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P Safar

Publications and source records attributed to P Safar.

At least 109 records · Page 6Linked to original sources
PubMed1993

Systematic development of cerebral resuscitation after cardiac arrest. Three promising treatments: cardiopulmonary bypass, hypertensive hemodilution, and mild hypothermia.

Since 1970 we have investigated postischemic anoxic encephalopathy and potential treatments for cerebral resuscitation after cardiac arrest by cardiopulmonary-cerebral resuscitation (CPCR). The post-resuscitation syndrome has been studied at the levels of cell, organ, organism and community. Short-term and long-term models in rats, dogs, and monkeys have been developed, and an international multicenter randomized clinical trial mechanism was established. Clinical studies disproved the 5-min limit of reversible cardiac arrest and yielded other valuable data on treatments and prognostication. Thiopental loading or calcium entry blocker therapy (lidoflazine) gave no significant improvement in patients. Free radical scavengers are under investigation in the laboratory. We hypothesize that post-arrest perfusion failure and necrotizing cascades require etiology-specific combination treatments. Standard (control) therapy in a current dog model of cardiac arrest (no flow) of 12.5-20 min, reperfusion with cardiopulmonary bypass, and intensive care for 72-96 h has consistently resulted in survival with brain damage. After ventricular-fibrillation (VF) arrest of 17 min, moderate hypothermia (28-32 degrees C) inconsistently improved cerebral outcome. After VF arrest of 12.5 min, hypertension plus hemodilution normalized the local (multifocal) cerebral hypoperfusion post-arrest and, again, inconsistently improved cerebral outcome. Additional mild hypothermia (34-36 degrees C), however, consistently improved cerebral outcome, whether induced before or during and after arrest.

Animals↗
PubMed1993

Cardiovascular function and neurologic outcome after cardiac arrest in dogs. The cardiovascular post-resuscitation syndrome.

We studied cardiovascular changes and neurologic outcome at 72 h in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We found no difference in resuscitability, mortality, neurologic deficit scores, or overall performance categories between the three insult groups. There was no major pulmonary dysfunction. During controlled normotension post-CPR, all dogs presented a transient reduction in cardiac output. In the 12.5-min cardiac arrest group the decrease in cardiac output persisted beyond 12 h post-CPR (P < 0.01) and was associated with more severe arrhythmias (P < 0.05) and worse morphologic myocardial damage (P < 0.01). Both cardiac and neurologic malfunction at 72 h correlated with arrest time. Only cardiac malfunction correlated with CPR time. Neurologic recovery correlated with mild (inadvertent) pre-arrest hypothermia, diastolic arterial pressure during CPR and absence of cardiovascular impairment at 12 h post-CPR. We conclude that prolonged cardiac arrest in previously healthy dogs is followed by persistent cardiovascular derangements that correlate with impaired neurologic recovery.

Animals↗
PubMed1993

Visceral, hematologic and bacteriologic changes and neurologic outcome after cardiac arrest in dogs. The visceral post-resuscitation syndrome.

We studied the post-resuscitation syndrome in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We reported previously, in the same dogs, no difference in resuscitability, mortality, or neurologic outcome between the three insult groups. There was no pulmonary dysfunction, but post-arrest cardiovascular failure, of greater severity in the 12.5 min arrest group. This report concerns renal, hematologic, hepatic and bacteriologic changes. Renal function recovered within 1 h after arrest, without permanent dysfunction. Clotting derangements at 1-24 h postarrest reflect transient disseminated intravascular coagulation with hypocoagulability, more severe after longer arrests, which resolved by 24 h after arrest. Hepatic dysfunction was transient but more severe in the animals that did not recover consciousness and correlated with neurologic dysfunction, but not with brain histologic damage. Bacteremia was present in all animals postarrest. We conclude that in the previously healthy organism after cardiac arrest of 7.5-12.5 min no flow, visceral and hematologic changes, although transient, can retard neurologic recovery.

Amino Acids↗
PubMed1993

Detoxification with hemabsorption after cardiac arrest does not improve neurologic recovery. Review and outcome study in dogs.

We and others hypothesized that noxious substances released after prolonged cardiac arrest from malfunctioning liver, kidneys, or intestine (e.g. bacterial toxins, aromatic amino acids), might hamper recovery of the brain. The highly detoxifying effect of hemabsorption (i.e. hemoperfusion) with microencapsulated activated carbon has been demonstrated in other diseases. We used our dog model of ventricular fibrillation cardiac arrest of 15 min (n = 2 x 4) or 12.5 min (n = 2 x 6), reversed by brief (high flow) cardiopulmonary bypass (CPB). In half of the dogs in each insult group, a charcoal filter (HemoKart) was inserted into the circuit of CPB at low flow, from start of reperfusion to 4 h. Intermittent positive pressure ventilation was to 20 h and intensive care to 96 h after cardiac arrest. Bacterial blood cultures were positive in most of the dogs in both groups 30 min to 20 h after cardiac arrest (but not later) and were uninfluenced by hemabsorption. In the control groups to 4 h after cardiac arrest, serum levels of potentially injurious aromatic amino acids (e.g. phenylalanine, tyrosine) and of branched-chain/aromatic amino acid ratios, remained unchanged. From 12 to 48 h after cardiac arrest, aromatic amino acid levels increased (worsened). The branched-chain/aromatic amino acid ratios changed accordingly in the opposite direction. In the hemabsorption groups to 4 h after cardiac arrest, all amino acid levels were reduced, aromatic amino acids more so than branched-chain amino acids, thus increasing (improving) the ratio, compared with controls (P < 0.01). There was no group difference after discontinuance of hemabsorption at 4 h. Outcome in terms of overall performance categories and neurologic deficit scores from 24 to 96 h and brain histopathologic damage scores 96 h after cardiac arrest, were not significantly different between groups. The lack of a beneficial outcome effect of hemabsorption to 4 h after cardiac arrest does not support the self-intoxication hypothesis. The amino acid levels later after cardiac arrest suggest that more prolonged hemabsorption and more encompassing detoxification treatments, such as plasma phoresis or total body blood washout, might be evaluated.

Amino Acids↗
PubMed1993

Cerebral resuscitation after cardiac arrest: research initiatives and future directions.

At present, fewer than 10% of cardiopulmonary resuscitation (CPR) attempts prehospital or in hospitals outside special care units result in survival without brain damage. Minimizing response times and optimizing CPR performance would improve results. A breakthrough, however, can be expected to occur only when cerebral resuscitation research has achieved consistent conscious survival after normothermic cardiac arrest (no flow) times of not only five minutes but up to ten minutes. Most cerebral neurons and cardiac myocytes tolerate normothermic ischemic anoxia of up to 20 minutes. Particularly vulnerable neurons die, in part, because of the complex secondary post-reflow derangements in vital organs (the postresuscitation syndrome) which can be mitigated. Brain-orientation of CPR led to the cardiopulmonary-cerebral resuscitation (CPCR) system of basic, advanced, and prolonged life support. In large animal models with cardiac arrest of 10 to 15 minutes, external CPR, life support of at least three days, and outcome evaluation, the numbers of conscious survivors (although not with normal brain histology) have been increased with more effective reperfusion by open-chest CPR or emergency cardiopulmonary bypass, an early hypertensive bout, early post-arrest calcium entry blocker therapy, or mild cerebral hypothermia (34 C) immediately following cardiac arrest. More than ten drug treatments evaluated have not reproducibly mitigated brain damage in such animal models. Controlled clinical trials of novel CPCR treatments reveal feasibility and side effects but, in the absence of a breakthrough effect, may not discriminate between a treatment's ability to mitigate brain damage in selected cases and the absence of any treatment effect. More intensified, coordinated, multicenter cerebral resuscitation research is justified.

Animals↗
PubMed1993

Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study.

OBJECTIVE: Previously, we documented that mild hypothermia (34 degrees C) induced immediately with reperfusion after ventricular fibrillation cardiac arrest in dogs improves functional and morphologic cerebral outcome. This study was designed to test the hypothesis that a 15-min delay in the initiation of cooling after reperfusion would offset this beneficial effect. DESIGN: Prospective, randomized, controlled study. SETTING: Animal intensive care unit. SUBJECTS: A total of 22 custom-bred coonhounds. INTERVENTIONS: Eighteen dogs underwent normothermic ventricular fibrillation arrest (no blood flow) of 12.5 mins, reperfusion with brief cardiopulmonary bypass, defibrillation within 5 mins, intermittent positive-pressure ventilation to 20 hrs, and intensive care to 96 hrs. Three groups of six dogs each were studied: group 1, normothermic controls; group 2, core temperature 34 degrees C from reperfusion to 1 hr; and group 3, delayed initiation of cooling until 15 mins after normothermic reperfusion, and 34 degrees C from 15 mins to 1 hr 15 mins after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Tympanic membrane temperature (which represented brain temperature) in group 2 reached 34 degrees C at 6 +/- 3 (SD) mins after reperfusion; and in group 3 at 29 +/- 1 mins after reperfusion. Best overall performance categories achieved (1, normal; 5, brain death) compared with group 1, were better in group 2 (p < 0.5) but not in group 3 (NS). Similar results were found with best neurologic deficit scores (0%, normal; 100%, brain death), i.e., 44 +/- 4% in group 1, 19 +/- 15% in group 2 (p < .01), and 38 +/- 9% in group 3 (NS). Total brain histologic damage scores (< 30 minimal damage; > 100 severe damage), however, were 150 +/- 32 in group 1, 81 +/- 13 in group 2 (p < .001 vs. group 1), and 107 +/- 17 in group 3 (p < .05 vs. group 1). CONCLUSIONS: Mild, resuscitative cerebral hypothermia induced immediately with reperfusion after cardiac arrest improves cerebral functional and morphologic outcome, whereas a delay of 15 mins in initiation of cooling after reperfusion may not improve functional outcome, although it may slightly decrease tissue damage.

Animals↗
PubMed1993

Mild hypothermia after cardiac arrest in dogs does not affect postarrest multifocal cerebral hypoperfusion.

BACKGROUND AND PURPOSE: Although mild resuscitative hypothermia (34 degrees C) immediately after cardiac arrest improves neurological outcome in dogs, its effects on cerebral blood flow and metabolism are unknown. METHODS: We used stable xenon-enhanced computed tomography to study local, regional, and global cerebral blood flow patterns up to 4 hours after cardiac arrest in dogs. We compared a normothermic (37.5 degrees C) control group (group I, n = 5) with a postarrest mild hypothermic group (group II, n = 5). After ventricular fibrillation of 12.5 minutes and reperfusion with brief cardiopulmonary bypass, the ventilation, normotension, normoxia, and mild hypocapnia were controlled to 4 hours after cardiac arrest. Group II received (minimal) head cooling during cardiac arrest, followed by systemic bypass cooling (to 34 degrees C) during the first hour of reperfusion after cardiac arrest. RESULTS: The postarrest homogeneous transient hyperemia was followed by global hypoperfusion from 1 to 4 hours after arrest, with increased "no-flow" and "trickle-flow" voxels (compared with baseline), without group differences. At 1 to 4 hours, mean global cerebral blood flow in computed tomographic slices was 55% of baseline in group I and 64% in group II (NS). No flow (local cerebral blood flow < 5 mL/100 cm3 per minute) occurred in 5 +/- 2% of the voxels in group I versus 9 +/- 5% in group II (NS). Trickle flow (5 to 10 mL/100 cm3 per minute) occurred in 10 +/- 3% voxels in group I versus 16 +/- 4% in group II (NS). Cerebral blood flow values in eight brain regions followed the same hyperemia-hypoperfusion sequence as global cerebral blood flow, with no significant difference in regional values between groups. The global cerebral metabolic rate of oxygen, which ranged between 2.7 and 4.5 mL/100 cm3 per minute before arrest in both groups, was at 1 hour after arrest 1.8 +/- 0.3 mL in normothermic group I (n = 3) and 1.9 +/- 0.4 mL is still-hypothermic group II (n = 5); at 2 and 4 hours after arrest, it ranged between 1.2 and 4.2 mL in group I and between 1.2 and 2.6 mL in group II. CONCLUSIONS: After cardiac arrest, mild resuscitative hypothermia lasting 1 hour does not significantly affect patterns of cerebral blood flow and oxygen uptake. This suggests that different mechanisms may explain its mitigating effect on brain damage.

Animals↗
PubMed1993

The effect of resuscitative moderate hypothermia following epidural brain compression on cerebral damage in a canine outcome model.

A canine model of temporary epidural cerebral compression and standardized intensive care was developed to evaluate the effect of resuscitative (postinsult) moderate systemic hypothermia. A balloon was inflated over the temporal region to maintain contralateral intraventricular pressure (IVP) at 62 mm Hg for 90 minutes. For a 66-hour period after initiation of brain compression, the intubated dogs received controlled ventilation and standard intensive care. From 66 to 90 hours postinjury, the extubated dogs were evaluated as to functional outcome. Morphological brain damage was evaluated at 90 hours or earlier if brain death occurred. Eight dogs in a control group were maintained at a body of temperature of 38 degrees C. Eight treated dogs had core body temperature reduced by surface cooling starting 15 minutes after balloon inflation, first to 31 degrees C for 5 hours and then to 35 degrees C from 5 to 62 hours after insult. Intraventricular pressure increased to 20 mm Hg or greater in the control group at a mean of 2.9 hours (range 2 to 4 hours) following the insult, and in the hypothermic group at a mean of 14.8 hours (range 5 to 30 hours)--that is, during the time period when the body temperature was 35 degrees C, not 31 degrees C (p = 0.01). There was no difference in peak pressures between the two groups. Brain death occurred in four of the eight dogs in the normothermic group at 18, 24, 24, and 48 hours (mean +/- standard deviation 28 +/- 13 hours) and in three of the eight in the hypothermic group at 27, 42, and 45 hours (mean 38 +/- 10 hours) (not significant). The animals surviving 90 hours (four in the normothermic and five in the hypothermic group) were neurologically near normal. The total mean macroscopically damaged brain volume was 2584 +/- 1890 cu mm in the normothermic versus 765 +/- 611 cu mm in the hypothermic group (p = 0.03). The mean necrotic volume was 741 +/- 599 cu mm in the normothermic versus 263 +/- 346 cu mm in the hypothermic group (p = 0.07). Microscopically, the damaged regions consisted of ischemic neurons, reactive glia, edema, vascular endothelial hypertrophy, and erythrocyte extravasation. It is concluded that, in this model, immediate postinsult hypothermia of 31 degrees C (not 35 degrees C) for 5 hours prevents a rise in IVP and significantly decreases cerebral tissue damage, but does not prevent brain herniation during rewarming.

Animals↗
PubMed1992

Dynamic heterogeneity of cerebral hypoperfusion after prolonged cardiac arrest in dogs measured by the stable xenon/CT technique: a preliminary study.

After prolonged cardiac arrest and reperfusion, global cerebral blood flow (gCBF) is decreased to about 50% normal for many hours. Measurement of gCBF does not reveal regional variation of flow or permit testing of hypotheses involving multifocal no-flow or low-flow areas. We employed the noninvasive stable Xenon-enhanced Computerized Tomography (Xe/CT) local CBF (LCBF) method for use in dogs before and after ventricular fibrillation (VF) cardiac arrest of 10 min. This was followed by external cardiopulmonary resuscitation (CPR) and control of cardiovascular pulmonary variables to 7 h postarrest. In a sham (no arrest) experiment, the three CT levels studied showed normal regional heterogeneity of LCBF values, all between 10 and 75 ml/100 cm3 per min for white matter and 20 and 130 ml/100 cm3 per min for gray matter. In four preliminary CPR experiments, the expected global hyperemia at 15 min after arrest, was followed by hypoperfusion with gCBF reduced to about 50% control and increased heterogeneity of LCBF. Trickle flow areas (LCBF less than 10 ml/100 cm3 per min) not present prearrest, were interspersed among regions of low, normal, or even high flow. Regions of 125-500 mm3 with trickle flow or higher flows, in different areas at different times, involving deep and superficial structures migrated and persisted to 6 h, with gCBF remaining low. These preliminary results suggest: no initial no-reflow foci (less than 10 ml/100 cm3 per min) larger than 125 mm3 persisting through the initial global hyperemic phase; delayed multifocal hypoperfusion more severe than suggested by gCBF measurements; and trickle flow areas caused by dynamic factors.

Animals↗
PubMed1992

Simpson's paradox and clinical trials: what you find is not necessarily what you prove.

Expensive clinical trials have become the gold standard for evaluating the efficacy of promising new therapeutic agents. Full exploration of the collected data is routine to maximize the yield of the information available. However, potential methodologic flaws in these extensive analyses may not be appreciated by investigators or readers. One such problem with subgroup analyses is discussed, using hypothetical examples and data from a recently completed clinical trial of brain resuscitation as illustrations.

Cardiovascular Diseases↗
PubMed1992

Hypertension with hemodilution prevents multifocal cerebral hypoperfusion after cardiac arrest in dogs.

BACKGROUND: Improved neurological outcome with postarrest hypertensive hemodilution in an earlier study could be the result of more homogeneous cerebral perfusion and improved O2 delivery. We explored global, regional, and local cerebral blood flow by stable xenon-enhanced computed tomography and global cerebral metabolism in our dog cardiac arrest model. METHODS: Ventricular fibrillation cardiac arrest of 12.5 minutes was reversed by brief cardiopulmonary bypass, followed by life support to 4 hours postarrest. We compared control group I (n = 5; mean arterial blood pressure, 100 mm Hg; hematocrit, greater than or equal to 35%) with immediately postarrest reflow-promoted group II (n = 5; mean arterial blood pressure, 140-110 mm Hg; hypervolemic hemodilution with plasma substitute to hematocrit, 20-25%). RESULTS: After initial hyperemia in both groups, during the "delayed hypoperfusion phase" at 1-4 hours postarrest, global cerebral blood flow was 51-60% of baseline in group I versus 85-100% of baseline in group II (p less than 0.01). Percentages of brain tissue voxels with no flow, trickle flow, or low flow were lower (p less than 0.01) and mean regional cerebral blood flow values were higher in group II (p less than 0.01). Global cerebral oxygen uptake recovered to near baseline values at 3-4 hours postarrest in both groups. Postarrest arterial O2 content, however, in hemodiluted group II was 40-50% of that in group I. Thus, the O2 uptake/delivery ratio was increased (worsened) in both groups at 2-4 hours postarrest. CONCLUSIONS: After prolonged cardiac arrest, immediately induced moderate hypertensive hemodilution to hematocrit 20-25% can normalize cerebral blood flow patterns (improve homogeneity of cerebral perfusion), but does not improve cerebral O2 delivery, since the flow benefit is offset by decreased arterial O2 content. Individualized titration of hematocrit or hemodilution with acellular O2 carrying blood substitute (stroma-free hemoglobin or fluorocarbon solution) would be required to improve O2 uptake/delivery ratio.

Animals↗
PubMed1992

Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs.

BACKGROUND AND PURPOSE: Mild cerebral hypothermia (34 degrees C) induced immediately after cardiac arrest improves outcome. Deep postarrest hypothermia (15 degrees C) has not been studied. METHODS: We used our dog model of normothermic ventricular fibrillation (no blood flow) of 12.5 minutes, reperfusion by brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 72 hours. Head surface cooling and bypass cooling were performed from start of reperfusion to 1 hour. Five groups of six dogs each were compared: group I, normothermic controls; group II, deep hypothermia (15 degrees C); group III, moderate hypothermia (30 degrees C); group IV, mild hypothermia (34 degrees C); and group V, mild hypothermia with head surface cooling begun during no flow. RESULTS: In control group I, five dogs remained comatose (overall performance category [OPC] 4) and one severely disabled (OPC 3). In group II, four dogs achieved OPC 4 and two dogs OPC 3 (NS versus group I). Compared with group I, OPCs were better in group III (p less than 0.05), group IV (p less than 0.05), and group V (p less than 0.05). Neurological deficit scores were also better in groups III, IV, and V than in groups I or II (p less than 0.05). Total brain histological damage scores were better in group III (p = 0.02), group IV (p = 0.06), and group V (p less than 0.05) than in group I. In group II, OPC and neurological deficit scores were the same and histological damage scores numerically worse than in group I and all were worse than in groups III, IV, and V (p less than 0.05). Cardiovascular complications and myocardial morphological damage in groups II and III were worse than in groups I, IV, and V (p less than 0.05). CONCLUSIONS: Mild or moderate cerebral hypothermia induced immediately after cardiac arrest improves cerebral outcome, more likely when initiated during arrest, whereas deep postarrest hypothermia can worsen cerebral and cardiac outcome.

Animals↗
PubMed1991

National medical response to mass disasters in the United States. Are we prepared?

Preparing for a resuscitation response to mass disasters, such as major earthquakes or industrial disasters, requires revisions of present local, regional, and national disaster plans. These should include the following: (1) life-supporting first aid and basic rescue capability of the lay public; (2) advanced trauma life support and advanced (heavy) rescue capability brought quickly to the scene from local and surrounding (regional) emergency medical services systems; and (3) trauma hospitals sending medical resuscitation teams to, and receiving casualties from, the disaster scene for resuscitative surgery and definitive care. Local and regional everyday emergency medical services systems would respond first. The armed forces should help, at least for transport and security. We propose that the National Disaster Medical System replace its civil defense model with an emergency medical services model, designed to mobilize rapid support for local emergency medical services systems from regional, state, and national resources. Coordination should be by one federal agency, such as the Federal Emergency Management Agency, which, however, needs to focus more on resuscitation through physician input.

Disaster Planning↗
PubMed1991

A comparison of cardiopulmonary resuscitation with cardiopulmonary bypass after prolonged cardiac arrest in dogs. Reperfusion pressures and neurologic recovery.

Resuscitability and outcome after prolonged cardiac arrest were compared in dogs with standard external cardiopulmonary resuscitation (CPR) vs. closed-chest emergency cardiopulmonary bypass (CPB). Ventricular fibrillation (VF) was with no blood flow from VF 0 min to VF 10 min. Subsequent CPR basic life support (BLS) was from 10 min to VF 15 min. Then, group I (n = 13) received CPR advanced life support (ALS) from VF 15 min until restoration of spontaneous circulation to occur not later than VF 40 min. Group II (n = 14) received CPR-ALS from VF 15 min to VF 20 min without defibrillation, and then total CPB to defibrillation attempts started at VF 20 min, followed by assisted CPB to 2 h. Total ischemia time (no-flow time plus CPR time of MAP less than 50 mmHg) was unexpectedly shorter in group I (14.3 +/- 2.5 min) than in group II (18.6 +/- 2.3 min) (P less than 0.01). During CPR-BLS, coronary perfusion pressures were 25 +/- 9 mmHg in group I and 18 +/- 8 mmHg in group II (NS). Epinephrine during CPR-ALS, before countershock, raised coronary perfusion pressure to 40 +/- 10 mmHg in group I and 27 +/- 10 mmHg in group II (NS). In group II, coronary perfusion pressure increased during total CPB to 58 +/- 16 mmHg (P less than 0.01 vs. group I). Spontaneous normotension was restored in 11/13 dogs of group I and all 14 dogs of group II (NS). Ten dogs in each group followed protocol and survived to 96 h. Five of ten in group I and six of ten in group II were neurologically normal (NS). We conclude that: (1) Reperfusion with CPB yields higher coronary perfusion pressures than reperfusion with CPR-ALS; and (2) even after no blood flow for 10 min, optimized CPR can result in cardiovascular resuscitability and neurologic recovery, similar to those achieved by CPB.

Animals↗
PubMed1991

A simple survival model of volume-controlled hemorrhagic shock in awake rats.

A simple rat model was developed for the study of spontaneous survival after volume-controlled hemorrhage. The objective was to determine in awake, unrestrained rats the shed blood volume (SBV) in ml/100 g body weight that without fluid resuscitation, would result in either a high or a low percentage of survivors within 24 h. About 24 h after cannulation under light anesthesia, the awake rats were insulted with arterial blood withdrawal at a constant rate over 20 min, while mean arterial pressure (MAP) was monitored (N = 78). Then, the arterial catheter was removed, and the rats were observed for 24 h or until death. With increasing SBV, survival rate decreased, SBV of 2.50 ml/100 g (group I) resulted in 74% survivors at 2 h and 24 h; SBV of 2.75 ml/100 g (group II), in 67% survivors at 2 h and 46% at 24 h; SBV of 3.00 ml/100 g (group III), in 35% survivors at 2 h and 20% at 24 h; and SBV of 3.50 ml/100 g (group IV), in no survivors to 2 h. MAP declined similarly over 20 min blood withdrawal in the four insult groups, without difference between ultimate survivors vs. nonsurvivors. All rats survived to the end of 20 min hemorrhage (i.e. hemorrhagic shock [HS] time = 0 min). Deaths at HS time 0-2 h occurred after SBV of 2.50 ml/100 g, at HS time 56 +/- 35 min; after SBV of 2.75 ml/100 g, at HS 81 +/- 26 min; after SBV of 3.00 ml/100 g, at HS 37 +/- 33 min; and after SBV of 3.50 ml/100 g, at HS 11 +/- 2 min. Weight may have affected MAP response and survival. We conclude that a volume-controlled HS model in rats without anesthesia or restraint is feasible. SBV of 2.50 ml/100 g should be suitable for testing additional insults. SBV of 3.00 ml/100 g should be suitable for testing resuscitative therapies. The model should be modified to allow monitoring of key variables after hemorrhage.

Animals↗
PubMed1991

Dying pattern in volume-controlled hemorrhagic shock in awake rats.

We previously determined that in awake, unmonitored Sprague-Dawley rats, bleeding of 2.5 ml/100 g over 20 min resulted in hemorrhagic shock (HS) with about a 75% survival rate over 24 h, and bleeding of 3.0 ml/100 g in about 25% survival to 24 h. In the present study, we monitored systolic and mean arterial pressure (MAP), central venous pressure (CVP), breathing movements, electroencephalogram (EEG), and arterial blood gases to 3 h in order to study dying patterns. After cannulation under light anesthesia and awakening for 2 h, the rats were bled over 20 min. Ten rats in each of four groups were studied. Shed blood volume (SBV) in group I was 2.0 ml/100 g; in group II, 2.5 ml; in group III, 3.0 ml; and in group IV, 3.5 ml. Three hour survival rates were 100% for group I, 80% for group II (survival time 149 +/- 65 [106-180] min), 40% for group III (survival time 116 +/- 72 [93-180] min), and 0% for group IV (survival time 32 +/- 38 [5-69] min). MAP decreased at end of bleeding, increased transiently to moderately hypotensive levels (attempted self-resuscitation), and then either recovered to normotension or declined to cardiac arrest (death), which was defined as simultaneous apnea, systolic arterial pressure less than or equal to 30 mmHg without pulsations, and isoelectric EEG. EEG depression began with hypotension to MAP less than or equal to 50 mmHg. During HS, PaO2 increased, and PaCO2, pHa, and Hct all decreased. The results suggest that this model with SBV of 3.25 ml/100 g would give a low, but not zero 3 h survival, and therefore would be suitable for the study of responses to field resuscitation potentials.

Animals↗
PubMed1991

Improved survival of hemorrhagic shock with oxygen and hypothermia in rats.

A previously established model in awake rats of hemorrhagic shock (HS) with 25% spontaneous survival rate (without resuscitation) was used to evaluate the effects of 4 novel life-supporting first aid (LSFA) measures on survival time and rate. After shed blood volume (SBV) of 3.25 ml/100 g, withdrawn over 20 min, hemodynamic and respiratory responses were recorded to 3 h and survival to 24 h. The 5 groups of 20 rats each (total n = 100) were as follows: group I, controls without treatment; II, oxygen 100% inhalation; III, external cooling to rectal temperature 30 degrees C; IV, Ringer's solution 5 ml/100 g rectally; and V, acoustic and surface stimuli for arousal. Survival rates were: control group I, 35% at 3 h and 15% at 24 h; oxygen group II, 75% (P less than 0.05 compared with group I) at 3 h and 60% (P less than 0.05 compared with group I) at 24 h; hypothermia group III, 65% at 3 h and 45% (P less than 0.05 compared with group I) at 24 h; rectal fluid group IV, 50% at 3 h and 40% at 24 h; stimulated group V, 15% at 3 h and 15% at 24 h. Compared with group I, median survival times during HS 0-3 h were longer in groups II and III; and self-resuscitation attempts were longer in groups II, III and IV. We conclude that in untreated severe hemorrhagic shock, chances of survival to delayed arrival of advanced life support with i.v. fluid resuscitation might be increased with O2 inhalation and/or moderate external cooling.

Animals↗