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Biomedical subjects

P Safar

Publications and source records attributed to P Safar.

At least 163 records · Page 9Linked to original sources
PubMed1987

Cardiopulmonary bypass after prolonged cardiac arrest in dogs.

Ventricular fibrillation (VF) cardiac arrest of more than ten minutes can be survived by cerebral neurons, but restoration of spontaneous circulation (ROSC) by external CPR is unreliable. Cardiopulmonary bypass (CPB) permits control of pressure, flow, oxygenation, temperature, and composition of blood. After 12 1/2 minutes of normothermic VF cardiac arrest, CPB was used as a research tool for reperfusion and assisted circulation for two hours in ten dogs without thoracotomy, with plasma substitute priming, and without preceding CPR (a deliberately nonclinical scenario). Recovery was compared with that in ten control dogs in which standard CPR with advanced life support (ALS) for up to 30 minutes was used to achieve ROSC. Both groups subsequently had blood pressure, blood gases, ventilation, and other parameters controlled for 20 hours, and intensive therapy to 72 hours. CPB achieved ROSC more successfully (ten of ten vs six of ten controls) (P less than .05), and more rapidly, with fewer defibrillation attempts and with less epinephrine (P less than .05). CPB improved 72-hour survival (seven of ten vs two of ten controls) (P = .025). Between two and 24 hours, of those with ROSC, intractable cardiogenic shock killed four of six control dogs (NS). CPB was followed by fewer arrhythmias. CPB increased recovery of consciousness (five of ten CPB vs zero of six controls with ROSC) (P = .037), but achieved neurologic normality in only one of ten. Cardiac arrest and CPB (without CPR) resulted in less myocardial morphologic damage than did standard CPR (P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cardiopulmonary bypass after cardiac arrest and prolonged closed-chest CPR in dogs.

We studied a clinically realistic field-to-hospital scenario in dogs with four-minute ventricular fibrillation (VF) cardiac arrest followed by 30-minute standard external CPR basic life support (BLS). At the end of this 34-minute insult, cardiopulmonary bypass (CPB) was used for early defibrillation and assisted circulation for one hour (n = 10). Recovery was compared with that of control dogs (n = 10) in which standard CPR with advanced life support (ALS) for another 30 minutes was used for restoration of spontaneous circulation (ROSC). Both groups had hemodilution and heparinization; controlled blood pressure, blood gases, ventilation, and other parameters for 20 hours; and intensive care to 72 hours. During CPR-BLS of 30 minutes in both groups signs of cerebral viability returned. CPB achieved ROSC more successfully (ten of ten vs five of ten CPR-ALS controls) (P less than .02); and more rapidly, with less defibrillation energy (first countershock in eight of ten) and with less epinephrine (P less than .01). CPB improved 72-hour survival (seven of ten vs three of ten controls) (P less than .05). Between two and 24 hours, of those with ROSC, cardiac complications killed three of ten CPB dogs (after weaning), and two of five CPR-ALS dogs (NS). All seven CPB survivors to 72 hours were neurologically normal; of the three CPR-ALS survivors, one remained with severe neurologic deficit and two were neurologically normal (seven of ten CPB vs two of ten controls, P = .025). Starting CPR-BLS within four minutes of arrest can maintain cerebral viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Deferred consent. A new approach for resuscitation research on comatose patients.

Methodological constraints inherent in the rapidly growing field of resuscitation research have created an apparent conflict with newly promulgated federal regulations, especially those concerning informed consent requirements. We propose that two new concepts be applied to resuscitation research to satisfy the current federal regulations governing biomedical research. The first of these concepts is "minimal differential risk," ie, in resuscitation medicine, the difference between the risk of an undesirable outcome when standard, commonly accepted therapy may be used and the risk of an undesirable outcome with experimental therapy is minimal. The second concept is "deferred consent," ie, obtaining consent to continue with an experimental therapy after administration of that therapy has already begun. We believe that the emergency exception to informed consent applies to resuscitation research. Recognition of the applicability of these concepts to resuscitation research should allow compliance with federal and state regulations that otherwise might inhibit or preclude such research endeavors.

Brain Diseases↗
PubMed1986

Comparison of open-chest cardiac massage techniques in dogs.

Manual compression of the heart during open-chest cardiac massage (OCPR) has been shown to be superior to closed-chest compression. Our study sought to determine, in a canine model, the optimal hand position for manual compression of the heart. Twelve dogs were anesthetized with ketamine, an orotracheal tube was placed, and anesthesia was maintained with halothane and nitrous oxide. Cannulae were placed to monitor diastolic (DBP) and systolic (SBP) blood pressures, intracranial pressure (ICP), and common carotid blood flow (CCBF). Control values were obtained under light general anesthesia, and ventricular fibrillation was induced. External CPR (ECPR) was performed with a mechanical compressor before opening the chest and pericardium through the left fifth interspace. The following sequence of three hand positions was used for OCPR: technique A, one-handed technique with thumb on left ventricle, fingers over the right ventricle, and apex in palm; technique B, two-handed technique with right ventricle cupped in left hand and fingers of right hand over left ventricle; and technique C, one-handed technique with fingers of right hand over left ventricle and heart against sternum. Each was done at a rate of 60 compressions per minute with the operator blind to results during performance. All three techniques produced significantly (P less than .05) greater DBPs and CCBFs when compared with ECPR. All three also produced significantly lower (P less than .05) ICPs when compared with ECPR. DBPs, SBPs, CCBFs, and cerebral perfusion pressures were similar for techniques B and C, and all were significantly greater (P less than .05) than those achieved with technique A.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
PubMed1986

Cerebral resuscitation after cardiac arrest: a review.

Cerebral neurons can tolerate at least 20 min of normothermic ischemic anoxia. Cerebral recovery from more than 5 min of cardiac arrest is hampered by complex secondary derangements of multiple organ systems after reperfusion. There is increasing support of our hypothesis that this "postresuscitation syndrome" includes the following: secondary cerebral perfusion failure, cerebral reoxygenation injury (cell-necrotizing cascades), and cerebral "intoxication" from derangements of extracerebral organs. To be optimal for the brain, CPR with optimal perfusion pressure must be started as promptly as possible. Significant though inconsistent mitigation of permanent brain damage after prolonged complete global brain ischemia has been achieved in animal outcome preparations with the use of the following treatments initiated at the start of reperfusion: brain-oriented extracerebral life support by protocol, intra-arterial hemodilution, hypertension, and artificial circulation, barbiturates, calcium-entry blockers, free-radical scavengers, and multifaceted treatments. We currently recommend treatment 1 for patient care and treatment 2 for clinical feasibility trials. Treatment 3, thiopental loading (starting 10 to 50 min after restoration of spontaneous circulation), was tested in a randomized clinical trial and was not shown to confer a statistically significant benefit. A calcium-entry blocker is under clinical investigation. Many other novel treatments appear promising but further animal studies are required. The complex multifactorial pathogenesis of postcardiac arrest encephalopathy requires systematic multicenter development of etiology-specific combination therapies.

Animals↗
PubMed1985

Resuscitation of dogs from cold-water submersion using cardiopulmonary bypass.

In cold-water drowning, attempts at restoration of spontaneous circulation (ROSC) by external cardiopulmonary resuscitation (CPR) often fail. We explored the longest period of asphyxial cardiac arrest from cold-water submersion (without inhalation of water) from which ROSC is possible using cardiopulmonary bypass (CPB). In 19 lightly anesthetized dogs the tracheal tube was clamped (simulating laryngospasm) and the dogs were immersed in ice water from 20, 40, 60, 90, or 120 minutes. Cardiac arrest occurred after six to 11 minutes of submersion. At start of resuscitation, rectal temperature ranged from 21 C (after 60 minutes) to 34 C (after 20 minutes of submersion), and cerebral temperature was between 7 C (after 120 minutes) and 27 C (after 20 minutes submersion). Resuscitation attempts were performed according to protocol in 16 dogs, using only CPB by venoarterial pumping with an oxygenator and a heat exchanger. Priming was with 400 to 800 mL Dextran 40 and Ringer's solution 1:1 plus heparin. CPB flows were 10 mL/kg/min, and they increased to achieve normotension and return of rectal temperature to 32 C. After one-half to three hours, of CPB, ROSC was successful in 75%. This percentage included one of three dogs after 90 minutes submersion, but not in the one dog after 120 minutes submersion. Spontaneous breathing and EEG activity returned in 56% at two to 24 hours, after 20 to 90 minutes of submersion. Failure of ROSC attempts apparently were due to clotting in large vessels during arrest and capillary leakage during reperfusion. CPB is effective for ROSC after prolonged hypothermic cardiac arrest, and it should be evaluated in animal outcome studies.

Animals↗
PubMed1985

Cerebral preservation during cardiopulmonary resuscitation.

Thirty-two dogs subjected to 4 min of ventricular fibrillation were equally divided into four treatment groups: (a) immediate defibrillation (control); or 30 min of (b) standard CPR (SCPR), (c) simultaneous ventilation-compression CPR (SVC-CPR), or (d) open-chest CPR (OCCPR). After 30 min of CPR, restoration of spontaneous circulation was attempted using drug therapy and countershocks and the animals maintained for 24 h or until refractory hypotension occurred. During CPR, OCCPR yielded higher mean arterial and lower central venous pressures than either external method. Circulation was restored in all control dogs, and by 24 h they had nearly normal neurologic deficit scores. In the SCPR group, the heart was restarted in six dogs. Five of these dogs had severe neurologic damage and did not survive 24 h. The animal that survived 24 h, however, was nearly normal neurologically. Although circulation was restored in five SVC-CPR dogs, all were brain-dead and none survived 24 h. In the OCCPR group, seven animals survived 24 h and their neurologic deficit scores were not significantly different from control values. We conclude that OCCPR is greatly superior to SCPR and SVC-CPR with respect to preservation of the brain during resuscitation.

Animals↗
PubMed1985

Long-term animal outcome models for cardiopulmonary-cerebral resuscitation research.

Controlled clinically relevant animal models are essential in the ongoing search for increasingly cost-effective methods to reverse clinical death. Acute (up to 12 h) and short-term (up to 24 h) experiments are useful for the study of dying mechanisms and restoration of spontaneous circulation. Although long-term models are difficult and expensive, they are essential to permit lesions to mature, treatments to take effect, secondary deterioration to be recognized, and survival and brain damage to be quantified and compared between treatment groups. The insults studied include temporary complete global head ischemia in monkeys, ventricular fibrillation cardiac arrest in dogs, asphyxial cardiac arrest in rats and dogs, and exsanguination arrest in dogs. Standard external CPR combined with advanced life support is less successful than open-chest CPR or emergency cardiopulmonary bypass after prolonged ventricular fibrillation. Postinsult monitoring of multiple organ systems can be used to explore the postresuscitation syndrome and evaluate novel treatment potentials. Outcome measurements include brain enzyme leakage into the cerebrospinal fluid, neurologic deficit scoring, overall performance categorization, incidence of secondary deterioration, and histopathologic damage scoring of brain and viscera.

Animals↗