Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs.

We previously found mild hypothermia (34-36 degrees C), induced before cardiac arrest, to improve neurologic outcome. In this study we used a reproducible dog model to evaluate mild hypothermia by head cooling during arrest, continued with systemic cooling (34 degrees C) during recirculation and for 1 h after arrest. In four groups of dogs, ventricular fibrillation (no flow) of 12.5 min at 37.5 degrees C was reversed with cardiopulmonary bypass and defibrillation in less than or equal to 5 min, and followed by controlled ventilation to 20 h and intensive care to 96 h. In Study A we resuscitated with normotension and normal hematocrit; Control Group A-I (n = 12) was maintained normothermic, while Treatment Group A-II (n = 10) was treated with hypothermia. In Study B we resuscitated with hypertension and hemodilution. Control Group B-I (n = 12) was maintained normothermic (6 of 12 were not hemodiluted), while Treatment Group B-II (n = 10) was treated with hypothermia. Best overall performance categories (OPCs) achieved between 24 and 96 h postarrest were in Group A-I: OPC 1 (normal) in 0 of 12 dogs, OPC 2 (moderate disability) in 2, OPC 3 (severe disability) in 7, and OPC 4 (coma) in 3 dogs. In Group A-II, OPC 1 was achieved in 5 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.001), OPC 3 in 1, and OPC 4 in 0 dogs. In Group B-I, OPC 1 was achieved in 0 of 12 dogs, OPC 2 in 6, OPC 3 in 5, and OPC 4 in 1 dog. In Group B-II, OPC 1 was achieved in 6 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.05), and OPC 3 or 4 in 0 dogs. Mean neurologic deficit and brain histopathologic damage scores showed similar significant group differences. Morphologic myocardial damage scores were the same in all four groups. We conclude that mild brain cooling during and after insult improves neurologic outcome after cardiac arrest.

Uncontrolled hemorrhagic shock outcome model in rats.

During uncontrolled hemorrhagic shock (UHS) in acute animals models, attempts to achieve normotension with i.v. fluid resuscitation (FR) caused further bleeding and higher acute mortality. In the absence of a published clinically realistic long-term animal outcome study of UHS, we developed such a model in rats. In the preliminary study, phase I of the model involved 60 min of simulated 'pre-hospital' UHS by tail amputation and different FR regimens. Phase II involved 120 min of simulated 'hospital' treatment with hemostasis and all-out FR, including blood infusion. Phase III involved observing recovery and survival to 72 h (3 days). Rats were maintained under very light N2O-O2-halothane anesthesia and spontaneous breathing via mask during phases I and II and were awake during phase III. Tail amputation-induced UHS alone, studied in 4 groups of 10 rats each, resulted in unpredictable spontaneous hemostasis and great variability in shed blood volume, severity of shock, and mortality. The final model, which achieved consistent blood loss and outcome, included an initial volume-controlled hemorrhage of 3 ml/100 g over 15 min and untreated HS for another 15 min, followed by tail amputation for UHS over another 60 min. This phase I of 90 min was followed by phase II of 60 min. In group 1, without FR in phases I and II, all 10 rats died by 12 h. In group 2, without FR in phase I and hemostasis plus all-out FR with lactated Ringer's solution and blood to hematocrit (Hct) 30% in phase II, 5 of 10 rats died at the end of phase I and 9 of 10 died at the end of phase III. This final volume-initiated UHS model may be suitable for comparing different pre-hospital treatment modalities in terms of outcome.

Delayed death after uncomplicated hot tub bathing in dogs and monkeys.

Prolonged heat exposure as in hot tub bathing, although frequently practiced, has occasionally resulted in fatalities that have been explained by an underlying disease. We explored the tolerance of hot water immersion of 60 min in five previously healthy animals (three dogs and two monkeys). With invasive monitoring, experimental body immersion in water at 40-45 degrees C, with core temperature kept at 40-42 degrees C for 60 min, caused no significant cardiovascular, pulmonary or metabolic changes during hyperthermia or for 2 h after return to normothermia. Then secondary deterioration occurred with progressive hypotension, petechial hemorrhages throughout the viscera, gross gastrointestinal hemorrhages and irreversible (hypovolemic) shock. These effects occurred earlier in the monkeys than in the dogs. This shock state did not respond to standard resuscitation attempts. One dog survived the secondary shock state. We conclude that during and after hot tub immersion, good initial tolerance to heat exposure can, several hours after return of normothermia, result in delayed secondary deterioration and death. We recommend that the mechanism of this delayed shock state with apparent capillary leakage be clarified.

Monkey model of severe volume-controlled hemorrhagic shock with resuscitation to outcome.

Seventeen cynomolgus monkeys under N2O analgesia and sedation were subjected to severe volume-controlled hemorrhagic shock (shed blood volume of 21 or 27 ml/kg). In 12 monkeys, resuscitation was started after increasing periods of hemorrhagic shock from 30 min to 5 h. In five additional monkeys, volume-controlled hemorrhage was modified at hemorrhagic shock 30 min to control MAP at 30 mmHg: resuscitation was started at hemorrhagic shock of 2 h. A clinically relevant resuscitation protocol consisted of a field phase from 0 to 6 h (lactated Ringer's solution, spontaneous breathing), and a hospital intensive care phase from 6 h to 48 h (blood, lactated Ringer's solution to mean arterial pressure (MAP) greater than or equal to 70 mmHg, controlled ventilation, advanced life support). Fifteen of the 17 monkeys survived. After outcome evaluation at 4 or 7 days, the eight monkeys with "moderate insult" had only transient functional impairment. Of the nine with "severe insult," three showed signs of moderate transient non-oliguric renal failure. Eight of the 12 monkeys studied morphologically showed scattered liver cell damage. None of the monkeys developed pulmonary dysfunction or functional or morphologic evidence of cerebral damage. This study establishes a new hemorrhagic shock-resuscitation model simulating field-to-hospital life support. Severe hemorrhagic shock with MAP 30-40 mmHg for 90-120 min (without trauma or sepsis) can lead to complete functional recovery after transient malfunction of liver and kidneys.

New monkey model of severe-volume controlled hemorrhagic shock.

Three series of experiments were conducted to develop a model of volume-controlled severe hemorrhagic shock in the unanesthetized analgesic cynomolgus monkey. This report concerns the insult without resuscitation. In Series I, seven monkeys were sedated with 75% N2O/25% O2, bled 40% of their measured blood volume over 20 min and observed until death. Mean arterial pressure (MAP) decreased to 21 +/- 6 mmHg, spontaneously increased to 46 +/- 5 mmHg, then gradually decreased to pulselessness at 146 +/- 42 min (range 101-213). Hemodynamic variables, lactate, base excess, electroencephalogram and sagittal sinus PO2 followed the same biphasic pattern. In Series II, eight monkeys were bled 27 ml/kg (43% of estimated blood volume) over 20 min under the same N2O analgesia and with similar responses as in Series I. In Series III 26 monkeys were bled 27 ml/kg over 20 min (time zero) as in Series II. Three developed apnea and pulselessness at end of hemorrhage. In 23 the shock period was prolonged for testing resuscitation therapies. Starting at 0 + 30 min, MAP was controlled with minute blood volume adjustments at 30 mmHg until 0 + 2 h. Three died due to inaccurate (preventable) MAP adjustments. At MAP 30 mmHg, all animals lost consciousness, EEG activity decreased, and brain stem reflexes disappeared. The "volume-pressure controlled" hemorrhagic shock model of Series III retains the initial natural response to bleeding, simulates the clinical picture of severe prolonged shock without anesthesia, and represents a more controllable insult than volume controlled hemorrhage alone.

Effect of cardiac arrest time on cortical cerebral blood flow during subsequent standard external cardiopulmonary resuscitation in rabbits.

Standard external cardiopulmonary resuscitation (SECPR) produces high cerebral venous and intracranial pressure peaks, low cerebral perfusion pressure, and low cerebral blood flow (CBF). Cerebral viability seems to require 20% of normal CBF, which SECPR cannot reliably generate. We tested the hypothesis that SECPR can produce adequate CBF if started immediately, but not if started after a long period of cardiac arrest (no flow, stasis). Cardiac arrest times of 1, 3, 5, 7 and 9 min were studied in rabbits. We measured unifocal cortical CBF with H2 clearance curves after saturation with H2 10%, O2 50% and N2O 40% by intermittent positive-pressure ventilation (IPPV). Measurements were made during spontaneous circulation (control condition), and then after resaturation immediately before induction of asystole by KCl i.v., and H2 clearance starting at end of arrest time during SECPR-basic life support with IPPV 100% and manual chest compressions (120/min) during asystole. Control cortical CBF was 30-40 ml/100 g brain per min. During asystole and SECPR, CBF greater than 20% normal was achieved only after no-flow of 1 min. After longer arrest (no-flow) times, CBF was less than 20% normal. Values were near zero after 7 and 9 min of cardiac arrest. Decrease in mean arterial pressures (MAP) produced by SECPR during asystole paralleled CBF values. Thus, the longer the preceding period of stasis, the lower the MAP and CBF generated by SECPR without epinephrine. This effect may be the result of anoxia-induced vasoparalysis and stasis-induced increased blood viscosity.

Effects of increased oxygen breathing in a volume controlled hemorrhagic shock outcome model in rats.

It is believed that victims of traumatic hemorrhagic shock (HS) benefit from breathing 100% O(2). Supplying bottled O(2) for military and civilian first aid is difficult and expensive. We tested the hypothesis that increased FiO(2) both during severe volume-controlled HS and after resuscitation in rats would: (1) increase blood pressure; (2) mitigate visceral dysoxia and thereby prevent post-shock multiple organ failure; and (3) increase survival time and rate. Thirty rats, under light anesthesia with halothane (0. 5% throughout), with spontaneous breathing of air, underwent blood withdrawal of 3 ml/100 g over 15 min. After HS phase I of 60 min, resuscitation phase II of 180 min with normotensive intravenous fluid resuscitation (shed blood plus lactated Ringer's solution), was followed by an observation phase III to 72 h and necropsy. Rats were randomly divided into three groups of ten rats each: group 1 with FiO(2) 0.21 (air) throughout; group 2 with FiO(2) 0.5; and group 3 with FiO(2) 1.0, from HS 15 min to the end of phase II. Visceral dysoxia was monitored during phases I and II in terms of liver and gut surface PCO(2) increase. The main outcome variables were survival time and rate. PaO(2) values at the end of HS averaged 88 mmHg with FiO(2) 0.21; 217 with FiO(2) 0.5; and 348 with FiO(2) 1. 0 (P<0.001). During HS phase I, FiO(2) 0.5 increased mean arterial pressure (MAP) (NS) and kept arterial lactate lower (P<0.05), compared with FiO(2) 0.21 or 1.0. During phase II, FiO(2) 0.5 and 1. 0 increased MAP compared with FiO(2) 0.21 (P<0.01). Heart rate was transiently slower during phases I and II in oxygen groups 2 and 3, compared with air group 1 (P<0.05). During HS, FiO(2) 0.5 and 1.0 mitigated visceral dysoxia (tissue PCO(2) rise) transiently, compared with FiO(2) 0.21 (P<0.05). Survival time (by life table analysis) was longer after FiO(2) 0.5 than after FiO(2) 0.21 (P<0. 05) or 1.0 (NS), without a significant difference between FiO(2) 0. 21 and 1.0. Survival rate to 72 h was achieved by two of ten rats in FiO(2) 0.21 group 1, by four of ten rats in FiO(2) 0.5 group 2 (NS); and by four of ten rats of FiO(2) 1.0 group 3 (NS). In late deaths macroscopic necroses of the small intestine were less frequent in FiO(2) 0.5 group 2. We conclude that in rats, in the absence of hypoxemia, increasing FiO(2) from 0.21 to 0.5 or 1.0 does not increase the chance to achieve long-term survival. Breathing FiO(2) 0.5, however, might increase survival time in untreated HS, as it can mitigate hypotension, lactacidemia and visceral dysoxia.

Thiopental combination treatments for cerebral resuscitation after prolonged cardiac arrest in dogs. Exploratory outcome study.

We postulate that mitigating the multifactorial pathogenesis of postischemic encephalopathy requires multifaceted treatments. In preparation for expensive definitive studies, we are reporting here the results of small exploratory series, compared with historic controls with the same model. We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading, and even more so with the further addition of phenytoin and methylprednisolone. Twenty-four dogs (four groups of six dogs each) received VF 12.5 min no-flow, reversed with brief cardiopulmonary bypass (CPB), controlled ventilation to 20 h, and intensive care to 96 h. Group 1 with normothermia throughout and randomized group 2 with mild hypothermia (from reperfusion to 2 h) were controls. Then, group 3 received in addition, thiopental 90 mg/kg i.v. over the first 6 h. Then, group 4 received, in addition to group 2 treatment, thiopental 30 mg/kg i.v. over the first 90 min (because the larger dose had produced cardiopulmonary complications), plus phenytoin 15 mg/kg i.v. at 15 min after reperfusion, and methylprednisolone 130 mg/kg i.v. over 20 h. All dogs survived. Best overall performance categories (OPC) achieved (OPC 1 = normal, OPC 5 = brain death) were better in group 2 than group 1 (< 0.05) and numerically better in groups 3 or 4 than in groups 1 or 2. Good cerebral outcome (OPC 1 or 2) was achieved by all six dogs only in group 4 (P < 0.05 group 4 vs. 2). Best NDS were 44 +/- 3% in group 1; 20 +/- 14% in group 2 (P = 0.002); 21 +/- 15% in group 3 (NS vs. group 2); and 7 +/- 8% in group 4 (P = 0.08 vs. group 2). Total brain histologic damage scores (HDS) at 96 h were 156 +/- 38 in group 1; 81 +/- 12 in group 2 (P < 0.001 vs. group 1); 53 +/- 25 in group 3 (P = 0.02 vs. group 2); and 48 +/- 5 in group 4 (P = 0.02 vs. group 2). We conclude that after prolonged cardiac arrest, the already established brain damage mitigating effect of mild immediate postarrest hypothermia might be enhanced by thiopental, and perhaps then further enhanced by adding phenytoin and methylprednisolone.

Mild hypothermia after cardiac arrest in dogs does not affect postarrest cerebral oxygen uptake/delivery mismatching.

PURPOSE: To compare measurements of cerebral arteriovenous oxygen content differences (oxygen extraction ratios, oxygen utilization coefficients) in dogs after cardiac arrest, resuscitated under normothermia vs. mild hypothermia for 1-2 h or 12 h. METHODS: In 20 dogs, we used our model of ventricular fibrillation (no blood flow) of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled ventilation, normotension, normoxemia, and mild hypocapnia to 24 h. We compared a normothermic control Group I (37.5 degrees C) (n = 8); with brief mild hypothermia in Group II (core and tympanic membrane temperature about 34 degrees C during the first hour after arrest) (n = 6); and with prolonged mild hypothermia in Group III (34 degrees C during the first 12 h after arrest) (n = 6). RESULTS: In Group I, the cerebral arteriovenous O2 content difference was 5.6 +/- 1.6 ml/dl before arrest; was low during reperfusion (transient hyperemia) and increased (worsened) significantly to 8.8 +/- 2.8 ml/dl at 1 h, remained increased until 18 h, and returned to baseline levels at 24 h after reperfusion. These values were not significantly different in hypothermic Groups II and III. The cerebral venous (saggital sinus) PO2 (PssO2) was about 40 mmHg (range 29-53) in all three groups before arrest and decreased significantly below baseline values, between 1 h and 18 h after arrest; the lowest mean values were 19 +/- 19 mmHg in Group I, 15 +/- 8 in Group II (NS), and 21 +/- 3 in Group III (NS). Postarrest PssO2 values of < or = 20 mmHg were found in 6/8 dogs in Group I, 5/6 in Group II and 4/6 in Group III. Among the 120 values of PssO2 measured between 1 h and 18 h after arrest, 32 were below the critical value of 20 mmHg. CONCLUSIONS: After prolonged cardiac arrest, critically low cerebral venous O2 values suggest inadequate cerebral O2 delivery. Brief or prolonged mild hypothermia after arrest does not mitigate the postarrest cerebral O2 uptake/delivery mismatching.

Multifocal cerebral blood flow by Xe-CT and global cerebral metabolism after prolonged cardiac arrest in dogs. Reperfusion with open-chest CPR or cardiopulmonary bypass.

Using the stable xenon-enhanced computed tomography (Xe-CT) method in dogs, we studied local, regional and global cerebral blood flow (LCBF, rCBF and gCBF) in two sham experiments and nine cardiac arrest experiments. Within the same experiments without arrest, gCBF and rCBF values were reproducible and stable. LCBF values varied over time. In group I (n = 4), ventricular fibrillation cardiac arrest (no blood flow) of 10 min was reversed by open-chest cardiopulmonary resuscitation (CPR). In group II (n = 5), ventricular fibrillation cardiac arrest of 12.5 min was reversed by brief closed-chest cardiopulmonary bypass. This was followed by controlled ventilation, normotension, normoxia, normocarbia and normothermia to 4 h (n = 7) or 20 h (n = 2) postarrest. The postarrest CBF patterns were similar in both groups. Open-chest CPR during ventricular fibrillation generated near-baseline gCBF and lower LCBF ranges. During postarrest spontaneous circulation, transient diffuse hyperemia was without low-flow regions, longer in brain stem and basal ganglia than in neocortex. During delayed hypoperfusion at 1-4 h postarrest (n = 9), mean gCBF was 44-60% baseline, rCBF in primarily gray matter regions was 15-49 ml/100 cm3 per min and LCBF voxels with trickle-flow and low-flow values, in percent of CT cut area, were increased over baseline. Global CMRO2 (n = 3 of group II) recovered to near baseline values between 1 and 4 h postarrest, while gCBF and O2 delivery were about 50% baseline (mismatching of O2 uptake and O2 delivery).

Adenosine by aortic flush fails to augment the brain preservation effect of mild hypothermia during exsanguination cardiac arrest in dogs - an exploratory study.

Most trauma cases with rapid exsanguination to cardiac arrest (CA) in the field, as well as many cases of normovolemic sudden cardiac death are 'unresuscitable' by standard cardiopulmonary-cerebral resuscitation (CPCR). We are presenting a dog model for exploring pharmacological strategies for the rapid induction by aortic arch flush of suspended animation (SA), i.e. preservation of cerebral viability for 15 min or longer. This can be extended by profound hypothermic circulatory arrest of at least 60 min, induced and reversed with (portable) cardiopulmonary bypass (CPB). SA is meant to buy time for transport and repair during pulselessness, to be followed by delayed resuscitation to survival without brain damage. This model with exsanguination over 5 min to CA of 15-min no-flow, is to evaluate rapid SA induction by aortic flush of normal saline solution (NSS) at room temperature (24 degrees C) at 2-min no-flow. This previously achieved normal functional recovery, but with histologic brain damage. We hypothesized that the addition of adenosine would achieve recovery with no histologic damage, because adenosine delays energy failure and helps repair brain injury. This dog model included reversal of 15-min no-flow with closed-chest CPB, controlled ventilation to 20 h, and intensive care to 72 h. Outcome was evaluated by overall performance, neurologic deficit, and brain histologic damage. At 2 min of CA, 500 ml of NSS at 24 degrees C was flushed (over 1 min) into the brain and heart via an aortic balloon catheter. Controls (n=5) received no drug. The adenosine group (n=5) received 2-chloro-adenosine (long acting adenosine analogue), 30 mg in the flush solution, and, after reperfusion, adenosine i.v. over 12 h (210 microg/kg per min for 3 h, 140 microg/kg per min for 9 h). The 24 degrees C flush reduced tympanic membrane temperature (T(ty)) within 2 min of CA from 37.5 to approximately 36.0 degrees C in both groups. At 72 h, final overall performance category (OPC) 1 (normal) was achieved by all ten dogs of the two groups. Final neurologic deficit scores (NDS; 0-10% normal, 100% brain death) were 5+/-3% in the control group versus 6+/-5% in the adenosine group (NS). Total brain histologic damage scores (HDS) at 72 h were 74+/-9 (64-80) in the control group versus 68+/-19 (40-88) in the adenosine group (NS). In both groups, ischemic neurons were as prevalent in the basal ganglia and neocortex as in the cerebellum and hippocampus. The mild hypothermic aortic flush protocol is feasible in dogs. The adenosine strategy used does not abolish the mild histologic brain damage.

Rapid induction of mild cerebral hypothermia by cold aortic flush achieves normal recovery in a dog outcome model with 20-minute exsanguination cardiac arrest.

OBJECTIVES: Resuscitation attempts in trauma victims who suffer cardiac arrest (CA) from exsanguination almost always fail. The authors hypothesized that an aortic arch flush with cold normal saline solution (NSS) at the start of exsanguination CA can preserve cerebral viability during 20-minute no-flow. METHODS: Twelve dogs were exsanguinated over 5 minutes to CA of 20-minute no-flow, resuscitated by cardiopulmonary bypass, followed by post-CA mild hypothermia (34 degrees C) continued to 12 hours, controlled ventilation to 20 hours, and intensive care to 72 hours. At CA 2 minutes, the dogs received a 500-mL flush of NSS at either 24 degrees C (group 1, n = 6) or 4 degrees C (group 2, n = 6), using a balloon-tipped catheter inserted via the femoral artery into the descending thoracic aorta. RESULTS: The flush at 24 degrees C (group 1) decreased tympanic membrane temperature [mean (+/-SD)] from 37.5 degrees C (+/-0.1) to 35.7 degrees C (+/-0.2); the flush at 4 degrees C (group 2) to 34.0 degrees C (+/-1.1) (p = 0.005). In group 1, one dog achieved overall performance category (OPC) 2 (moderate disability), one OPC 3 (severe disability), and four OPC 4 (coma). In group 2, four dogs achieved OPC 1 (normal), one OPC 2, and one OPC 3 (p = 0.008). Neurologic deficit scores (0-10% normal, 100% brain death) [median (25th-75th percentile)] were 62% (40-66) in group 1 and 5% (0-19) in group 2 (p = 0.01). Total brain histologic damage scores were 130 (62-137) in group 1 and 24 (10-55) in group 2 (p = 0.008). CONCLUSIONS: Aortic arch flush of 4 degrees C at the start of CA of 20 minutes rapidly induces mild cerebral hypothermia and can lead to normal functional recovery with minimal histologic brain damage. The same model with aortic arch flush of 24 degrees C results in survival with brain damage in all dogs, which makes it suitable for testing other (e.g., pharmacologic) preservation potentials.

Hyperthermia-induced cardiac arrest in monkeys: limited efficacy of standard CPR.

BACKGROUND: Successful resuscitation from heatstroke cardiopulmonary arrest has been only partially explored and the data covering the post resuscitation pathophysiology leading to secondary arrest is, in most cases, insufficient. HYPOTHESIS: Following heatstroke-cardiopulmonary arrest, successful resuscitation may be achieved by standard CPR with surface cooling and administration of glucose. We ponder the sequence of early circulatory responses and the pathophysiological changes following successful resuscitation. METHODS: We exposed 12 pigtail monkeys to total-body hyperthermia (cerebral T 42 degrees C) until cardiac arrest ensued. Standard external CPR with surface cooling and glucose 5% IV were administered for up to 30 min. Control group A (n = 6) was compared with experimental group B (n = 6), which received additional steroid, glucagon and hypertonic glucose during CPR attempts. RESULTS: No significant differences were found between the outcome of the two groups. The 30-min CPR attempt succeeded in restoration of spontaneous circulation (ROSC) in 8/12 monkeys-5 animals from group A and 3 in group B. The animals in whom resuscitation was unsuccessful had significantly prolonged periods of rectal temperature exceeding 42.5 degrees C (p < 0.05), and significantly higher rectal temperatures at the end of 30 min of CPR and cooling (p < 0.05). All the resuscitated animals later rearrested at 158 +/- 68 (95-228) min after ROSC; pulmonary edema occurred in 6/8 animals. CONCLUSIONS: We conclude that experimentally-induced heatstroke can be transiently reversed by standard resuscitative procedures, but is followed by a delayed, irreversible, secondary shock state, which could not be prevented by the treatment we employed. We were, however, able to document in detail the pathophysiologic processes involved in the resuscitation, and the irreversible shock one sees after "successful" CPR.

Rat brain osmolality during barbiturate anesthesia and global brain ischemia.

Ischemic brain damage can be partially ameliorated by barbiturate therapy applied postinsult. Catabolism-induced brain hyperosmolality during ischemia may contribute to the development of brain edema after restoration of circulation. To determine changes in brain osmolality during ischemia and the effect of barbiturate anesthetics in altering its course, we measured whole and regional (cerebral cortex, diencephalon-midbrain, and cerebellum) brain osmolality for up to 2 hours after decapitation ischemia in unanesthetized and pentobarbital anesthetized rats. Normal (nonischemic) brain osmolality in pentobarbital anesthetized rats was 319 +/- 2 mOsm/1 (mean +/- SEM) and higher than in unanesthetized rats (307 +/- 6 mOsm/1). The rate of increase in whole brain osmolality was 60% slower in pentobarbital anesthetized rats in the first 60 minutes of ischemia and regional brain osmolality increased by a maximum of 32 mOsm/1 compared to 45 mOsm/1 in unanesthetized rats. The potential for edema based on percent change in brain osmolality as well as the rapidity of the change was greater in unanesthetized rats. The significance of the increase in brain osmolality with barbiturate anesthesia and its attenuation of the rate and magnitude of increase during ischemia is discussed.

Glucose transport across the rat blood-brain barrier during anesthesia.

The authors studied blood-brain barrier (BBB) glucose transport kinetics in awake rats and in pentobarbital- and halothane-anesthetized rats, using a 3H2O/14C-D-glucose double-indicator method corrected for cerebral blood flow at glucose concentrations from 1 to 80 mM. At normal glucose concentrations (5 mM), total brain glucose influx was unaltered by pentobarbital. In contrast, halothane attenuated glucose transport capacity from 1.9 to 0.4 mumol/g-min-1 and increased diffusional transport, Km (Michaelis constant) was decreased sixfold, from 12 to 2 mM. Halothane appears to inhibit BBB glucose transport by competing for the glucose carrier and by altering the affinity of the carrier for glucose, perhaps by altering the environment of the carrier or the carrier itself. The finding of halothane-induced increased diffusional transport of glucose across the BBB corroborates earlier reports and more recent evidence that halothane increases the permeability of the BBB to diffusional processes.

[Short-term transtracheal jet for reversible support of respiration in the rat]. / Zeitlicher transtrachealer Jet für die reversible Unterstützung der Atmung bei Ratten.

A method is described for reversible controlled ventilation of rats by transtracheal catheter (20 or 22 G). A small rodent ventilator is used, rather then a jet ventilator, because the former enables the mixing of inhalation anesthetics with the carrying gas mixture. The method proved to be the most successful one for weaning from controlled ventilation after cardiac arrest and resuscitation of rats. In general, the method can be considered as an alterative to oral intubation and tracheotomy for controlled ventilation in rats.

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.