Pig Model Of Ventricular Fibrillation Research Articles

Erythropoietin administration facilitates return of spontaneous circulation and improves survival in a pig model of cardiac arrest

BackgroundIn addition to its role in the endogenous control of erythropoiesis, recombinant human erythropoietin (rh-EPO) has been shown to exert tissue protective properties in various experimental models. However, its role in the cardiac arrest (CA) setting has not yet been adequately investigated. AimThe aim of this study is to examine the effect of rh-EPO in a pig model of ventricular fibrillation (VF)-induced CA. MethodsVentricular fibrillation was electrically induced in 20 piglets and maintained untreated for 8 minutes before attempting resuscitation. Animals were randomized to receive rh-EPO (5000 IU/kg, erythropoietin [EPO] group, n = 10) immediately before the initiation of chest compressions or to receive 0.9% Sodium chloride solution instead (control group, n = 10). ResultsCompared with the control, the EPO group had higher rates of return of spontaneous circulation (ROSC) (100% vs 60%, P = .011) and higher 48-hour survival (100% vs 40%, P = .001). Diastolic aortic pressure and coronary perfusion pressure during cardiopulmonary resuscitation were significantly higher in the EPO group compared with the control group. Erythropoietin-treated animals required fewer number of shocks in comparison with animals that received normal saline (P = .04). Furthermore, the neurologic alertness score was higher in the EPO group compared with that of the control group at 24 (P = .004) and 48 hours (P = .021). ConclusionAdministration of rh-EPO in a pig model of VF-induced CA just before reperfusion facilitates ROSC and improves survival rates as well as hemodynamic variables.

High-dose erythropoietin during cardiac resuscitation lessens postresuscitation myocardial stunning in swine

We investigated the metabolic and functional myocardial effects of erythropoietin (EPO) administered during resuscitation from cardiac arrest using an open-chest pig model of ventricular fibrillation and resuscitation by extracorporeal circulation, after having reported in rats a reversal of postresuscitation myocardial dysfunction associated with activation of mitochondrial protective pathways. Ventricular fibrillation was induced in 16 male domestic pigs and left untreated for 8 minutes, after which extracorporeal circulation was started and maintained for 10 additional minutes, adjusting the extracorporeal flow to provide a coronary perfusion pressure of 10 mmHg. Defibrillation was accomplished and the extracorporeal flow was adjusted to secure a mean aortic pressure of 40 mmHg or greater during spontaneous circulation for up to 120 minutes. Pigs were randomized 1:1 to receive EPO (1200 U/kg) or 0.9% NaCl before starting extracorporeal circulation. Severe postresuscitation myocardial dysfunction developed in both groups. However, recovery of myocardial function-comparing baseline with 120 minutes postresuscitation-was better in pigs treated with EPO than NaCl, as shown for left ventricular ejection fraction (from 45 ± 8% to 36 ± 9% in EPO, not significant; and from 46 ± 8% to 26 ± 8% in NaCl, P < 0.001) and for peak systolic pressure/end-systolic volume (from 2.7 ± 0.8 mmHg/mL to 2.4 ± 0.7 mmHg/mL in EPO, not significant; and from 3.0 ± 1.1 mmHg/mL to 1.8 ± 0.6 mmHg/mL, P < 0.001 in NaCl). The EPO effect was associated with significantly higher myocardial O2 consumption (12 ± 6 mL/min/unit of tissue vs 6 ± 2 mL/min/unit of tissue, P < 0.017) without effects on myocardial lactate consumption. Thus, EPO administered during resuscitation from ventricular fibrillation lessened postresuscitation myocardial stunning-an effect that could be useful clinically to help promote postresuscitation hemodynamic stability.

The effects of phase duration on defibrillation success of dual time constant biphasic waveforms

Aim of Study The effects of first and second phase duration of biphasic waveforms on defibrillation success were evaluated in a guinea pig model of ventricular fibrillation (VF). We hypothesized that waveform duration, and especially the first phase duration, played a main role on defibrillation efficacy in comparison to energy, current and voltage, when a dual time constant biphasic shock was employed. Methods VF was induced and untreated for 5 s in 30 male guinea pigs, prior to attempting a single defibrillatory shock with one of 5 defibrillation waveforms which had different durations of the first and second phase. A five step up–down protocol was utilized for determining the defibrillation efficacy. After a 3-min interval, the procedure was repeated. A total of 25 cardiac arrest events and defibrillations were investigated for each animal. Results The defibrillation waveforms with an intermediate first phase of 5 ms, yielded the highest defibrillation success ( p < 0.05). These waveforms also presented significantly lower energy, current and voltage in comparison to waveforms with shorter or longer first phase durations ( p < 0.001). However, no differences on defibrillation success were observed among waveforms with different second phase durations varying from 1.5 ms to 3.5 ms. Conclusions For dual time constant biphasic waveforms, the first phase duration played a main role on defibrillation success. The intermediate first phase duration of 5 ms, yielded the best defibrillation efficacy compared with shorter or longer first phase durations. While the second phase duration did not affect defibrillation outcomes.

Cariporide given during resuscitation promotes return of electrically stable and mechanically competent cardiac activity

Episodes of ventricular fibrillation (VF) and myocardial dysfunction commonly occur after cardiac resuscitation compromising the return of stable circulation. We investigated in a pig model of VF whether limiting Na +-induced cytosolic Ca 2+ overload using the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) inhibitor cariporide promotes resuscitation with stable circulation. Methods VF was electrically induced in 20 male pigs and left untreated for 6 min after which CPR was initiated and continued for 8 min before attempting defibrillation. Pigs were randomized to receive 3-mg/kg cariporide ( n = 10) or 0.9%-NaCl ( n = 10) before chest compression. Results Seven of 10 pigs in each group were successfully resuscitated and survived 2 h. Cariporide ameliorated post-resuscitation ventricular ectopic activity such that fewer singlets (5 ± 5 vs. 26 ± 21; p < 0.05) and fewer bigemini (1 ± 3 vs. 33 ± 25; p < 0.05) were observed during the initial 5 min post-resuscitation. Additionally, cariporide-treated pigs did not require additional post-resuscitation shocks for ventricular tachycardia or recurrent VF (0.0 ± 0.0 vs. 5.3 ± 7.8 shocks; p = 0.073). During the initial 60 min cariporide-treated pigs had higher, cardiac index (6.1 ± 0.7 vs. 4.4 ± 1.1 L/min/m 2; p < 0.01), left ventricular stroke work index (45 ± 9 vs. 36 ± 10 gm m/beat/m 2; p < 0.05), and numerically higher mean aortic pressure (104 ± 11 vs. 91 ± 12 mmHg; p = 0.054). Conclusion Cariporide administered at the start of chest compression may help restore electrically and mechanically stable circulation after resuscitation from cardiac arrest.

Gasping, Survival, and the Science of Resuscitation

The study in the current issue of Circulation by Bobrow et al1 is important for a multitude of reasons. This study revolves around the concept of “gasping” as it relates to cardiac arrest. The study questions both the incidence of gasping and its impact on and relationship to survival in patients who suffer out-of-hospital cardiac arrest (OHCA). Article p 2550 The authors demonstrate that gasping after cardiac arrest is common, that it is most frequent soon after cardiac arrest, and that its frequency decreases over time. Additionally, the presence of gasping is associated with an increased survival to discharge from the hospital. It is interesting to note that the survival rate was not necessarily related to the institution of bystander cardiopulmonary resuscitation (CPR) because the same percentage of “gaspers” and “nongaspers” received bystander CPR. Yet among the gaspers, the authors found a 39% survival rate versus only a 9% survival rate in the nongaspers. Although the true incidence of gasping after cardiac arrest is unclear, more perplexing is the question, what is the cause of the ostensible protective benefit of gasping? Equally important, as the authors point out, is that first responders and medical professionals recognize gasping as a symptom of cardiac arrest and institute CPR immediately rather than confuse it with normal breathing and thereby delay CPR. Previous experimental work exists with regard to gasping and cardiac arrest. Xie et al2 studied the effects of gasping during untreated ventricular fibrillation in an animal model, showing that gasping during ventricular fibrillation increased both ventilation and cardiac output during cardiac arrest. Srinivasan et al3 studied the effects of gasping in a pig model of ventricular fibrillation and showed that spontaneous gasping decreased intracranial pressure and increased cerebral perfusion pressure. The article by Srinivasan and colleagues thus provides a …

Spontaneous gasping decreases intracranial pressure and improves cerebral perfusion in a pig model of ventricular fibrillation

Spontaneous gasping is associated with increased survival in animal models of cardiac arrest and in observational studies of humans. The potential beneficial effect of gasping on cerebral perfusion may underlie the observed survival benefit, but mechanisms remain unknown. We hypothesized that spontaneous gasping in a pig model of ventricular fibrillation (VF) decreases intracranial pressure (ICP) and increases cerebral perfusion pressure (CePP) during VF in a pig model. The 13 female farm pigs, weighing between 16 and 33 kg, were anesthetized with propofol and intubated, and then had VF induced for 8 min without intervention. Intrathoracic pressure (ITP), aortic pressure (AoP), and ICP were measured continuously. CePP and ITP were recorded simultaneously during three maximal gasps and correlated with gasping by Spearman rank correlation. Gasping during VF occurred in 13/13 pigs and followed a crescendo-decrescendo pattern. Each gasp was associated with a biphasic AoP (initial fall, then rise) and ICP (initial rise, then fall) morphology. Time to first gasp (r(2)=0.06), time to maximal gasp (r(2)=0.02), duration of gasping (r(2)=0.11) and frequency of gasping (r(2)=0.32) did not correlate significantly with CePP during gasping while depth of gasping exhibited a weak but significant correlation with CePP (r(2)=0.35, p=0.05). Maximal gasping occurred at 202+/-34 s from onset of VF and resulted in an average decrease in ICP from 27.4+/-5.8 to 20+/-6.7 mmHg, p<0.01 along with an increase in CePP from -0.05+/-10.9 to 11.5+/-12.6 mmHg, p<0.05. Spontaneous gasping during cardiac arrest decreased intra-cranial pressure and increased cerebral perfusion pressure significantly. These results may help explain why gasping is associated with improved cardiac arrest survival rates. Based upon this new understanding of the physiology of gasping, we speculate that investigation of devices that can enhance the physiological effects of gasping on intracranial pressure and cerebral perfusion should be prioritized.

Cardiopulmonary resuscitation (CPR) using periodic acceleration (pGz) in an older porcine model of ventricular fibrillation.

Cardiopulmonary resuscitation (CPR) can be achieved by repetitive motion of the body headwards to footwards in the spinal axis, at 2 Hz and +/- 0.6 G in a juvenile pig model of ventricular fibrillation. Return of spontaneous circulation and normal neurological outcome occurred after a total of 22 min of ventricular fibrillation that included a 3-min noninterventional period [Resuscitation 56 (2003) 215; Resuscitation 51 (2001) 55]. Since older pigs have stiffer rib cages than juvenile pigs and their hemodynamic response to various stimuli might differ, this study was carried out to determine whether this method of CPR, termed pGz-CPR, was just as effective in older pigs. pGz-CPR was also compared to chest compression CPR using an automated mechanical device (CONV-CPR). Ventricular fibrillation was instituted in older pigs weighing 23-34 kg and a 3-min noninterventional period was observed, followed by 15 min pGz-CPR in eight pigs or 15 min CONV-CPR in eight pigs. Return of spontaneous circulation (ROSC) occurred after defibrillation in all eight pigs with pGz-CPR and in six of eight pigs with CONV-CPR. Two of eight pigs with CONV-CPR and none of the eight pigs with pGz-CPR had rib fractures. Hemodynamic instability 15 min after ROSC occurred in all animals with CONV-CPR whereas only three of eight pigs with pGz-CPR demonstrated hemodynamic instability (P < 0.05). We conclude that pGz-CPR in older pigs produces similar ROSC reported by other investigators in pigs without the risk of rib fractures. Further, pGz-CPR is associated with a lower incidence of periods of hemodynamic instability following ROSC than CONV-CPR.

Vasopressin Improves Vital Organ Blood Flow During Closed-Chest Cardiopulmonary Resuscitation in Pigs

This study was designed to compare the effects of epinephrine with those of vasopressin on vital organ blood flow during closed-chest cardiopulmonary resuscitation (CPR) in a pig model of ventricular fibrillation. Vasopressin was compared with epinephrine by randomly allocating 28 pigs to receive either 0.2 mg/kg epinephrine (n = 7), 0.2 U/kg vasopressin (low dose) (n = 7), 0.4 U/kg vasopressin (medium dose) (n = 7), or 0.8 U/kg vasopressin (high dose) (n = 7) after 4 minutes of ventricular fibrillation and 3 minutes of closed-chest CPR. Left ventricular myocardial blood flow, determined by use of radiolabeled microspheres during CPR, before and then 90 seconds and 5 minutes after drug administration was 17 +/- 2, 43 +/- 5, and 22 +/- 3 mL.min-1.100 g-1 (mean +/- SEM) in the epinephrine group; 18 +/- 2, 50 +/- 6, and 29 +/- 3 mL.min-1.100 g-1 in the low-dose vasopressin group; 17 +/- 3, 52 +/- 8, and 52 +/- 6 mL.min-1.100 g-1 in the medium-dose vasopressin group; and 18 +/- 2, 95 +/- 9, and 57 +/- 6 mL.min-1.100 g-1 in the high-dose vasopressin group (P < .001 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin, and P < .01 at 5 minutes between epinephrine and medium-dose vasopressin). At the same times, calculated coronary systolic perfusion pressures were 12 +/- 2, 36 +/- 5, and 18 +/- 2 mm Hg in the epinephrine group; 10 +/- 1, 39 +/- 6, and 26 +/- 5 mm Hg in the low-dose vasopressin group; 11 +/- 2, 49 +/- 6, and 38 +/- 5 mm Hg in the medium-dose vasopressin group; and 10 +/- 2, 70 +/- 5, and 47 +/- 6 mm Hg in the high-dose vasopressin group (P < .01 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin); and calculated coronary diastolic perfusion pressures were 15 +/- 2, 24 +/- 2, and 19 +/- 2 mm Hg in the epinephrine group; 13 +/- 1, 25 +/- 2, and 20 +/- 1 mm Hg in the low-dose vasopressin group; 13 +/- 2, 25 +/- 2, and 21 +/- 2 mm Hg in the medium-dose vasopressin group; and 13 +/- 2, 35 +/- 3, and 24 +/- 2 mm Hg in the high-dose vasopressin group (P < .05 at 90 seconds between epinephrine and high-dose vasopressin). Total cerebral blood flow was significantly higher after high-dose vasopressin than after epinephrine (P < .05 at 90 seconds and P < .01 at 5 minutes between groups). Five animals in the epinephrine, 5 in the low-dose vasopressin, 7 in the medium-dose vasopressin, and 6 in the high-dose vasopressin groups were successfully resuscitated and survived the 1-hour observation period. We conclude that administration of vasopressin leads to a significantly higher coronary perfusion pressure and myocardial blood flow than epinephrine during closed-chest CPR in a pig model of ventricular fibrillation.