Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: Observations

Mar-9-2015

Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: ObservationsNonseptic Study
The infusion of dobutamine was associated with a modest fall in the mean blood pressure at the 10μg/kg/ min dose but was without effect on the mean pulmonary arterial pressure at either dose (Table 1 ana r lg l). The cardiac output increased progressively with both doses, while the measured pulmonary arterial wedge pressure, left atrial pressure, and calculated Pmv remained unchanged. Systemic oxygen transport increased at both doses, and the Pv02 increased concurrently. Dobutamine did not signficantly affect QL or the [L/P]TP at either dose. The calculated mean 7rpmv fell with both doses (p<0.05), although the Trmv-TTpmv gradient was unchanged from baseline. Therefore, the CLP remained unchanged from baseline during the infusion of dobutamine of either dose. We found no significant relationship between changes in QL and cardiac output (CO) at either dose (5μLg/kg/min, AQL=1.3 —0.66 ACO; r= — 0.12) (10μg/kg/min, AQL = 1.70 — 0.311 ACO; r= -0.36), unlike data reported by Coates et al, where with exercise an increase in QL was significantly related to an increase in the cardiac output.

Septic Study
With definition of the “sepsis syndrome,” all sheep demonstrated a higher mean systemic blood pressure, mean pulmonary arterial pressure, heart rate, and PaC02 (Table 1 and 2; Fig 1). Similarly, when compared to the baseline nonseptic study, QL had increased, while the values for [L/P]TP ratios were unchanged; CLP, therefore, was also increased above baseline nonseptic study. Both the TTmv and Trpmv had declined by the baseline septic study, although the Trmv-Trpmv gradient remained unchanged (Table 2). Again, we found no correlation between the cardiac output and Q L at baseline, when combining both septic and nonseptic studies (r = 0.22; p not significant). We have previously interpreted the finding of an increase in QL, without a significant fall in [L/P]TP ratios, as indicative of a permeability lesion within the pulmonary microvasculature of sheep with an intraperitoneal focus of sepsis. canadian neightbor pharmacy

During the septic study, the infusion of dobutamine was associated with a progressive decline in the mean systemic blood pressure throughout the two dosing regimens employed (Table 2); however, it was without effect on the mean pulmonary arterial pressure. Since the cardiac output increased with both doses, the calculated PVRI, therefore, fell. Systemic oxygen transport increased at both doses, although the Pa02 and systemic Vo2 remained unchanged. The calculated Pmv did not change, while the pulmonary arterial wedge pressure increased significantly above baseline at only the 5μg/kg/min dose (+ 22 percent) and the left atrial pressure remained unchanged from baseline at both doses.
A significant increase in QL was noted with low-dose infusion ( + 24 percent) but not at the higher dose; [L/P]TP ratios also fell at the low dose but not at the higher dose. Therefore, CLP increased significantly from the baseline septic study only with the 5μ/kg/ min dose and not with the 10μg/kg/min dose. Except for the highest dose employed (10μg/kg/min, y = 0.37 + 0.91x; r = 0.67), no significant relationship was found between changes in QL and changes in the cardiac ouput (CO) (5 μg/kg/min, AQL = 1.31+ 0.13 CO; r = 0.014).
Table 1—Infusion of Dobutamine in Ten Nonseptic Sheep

Data* Baseline Dobutaminet 5|xg/kg/min 10|jLg/kg/min
Mean BP, mm Hg 95 ±7 98 ±6 89 ± 7f§
HR, beats per min 113 ±24 148 ±30 192 ±31
Mean PAP, mm Hg 19.3±4.9 19.4±4.3 19.5±3.9
PCWP, mm Hg 5.8±4.2 6.6±3.6 7.2±4.5
LAP, mm Hg 2.1±2.9 2.0±3.3 2.0±3.6
CO, L/min 5.96± 1.4 7.18 ±1.6$ 7.99 ± 1.8$
SVI, ml/beat/m2 50 ±16 46 ±12 37 ±9$
PVRI, dynes*sec*cm_5/m2 201 ±41 161 ±30$ 137 ±29$
Pa02, mm Hg 97.6 ±20.3 94.7 ±12.8 91.1± 13.4
Pv02, mm Hg 42.3±5.2 49.4 ±5.1$ 51.7±5.9$
PaC02, mm Hg 37.2±5.8 36.0±3.4 37.2±4.2
Vo2, ml/m in/m2 196 ±78 145 ±30 148 ±36
02t, ml/min/m2 705 ±215 950 ±272$ 1,009 ±247$
Pmv, mm Hg 11.2±4.1 11.6±3.6 12.3±4.2
Trmv, mm Hg 17.9±3.1 17.8±2.9 17.4±2.4
TTpmv, mm Hg 10.6±2.4 9.8±2.7$ 9.8±2.7$
7imv-7rpmv, mm Hg 7.4± 1.9 7.8± 1.4 7.3± 1.9
Ql, ml/15 min 2.99± 1.8 3.41 ±2.1 3.20± 1.9
[L/P]TP 0.68 ±0.08 0.64 ±0.07 0.64 ±0.09
[L/P] albumin 0.76 ±0.08 0.75 ±0.11 0.71 ±0.08
Clp 1.99 ±1.09 2.34± 1.61 2.09 ±1.37

Table 2—Infusion of Dobutamine in Septic Sheep

Data* Baseline Dobutaminef
5fJig/kg/min 10|xg/kg/min
Mean BP, mm Hg 102 ±10$ 92± 17§ 79± 13§
HR, beats per min 134 ±39$ 182 ± 58.1§ 205 ± 49§
Mean PAP, mm Hg 27.6 ± 13.3$ 28.1 ±12.5 27.3 ±13.1
PCWP, mm Hg 9.5±7.8 11.6±8.9§ 12.1 ±10.4
LAP, mm Hg 3.2±6.9 3.5±8.0 4.4±9.7
CO, L/min 6.99± 1.9 8.7±1.8§ 9.19±2.5§
SVI, ml/beat/m2 53 ±18 49 ±19 44 ±15
PVRI,dynes*sec*cm _5/m2 235 ±124 182 ± 94§ 58 ± 71§
Pa02, mm Hg 87.5 ±12.7 88.1 ±14.6 83.3 ±15.5
Pv02, mm Hg 45.3±4.4 48.1 ±5.8 48.8±4.6
PaC02, mm Hg 43.3 ±6.3$ 40.3 ± 7.6§ 42.5±6.4
Vo2, ml/m in/m2 156 ±52 163 ±39 156 ±56
02t, ml/min/m2 720 ±197 930±271§ 907 ± 245§
Pmv, mm Hg 16.7±9.7 17.3± 10.2 18.0± 11.5
‘Trmv, mm Hg 13.8 ±2.8$ 13.2±2.3 12.2±2.2
Trpmv, mm Hg 7.1 ±3.3$ 6.2±3.0§ 6.1±2.9
Trmv-Trpmv, mm Hg 6.7±2.8 7.1±2.4 6.1± 1.7
Ql/15 min 7.0±3.9$ 8.7±4.8§ 7.8±5.8
[L/P]TP 0.57±0.2 0.52±0.2§ 0.53±0.2
[L/P]albumin 0.59 ±0.22 0.57±0.21 0.61 ±0.17
Clp 3.58 ±1.52$ 4.28±2.14§ 4.00 ±2.46

Figure 1. Changes in cardiac output, lung lymph flow, [L/P]TP ratios, and mean pulmonary arterial wedge pressure during one experiment.

Figure 1. Changes in cardiac output, lung lymph flow, [L/P]TP ratios, and mean pulmonary arterial wedge pressure during one experiment.