In this randomized, blinded study, we sought to determine whether the vasoconstriction produced by ropivacaine after subcutaneous injection is sufficient to decrease surgical bleeding. Anesthesia was induced in seven piglets (weight, 12.2-20.4 kg) with intraperitoneal thiopental and maintained with intravenous methohexital. Five sites were injected with 10 ml of one of the following solutions: 0.25% ropivacaine, 0.25% bupivacaine, either solution plus 5 micrograms/ml epinephrine, or saline. Another site was left uninjected for control. Capillary blood flow was measured at each site with a laser Doppler before and ten minutes after the injections. An incision 5 cm in length was then made through the dermis, and blood loss was measured over ten minutes. We found no significant differences in capillary blood flow and blood loss between bupivacaine and ropivacaine. Addition of epinephrine decreased capillary blood flow (p less than 0.05) and tended to decrease blood loss. Capillary blood flow correlated with blood loss (r2 = 0.106; p less than 0.05). We conclude that, in contrast to previous studies, ropivacaine did not decrease capillary blood flow in our model. Similarly, ropivacaine did not reduce bleeding from surgical incisions. The reason for these surprising results is not clear but is unlikely to be the larger volume of solutions injected because no such effect was observed with saline alone.

Lung injuries were produced by instilling 2.5 ml/kg of 0.1 N HCl into the trachea of lightly anesthetized goats with previously implanted lung lymph fistulas. Lymph flow (QL), lymph-to-plasma protein concentration ratio (L/P), pulmonary arterial and wedge pressures (Ppa, Pw), percent shunt (Qs/QT), and postmortem extravascular lung water (EVLW) were then measured for up to 48 h. QL began to increase within 15 min of injury from a baseline value of 7.2 ml/h to reach a peak of 231% of base line by 1.5 h, then decreased to 160% at 24 h and returned to base line by 48 h. Average L/P increased from 0.66 to a peak of 0.73 at 2 h. Ppa increased from 17.0 cmH2O to a first peak of 25.3 cmH2O at 15 min, then decreased to base line by 75 min. There was a second rise that peaked at 3 h before returning to base line at 24-48 h; Pw was unchanged throughout. Qs/QT increased from 8.5 to a peak of 34% at 1 h, then decreased to 15% at 4 h, and stabilized at 17-20% at 48 h. EVLW was 237% of base line at 4 h and declined somewhat but remained elevated at 194% of base line at 24 and 48 h. Qs/QT was less than expected based on the reduction in lung volume after aspiration. We conclude that microvascular permeability was increased after acid and that a protective vasoconstriction, probably due to local hypoxia, directed blood away from nonventilated alveoli.

Pressure-volume curves were obtained from excised left lungs of goats at 4, 24, and 48 h after tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Air total lung capacity (TLC) at transpulmonary pressure (PL) = 35 cmH2O was 38.8 ml/kg body weight before acid, and was reduced sharply to 21.1 at 4 h, then increased to 25.6 at 24 h and 32.1 at 48 h. Excess extravascular lung water (EVLW) could account for only part of the volume reductions. Specific compliance ratio of transpulmonary pressure to total lung capacity (CL/TLC) between PL of 5 and 0 cmH2O was reduced from 0.074/cmH2O to 0.050, 0.048, and 0.053/cmH2O, respectively. Saline TLC (PL = 10 cmH2O) changed from 44.8 to 32.4, 34.3, and 45.4 ml/kg, respectively, but CL/TLC did not, suggesting airway obstruction. After injury, trapped volume at PL = 0 increased from 24.9 to 29.2, 43.3, and 37.3% TLC with air, and from 20.3 to 38.5, 33.1, and 28.5%, respectively, with saline. Air volume at a PL = 10 cmH2O on deflation fell from 82.0 to 72.1% TLC at 4 h, but was near control at 24 and 48 h. The reduction in ventilated volume was not reflected in proportionately increased shunt; therefore, some compensatory vasoconstriction must have occurred. We suggest that in affected regions increased surface forces, increased EVLW, and airway obstruction caused reductions of lung volume.

The effect of dazoxiben, a selective thromboxane (Tx) synthetase inhibitor, on systemic and pulmonary hemodynamics, eicosanoids, and lung permeability was assessed in awake goats with lung lymph fistulae following infusion of Escherichia coli endotoxin (1 microgram/kg). Animals received endotoxin either with no treatment or pretreatment with a bolus (25 mg/kg) followed by a maintenance infusion (10 mg/kg per h) of dazoxiben. In untreated animals, the peak rise of 26.8 cm H2O in pulmonary artery (Ppa) and of 13.5 cm H2O in wedge (Pw) pressures occurred at the same time as the peak elevations in plasma thromboxane B2 (T X B2). Maximum reduction in cardiac output (Qt) also occurred at the same time. Lung lymph flow (QL) increased during this period and remained elevated for at least 6 h after endotoxin. T X B2 levels had returned from a peak of 13.1 to 0.7 ng/ml by 2 h. In dazoxiben-treated animals, plasma concentrations of T X B2 were never significantly elevated. Increases in Ppa and Pw were markedly reduced and decreased Qt was transient. QL in treated animals began to increase by 30 min after endotoxin and reached a peak by 2 h. Increased QL in treated animals was not as great as in the untreated animals. Moreover, lymph-plasma protein ratios increased significantly in treated animals. Plasma prostaglandin (PG)F2 alpha and 6-keto-PGF1 alpha concentrations were elevated in both groups after endotoxin with values significantly greater in treated animals. We conclude that selective inhibition of Tx ameliorates many adverse hemodynamic consequences of endotoxemia but does not prevent lung permeability changes.

This study has demonstrated in an awake goat the differential effects of infusing low dose epinephrine and norepinephrine. Epinephrine increases pulmonary fluid exchange, possibly as a result of β stimulation to the heart; whereas norepinephrine results in little change in pulmonary fluid balance, primarily affecting vascular vasoreactivity. This study underscores the importance of testing drug responses in awake animal models.

We have attempted to determine the membrane parameters, permeability-surface area product (PS) and reflection coefficient (sigma), necessary to describe solute exchange in the pulmonary circulation. Experimental lymph-to-plasma ratios were obtained for total protein (Rtot) and albumin (Ralb) using lung lymph collected from goats with chronic lung lymph fistulae. Lymph flow (QL) and solute flow (QS) were varied by increasing microvascular pressure in a stepwise manner by inflating a balloon in the left atrium. The increased QL and decreased Ralb from multiple experiments in four goats were used to plot PS vs. sigma using the equation of Patlak et al. (J. Theor. Biol. 5: 426-442, 1963). The region of intersection of two or more such curves should identify the two membrane constants. However, these curves rarely intersected suggesting that perhaps the lung barrier was not adequately represented by a single homoporous membrane. To evaluate heteroporosity, the three-pore model of Blake and Staub (Microvasc. Res. 12: 197-220, 1976) was investigated. By use of their pore sizes and relative pore distributions, values for the fluid filtration coefficient, PS, and sigma of each pore type were calculated, and finally QL and R were predicted at various microvascular pressures. When these calculated values of QL and R were plotted using the equation of Patlak et al., an equivalent homoporous PS and sigma could still be found. Therefore, a heteroporous membrane does not appear to explain the failure of our data plots to intersect. Possible alternative models are suggested.

Pure lung lymph has previously been obtained in awake sheep and goats via a cannula placed in an efferent duct of the caudal mediastinal lymph node (CMN). We describe a modification in goats wherein a segment of the thoracic duct collecting pulmonary efferents is isolated and cannulated. Lymph purity and responses to elevation of pulmonary microvascular pressure are illustrated and are found to be comparable to data obtained from a series of animals prepared by standard CMN cannulation. We have adopted the alternative procedure whenever, at cannulation may be complicated. When used in combination with the CMN approach, the overall rate of successful cannulation has increased from 50% to about 80%.

Goats have been prepared with chronic lung lymph fistulas in a manner similar to that described in sheep. Only one thoracotomy is needed to resect the posterior portion of the caudal mediastinal lymph node and to cannulate the main efferent duct. Comparison of data from the goat and from the sheep was accomplished by infusion histamine and by increasing left atrial and systemic venous pressures. Histamine infusion resulted in an increase in lymph flow (QL) from a base-line level of 7.3 36 ml/h and an increase in lymph-to-plasma protein ratio (L/P) FROM 0.70 to 0.82 (n = 2). In goats subjected to an increase in microvascular pressure averaging 18.2 cmH2O, QL increased from a base line of 6.7 to 23.0 ml/h, while the L/P decreased by 0.21 (n = 5). Elevation of systemic venous pressure by 8-9 cmH2O did not change QL (n = 4). Thus, the cannulation in the goat is similar to the sheep in response to induced permeability edema and hydrostatic edema, and similar with respect to lymph purity tests.