Differences of postresuscitation myocardial dysfunction in ventricular fibrillation versus asphyxiation
a b s t r a c t
Purpose: This study aims to characterize Postresuscitation myocardial dysfunction in 2 Porcine models of cardiac arrest : Ventricular fibrillation cardiac arrest (VFCA) and asphyxiation cardiac arrest (ACA).
Methods: Thirty-two pigs were randomized into 2 groups. The VFCA group (n = 16) were subject to programed electrical stimulation, and the ACA group (n = 16) underwent endotracheal tube clamping to induce CA. Once induced, CA remained untreated for 8 minutes. Two minutes after initiation of cardiopulmonary resuscitation (CPR), defibrillation was attempted until return of spontaneous circulation (ROSC) was achieved or animals died.
Results: Return of spontaneous circulation was 100% successful in VFCA and 50% successful in ACA. Cardiopulmonary Resuscitation duration in VFCA was about half as short as in ACA. The survival time of VFCA was significantly longer than that of ACA. Ventricular fibrillation cardiac arrest had better mean arterial pressure, cardiac output, and left ventricular +- dp/dtmax after ROSC than ACA. Echocardiography revealed significantly lower left ventricular ejection fraction in ACA than in VFCA. myocardial perfusion imaging using single-photon emission computed tomography demonstrated that myocardial injuries after ACA were more severe and widespread than after VFCA. Under a transmission electron microscope, the overall heart morphologic structure and the mitochondrial crista structure were less severely injured in the VFCA group than in the ACA group. Moreover, the percentage of apoptotic cardiomyocytes was higher in ACA than in VFCA.
Conclusions: Compared with VFCA, ACA causes more severe cardiac dysfunction associated with less successful resuscitation and shorter survival time.
(C) 2013
Introduction
Cardiopulmonary resuscitation (CPR) yields a functional survival rate of only 1.4% to 5% [1]. Profound postresuscitation myocardial dysfunction has been demonstrated in both laboratory and clinical studies [2-5]. Insights into the pathophysiological processes of postresuscitation myocardial dysfunction have, at least in part, been gained from animal studies. It is generally accepted that the closer the animal models resemble human diseases, the more reliable is the extrapolation of results from animal studies.
The 2 most prevalent causes of sudden cardiac death are ventricular fibrillation cardiac arrest (VFCA) and asphyxiation cardiac arrest (ACA) [6]. Correspondingly, VFCA and ACA are the 2 most frequently used animal models of CA in basic research that mirror more closely the clinical course of CA and CPR [7-9]. The development of ACA is gradual in contrast to the pulselessness and loss of consciousness after the
? Sources of funding: This study was supported by the Beijing Natural Science Foundation (No. 81372025).
?? Conflict of interest statement: The authors report no conflicts of interest.
* Corresponding author. Department of Emergency, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. Tel./fax: +86 010 85231051.
E-mail address: lcscyyy@163.com (C.-S. Li).
sudden onset of ventricular fibrillation (VF). It is well known that postresuscitation syndrome can be established and myocardial dysfunction is a critical issue contributing to low survival rates in these 2 CA animal models. However, the strategies for resuscitation on unresponsive victims whose pathology cannot be immediately iden- tified by rescuers are identical. To date, there have been no consent guidelines or common criteria for selection of CA models for experimental studies on CPR; thus, even under identical experimental conditions, results from using ACA or VFCA have been largely variable [6,10-12]. We hypothesized that VFCA and ACA are 2 distinct models of CA that can cause different secondary myocardial dysfunctions and derangements after return of spontaneous circulation (ROSC). The purpose of this study was to examine this hypothesis by carrying out comprehensive comparative analyses on the characteristics of cardiac function and structure in pig models of VFCA and ACA.
Methods
Preparation of animals
This prospective, randomized, animal study was conducted with the approval of the Animal Care and Use Committee of Chaoyang Hospital, affiliated with the Capital Medical University. The study was
0735-6757/$ – see front matter (C) 2013 http://dx.doi.org/10.1016/j.ajem.2013.08.017
performed according to Utstein-style guidelines [13] on 32 healthy Wu Zhishan inbred miniature pigs of both sexes aged 6 to 8 months and weighing 20 +- 2 kg. Before experimental procedures, animals were randomized into 2 groups in a blinded manner: VFCA group (n = 16) and ACA group (n = 16). The number of animals used in this study was determined on the basis of our pilot study and was anticipated to ensure an adequate statistical power for ROSC analysis. Initial sedation in each animal was achieved by Intramuscular injection of ketamine (10 mg/kg), followed by ear vein injection of propofol (1.0 mg/kg). The anesthetized animals were intubated with a 6.5-mm cuffed endotracheal tube via direct laryngoscopy. Propofol (1.0 mg/kg) and fentanyl (4 ug/kg) were then administered intravenously to reach the desired depth of anesthesia and analgesia, followed by 9 mg kg-1 h-1 propofol and fentanyl 1 ug kg-1 h-1 (intravenously [IV]) to maintain the anesthesia level. Additional doses of these drugs were administered when the heart rate exceeded 120 beats per minute and/ or the systolic blood pressure exceeded 120 mm Hg. Animals were mechanically ventilated with a volume-controlled ventilator (Servo 900c, Siemens, Berlin, Germany) using a tidal volume of 8 mL/kg and a respiratory frequency of 12/min with room air. End-tidal PCO2 was monitored with an inline infrared capnography system (CO2SMO Plus monitor, Respironics Inc, Murrysville, Pennsylvania). The respiratory frequency was adjusted to maintain end-tidal PCO2 between 35 and 40 mm Hg. aortic pressure was measured with a fluid-filled catheter advanced from the left femoral artery into the thoracic aorta. A Swan- Ganz catheter (7F; Edwards Life Sciences, Irvine, California) was advanced from the left femoral vein and flow-directed into the pulmonary artery to measure right atrial pressure and cardiac output (CO) and to collect the mixed venous blood. Cardiac output was determined by the thermodilution technique. A 5F pacing catheter was advanced from the Right internal jugular vein into the right ventricle to induce VF. Left ventricular (LV) function was measured using a fluid- filled polyurethane catheter that was introduced from the right carotid artery to the LV to determine the maximum rate of LV pressure increase (+dp/dtmax) or decline (-dp/dtmax) (BL-420F Data Acquisition & Analysis System, China). All catheters were calibrated before use, and their tip positions were confirmed by the presence of characteristic pressure traces. An electrocardiograph was continuously recorded with a multichannel physiological recorder (BL-420F Data Acquisition & Analysis System). All hemodynamic parameters were monitored by a multifunction monitor (M1165; Hewlett-Packard Co, Palo Alto, California). Total fluid management consisted of 250 to 500 mL of normal saline solution administered intravenously throughout the 2- to
3-hour preparatory period.
Experimental protocols
After surgery, the animals were allowed to equilibrate for 60 minutes to achieve a stable resting level, and then baseline data were collected. In the VFCA group, VF was induced by programed electrical stimuli (GY-600A; KaiFeng Huanan Instrument Co, Kaifeng, Henan, China) and was verified by the presence of a characteristic electrocardiographic waveform and an immediate drop in aortic blood pressure. In the ACA group, animals were paralyzed with cisatracurium (0.2 mg/kg) to avoid gasping, and then CA was induced by clamping the endotracheal tube. The animals were asphyxiated
Characteristics of the baseline measurements (means +- SD)
VFCA group (n = 16) ACA group (n = 16)
Male/female 9/7 10/6
Body weights (kg) 20.3 +- 1.3 20.0 +- 1.4
End-tidal CO2 (mm Hg) 37.4 +- 7.1 38.0 +- 6.3
Time of preparatory phase (min) 65.5 +- 14.7 67.0 +- 16.1
Fig. 1. Survival function analysis of animals after ROSC in the VFCA group (n = 16) and ACA group (n = 16).
until simulated pulselessness was observed, defined as an aortic systolic pressure less than 30 mm Hg [7].
After CA had been successfully induced, mechanical ventilation and anesthetic/analgesic administration were ceased, and the endo- tracheal tube was opened in the ACA group. After 8 minutes of untreated CA (equivalent to the average time it takes for emergency medical services to arrive [14]), mechanical ventilation was resumed with 100% oxygen, and CPR was performed manually. Manual chest compressions were conducted by a designated CPR technician who compressed approximately one third of the anteroposterior diameter of the thorax at a rate of 100 compressions per minute with equal compression-relaxation duration. The Quality of chest compressions was controlled by a HeartStart MRx Monitor/Defibrillator with Q-CPR (Philips Medical Systems, Best, Holland).
After 2 minutes of CPR, epinephrine (0.02 mg/kg) was injected into the right atrium, and then CPR was performed manually for another 2 minutes. After 4 minutes of CPR, defibrillation (SMART Biphasic) was attempted using 4 J/kg for the first attempt. Cardiopulmonary resuscitation was resumed for another 2 minutes after the attempted defibrillation. The sequence continued until ROSC or for 30 minutes if ROSC was not achieved. Return of spontaneous circulation was defined as the maintenance of a systolic blood pressure 50 mm Hg or greater for 10 min or more.
The animals, in which spontaneous circulation was restored, received intensive care for 6 hours, and mechanical ventilation was resumed with the same settings as before CA. In 6 hours after ROSC, dopamine was injected to maintain the systolic blood pressure 50 mm Hg or greater if the systolic blood pressure less than 50 mm Hg and the initial dosage of dopamine was 2 ug kg-1 min-1. After 6 hours of postresuscitation monitoring, all catheters were removed by surgical procedure [15]. Six hours after ROSC, the animals were killed with a bolus of propofol 60 mg (IV) and then 20 mL of 10 mol/L potassium chloride (IV).
Echocardiography
Echocardiography was conducted by an observer blinded to the experiment, and measurements were taken before CA and at 3.5 hours after ROSC. A 2- or 4-chamber long-axis view was obtained using the Hewlett-Packard Sonos 2500 echocardiographic system (Hewlett- Packard, Andover, Massachusetts) with a 5.5/7.5-Hz biplane Doppler transesophageal echocardiographic transducer and a four-way
Fig. 2. Comparison of cardiac function and hemodynamic parameters between VFCA and ACA groups. The measurements were made at baseline and varying time points up to 6 hours after ROSC. Heart rate (A); MAP (B); CO (C); LV +dp/dtmax (D); LV -dp/dtmax (E). The values are presented as mean +- SD. *P b .05 and **P b .01 vs baseline (one-way repeated- measures analysis of variance); #P b .05 and ##P b .01 vs ACA group (Student t test).
flexure. Left ventricular end-systolic (LVESV) and end-diastolic volumes (LVEDV) were calculated by the disk method (Acoustic Quantification Technology, Hewlett-Packard). These parameters were used to determine LV ejection fraction (LVEF).
Myocardial perfusion imaging
To assess myocardial perfusion, we performed technetium Tc 99m hexakis-2- methoxyisobutylisonitrile (Tc-99m-MIBI) single-photon emission computed tomography (SPECT) at baseline and 4 hours after ROSC. The SPECT image of the LV was divided into 17 semiquantifiable segments for assessment of the regional defect score. Severity of perfusion deficit for each segment was visually graded by assigning scores between 0 and 4 (0, normal tracer uptake; 1, mildly reduced tracer uptake; 2, moderately reduced tracer uptake; 3, obviously reduced tracer uptake; and 4, absent tracer uptake) [4]. A score 1 or higher indicated a significant perfusion deficit. Scores for all 17 segments were added to create a summed score of perfusion (SSP) and were calculated by 2 experienced cardiologists who were unaware of any clinical data for this study.
Pathologic examination and TUNEL assay
After the animals were killed at 6 hours after ROSC, the heart was excised and the right ventricle and both atria were removed. Left ventricular tissue samples were quickly dissected and preserved in 10% formaldehyde and 4% paraformaldehyde for pathologic exami- nations of tissue ultramicrostructure under a transmission electron microscope (TEM) by one experienced pathologists who was unaware of any clinical data for this study. Terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end label-
ing (TUNEL) assay was used to label cells that suffered severe DNA damage/fragmentation induced by apoptotic signaling cascades. The TUNEL-positive cells were counted by 2 experienced pathologists who were unaware of any clinical data for this study to determine the apoptotic index (AI). AI = (apoptotic cells stained brown)/(total TUNEL-positive cells).
Statistical analysis
Statistical analysis was performed using SPSS 17.0 software (SPSS Inc, Chicago). Data are shown as mean +- SD. Continuous variables were compared between groups using the Student t test. One-way repeated-measures analysis of variance or paired t test was used to determine differences over time within groups, as appropriate, and the Bonferroni t test for multiple comparisons. A log-rank test was
Table 2
Echocardiographic measurements at baseline and 3.5 hours after successful resuscitation
Group |
VFCA group |
ACA group |
||||
Baseline |
ROSC 3.5 hours |
Baseline |
ROSC 3.5 hours |
|||
LVEDD (mm) |
24.69 +- 1.70 |
26.75 +- 1.77?? |
25.85 +- 1.95 |
31.14 +- 1.95??## |
||
LVESD (mm) |
17.50 +- 1.26 |
21.00 +- 1.32?? |
17.85 +- 2.04 |
24.71 +- 1.80??## |
||
LVEDV (mL) |
21.13 +- 2.63 |
22.00 +- 2.57 |
19.75 +- 2.02 |
27.29 +- 1.89??## |
||
LVESV (mL) |
7.94 +- 1.39 |
11.13 +- 1.86?? |
8.50 +- 1.79 |
17.14 +- 3.29??## |
||
EF |
0.66 +- 0.03 |
0.45 +- 0.04?? |
0.68 +- 0.02 |
0.31 +- 0.06??## |
Abbreviations: LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; EF, ejection fraction. Values are presented as mean +- SD.
*P b .05 vs baseline (paired t test).
#P b .05 vs VFCA (Student t test).
?? P b .01 vs baseline (paired t test).
## P b .01 vs VFCA (Student t test).
Fig. 3. Examples of porcine cardiac perfusion at rest by Tc-99m-MIBI SPECT obtained at baseline and 4 hours after ROSC. A, Myocardial perfusion imaging before cardiac arrest; B, myocardial perfusion imaging of the VFCA group 4 hours after successful resuscitation; C, myocardial perfusion imaging of the ACA group 4 hours after successful resuscitation. The bright areas indicate blood flow. In (C), the axial direction was different from (A) and (B).
Fig. 4. The SSP of myocardial perfusion imaging of the VFCA group (n = 14) and the ACA group (n = 7) at baseline and 4 hours after successful resuscitation. The SPECT image of the left ventricle was divided into 17 semiquantifiable segments for assessment of the regional defect score. Severity of perfusion deficit for each segment was visually graded by assigning scores between 0 and 4 (0, normal tracer uptake; 1, mildly reduced tracer uptake; 2, moderately reduced tracer uptake; 3, obviously reduced tracer uptake; and 4, absent tracer uptake). Scores for all 17 segments were added to create an SSP. We found that the SSP was significantly increased in both groups at 4 hours after successful resuscitation when compared with baseline. In addition, this increase was more in the ACA group when compared with the VFCA group. Deep black represents the VFCA group, and light gray represents the ACA group.
**P b .01 vs baseline (paired t test); ##P b .01 vs VFCA group (Student t test).
used for survival analysis. Fisher exact test was used for ROSC analysis. A two-sided P b .05 was considered statistically significant.
Results
Characteristics of animals and dosages of vasopressors
The extra doses of propofol and fentanyl administered during the preparatory phase did not differ significantly between the groups (propofol: 121 +- 11 vs 123 +- 9 mg and fentanyl: 73 +- 9 vs 71 +- 10 ug in the VFCA and ACA group, respectively). The characteristics and baseline measurements were not significantly different between the 2 groups of animals (Table 1).
The average dosages of vasopressors used in Resuscitated animals in the VFCA group were lower than those in the ACA group (epinephrine: 0.03 +- 0.01 vs 0.07 +- 0.02 mg/kg and dopamine:
1.97 +- 1.30 vs 7.57 +- 1.76 ug kg-1 min-1).
Comparison of survival function and arrhythmias
CA was induced in all animals in both study groups. The duration of asphyxia between clamping of the tube and CA ranged between 13 and 18 minutes (15.4 +- 1.3 min). Return of spontaneous circulation was achieved in 16 (100%) of 16 of the VFCA animals and in only 8 (50%) of 16 of the ACA animals (P b .01). At the observation end point of 6 hours after ROSC, 14 animals survived in VFCA group and 6 animals in ACA group. Six-hour survival function analysis (6 hours
Fig. 5. Images showing the ultrastructural changes of the myocardial ultramicrostructure 6 hours after successful resuscitation (magnification: A and B, x4000; C and D, x10000). Ventricular fibrillation cardiac arrest animals (A and C) demonstrated less degrees of ultrastructural deterioration in cardiomyocytes than ACA animals (B and D). Ventricular fibrillation cardiac arrest hearts showed no obviously broken myofilaments. Most of the mitochondria and myocardial fiber were normal, and only a small proportion was partially broken with vague mitochondrial cristae. By comparison, in ACA hearts, myocardial fiber, myocomma, and cross striation were obviously disordered, broken, and even dissolved. Most of the mitochondria were severely broken with vacuolar degeneration and deranged or disrupted cristae.
Myocardial histology and apoptosis”>after ROSC was observation end point in this study and then the animals were killed to obtain their heart tissues) indicated that the average survival time in VFCA (n = 16) was longer than in the ACA group (n = 16) (5.7 +- 0.2 vs 2.4 +- 0.9 hours, P b .01; Fig. 1).
At 8 minutes after untreated CA, all animals in the VFCA group developed persistent VF, whereas in the ACA group, VF occurred in 5, pulseless electrical activity occurred in 1, and asystole occurred in 10 animals. Asystole and pulseless electrical activity did not deteriorate in VF in ACA group.
Comparisons of hemodynamic parameters
Heart rate, mean arterial pressure (MAP), CO, +dp/dtmax, and
-dp/dtmax at baseline did not differ significantly between the VFCA and ACA groups (P N 0.05; Fig. 2). The values of CO, +dp/dtmax, and -dp/dtmax were significantly decreased after ROSC relative to the baseline values in both groups (P b .05; Fig. 2). The values of these parameters were significantly greater in the VFCA group than of those in the ACA group 1 to 6 hours after ROSC (P b .05; Fig. 2), indicating less severe impairment of LV function in VFCA animals.
Left ventricular function as reported by echocardiography
The baseline values of LV end-diastolic diameter, LV end-systolic diameter, LVEDV, LVESV, and LVEF were in the same range for the VFCA and ACA animals. However, 3.5 hours after ROSC, LVEF declined significantly from the baseline value in both groups (P b .05), but the extent of reduction was greater in the ACA animals than in the VFCA animals, resulting in a significantly higher LVEF in the VFCA group than in the ACA (0.45 +- 0.04 vs 0.31 +- 0.06, P b .01; Table 2).
Fig. 6. Representative images of TUNEL staining of myocardial apoptosis 6 hours after successful resuscitation (original magnification, x400). There were significantly higher numbers of apoptotic cells in the ACA group (B) than in the VFCA group (A). Brown nucleolus indicated apoptotic cardiomyocytes.
Left ventricular function as reported by myocardial perfusion imaging
Severe radioactive sparse defects in the inferior, posterior, and anterior wall of the left ventricle in both VFCA and ACA animals were observed with myocardial perfusion imaging. However, the radioac- tive sparse defects were less severe in the VFCA group than in the ACA group (Fig. 3). When compared with the baseline the SSP values at 4 hours after ROSC, both groups were significantly increased: 0.4 +- 0.6 vs 9.4 +- 3.1 (P b .05) in the VFCA group (n = 14) and 0.4 +- 0.5 vs 21.9
+- 3.4 (P b .05) in the ACA group (n = 7). In addition, this increase was more in the ACA group when compared with the VFCA group (21.9 +- 3.4 vs 9.4 +- 3.1, P b .05; Fig. 4).
Myocardial histology and apoptosis
Several derangements in the myocardium were identified under a TEM. The intercalated disks were disorganized, fragmented, and even dissolved. Some of the mitochondria were severely damaged, exhibiting vacuolar degeneration, and the cristae were vague, irregularly arranged, or disrupted. By comparison, the overall heart morphologic structure and the mitochondrial crista structure were less severely injured in the VFCA group than that in the ACA group (Fig. 5). TUNEL assay revealed that there were greater numbers of apoptotic cardiomyocytes in the ACA group than in the VFCA group; thus, the AI was significantly higher in the ACA than that in the VFCA (78.91 +- 11.21% vs 49.63 +- 9.23%, P b .01; Fig. 6).
Discussion
Here, we presented a comprehensive study comparing the basic characteristics of ACA and VFCA and a wide spectrum of parameters relevant to cardiac dysfunction, myocardial injuries, and morpholog- ical/structural derangements in both models. The major finding in the present study was that although significant myocardial dysfunction and derangements occur in both VFCA and ACA models, compared with VFCA, ACA caused more severe cardiac dysfunction, myocardium injury, and Energy metabolism hindrance associated with less successful resuscitation and shorter survival time. These results imply that ACA and VFCA should be treated as different pathological entities. Two published studies have generated experimental evidence suggesting that ACA resulted in significantly lesser impairment of postresuscitation myocardial function than VFCA [6,16], which is in contrast to our results presented in this study. Several possible explanations may account for this disparity. The first possibility is the different animal species used for investigation. Swine, whose heart size, structure, and functional properties more closely resemble those of the human heart, were used in the present study, whereas rodents, whose hearts have certain important differences from the human heart in many aspects including automated defibrillation, were used in the previous studies [17-19]. The second explanation is that the durations of CA before CPR were different: CA was left untreated for 8 minutes in our study, while 4- and 7-minute lags for CPR were allowed in the studies reported by the other 2 laboratories [6,16]. Finally, we used a longer duration (13-16 minutes) of asphyxia before CA for our ACA model, whereas a much shorter pre-CA asphyxia duration (only 3-8 minutes) was used in the other studies. We used a validated model of asphyxiation by clamping the endotracheal tube in the presence of room air ventilation with full muscle paralysis, which reliably prevented any forms of gasping that would be a severe confounding variable in an asphyxia model. Some studies showed that after ACA, a period of 8 minutes without intervention is absolutely necessary to avoid successful resuscitation with ventilation and chest compressions alone [7,20]. Except for the longer lag time between the commencement of asphyxia and of CA, other conditions were
essentially the same as in previously published studies.
Our results clearly showed that ejection fraction of LV were markedly impaired after successful resuscitation in both CA models. The ACA model had significantly greater decreases in MAP and CO compared with the VFCA model. These results strongly indicate that cardiac dysfunction and myocardial damage are more severe in the ACA model than in the VFCA model in otherwise identical experimental conditions.
The etiology of postresuscitation myocardial injuries is as yet unclear but is thought to mimic ischemia/reperfusion injuries: ischemia during CA and CPR efforts, and reperfusion after resuscita- tion or restoration of circulation. To get some mechanistic insight into what makes the 2 models have such distinct cardiac outcomes, we used SPECT to compare myocardial perfusion. Our results showed that myocardial radioactive sparse defects were significantly increased in the ACA group when compared with the VFCA group, which demonstrated that myocardial perfusion and microcirculation distur- bance after ACA were much more severity. The SPECT myocardial Perfusion defects are characterized by their extent, severity, and location. American College of Cardiology/American Heart Association/ American Society for Nuclear Cardiology guidelines recommend a Semiquantitative analysis on a validated segmental scoring system [21]. A 17-segment model analysis is proposed using a 5-point scale system in direct proportion to the observed count density of the segment. Calculations of the summed scores can also be performed incorporating the total extent and severity of a perfusion abnormality. In this study, the average SSP at 4 hours after ROSC suggested that myocardial perfusion reduce more heavily in ACA group.
To further investigate the differences of myocardial dysfunction after CA between the 2 groups, we performed histological examination under a TEM, which revealed significant derangements of myocardium and organelles such as mitochondria within the cells. Compared with VFCA, ACA caused more diffuse myocardial injuries and mitochondrial damage and, thus, less successful resuscitation [22]. This notion was also supported by the data showing more apoptotic cells in the ACA group than in the VFCA group and was consistent with the fact that VFCA animals were more susceptible to resuscitation than the ACA animals. It also may be an explanation why the average dosages of vasopressors used in resuscitated animals in the VFCA group were lower than in the ACA group including both stages of CPR and after ROSC.
Limitations
Some limitations of this study should be noted, including usage of potent anesthetics, epinephrine, and dopamine used after ROSC, which may have impaired Cardiovascular function and autonomic control [23]. We used young, healthy pigs, whereas in clinical practice, most individuals with CA have underlying pathologic alterations. Thus, precaution must be exercised when extrapolating our results into clinical practice.
Conclusions
In summary, our findings suggest that in the 2 most frequently used animal models of CA in basic research, the myocardial injury caused by ACA and subsequent resuscitation appears to be more severe and more widespread than by VFCA under otherwise identical conditions. Therefore, researchers should choose the most appropri- ate CA models based on their study design.
Acknowledgments
The authors thank Zhi-Jun Guo, Shuo Wang, Xin-Hua He, and Wei Jiang for excellent technical assistance.
References
- Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics- 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:480-6.
- Tang W, Weil MH, Sun S, et al. Progressive myocardial dysfunction after cardiac resuscitation. Crit Care Med 1993;21:1046-50.
- Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group. N Eng J Med 1992;327:1051-5.
- Ji XF, Yang L, Zhang MY, et al. Shen-fu injection attenuates postresuscitation myocardial dysfunction in a porcine model of cardiac arrest. Shock 2011;35: 530-6.
- Gazmuri RJ, Weil MH, Bisera J, et al. Myocardial dysfunction after cardiac resuscitation from cardiac arrest. Crit Care Med 1996;24:992-1000.
- Vaagenes P, Safar P, Moossy J, et al. Asphyxiation versus ventricular fibrillation cardiac arrest in dogs. Differences in cerebral resuscitation effects–a preliminary study. Resuscitation 1997;35:41-52.
- Pantazopoulos IN, Xanthos TT, Vlachos I, et al. Use of the impedance threshold device improves survival rate and neurological outcome in a swine model of Asphyxial cardiac arrest. Crit Care Med 2012;40:1-8.
- Gu W, Li C, Yin W, et al. Shen-fu injection reduces postresuscitation myocardial dysfunction in a porcine model of cardiac arrest by modulating apoptosis. Shock 2012;38:301-6.
- Ji Xian-Fei, Li Chun-Sheng, Wang Shuo, et al. Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest. Resuscitation 2010;81:1031-6.
- Lindner KH, Prengel AW, Pfenninger EG, et al. Vasopressin improves vital organ blood flow during closed-chest CPR in pigs. Circulation 1995;91:215-21.
- Wenzel V, Lindner KH, Krismer AC, et al. Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs. Circula- tion 1999;99:1379-84.
- Voelckel WG, Lurie KG, McKnite S, et al. Comparison of epinephrine and vasopressin in a pediatric porcine model of asphyxial cardiac arrest. Crit Care Med 2000;28:3777-83.
- Idris AH, Becker LB, Ornato JP, et al. Utstein-Style Guidelines for Uniform Reporting of Laboratory CPR Research: a Statement for Healthcare Professionals From a Task Force of the American Heart Association, the American College of Emergency Physicians, the American College of Cardiology, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for Resuscitation Research, and the Society for Academic Emergency Medicine Writing Group. Circulation 1996;94: 2324-36.
- van Alem AP, Vrenken RH, de Vos R, et al. Use of automated external defibrillator by First responders in out of hospital cardiac arrest: prospective controlled trial. BMJ 2003;327:1312-7.
- Xanthos T, Bassiakou E, Koudouna E, et al. Baseline hemodynamics in anesthetized Landrace-Large White swine: reference values for research in cardiac arrest and cardiopulmonary resuscitation models. J Am Assoc Lab Anim Sci 2007;46:21-5.
- Kamohara T, Weil MH, Tang W, et al. A comparison of myocardial function after primary cardiac and primary asphyxial cardiac arrest. Am J Respir Crit Care Med 2001;164:1221-4.
- Katz L, Ebmeyer U, Safar P, et al. Outcome model of asphyxia cardiac arrest in rats. J Cereb Blood Flow Metab 1995;15:1032-9.
- Song L, Weil MH, Tang W, et al. Cardiopulmonary resuscitation in the mouse. J Appl Physiol 2002;93:1222-6.
- von Planta I, Weil MH, von Planta M, et al. Cardiopulmonary resuscitation in the rat. J Appl Physiol 1988;65:2641-7.
- Mayr VD, Wenzel V, Voelckel WG, et al. Developing a vasopressor combination in a pig model of adult asphyxial cardiac arrest. Circulation 2001;104:1651-6.
- Dilsizian V, Bacharach SL, Beanlands RS, et al. ASNC Imaging Guidelines for Nuclear Cardiology Procedures. PET myocardial perfusion and metabolism clinical imaging. J Nucl Cardiol 2009;16:651.
- Tsai MS, Huang CH, Tsai SH, et al. The difference in myocardial injuries and mitochondrial damages between asphyxial and ventricular fibrillation cardiac arrests. Am J Emerg Med 2012;30:1540-8.
- Zhong JQ, Dorian P. Epinephrine and vasopressin during cardiopulmonary resuscitation. Resuscitation 2005;66:263-9.