Biomedical subjects

S W Stezoski

Publications and source records attributed to S W Stezoski.

At least 37 records · Page 2Linked to original sources

PubMed1991

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.

Animals↗

PubMed1990

Emergency cardiopulmonary bypass for resuscitation from prolonged cardiac arrest.

After cardiac arrest (no flow) of more than approximately 5 minutes' duration, standard external cardiopulmonary resuscitation (CPR) basic, advanced, and prolonged life support (BLS, ALS, PLS) do not reliably produce cerebral and coronary perfusion pressures to maintain viability and achieve stable spontaneous normotension; nor do they provide prolonged control over pressure, flow, composition, and temperature of blood. Since these capabilities are often needed to achieve conscious survival, emergency closed-chest cardiopulmonary bypass (CPB) by veno-arterial pumping via oxygenator is presented in this review as a potential addition to ALS-PLS for selected cases. In six dog studies by the Pittsburgh group (n = 221; 1982 through 1988), all 179 dogs that received CPB after prolonged cardiac arrest (no flow) or after CPR (low flow) states had restoration of stable spontaneous circulation. The use of CPB enhanced survival and neurological recovery over those achieved with CPR-ALS attempts only. With CPB and standard intensive care, it was possible to reverse normothermic ventricular fibrillation (VF) cardiac arrest (no flow) of up to 15 minutes and to achieve survival without neurologic deficit; VF of 20 minutes to achieve survival but with neurologic deficit; and VF of 30 minutes to achieve transient restoration of spontaneous circulation followed by secondary cardiac death. CPB could restore stable spontaneous circulation after ice water submersion of up to 90 minutes. Other groups' laboratory and clinical results agree with these findings in general. Clinical feasibility trials are needed to work out logistic problems and to meet clinical challenges. Future possibilities for emergency CPB require further research and development.

Animals↗

PubMed1990

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.

Animals↗

PubMed1989

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.

Animals↗

PubMed1989

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.

Animals↗

PubMed1989

Effect of excitatory amino acid receptor blocker MK-801 on overall, neurologic, and morphologic outcome after prolonged cardiac arrest in dogs.

Excitatory amino acids accumulating in the brain during ischemia may cause selective neuronal damage postischemia. This hypothesis was tested in a series of studies using MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, in a reproducible outcome model of prolonged cardiac arrest in dogs. After normothermic ventricular fibrillation cardiac arrest, the dogs were resuscitated with closed-chest femoral veno-arterial cardiopulmonary bypass. At 4 h they were separated from bypass, ventilation was controlled for 20 h, and intensive care was continued to 96 h. In Study I, ventricular fibrilation cardiac arrest (no-flow) was 17 min; starting immediately with reperfusion, MK-801 1200 mg/kg (n = 5) or an equal volume of placebo (n = 5) was infused over 12 h in blinded, randomized fashion. In Study II, the duration of the no-flow period was reduced to 15 min, and MK-801 2400 mg.kg-1 (n = 4) or placebo (n = 4) was infused. In Study III, no-flow lasted for 15 min, and MK-801 2400 mg/kg was started 30 min before ventricular fibrillation (n = 4); comparison was with Study II controls. In all three studies, MK-801 plasma concentrations peaked at greater than 50 ng/ml and were 15-30 ng/ml over 12 h. All 22 dogs of experiments within protocol survived with severe brain damage. MK-801 delayed return of pupillary reactivity, EEG activity, consciousness, and respiration, necessitating longer periods of controlled ventilation. Neurologic deficit scores, overall performance categories, and brain and heart morphologic damage scores at 96 h did not differ between placebo and MK-801 pretreatment or post-treatment groups. These negative outcome results after prolonged cardiac arrest do not negate the hyperexcitability hypothesis of selective vulnerability, but suggest the existance of additional mechanisms of secondary brain damage.

Animals↗

PubMed1986

Insulin worsens ischemia-induced myocardial contracture in the isolated rat heart.

We used a modification of Langendorff's isolated perfused nonworking rat-heart model to study the effects of diabetes, insulin-treated diabetes, and hyperinsulinemia on left ventricular pressure, force of ventricular contraction, and myocardial contracture, before, during, and after 20 min of complete normothermic global ischemia. Untreated diabetic rat hearts behaved the same as normal hearts, but insulin-treated diabetic hearts had more ischemic and postischemic contracture (p less than .01), and less return of left ventricular function. Chronic insulin treatment potentiated ischemic contracture in diabetic and nondiabetic rat hearts. These results support the hypotheses that insulin can increase Ca++ actin-myosin ATPase activity, and increase the affinity of myofibrillar receptors for calcium, which may lead to increased ischemic contracture. Insulin as a risk factor in myocardial ischemia, cardiothoracic surgery and cardiac resuscitation, and other pathogenetic factors of "stone heart" development, deserve further investigation.

Animals↗

PubMed1986

Calcium uptake during insulin-aggravated ischemic myocardial contracture in the rat heart.

Perfusion of isolated, nondiabetic rat hearts with high concentrations of regular insulin (10 mU/ml) produced earlier onset of myocardial contracture during ischemia than control perfusions without insulin. High insulin concentrations also increased total myocardial calcium content (p less than .001) and myocardial Ca-45 uptake postischemia (p less than .05). Insulin perfusion before ischemia did not enhance calcium uptake. These results support the hypothesis that insulin may increase calcium movement across myocardial cell membranes, which may lead to increased ischemic contracture. Insulin-aggravated myocardial ischemia in cardiothoracic surgery and cardiac resuscitation deserves further investigation.

Animals↗

PubMed1984

[Short-term transtracheal jet for reversible support of respiration in the rat].

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.

Animals↗

PubMed1980

Augmentation of postischemic brain damage by severe intermittent hypertension.

The neurological recovery and histological changes were studied in monkeys after intermittent postischemic arterial hypertension after 16 min of global brain ischemia. Ischemia was produced with a high pressure (1500 mm Hg) neck tourniquet and systemic arterial hypotension. Intensive care and life support, including monitoring of physiological variables, were provided for 7 days. Postischemia all monkeys were immobilized; ventilation was controlled and mean arterial pressure was maintained between 85--115 mm Hg for the first 48 hours. Immediately postischemia in four monkeys, intermittent arterial hypertension (i.e., 150--190 mm Hg) was induced by norepinephrine infusion for 3--5 min. Hypertensive episodes were repeated at 15, 30, 60, and 120 min postischemia, once every hour for the first 24 hours and once every 2 hours between 24 and 48 hours. Thereafter, the monkeys were allowed to breathe spontaneously. Four control monkeys were similarly treated except that arterial hypertension was not induced. Neurological recovery was evaluated by EEG, intracranial pressure, neurological deficit scoring, and histological examination of the brain after killing on day 7 postischemia. The neurological deficit score (100 % = brain death; 50% = vegetative state; 0% = normal) in control monkeys on day 7 was 17.8 +/- 1.8 (SEM) % compared to 46.3 +/- 6.5% (p less than 0.05) in the hypertension group. EEG recovery was delayed and the postischemic increase in intracranial pressure was prolonged in the hypertension group. Histological damage scores in the brain correlated with neurological deficit scores. Severe intermittent hypertension has a deleterious effect on neurological recovery after global brain ischemia.

Animals↗

PubMed1978

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.

Anesthesia, Intravenous↗

PubMed1977

Brain blood flow autoregulation and metabolism during halothane anesthesia in monkeys.

Past studies suggest that halothane causes cerebrovascular dilatation and increased cerebral blood flow (CBF); these properties may be relevant to its use for neurosurgical procedures. We studied CBF autoregulation in monkeys during anesthesia with 66% N2O/33% O2 and with 0.5%, 1.0%, and 2.0% inspired halothane at various cerebral perfusion pressures (CPP) achieved by infusion of trimethaphan camsylate or phenylephrine. CBF was measured by monitoring brain xenon-133 clearance after intra-arterial injection of the isotope in saline. CBF autoregulation was intact during N2O/O2 and during 0.5% halothane/N2O/O2 anesthesia at CPPs ranging from 50 to 100 mmHg, but began to fail at 1.0% halothane. Complete loss of autoregulation occurred during 2% halothane/N2O/O2 anesthesia. Estimated brain O2 consumption fell by 30%, 40%, and 50% during 0.5%, 1.0%, and 2.0% halothane anesthesia, respectively, compared to O2 consumption during N2O/O2 anesthesia (100%).

Anesthesia↗

PubMed1977