Biomedical subjects

Stephanie A Savage

Publications and source records attributed to Stephanie A Savage.

3 recordsLinked to original sources

PubMed2005

Prolonged low-volume resuscitation with HBOC-201 in a large-animal survival model of controlled hemorrhage.

BACKGROUND: Military guidelines call for two 500-mL boluses of Hextend for resuscitation in far-forward environments. This study compared a hemoglobin-based oxygen carrier (HBOC-201; Hemopure) to Hextend when used to treat hemorrhagic shock in situations of delayed definitive care military operations. METHODS: Yorkshire swine (55-65 kg) were hemorrhaged to a mean arterial blood pressure (MAP) of 30 mmHg. Hypotension was maintained for 45 minutes followed by resuscitation with either Hextend (HEX) (n = 8) or HBOC-201 (HBOC) (n = 8). Over 8 hours, animals received up to 1,000 mL of either fluid in an effort to sustain an MAP of 60 mmHg. At the end of 8 hours, HEX animals received 2 L of lactated Ringer's solution followed by shed blood. HBOC animals received 4 L of lactated Ringer's solution only. Animals were killed and necropsied on postprocedure day 5. Hemodynamic data were collected during shock and resuscitation. Complete blood counts, amylase, lactate, coagulation studies, and renal and liver function were measured throughout the experiment. RESULTS: Equivalent volumes were hemorrhaged from each group (HBOC, 44.3 +/- 2.2 mL/kg; HEX, 47.4 +/- 3.0 mL/kg). The HBOC group achieved the goal MAP (HBOC, 60.0 +/- 2.3 mmHg; HEX, 46.4 +/- 2.3 mmHg; p < 0.01) and required less volume during the initial 8 hours (HBOC, 12.4 +/- 1.4 mL/kg; HEX, 17.3 +/- 0.3 mL/kg; p < 0.01). The HBOC group had lower SvO2 (HBOC, 46.3 +/- 2.4%; HEX, 50.7 +/- 2.5%; p = 0.12) and cardiac output (HBOC, 5.8 +/- 0.4 L/min; HEX, 7.2 +/- 0.6 L/min; p = 0.05), but higher systemic vascular resistance (HBOC, 821.4 +/- 110.7 dynes . s . cm-5; HEX, 489.6 +/- 40.6 dynes . s . cm-5; p = 0.01). Base excess, pH, lactate, and urine output did not differ between groups. HEX group survival was 50% (four of eight) versus 88% for the HBOC group (seven of eight). All animals survived the initial 8 hours. Animals surviving 5 days displayed no clinical or laboratory evidence of organ dysfunction in either group. CONCLUSION: HBOC-201 more effectively restored and maintained perfusion pressures with lower volumes, and allowed for improved survival. These data suggest that hemoglobin-based oxygen carriers are superior to the current standard of care for resuscitation in far-forward military operations.

Alanine Transaminase↗

PubMed2005

Endothelial dysfunction after lactated Ringer's solution resuscitation for hemorrhagic shock.

BACKGROUND: Endothelial dysfunction is presumed to occur after hemorrhagic shock and resuscitation. This study uses a novel large-animal model to evaluate the effects of diverse resuscitation regimens on endothelial function. METHODS: Twenty-seven adult domestic pigs (Sus scrofa) were used in this study. Control pigs (n = 3) underwent instrumentation alone. The remaining pigs experienced controlled hemorrhagic shock to a mean arterial blood pressure of 30 +/- 5 mm Hg for 45 minutes. Pigs were resuscitated to their baseline mean arterial blood pressure +/-5 mm Hg with either shed blood (SB; n = 8), lactated Ringers solution (40 mL/kg) followed by shed blood (LRSB; n = 8), or lactated Ringers solution alone (LR; n = 8). At baseline, 1 and 4 hours after resuscitation, acetylcholine (5, 10, and 15 microg/min) was infused into the proximal iliac artery to measure endothelial dependent relaxation (EDR). Sodium nitroprusside was infused to determine endothelial independent relaxation at the end of the study to insure smooth muscle vasomotor integrity. External iliac artery luminal diameter was measured using motion-mode ultrasonography. Statistical analysis was performed using repeated-measures analysis of variance with Tukey's post-hoc analysis. RESULTS: All pigs survived the experiment. Pigs required ninefold more resuscitation with LR (370.58 +/- 29 mL/kg) versus SB (41.45 +/- 3.5 mL/kg) or LRSB (76.4 +/- 1.1 mL/kg) (p < 0.05). EDR for LR pigs 1 hour after initiation of resuscitation (R1) was 70.4 +/- 14.4% compared with 94.2 +/- 13.4% for SB and 106.1 +/- 8.2% for LRSB (p < 0.05). At 4 hours after resuscitation (R4), systolic luminal diameters were larger in the SB (0.45 +/- 0.01 cm) and LRSB (0.51 +/- 0.02 cm) groups compared with LR (0.41 +/- 0.03 cm) (LRSB versus LR; p = 0.01). At R4, EDR for the LR group was 78.3 +/- 10.7% compared with SB (101.4 +/- 8.3%) and LRSB (106.4 +/- 7.4%) (p < 0.05). Infusion of sodium nitroprusside confirmed integrity of smooth muscle vasorelaxation. Analysis of serum nitric oxide levels revealed decreased values after resuscitation with LR (9.44 +/- 0.76 mol/L) compared with SB (26.3 +/- 7.8 mol/L) and LRSB (16.3 +/- 1.0 mol/L) (p = not significant). CONCLUSION: This is the first description of a large-animal model to evaluate EDR after hemorrhagic shock. Resuscitation with LR requires significantly larger volumes than SB or LRSB. LR resuscitation leads to endothelial dysfunction, as determined by decreased EDR, versus SB or LRSB. Resuscitation with blood products may preserve nitric oxide bioactivity when compared with crystalloid resuscitation in the setting of hemorrhagic shock.

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PubMed2004

Resuscitation with a blood substitute causes vasoconstriction without nitric oxide scavenging in a model of arterial hemorrhage.

BACKGROUND: The purpose of this study was to determine if a hemoglobin-based oxygen carrier, HBOC-201 (Hemopure, Biopure Corp), alters endothelial function and nitric oxide physiology when used for hemorrhagic shock. STUDY DESIGN: Female swine (Sus scrofa) underwent catheterization of the femoral, circumflex iliac, and pulmonary arteries. Control animals (n = 3) underwent instrumentation only. Study animals underwent hemorrhage to mean arterial pressure of 30 +/- 5 mmHg, were maintained for 45 minutes, and resuscitated to the baseline mean arterial pressure for 4 hours. Resuscitation fluids included: shed blood (SB) (n = 8), lactated Ringers plus shed blood (LRSB) (n = 8), and HBOC (n = 8). At baseline, 1, and 4 hours after resuscitation, acetylcholine was infused into the proximal iliac artery and endothelial-dependent relaxation was measured with M-mode ultrasonography. Nitric oxide levels were determined using a chemiluminescent assay. RESULTS: HBOC, SB, and LRSB provided equivalent survival and resuscitation as measured by mean arterial pressures (65.3 +/- 2.48 mmHg); pulmonary artery mean pressures (15.8 +/- 0.84 mmHg); and lactate levels (1.22 +/- 0.19 mmol/L). HBOC group animals required the lowest resuscitation volume (SB, 41.5 +/- 3.5 mL/kg; LRSB, 76.4 +/- 1.1 mL/kg, HBOC, 14.6 +/- 2.1 mL/kg, p < 0.001). Response to acetylcholine was normal in the SB and LRSB groups, but the HBOC group had diminished acetylcholine response (29.5% endothelial-dependent relaxation end resuscitation, p < 0.001). Arterial nitric oxide levels did not differ between study groups (p = 0.69). CONCLUSIONS: HBOC might be an alternative resuscitation agent in patients with hemorrhagic shock. Resuscitation with HBOC requires less volume than blood or crystalloid. These data suggest HBOC-201 has a vasoconstrictive effect that cannot be attributed soley to nitric oxide scavenging.

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