Relationship among Plasma Amino Acids, C‐Reactive Protein, Illness Severity, and Outcome in Critically Ill Dogs
Authors: Chan D.L. , Rozanski E.A. , Freeman L.M. 
Published: March 2009

Background: Alterations in circulating amino acids have been documented in animal models and in critically ill people but have not been evaluated in dogs with spontaneously occurring disease.

Hypothesis/Objectives: To compare amino acid concentrations in critically ill dogs and healthy controls and to investigate potential relationships among amino acids, markers of inflammation, illness severity, and clinical outcome.

Animals: Forty‐eight critically ill dogs and 24 healthy control dogs.

Methods: Plasma was analyzed for amino acids and C‐reactive protein (CRP) was measured in serum. The Fischer ratio (the molar ratio of branched chain amino acids [BCAA] to aromatic amino acids [AAA]) and survival prediction index (SPI2) were calculated.

Results: Median CRP concentrations were significantly higher in the critically ill dogs compared with controls (P < .001). Critically ill dogs had significantly lower concentrations of alanine (P= .001), arginine (P < .001), citrulline (P < .001), glycine (P < .001), methionine (P < .001), proline (P < .001), and serine (P= .001) but significantly higher concentrations of lysine (P= .02) and phenylalanine (P < .001; Table 1). This pattern resulted in a significantly lower Fischer ratio (P= .001) in the critically ill group. Median SPI2 score was significantly higher in dogs that survived (P= .03). Concentrations of arginine (P= .02), isoleucine (P= .01), leucine (P= .04), serine (P= .04), valine (P= .04), total BCAA (P= .03), and the Fischer ratio (P= .03) were significantly higher in survivors compared with nonsurvivors.

 Comparison between critically ill and healthy control dogs and among different subgroups of diseases within the critically ill group.

Controls
All Critically Ill
P

c
‐Value
Sepsisd
Pancreatitisd
Traumad

n
24
48
23
23
14
11

Age
5.5 (2.0–15.0)
7.3 (1.3–15.9)
.09
9.7 (1.3–13.5)
7.8 (3.2–15.9)
5.0 (2.0–11.0)

Sex

.18

Male
8 (8 castrated)
26 (21 castrated)

12 (8 castrated)
8 (7 castrated)
6 (6 castrated)

Female
16 (14 spayed)
22 (17 spayed)

11 female (7 spayed)
6 (6 spayed)
5 (4 spayed)

Weight (kg)
26.7 (3.7–47.7)
26.4 (3.2–66.0)
.88
34.4 (3.2–66.0)
15.5 (4.5–63.6)
18.1 (5.5–41.0)

CRP (μg/mL)
3.2 (2.5–23.1)
57.7 (2.6–98.4)
< .001
55.7 (9.4–98.4)
57.7 (40.1–69.0)
71.7 (2.6–92.6)

SPI2
—
0.62 (0.23–0.91)
—
0.58 (0.36–0.88)a
0.63 (0.23–0.91)a,b
0.72 (0.54–0.83)b

Alanine
480.6 (259.8–702.7)
325.0 (75.6–1,635.0)
.001
365.6 (75.6–1,635.0)
268.4 (102.5–570.0)
354.0 (102.7–704.9)

Arginine
117.7 (64.8–165.9)
64.0 (0.0–251.8)
< .001
64.3 (2.0–173.4)
68.5 (0.0–251.8)
61.6 (0.0–102.0)

Aspartic acid
5.7 (2.8–10.5)
6.2 (2.2–21.0)
.39
7.2 (2.4–21.0)
6.0 (2.5–9.4)
5.0 (2.2–15.2)

Asparagine
47.4 (32.0–89.1)
49.0 (12.6–147.0)
.82
50.9 (13.8–143.5)
61.0 (14.9–147.0)
36.2 (12.6–89.0)

Citrulline
57.6 (33.7–143.2)
22.6 (0–55.0)
< .001
19.0 (0.0–50.5)
21.5 (6.6–55.0)
33.8 (19.0–47.4)

Cysteine
6.7 (2.0–24.8)
7.4 (1.0–53.2)
.52
11.0 (1.5–53.2)
7.3 (1.9–30.0)
4.5 (1.0–15.0)

Glutamic acid
46.2 (26.5–101.3)
42.7 (19.0–149.8)
.07
44.5 (19.1–81.2)a
49.5 (19.5–149.8)a
28.5 (19.0–50.7)b

Glutamine
706.5 (168.8–942.3)
591.9 (132.0–1,286.0)
.13
630.0 (132.0–1,286.0)
587.1 (139.8–853.1)
527.9 (376.1–940.9)

Glycine
249.5 (175.3–606.8)
160.1 (61.1–407.0)
< .001
163.9 (61.5–407.0)
159.5 (61.1–267.0)
150.6 (101.4–261.7)

Histidine
75.2 (54.7–98.0)
72.8 (33.4–162.0)
.57
71.5 (45.5–162.0)
70.9 (37.5–97.0)
79.0 (33.4–150.3)

Isoleucine
65.3 (38.3–114.9)
74.7 (14.2–213.8)
.50
67.1 (26.0–213.8)a
101.0 (31.4–148.4)b
85.7 (14.2–127.0)a,b

Leucine
155.1 (97.0–245.1)
176.5 (51.0–384.1)
.46
158.1 (74.3–384.1)
201.4 (51.0–367.0)
173.5 (51.6–270.2)

Lysine
163.6 (102.3–258.0)
186.9 (48.6–500.0)
.02
168.0 (78.3–396.7)
232.5 (91.0–500.0)
202.5 (48.6–394.5)

Methionine
67.5 (39.3–131.6)
44.7 (11.5–115.2)
< .001
44.0 (11.5–115.2)
57.2 (22.1–95.0)
36.7 (23.7–80.0)

Ornithine
14.7 (5.8–30.3)
17.6 (2.7–97.8)
.24
14.4 (6.4–79.0)
17.8 (2.7–97.8)
27.3 (12.7–87.8)

Phenylalanine
56.1 (46.2–92.0)
103.2 (29.0–188.8)
< .001
98.0 (62.8–188.8)
111.3 (61.3–155.0)
107.2 (29.0–147.6)

Proline
107.7 (54.2–258.5)
45.4 (10.1–217.0)
< .001
45.5 (10.1–217.0)
51.6 (11.6–154.0)
37. (13.9–134.0)

Serine
128.9 (85.0–193.9)
88.1 (32.7–206.7)
.001
89.3 (32.7–206.7)
109.3 (36.5–169.2)
62.7 (32.8–117.4)

Taurine
104.0 (47.1–193.4)
97.5 (20.6–1,374.0)
.87
102.4 (20.6–1,374.0)
67.6 (24.5–293.0)
114.8 (49.6–270.1)

Threonine
200.0 (110.7–314.8)
209.1 (66.4–626.0)
.79
211.2 (66.4–475.8)
205.4 (77.6–626.0)
222.2 (80.7–383.0)

Tryptophan
67.5 (13.7–134.4)
37.4 (2.0–111.7)
.10
35.2 (2.0–91.5)
33.8 (13.2–103.5)
45.8 (12.2–111.7)

Tyrosine
46.7 (30.9–77.5)
42.6 (17.1–123.6)
.93
41.9 (21.5–92.1)
43.1 (28.2–99.0)
50.1 (17.1–123.6)

Valine
182.0 (123.2–324.9)
215.4 (65.2–511.0)
.15
195.0 (100.3–434.9)
246.6 (93.0–511.0)
205.9 (62.2–363.4)

BCAA
407.1(260.0–684.9)
465.2 (128.0–1,032.8)
.24
425.4 (219.9–1,032.8)
538.7 (176.0–996.0)
465.1 (128.0–760.6)

Fischer ratio
3.9 (2.4–5.8)
3.1 (1.1–5.2)
.001
2.9 (1.6–4.3)
3.6 (1.6–5.2)
3.0 (1.1–4.2)

Data are presented as median (range). Amino acid concentrations are in nmol/mL.

Comparison of all critically ill dogs (n = 48) to healthy controls (n = 24).

d
Comparison of values among different disease groups of critically ill dogs (ie, sepsis versus pancreatitis versus trauma). Data within a row with a different superscript letters are significantly different.

CRP, C‐reactive protein; SPI2, survival prediction index; BCAA, branched chain amino acids; AAA, aromatic amino acids.

Conclusions and Clinical Importance: Critically ill dogs have altered amino acid profiles and additional research to investigate potential benefits of amino acid supplementation is warranted.