blood via the portal vein. The stable TxA2 (STA2; 20 micrograms, n = 5) and histamine (5 micrograms, n = 6) similarly increased the hepatic total vascular resistance, 2.5- and 2.4-fold, respectively. The increase in the hepatic venous resistance was significantly greater than that of the portal resistance (threefold vs. 1.9-fold for STA2; threefold vs. 1.8-fold for histamine). Predominant hepatic venoconstriction induced by both agents was confirmed in livers perfused in a reverse direction from the hepatic vein to the portal vein, as shown by marked precapillary vasoconstriction. STA2 transiently increased liver weight loss (-3.6 g/100 g liver weight), followed by a gradual weight gain (9.0 g/100 g). Histamine caused a progressive weight gain (9.1 g/100 g). In conclusion, similar to histamine, TxA2 constricts predominantly the hepatic vein in isolated canine livers.

Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs

This study was designed to determine the effects of thromboxane A2 (TxA2) on the distribution of vascular resistance, lung weight, and microvascular permeability in isolated dog lungs perfused at a constant pressure with autologous blood. The stable TxA2 analogue (STA2; 30 μg, n = 5) caused an increase in pulmonary capillary pressure (Pc) assessed as double-occlusion pressure to 14.0 ± 0.4 mmHg from the baseline of 7.9 ± 0.3 mmHg with progressive lung weight gain. Pulmonary vascular resistance increased threefold exclusively due to pulmonary venoconstriction. Pulmonary venoconstriction was confirmed in lungs perfused in a reverse direction from the pulmonary vein to the artery (n = 5), as evidenced by marked precapillary vasoconstriction and a sustained lung weight loss. Furthermore, in lungs perfused at a constant blood flow (n = 5), STA2 also caused selective pulmonary venoconstriction. Vascular permeability measured by the capillary filtration coefficient and the isogravimetric Pc at 30 and 60 min after STA2 infusion did not change significantly from baseline in any lungs studied. Moreover, elevation of Pc by raising the venous reservoir of the intact lobes (n = 5) to the same level as the STA2 lungs caused a greater or similar weight gain compared with the STA2 lungs. Thus, we conclude that TxA2 constricts selectively the pulmonary vein resulting in an increase in Pc and lung weight gain without significant changes in vascular permeability in isolated blood-perfused dog lungs.

EFFECT OF ONO-5046, A SPECIFIC NEUTROPHIL ELASTASE INHIBITOR, ON THE PHORBOL MYRISTATE ACETATE-INDUCED INJURY IN ISOLATED DOG LUNG

Phorbol myristate acetate (PMA) activates neutrophils and causes acute lung injury. We determined the effect of ONO-5046, a specific neutrophil elastase inhibitor, on the increase in microvascular permeability induced by PMA in isolated dog lung perfused with autologous blood at a constant perfusion flow. The vascular permeability was assessed by the capillary filtration coefficient (Kf, c) and the solvent-drag reflection coefficient (sigma f). PMA (13.3 micrograms) increased vascular permeability, as evidenced by an increase in Kf, c from 0.18 +/- 0.02 to 0.92 +/- 0.14 mL/min/cmH2O/100 g and a decrease in sigma f to 0.35 +/- 0.01 as compared to control values of 0.69 +/- 0.06. The PMA-induced changes in Kf, c and sigma f were dose-dependently attenuated by pretreatment with ONO-5046 (2-20 mg). We conclude that ONO-5046 can effectively attenuate the PMA-induced injury in the isolated blood-perfused dog lungs.

Lecithinized superoxide dismutase attenuates phorbol myristate acetate-induced injury in isolated dog lung

Lecithinized superoxide dismutase, a lecithin derivative bound to recombinant human CuZn superoxide dismutase, has a higher affinity for cells such as polymorphonuclear leukocytes and endothelial cells than recombinant human CuZn superoxide dismutase has. We determined the protective effects of lecithinized superoxide dismutase on the increased microvascular permeability induced by phorbol myristate acetate (PMA) in isolated dog lungs. Microvascular permeability was assessed by the capillary filtration coefficient (Kf,c) and solvent drag reflection coefficient (sigma(f)). PMA (13.3 microg) increased microvascular permeability, as evidenced by an increase in Kf,c and the small sigma(f) value. Lecithinized superoxide dismutase at both low (4800 U) and high doses (48,000 U) inhibited the PMA-induced increase in Kf,c, but only the high dose of lecithinized superoxide dismutase attenuated the decrease in sigma(f). Recombinant human CuZn superoxide dismutase did not affect the PMA-induced increase in vascular permeability at either a low (4800 U) or a high dose (48,000 U). These findings suggest that lecithinized superoxide dismutase has a protective effect against oxygen radical-induced lung injury in isolated dog lungs.

Effect of platelet-activating factor on hepatic capillary pressure in isolated dog liver

We determined the effects of platelet-activating factor (PAF), a potent vasoactive autacoid phospholipid, on the capillary pressure and liver weight (Wt) in isolated canine livers perfused with blood bivascularly via the portal vein and hepatic artery. PAF (0.01-33 microg) administered intraportally produced dose-dependent increases in the hepatic capillary pressure, as assessed by triple vascular occlusion pressure (Pto), and Wt. An intraportal injection of 10 microg PAF produced increases in Pto by 10 mmHg and Wt by 35 g/100 g liver weight. This hepatic vasoconstriction was attributed to a threefold increase in the portal vein resistance and a fourfold increase in the hepatic vein resistance. The hepatic arterial resistance was not changed when PAF was arterially or intraportally injected. In conclusion, in isolated perfused dog livers, PAF increases the hepatic capillary pressure and liver weight due to contraction of both the portal vein and hepatic vein, but not the hepatic artery.

Participation of nitric oxide in the sympathetic response to anaphylactic hypotension in anesthetized dogs

The role of nitric oxide (NO) was determined using a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg bolus and 0.05 mg/kg per min) in the renal sympathetic and hypotensive response to systemic anaphylaxis induced by Ascaris suum antigen (10 mg, i.v.) in naturally sensitized anesthetized dogs. Renal nerve activity (RNA) in animals pretreated with D-NAME, the biologically inactive enantiomer (n = 7), showed an initial increase (192 +/- 32%, (mean +/- SE) followed by a decrease (61 +/- 14%) after antigen. Pretreatment with L-NAME (n = 7) did not affect the initial sympathoexcitation but abolished the secondary sympathoinhibition (110 +/- 13%). However, the depressor response to antigen was not different between the L-NAME and D-NAME groups (-87 +/- 13 mmHg and -84 +/- 12 mmHg). In conclusion, NO is involved in the anaphylaxis-induced renal sympathoinhibitory response but not hypotension in anesthetized dogs.

The role of endogenous nitric oxide in the sympathetic and hemodynamic response to platelet activating factor-induced hypotension in anesthetized dogs

We previously demonstrated that platelet-activating factor (PAF) when injected intravenously decreases renal sympathetic nerve activity in anesthetized dogs. Recently, nitric oxide (NO) has been shown to inhibit renal sympathetic nerve activity. The present study was designed to determine, using the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), whether endogenous NO contributes to the PAF-induced renal sympathoinhibition in anesthetized dogs. We also determined the role of NO in systemic and pulmonary hemodynamics during PAF-induced hypotension. In response to PAF (10 μg · kg−1, intravenously), renal sympathetic nerve activity showed similar responses in animals pretreated with L-NAME (n = 7; 20 mg · kg−1 bolus and .05 mg · kg−1 · min−1), D-NAME (n = 7), and phenylephrine (n = 7), as characterized by an initial increase (230%) followed by a decrease (56%). The depressor response to PAF was also similar as early as 10 min after injection in all PAF-injected groups. In contrast, L-NAME pretreatment potentiated PAF-induced pulmonary hypertension. Pulmonary arterial pressure 10 min after PAF in the L-NAME group (25 ± 2 mmHg) was significantly greater than that in the D-NAME group (12 ± 3 mmHg). In conclusion, endogenously produced NO is not involved in PAF-induced renal sympathetic nerve response or hypotension but attenuates PAF-induced pulmonary hypertension at the early stage in anesthetized dogs.

Changes in tissue blood flow and sympathetic activities to various organs during prolonged hemorrhagic hypotension in monkeys

This experiment was designed to determine whether prolonged hemorrhagic hypotension in anesthetized monkeys produces differential control of tissue blood flow and sympathetic nerve activities to various organs (heart, kidney, liver, spleen, and hind-limb). We performed simultaneous multifiber recording of sympathetic nerve activity to the kidney (RNA), heart (CNA), spleen (SpNA), liver (HNA), and hind-limb (LNA) during sustained hemorrhagic hypotension at a mean blood pressure of 40 mmHg for 2 h. Immediately after bleeding, all of the sympathetic nerve activities increased significantly (Stage I) and then gradually decreased towards the prebleeding levels (Stage II). Thereafter, the secondary sympathetic excitation was observed (Stage III), followed by a gradual decrease in sympathetic activities below the prebleeding levels (Stage IV). The shed blood started to return to the animals at this final stage. Time course of changes in sympathetic nerve activities did not differ among organs innervated. However, tissue blood flow of the renal cortex, liver, skeletal muscle and spleen significantly decreased at Stage I and remained at low levels until the end of the experimental period. In contrast, blood flow of the renal medulla and heart was preserved until Stage III and Stage IV, respectively. These results indicate that although the sympathetic response to prolonged hemorrhagic hypotension of 40 mmHg did not differ among organs, changes in tissue blood flow were variable and blood flow to the heart and renal medulla was maintained at a steady level until a late stage of hemorrhage.