Bovine polymerized hemoglobin increases cardiac oxygen consumption and alters myocardial substrate metabolism in conscious dogs: role of nitric oxide.

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Bovine polymerized hemoglobin increases cardiac
oxygen consumption and alters myocardial
substrate metabolism in conscious dogs role of
nitric oxide. Loke KE, Forfia PR, Recchia FA, Xu
X, Osorio JC, Ochoa M, Gawryl M, Hintze TH.
Department of Physiology, New York Medical
College, Valhalla 10595, USA.
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Figure 1. Temporal distribution of all trauma
deaths, including deaths at the scene (n
2,944). Note the absence of the third peak (gt7
days) described in the classic trimodal
distribution of trauma deaths. J Am Coll Surg
2005201343-348
Figure 2. Temporal distribution of trauma deaths
according to mechanism of injury (n 2,944).
Note the major differences between penetrating
(white bars, n 1,521) and blunt (black bars, n
1,423) trauma and the absence of the third peak
(gt7 days) described in the classic trimodal
distribution of trauma deaths. J Am Coll Surg
2005201343-348
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Confounding Influences
Project Anesthesia paralysed Ventilation O2 atropine Splenetomy Others
2-1 v v v
2-2 v v v Female
2-3 v
2-4 v Laparotomy
2-5 v v
2-6 v v v
3-1 v
3-2 v v v
3-3 v
3-4 v v
4-1 v
4-2 v v
4-3 v v
4-4 v v
4-5 v v
5-1 v v v v v
5-2 v v v v
5-3 v v v v
6-1 v v v HCT up spleen contraction
6-2 v v
6-3 v v v
7-1 Surgery (Lidocaine)
7-2 v
K004-02 v v v
8 v v v
9 v v v (ascaris)
10 v v v v
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Baseline Hemodynamics (1)
Project number CO (L/min) MAP mmHG HR b/min
2-1 ECMO
2-2 6 75
2-3 5-7 80 80
2-4 4-6.5 70
2-5 70-90
2-6 7-9 80-90 69-72
3-1 83-86
3-2 2-4 100-120
3-3 3-4 100
3-4 (CI) 90-100 60
4-1 5 (CI) 60-80 140(atropine)
4-2
4-3
4-4 4.5-5.5 (CI) 60-70 120-160
4-5 (SVI) 60-90 Atropine
5-1 3.5 100 80
5-2 3.8 80 75
5-3 90
6-1 4.4-4.9 (CI) 89-93 115-126
6-2 3.5 77
6-3 4 80-90
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Baseline Hemodynamics (2)
Project number CO (L/min) MAP mmHG HR b/min

7-1 RAT
7-2 RAT 672.6
K004-02 4.9 (CI) 75-100 144
8 3-4 (CI) 2.7-3.9 65-90 100-115 100-130
9 4.3-4.8 4.4-4.8 4.6-4.9 89-93 115-127
10 3.4-3.3 3.4-3.5 3.5-3.6 3.4-3.4 74-77 134-154
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Project number Project applicability Compound Survival
2-1 ECMO NA HB-201 8 hr
2-2 Y HBOC-201 blood LR 4 hr
2-3 Y Heta starch HBOC-201 All-8 hr 4/8 heta-5 D 7/8 HBOC-5 D
2-4 Lapanatomy Y HBOC-201 4 hr 3 days
2-5 Y HBOC-201 blood LR 4 hr 100 HBOC
2-6 Y 6 solutions HBOC-201 4 hr 100 HBOC
3-1 Brain injury NA HBOC-301 72 hr LR Died 6 hr
3-2 NA LR, Blood, rHB, DCLHB
3-3 Brain injury NA DCLHB 1/8-3/8 HBOC
3-4 Lung trauma NA Polymerized HB Saline No mortality 8hr
4-1 Liver injury Y HBOC-201 7/8 4 hr 7/8 72 hr 1/8 Hex
4-2 Rectus crush Y HBOC-201 hex 8/8 HBOC 7/8 Hex 72 hr
4-3 Rectus crush Y HBOC-201 hex As above
4-4 Rectus crush Y HBOC-201 hex 8/8 HBOC 7/8 Hex 72 hr
4-5 Rectus crush Y HBOC-201 hex 7/7 HBOC 7/8 Hex 4 hr
5-1 Y HBOC-201 LR 10/10 HBOC 2 hr
5-2 Y HBOC-201 No mortality 2hr
5-3 Y HBOC-201 2 hr
6-1 Liver bleeding Y HBOC-201 heta starch 8/8 HBOC 40 min 7/8 HBOC 96 hr
6-2 Liver bleeding Y HBOC-201 LR 7/8 HBOC 2 hr
6-3 Aortic baloon NA HBOC-201 6/6 HBOC 0/6 LR
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Project number Project applicability Compound Survival
7-1 rat awake NA Polyhem
7-2 anest. rat Y HB-201 C-102 20m HBOC-228 31 min
K004-02 rectus crush Y HB-201 96 HBOC 58 Hex
8 Iliac bleeding Y SalineHBOC-201hex Survival lowest with HBOC
9 Liver crush Y No fluid, hex, HBOC-201 8/8 HBOC-24 hr 7/8 HBOC-96 hr
10 Liver laceration Y 1/10 LR 7/7 HBOC 129 min
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Executive summary BPAC Meeting on RESUS, Use
ofHBOC-201. T Hintze, New York Medical College
Major technical concerns 1) All/many of the
studies in pigs (excluding the 2 in rats) used
anesthesia, ventilation, paralysis, splenectomy,
laparotomy, ventilation with oxygen at different
times and to different end-points and especially
used atropine (I suspect to block tracheal
secretions from the anesthesia) which has marked
effects on heart rate (tachycardia) and
circulating catecholamines. 2) The hemorrhage
was almost always sterile unlike RESUS. 3) The
fluid administered was often warmed and the pig
was warmed. 4) Measurements of cardiac output
and heart rate were variable prior to hemorrhage
due to anesthesia, atropine and variability in
use of thermodilution (even though it is used
longitudinally in each animal, see range of
cardiac outputs and CI in studies). 5) It is
obvious that all hemoglobin solutions are not the
same, This includes recombinant HB, Diasprin
hemoglobin, 70 poly hemoglobin etc. Those
studies indicate caution but the outcomes can not
be directly extrapolated to HBOC-20 1. In fact
the one study using HBOC-301 should also be
viewed separately. 6) The nature of the invasive
measurements (mostly to examine mechanisms)
during the preclinical phase (from hemorrhage
to blood, simulated in hospital, support) not
only confounds the conclusions but will not be
used in RESUS. 7) The removal of blood from the
abdomen in experimental studies to measure total
hemorrhage volume is unlike RESUS (may build up
and suppress bleeding). 8) In many instances
(most) HBOC-201 is administered to a fixed volume
and certainly not to a high systolic pressure.
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• Executive summary BPAC Meeting on RESUS, Use
  ofHBOC-201.
• T Hintze, New York Medical College
• Major conclusions with HBOC-201
• In general the use of HBOC- 201 increased
  survival to simulated hospital arrival and for
  longer periods
• 2) The results are uniform across many models
  including hemorrhage and injury to
• a) the brain,b) the liver, 3) the lung, 4) the
  abdomen (iliac bleeding) and 5) rectus
• crush (skeletal muscle).
• 3) The results are applicable to varying times to
  treatment and times to simulated hospital
  arrival.
• 4) Generally the use ofHBOC to support pressure
  to various levels (50 mmHg, 60 mmHg and above)
  after hemorrhage is beneficial.
• 5) Generally less fluid is needed for
  resuscitation when giving HBOC-201.
• 6) Generally, there appears to be
  vasoconstriction after HBOC-201, either pressure
  rises more or calculated resistance rises more
  than with LR (or other fluids)
• 7) There may be some utility in measuring lactate
  or tissue oxygen levels (non- invasively) if the
  time to hospital is long (and technically
  feasible).