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Biomedical subjects

M H Weil

Publications and source records attributed to M H Weil.

At least 55 records · Page 3Linked to original sources

High-energy defibrillation increases the severity of postresuscitation myocardial dysfunction.

BACKGROUND: The fatal outcome of victims after initially successful resuscitation from cardiac arrest has been attributed both to global myocardial ischemia during the interval of cardiac arrest and to the adverse effects of reperfusion. The present study was prompted by earlier experimental observation that the magnitude of myocardial dysfunction was in part related to the energy delivered during electrical defibrillation. METHODS AND RESULTS: Ventricular fibrillation (VF) was induced in 15 Sprague-Dawley rats. Precordial compression was begun together with mechanical ventilation after 4 minutes of untreated VF and continued for 6 minutes. Spontaneous circulation was restored in each animal after external defibrillation with a single stored 2-, 10-, or 20-J countershock. Cardiac index and the rate of left ventricular pressure rise at left ventricular pressure of 40 mm Hg (dP/dt40) and fall (negative dP/dt) during the 240-minute interval after successful resuscitation were decreased, and left ventricular diastolic pressure was increased. These decreases in myocardial function were closely related to the energy of electrical defibrillation. After a 20-J shock, animals survived for only 5+/-3 hours; after a 10-J shock, animals survived for 15+/-4 hours; and after a 2-J shock, all animals survived for >24 hours. CONCLUSIONS: The severity of postresuscitation myocardial dysfunction is related, at least in part, to the magnitude of the electrical energy of the delivered shock.

Animals↗

Phased chest and abdominal compression-decompression. A new option for cardiopulmonary resuscitation.

BACKGROUND: We describe a new manual method of phased chest and abdominal compression-decompression with a Lifestick resuscitator for cardiopulmonary resuscitation (CPR). METHODS AND RESULTS: Ventricular fibrillation (VF) was induced in 20 domestic pigs. After either 5 or 7 minutes of untreated VF, either phased chest and abdominal compression-decompression (Lifestick resuscitator) or precordial compression was initiated. Defibrillation was attempted at 2 minutes after the start of CPR. For the animals in which VF was untreated for 7 minutes, epinephrine was administered in doses of 20 micrograms/kg at 2 minutes after start of CPR. The coronary perfusion pressure generated by the Lifestick resuscitator was more than twofold greater (P < .01) than that generated by conventional precordial compression. Of 5 control animals, none were resuscitated after 5 minutes of VF. However, each of 5 animals treated with the Lifestick resuscitator was resuscitated (P < .01) and survived after 48 hours (P < .01). When untreated VF was prolonged to 7 minutes and epinephrine was administered, only 2 of the 5 control animals were resuscitated, and none of them survived for more than 4 hours. However, each of the Lifestick-treated animals was resuscitated and survived for more than 48 hours (P < .01). CONCLUSIONS: Phased chest and abdominal compression-decompression substantially increased hemodynamic efficacy of CPR and outcome in terms of successful resuscitation, 48-hour survival, and cerebral recovery.

Abdomen↗

Cardiopulmonary resuscitation: a promise as yet largely unfulfilled.

After failure of initial external defibrillation, restoration of spontaneous circulation is largely contingent on rapid and effective reversal of myocardial ischemia by both mechanical and pharmacologic means. Despite the introduction of modern cardiopulmonary resuscitation (CPR) more than 35 years ago, its universal acceptance, and its wide implementation, no improvements in outcome excepting early defibrillation have been documented over these many years. The science of CPR therefore is still in its infancy. It was incorrectly assumed that all that needs to be known is known and that the need for scientific research was therefore not apparent. Accordingly, serious resuscitation research was neither encouraged nor equitably supported. The ABCs of CPR currently provide for the establishment of a patent airway (A) and intermittent positive pressure ventilation, preferably with oxygen-enriched air (B). These are to be immediately followed with precordial compression (C). This ordering of priorities, however, is based on consensus rather than objective outcome measurements. The ABCs recently have been seriously challenged on the basis of results of both experimental and clinical studies. Conventional external precordial compression restores systemic blood flow. It may be used by both professional and nonprofessional CPR providers, especially bystanders, because of its apparent simplicity and noninvasiveness. However, manual or mechanical external precordial compression typically generates cardiac outputs that represent less than 30% of normal values. Coronary blood flow, which is critical for restoration of spontaneous circulation, is correspondingly reduced. Accordingly, several alternatives to conventional precordial compression have been proposed with the intent of increasing cardiac output and both coronary and cerebral blood flows. Among the large number of pharmaceutical agents initially recommended for cardiac resuscitation, only agents that produce peripheral vasoconstriction are of proved benefit. Epinephrine has been the preferred vasopressor agent for the management of cardiac arrest for more than 35 years because of its alpha-adrenergic effects. However, the potentially adverse effects of epinephrine are related to its beta-adrenergic inotropic actions. The beta-adrenergic actions account for disproportionate increases in myocardial oxygen consumption with increased severity of myocardial ischemic injury and provocation of ectopic ventricular tachycardia and ventricular fibrillation. Nevertheless, epinephrine remains the drug of choice, although adrenergic drugs with selective alpha-adrenergic actions or nonadrenergic vasoconstrictor drugs are likely to emerge as useful alternatives. Experimental and clinical observations have led to identification of continuous monitoring of both end-tidal carbon dioxide and ventricular fibrillation waveforms as practical noninvasive guides because they are highly correlated with both cardiac output and coronary blood flow. Both end-tidal carbon dioxide and ventricular fibrillation waveforms now serve as predictors of the likelihood of successful resuscitation. These two measurements may now be used to guide interventions and especially to assure optimal precordial compression. It is well established that sudden death among adults is predominantly due to malignant ventricular arrhythmias and ventricular fibrillation. Early defibrillation serves as an unequivocally effective immediate intervention. Minimally trained first responders and members of the general public are being enfranchised to use automated external defibrillators for very early defibrillation. Use of these devices by bystanders is the most promising new intervention since CPR was first proposed in the early 1960s. Postresuscitation ventricular dysrhythmias and heart failure are now called postresuscitation myocardial dysfunction. This complication has been recognized as a leading cause of the high postresuscitation mor

Adrenergic alpha-Agonists↗

Adverse effects of interrupting precordial compression during cardiopulmonary resuscitation.

OBJECTIVES: In the current operation of automated external defibrillators, substantial time may be consumed for a "hands off" interval during which precordial compression is discontinued to allow for automated rhythm analyses before delivery of the electric countershock. The effects of such a pause on the outcomes of cardiopulmonary resuscitation were investigated. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was electrically induced in 25 Sprague-Dawley rats. After 4 mins of untreated ventricular fibrillation, precordial compression was begun and continued for 6 mins. Animals were then randomized to receive an immediate defibrillation shock or the defibrillation attempt was delayed for intervals of 10, 20, 30, or 40 secs. MEASUREMENTS AND MAIN RESULTS: Immediate defibrillation restored spontaneous circulation in each instance. When defibrillation was delayed for 10 or 20 secs, spontaneous circulation was restored in three of five animals in each group. After a 30-sec delay, spontaneous circulation was restored in only one of five animals (p < .05). No animal was successfully resuscitated after a 40-sec delay (p < .01). With increasing delays, 24- and 48-hr survival rates were correspondingly reduced. CONCLUSIONS: During resuscitation from ventricular fibrillation, prolongation of the interval between discontinuation of precordial compression and delivery of the first electric countershock substantially compromises the success of cardiac resuscitation. Accordingly, automated defibrillators are likely to be maximally effective if they are programmed to secure minimal "hands off" delay before delivery of the electric countershock.

Animals↗

Esophageal PCO2 as a monitor of perfusion failure during hemorrhagic shock.

Measurement of gastric wall PCO2 (PgCO2) by tonometric method has emerged as an attractive option for estimating visceral perfusion during circulatory shock. However, gastric acid secretion obfuscates the tonometric measurement. We, therefore, investigated the option of measuring PCO2 in the esophagus to minimize these restraints. Hemorrhagic shock was induced in five Sprague-Dawley rats, and five rats served as sham controls. PgCO2 was measured with an ion-sensitive field effect transistor that was surgically implanted into the gastric wall. Esophageal luminal PCO2 (PeCO2) was measured by a second ion-sensitive field effect transistor sensor. During hemorrhagic shock, mean aortic pressure declined from 150 to 50 mmHg. Gastric blood flow decreased from 58 to 12 ml.min-1.100 g-1 (21% of preshock) and esophageal blood flow from 44 to 7 ml.min-1.100 g-1 (16% of preshock). PgCO2 simultaneously increased from 47 to 116 Torr and PeCO2 from 47 to 127 Torr. The increases in PgCO2 were highly correlated with increases in PeCO2 (r = 0.90). Esophageal tonometry may, therefore, serve as a practical alternative to gastric tonometry.

Animals↗

Research on CPR: reordering priorities.

The "ABCs" of CPR, i.e., airway, breathing, and circulation, represent the sequence of interventions currently advised and taught to providers of both basic life support (BLS) and advanced life support (ALS) by the American Heart Association. Nevertheless, in the settings of suspected or confirmed ventricular fibrillation, the ABCs may be deferred such that external electrical countershock(s) take(s) precedence. However, efforts to restore circulation by chest compression (or alternative mechanical means) remain the lowest of the three priorities for both BLS and ALS as presently prescribed. This ordering of priorities is based largely on the consensus rather than objective experimental or clinical evidence of improved outcomes. During the last 5 yrs, both clinical and experimental studies demonstrated that the A and B of these ABCs, and specifically positive-pressure ventilation, may not be essential during the initial 6 to 12 mins of CPR under conditions of sudden dysrhythmic cardiac arrest and in the absence of asphyxia. Recent studies further suggested that either or both precordial compression and spontaneous gasping may of itself generate sufficient alveolar ventilation during the initial 6 mins of CPR. Defibrillation now emerges as the highest priority. Automated defibrillators have a pivotal role. The need for objective controlled research, including experience with devices in clinical settings and technical improvements of operation, are essential.

Cardiopulmonary Resuscitation↗

Future directions for resuscitation research. III. External cardiopulmonary resuscitation advanced life support.

This discussion about advanced cardiac life support (ACLS) reflects disappointment with the over 50% of out-of-hospital cardiopulmonary resuscitation (CPR) attempts that fail to achieve restoration of spontaneous circulation (ROSC). Hospital discharge rates are equally poor for in-hospital CPR attempts outside special care units. Early bystander CPR and early defibrillation (manual, semi-automatic or automatic) are the most effective methods for achieving ROSC from ventricular fibrillation (VF). Automated external defibrillation (AED), which is effective in the hands of first responders in the out-of-hospital setting, should also be used and evaluated in hospitals, inside and outside of special care units. The first countershock is most important. Biphasic waveforms seem to have advantages over monophasic ones. Tracheal intubation has obvious efficacy when the airway is threatened. Scientific documentation of specific types, doses, and timing of drug treatments (epinephrine, bicarbonate, lidocaine, bretylium) are weak. Clinical trials have failed so far to document anything statistically but a breakthrough effect. Interactions between catecholamines and buffers need further exploration. A major cause of unsuccessful attempts at ROSC is the underlying disease, which present ACLS guidelines do not consider adequately. Early thrombolysis and early coronary revascularization procedures should also be considered for selected victims of sudden cardiac death. Emergency cardiopulmonary bypass (CPB) could be a breakthrough measure, but cannot be initiated rapidly enough in the field due to technical limitations. Open-chest CPR by ambulance physicians deserves further trials. In searches for causes of VF, neurocardiology gives clues for new directions. Fibrillation and defibrillation thresholds are influenced by the peripheral sympathetic and parasympathetic nervous systems and impulses from the frontal cerebral cortex. CPR for cardiac arrest of the mother in advanced pregnancy requires modifications and outcome data. Until more recognizable critical factors for ROSC are identified, titrated sequencing of ACLS measures, based on physiologic rationale and sound judgement, rather than rigid standards, gives the best chance for achieving survival with good cerebral function.

Animals↗

Adrenergic vasopressor agents and mechanical ventilation for the treatment of experimental septic shock.

OBJECTIVE: Vasopressor agents and mechanical ventilation are routine interventions for the treatment of sepsis complicated by hypotension. It was our hypothesis that such treatment singly or in combination increases the duration of survival. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Thirty male Sprague-Dawley rats anesthetized with intraperitoneal injection of pentobarbital. INTERVENTIONS: Peritonitis was induced by cecal ligation and spillage of cecal contents into the abdominal cavity. The first phase of this study was performed on 15 spontaneously breathing Sprague-Dawley rats that were randomized to three groups of five animals each. One group received treatment with dopamine. The second group received norepinephrine. The third group received only the diluent as a placebo. Concentrations of the vasopressor agents were increased such that mean arterial pressure was maintained at approximately 80% of baseline values; the volumes infused were kept constant. For the second phase of this study, the grouping of animals and the techniques of study were identical, except that rats were mechanically ventilated. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure was best maintained with norepinephrine. However, no statistically significant differences in duration of survival, cardiac index, arterial blood lactate concentration, or arterial and venous PCO2 and PO2 values were identified between groups. With mechanical ventilation, survival was prolonged (p < .01). Survival was increased from an average of 291 mins to 342 mins with dopamine, from 257 mins to 352 mins in placebo controls, and from 280 mins to 329 mins with norepinephrine. Again, no significant differences in hemodynamic and blood gas measurements, or in the duration of survival between vasopressor-treated and control animals were documented. CONCLUSIONS: No benefit or detriment was demonstrated when vasopressor agents were administered to sustain arterial pressure in the course of experimental peritonitis in this murine model of septic shock. This finding contrasted with highly significant prolongation of survival when animals were mechanically ventilated. There was no evidence that routine vasopressor therapy, under these controlled experimental conditions in rats, improved duration of survival.

Adrenergic alpha-Agonists↗

Myocardial dysfunction after successful resuscitation from cardiac arrest.

OBJECTIVE: To investigate the functional and metabolic changes in the myocardium after successful resuscitation from cardiac arrest. DESIGN: Prospective, randomized, sham-controlled study. SETTING: Animal laboratory at a university center. SUBJECTS: Domestic pigs. INTERVENTIONS: Electric induction of ventricular fibrillation by alternating current delivered to the right ventricular endocardium through a pacing electrode. Electric defibrillation was attempted after an interval of 12 mins of ventricular fibrillation, which included 4 mins of untreated ventricular fibrillation and 8 mins of precordial compression in 13 animals, seven of which were successfully resuscitated. Seven additional animals were randomized to serve as "sham" controls, in which cardiac arrest was not induced. MEASUREMENTS AND MAIN RESULTS: Left ventricular pressure-volume relationships utilizing the conductance method were obtained in conjunction with conventional hemodynamic and metabolic measurements at baseline and during a 6-hr interval after successful cardiac resuscitation. Progressive and striking increases in left ventricular volumes were observed after successful cardiac resuscitation. The end-diastolic volume increased from a prearrest level of 89 +/- 21 mL to a maximum of 154 +/- 53 mL (p<.05) at 360 mins after successful resuscitation. The time-coincident end-systolic volume increased from 54 +/- 21 to 126 +/- 54 mL (p<.05), such that the ejection fraction was reduced from 0.41 +/- 0.10 to 0.20 +/- 0.07 ( p<.05). Ventricular dilation was associated with marked reductions in stroke volume and ventricular work. However, compensatory increases in heart rate maintained cardiac output at levels that sustained adequate systemic oxygen delivery. The slope of the end-systolic pressure-volume relationships progressively decreased from 5.04 +/- 1.88 to 2.00 +/- 0.57 mm Hg/mL (p<.05) at 360 mins after successful resuscitation. The volume intercept at left ventricular pressure of 100 mm Hg increased from 43 +/- 19 to 94 +/- 51 mL (p=.03). Both the decrease in the slope and the increase in the volume intercept were characteristic of progressive impairment in contractile function. The rate of left ventricular pressure decrease was unchanged. Accordingly, no substantial changes in lusitropic properties were identified. Despite large increases in end-diastolic volume, the end-diastolic pressure remained unchanged. CONCLUSION: Postresuscitation myocardial dysfunction in this animal model was characterized by impaired contractile function, decreased work capability, and ventricular dilation.

Animals↗

Effects of buffer agents on postresuscitation myocardial dysfunction.

OBJECTIVES: Earlier studies demonstrated that hypertonic buffer agents administered during cardiopulmonary resuscitation (CPR) altered neither myocardial pH nor cardiac resuscitability. The rationale for the routine use of buffer agents for CPR has therefore been challenged. However, when these buffer agents are administered during CPR, they may have favorable effects on the postresuscitation course. Postresuscitation myocardial dysfunction has more recently emerged as a potentially fatal complication after successful cardiac resuscitation. Options for prevention and management of this complication have prompted the present studies, in which the effects of buffer agents administered during CPR are evaluated as to their effects on postresuscitation myocardial function and survival. DESIGN: Prospective, randomized, controlled animal study. SETTING: University animal laboratory. SUBJECTS: Forty male Sprague-Dawley rats (450 to 570 g). INTERVENTIONS: Ventricular fibrillation was induced electrically. Mechanical Ventilation and percordial compression were initiated after either a 4- or an 8-min interval of untreated cardiac arrest. Sodium bicarbonate as a CO2-generating buffer, Carbicarb and tromethamine as CO2-consuming buffers, or hypertonic saline placebo were injected as a bolus into the right atrium during CPR. Defibrillation after 10 mins of cardiac arrest and CPR was successful in each instance. No differences in the electric power required for successful resuscitation were documented. Left ventricular pressure, rate of left ventricular pressure increase measured at a left ventricular pressure of 40 mm Hg (dP/dt40), rate of left ventricular pressure decline (-dP/dt), and end-tidal PCO2 were continuously measured for 240 mins after successful resuscitation. MEASUREMENTS AND MAIN RESULTS: Decreases in coronary perfusion pressure were observed after each buffer or placebo injection. As anticipated, end-tidal PCO2 increased after bicarbonate and decreased after Carbicarb or tromethamine. Postresuscitation left ventricular function was significantly decreased in all animals. However, there was significantly less depression in rate of left ventricular pressure increase measured at a left ventricular pressure of 40 mm Hg (dP/dt40), rate of left ventricular pressure decline (-dP/dt), and a lower left ventricular diastolic pressure with both Carbicarb and tromethamine in association with significant increases in postresuscitation survival rate. When the duration of untreated cardiac arrest was increased to 8 mins, the severity of postresuscitation left ventricular dysfunction was magnified and postresuscitation myocardial function and survival were significantly improved with both CO2-generating and CO2-consuming buffer agents. CONCLUSION: Although buffer agents may not improve the success of resuscitation when administered during CPR, they may ameliorate postresuscitation myocardial dysfunction and thereby improve postresuscitation survival.

Animals↗