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Biomedical subjects

M H Weil

Publications and source records attributed to M H Weil.

At least 19 recordsLinked to original sources
PubMed1995

Epinephrine increases the severity of postresuscitation myocardial dysfunction.

BACKGROUND: Epinephrine has been the mainstay for cardiac resuscitation for more than 30 years. Its vasopressor effect by which it increases coronary perfusion pressure is likely to favor initial resuscitation. Its beta-adrenergic action, however, may have detrimental effects on postresuscitation myocardial function when administered before resuscitation because it increases myocardial oxygen consumption. In the present study, our focus was on postresuscitation effects of epinephrine when this adrenergic agent was administered during cardiopulmonary resuscitation. Postresuscitation myocardial functions were compared with those of a selective alpha-adrenergic agent, phenylephrine, when epinephrine was combined with a beta 1-adrenergic blocking agent, esmolol, and saline placebo. METHODS AND RESULTS: Ventricular fibrillation was induced in 40 Sprague-Dawley rats. Mechanical ventilation and precordial compression was initiated either 4 or 8 minutes after the start of ventricular fibrillation. The adrenergic drug or saline placebo was administered as a bolus after 4 minutes of precordial compression. Defibrillation was attempted 4 minutes later. Left ventricular pressure, dP/dt40, and negative dP/dt were continuously measured for an interval of 240 minutes after successful cardiac resuscitation. Except for saline placebo, comparable increases in coronary perfusion pressure were observed after each drug intervention. The number of countershocks required for restoration of spontaneous circulation was significantly greater for epinephrine-treated animals (10 +/- 8) when compared with phenylephrine-treated animals (1.8 +/- 0.4, P < .01) and with animals treated with epinephrine combined with esmolol (1.6 +/- 0.9, P < .01). After resuscitation, dP/dt40 and negative dP/dt were significantly decreased and left ventricular end-diastolic pressure was significantly increased in each animal when compared with prearrest levels. However, the greatest impairment followed epinephrine, and this was associated with significantly greater heart rate and the shortest interval of postresuscitation survival of 8 +/- 4 hours, whereas placebo controls survived for 12 +/- 11 hours. Phenylephrine-treated animals survived for 41 +/- 10 hours (P < .01 versus epinephrine), and animals that received a combination of epinephrine and esmolol survived for 35 +/- 11 hours (P < .01 versus epinephrine). When the duration of untreated cardiac arrest was increased from 4 to 8 minutes, the severity of postresuscitation left ventricular dysfunction was magnified, but disproportionate decreases in postresuscitation survival were again observed with placebo and epinephrine when compared with alpha-adrenergic agonists. CONCLUSIONS: In an established rodent model after resuscitation following cardiac arrest, epinephrine significantly increased the severity of postresuscitation myocardial dysfunction and decreased duration of survival. More selective alpha-adrenergic agonist or blockade of beta 1-adrenergic actions of epinephrine reduced postresuscitation myocardial impairment and prolonged survival.

Adrenergic Agonists↗
PubMed1995

Effect of arrest time on the hemodynamic efficacy of precordial compression.

OBJECTIVES: To evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO2 as predictors of resuscitability after prolonged cardiac arrest. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one Sprague-Dawley rats, including three groups of seven animals in each group. INTERVENTIONS: Ventricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: All animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO2 produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest. CONCLUSIONS: The efficacy of precordial compression--as measured by coronary perfusion pressure and end-tidal CO2 concentration after prolongation of untreated cardiac arrest--was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO2 failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest.

Animals↗
PubMed1995

Mechanisms of myocardial hypercarbic acidosis during cardiac arrest.

During the global myocardial ischemia of cardiac arrest and during regional myocardial ischemia due to local impairment of coronary blood flow, intramyocardial carbon dioxide tensions (Pmco2) of ischemic myocardium increase to levels exceeding 400 Torr. The mechanism of such myocardial hypercarbic acidosis is as yet incompletely understood, specifically whether these increases in Pmco2 are due to increased oxidative metabolism, decreased CO2 removal, or buffering of metabolic acids. We therefore measured Pmco2 and the total CO2 content of rat hearts harvested before, during, and after resuscitation from cardiac arrest. Pmco2 significantly increased from an average of 63 to 209 Torr during a 4-min interval of untreated ventricular fibrillation. This was associated with concurrent decreases in intracellular pH from an average of 7.03 to 6.02 units. The total CO2 content of the myocardium simultaneously decreased from 17.0 to 16.5 mmol/kg. Accordingly, increases in Pmco2 and [H+] were observed in the absence of increases in the total CO2 content and therefore the calculated myocardial bicarbonate. These observations in the rat model implicate buffering of metabolic acids by bicarbonate rather than increases in CO2 production or decreases in CO2 removal as the predominant mechanism accounting for myocardial hypercarbia.

Acidosis↗
PubMed1995

Mechanical ventilation may not be essential for initial cardiopulmonary resuscitation.

BACKGROUND: In a rodent model of cardiac arrest and resuscitation in which the inspired gas mixture was enriched with oxygen, resuscitability and survival were unaffected by positive pressure ventilation. In the present study, in a larger animal model, tidal volumes generated during precordial compression and with spontaneous gasping were quantitated. METHODS: Domestic pigs with an average weight of 34 kg were anesthetized with pentobarbital. Ventricular fibrillation (VF) was induced electrically. Precordial compression was begun after 4 min of untreated VF. Each of 22 animals received one of two interventions in conjunction with precordial compression: positive pressure ventilation with oxygen or oxygen supplied at the port of a tracheal tube at ambient pressure. After 8 min of precordial compression, defibrillation was attempted. RESULTS: Only very moderate increases in arterial PCO2 were documented during cardiopulmonary resuscitation in the absence of mechanical ventilation but arterial oxygen tension was consistently in excess of 100 mm Hg. Cardiac resuscitability and 48-h survival were approximately the same in animals maintained on inspired oxygen whether or not they were mechanically ventilated (7/11 or 8/11). In the absence of mechanical ventilation, precordial compression and spontaneous gasping yielded minute volumes that exceeded 5 L. CONCLUSION: Positive pressure mechanical ventilation did not improve resuscitability or postresuscitation outcome in this porcine model of cardiac arrest.

Animals↗
PubMed1995

Airway protection during experimental CPR.

BACKGROUND: Experimental studies recently demonstrated that positive pressure ventilation may not be essential for initial cardiopulmonary resuscitation. Nevertheless, oxygen enrichment of inspired gas mixtures and spontaneous gasping were associated with increased resuscitability and survival after cardiac arrest. However, as yet unresolved is the benefit of early airway control under conditions simulating "sudden death" due to ventricular fibrillation. METHODS: Twenty adult, male Sprague-Dawley rats were randomly assigned to one of two groups in which the airway was unprotected or protected by an oropharyngeal airway of our design. Cardiac arrest was induced by an alternating current delivered to the right ventricular endocardium. Oxygen was delivered to a hood that was loosely applied over the head of the each animal at a flow rate of 1 L/min. Precordial compression was initiated after 4 min of untreated ventricular fibrillation and defibrillation was attempted 6 min later. After spontaneous circulation had been restored, a tracheostomy was performed and the animals were mechanically ventilated with 100% oxygen for an additional interval of 1 h. Animals were then returned to their cages and observed for an additional 24 h. RESULTS: Spontaneous circulation was restored in each of the animals who had an oropharyngeal airway and nine of ten animals in the absence of an artificial airway. In each group, seven animals survived for more than 24 h. Animals in which the airway had been protected had significantly greater frequency of spontaneous gasping (28 +/- 13/min vs 13 +/- 9/min; p < 0.05) and significantly higher arterial oxygen saturation (77 +/- 19% vs vs 55 +/- 25%; p < 0.05). CONCLUSION: In the setting of experimental cardiac resuscitation, the insertion of an artificial airway increased the frequency of spontaneous gasping and arterial oxygenation. Nevertheless, no significant differences in resuscitability or postresuscitation survival were associated with insertion of the artificial airway.

Airway Obstruction↗
PubMed1992

Extracorporeal circulation as an alternative to open-chest cardiac compression for cardiac resuscitation.

Open-chest direct cardiac compression represents a more potent but highly invasive option for cardiac resuscitation when conventional techniques of closed-chest cardiac resuscitation fail after prolonged cardiac arrest. We postulated that venoarterial extracorporeal circulation might be a more effective intervention with less trauma. In the setting of human cardiac resuscitation, however, controlled studies would be limited by strategic constraints. Accordingly, the effectiveness of open-chest cardiac compression was compared with that of extracorporeal circulation after a 15-min interval of untreated ventricular fibrillation in a porcine model of cardiac arrest. Sixteen domestic pigs were randomized to resuscitation by either peripheral venoarterial extracorporeal circulation or open-chest direct cardiac compression. During resuscitation, epinephrine was continuously infused into the right atrium, and defibrillation was attempted by transthoracic countershock at 2-min intervals. Systemic blood flows averaged 198 ml.kg-1.min-1 with extracorporeal circulation. This contrasted with direct cardiac compression, in which flows averaged only 40 ml.kg-1.min-1. Coronary perfusion pressure, the major determinant of resuscitability on the basis of earlier studies, was correspondingly lower (94 vs 29 mm Hg). Extracorporeal circulation, in conjunction with transthoracic DC countershock and epinephrine, successfully reestablished spontaneous circulation in each of eight animals after 15 min of untreated ventricular fibrillation. This contrasted with the outcome after open-chest cardiac compression, in which spontaneous circulation was reestablished in only four of eight animals (p = .038). We conclude that extracorporeal circulation is a more effective alternative to direct cardiac compression for cardiac resuscitation after protracted cardiac arrest.

Acidosis↗
PubMed1992

Cardiac anaphylaxis in the Sprague-Dawley rat.

Anaphylactic shock was induced in pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats that had been sensitized 21 days earlier to crystallized ovalbumin. The sensitization was confirmed by passive cutaneous anaphylaxis test. Antigen challenge produced an immediate reduction in mean aortic pressure from 168 to 67 mm Hg within 1 minute after intravenous injection of ovalbumin. Plasma histamine increased from 4.5 to 128 ng/ml within 5 minutes after injection of antigen. There were no changes in airway or esophageal pressures after antigen challenge. Left ventricular diastolic pressure was increased, and contractility, as measured by the rate of change of left ventricular pressure (dP/dt), was decreased over an interval exceeding 90 minutes. When isolated, constant flow--perfused hearts from sensitized Sprague-Dawley rats were challenged with antigen, decreases in left ventricular function were observed associated with decreased positive and negative maximum rate of change of left ventricular pressure (dP/dtmax). This experimental model in the rat therefore demonstrated selective myocardial impairment with reduced inotropism and lusitropism after anaphylaxis.

Anaphylaxis↗
PubMed1992

Monophosphoryl lipid A attenuates the effects of endotoxic shock in pigs.

Monophosphoryl lipid A (MPL) is a nontoxic lipid A derivative that maintains many of the beneficial immunomodulatory activities of the parent lipopolysaccharide molecule, including the induction of tolerance to endotoxin. The hemodynamic effects of Salmonella minnesota MPL (300 mg/kg) and S. minnesota lipopolysaccharide (300 micrograms/kg) were compared in 20 minipigs. Decreases in cardiac output and arterial pressure and increases in pulmonary artery pressure and lactic acidosis were significantly greater in animals treated with lipopolysaccharide. These changes were associated with peak tumor necrosis factor (TNF) levels of 1373 +/- 79 U/ml in animals treated with LPS and 157 +/- 31 U/ml in animals treated with MPL. Ten minipigs were subsequently randomized to receive S. minnesota MPL (30 micrograms/kg) or diluent intravenously 48 hours before receiving S. minnesota lipopolysaccharide (300 micrograms/kg IV). MPL significantly attenuated lipopolysaccharide-induced decreases in mean arterial pressure, cardiac index, stroke volume index, and mixed venous oxygen saturation. At baseline, no significant difference could be seen in TNF levels between diluent and MPL pigs. TNF levels peaked 2 hours after LPS infusion at 1190 +/- 156 U/ml in diluent pigs and at 539 +/- 126 U/ml in MPL pigs (p less than 0.05). Each of the pigs pretreated with MPL survived endotoxic shock, whereas only one of the five diluent pigs survived. These observations are consistent with the induction of endotoxin tolerance by pretreatment with MPL.

Animals↗
PubMed1991

Buffer solutions may compromise cardiac resuscitation by reducing coronary perfusion presssure.

OBJECTIVE: --To investigate the effects of hypertonic buffer solutions on coronary perfusion pressure (CPP) and resuscitability during experimental closed-chest cardiac resuscitation. DESIGN: --Randomized, placebo-controlled trial. SETTING: --Mammalian research laboratory. PARTICIPANTS: --Forty-four domestic pigs. INTERVENTIONS: --Cardiac arrest was induced by ventricular fibrillation in mechanically ventilated pigs anesthetized with pentobarbital sodium. Precordial compression was started at the third minute of untreated ventricular fibrillation and maintained for an interval of 8 minutes. A hypertonic solution of sodium bicarbonate, Carbicarb (an equimolar mixture of sodium bicarbonate and sodium carbonate [International Medication Systems, Ltd]), or sodium chloride or an isotonic solution of sodium chloride was infused into the right atrium over a 1-minute interval starting at the sixth minute of ventricular fibrillation. Restoration of spontaneous circulation was attempted by DC transthoracic countershock after 11 minutes of ventricular fibrillation. MAIN OUTCOME MEASURES: --Plasma osmolality, CPP, and cardiac resuscitability. RESULTS: --Infusion of hypertonic buffer and sodium chloride solutions increased plasma osmolality from an average of 280 to 330 mOsm/kg. This was accompanied by a significant decrease in the aortic pressures and CPPs generated during precordial compression. No such changes occurred after infusion of isotonic sodium chloride. Restoration of spontaneous circulation, as in earlier studies, was contingent on the levels of CPP prior to attempted defibrillation. Accordingly, none of 13 animals in which the CPP declined to less than 10 mm Hg after infusion of the hypertonic solutions were successfully resuscitated. This contrasted with nine animals that received isotonic sodium chloride and served as controls. Coronary perfusion pressure consistently exceeded 10 mm Hg in these control animals, and spontaneous circulation was restored in each instance. CONCLUSIONS: --Hypertonic solutions and specifically buffer solutions administered in the absence of vasopressor agents may adversely affect cardiac resuscitation efforts by reducing CPP below critical thresholds.

Animals↗
PubMed1991

Long-term survival of patients with AIDS, Pneumocystis carinii pneumonia, and respiratory failure.

OBJECTIVE: --To evaluate the long-term survival of patients admitted to the medical intensive care unit, Cook County Hospital, Chicago, Ill, with Pneumocystis carinii pneumonia and acute respiratory failure. DESIGN: --Cohort study over a 4-year period. SETTING: --Municipal teaching hospital. PATIENTS: --Seventy-three consecutive patients who had 75 episodes of P carinii pneumonia and acute respiratory failure were followed up from the time of hospital admission until their deaths or the termination of the study. OUTCOME MEASURES: --Duration of survival from the time of initial hospital admission with diagnoses of P carinii pneumonia and acute respiratory failure. RESULTS: --Consistent with recent reports of improved short-term outcome, the immediate hospital survival was 47% (35/75). The 1-year survival was 37% (95% confidence interval, 26% to 49%). Two patients have survived for 40 months. Almost three quarters of the patients who survived hospitalization lived for at least 1 year. CONCLUSIONS: --The long-term prognosis for patients with the acquired immunodeficiency syndrome, P carinii pneumonia, and acute respiratory failure is now substantially better than anticipated. Respiratory failure due to P carinii pneumonia does not necessarily signify the terminal phase of human immunodeficiency virus infection. Accordingly, patients with the acquired immunodeficiency syndrome, P carinii pneumonia, and acute respiratory failure can be appropriate candidates for life support in medical intensive care units.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Reversible impairment of myocardial contractility due to hypercarbic acidosis in the isolated perfused rat heart.

BACKGROUND AND METHODS: Striking increases in PCO2 of the myocardium have recently been documented during cardiac arrest. The purpose of the present study was to investigate selective effects of hypercarbia as distinct from acidosis on left ventricular contractile function and oxygen utilization. An isolated, spontaneously beating rat heart preparation was utilized. The perfusate was equilibrated with gases containing 5%, 10%, 20%, and 30% CO2. In a subset of experiments, the [H+] was adjusted independently of PCO2 by decreasing the concentration of HCO3-. RESULTS: When the PCO2 of the perfusate was progressively increased from 36 to 146 torr (4.8 to 29.5 kPa), the left ventricular systolic pressure (LVSP) generated by the isolated heart and the maximum rate of pressure change in the left ventricle (dP/dt) were decreased to 20% of their control values. However, comparable acidosis in the absence of hypercarbia produced only minimal decreases in the LVSP or dP/dt such that contractility remained at greater than or equal to 88%. Increases in the perfusate PCO2 but not in the perfusate H+ were highly correlated with decreases in both myocardial contractility and oxygen consumption (r2 = .88). CONCLUSION: Hypercarbia rather than acidosis accounts for decreased contractility and oxygen utilization in the isolated perfused rat heart.

Acidosis↗
PubMed1991

Unaccounted for anion in metabolic acidosis during severe sepsis in humans.

OBJECTIVE: To quantitate the contribution of lactate, phosphate, urate, total serum proteins, and unidentified anions to the anion gap in patients with severe sepsis. DESIGN: Thirty critically ill patients with evidence of severe sepsis and systemic hypoperfusion were prospectively studied. MEASUREMENTS: The anion gap was calculated as [Na+] + [K+] - [Cl-] - [HCO3]. A corrected anion gap was calculated as the anion gap minus the anionic contribution of lactate, phosphate, urate, and total serum proteins. The corrected anion gap is a marker of unmeasured anion less unmeasured cation concentration. RESULTS: The mean anion gap was 21.8 +/- 1.4 mmol/L and the corrected anion gap was 3.7 +/- 0.8 mmol/L. The mean arterial blood lactate concentration was 5.9 +/- 0.8 mmol/L. The magnitude of the lactate concentration correlated linearly with the anion gap (r2 = .61, lactate = 0.4 anion gap - 3.9, n = 30, p less than .01). The corrected anion gap was greater than 0 in 24 (80%) of 30 patients. The magnitude of the corrected anion gap correlated linearly with the anion gap (r2 = .66, corrected anion gap = 0.5 anion gap - 6.3, n = 30, p less than .01). Since the slope of the regression line for estimating corrected anion gap from anion gap was 0.5, the contribution of unmeasured anions was as important as lactate in determining the anion gap. CONCLUSION: These data indicate that lactic acidosis does not entirely account for the metabolic acidosis during severe sepsis. Furthermore, the increased corrected anion gap suggests the presence of an unidentified anion (or anions) that is (or are) responsible, in large part, for the development of metabolic acidosis in patients with sepsis.

Acid-Base Equilibrium↗
PubMed1991

Hypercarbic acidosis reduces cardiac resuscitability.

BACKGROUND AND METHODS: Marked increases in myocardial hypercarbia and acidosis accompany cardiac arrest and resuscitation. To investigate whether hypercarbic acidosis independent of oxygenation is of itself detrimental to cardiac resuscitation, three groups of six Sprague-Dawley rats were ventilated with gas mixtures containing concentrations of inspired CO2 (FICO2) of 0.0, 0.3, or 0.5, with oxygen fractions held constant at 0.5. After 4 mins of ventricular fibrillation, mechanical chest compressions were initiated with a pneumatic thumper; 2 mins later, transthoracic defibrillation was attempted. RESULTS: Each animal ventilated with FICO2 of 0.0 or 0.3 was successfully resuscitated. However, none of the animals ventilated with FICO2 of 0.5, in which aortic pH was less than 6.67 and aortic PCO2 was greater than 200 torr (greater than 26.7 kPa), was resuscitated (p less than .001). This finding contrasted with a second control group of seven identically treated animals which, in the absence of cardiac arrest, demonstrated no adverse effects after ventilation with an FICO2 of 0.5. CONCLUSIONS: Increases in FICO2 to levels of 0.5 under conditions of constant arterial oxygenation and controlled coronary perfusion pressure preclude successful resuscitation in this rodent model of CPR.

Acidosis, Respiratory↗