Gavage approach to oxygen supplementation with oxygen therapeutic Ox66™ in a hypoventilation rodent model of respiratory distress

Figures & data

Figure 1. Oxygen delivery to the spinotrapezius muscle. Measurements were collected at 15 min intervals. Baseline (BL) followed stabilization from surgery and was collected during normal breathing. Hypoventilation (60% tidal volume with normal breath rate) was then initiated and maintained for the duration of the experiment. The first gavage occurred following the 60 min measurement and the second after 120 min as demarcated by the dotted lines. Of note, the second Ox66^™ gavage had a longer duration of impact on oxygen delivery than the first, but both produced significant P_ISFO₂ responses within 15 min of treatment.

Data are mean ± SEM; N = 26 sites/group.

*Indicates p<.05 compared to BL.

β Indicates p<.05 between groups.

Table 1. Systemic variables.

Metric	Group	BL	HV-ARDS				HV-ARDS + G1				HV-ARDS + G2
		0	15	30	45	60	75	90	105	120	135	150	165	180
MAP	Saline	123 ± 6	104 ± 6	97 ± 9*	95 ± 8*	97 ± 6*	95 ± 6*	93 ± 6*	95 ± 5*	92 ± 5*	87 ± 5*	89 ± 6*	87 ± 6*	89 ± 5*
	Ox66™	112 ± 7	88 ± 8*	89 ± 9*	86 ± 6*	90 ± 5*	102 ± 7*	97 ± 6*	99 ± 5	95 ± 7*	102 ± 8	101 ± 9	100 ± 7	97 ± 8
HR	Saline	455 ± 11	445 ± 14	445 ± 7	442 ± 7	433 ± 9	431 ± 8	424 ± 11	415 ± 7*	405 ± 13*	396 ± 14*	397 ± 15*	393 ± 15*	396 ± 12*
	Ox66™	446 ± 12	426 ± 14	411 ± 14	417 ± 15	422 ± 18	427 ± 9	437 ± 13	434 ± 11	431 ± 11	428 ± 11	421 ± 10	415 ± 10	421 ± 10
PP	Saline	29 ± 1.7	29 ± 2.3	30 ± 1.9	29 ± 1.2	29 ± 1.8	29 ± 1.9	30 ± 2.8	29 ± 2.0	32 ± 3.7	26 ± 2.4	26 ± 2.0	26 ± 1.9	30 ± 1.8
	Ox66™	25 ± 1.8	25 ± 2.1	23 ± 1.5	28 ± 1.7	28 ± 2.2	30 ± 2.5	31 ± 3.0	29 ± 3.0	25 ± 3.9	27 ± 4.2	24 ± 4.1	26 ± 1.8	24 ± 3.8
PuOx	Saline	80 ± 2.9	76 ± 2.5	77 ± 2.7	77 ± 1.9	77 ± 2.1	67 ± 4.6	72 ± 3.9	71 ± 4.0	69 ± 4.2*	71 ± 3.8*	74 ± 4.0	72 ± 3.2	71 ± 3.6*
	Ox66™	71 ± 3.4	71 ± 2.2	71 ± 4.1	69 ± 5.0	72 ± 3.5	69 ± 4.9	72 ± 4.5	70 ± 6.6	68 ± 5.4	71 ± 5.0	69 ± 4.0	73 ± 3.4	72 ± 3.8
Temp	Saline	37.0 ± 0.2	36.8 ± 0.1	36.8 ± 0.1	36.8 ± 0.2	36.8 ± 0.2	36.7 ± 0.2	36.9 ± 0.2	36.9 ± 0.2	37.0 ± 0.2	36.9 ± 0.2	36.9 ± 0.2	36.9 ± 0.3	36.9 ± 0.3
	Ox66™	36.8 ± 0.2	36.5 ± 0.2	36.3 ± 0.3	36.2 ± 0.4	36.2 ± 0.4	36.2 ± 0.4	36.3 ± 0.4	36.3 ± 0.4	36.4 ± 0.4	36.5 ± 0.3	36.4 ± 0.4	36.3 ± 0.4	36.4 ± 0.4

Mean arterial pressure (MAP; mmHg), heart rate (HR; BPM), pulse pressure (PP; mmHg), hind limb pulse oximetry (PuOx, %).

n: time in minutes; BL: baseline; HV-ARDS: period of 40% reduction in tidal volume; G1: period following first gavage treatment; G2: period following second gavage treatment.

Tidal volume was controlled through a ventilator and modified from 100 to 60% after the BL measurement at time 0. After 60 min of a 40% reduction in tidal volume (HV-ARDS; continued to end of study), the first gavage (G1) treatment was administered, and an additional gavage (G2) was given after the 120-min time point. Data are mean ± SEM. N = 9 for saline, N = 8 for Ox66^™.

*Indicates p < .05 compared to BL.

Intergroup comparisons failed to detect significant differences.

Table 2. Arterial blood gases and chemistry.

Metric	Group	BL	HV-ARDS	HV-ARDS + G1		HV-ARDS + G2
		0	60	90	120	150	180
PaCO2	Saline	35 ± 1.3	36 ± 2.8	35 ± 2.4	35 ± 3.0	34 ± 3.0	34 ± 3.0
	Ox66^™	34 ± 0.8	38 ± 2.7	38 ± 3.1	39 ± 3.0	38 ± 2.9	38 ± 2.5
PaO2	Saline	85 ± 2.4	76 ± 2.8*	75 ± 3.4*	72 ± 2.4*	71 ± 1.4*	73 ± 2.8*
	Ox66^™	85 ± 2.7	77 ± 3.9	72 ± 2.3*	70 ± 3.2*	73 ± 3.0	73 ± 2.8
tHb	Saline	13 ± 0.4	14 ± 0.3	14 ± 0.3	14 ± 0.4	13 ± 0.4	13 ± 0.2
	Ox66^™	13 ± 0.3	13 ± 0.5	13 ± 0.4	14 ± 0.4*	14 ± 0.4*	14 ± 0.4
SO2	Saline	90 ± 0.9	85 ± 2.7	84 ± 2.3*	83 ± 1.9*	83 ± 1.1*	84 ± 1.3*
	Ox66^™	89 ± 1.1	83 ± 3.4	81 ± 2.8	80 ± 3.4	83 ± 2.2	84 ± 2.0
COHb	Saline	0.3 ± 0.1	0.4 ± 0.1	0.4 ± 0.1	0.4 ± 0.1	0.5 ± 0.0	0.5 ± 0.0*
	Ox66^™	0.3 ± 0.1	0.4 ± 0.1	0.5 ± 0.1	0.5 ± 0.1	0.4 ± 0.1	0.4 ± 0.1
metHb	Saline	0.1 ± 0.04	0.1 ± 0.04	0.1 ± 0.03	0.0 ± 0.03	0.1 ± 0.03	0.1 ± 0.03
	Ox66^™	0.1 ± 0.04	0.1 ± 0.04	0.1 ± 0.03	0.1 ± 0.06	0.1 ± 0.02	0.1 ± 0.03
Glu	Saline	100 ± 3.3	105 ± 5.2	103 ± 3.2	106 ± 4.5	107 ± 4.7	114 ± 6.4
	Ox66^™	98 ± 3.8	96 ± 4.4	105 ± 10.1	109 ± 5.8	111 ± 5.3	114 ± 8.6
Lac	Saline	7 ± 1.2	7 ± 1.5	9 ± 1.5	10 ± 1.3	13 ± 1.5*	14 ± 1.6*
	Ox66^™	10 ± 0.7	9 ± 2.2	10 ± 1.8	11 ± 2.4	13 ± 2.9	14 ± 2.5
pH	Saline	7.36 ± 0.01	7.35 ± 0.03	7.33 ± 0.02	7.32 ± 0.02	7.31 ± 0.02	7.31 ± 0.02
	Ox66^™	7.35 ± 0.01	7.32 ± 0.02	7.29 ± 0.02	7.30 ± 0.02	7.31 ± 0.02	7.32 ± 0.02
Base Def	Saline	–6 ± 0.7	–7 ± 0.5	–8 ± 0.6*	–8 ± 1.0*	–9 ± 0.9*	–9 ± 0.9*
	Ox66^™	–7 ± 0.7	–7 ± 0.6	–8 ± 0.7	–7 ± 1.1	–8 ± 1.1	–7 ± 0.4
HCO3^–	Saline	19 ± 1.4	19 ± 0.4	18 ± 0.3	18 ± 0.5	17 ± 0.5	18 ± 0.5
	Ox66^™	19 ± 0.5	19 ± 0.4	18 ± 0.3	19 ± 0.6	19 ± 0.7	19 ± 0.3
PaO2/ FiO2	Saline	404 ± 11	363 ± 12*	355 ± 15*	343 ± 12*	337 ± 6*	349 ± 14*
	Ox66^™	404 ± 12	366 ± 18	342 ± 10*	334 ± 14*	350 ± 13	346 ± 12

Partial pressure of carbon dioxide and oxygen (P_aCO₂, P_aO₂; mmHg); total haemoglobin (tHb; g/dL); arterial oxyhaemoglobin, carboxyhaemoglobin, and methaemoglobin (SO₂, COHb, metHb; %); glucose and lactate (Glu, Lac; mg/dL); base deficit and bicarbonate ion (Base Def, HCO3; mmol/L), ratio of arterial O₂ to fractional inspired O₂ (P_aO₂/FiO₂).

BL: baseline; HV-ARDS: period of 40% reduction in tidal volume; G1: period following first gavage treatment; G2: period following second gavage treatment.

Arterial blood samples were drawn at time zero (BL) when tidal volume was 100%. Tidal volume was decreased by 40% (HV-ARDS; maintained until study end) and the next sample at 60 min occurred immediately prior to the first gavage (G1). Subsequent sampling was at 30-min intervals, and an additional gavage (G2) was given after the 120-min time point. Data are mean ± SEM. N = 9 for saline, N = 8 for Ox66^™.

*Indicates p < .05 compared to BL.

Intergroup comparisons failed to detect significant differences.

Figure 2. Diameters of resistance arterioles. Arterial diameters, as an indicator of resistance to blood flow, were imaged every hour using intravital microscopy. Reductions in diameter indicate increased peripheral resistance to blood flow. The first measurement (0 min) occurred before the onset of hypoventilation. The 60-min measurement reflects 60 min of hypoventilation without treatment. Gavages were administered following 60- and 120-min. Measurements used a digital ruler calibrated to a standard microscope stage micrometer. Raw measurements were normalized to 0 min (BL) and reported as mean ± SEM. N = 17 and 11 arterioles for Saline and Ox66^™ respective.

*Indicates p<.05 compared to BL.

Intergroup comparisons did not reveal significant differences.