A randomized trial of the effects of the noble gases helium and argon on neuroprotection in a rodent cardiac arrest model

Zuercher, Patrick; Springe, Dirk; Grandgirard, Denis; Leib, Stephen L.; Grossholz, Marius; Jakob, Stephan; Takala, Jukka; Haenggi, Matthias

doi:10.1186/s12883-016-0565-8

Table 2 Results of neurobehavioral tests

From: A randomized trial of the effects of the noble gases helium and argon on neuroprotection in a rodent cardiac arrest model

		Helium/oxygen	Argon/oxygen	Air/oxygen	Kruskall - Wallis	Non-ischemic sham
Weight^a [g]	Baseline (Before)	358 [343–383]	343 [334–367]	345 [326–372]	p = 0.375	400 [375–413]
	Day 1	342 [328–367]	335 [314–361]	339 [322–360]		384 [360–409]
	Wilcoxon Test p	0.01	<0.01	0.02		0.04
	Day 2	338 [322–354]	323 [306–351]	323 [304–345]		389 [365–404]
	Day 3	342 [327–362]	327 [306–355]	330 [308–343]		391 [361–408]
	Day 4	339 [327–372]	329 [309–365]	328 [313–345]		400 [369–410]
	Day 5	348 [324–380]	341 [319–370]	332 [318–355]		401 [374–415]
Friedman-Test p		<0.001 ^a	<0.001 ^a	<0.001 ^a		<0.001 ^a
Linear regression with clustered robust SE p = 0.302
(Coef. helium: −11.9 CI −33.0 to 9.2; Coef. argon: −15.2 CI −36.1 to 5.6)
Time effect: fractional polynomial regression p = 0.001
Tape Removal Test^a [seconds]	Baseline (Before)	18 [11–29]	9 [5–12]	13 [8–23]	p = 0.06	17 [14–39]
	Day 1	74 [21–120]	120 [35–120]	85 [23–120]		10 [8–21]
	Wilcoxon Test p	0.01	<0.01	<0.01		0.38
	Day 2	21 [12–76]	18 [11–111]	17 [9–120]		14 [7–18]
	Day 3	20 [8–113]	16 [11–120]	31 [9–88]		18 [15–95]
	Day 4	14 [10–113]	11 [7–59]	17 [9–120]		19 [7–96]
	Day 5	12 [7–45]	9 [5–44]	11 [7–93]		12 [7–17]
Friedman-Test p		0.018 ^a	0.002 ^a	0.023 ^a		0.086
Linear regression with clustered robust SE p = 0.980
(Coef. helium: −2.01 CI −35.88 to 31.86; Coef. argon: −3.24 CI −36.49 to 30.01)
Time effect: fractional polynomial regression p < 0.001
Neuro Deficit Score^a [range: 0–100]	Baseline (Before)	0 [0–0]	0 [0–0]	0 [0–0]	p = 0.37	0 [0–0]
	Day 1	2.5 [0–3.0]	3.0 [0.5–3.0]	2.5 [0.5–3.0]		0 [0–0]
	Wilcoxon Test p	0.02	0.02	0.03		1.0
	Day 2	0 [0–2.3]	0 [0–2.0]	0 [0–1.5]		0 [0–0]
	Day 3	0 [0–0.3]	0 [0–1.3]	0 [0–0.5]		0 [0–0]
	Day 4	0 [0–0.3]	0 [0–0.5]	0 [0–0]		0 [0–0]
	Day 5	0 [0–0.3]	0 [0–0.3]	0 [0–0]		0 [0–0]
Friedman-Test p		<0.001^a	<0.001^a	<0.001^a		1.0
Linear regression with clustered robust SE p = 0.612
(Coef. helium: 0.50 CI −0.68 to 1.69; Coef. argon: 0.35 CI −0.63 to 1.32)
Time effect: fractional polynomial regression p < 0.001
Vertical Pole Test^a [range: 0–3]	Baseline (Before)	0 [0–0]	0 [0–0]	0 [0–0]	p = 0.60	0 [0–0]
	Day 1	2.5 [0.25–3.0]	3.0 [1.0–3.0]	2.5 [1.5–3.0]		0 [0–0]
	Wilcoxon Test p	0.03	0.02	0.03		1.0
	Day 2	0 [0–2.0]	0 [0–1.5]	0 [0–1.0]		0 [0–0]
	Day 3	0 [0–0]	0 [0–1.0]	0 [0–0]		0 [0–0]
	Day 4	0 [0–0]	0 [0–0]	0 [0–0]		0 [0–0]
	Day 5	0 [0–0]	0 [0–0]	0 [0–0]		0 [0–0]
Friedman-Test p		<0.001^a	<0.001^a	<0.001^a		1.0
Linear regression with clustered robust SE p = 0.663
(Coef. helium: 0.15 CI −0.34 to 0.64; Coef. argon: 0.21 CI −0.32 to 0.75)
Time effect: fractional polynomial regression p < 0.001
Open Field Test: distance^a [cm]	Baseline (Before)	1691 [1327–1900]	1769 [1620–2101]	1580 [1520–1951]	p = 0.23	1693 [1378–1938]
	Day 4	1673 [1161–1919]	1320 [1144–1712]	2058 [1698–2403]		1034 [799–1698]
	Day 5	851 [758–1343]	1240 [658–1606]	962 [711–1629]		774 [698–1196]
Friedman-Test p		0.06	0.07	0.24		0.02^a
Linear regression with clustered robust SE p = 0.156
(Coef. helium: −244 CI −528 to 39; Coef. argon: −5 CI −465 to 455)
Time effect: fractional polynomial regression p = 0.002
Open Field Test: mobility/immobility ratio^a [%]	Baseline (Before)	82 [77–88]	88 [81–92]	84 [82–87]	p = 0.24	83 [80–85]
	Day 4	81 [71–84]	81 [75–88]	85 [82–87]		65 [54–84]
	Day 5	59 [51–72]	77 [50–86]	67 [46–82]		56 [41–65]
Friedman-Test p		0.15	0.20	0.06		<0.01 ^a
Linear regression with clustered robust SE p = 0.112
(Coef. helium: −4.63 CI −11.87 to 2.62; Coef. argon: 2.51 CI −6.22 to 11.24)
Time effect: fractional polynomial regression p < 0.001
Open Field Test: extern/intern ratio^a [%]	Baseline (Before)	94 [93–96]	94 [93–96]	96 [94–97]	p = 0.84	96 [93–98]
	Day 4	99 [97–100]	98 [96–99]	95 [95–97]		100 [97–100]
	Day 5	100 [99–100]	99 [99–100]	99 [95–100]		100 [98–100]
Friedman-Test p		0.02 ^a	0.03 ^a	0.03 ^a		0.03 ^a
Linear regression with clustered robust SE p = 0.501
(Coef. helium: 0.68 CI −1074 to 2.10; Coef. argon: 0.33 CI −1.55 to 2.22)
Time effect: fractional polynomial regression p = 0.003
Open Field Test: rears/vertical^a [count]	Baseline (Before)	15 [12–23]	20 [19–23]	19 [16–22]	p = 0.21	17 [14–22]
	Day 4	6 [5–8]	5 [3–10]	8 [5–9]		9 [7–13]
	Day 5	3 [1–4]	6 [2–9]	4 [2–7]		7 [4–9]
Friedman-Test p		<0.001 ^a	<0.001 ^a	<0.001 ^a		<0.001 ^a
Linear regression with clustered robust SE p = 0.107
(Coef. helium: −2.73 CI −5.58 to 0.11; Coef. argon: −0.40 CI −4.13 to 3.33)
Time effect: fractional polynomial regression p < 0.001

Comparisons of baseline were calculated with the Kruskal-Wallis ANOVA on ranks. Differences between the groups were computed with a linear regression with clustered robust SE, time effect with fractional polynomial regression. The animals in the non-ischemic sham group were not randomized, and thus indicated in italic style. These animals are not included in the main statistical analysis. The post-hoc Kruskall Wallis; Wilcoxon and Friedman tests were performed to compare groups at baseline and the time effect within the groups, but should be interpreted with caution (see text). Data are given as median and [interquartile ranges]
^a denotes significant time effects

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