Non-toxicity of IV Injected Perfluorocarbon Oxygen Carrier in an Animal Model of Liver Regeneration Following Surgical Injury

Figures & data

Table 1. The experimental sub-groups

		PFC		Saline
Doses (day 1)		LI (+)	LI (−)	LI (+)	LI (−)
Low	2 g/kg	6	6	6	6
High	5 g/kg	6	6	6	6
Durations		Terminations (3 of each dose group above)
Short	Day 2	6	6	6	6
Long	Day 4	6	6	6	6
	Total surgery	12		12
	TOTAL				48

Table 2. Measured variables and units

Variable	Explanation	Unit
LI	liver injury
PFC	perfluorocarbon
SAL	saline
BW	mean body weight	g
+ and −	with and without
ΔBW	change in mean body weight	g
spleen	mean spleen weight	g
spleen/BW	mean percentage spleen to body weight ratio	%
Δspleen/BW	mean change in percentage spleen to body weight ratio	%
liver	mean liver weight	g
liver/BW	mean percentage liver to body weight ratio	%
Δliver/BW	mean change in percentage liver to body weight ratio	%
Alb	mean plasma albumin concentration	g/l
ALT	plasma alanine amino transferase concentration	U/l at 37 ^oC
AST	plasma aspartate amino transferase concentration	U/l at 37 ^oC
Urea	plasma urea concentration	Mmol/l
Bili-T	plasma total bilirubin concentration	µmol/l
Ammo	plasma ammonia concentration	µmol/l
RCC	blood red cell count	×10^12/ l
Hkt	hematocrit	% l/l
WCC	blood white cell count	×10^9/ l
Ab-Neutr	absolute neutrophil count	×10^9/ l
Ab-Lymp	absolute lymphocyte count	×10^9/ l
Ab-Mono	absolute monocyte count	×10^9/ l
Plt-C	platelet count	×10^9/ l

Table 3. Weight changes, biochechemistry and hematology

		Groups
Variable	Baseline (N = 24)	2-days +LI + PFC (N = 6)	2-days +LI +SAL (N = 3)	2-days −LI +PFC (N = 6)	2-days −LI +SAL (N = 3)	4-days +LI +PFC (N = 6)	4-days +LI +SAL (N = 3)	4-days −LI +PFC (N = 6)	4-days −LI +SAL (N = 3)
BW	210.97±27.91	215.62±9.01	204.73±13.68	207.13±29.13	222.60±8.28	211.82±6.58	183.30±21.71	225.50±7.40	232.70±8.62
▵BW		−29.45±16.28	−13.97±9.16	−3.42±2.56	0.40±3.40	−25.60±5.30	−18.63±5.08	−5.20±7.78	0.70±4.59
spleen	0.688±0.269	0.637±0.142	0.542±0.305	0.652±0.059	0.540±0.023	0.756±0.286	0.472±0.033	1.02±0.38	0.56±0.11
spleen/BW	0.326±0.111	0.262±0.068	0.246±0.138	0.314±0.050	0.243±0.003	0.318±0.118	0.235±0.020	0.44±0.15	0.24±0.04
▵spleen/BW		0.064±0.068	0.080±0.138	0.012±0.050	0.083±0.003	0.008±0.118	0.091±0.020	−0.114±0.146	0.085±0.04
liver	7.364±1.008	5.107±0.528	4.307±0.673	8.008±0.738	6.818±0.634	6.090±0.724	5.147±0.713	8.311±0.596	6.662±0.764
liver/BW	3.523±0.457	2.104±0.351	1.966±0.269	3.842±0.399	3.078±0.394	2.566±0.300	2.559±0.352	3.605±0.228	2.874±0.342
▵liver/BW		1.419±0.351	1.557±0.269	−0.319±0.399	0.445±0.394	0.957±0.300	0.964±0.352	−0.082±0.228	0.649±0.342
Alb	43.8±2.1	33.1±1.8	36.17±2.23	38.07±2.27	47.70±3.25	31.20±2.80	33.13±2.27	35.48±2.08	41.70±0.95
ALT	44±6	338±202	450±223	53±19	62±33	66±12	56±5	39±8	41±9
AST	65±9	541±180	891±723	80±27	66±15	123±29	81±9	48±6	50.7±4.9
Urea	7.4±0.9	6.2±1.3	6.9±3.2	5.2±1.2	6.1±1.7	5.2±1.4	5.5±1.5	6.3±0.9	5.8±4.9
Bili-T	4.1±0.8	23.8±4.7	14.3±2.7	4.2±1.2	5.2±1.5	6.9±1.9	5.6±1.4	5.5±2.9	5.6±2.8
Ammo	52.1±20.8	76.2±32.5	123.3±136.7	31.6±5.3	32.8±15.7	53.8±16.5	44.2±17.4	29.2±9.03	49.6±15.2
RCC	8.63±0.95	7.34±0.78	6.25±2.30	8.65±0.64	8.24±0.18	7.46±0.70	8.17±0.24	8.54±0.47	8.70±0.23
Hkt	43.5±1.4	36.2±0.04	30.7±11.0	42.5±1.9	40.0±1.7	38.2±3.1	41.7±1.5	42.0±1.80	42.7±0.06
WCC	7.90±1.29	10.35±3.75	13.58±6.45	5.72±1.17	4.94±1.31	5.98±0.92	12.99±1.67	6.08±1.78	7.53±1.36
Ab-Neutr	0.76±0.41	4.64±1.77	8.26±3.47	1.12±0.41	1.15±0.72	2.70±1.18	4.32±0.84	0.65±0.61	0.58±0.23
Ab-Lymp	6.82±1.35	5.20±2.33	3.82±2.76	4.35±0.90	3.23±1.37	3.34±1.10	7.05±1.27	5.14±1.52	6.48±1.36
Ab-Mono	0.24±0.21	0.33±0.20	1.27±0.99	0.14±0.08	0.50±0.4	0.27±0.20	1.53±0.92	0.20±0.12	0.34±0.04
Plt-C	491±387	783±145	803±209	686±130	555±425	425±207	550±109	366±158	1051±112

Notes:

1. In this table the high-dose and low-dose PFC groups were summed as no difference could be detected between them in the raw data.

2. All values are presented as mean±std deviation.

3. Δ = change in value.

Figure 1.  Liver regeneration projections, assuming linear re-growth. The rate of regeneration after liver injury and IV dosing of PFC or saline is not significantly different. The y-intercept indicates the amount of liver initially resected. A liver/BW value of 1.5 equates to approximately a 60% liver weight resection. The projected time to complete liver weight regeneration, i.e. to a liver/BW ratio of 3.5, is 7-8 days. This duration is in agreement with prior experience with this surgical model 18–23.