Pharmacodynamic Study of Polyethylene Glycol Conjugated Bovine Hemoglobin (PEG-bHb) in Rats

Figures & data

Table 1. The treatment groups of rats

Groups shock model	No. in groups	Groups exchange model	No. in groups	Resuscitation fluids
S1	26	E1	26	No resuscitation fluids were given
S2	34	E2	34	Whole blood (isovolume of hemorrhage)
S3	8	E3	7	Whole blood (1/2 volume of hemorrhage)
S4	36	E4	38	PEG-bHb (1/2 volume of hemorrhage)
S5	42	E5	59	PEG-bHb (isovolume of hemorrhage)
S6	39	E6	43	PEG-bHb (1.5-fold volume of hemorrhage)
S7	35	E7	35	Dextran (isovolume of hemorrhage)

Figure 1. Survival of rats at 24, 48, and 72 h in shock model. (View this art in color at www.dekker.com.)

Figure 2. Survival of rats at 24, 48, and 72 h in exchanged transfusion model. (View this art in color at www.dekker.com.)

Figure 3. The MAP of rats in hemorrhage shock model. Blood pressure increased when treatment fluids infused. (View this art in color at www.dekker.com.)

Figure 4. The heart rate of rats in hemorrhage shock model. The heart rate increased with MAP elevation. (View this art in color at www.dekker.com.)

Figure 5. MAP of rats in exchange transfusion model. Efficacy in blood pressure recovery of PEG-bHb was outstanding. (View this art in color at www.dekker.com.)

Figure 6. Heart rate of rats in exchange transfusion model. (View this art in color at www.dekker.com.)

Table 2. Concentration change of Cl⁻ of rats in shock model (mmol/L, x ± s)

		After infusion
Groups (no.)	Normal state	30 min	180 min
S1 (16)	110.69 ± 4.84	114.86 ± 5.13	111.88 ± 5.41
S2 (15)	119.96 ± 7.32	123.51 ± 7.76	118.38 ± 7.07
S4 (8)	114.25 ± 8.32	122.05 ± 12.52	121.05 ± 7.85
S5 (30)	116.76 ± 13.38	121.76 ± 15.97	120.87 ± 14.48
S6 (26)	116.95 ± 13.39	122.56 ± 13.51	117.27 ± 7.31
S7 (21)	120.93 ± 13.59	132.02 ± 14.47	125.61 ± 14.44

There is no significant difference among groups.

Table 3. Concentration change of Cl⁻ of rats in exchange transfusion model (mmol/L, x ± s)

		After exchange transfusion
Groups (no.)	Normal state	30 min	180 min
E1 (15)	118.44 ± 9.87	124.64 ± 15.53	117.45 ± 0.21
E2 (21)	118.91 ± 9.63	127.09 ± 8.62	118.07 ± 5.78
E4 (7)	121.69 ± 10.57	123.13 ± 6.43	121.79 ± 8.65
E5 (46)	118.74 ± 7.63	123.53 ± 10.72	120.36 ± 10.86
E6 (32)	117.36 ± 10.56	124.82 ± 8.32	125.80 ± 12.33
E7 (22)	123.48 ± 7.85	133.37 ± 15.47	128.85 ± 12.04

Table 4. Changes of blood viscosity of shock model rats at different shearing stress of 5 p/s and 200 p/s (x ± s)

	5 p/s			200 p/s
		After infusion			After infusion
Groups (no.)	Normal	30 min	180 min	Normal	30 min	180 min
S1 (26)	6.78 ± 1.31	6.33 ± 1.05	5.55 ± 1.69	2.91 ± 0.41	1.91 ± 0.33	2.22 ± 0.31
S2 (34)	9.13 ± 2.28	9.14 ± 2.17	8.24 ± 3.41	3.15 ± 0.31	3.32 ± 0.60	2.97 ± 0.45
S4 (36)	7.12 ± 1.60	4.55 ± 0.86	3.51 ± 0.46	2.69 ± 0.23	1.96 ± 0.11	1.76 ± 0.07
S5 (42)	9.43 ± 1.14	4.02 ± 1.19	3.41 ± 0.48	2.66 ± 0.55	1.70 ± 0.35	1.77 ± 0.06
S6 (39)	7.63 ± 1.74	3.51 ± 0.69	3.65 ± 0.44	2.88 ± 0.50	1.63 ± 0.37	1.77 ± 0.13
S7 (35)	8.94 ± 2.97	3.75 ± 1.10	3.70 ± 0.82	3.23 ± 1.21	1.94 ± 0.34	1.87 ± 0.21

Table 5. Changes of blood viscosity of exchange model rats at different shearing stress of 5 p/s and 200 p/s (x ± s)

	5 p/s			200 p/s
		After infusion			After infusion
Groups (no.)	Normal	30 min	180 min	Normal	30 min	180 min
E1 (26)	6.44 ± 2.55	6.02 ± 2.6	6.89 ± 2.35	2.59 ± 0.7	2.60 ± 0.94	2.97 ± 0.80
E2 (34)	9.33 ± 2.76	8.39 ± 1.84	7.49 ± 1.91	3.29 ± 0.68	2.95 ± 0.36	2.82 ± 0.42
E4 (38)	9.51 ± 3.11	4.26 ± 0.74	3.86 ± 0.69	3.06 ± 0.59	2.01 ± 0.19	1.93 ± 0.31
E5 (59)	8.98 ± 1.81	4.56 ± 0.37	4.05 ± 1.54	3.32 ± 0.55	2.17 ± 0.13	2.08 ± 0.17
E6 (43)	8.69 ± 3.03	4.33 ± 0.21	4.37 ± 0.41	3.19 ± 0.91	1.95 ± 0.16	1.93 ± 0.2
E7 (35)	8.59 ± 1.88	5.46 ± 0.84	5.81 ± 1.66	3.19 ± 0.45	2.34 ± 0.26	2.45 ± 0.57

Figure 7. The flow rate of arteriole in hemorrhage shock model rats. (View this art in color at www.dekker.com.)

Figure 8. The flow rate of venula in hemorrhage shock model rats. The blood flow rate of venula recovered nearly to normal level when PEG-bHb transfused. (View this art in color at www.dekker.com.)

Figure 9. The flow rate of arteriole in exchange transfusion model rats. The blood flow rate of arteriole recovered nearly to normal level when PEG-bHb transfused. (View this art in color at www.dekker.com.)

Figure 10. The flow rate of venula in exchange transfusion model rats. (View this art in color at www.dekker.com.)

Table 6. Oxygenation of liver throughout the study in shock model rats (% change from basal, x ± s)

	Shock		After reinfusion
Groups	0 min	60 min	0 min	30 min	60 min
S1	−92.56 ± 3.13	−95.50 ± 0.34	−96.95 ± 2.66	−94.55 ± 0.51	−95.46 ± 0.46
S2	−94.49 ± 3.77	−98.07 ± 0.33	−7.57 ± 19.47	−26.30 ± 15.39	−24.98 ± 17.91
S4	−93.89 ± 4.23	−97.19 ± 2.37	−49.24 ± 22.04	−58.12 ± 7.51	−59.15 ± 6.58
S5	−92.72 ± 7.24	−93.03 ± 5.41	−43.48 ± 24.74	−43.35 ± 23.12	−55.37 ± 15.74
S6	−95.33 ± 1.18	−97.66 ± 1.13	−40.16 ± 12.47	−38.16 ± 5.10	−40.15 ± 18.53
S7	−95.08 ± 3.66	−95.71 ± 3.37	−59.11 ± 21.17	−73.47 ± 17.66	−78.75 ± 20.63

Table 7. Oxygenation of muscle throughout the study in shock model rats (% change from basal, x ± s)

	Shock		After reinfusion
Groups	0 min	60 min	0 min	30 min	60 min
S1	−62.06 ± 5.42	−69.02 ± 11.30	−69.02 ± 11.30	−85.81 ± 5.84	−82.06 ± 6.97
S2	−69.72 ± 14.67	−81.41 ± 6.40	−17.54 ± 5.46	−7.97 ± 13.44	−26.65 ± 9.28
S4	−67.96 ± 13.46	−74.35 ± 28.22	−35.75 ± 29.04	−18.62 ± 20.94	−30.85 ± 17.48
S5	−77.33 ± 10.02	−89.78 ± 8.60	−22.09 ± 27.36	−16.58 ± 14.77	−22.08 ± 12.88
S6	−75.76 ± 14.13	−84.99 ± 6.11	−15.93 ± 7.19	−13.71 ± 12.45	−18.32 ± 31.67
S7	−75.50 ± 18.45	−86.37 ± 12.79	−73.51 ± 28.33	−60.36 ± 20.99	−58.27 ± 18.01

Table 8. Oxygenation of intestine throughout the study in shock model rats (% change from basal, x ± s)

	Shock		After reinfusion
Groups	0 min	60 min	0 min	30 min	60 min
S1	−79.55 ± 16.85	−77.18 ± 8.69	−77.18 ± 8.69	−85.23 ± 7.41	−84.49 ± 12.27
S2	−81.83 ± 10.47	−85.14 ± 8.21	−36.36 ± 30.75	−46.86 ± 22.48	−39.77 ± 37.76
S4	−78.17 ± 20.75	−86.54 ± 13.77	−45.24 ± 32.12	−48.87 ± 34.87	−60.59 ± 25.55
S5	−76.28 ± 17.02	−80.60 ± 14.92	−24.63 ± 36.88	−48.76 ± 21.36	−53.43 ± 20.42
S6	−79.00 ± 18.70	−81.37 ± 19.46	−41.18 ± 19.77	−44.10 ± 22.35	−46.52 ± 31.46
S7	−90.04 ± 5.69	−91.08 ± 8.00	−63.63 ± 28.30	−70.56 ± 28.44	−72.85 ± 28.57

Table 9. Oxygenation of tissues throughout the study in exchange model rats (% change from basal, x ± s)

		After transfusion
Tissues	Groups	0 min	30 min	1 h	1.5 h	2 h
Liver	S1	−98.02 ± 1.12	−94.49 ± 6.60	−84.47 ± 24.61	−97.26 ± 3.36	−97.77 ± 2.67
	S2	−13.24 ± 14.90	−32.23 ± 13.06	−43.34 ± 10.80	−52.23 ± 13.56	−57.67 ± 10.72
	S4	−31.20 ± 11.05	−44.49 ± 9.87	−52.92 ± 10.87	−60.76 ± 8.58	−62.45 ± 9.80
	S5	−38.76 ± 14.84	−49.70 ± 11.20	−64.08 ± 8.95	−67.58 ± 4.60	−70.87 ± 4.09
	S6	−46.47 ± 8.30	−58.90 ± 10.73	−67.01 ± 8.06	−71.86 ± 6.58	−73.50 ± 4.60
	S7	−80.01 ± 3.84	−79.54 ± 7.26	−81.79 ± 10.3	−91.37 ± 4.55	−91.30 ± 4.00
Muscle	S1	−80.31 ± 20.27	−77.58 ± 21.78	−88.62 ± 12.94	−95.08 ± 6.77	−96.01 ± 6.50
	S2	−11.36 ± 15.96	−12.77 ± 29.19	−29.92 ± 15.73	−41.89 ± 10.68	−52.47 ± 12.84
	S4	−20.32 ± 24.89	−33.24 ± 24.56	−41.51 ± 24.74	−49.66 ± 15.24	−61.14 ± 11.98
	S5	−19.46 ± 28.37	−31.66 ± 16.43	−44.01 ± 9.13	−54.98 ± 11.11	−63.50 ± 12.84
	S6	−16.27 ± 21.57	−29.03 ± 19.96	−35.15 ± 15.72	−51.97 ± 20.16	−67.41 ± 16.37
	S7	−65.98 ± 20.63	−59.74 ± 11.85	−70.04 ± 13.38	−78.62 ± 11.36	−81.34 ± 11.94
Intestine	S1	−75.11 ± 29.86	−82.02 ± 29.50	−91.95 ± 7.57	−93.72 ± 7.38	−95.20 ± 7.34
	S2	−23.89 ± 22.45	−26.90 ± 36.16	−32.06 ± 19.25	−37.07 ± 24.75	−40.18 ± 25.53
	S4	−39.98 ± 14.54	−40.39 ± 13.01	−46.46 ± 12.59	−55.08 ± 8.42	−52.02 ± 10.37
	S5	−47.06 ± 4.89	−45.65 ± 12.21	−46.74 ± 21.97	−50.14 ± 15.44	−50.56 ± 15.30
	S6	−17.45 ± 14.49	−31.73 ± 25.41	−39.88 ± 19.30	−43.02 ± 17.02	−46.05 ± 7.99
	S7	−63.05 ± 15.69	−72.33 ± 13.03	−72.62 ± 20.74	−70.66 ± 33.37	−70.46 ± 31.58