A comparison of myocardial function after primary cardiac and primary asphyxial cardiac arrest.

Although myocardial dysfunction after resuscitation from ventricular fibrillation (VF) has been extensively investigated, less is known of the function of the myocardium after asphyxial cardiac arrest. The present experimental study was designed to compare postresuscitation left ventricular (LV) function after cardiac arrest caused by asphyxia with that of cardiac arrest induced by dysrhythmia. Four groups of Sprague-Dawley rats, which included eight animals in each group, were investigated. In the first two groups, cardiac arrest followed asphyxia produced by neuromuscular blockade with and without airway obstruction. In a third group, cardiac arrest was induced by electrical fibrillation of the ventricle. The fourth group represented animals in which the duration of asphyxial cardiac arrest was maintained for a time interval corresponding to that of the VF group. The fourth group received approximately the same number of electrical shocks as the third (VF) group. All animals were successfully resuscitated with precordial compression and mechanical ventilation. Postresuscitation measurements, including cardiac output, LV end-diastolic pressure (LVEDP), rate of pressure rise at LV pressure of 40 mm Hg (LV dP/dt40), and negative LV dP/dt, demonstrated decreased myocardial function in each group. No differences in cardiac function were observed between the animals with primary respiratory arrest whether or not the airway was obstructed. However, disproportionate and consistently greater impairment in myocardial function followed primary cardiac arrest due to VF when compared with equal duration of asphyxial cardiac arrest. We conclude that in this healthy animal model, asphyxial cardiac arrest resulted in significantly lesser impairment of postresuscitation myocardial function when compared with cardiac arrest caused by VF.     

Beta-adrenergic blockade reduces myocardial injury during experimental cardiopulmonary resuscitation

Objectives. We attempted to determine the effects of beta-adrenergie blockade during cardiopulmonary resuscitation (CPR) on defibrillation rates and postresuscitation left ventricular function.Background. The results of previous studies suggest that propranolol administration can both reduce myocardial oxygen requirements and increase coronary perfusion pressure during CPR.Methods. Left ventricular pressure and segment length were measured before and after 5 min of CPR in 22 dogs either given epinephrine (0.015 mg/kg body weight at the onset and after 4 min) or pretreated with propranolol (2 mg/kg) and given epinephrine during CPR.Results. Despite identical epinephrine doses, coronary perfusion pressure during CPR was higher in the epinephrine plus propranolol group (p < 0.05), and defibrillation was successful in 9 of 11 dogs given both epinephrine and propranolol versus 6 of 11 dogs given epinephrine alone (p = NS). Peak and developed left ventricular pressures, left ventricular end-diastolic pressure and the peak rate of left ventricular pressure development (+dP/dt) did not differ between study groups when measured either 5 or 15 min after successful defibrillation. However, when survivors in the epinephrine group were given propranolol after CPR to eliminate compensatory sympathetic stimulation, left ventricular developed pressure and peak +dP/dt were lower (p < 0.05) despite trends toward higher left ventricular end-diastolic pressures and normalized end-diastolic segment lengths compared with dogs given propranolol before CPR.Conclusions. These findings suggest that beta-adrenergic blockade reduces myocardial injury during CPR without decreasing the likelihood of successful defibrillation or compromising spontaneous postresuscitation left ventricular function.     

A comparison of biphasic and monophasic waveform defibrillation after prolonged ventricular fibrillation

STUDY OBJECTIVE: To compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function, and duration of survival after prolonged duration of untreated ventricular fibrillation (VF), including the effects of epinephrine. DESIGN: Prospective, randomized, animal study. SETTING: Animal laboratory and university-affiliated research and educational institute. PARTICIPANTS: Domestic pigs. INTERVENTIONS: VF was induced in 20 anesthetized domestic pigs receiving mechanical ventilation. After 10 min of untreated VF, the animals were randomized. Defibrillation was attempted with up to three 150-J biphasic waveform shocks or a conventional sequence of 200-J, 300-J, and 360-J monophasic waveform shocks. When reversal of VF was unsuccessful, precordial compression was performed for 1 min, with or without administration of epinephrine. The protocol was repeated until spontaneous circulation was restored or for a maximum of 15 min. MEASUREMENTS AND RESULTS: No significant differences in the success of initial resuscitation or in the duration of survival were observed. However, significantly less impairment of myocardial function followed biphasic shocks. Administration of epinephrine reduced the total electrical energy required for successful resuscitation with both biphasic and monophasic waveform shocks. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher-energy monophasic waveform shocks for restoration of spontaneous circulation after 10 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation. Administration of epinephrine after prolonged cardiac arrest decreased the total energy required for successful resuscitation.     

Monophasic versus biphasic transthoracic countershock after prolonged ventricular fibrillation in a swine model

OBJECTIVE: We sought to compare the defibrillation efficacy of a low-energy biphasic truncated exponential (BTE) waveform and a conventional higher-energy monophasic truncated exponential (MTE) waveform after prolonged ventricular fibrillation (VF). BACKGROUND: Low energy biphasic countershocks have been shown to be effective after brief episodes of VF (15 to 30 s) and to produce few postshock electrocardiogram abnormalities. METHODS: Swine were randomized to MTE (n = 18) or BTE (n = 20) after 5 min of VF. The first MTE shock dose was 200 J, and first BTE dose 150 J. If required, up to two additional shocks were administered (300, 360 J MTE; 150, 150 J BTE). If VF persisted manual cardiopulmonary resuscitation (CPR) was begun, and shocks were administered until VF was terminated. Successful defibrillation was defined as termination of VF regardless of postshock rhythm. If countershock terminated VF but was followed by a nonperfusing rhythm, CPR was performed until a perfusing rhythm developed. Arterial pressure, left ventricular (LV) pressure, first derivative of LV pressure and cardiac output were measured at intervals for 60 min postresuscitation. RESULTS: The odds ratio of first-shock success with BTE versus MTE was 0.67 (p = 0.55). The rate of termination of VF with the second or third shocks was similar between groups, as was the incidence of postshock pulseless electrical activity (15/18 MTE, 18/20 BTE) and CPR time for those animals that were resuscitated. Hemodynamic variables were not significantly different between groups at 15, 30 and 60 min after resuscitation. CONCLUSIONS: Monophasic and biphasic waveforms were equally effective in terminating prolonged VF with the first shock, and there was no apparent clinical disadvantage of subsequent low-energy biphasic shocks compared with progressive energy monophasic shocks. Lower-energy shocks were not associated with less postresuscitation myocardial dysfunction.     

The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function.

OBJECTIVES: The purpose of this study was to compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function and duration of survival after prolonged ventricular fibrillation (VF). BACKGROUND: We have recently demonstrated that the severity of postresuscitation myocardial dysfunction was closely related to the magnitude of the electrical energy of the delivered defibrillation shock. In the present study, the effects of fixed 150-J low-energy biphasic waveform shocks were compared with conventional monophasic waveform shocks after prolonged VF. METHODS: Twenty anesthetized, mechanically ventilated domestic pigs were investigated. VF was induced with an AC current delivered to the right ventricular endocardium. After either 4 or 7 min of untreated ventricular fibrillation (VF), the animals were randomized for attempted defibrillation with up to three 150-J biphasic waveform shocks or conventional sequence of 200-, 300- or 360-J monophasic waveform shocks. If VF was not reversed, a 1-min interval of precordial compression preceded a second sequence of up to three shocks. The protocol was repeated until spontaneous circulation was restored or for a total of 15 min. RESULTS: Monophasic waveform defibrillation after 4 or 7 min of untreated VF resuscitated eight of 10 pigs. All 10 pigs treated with biphasic waveform defibrillation were successfully resuscitated. Transesophageal echo-Doppler, arterial pressure and heart rate measurements demonstrated significantly less impairment of cardiovascular function after biphasic defibrillation. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher energy monophasic waveform shocks for restoration of spontaneous circulation after 4 and 7 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation.     

Employing vasopressin during cardiopulmonary resuscitation and vasodilatory shock as a lifesaving vasopressor

Epinephrine during cardiopulmonary resuscitation (CPR) is being discussed controversially due to its beta-receptor mediated adverse effects such as increased myocardial oxygen consumption, ventricular arrhythmias, ventilation-perfusion defect, postresuscitation myocardial dysfunction, ventricular arrhythmias and cardiac failure. In the CPR laboratory simulating adult pigs with ventricular fibrillation or postcountershock pulseless electrical activity, vasopressin improved vital organ blood flow, cerebral oxygen delivery, resuscitability, and neurological recovery better than did epinephrine. In paediatric preparations with asphyxia, epinephrine was superior to vasopressin, whereas in both paediatric pigs with ventricular fibrillation, and adult porcine models with asphyxia, combinations of vasopressin and epinephrine proved to be highly effective. This may suggest that a different efficiency of vasopressors in paediatric vs. adult preparations; and different effects of dysrhythmic vs. asphyxial cardiac arrest on vasopressor efficiency may be of significant importance. Whether these theories can be extrapolated to humans is unknown at this point in time. In patients with out-of-hospital ventricular fibrillation, a larger proportion of patients treated with vasopressin survived 24 h compared with patients treated with epinephrine; during in-hospital CPR, comparable short-term survival was found in groups treated with either vasopressin or epinephrine. Currently, a large trial of out-of-hospital cardiac arrest patients being treated with vasopressin vs. epinephrine is ongoing in Germany, Austria and Switzerland. The new CPR guidelines of both the American Heart Association, and European Resuscitation Council recommend 40 U vasopressin intravenously, and 1 mg epinephrine intravenously as equally effective for the treatment of adult patients in ventricular fibrillation; however, no recommendation for vasopressin was made to date for adult patients with asystole and pulseless electrical activity, and paediatrics due to lack of clinical data. When adrenergic vasopressors were unable to maintain arterial blood pressure in patients with vasodilatory shock, continuous infusions of vasopressin ( approximately 0.04 to approximately 0.1 U/min) stabilised cardiocirculatory parameters, and even ensured weaning from catecholamines.     

Evolution of the stone heart after prolonged cardiac arrest

OBJECTIVES: We hypothesized that progressive impairment in diastolic function during cardiopulmonary resuscitation (CPR) precedes evolution of the "stone heart" after failure of CPR. We therefore measured sequential changes in left ventricular (LV) volumes and free-wall thickness of the heart during CPR in an experimental model. DESIGN: Prospective, observational animal study. SETTING: Medical research laboratory in an university-affiliated research and educational institute. SUBJECTS: Domestic pigs. METHODS: Ventricular fibrillation (VF) was induced in 40 anesthetized male domestic pigs weighing between 38 kg and 43 kg. After 4 min, 7 min, or 10 min of untreated VF, electrical defibrillation was attempted. Failing to reverse VF in each instance, precordial compression at a rate of 80/min was begun coincident with mechanical ventilation. Coronary perfusion pressures (CPPs) were computed from the differences in time-coincident diastolic aortic and right atrial pressures. Left ventricular (LV) systolic and diastolic ventricular volumes and thickness of the LV free wall were estimated with transesophageal echocardiography. The stroke volumes (SVs) were computed from the differences in decompression diastolic and compression systolic volumes. Free-wall thickness was measured on the hearts at autopsy. RESULTS: Significantly greater CPPs were generated with the 4 min of untreated cardiac arrest. Progressive reductions in LV diastolic and SV and increases in LV free-wall thickness were documented with increasing duration of untreated VF. A stone heart was confirmed at autopsy in each animal that failed resuscitative efforts. Correlations with indicator dilution method and physical measurements at autopsy corresponded closely with the echocardiographic measurements. CONCLUSION: Progressive impairment in diastolic function terminates in a stone heart after prolonged intervals of cardiac arrest.     

Epinephrine and norepinephrine in cardiopulmonary resuscitation. Effects on myocardial oxygen delivery and consumption

Norepinephrine, an alpha 1,2-beta 1,2-adrenergic agonist, seems to be an alternative to epinephrine, an alpha 1,2-beta 1,2-agonist, for restoration of spontaneous circulation in VF. We therefore studied the effect of epinephrine and norepinephrine on MDO2 and MVO2 using OCCM after five minutes of cardiopulmonary arrest in 21 pigs. After OCCM of three minutes, seven animals each received placebo (controls) or epinephrine (45 micrograms/kg) or norepinephrine (45 micrograms/kg). All drugs were given blindly. At 90 seconds after epinephrine or norepinephrine, mean arterial blood pressure was significantly higher than in the control group. Prior to cardiac arrest, MBF, measured with radioactive microspheres, was 193 +/- 30 ml/min/100 g. During CPR but before drug administration, MBF was 51 +/- 23 in the control group, 71 +/- 10 in the group with epinephrine, and 74 +/- 11 ml/min/100 g in the group with norepinephrine. At 90 seconds after epinephrine, MBF increased to 126 +/- 18 and after norepinephrine to 107 +/- 30 ml/min/100 g (p less than 0.05). Compared to OCCM alone, MDO2 increased from 9.6 +/- 1.7 to 17.1 +/- 3.2 ml/min/100 g after epinephrine and from 9.4 +/- 1.8 to 13.6 +/- 4.2 ml/min/100 g after norepinephrine (p less than 0.05). There was an increase in MVO2 from 4.0 +/- 1.5 to 9.4 +/- 3.0 ml/min/100 g after epinephrine (p less than 0.05), whereas MVO2 increased only from 4.2 +/- 0.8 to 5.1 +/- 2.0 ml/min/100 g after norepinephrine. Because epinephrine led to a greater increase in MVO2 than norepinephrine, the myocardial oxygen ER remained unchanged. The oxygen requirements of the fibrillating heart seemed to be increased via beta 2-adrenergic stimulation. In both the control and epinephrine-treated groups, only three of the seven animals could be successfully resuscitated, whereas all of the animals in the group with norepinephrine survived the 15-minute period of observation. In this model, norepinephrine, in contrast to epinephrine, improves the balance between MDO2 and MVO2 and eases restoration of spontaneous circulation.     

Precountershock cardiopulmonary resuscitation improves ventricular fibrillation median frequency and myocardial readiness for successful defibrillation from prolonged ventricular fibrillation: a randomized,controlled swine study

STUDY OBJECTIVE: After prolonged ventricular fibrillation (VF), precountershock cardiopulmonary resuscitation (CPR) will improve myocardial "readiness" for defibrillation compared with immediate defibrillation. METHODS: After 10 minutes of untreated VF, 32 swine (27+/-1 kg) were randomly assigned to receive immediate countershocks (DEFIB), CPR for 3 minutes followed by countershocks (CPR), or CPR for 3 minutes plus intravenous epinephrine followed by countershocks (CPR+EPI). VF waveform was evaluated by fast Fourier transformation. RESULTS: VF amplitude and median frequency by fast Fourier transformation decreased during the untreated VF interval in all groups, and the median frequency subsequently increased during each minute of precountershock CPR. Although the VF median frequency in the 3 groups did not differ after 10 minutes of untreated VF (8.9+/-0.8 Hz versus 8.4+/-0.5 Hz versus 7.3+/-0.5 Hz, respectively), immediately before the first shock the VF median frequency was much lower in the DEFIB group than in either the CPR or CPR+EPI groups (8.9+/-0.8 Hz versus 13.1+/-0.8 Hz versus 13.8+/-0.9 Hz, respectively; P <.01). None of the 10 animals in the DEFIB group attained return of spontaneous circulation after the first set of shocks versus 5 of 10 animals in the CPR group and 6 of 12 animals in the CPR+EPI group (DEFIB versus each CPR group; P <.05). Cardiac output 1 hour after resuscitation was substantially worse in the DEFIB group than in the CPR or CPR+EPI groups (74+/-7 mL/kg per minute versus 119+/-7 mL/kg per minute versus 104+/-15 mL/kg per minute; P <.05). CONCLUSION: Precountershock CPR can result in substantial physiologic benefits compared with immediate defibrillation in the setting of prolonged VF. Moreover, these benefits can be attained with or without the addition of intravenous epinephrine.     

Use of cardiopulmonary bypass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from post-countershock electromechanical dissociation.

STUDY OBJECTIVE: To determine the effects of cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, and standard-dose epinephrine on perfusion pressures, myocardial blood flow, and resuscitation from post-countershock electromechanical dissociation. DESIGN: Prospective, controlled laboratory investigation using a canine cardiac arrest model randomized to receive one of three resuscitation therapies. INTERVENTIONS: After the production of post-countershock electromechanical dissociation, 25 animals received ten minutes of basic CPR and were randomized to receive cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, or standard-dose epinephrine. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow was measured using a colored microsphere technique at baseline, during basic CPR, and after intervention. Immediate and two-hour resuscitation rates were determined for each group. Return of spontaneous circulation was achieved in eight of eight cardiopulmonary bypass with standard-dose epinephrine compared with four of eight high-dose epinephrine and three of eight standard-dose epinephrine animals (P less than .04). One animal was resuscitated with CPR alone and was excluded. Survival to two hours was achieved in five of eight cardiopulmonary bypass with standard-dose epinephrine, four of eight high-dose epinephrine, and three of eight standard-dose epinephrine animals (NS). Coronary perfusion pressure increased significantly in the cardiopulmonary bypass with standard-dose epinephrine group when compared with the other groups (cardiopulmonary bypass with standard-dose epinephrine, 76 +/- 45 mm Hg; high-dose epinephrine, 24 +/- 12 mm Hg; standard-dose epinephrine, 3 +/- 14 mm Hg; P less than .005). Myocardial blood flow was higher in cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine animals compared with standard-dose epinephrine animals but did not reach statistical significance. Cardiac output increased during cardiopulmonary bypass with standard-dose epinephrine (P = .001) and standard-dose epinephrine (NS) compared with basic CPR but decreased after epinephrine administration in the high-dose epinephrine group (NS). CONCLUSION: Resuscitation from electromechanical dissociation was improved with cardiopulmonary bypass and epinephrine compared with high-dose epinephrine or standard-dose epinephrine alone. However, there was no difference in survival between groups. Cardiopulmonary bypass with standard-dose epinephrine resulted in higher cardiac output, coronary perfusion pressure, and a trend toward higher myocardial blood flow. A short period of cardiopulmonary bypass with epinephrine after prolonged post-countershock electromechanical dissociation cardiac arrest can re-establish sufficient circulation to effect successful early resuscitation.     

Myocardial dysfunction after resuscitation from cardiac arrest: An example of global myocardial stunning

Objectives. This study investigated the effect of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on left ventricular systolic and diastolic function.Background. Cardiac arrest from ventricular fibrillation results in cessation of forward blood flow, including myocardial blood flow. During cardiopulmonary resuscitation, myocardial blood flow remains suboptimal. Once the heart is defibrillated and successful resuscitation achieved, reversible myocardial dysfunction, or “stunning,” may occur. The magnitude and time course of myocardial stunning from cardiac arrest is unknown.Methods. Twenty-eight domestic swine (26 ± 1 kg) were studied with both invasive and noninvasive measurements of ventricular function before and after 10 or 15 min of untreated cardiac arrest. Contrast left ventriculograms, ventricular pressures, cardiac output, isovolumetric relaxation time (tau) and transthoracic Doppler-echocardiographic studies were obtained.Results. Twenty-three of 28 animals were successfully resuscitated and postresuscitation data obtained. Left ventricular ejection fraction showed a significant reduction 30 min after resuscitation (p < 0.05). Regional wall motion analysis revealed diffuse, global left ventricular systolic dysfunction. Left ventricular end-diastolic pressure increased significantly in the postresuscitation period (p < 0.05). Isovolumetric relaxation time (tau) was significantly increased over baseline by 2 h after resuscitation (p < 0.05). Similar findings were noted with the Doppler-echocardiographic analysis, including a reduction in fractional shortening (p <0.05), a reduction in mitral valve deceleration time (p < 0.05) and an increase in left ventricular isovolumetric relaxation time in 5 h after resuscitation (p < 0.05). By 24 h, these invasive and noninvasive variables of systolic and diastolic left ventricular function had begun to improve. At 48 h, all measures of left ventricular function had returned to baseline levels.Conclusions. Myocardial systolic and diastolic dysfunction is severe after 10 to 15 min of untreated cardiac arrest and successful resuscitation. Full recovery of this postresuscitation myocardial stunning is seen by 48 h in this experimental model of ventricular fibrillation cardiac arrest.     

Comparison of standard external CPR, open-chest CPR, and cardiopulmonary bypass in a canine myocardial infarct model

STUDY OBJECTIVES: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. TYPE OF PARTICIPANTS: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). DESIGN AND INTERVENTIONS: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. MEASUREMENTS: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. MAIN RESULTS: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02). CONCLUSION: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB.     

End tidal carbon dioxide as an haemodynamic determinant of cardiopulmonary resuscitation in the rat

End tidal PCO2 (PETCO2) has been found to be a good prognostic indicator of successful resuscitation from cardiac arrest. To explore the value of this measurement further, we carried out a series of experiments during cardiac arrest and closed chest resuscitation in 14 mechanically ventilated Sprague-Dawley rats. Ventricular fibrillation (VF) was induced by a 10 mA current delivered to the right ventricular endocardium. After 4 min of VF, precordial compression was begun with a mechanical thumper and defibrillation was attempted 2 min later. PETCO2 decreased abruptly during cardiac arrest to 0.3 mm Hg (0.04 kPa). With precordial compression, it increased to 11 mm Hg (1.5 kPa). Within 3 min of successful defibrillation, there was an overshoot in the PETCO2 to 44 mm Hg (5.8 kPa) with return to baseline levels approximating those of the pre-arrest control measurements over the 60 min that followed restoration of spontaneous circulation. The PETCO2 measurement during precordial compression predicted the success of defibrillation with return of spontaneous circulation. When PETCO2 exceeded 9 mm Hg (1.2 kpA), 7 of 8 animals were successfully resuscitated. When PETCO2 was less than 9 mm Hg during precordial compression, none of six animals were successfully resuscitated. The PETCO2 correlated with the mean aortic (r = 0.71) and coronary perfusion pressure (r = 0.80) generated during precordial compression. In corroboration of previously reported observations on pigs, dogs, and human patients, PETCO2 served as a non-invasive monitor of the effectiveness of precordial compression for maintaining coronary perfusion and therefore cardiac viability during CPR. The PETCO2 was also useful in that it promptly signalled restoration of spontaneous circulation.     

The effectiveness of bystander CPR in an animal model

Several clinical studies have yielded conflicting results in examining the effectiveness of bystander CPR (BCPR). The purpose of this pilot study was to determine the effectiveness of BCPR in an animal model of cardiac arrest and resuscitation. Ten swine were instrumented for hemodynamic and regional blood flow measurements with tracer microspheres. After two minutes of ventricular fibrillation (VF), the animals received eight minutes of either BCPR (five) or no-bystander CPR (NBCPR; five). Defibrillation was then attempted in both groups. If unsuccessful, CPR was begun and epinephrine 0.02 mg/kg was administered. Defibrillation was attempted again three and one-half minutes after epinephrine administration. Regional myocardial and cerebral blood flows were measured 30 seconds and five and one-half minutes after initiation of BCPR and one minute after epinephrine administration. In the BCPR group, myocardial blood flow was initially 29.0 +/- 33.2 and decreased to 15.0 +/- 21.5 mL/min/100 g during the last two and one-half minutes of BCPR. Cortical cerebral blood flow was initially 2.0 +/- 2.8 and fell to 0.6 +/- 0.8 mL/min/100 g during the last two and one-half minutes of BCPR. There were no statistical differences in myocardial blood flow and cerebral blood flow between the initial or late stages of BCPR (P greater than .14). There were no statistical differences in myocardial blood flow and cerebral blood flow between BCPR and NBCPR groups after epinephrine administration (P greater than .09).(ABSTRACT TRUNCATED AT 250 WORDS)     

Targeted alpha(1A)-adrenergic receptor overexpression induces enhanced cardiac contractility but not hypertrophy

Activation of the alpha(1A)-adrenergic receptor (alpha(1A)-AR)/Gq pathway has been implicated as a critical trigger for the development of cardiac hypertrophy. However, direct evidence from in vivo studies is still lacking. To address this issue, transgenic mice with cardiac-targeted overexpression of the alpha(1A)-AR (4- to 170-fold) were generated, using the rodent alpha-myosin heavy chain promoter. Heterozygous animals displayed marked enhancement of cardiac contractility, evident from increases in dP/dt(max) (80%, P<0.0001), dP/dt(max)/LVP(inst) (76%, P<0.001), dP/dt(max):dP/dt(min) (104%, P<0.0001), and fractional shortening (33%, P<0.05). Moreover, changes in the dP/dt(max)-end-diastolic volume relationship provided load-independent evidence of a primary increase in contractility. Blood pressure and heart rate were largely unchanged, and there was a small increase in (-)norepinephrine-stimulated, but not basal, phospholipase C activity. Increased contractility was directly related to the level of receptor overexpression and could be completely reversed by acute alpha(1A)- but not beta-AR blockade. Despite the robust changes in contractility, transgenic animals displayed no morphological, histological, or echocardiographic evidence of left ventricular hypertrophy. In addition, apart from an increase in atrial natriuretic factor mRNA, expression of other hypertrophy-associated genes was unchanged. To our knowledge, these data provide the first in vivo evidence for an inotropic action of the alpha(1A)-AR.     

The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation

This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival.     

Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction

BACKGROUND: It is known that left ventricular systolic function at rest does not correlate well with exercise capacity of patients with heart failure. However, the contribution of left ventricular diastolic dysfunction, especially during exercise, to exercise capacity of cardiac patients remains to be determined. OBJECTIVE: To determine the impact of left ventricular systolic and diastolic function during exercise on exercise capacity of patients with left ventricular dysfunction after myocardial infarction. METHODS: A symptom-limited exercise test was performed with measurements for hemodynamics and uptake of oxygen (Vo2) of 26 men who had previously suffered myocardial infarction. These patients were divided into two groups according to their peak Vo2 (group 1 with peak Vo2 > or = 16 ml/kg per min, n= 13; and group 2 with peak Vo2 < 16 ml/kg per min, n= 13). Pulmonary arterial pressure, left ventricular and systemic arterial pressure, and cardiac output were measured at rest and during exercise. RESULTS: At rest, there was no difference between the two groups in terms of hemodynamic parameters except for minimal dP/dt, minimal left ventricular pressure (LVP) and time constant for decay of left ventricular pressure (tau). During peak exercise, cardiac output, left ventricular end-diastolic pressure (EDP), minimal dP/dt, minimal LVP, and tau for the two groups were significantly different. Furthermore, peak Vo2 was significantly correlated with T, minimal LVP, minimal dP/dt, EDP, and maximal dP/dt during peak exercise for the whole group of patients. CONCLUSION: Left ventricular diastolic function during exercise, i.e. diastolic reserve, may be an important determinant of exercise capacity of patients with left ventricular dysfunction after myocardial infarction.     

Immediate countershock versus cardiopulmonary resuscitation before countershock in a 5-minute swine model of ventricular fibrillation arrest

STUDY OBJECTIVE: Prior laboratory and clinical studies demonstrate that cardiopulmonary resuscitation (CPR) preceding countershock of prolonged ventricular fibrillation (VF) increases the likelihood of successful cardiac resuscitation. The lower limit of VF duration at which time preshock CPR provides no benefit has not been specifically studied. The purpose of this study was to compare countershock and cardiac resuscitation outcome between immediate countershock of VF of 5-minute duration and CPR without drug therapy before countershock in a swine model. METHODS: VF was induced in anesthetized and instrumented swine. After 5 minutes of VF, animals received 1 of 2 treatments. Animals in group 1, a "historical" control group (n=20), received immediate countershock followed by CPR and repeated shocks if needed. Group 2 animals (n=11) received CPR for 90 seconds preceding countershock, then continued CPR and repeated countershock if necessary. Drugs were not administered to either group, and resuscitation efforts were discontinued if a perfusing rhythm was not restored within 10 minutes of the first countershock. First shock success rate (defined as termination of VF), the number of shocks required to terminate VF, and the cardiac resuscitation rate were compared between groups. RESULTS: The first shock terminated VF in 13 of 20 group 1 animals and 2 of 11 group 2 animals (P =.023). All but 1 animal in group 1 developed pulseless electrical activity after countershock. All but 1 animal in group 1 were eventually successfully resuscitated with CPR and repeated shocks if necessary. Four group 2 animals could not be resuscitated (P =.042). CONCLUSION: Although effective in improving outcome of prolonged VF, CPR preceding countershock of VF of 5-minute duration does not improve the response to the first shock, decrease the incidence of postshock pulseless electrical activity, or the rate of return of circulation. In this study, CPR preceding countershock resulted in a significantly lower cardiac resuscitation rate.     

Cardiopulmonary resuscitation with a novel chest compression device in a porcine model of cardiac arrest: improved hemodynamics and mechanisms

OBJECTIVES: The goal of this study was to determine the magnitude and mechanisms of hemodynamic improvement of an automated, load-distributing band device (AutoPulse, Revivant Corp., Sunnyvale, California) compared with conventional cardiopulmonary resuscitation (C-CPR). BACKGROUND: Improved blood flow during cardiopulmonary resuscitation (CPR) enhances survival from cardiac arrest. METHODS: AutoPulse CPR (A-CPR) and C-CPR were performed on 30 pigs (16 +/- 4 kg) 1 min after induction of ventricular fibrillation. Aortic and right atrial pressures were measured with micromanometers. Regional flows were measured with microspheres; A-CPR and C-CPR were performed with 20% anterior-posterior chest compression, with (n = 10) and without (n = 10) epinephrine. A pressure transducer was advanced down the airways during chest compressions (n = 10), and magnetic resonance imaging (MRI) was performed. RESULTS: AutoPulse CPR improved coronary perfusion pressure (CPP) (aortic - right atrial pressure) without epinephrine (A-CPR 21 +/- 8 mm Hg vs. C-CPR 14 +/- 6 mm Hg, mean +/- SD, p < 0.0001) and with epinephrine (A-CPR 45 +/- 11 mm Hg vs. C-CPR 17 +/- 6 mm Hg, p < 0.0001). AutoPulse CPR improved myocardial flow without epinephrine and cerebral and myocardial flow with epinephrine (p < 0.05). AutoPulse CPR also produced greater myocardial flow at every CPP (p < 0.01). With A-CPR, high airway pressure was noted distal to the carina, which corresponded to an area of airway collapse on MRI, and which was not present with C-CPR. CONCLUSIONS: AutoPulse CPR improved hemodynamics over C-CPR in this pig model. AutoPulse CPR with epinephrine can produce pre-arrest levels of myocardial and cerebral flow. The improved hemodynamics with A-CPR appear to be mediated through airway collapse, which likely impedes airflow and helps maintain higher levels of intrathoracic pressure.     

Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock.

BACKGROUND. Early countershock of ventricular fibrillation has been shown to improve immediate and long-term outcome of cardiac arrest. However, a number of investigations in the laboratory and in the clinical population indicate that immediate countershock of prolonged ventricular fibrillation most commonly is followed by asystole or a nonperfusing spontaneous cardiac rhythm, neither of which rarely respond to current therapy. The use of epinephrine in doses greater than those currently recommended has recently been shown to improve both cerebral and myocardial perfusion during cardiopulmonary resuscitation (CPR). The purpose of this study was to compare cardiac resuscitation outcome between immediate countershock of prolonged ventricular fibrillation with high-dose epinephrine therapy and conventional CPR before countershock of prolonged ventricular fibrillation in a canine model. METHODS AND RESULTS. After sedation, intubation, induction of anesthesia, and instrumentation, ventricular fibrillation was electrically induced in 28 dogs. After 7.5 minutes of ventricular fibrillation, animals were randomly allocated to two treatment groups: group 1, immediate countershock followed by recommended advanced cardiac life support (ACLS) interventions, or group 2, 0.08 mg/kg epinephrine and manual closed-chest CPR before countershock and ACLS. In both groups, ACLS was continued until a spontaneous perfusing rhythm was restored or for 20 minutes (total arrest time, 27.5 minutes). A spontaneous perfusing rhythm was restored in three of 14 group 1 animals and in nine of 14 group 2 animals (p = 0.014 by sequential analysis method of Whitehead). Coronary perfusion pressure (aortic minus right atrial pressure during CPR diastole) before countershock was significantly greater in group 2 (21 +/- 7 mm Hg) when compared with mean circulatory pressure in group 1 (9 +/- 8, p less than 0.01). CONCLUSIONS. The findings of this study suggest that a brief period of myocardial perfusion before countershock improves cardiac resuscitation outcome from prolonged ventricular fibrillation.