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(Circulation. 1995;92:3089-3093.)
© 1995 American Heart Association, Inc.

Articles

Epinephrine Increases the Severity of Postresuscitation Myocardial Dysfunction

Wanchun Tang, MD; Max Harry Weil, MD, PhD; Shijie Sun, MD; Marko Noc, MD; Liying Yang, MD; Raúl J Gazmuri, MD

From the Institute of Critical Care Medicine, Palm Springs, Calif.

Correspondence to Max Harry Weil, MD, PhD, Institute of Critical Care Medicine, 1695 North Sunrise Way, Palm Springs, CA 92262.

	Abstract

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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 ß-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 -adrenergic agent, phenylephrine, when epinephrine was combined with a ß₁-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 -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 -adrenergic agonist or blockade of ß₁-adrenergic actions of epinephrine reduced postresuscitation myocardial impairment and prolonged survival.

Key Words: myocardium • cardiopulmonary resuscitation

	Introduction

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Until recently, cardiac resuscitation research focused primarily on the success of the initial stage of cardiac resuscitation and therapeutic options by which a viable rhythm and spontaneous circulation would be restored. We have designated this stage as stage 1. However, experimental studies by our group have demonstrated substantial impairment of ventricular function after resuscitation from cardiac arrest, which accounted for a high incidence in postresuscitation fatalities. We have now designated this stage as stage 2.¹ Indeed, postresuscitation myocardial dysfunction may explain, at least in part, the fatality rate (>30%) that has been documented in human patients within the first 72 hours after initially successful resuscitation from cardiac arrest.^{2 3}

Epinephrine has been the preferred adrenergic amine for the treatment of human cardiac arrest for almost 30 years.^{4 5 6 7 8 9} There is persuasive evidence that its efficacy is due to its -adrenergic vasopressor effects. The ß-adrenergic actions, however, are not of proven benefit. To the contrary, potential adverse effects of epinephrine have been identified. These are likely to be due to its ß-inotropic actions, which provoke disproportionate increases in myocardial oxygen consumption and thereby increase the severity of myocardial ischemia.^{10 11 12}

The present study was designed to examine whether these ß-adrenergic effects of epinephrine, when administered during cardiopulmonary resuscitation (CPR), adversely affect postresuscitation myocardial function when compared with those of a more selective -agonist, phenylephrine, and when epinephrine was combined with a short-acting ß₁-adrenergic blocking agent. The duration of untreated ventricular fibrillation and CPR before attempted defibrillation was adjusted to secure the success of cardiac resuscitation for the purpose of this study, which was with focus on postresuscitation myocardial dysfunction.

	Methods

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All animals received humane care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and published by the National Institute of Health (NIH publication 86-32, revised 1985).

Preparation
The experiments were performed in a previously described rat model of cardiac arrest and cardiac resuscitation. This model has provided cardiopulmonary and metabolic measurements that are comparable to those documented in larger mammals and human patients.^{13 14} Briefly, 40 Sprague-Dawley rats (450 to 570 g) were fasted overnight except for free access to water. The animals were anesthetized by intraperitoneal injection of 45 mg/kg pentobarbital sodium supplemented with additional doses of 10 mg/kg at hourly intervals, except that no pentobarbital was administered for 30 minutes before induction of cardiac arrest. The trachea was orally intubated with a 14-gauge cannula (Quick-Cath, Vicra Division, Travenol Laboratory) mounted on a blunt needle with a 145° angled tip. For measurement of P_ETCO₂, the respiratory gas was sampled through a side manifold interposed between the tracheal cannula and the respirator. The PCO₂ was measured with a side-stream infrared CO₂ analyzer (model 200, Instrumentation Laboratories). For measurement of left ventricular pressure and both dP/dt₄₀ and negative dP/dt, a Teflon catheter (UTX 022; internal diameter, 0.6 mm; outer diameter, 0.97 mm; length, 8 cm; Becton Dickinson) was advanced into the left ventricle from the right carotid artery. Through the left external jugular vein, an 18-gauge polyethylene catheter (CPMS-401J-Fa, Cook) was advanced through the superior vena cava into the right ventricle. Guided by pressure monitoring, the catheter was slowly withdrawn into the right atrium. Right atrial pressure was measured with reference to the midchest with a high-sensitivity transducer (P-23-9b, Spectramed). This catheter was also used to sample blood from the right atrium. Through the right external jugular vein, a 3F pediatric radial artery catheter (model C-PUM-301J, Cook) was advanced into the right atrium. A precurved guide wire supplied with the catheter was then advanced through the catheter into the right ventricle until an endocardial ECG was observed. Through the right femoral artery, a Teflon catheter (UTX 022, Becton Dickinson) was advanced into the thoracic aorta for measurement of aortic pressure with a model TNF-R transducer (Abbott Critical Care). Through the left femoral artery and left femoral vein, catheters (UTX 022, Becton Dickinson) were advanced into the abdominal aorta and inferior vena cava for sampling arterial blood and blood replacement. Rectal temperature was measured continuously with a rectal thermistor. Conventional lead II ECGs were recorded with skin electrodes (model E220, In-vivo Metric).

Experimental Procedure
Experiments were performed in two groups of animals. In group 1, the duration of untreated ventricular fibrillation (VF) was 4 minutes; in group 2, the duration of untreated VF was 8 minutes. Accordingly, the study was performed in 8 subsets of animals. The investigators were blinded to the intervention until immediately before induction of VF, at which time the principal investigator opened a sealed envelope, the contents of which provided for randomization of the animal to receive either epinephrine, phenylephrine, epinephrine with esmolol, or saline placebo.

The tracheal tube was connected to a volume-controlled ventilator as previously described.^{13 14} Ventilation was initially established at a tidal volume of 0.65 mL/100 g animal weight and a frequency of 100 breaths per minute 15 minutes before induction of cardiac arrest. The tidal volume was then adjusted to compensate for the volume of gas sampled by the CO₂ analyzer to maintain P_ETCO₂ between 30 and 35 mm Hg. The inspired O₂ fraction (FIO₂) was 1.0. A progressive increase in 60-Hz current to a maximum of 8 mA was then delivered to the right ventricular endocardium, and current flow was continued for 3 minutes. Mechanical ventilation was discontinued immediately after induction of VF. Either 4 or 8 minutes after onset of VF, precordial compression was initiated and continued for 8 minutes with a pneumatically driven mechanical chest compressor. Compression was maintained at a rate of 200 · min^-1 with equal compression-relaxation duration (ie, 50% duty cycle). Compression depth was equivalent to 30% of the anteroposterior diameter of the chest and was adjusted to maintain coronary perfusion pressure (CPP) at 25 to 30 mm Hg. Coincident with the start of precordial compression, mechanical ventilation was resumed. Compression and ventilation were synchronized to maintain two compressions for each ventilation.

After 4 minutes of precordial compression, 0.2 mL of either epinephrine (30 µg/kg), phenylephrine (300 µg/kg), epinephrine with esmolol (30 µg + 300 µg/kg), or 0.9N NaCl solution (saline placebo) was bolus injected into the right atrium. After 8 minutes of precordial compression, a 2-J DC countershock was delivered between the anterior chest and the back. If VF was not reversed within 2 seconds, a second 2-J DC countershock was delivered. In unsuccessfully resuscitated animals, precordial compression was then resumed for 30 seconds before delivery of a second sequence of countershocks. Resuscitated animals were monitored for an additional 4 hours. One hour after successful resuscitation, each of the resuscitated animals was reanesthetized with pentobarbital in doses of 10 mg/mg. These doses were repeated at hourly intervals thereafter for a total of 4 doses. All catheters including the endotracheal tube were then removed. The animals were then observed for a total of 48 hours, after which they were euthanized by intraperitoneal injection of pentobarbital (150 mg/kg). Autopsy was routinely performed to identify adverse effects of the interventions and especially traumatic injuries of thoracic and/or abdominal organs.

Measurements
A 2-mL bolus of arterial blood from a donor rat of the same colony was transfused into the inferior vena cava 30 seconds before withdrawal of 1 mL aliquots of blood each from the aorta and the right atrium. PO₂, PCO₂, and lactic acid were measured on these samples by techniques previously described.¹⁵ At 1 and 7 minutes of precordial compression and at 5, 30, 60, 120, 180, and 240 minutes after resuscitation, these measurements were repeated. Aortic, left ventricular, and right atrial pressures, ECG, and P_ETCO₂ were continuously monitored on a six-channel recorder (model 2600, Gould Inc) and recorded on a PC-based data acquisition system supported by CODAS software. The CPP was calculated as the difference between decompression diastolic aortic and time-coincident right atrial pressure measured at the end of each minute of precordial compression.

Myocardial function was assessed from measurements of left ventricular pressure. The rate of left ventricular pressure increase was measured at a left ventricular pressure of 40 mm Hg (dP/dt₄₀) as indicative of isovolemic contractility.^{16 17} The rate of left ventricular pressure decline (-dP/dt) was measured as an estimate of myocardial relaxation. These were measured by analog differentiation of the left ventricular pressure. The frequency response of the system was 35 Hz with optimal damping.

Statistical Analysis
For measurements between groups, ANOVA and Scheffé's multicomparison techniques were used. Comparisons between time-based measurements within each group were performed with ANOVA repeated measurements. The outcome differences were analyzed with Fisher's exact test. Measurements are reported as mean±SD. A value of P<.05 was considered significant.

	Results

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Baseline hemodynamic and blood analytical measurements did not differ significantly among the eight subsets. There were no differences in aortic systolic pressure and blood gas measurements between groups during CPR and after successful resuscitation. After intra-atrial injection of epinephrine, CPP increased from 25±2 to 35±4 mm Hg (P<.01). Comparable increases in CPP were observed with phenylephrine (26±1 to 37±2 mm Hg, P<.01) and with the epinephrine-esmolol combination (24±2 to 33±3 mm Hg). There was no increase in CPP after intra-atrial injection of placebo. Increases in CPP after injection of each of the adrenergic drugs in the subsets in which untreated VF was prolonged to 8 minutes were approximately the same. All animals treated with adrenergic agents were successfully resuscitated with transthoracic countershock. After saline placebo, 4 of 5 animals were successfully resuscitated when untreated VF was of 4-minute duration and 3 of 5 when it was of 8-minute duration (Table). The duration of survival after successful resuscitation was significantly decreased in epinephrine-treated and placebo-treated animals when compared with phenylephrine-treated and epinephrine-esmolol–treated animals after 4 or 8 minutes of untreated VF. The total energy required for successful defibrillation after both 4 and 8 minutes was significantly greater in placebo-treated animals (P<.01) and epinephrine-treated animals (P<.01) when compared with animals treated with phenylephrine or epinephrine-esmolol.

View this table: [in this window] [in a new window]   Table 1. Effects of Adrenergic Agents or Placebo on Resuscitability, Survival, and Total Delivered Transthoracic Energy Before Successful Defibrillation

As previously observed by us,¹ myocardial contractility as measured by dP/dt₄₀ was significantly decreased in all animals after successful resuscitation. When the duration of untreated cardiac arrest was increased from 4 to 8 minutes, such decreases in dP/dt₄₀ were magnified. However, the greatest impairment of myocardial contractility followed treatment with epinephrine (Fig 1). The decreases in negative dP/dt (Fig 2), the increases in left ventricular end-diastolic pressure (Fig 3), and heart rate (Fig 4) also were magnified after placebo and after epinephrine.

View larger version (46K): [in this window] [in a new window]   Figure 1. Plots show effects of epinephrine, phenylephrine, epinephrine with esmolol, or with saline placebo on postresuscitation left ventricular dP/dt40. Mean±SD values are shown. Top, Effects of the adrenergic drug or placebo on untreated ventricular fibrillation (VF) of 4-minute duration are shown. Bottom, Duration of untreated VF was prolonged to 8 minutes. DF indicates defibrillation; PC, 8 minutes of precordial compression; PH., phenylephrine; E+E, epinephrine with esmolol; SAL., saline placebo; EPI., epinephrine; Rx, injection of adrenergic drug or placebo; and BL, baseline. *P<.01 vs epinephrine-treated animals.

View larger version (46K): [in this window] [in a new window]   Figure 2. Plots show effects of epinephrine, phenylephrine, epinephrine with esmolol, or with saline placebo on postresuscitation left ventricular negative dP/dt. Mean±SD values are shown. Top, Effects of the adrenergic drug or placebo on untreated ventricular fibrillation (VF) of 4-minute duration are shown. Bottom, Duration of untreated VF was prolonged to 8 minutes. DF indicates defibrillation; PC, 8 minutes of precordial compression; PH., phenylephrine; E+E, epinephrine with esmolol; SAL., saline placebo; EPI., epinephrine; BL, baseline; and Rx, injections of adrenergic drug or placebo. *P<.01 vs epinephrine-treated animals.

View larger version (47K): [in this window] [in a new window]   Figure 3. Plots show effects of epinephrine, phenylephrine, epinephrine with esmolol or with saline placebo on postresuscitation left ventricular end-diastolic pressure (LVEDP). Mean±SD values are shown. Top, Interval of untreated ventricular fibrillation (VF) was 4 minutes. Bottom, Interval was prolonged to 8 minutes. DF indicates defibrillation; PC, 8 minutes of precordial compression; PH., phenylephrine; E+E, epinephrine with esmolol; SAL., saline placebo; EPI., epinephrine; BL, baseline; and Rx, injection of adrenergic drug or placebo. *P<.01 vs epinephrine-treated animals.

View larger version (53K): [in this window] [in a new window]   Figure 4. Plots show effects of epinephrine, phenylephrine, epinephrine with esmolol, or saline placebo on postresuscitation heart rate. Mean±SD values are shown. Top, Interval of untreated ventricular fibrillation (VF) was 4 minutes. Bottom, Interval was prolonged to 8 minutes. DF indicates defibrillation; PC, 8 minutes of precordial compression; PH., phenylephrine; E+E, epinephrine with esmolol; SAL., saline placebo; EPI., epinephrine; BL, baseline; and Rx, injection of adrenergic drug or placebo. *P<.01 vs epinephrine-treated animals.

	Discussion

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The present study demonstrated that in this rat model of cardiac arrest and resuscitation, the reversal of global myocardial ischemia after cardiac resuscitation is followed by myocardial dysfunction. Its severity is increased with increasing duration of untreated cardiac arrest. Epinephrine significantly increases the severity of postresuscitation myocardial dysfunction with consequent reduction in duration of postresuscitation survival when compared with the selective -agonist phenylephrine and after epinephrine was combined with the ß₁-blocking agent esmolol. We also observed that epinephrine-treated animals required a larger number of electrical countershocks before successful conversion to a viable rhythm and restoration of spontaneous circulation.

The doses of epinephrine were empirically established by earlier trials such as to ensure that it resulted in increased coronary perfusion pressure to minimal levels of 30 mm Hg. This yielded both a sufficiently severe global ischemic insult to the heart and consequently substantial postresuscitation contractile dysfunction, yet with 95% resuscitability.

In 1906, Crile and Dolley¹⁸ demonstrated that epinephrine restored spontaneous circulation in a dog model when cardiac arrest was induced by asphyxia. During the 1960s, Redding and Pearson^{19 20 21 22} reexamined the effects of epinephrine together with those of selective -agonist, methoxamine, in the same setting of asphyxia-induced VF in dogs. They observed greater success when a more selective -adrenergic amine was administered. More recently, Roberts et al²³ compared the effects of a pure -agonist, methoxamine, and epinephrine on myocardial and cerebral blood flow during CPR in dogs. They found that methoxamine produced significantly greater myocardial and cerebral blood flow during precordial compression. This was associated with significantly improved postresuscitation cardiac output and survival when compared with epinephrine. These experimental observations have not yet affected the American Heart Association Guidelines for CPR, in which epinephrine remains as the adrenergic agent of first choice.^{5 6 7} Moreover, there is currently little distinction between the benefits and detriments of adrenergic vasopressor drugs in clinical settings of sudden death due to cardiac cause and the much smaller incidence of cardiac arrest due to noncardiac causes including asphyxiation. The present study uses a model in which a primary cardiac insult is induced.

The mechanism by which epinephrine administered during CPR increases the severity of postresuscitation myocardial dysfunction after primary VF was initially suggested by Ditchey and Lindenfeld.¹¹ These investigators pointed to its ß effects, by which the myocardial oxygen requirement was increased. During cardiac resuscitation in dogs, a bolus injection of 1 mg of epinephrine followed by continuous infusion of 0.2 mg/min over an interval of 10 minutes increased myocardial lactate content and decreased myocardial ATP content even though coronary blood flow was doubled. Comparable increases in myocardial blood flow that followed infusion of a more selective ₁-agonist, methoxamine, were not accompanied by such increases in the oxygen consumption.¹⁰ The importance of distinguishing between benefits and detriments of ß-agonists was emphasized by Halperin and Guerci.¹² The normal balance of myocardial energy supply and demand is disrupted during VF because the demand of the myocardium for energy exceeds that which is available from a reserve of high-energy phosphates and from anaerobic glycolysis. Consequently, the net supply of ATP available to the myocyte decreases to a critical level.^{24 25} Decreases in myocardial tissue ATP during ischemia are correlated with the severity of myocardial injury and therefore predictive of myocyte survival when coronary perfusion is restored.^{26 27 28}

Equally important, the severity of postresuscitation myocardial dysfunction was significantly reduced in the present studies when epinephrine was administered in combination with esmolol. Since esmolol blocked ß₁-adrenergic receptors, it would be likely to decrease the oxygen requirements of the myocardium during VF and thereby minimize global ischemic injury. Ditchey et al²⁹ had earlier presented experimental evidence in dogs that both resuscitability and postresuscitation myocardial function were improved after nonspecific ß-adrenergic blockade with propranolol. In their studies, coronary perfusion pressure was augmented when epinephrine was combined with propanolol. In the present study, in which epinephrine was combined with a more selective ß₁-adrenergic blocking agent, this effect was not apparent. This would further support the hypothesis proposed by Ditchey et al²⁹ in that ß₂-blockade may have accounted for the increases in CPP reported by them. Additional evidence that epinephrine has unfavorable postresuscitation cardiovascular effects was published by Berg et al.³⁰ In a pig model of CPR, high doses of epinephrine (0.2 mL/kg) administered during CPR were followed by postresuscitation tachycardia and a substantial increase in early mortality.

In the present study, we also observed that epinephrine-treated animals required a larger number of electrical countershocks for conversion of VF to a regular rhythm. This was consistent with earlier reports by Niemann and his associates³¹ and by Wright et al,³² which provided evidence that the ß-adrenergic actions of epinephrine increased the severity of myocardial ischemic injury and thereby the likelihood of reentrant and ectopic ventricular dysrhythmias.^{31 32}

We conclude that epinephrine, when administered during CPR under the experimental conditions of this and predecessor studies in other species, significantly increases the severity of postresuscitation myocardial dysfunction in consequence of its ß₁-adrenergic actions. This is associated with significantly greater postresuscitation mortality. It would be appropriate to reevaluate epinephrine as the drug of first choice for cardiac resuscitation after "sudden death."

	Acknowledgments

 
This study was supported in part by an American Heart Association Grant-in-Aid and the Laerdal Foundation for Acute Medicine, Inc, Stavanger, Norway.

Received March 6, 1995; revision received May 29, 1995; accepted July 5, 1995.

	References

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				American Heart Association 2005 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of Pediatric and Neonatal Patients: Pediatric Advanced Life Support Pediatrics, May 1, 2006; 117(5): e1005 - e1028. [Full Text] [PDF]

				G. A.A.M. Cammarata, M. H. Weil, S. Sun, L. Huang, X. Fang, and W. Tang Levosimendan Improves Cardiopulmonary Resuscitation and Survival by KATP Channel Activation J. Am. Coll. Cardiol., March 7, 2006; 47(5): 1083 - 1085. [Full Text] [PDF]

				C. L. McCaul, P. J. McNamara, D. Engelberts, G. J. Wilson, A. Romaschin, A. N. Redington, and B. P. Kavanagh Epinephrine Increases Mortality after Brief Asphyxial Cardiac Arrest in an In Vivo Rat Model Anesth. Analg., February 1, 2006; 102(2): 542 - 548. [Abstract] [Full Text] [PDF]

				Part 7.2: Management of Cardiac Arrest Circulation, December 13, 2005; 112(24_suppl): IV-58 - IV-66. [Full Text] [PDF]

				Part 12: Pediatric Advanced Life Support Circulation, December 13, 2005; 112(24_suppl): IV-167 - IV-187. [Full Text] [PDF]

				A. A. El-Menyar The Resuscitation Outcome: Revisit the Story of the Stony Heart Chest, October 1, 2005; 128(4): 2835 - 2846. [Abstract] [Full Text] [PDF]

				L. Huang, M. H. Weil, S. Sun, W. Tang, and X. Fang Carvedilol Mitigates Adverse Effects of Epinephrine During Cardiopulmonary Resuscitation Journal of Cardiovascular Pharmacology and Therapeutics, April 1, 2005; 10(2): 113 - 120. [Abstract] [PDF]

				J. Kolarova, Z. Yi, I. M. Ayoub, and R. J. Gazmuri Cariporide Potentiates the Effects of Epinephrine and Vasopressin by Nonvascular Mechanisms During Closed-Chest Resuscitation Chest, April 1, 2005; 127(4): 1327 - 1334. [Abstract] [Full Text] [PDF]

				S. Sun, M. H. Weil, W. Tang, T. Kamohara, and K. Klouche {delta}-Opioid receptor agonist reduces severity of postresuscitation myocardial dysfunction Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H969 - H974. [Abstract] [Full Text] [PDF]

				P. C. Dyke II and J. D. Tobias Vasopressin: Applications in Clinical Practice J Intensive Care Med, July 1, 2004; 19(4): 220 - 228. [Abstract] [PDF]

				C. R. Killingsworth, C.-C. Wei, L. J. Dell'Italia, J. L. Ardell, M. A. Kingsley, W. M. Smith, R. E. Ideker, and G. P. Walcott Short-Acting {beta}-Adrenergic Antagonist Esmolol Given at Reperfusion Improves Survival After Prolonged Ventricular Fibrillation Circulation, May 25, 2004; 109(20): 2469 - 2474. [Abstract] [Full Text] [PDF]

				W. Tang, M. H. Weil, S. Sun, D. Jorgenson, C. Morgan, K. Klouche, and D. Snyder The effects of biphasic waveform design on post-resuscitation myocardial function J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1228 - 1235. [Abstract] [Full Text] [PDF]

				J. T. Niemann, D. Garner, E. Khaleeli, and R. J. Lewis Milrinone Facilitates Resuscitation From Cardiac Arrest and Attenuates Postresuscitation Myocardial Dysfunction Circulation, December 16, 2003; 108(24): 3031 - 3035. [Abstract] [Full Text] [PDF]

				T. Pellis, M. H. Weil, W. Tang, S. Sun, J. Xie, L. Song, and P. Checchia Evidence Favoring the Use of an {alpha}2-Selective Vasopressor Agent for Cardiopulmonary Resuscitation Circulation, November 25, 2003; 108(21): 2716 - 2721. [Abstract] [Full Text] [PDF]

				Y. Ji, B. Li, T. D. Reed, J. N. Lorenz, M. A. Kaetzel, and J. R. Dedman Targeted Inhibition of Ca2+/Calmodulin-dependent Protein Kinase II in Cardiac Longitudinal Sarcoplasmic Reticulum Results in Decreased Phospholamban Phosphorylation at Threonine 17 J. Biol. Chem., June 27, 2003; 278(27): 25063 - 25071. [Abstract] [Full Text] [PDF]

				L. Cao, M. H. Weil, S. Sun, and W. Tang Vasopressor Agents for Cardiopulmonary Resuscitation Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2003; 8(2): 115 - 121. [Abstract] [PDF]

				L. Song, M. H. Weil, W. Tang, S. Sun, and T. Pellis Cardiopulmonary resuscitation in the mouse J Appl Physiol, October 1, 2002; 93(4): 1222 - 1226. [Abstract] [Full Text] [PDF]

				K. Klouche, M. H. Weil, S. Sun, W. Tang, H. P. Povoas, T. Kamohara, and J. Bisera Evolution of the Stone Heart After Prolonged Cardiac Arrest* Chest, September 1, 2002; 122(3): 1006 - 1011. [Abstract] [Full Text] [PDF]

				T. KAMOHARA, M. H. WEIL, W. TANG, S. SUN, H. YAMAGUCHI, K. KLOUCHE, and J. BISERA A Comparison of Myocardial Function after Primary Cardiac and Primary Asphyxial Cardiac Arrest Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1221 - 1224. [Abstract] [Full Text] [PDF]

				W. Tang, M. H. Weil, S. Sun, H. P. Povoas, K. Klouche, T. Kamohara, and J. Bisera A Comparison of Biphasic and Monophasic Waveform Defibrillation After Prolonged Ventricular Fibrillation Chest, September 1, 2001; 120(3): 948 - 954. [Abstract] [Full Text] [PDF]

				K. G. Lurie, W. G. Voelckel, T. Zielinski, S. McKnite, P. Lindstrom, C. Peterson, V. Wenzel, K. H. Lindner, N. Samniah, and D. Benditt Improving Standard Cardiopulmonary Resuscitation with an Inspiratory Impedance Threshold Valve in a Porcine Model of Cardiac Arrest Anesth. Analg., September 1, 2001; 93(3): 649 - 655. [Abstract] [Full Text] [PDF]

				A. C. Krismer, Q. H. Hogan, V. Wenzel, K. H. Lindner, U. Achleitner, S. Oroszy, B. Rainer, A. Wihaidi, V. D. Mayr, P. Spencker, et al. The Efficacy of Epinephrine or Vasopressin for Resuscitation During Epidural Anesthesia Anesth. Analg., September 1, 2001; 93(3): 734 - 742. [Abstract] [Full Text] [PDF]