Biomedical subjects
Publications and source records attributed to L B Becker.
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Efforts to minimize hypoxic injury may gain insight from considering treatments directed at different levels of biological organization, from cellular physiology to societal norms. At the cellular level, it appears that cells do not actually die during ischemia, but rather during reperfusion or resuscitation. Free radicals are implicated because antioxidants reduce cell death from ischemia/reperfusion, but typically fail to protect when only given during reperfusion. In preliminary work, two synergistic antioxidants were seen to offer significant protection even if used only during reperfusion. These findings suggest some cell death may be treatable at reperfusion and antioxidants targeted specifically at radical generation hold promise as a future therapy. On the organism level, blood flow during cardiopulmonary resuscitation (CPR) may be improved with a new manual device that combines the advantages of active-decompression CPR with interposed-abdominal-compression CPR; preliminary hemodynamic data in animals are encouraging. Possible worsening of injury in the postarrest period may occur from overuse of beta-agonists, excessive defibrillation energy, untreated hypotension, and lack of attention to intensive care principals. At the societal level, we have failed to provide simple treatments that are known to save lives, particularly basic CPR and early defibrillation. Bystander CPR suffers from poor quality of performance and from lack of initiation due to concern over disease transmission. The technology for rapid public defibrillation exists, yet is not commonly employed. Collectively, survival likelihood may be predicted with a multifactor equation which may be useful as we develop future therapies.
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The extent of cardiac injury incurred during reperfusion as opposed to that occurring during ischemia is unclear. This study tested the hypothesis that simulated ischemia followed by simulated reperfusion causes significant "reperfusion injury" in isolated chick cardiomyocytes. Cells were exposed to hypoxia, hypercarbic acidosis, hyperkalemia, and substrate deprivation for 1 h followed by 3 h of reperfusion. Irreversible cell membrane injury, measured by propidium iodide uptake, increased from 4% of cells at the end of ischemia to 73% after reperfusion; death occurred in only 17% of cells kept ischemic for 4 h. Lactate dehydrogenase release was consistent with these changes. Lengthening ischemia from 30 to 90 min increased cell injury as expected, but of the total cell death, > 90% occurred during reperfusion. "Chemical hypoxia" composed of cyanide (2.5 mM) plus 2-deoxyglucose augmented injury before reperfusion compared with simulated ischemia. Inhibition of oxygen radical generation by use of metal chelator 1,10-phenanthroline reduced cell death from 73% to 40% after reperfusion (P = 0.001). We conclude that simulated reperfusion significantly augments the cellular membrane damage elicited by simulated ischemia in isolated cardiomyocytes devoid of other factors and suggest that reactive oxygen species, perhaps from the mitochondria, participate in this injury.
Studies of intact hearts suggest that cardiac myocytes may have the ability to reversibly suppress metabolic activity and energy demand in states of regional hypoperfusion. However, an ability to suppress respiration in response to hypoxia has never been demonstrated in isolated myocytes. To test this, isolated embryonic chick cardiac myocytes were exposed to progressive hypoxia while their rate of O2 uptake and concentrations of lactate, ATP, ADP, AMP, and phosphocreatine were measured. Compared with the value obtained at an oxygen tension (PO2) of 120 Torr, cellular O2 uptake decreased by 28 +/- 14% (SD) at PO2 = 50 Torr and by 64 +/- 25% at PO2 = 20 Torr (P < 0.05). This decrease was similar after 1 min or 2 h of hypoxia, was sustained for 16 h, and was completely reversible within 2 min after reoxygenation. The reduction in O2 uptake was associated with a decrease in the rate of ATP turnover, but no change in adenine nucleotide or phosphocreatine concentrations. In myocytes adherent to glass cover-slips, O2 uptake and contractile motion were decreased after 30-60 min at 50 and 20 Torr, compared with normoxic values. O2 uptake also was significantly decreased at 50 and 20 Torr in myocytes incubated with N,N,N',N'-tetramethyl-p-phenylenediamine, which suggests that the catalytic activity of cytochrome-c oxidase was partially inhibited during hypoxia. In summary, these results demonstrate that embryonic chick cardiac myocytes can suppress their rates of ATP demand, ATP utilization, and O2 uptake during moderate hypoxia through a mechanism that involves a reversible inhibition of cytochrome-c oxidase. This mechanism may represent a protective response to cellular hypoxia.
STUDY OBJECTIVE: In a previous cardiopulmonary resuscitation (CPR) study in swine, ventilation was associated with improved rate of return of spontaneous circulation (ROSC) compared with nonventilated animals, which had greater hypoxia and hypercarbic acidosis. We used the same model to determine the independent effect of hypoxia and hypercarbic acidosis on ROSC after cardiac arrest. DESIGN: Laboratory model of cardiac arrest. SETTING: University teaching hospital laboratory. PARTICIPANTS: Domestic swine (23 to 61 kg). INTERVENTIONS: Twenty-four swine were randomly assigned to three groups receiving ventilation during CPR with 85% O2/15% N2 (control), 95% O2/5% CO2 (hypercarbia), or 10% O2/90% N2 (hypoxia). All animals had ventricular fibrillation for 6 min without CPR, then CPR with one of the ventilation gases for 10 min, then defibrillation. Animals without ROSC received epinephrine, 85% O2, CPR for another 3 min, and defibrillation. MEASUREMENTS AND RESULTS: During the tenth minute of CPR, the hypercarbic group had more mean (SD) arterial hypercarbia than the control group (PCO2, 47 +/- 6, compared with 34 +/- 6; p < 0.01), and greater mixed venous hypercarbia (PCO2, 72 +/- 14, compared with 59 +/- 8; p < 0.05), while mean arterial and mixed venous PO2 was not significantly different. The hypoxic group had significantly less mean arterial (43 +/- 9 compared with 228 +/- 103 mm Hg) and mixed venous (22 +/- 5 compared with 35 +/- 7 mm Hg) PO2 when compared with the control group (p < 0.01), while mean arterial and mixed venous PCO2 were not significantly different. Thus, the model succeeded in producing isolated hypercarbia without hypoxia in the hypercarbic group and isolated hypoxia without hypercarbia in the hypoxic group. The rate of ROSC was 6/8 (75%) for the control group, 1/8 (13%) for the hypercarbic group, and 1/8 (13%) for the hypoxic group (p < 0.02). CONCLUSIONS: Both hypoxia and hypercarbia independently had an adverse effect on resuscitation from cardiac arrest. In this model with a prolonged interval of untreated cardiac arrest, adequate ventilation was important for resuscitation.
OBJECTIVE: To compare the tidal volume, minute ventilation, and gas exchange caused by mechanical chest compression with and without mechanical ventilatory support during cardiopulmonary resuscitation (CPR) in a laboratory model of cardiac arrest. DESIGN: A laboratory swine model of CPR was used. Eight animals with and eight animals without mechanical ventilation received chest compression (100/min) for 10 min. Coronary perfusion pressure, tidal volume, and minute ventilation were recorded continuously. INTERVENTIONS: Ventricular fibrillation for 6 min without CPR, then mechanical chest compression for 10 min. RESULTS: During the first minute of chest compression, mean (+/- S.D.) minute ventilation was 11.2 +/- 5.9 l/min in the mechanically ventilated group and 4.5 +/- 2.8 l/min in the group without mechanical ventilation (P = 0.01). Minute ventilation gradually declined to 5.8 +/- 1.4 l/min and 1.7 +/- 1.6 l/min, respectively, during the last minute of chest compression (P < 0.0001). After 10 min of chest compression, mean arterial pH was significantly more acidemic in the group without mechanical ventilation (7.16 +/- 0.13 compared with 7.30 +/- 0.07 units) and PCO2 was higher (62 +/- 19 compared with 35 +/- 9 mmHg). Mixed venous PCO2 was also higher (76 +/- 15 compared with 61 +/- 8 mmHg). CONCLUSION: Standard chest compression alone produced measurable tidal volume and minute ventilation. However, after 10 min of chest compression following 6 min of untreated ventricular fibrillation, it failed to sustain pulmonary gas exchange as indicated by significantly greater arterial and mixed venous hypercarbic acidosis when compared with a group receiving mechanical ventilation.
BACKGROUND: Researchers are interested in improved uniformity of definitions and standards of reporting data for human CPR studies, and international guidelines (Utstein style) have been developed. However, no guidelines exist for animal CPR investigations. OBJECTIVE: To assess published animal CPR studies for adequacy of reporting and uniformity of methods and definitions regarding such important factors as the interval from the onset of ventricular fibrillation to the start of CPR (the nonintervention interval), ventilation, chest compression, coronary perfusion pressure, and return of spontaneous circulation. DESIGN: A blinded review of the methodology described in 42 articles concerned with animal CPR research published during the last ten years. An article had to report cardiac arrest and CPR as part of the protocol and return of spontaneous circulation as one of the outcome variables in order to be included in this study. We excluded abstracts, nonresuscitation models, and human CPR studies. MEASUREMENTS AND MAIN RESULTS: There was wide variation in the experimental methods reported in the studies. The nonintervention interval ranged from 0 to 15 minutes. The majority of studies initiated CPR within three minutes after the onset of ventricular fibrillation. Twenty-two percent of studies reported tidal volume, and 18% reported minute ventilation. Of the 14 studies that used blood pressure or coronary perfusion pressure as a target for titration of chest compression force, 12 used different target blood pressure values. We found 29 different definitions of return of spontaneous circulation. The duration of return of spontaneous circulation ranged from 30 seconds to 60 minutes; however, 52% of studies did not report a duration. CONCLUSION: Important differences exist in animal CPR research methodology among laboratories. Failure to define or report minute ventilation, coronary perfusion pressure, and return of spontaneous circulation made it difficult to compare studies. In order to make valid comparisons of studies, blood flow and ventilation should be measured and controlled when they are not experimental variables. Uniform definitions and guidelines for reporting should be developed for laboratory CPR research.
BACKGROUND: The need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest. METHODS AND RESULTS: Twenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of > 80 mm Hg for > 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 minutes without chest compression, followed by mechanical chest compression for 10 minutes and then attempted defibrillation. Animals without return of spontaneous circulation were given epinephrine, ventilation, and chest compression for an additional 3 minutes. Defibrillation was again attempted, and animals were assessed for return of spontaneous circulation. There were no significant differences between the two groups in baseline prearrest mean cardiac index, coronary perfusion pressure, or arterial and mixed venous blood gases. However, after 9 minutes of chest compression, significant differences were noted between the ventilated and nonventilated groups. The nonventilated group had significantly (P < .05) lower mean arterial PO2 (38 +/- 17 mm Hg compared with 216 +/- 104 mm Hg) and higher PCO2 (62 +/- 16 mm Hg compared with 35 +/- 8 mm Hg), lower mixed venous PO2 (15 +/- 7 mm Hg compared with 60 +/- 7 mm Hg). Nine of 12 (75%) of the ventilated animals, and only 1 of 12 (8%) of the nonventilated animals had return of spontaneous circulation after cardiac arrest (P < .002). CONCLUSIONS: In this animal model of cardiac arrest, ventilation was important for resuscitation. The importance of ventilation could be related to the prolonged duration of untreated ventricular fibrillation and the significantly greater hypoxia and hypercarbic acidosis found in the nonventilated animals.
BACKGROUND: Differences between blacks and whites have been reported in the incidence of several forms of cardiovascular disease, including hypertension and stroke. We examined racial differences in the incidence of cardiac arrest in a large urban population and in subsequent survival. METHODS: We collected data on all nontraumatic, out-of-hospital cardiac arrests in Chicago from January 1, 1987, through December 31, 1988, and compared the incidence and survival rates for blacks and whites. We examined the association between survival and race and seven other known risk factors by logistic-regression analysis. We computed incidence rates by coupling our data with U.S. Census population data. RESULTS: Our study population comprised 6451 patients: 3207 whites, 2910 blacks, and 334 persons of other races. The incidence of cardiac arrest was significantly higher for blacks than for whites in every age group. The survival rate after cardiac arrest was 2.6 percent in whites, as compared with 0.8 percent in blacks (P < 0.001). Blacks were significantly less likely to have a witnessed cardiac arrest, bystander-initiated cardiopulmonary resuscitation, or a "favorable" initial rhythm or to be admitted to the hospital. When they were admitted, blacks were half as likely to survive. The association between race and survival persisted even when other recognized risk factors were taken into account. We did not find important differences between blacks and whites in the response times of the emergency medical services. CONCLUSIONS: The black community in our study was at higher risk for cardiac arrest and subsequent death than the white community, even after we controlled for other variables.
STUDY OBJECTIVES: To add to our understanding of survival rates in out-of-hospital cardiac arrest studies, we examined the incidence of cardiac arrest in the published literature. We specifically estimated if incidence rates are uniform between communities and if any relationship exists between incidence and the reported survival rates. DESIGN: A retrospective study of nearly 100 cardiac arrest peer-reviewed articles from 1970 to 1989 was performed to identify reports that included rates for incidence and survival or provided sufficient data for the calculation of these rates. MEASUREMENTS AND MAIN RESULTS: We were able to obtain reported or calculated incidence and survival rates for 20 communities. Statistical analysis was performed to compare incidence rates between communities and examine the relationship across these 20 studies between incidence rates and reported survival rates. Incidence rates ranged significantly from 35.7 to 128.3 per 100,000, with a mean of 62. Survival rates ranged significantly from 1.6% to 20.7%. Incidence rates in these communities were negatively related to survival rates; that is, as the incidence rate increased, the survival rate decreased. We determined the regression curve that describes this inverse relationship. This nomogram can be used to identify survival/incidence rate combinations that are significantly above or below average. CONCLUSION: The marked variations in incidence and inverse relationship between incidence and survival could be due to true variation in risk among the populations reported (ie, some populations may be older or sicker than others). Also, different research methodologies may create artifactual differences among studies as standards for designing studies, terminology, and reporting data have not been uniform. Therefore, these findings may reflect methodological differences and true epidemiological differences among communities. Future reports should include a method, such as an incidence/survival nomogram, to analyze survival rates while taking into account the community incidence rate of cardiac arrest. Further analysis of incidence and survival is necessary to improve intersystem comparisons, a prerequisite to sound decisions about cardiac arrest treatment, health policy, and allocation of resources.
To improve emergency cardiac care (ECC) on the national or international level, we must translate to the rest of our communities the successes found in cities with high survival rates. In recent years, important developments have evolved in our understanding of the treatment and evaluation of cardiac arrest. Some of the most important of these developments include 1) recognition of the chain of survival, which is necessary to achieve high survival rates; 2) widespread acceptance that survival rates must be assessed routinely to ensure continuous quality improvements in the emergency medical services (EMS) system; and 3) development of improved methods for performing survival rate studies that will maximize the effectiveness of information gathering and analysis. While each community should determine how to optimize their own ECC services, some general guidelines are useful. Successful treatment of cardiac arrest starts in the community with prevention and education, including early recognition of the signs and symptoms of cardiovascular ischemia. Obtaining 911 service (and preferably enhanced 911) should be a top priority for all communities. EMS dispatchers should dispatch the unit to the scene in less than one minute, provide critical information to the responders regarding the type of emergency, and offer the caller telephone-assisted CPR instructions. The EMS first-responders should strive to arrive at the patient's side in less than four minutes, be able to immediately defibrillate if necessary, and begin basic CPR. An excellent strategy to accomplish this is to equip and train all fire-fighting units in the operation of automatic external defibrillators and dispatch them as a first-responder team. To manage the cardiac arrest patient, a minimum of two rescuers trained in advanced cardiac life support plus two or more rescuers trained in basic life support are needed. Furthermore, an EMS system is not complete without on-going evaluation. Therefore, the 1992 National Conference on CPR and ECC strongly endorses the position that all ECC systems assess their survival rates through an ongoing quality improvement process and that all members of the chain of providers should be represented in the outcome assessment team. We still have much to discover regarding optimal techniques of CPR, methods for data collection, and optimal structure of an EMS system. Research in these areas will provide the foundation for future changes in EMS systems development.
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Nutmeg is a common household spice sometimes abused for its hallucinogenic properties. This abuse is well reported in the medical literature over the last century. Ingestion of less than one tablespoon can produce symptoms similar to those of an anticholinergic toxic episode. Common presenting complaints are hallucinations, palpitations, and feelings of impending doom. We report a case of intentional nutmeg intoxication in a 23-year-old college student. As laboratory tests are usually normal, this diagnosis should be considered in patients presenting with an acute psychotic break accompanied by symptoms resembling an anticholinergic toxic episode. Treatment is primarily supportive once other life-threatening conditions have been ruled out.