Cardiac function during resuscitation from hemorrhagic shock with polymerized bovine hemoglobin-based oxygen therapeutic

Figures & data

Figure 1. Representation of experimental setup. Hamster temperature was maintained at 37 °C. Tracheotomy allows animal mechanical ventilation and administration of anesthetic (isoflurane). Pressure–volume conductance catheter was inserted through carotid artery and advanced into the left ventricle. Femoral artery was catheterized for blood withdrawal, blood sample collection, and pressure measurements. Jugular vein was catheterized for fluid administration. Cardiac function and systemic hemodynamics measurements were using analog to digital acquisition system and stored for off-line analysis.

Table 1. Resuscitation fluid and blood physical properties.

	Blood	Dextran 70	PolyHb 8.5	PolyHb 11.5
Hb, g/dL	14.7 ± 0.3	–	8.5 ± 0.1	11.5 ± 0.1
P50, mmHg	32.1 ± 0.9	–	42.0 ± 1.3	41.0 ± 1.1
Hill number	2.9 ± 0.1	–	1.2 ± 0.1	1.2 ± 0.1
Viscosity, cP^a	4.3 ± 0.3	3.8 ± 0.1	2.4 ± 0.2	2.7 ± 0.2
COP, mmHg	24.2 ± 1.2	42 ± 1.1	28.6 ± 0.8	35.2 ± 1.2
MetHb, %	–	–	4.2 ± 1.4	3.7 ± 1.0

Values are means ± SD (n = 4).

Hb: hemoglobin; P50: oxygen tension at which hemoglobin is 50% saturated; Hill number: Hb cooperative binding; COP: colloid osmotic pressure; MetHb: methemoglobin.

^a Viscosity at 300^−s and 37 °C.

PolyHb properties, average weight: 250 kDa; in vivo half-life: 19 h; and shelf-life 3yrs.

Figure 2. Mean arterial pressure and heart rate during the hemorrhagic shock resuscitation protocol. †, P < .05 compared to baseline; ‡, P < .05 compared to Dextran 70; and ¶, P < .05 compared to PolyHb 8.5.

Table 2. Hematocrit, hemoglobin, and blood gases.

		Dextran 70	PolyHb 8.5	PolyHb 11.5
Hematocrit, %	Baseline	48.5 ± 2.1	48.2 ± 1.8	47.5 ± 1.4
	Shock	37.3 ± 2.3^a	38.0 ± 2.1^a	37.4 ± 2.2^a
	R10	24.5 ± 1.8^a	25.6 ± 2.1^a	24.9 ± 2.0^a
	R60	23.5 ± 2.7^a	27.1 ± 1.9^a	26.5 ± 2.9^a
Hb, g/dL	Baseline	15.3 ± 0.8	14.8 ± 0.6	14.2 ± 0.8
	Shock	11.2 ± 0.5^a	11.8 ± 0.5^a	11.1 ± 0.6^a
	R10	7.7 ± 0.4^a	11.7 ± 0.6^a^,^b	12.7 ± 0.5^a^,^b^,^c
	R60	7.3 ± 0.4^a	11.1 ± 0.5^a^,^b	11.9 ± 0.4^a^,^b^,^c
Plasma Hb, g/dL
	R10	–	3.5 ± 0.3	4.2 ± 0.3^c
	R60	–	2.4 ± 0.2	3.3 ± 0.4^c
Arterial pH	Baseline	7.38 ± 0.03	7.38 ± 0.04	7.36 ± 0.05
	Shock	7.31 ± 0.04^a	7.31 ± 0.04^a	7.32 ± 0.04^a
	R10	7.37 ± 0.06	7.36 ± 0.07	7.36 ± 0.08
	R60	7.38 ± 0.05	7.35 ± 0.07	7.35 ± 0.04
PCO2, mmHg	Baseline	42.2 ± 6.2	43.7 ± 5.8	44.1 ± 8.5
	Shock	22.1 ± 4.4^a	23.3 ± 5.7^a	23.5 ± 4.4^a
	R10	32.5 ± 4.7^a	36.8 ± 5.2^a	34.3 ± 5.1^a
	R60	34.8 ± 5.2^a	38.7 ± 5.1^a	36.5 ± 5.5^a
PO2, mmHg	Baseline	86.8 ± 8.6	87.1 ± 8.8	84.5 ± 7.9
	Shock	131.1 ± 10.6^a	126.9 ± 9.9^a	123.5 ± 8.2^a
	R10	127.9 ± 10.9^a	132.7 ± 9.4^a	134.5 ± 8.9^a
	R60	109.9 ± 9.5^a	125.3 ± 9.2^a^,^b	139.1 ± 9.4^a^,^b^,^c

Values are means ± SD. All groups were similar at baseline (P  > .30).

Hct: systemic hematocrit; Hb: hemoglobin; plasma Hb: acellular hemoglobin; PO₂: arterial partial O₂ pressure; PCO₂: arterial partial pressure of CO₂

^a P < .05 compared to baseline

^b P < .05 compared to Dextran 70

^c P < .05 compared to PolyHb 8.5

Figure 3. Stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), and oxygen delivery (DO₂) during the hemorrhagic shock resuscitation protocol. Estimated oxygen consumption (VO₂) at baseline is presented in the DO₂ panel. †, P < .05 compared to baseline; ‡, P < .05 compared to Dextran 70; and ¶, P < .05 compared to PolyHb 8.5.

Figure 4. Indices of left ventricle cardiac function during the hemorrhagic shock resuscitation protocol. Directly measured indices of left ventricle cardiac function were end systolic pressure (P_es) and end diastolic pressure (P_ed). Calculated indices of left ventricle cardiac function were ejection fraction (EF), maximum rate of pressure change (dP/dt_max), minimum rate of pressure change (dP/dt_min), and maximum filling volume rate (dV/dt_max). †, P < .05 compared to baseline; ‡, P < .05 compared to Dextran 70; and ¶, P < .05 compared to PolyHb 8.5.

Figure 5. Energetic indices of left ventricle cardiac function during the hemorrhagic shock resuscitation protocol. Calculated external left ventricle cardiac work was estimated using stroke work, and energy metabolism utilization estimated using the internal energy utilization (Doyle et al. 2013). †, P < .05 compared to baseline; ‡, P < .05 compared to Dextran 70; and ¶, P < .05 compared to PolyHb 8.5.

Doyle M, Weinberg N, Pohost GM, Merz CNB, Shaw LJ, Sopko G, et al. 2013. Left ventricular energy model predicts adverse events in women with suspected myocardial ischemia: results from the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE) study. Cardiovasc Diagn Ther. 3:64.

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