The effects of potassium-ATP channel modulation on ventricular fibrillation and defibrillation in the pig heart

BACKGROUND: Drugs acting on the cardiac ATP-sensitive potassium (K-ATP) channels may modulate responses to ischaemia and arrhythmogenesis. We investigated the effects of K-ATP channel modulation on frequency patterns of ventricular fibrillation (VF) and on defibrillation threshold (DFT). METHODS AND RESULTS: Each group of 24 pigs randomly received intravenous levcromakalim (LKM) 40 microgram/kg (K-ATP agonist), glibenclamide (Glib) 20 mg/kg (K-ATP antagonist), saline or vehicle. Firstly, QTc interval was measured before and after drug. VF was then induced by endocardial stimulation and its power spectra and dominant frequencies over 15 min determined by fast Fourier transformation. Secondly, transthoracic DFT was determined (step-up/step-down protocol) before and after each drug. LKM reduced QTc interval (e.g., lead II, 354-321 ms, P<0.05) and increased the dominant VF frequency between 6 and 8 min (9.5+/-0.5 Hz at 6.5 min compared with 7.2+/-0.6 Hz (saline), 7.4+/-0.8 Hz (vehicle), 6.8+/-0.5 Hz (Glib), P=0.03). LKM reduced (to 57.2+/-2.1 mmHg) and Glib increased (to 107.8+/-6.1) mean arterial BP compared with saline (80.3+/-5.6) and vehicle (87. 6+/-7.1; P<0.01). There was no significant difference in defibrillation threshold energy, current or voltage, after any drug. CONCLUSIONS: Activation of K-ATP channels reduced blood pressure and QTc interval. The lack of major effect on VF dominant frequency and DFT of either LKM or Glib suggests that prior administration of similar drugs to patients should not prejudice outcome from VF cardiac arrest.     

Automated external defibrillation versus manual defibrillation for prolonged ventricular fibrillation: lethal delays of chest compressions before and after countershocks

STUDY OBJECTIVE: We sought to determine whether the delays in chest compressions and defibrillation associated with an automated external defibrillator would adversely affect outcome compared with manual defibrillation in a swine model of out-of-hospital prolonged ventricular fibrillation. METHODS: After 8 minutes of untreated ventricular fibrillation, 16 swine (33+/-4 kg) were randomly assigned to automated external defibrillator defibrillation or manual defibrillation with the same biphasic truncated exponential waveform 150-J shock through the same type of pads. Defibrillation with the automated external defibrillator was performed as recommended by the manufacturer, and manual defibrillation was provided per American Heart Association Guidelines. The primary outcome measure was 24-hour survival with good neurologic outcome. Data are described as means+/-SD. RESULTS: None of 8 animals in the automated external defibrillator group survived for 24 hours, whereas 5 of 8 animals in the manual defibrillation group survived 24 hours, all with good neurologic outcome (P=.027). The time interval from simulated defibrillator arrival to first compressions was 98+/-18 seconds in the automated external defibrillator group versus 68+/-15 seconds in the manual defibrillation group. In particular, the interval from first shock to first chest compressions was 46+/-18 seconds versus 22+/-16 seconds, respectively. The mean percentage of time that chest compressions were performed in the first minute after the first countershock was 15%+/-13% versus 40%+/-15%, respectively. As a result, return of spontaneous circulation within 5 minutes of simulated defibrillator arrival occurred in only 1 of 8 animals in the automated external defibrillator group versus 6 of 8 animals in the manual defibrillation group. CONCLUSION: The longer delays in chest compressions with automated external defibrillator defibrillation versus manual defibrillation can worsen the outcome from prolonged ventricular fibrillation.     

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.     

Myocardial oxygen delivery/consumption during cardiopulmonary resuscitation: a comparison of epinephrine and phenylephrine

Our study compared the effect of high-dose epinephrine with the pure alpha-agonist phenylephrine on regional myocardial blood flow (MBF), myocardial oxygen delivery (MDO2), myocardial oxygen consumption (MVO2), and defibrillation rates during CPR. Fifteen swine weighing more than 15 kg were instrumented for measurement of regional MBF using radiolabeled tracer microspheres. Measurements of regional MBF, MDO2, and MVO2 were made during normal sinus rhythm. Ventricular fibrillation was induced and persisted for ten minutes. CPR was begun using a pneumatic compression device. Regional MBF, MDO2, and MVO2 were measured during CPR. Following three minutes of CPR, animals (N = 15) were allocated to one of three groups (n = 5): Group 1, epinephrine 0.2 mg/kg; Group 2, phenylephrine 0.1 mg/kg; or Group 3, phenylephrine 1.0 mg/kg. Measurements of regional MBF, MDO2, and MVO2 were repeated after drug administration. Extraction ratios, defined as MVO2/MDO2, were calculated during normal sinus rhythm, CPR, and after drug administration. Defibrillation was attempted 3 1/2 minutes after drug administration. There was no significant difference in MBF, MDO2, MVO2, and extraction ratio during normal sinus rhythm and CPR for any of the groups. Total MBF following drug administration was 67.2 +/- 49.4 mL/min/100 g for the group receiving epinephrine 0.2 mg/kg; 7.0 +/- 7.1 mL/min/100 g for the group receiving phenylephrine 0.1 mg/kg; and 36.7 +/- 21.1 mL/min/100 g for the group receiving phenylephrine 1.0 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Median frequency--a new parameter for predicting defibrillation success rate

STUDY HYPOTHESIS: Current American Heart Association guidelines recommend immediate defibrillation of ventricular fibrillation. When this is unsuccessful, there are no guidelines to help determine the optimum time at which to defibrillate after the administration of an alpha-adrenergic agonist. Previous studies have shown that the median frequency of the ventricular fibrillation ECG signal correlates with myocardial perfusion during CPR. We hypothesized that median frequency could predict the success of defibrillation and thus accurately determine the most appropriate time at which to defibrillate during ventricular fibrillation. STUDY POPULATION: Twenty-two mixed-breed swine weighing more than 15 kg were studied. METHODS: Ventricular fibrillation was induced electrically, and the ventricular fibrillation ECG signal was analyzed using fast Fourier analysis. After ten minutes of ventricular fibrillation, mechanical CPR was begun. After three minutes of CPR, the animals received one of three alpha-adrenergic agonists and CPR was continued. Defibrillation was attempted three and one-half minutes after drug administration. The average median frequency 20 seconds before defibrillation was calculated. Sensitivity and specificity of median frequency with respect to defibrillation success were determined. RESULTS: A median frequency of 9.14 Hz had a sensitivity of 100% and a specificity of 92.31% in predicting the results of defibrillation in this model. CONCLUSION: The median frequency may serve as a valuable parameter to guide defibrillation therapy during ventricular fibrillation.     

Effect of application of force to self-adhesive defibrillator pads on transthoracic electrical impedance and countershock success.

STUDY OBJECTIVE: To examine the effect of the application of force to self-adhesive defibrillator pads on transthoracic electrical impedance and countershock success. METHODS: A prospective, randomized, controlled pilot study was carried out in an experimental animal laboratory, involving 32 mixed-breed swine weighing 36.5 to 55.7 kg each. Ventricular fibrillation (VF) was induced, and the animals were randomly allocated to 1 of 4 groups, with 8 animals per group. Animals in groups I and II remained in VF for 30 seconds; those in groups III and IV remained in VF for 5 minutes. At the end of the VF period, up to 3 countershocks were given. In groups I and III, countershocks were delivered through the self-adhesive defibrillator pads alone; in groups II and IV, they were delivered through the defibrillator pads with 25 lb of applied force. Any animal without return of spontaneous circulation after 3 countershocks was given epinephrine after 1 minute of CPR, followed by 1 additional minute of CPR and 1 additional countershock if required. RESULTS: The main measurements included baseline and countershock transthoracic impedance, cumulative countershock success rate, and 30-minute survival rate. Application of 25 lb of force to the defibrillator pads significantly decreased transthoracic impedance, compared with baseline values (group II, 15. 1% decrease; group IV, 16.1% decrease). The first-shock success rate was higher when force was applied during the countershock (87.5% versus 50% for groups II and I, respectively; 62.5% and 37.5% for groups IV and III, respectively). In the animals who experienced 5 minutes of VF, there were greater rates of success after the second, third, and fourth countershocks when force was applied (group IV) than when no force was applied (group III). Groups I and II (VF for 30 seconds) demonstrated 100% survival at 30 minutes. Group IV had a higher 30-minute survival rate (3/8 animals) than did group III (1/8). However, the rates of countershock success and 30-minute survival were not statistically different among the groups. CONCLUSION: Application of force to self-adhesive defibrillator pads decreases transthoracic impedance during countershock. This effect may contribute to improving the countershock success rate.     

Rapid induction of cerebral hypothermia is enhanced with active compression-decompression plus inspiratory impedance threshold device cardiopulmonary resusitation in a porcine model of cardiac arrest.

OBJECTIVES: A rapid, ice-cold saline flush combined with active compression-decompression (ACD) plus an inspiratory impedance threshold device (ITD) cardiopulmonary resusitation (CPR) will cool brain tissue more effectively than with standard CPR (S-CPR) during cardiac arrest (CA). BACKGROUND: Early institution of hypothermia after CPR and return of spontaneous circulation improves survival and outcomes after CA in humans. METHODS: Ventricular fibrillation (VF) was induced for 8 min in anesthetized and tracheally intubated pigs. Pigs were randomized to receive either ACD + ITD CPR (n = 8) or S-CPR (n = 8). After 2 min of CPR, 30 ml/kg ice-cold saline (3 degrees C) was infused over the next 3 min of CPR via femoral vein followed by up to three defibrillation attempts (150 J, biphasic). If VF persisted, epinephrine (40 microg/kg) and vasopressin (0.3 U/kg) were administered followed by three additional defibrillation attempts. Hemodynamic variables and temperatures were continuously recorded. RESULTS: All ACD + ITD CPR pigs (8 of 8) survived (defined as 15 min of return of spontaneous circulation [ROSC]) versus 3 of 8 pigs with S-CPR (p < 0.05). In survivors, brain temperature (degrees C) measured at 2-cm depth in brain cortex 1 min after ROSC decreased from 37.6 +/- 0.2 to 35.8 +/- 0.3 in ACD + ITD CPR versus 37.8 +/- 0.2 to 37.3 +/- 0.3 in S-CPR (p < 0.005). Immediately before defibrillation: 1) right atrial systolic/diastolic pressures (mm Hg) were lower (85 +/- 19, 4 +/- 1) in ACD + ITD CPR than S-CPR pigs (141 +/- 12, 8 +/- 3, p < 0.01); and 2) coronary perfusion pressures (mm Hg) were higher in ACD + ITD CPR (28.3 +/- 2) than S-CPR pigs (17.4 +/- 3, p < 0.01). CONCLUSIONS: A rapid ice-cold saline infusion combined with ACD + ITD CPR during cardiac arrest induces cerebral hypothermia more rapidly immediately after ROSC than with S-CPR.     

Modification of ventricular fibrillation activation patterns induced by local stretching

INTRODUCTION: We hypothesize that local modifications in electrophysiological properties, when confined to zones of limited extent, induce few changes in the global activation process during ventricular fibrillation (VF). To test this hypothesis, we produced local electrophysiological modifications by stretching a circumscribed zone of the left ventricular wall in an experimental model of VF. METHODS AND RESULTS: In 23 Langendorff-perfused rabbit hearts frequency, time-frequency and time-domain techniques were used to analyze the VF recordings obtained with two epicardial multiple electrodes before, during, and after local stretching produced with a left intraventricular device. Acute local stretching accelerated VF in the stretched zone reversibly and to a variable degree, depending on the magnitude of stretch and the time elapsed from its application. In the half time (5 minutes) of the analyzed period, a longitudinal lengthening of 12.1 +/- 4.5% (vertical axis) and 11.8 +/- 6.2% (horizontal axis) in the stretched zone produced an increase in the dominant frequency (DFr) (15.2 +/- 1.9 versus 18.8 +/- 2.5 Hz, P < 0.0001), a decrease in mean VV interval (63 +/- 8 versus 53 +/- 6 msec, P < 0.001), and an increase in the complexity of the activation maps-with more areas of conduction block and more breakthrough patterns (23% versus 37%, P < 0.01), without significant changes in the percentages of complete reentry patterns (9% versus 9%, ns). Simultaneously, in the nonstretched zone, no variations were observed in the DFr (15.2 +/- 2.1 versus 15.3 +/- 2.5 Hz, ns), mean VV intervals (66 +/- 8 versus 65 +/- 8 msec, ns), or types and percentages of maps with breakthrough (25% versus 20%, ns) or reentry patterns (12% versus 8%, ns). No significant correlation was observed between the DFr in the two zones (R = 0.24, P = 0.40). CONCLUSION: Local stretching increases the electrophysiological heterogeneity of myocardium and accelerates and increases the complexity of VF in the stretched area, without significantly modifying the occurrences of the types of VF activation patterns in the nonstretched zone.     

Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs

BACKGROUND: It is unknown whether repeated dosages of vasopressin or epinephrine given early or late during basic life support cardiopulmonary resuscitation (CPR) may be able to increase coronary perfusion pressure above a threshold between 20 and 30 mm Hg that renders defibrillation successful. METHODS AND RESULTS: After 4 minutes of cardiac arrest, followed by 3 minutes of basic life support CPR, 12 animals were randomly assigned to receive, every 5 minutes, either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 U/kg, respectively; n=6) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively; n=6). Another 12 animals were randomly allocated after 4 minutes of cardiac arrest, followed by 8 minutes of basic life support CPR, to receive, every 5 minutes, either vasopressin (late vasopressin: 0.4 and 0.8 U/kg, respectively; n=6), or epinephrine (late epinephrine: 45 and 200 microg/kg, respectively; n=6). Defibrillation was attempted after 22 minutes of cardiac arrest. Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after early vasopressin compared with early epinephrine (50+/-4 versus 34+/-3 mm Hg, P<0.02; 42+/-5 versus 15+/-3 mm Hg, P<0.0008; and 37+/-5 versus 11+/-3 mm Hg, P<0. 002, respectively). Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after late vasopressin compared with late epinephrine (40+/-3 versus 22+/-4 mm Hg, P<0.004, and 32+/-4 versus 15+/-4 mm Hg, P<0.01, respectively). All vasopressin animals survived 60 minutes, whereas no epinephrine pig had return of spontaneous circulation (P<0.05). CONCLUSIONS: Repeated administration of vasopressin but only the first epinephrine dose given early and late during basic life support CPR maintained coronary perfusion pressure above the threshold that is needed for successful defibrillation.     

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)     

Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model.

STUDY OBJECTIVES: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING: Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS: Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation.     

Prehospital experience with defibrillation of coarse ventricular fibrillation: a ten-year review

Early defibrillation of patients with coarse ventricular fibrillation has been implicated as a predictor of survival in prehospital cardiac arrest. A retrospective study of our experience with prehospital defibrillation was conducted to define the relationship between rapid delivery of first countershock and survival, determine whether a relationship exists between the number of countershocks delivered and the save rate, and assist clinicians with general guidelines for termination of advanced life support efforts in the presence of ventricular fibrillation refractory to multiple defibrillation attempts. During the ten-year study period, adult, nontraumatic, nonpoisoned, witnessed arrests with an initial rhythm of coarse ventricular fibrillation were reviewed. Of 1,497 patients, 25% survived, 13% were paramedic-witnessed (PW) arrests, and 87% were non-paramedic-witnessed (NPW) arrests. The mean PW shock time, defined as time from arrest to first shock, was 1.6 +/- 3.7 minutes with a save rate of 37%. The mean NPW shock time was 10.2 +/- 5.1 minutes with a save rate of 23% (P less than or equal to .001). Thirty-two percent of PW arrests were converted to a spontaneous rhythm with pulses after the first countershock compared with 9% of NPW arrests (P less than or equal to .001). There was a dramatic decrease in PW arrests obtaining a perfusing rhythm after the first countershock attempt with each minute delay in electrical countershock up to three minutes; a plateau effect was evident after three minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Ionized hypocalcemia during prolonged cardiac arrest and closed-chest CPR in a canine model

STUDY BACKGROUND: Free or ionized calcium (Ca+2) is known to play a critical role in normal cardiovascular function, and Ca+2 administration in the setting of ionized hypocalcemia has been shown to improve indexes of cardiac function. The value of Ca+2 administration in the setting of cardiac arrest and resuscitation is unproven and controversial, in large part because ionized Ca+2 levels during cardiac arrest and resuscitation have not been adequately studied and exogenous calcium therapy may worsen ischemic cellular injury. STUDY PURPOSE: To measure free calcium during prolonged cardiac arrest and CPR in a canine model. METHODS AND MEASUREMENTS: Central arterial and venous catheters were positioned in nine dogs, and ventricular fibrillation (VF) was induced electrically. After seven and one-half minutes of VF, countershocks were administered, and CPR was initiated and performed in accordance with current recommendations for 20 minutes. At five-minute intervals during resuscitation efforts, arterial pH, ionized Ca+2, and lactate as well as aortic pressure were measured. RESULTS: During resuscitation, average systolic arterial pressure was 50 mm Hg. Within five minutes of instituting CPR, ionized Ca+2 significantly decreased from control values (5.1 +/- 0.1 at control to 4.0 +/- 0.1 mg/dL); after 20 minutes of attempted resuscitation, it averaged 3.2 +/- 0.2 mg/dL (P less than .05 vs control). There was no change in total Ca+2 during the arrest period (9.2 +/- 0.5 at control to 8.6 +/- 0.8 mg/dL at 27.5 minutes). Arterial lactate significantly increased throughout the arrest and resuscitation period (1.9 +/- 0.2 at control to 7.5 +/- 0.4 mM/L at 27.5 minutes). A significant correlation was demonstrated between ionized Ca+2 and lactate concentrations (r = -.72, P less than .001) but not between ionized calcium and pH (r = -.22, P greater than .20). CONCLUSION: Ionized hypocalcemia occurs during prolonged cardiac arrest and resuscitation, and ionized hypocalcemia during prolonged arrest and resuscitation may be due to binding by lactate, as has been demonstrated in vitro.     

Preshock phase singularity and the outcome of ventricular defibrillation

BACKGROUND: Phase singularity (PS) is a topological defect that serves as a source of ventricular fibrillation (VF). Whether or not the quantity of preshock PS determines defibrillation outcome is unclear. OBJECTIVE: The purpose of this study was to test the hypothesis that the number of PSs at the time of shock is an important factor that determines the shock outcome. METHODS: Isolated, perfused rabbit hearts (n = 7) were optically mapped with a potentiometric dye (di-4-ANNEPS). Shocks were delivered during short (10 seconds) and long (1 minute) VF, and the outcome was classified as successful type A (immediate termination), type B (postshock repetitive responses before termination), and unsuccessful. RESULTS: When shock strengths of 50% probability of successful defibrillation (DFT50) +/- 50 V were given in short VF, the types A and B and unsuccessful shocks were associated with a preshock PS number of 0.3 +/- 0.4, 1.4 +/- 0.3, and 1.5 +/- 0.4 (P <.01 by analysis of variance) and shock strengths of 205 +/- 77, 207 +/- 65, and 173 +/- 74 V (P <.01), respectively. When the same shocks were applied during long VF, the PS numbers were 1.7 +/- 0.5, 3.0 +/- 0.5, and 3.5 +/- 0.6, respectively (P <.01), and the shock strengths were 282 +/- 100, 283 +/- 135, and 256 +/- 126 V, respectively (P <.01). If we only analyze shocks with strength at DFT(50), the preshock PS number was still significantly different for short VF (0.6 +/- 0.5, 1.6 +/- 0.9, and 1.5 +/- 0.8; P <.05) and for long VF (1.4 +/- 0.5, 2.7 +/- 0.6, and 2.7+/-1.3; P <.05), respectively. All preshock PSs were eliminated by shocks. However, rapid repetitive activity was then reinitiated in unsuccessful and type B successful shocks but not in type A successful shocks. CONCLUSIONS: A low number or an absence of preshock PS was associated with type A successful defibrillation. There was no difference in preshock PS numbers between unsuccessful and type B successful defibrillation.     

Existence of both fast and slow channel activity during the early stages of ventricular fibrillation.

Although sodium channels have been reported to be inactive after 5-10 minutes of ventricular fibrillation (VF), their state during early VF is unknown. In 12 open-chest dogs, a floating glass microelectrode was used to record intracellular action potentials from the right ventricle during pacing and during electrically induced VF. Before any drug was administered, an initial episode of VF was continuously recorded for at least 20 seconds followed by defibrillation. Recordings were made during VF episodes after superfusion for 15 minutes around the microelectrode site by low (2.8 x 10(-5) M) and high (10(-4) M) concentrations of tetrodotoxin (TTX) in five dogs, or by low (4 microM) and high (100 microM) concentrations of verapamil in another four dogs. In three dogs, VF was induced without drugs three times to determine if the effects observed in the previous dogs were caused by the drugs or by successive episodes of VF. Ten consecutive action potentials were analyzed at the onset and after 5, 10, 15, and 20 seconds of VF. Action potential amplitude and duration during paced rhythm or VF were not changed by the local perfusion of either TTX or verapamil. In the TTX group, the maximum upstroke rate of depolarization of an action potential (Vmax) during paced rhythm was 104 +/- 14 V/sec for control cycles before any drug was given, 86 +/- 15 V/sec for the low TTX concentration, and 55 +/- 14 V/sec for the high TTX concentration (p less than 0.05 versus other two). Vmax decreased from 55 +/- 32 V/sec at the beginning of VF to 37 +/- 27 V/sec after 20 seconds of VF for predrug VF, from 39 +/- 20 V/sec to 18 +/- 11 V/sec for low-dose TTX VF, and from 18 +/- 13 V/sec to 12 +/- 7 V/sec for high-dose TTX VF (p less than 0.05 among the three groups). In the dogs receiving verapamil, VF was still inducible with Vmax not significantly different from predrug VF at the onset and after 5 or 20 seconds of VF but with Vmax smaller (p less than 0.05) for verapamil than for predrug VF after 10 or 15 seconds of VF. In three dogs, Vmax was not significantly different during three successive episodes of VF when no drug was given between the episodes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Blockade of the inward rectifying potassium current terminates ventricular fibrillation in the guinea pig heart

INTRODUCTION: Stable high-frequency rotors sustain ventricular fibrillation (VF) in the guinea pig heart. We surmised that rotor stabilization in the left ventricle (LV) and fibrillatory conduction toward the right ventricle (RV) result from chamber-specific differences in functional expression of inward rectifier (Kir2.x) channels and unequal IK1 rectification in LV and RV myocytes. Accordingly, selective blockade of IK1 during VF should terminate VF. METHODS AND RESULTS: Relative mRNA levels of Kir2.x channels were measured in LV and RV. In addition, LV (n = 21) and RV (n = 20) myocytes were superfused with BaCl2 (5-50 micromol/L) to study the effects on IK1. Potentiometric dye-fluorescence movies of VF were obtained in the presence of Ba2+ (0-50 micromol/L) in 23 Langendorff-perfused hearts. Dominant frequencies (DFs) were determined by spectral analysis, and singularity points were counted in phase maps to assess VF organization. mRNA levels for Kir2.1 and Kir2.3 were significantly larger in LV than RV. Concurrently, outward IK1 was significantly larger in LV than RV myocytes. Ba2+ decreased IK1 in a dose-dependent manner (LV change > RV change). In baseline control VF, the fastest DF domain (28-40 Hz) was located on the anterior LV wall and a sharp LV-to-RV frequency gradient of 21.2 +/- 4.3 Hz was present. Ba2+ significantly decreased both LV frequency and gradient, and it terminated VF in a dose-dependent manner. At 50 micromol/L, Ba2+ decreased the average number of wavebreaks (1.7 +/- 0.9 to 0.8 +/- 0.6 SP/sec x pixel, P < 0.05) and then terminated VF. CONCLUSION: The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics.     

Better outcome after pediatric defibrillation dosage than adult dosage in a swine model of pediatric ventricular fibrillation

OBJECTIVES: This study was designed to compare outcome after adult defibrillation dosing versus pediatric dosing in a piglet model of prolonged prehospital ventricular fibrillation (VF). BACKGROUND: Weight-based 2 to 4 J/kg monophasic defibrillation dosing is recommended for children in VF, but impractical for automated external defibrillator (AED) use. Present AEDs can only provide adult shock doses or newly developed attenuated adult doses intended for children. A single escalating energy sequence (50/75/86 J) of attenuated adult-dose biphasic shocks (pediatric dosing) is at least as effective as escalating monophasic weight-based dosing for prolonged VF in piglets, but this approach has not been compared to standard adult biphasic dosing. METHODS: Following 7 min of untreated VF, piglets weighing 13 to 26 kg (19 +/- 1 kg) received either biphasic 50/75/86 J (pediatric dose) or biphasic 200/300/360 J (adult dose) therapies during simulated prehospital life support. RESULTS: Return of spontaneous circulation was attained in 15 of 16 pediatric-dose piglets and 14 of 16 adult-dose piglets. Four hours postresuscitation, pediatric dosing resulted in fewer elevations of cardiac troponin T (0 of 12 piglets vs. 6 of 11 piglets, p = 0.005) and less depression of left ventricular ejection fraction (p < 0.05). Most importantly, more piglets survived to 24 h with good neurologic scores after pediatric shocks than adult shocks (13 of 16 piglets vs. 4 of 16 piglets, p = 0.004). CONCLUSIONS: In this model, pediatric shocks resulted in superior outcome compared with adult shocks. These data suggest that adult defibrillation dosing may be harmful to pediatric patients with VF and support the use of attenuating electrodes with adult biphasic AEDs to defibrillate children.     

Predictive indices of successful cardiac resuscitation after prolonged arrest and experimental cardiopulmonary resuscitation

To determine if clinically accessible hemodynamic and blood gas measurements are of value in predicting outcome of countershock after prolonged ventricular fibrillation (VF) and artificial cardiopulmonary support, 14 dogs were studied during 30 minutes of VF using two randomly assigned closed-chest techniques. Seven dogs underwent conventional CPR; the other seven were supported with a pneumatic thoracic vest and abdominal binder, which were inflated synchronously with the airway. Ascending aortic (Ao), right atrial (RA), and instantaneous coronary perfusion pressures (Ao - RA) were measured at five-minute intervals. Ao and RA blood samples were analyzed at 10, 20, 25 and 30 minutes for PO2, PCO2, and pH. After 25 minutes, 1 mg epinephrine was given intravenously, and five minutes later defibrillation was attempted. If unsuccessful, repeated countershocks, conventional pharmacologic therapy, and artificial support were continued. If a perfusing spontaneous cardiac rhythm did not result within an additional 30 minutes, the experiment was terminated. Six animals developed a perfusing cardiac rhythm after one or more countershocks (Group 1); eight failed to develop a perfusing rhythm after repeated countershocks and an additional 30 minutes of resuscitative effort (Group 2). Five Group 1 dogs received vest/binder artificial support. When measured values were averaged over the study period, Group 1 was found to have a significantly greater Ao end-diastolic pressure (AoEDP) and peak diastolic coronary perfusion pressure (CPP) when compared to Group 2 (23 +/- 6 vs 14 +/- 8 mm Hg, P less than .05; and 22 +/- 6 vs 5 +/- 10 mm Hg, P less than .01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of induction method on defibrillation threshold and ventricular fibrillation cycle length

INTRODUCTION: Since no clinical data are available on the comparison of the "shock on T-wave" and "high frequency burst" ventricular fibrillation (VF) induction modes during defibrillation threshold (DFT) testing, we aimed to compare these two methods during implantable cardioverter defibrillator implantation. METHODS: The DFT was determined with a step-down protocol using biphasic, anodal polarity (100%, 40%, 20% voltage control) shocks. Patients were randomized: VF was induced by 50 Hz burst in group B (n = 45) and T-wave shock in group T (n = 41). The DFT was defined as the lowest energy level that terminated VF; confirmed DFT (DFTc) was defined as the minimal energy level that consecutively terminated VF twice. Success rate of DFTc was calculated during an intraindividual test for the alternate induction method. RESULTS: A total of 546 episodes of VF were induced: n = 278 (B) vs n = 268 (T). Incidence of VT during inductions was 9.9% (B) vs 2.7% (T), P < 0.05. Neither the DFT, 8.8 +/- 4.0 J (B) vs 9.7 +/- 4.2 J (T), nor the DFTc, 10.6 +/- 5.1 J (B) vs 10.8 +/- 4.2 J (T), proved to be significantly different. A significant correlation was found between VF cycle length (CL) and the concomitant DFT (r = 0.298, P < 0.05) in group T only. Subgroup analysis of patients under chronic class III antiarrhythmic treatment showed no increase of the DFT in either group and significantly lower incidence of VT induction in group T regardless of antiarrhythmic treatment. CONCLUSION: The DFT and the VFCL proved to be independent of the VF induction method. The T-wave shock was more unlikely to induce VT during DFT testing. These results suggest that both methods are reliable in DFT determination, though T-wave shock application is a more reliable method for DFT testing.