Article, Cardiology

A comparison of transoesophageal cardiac pacing and epinephrine for cardiopulmonary resuscitation

Original Contribution

A comparison of transoesophageal cardiac pacing and epinephrine for cardiopulmonary resuscitationB

Meng-Hua Chena,*, Tang-Wei Liua, Lu Xieb, Feng-Qing Songa, Tao Hea

aInstitute of Cardiovascular Diseases, the First Affiliated Hospital of Guangxi Medical University, Nanning 530027, PR China

bDepartment of Physiology, School of Pre-Clinical Sciences, Guangxi Medical University, Nanning 530027, PR China

Received 3 January 2006; accepted 26 January 2006

Abstract The use of cardiac pacing to deal with bradycardia is well established. There is debate as to the benefits during cardiopulmonary resuscitation (CPR). This study was performed to compare the effects of transoesophageal cardiac pacing and high-dose epinephrine on the benefits of cardiopulmonary resuscitation after Asphyxial cardiac arrest in rats. Thirty Sprague-Dawley rats of both sexes were randomly selected to a saline group (Sal-gro, treated with normal saline 1 mL IV, n = 10), an epinephrine group (Epi-gro, treated with epinephrine 0.4 mg/kg IV, n = 10), or a pacing group (Pac-gro, treated with normal saline 1 mL IV combined with transoesophageal cardiac pacing, n = 10) in a blinded fashion during resuscitation after 10 minutes of asphyxial cardiac arrest. Manual chest compression was in all cases performed using the same methodology by the same personnel who was blinded to hemodynamic monitor tracings. The rate of restoration of spontaneous circulation was 1 (10%), 7 (70%), and 8 (80%) of 10 in Sal-gro, Epi-gro, and Pac-gro, respectively. The rate of ventilator withdrawal within 60 minuets after resuscitation in Pac-gro was higher than that of Epi-gro (8/8 vs 1/7, respectively; P = .001); the survival rate after 2 hours in Pac-gro was significantly higher than that in Epi-gro (7/8 vs 1/7, respectively; P = .01). The data demonstrate that both epinephrine and transoesophageal cardiac pacing are effective within 10 minutes of asphyxia in rats. It is worth noting that transoesophageal cardiac pacing produced a better outcome with respiration and longer survival time compared with epinephrine after restoration of spontaneous circulation.

D 2006

Introduction

The increasing emphasis on early management of out- of-hospital arrhythmias and cardiac arrest has led to

B This study was supported by the Guangxi Department of Education and the Guangxi Natural Science Foundation of China (no. 0135038).

* Corresponding author. Tel.: +86 771 5356536; fax: +86 771

5350031.

E-mail address: [email protected] (M.-H. Chen).

the development of sophisticated systems of prehospital care using improved equipment and techniques to deal with these medical challenges. The use of external pacing was first described by Zoll [1] in 1952 using a ground electrode attached to the skin and a subcutaneous needle electrode over the precordium. Zoll later introduced an external transcutaneous pacing machine using two 3-cm cutaneous electrodes, with numerous successful results in cases of acute and chronic complete heart block, and additionally, some reported cases of bventricular standstillQ [2-4].

0735-6757/$ – see front matter D 2006 doi:10.1016/j.ajem.2006.01.024

Transcutaneous pacing offers many advantages over temporary transvenous pacing. These include, but are not limited to, the lack of time delay for application, the avoid- ance of the complications of the invasive transvenous technique including pneumothorax, bleeding, infection, and iatrogenic malignant ventricular arrhythmias [5,6].

Many positive results on noninvasive cardiac pacing have been reported [7-12].

During the management of CA, external cardiac pacing can be used easily in the prehospital environment. Known contradictions are pain in the associated stimulation of skin and skeletal muscle and difficulty in recognition of Cardiac responses [13]. Additional reports indicated a high frequen- cy of electrical capture (93%), but a low frequency of palpable pulses (11%) showed that pacing did not result in any increase in survival in CA patients [14]. Similar negative results had also been reported [15-18].

These discrepancies may be accounted for because most data originate via clinical situations. Complicated clinical settings include differences in arrest (no-flow) times and cardiopulmonary resuscitation (CPR) (low-flow) times, different pharmacokinetics, different dose/response require- ments, and different timing of drug administration during low-flow CPR as opposed to during spontaneous circula- tion. It is unlikely the discrepancies in results could be avoided. Consequently, to establish the effectiveness of cardiac pacing in CPR, further investigation is needed. An advantage of animal models in CPR research is the ability to control differing variables that may be impractical to standardize in clinical trials. Unfortunately little research has been done in this field, only a few reports have been published that describe the effects of cardiac pacing on the outcomes of CPR on animals [19-21].

Considering cardiac pacing has been used to deal with bradycardia arrhythmia for many years and proven to be a valid treatment, it is hypothesized that cardiac pacing would improve the outcomes of CPR after bradyasystolic CA. In previous studies this assumption was validated by using transoesophageal cardiac pacing during CPR after asphyxial cardac arrest in rats [22].

To date, epinephrine is still the preferred resuscitated drug during CA and CPR. Whether transoesophageal cardiac pacing holds the same efficiency during CPR as epinephrine remains to be established. High-dose epinephrine enhanced myocardial perfusion pressure and Myocardial blood flow could possibly improve rates of restoration of spontaneous circulation [23,24]. High dose did not produce increased direct complications in the CA population com- pared with standard-dose epinephrine [25]. It is assumed that a relative high-dose epinephrine might benefit the rats that suffered from CA. The purpose of this study was to compare the efficiency of high-dose epinephrine and transoesophageal cardiac pacing on the outcome of CPR after asphyxial cardac arrest in rats under the same experimental conditions. The hypothesis was both epinephrine and transoesophageal cardiac pacing hold the same efficacy for CPR.

Materials and methods

This study was approved by the animal investigation committee at our university and was performed in accor- dance with National Institutes of Health guidelines for ethical animal research.

Animal preparation

Sprague-Dawley rats of both sexes, weighing 180 to 220 g, were fasted overnight with the exception of access to water. The animals were anesthetized by intraperitoneal injection of 1 g/kg urethane, placed in a supine position on a surgical board having the extremities immobilized. The proximal trachea was surgically exposed in the animals and a 14-gauge cannula inserted through a tracheostomy 10 mm caudal to the larynx. The cannula was advanced for a distance of 1 cm into the trachea and secured by ligature, which was also anchored to the skin.

Through the right external jugular vein, an 20-gauge polyethylene catheter was advanced through the superior vena cava into the right atrium. right atrial pressure was measured with reference to the midchest with a high- sensitivity pressure transducer. Another 20-gauge polyeth- ylene catheter was advanced from the left carotid artery into the thoracic aorta for measurement of aortic pressure with the high-sensitivity pressure transducer. The void space of the catheters was filled with physiologic salt solution containing 5 IU/mL of bovine heparin. The core temperature was measured through a rectal temperature probe. Conven- tional lead II electrocardiograms were recorded with subcutaneous needles.

The electrocardiogram (lead II), and aortic and right atrial pressures were continuously recorded on a desktop computer via 4-channel physiologic recorder (BL-420 E Bio-systems, The Chengdu Technology & Market Co Ltd, Chengdu, China) for subsequent analyses. The coronary perfusion pressure was calculated as the difference of minimal diastolic aortic and simultaneously recorded right atrial pressure.

Experimental protocol

After a 10- to 15-minute equilibration period after surgery, 10 minutes of asphyxial CA was induced with asphyxiation by clamping the tracheal tubes. Cardiac arrest was determined by loss of aortic pulsations and mean aortic pressure (MAP) of less than 10 mm Hg together with asystole or pulseless electrical activity [26].

Thirty Sprague-Dawley rats were prospectively random- ized to a saline group (Sal-gro, treated with normal saline 1 mL IV, n = 10), an epinephrine group (Epi-gro, treated with epinephrine 0.4 mg/kg IV, n = 10), or a pacing group (Pac-gro, treated with normal saline 1 mL IV combined with transoesophageal cardiac pacing, n = 10) in a con- cealed fashion during resuscitation after 10 minutes of asphyxial CA.

Groups

n

ROSC, n (%)

Time from CPR to ROSC (seconds, mean F SD)

Sal-gro

10

1 (10)

200

Epi-gro

10

7 (70)*

82 F 62

Pac-gro

10

8 (80)**

124 F 76

At the end of 10 minutes of asphyxiation CPR was introduced. Each drug was administered, and transoepha- geal cardiac pacing was initiated in Pac-gro at the same time. Drug administration was introduced only once at this point in all groups. Ventilation was performed by a volume- controlled small animal ventilator (DH-150, the medical instrument of Zhejiang University, China), with room air at 70 breaths per minute and tidal volume adjusted to 6 mL/kg. Ventilation was maintained until spontaneous breathing started or until 1 hour after ROSC. This imitated the sce- nario of no oxygen available in some circumstance. Manual chest compression at a rate of 180 compressions per minute with equal compression-relaxation duration was always per- formed by the same investigator who was excluded from the hemodynamic monitor tracings and guided only by acoustic audio tones emitted from the cardiac electrophysiologic stimulus apparatus. Compression depth was about 30% the anteroposterior chest diameter at maximal compression. Restoration of spontaneous circulation was defined as the return of supraventricular rhythm with an MAP of 20 mm Hg or higher for a minimum of 5 minutes. Failure to restore spontaneous circulation resulted in discontinuation of resuscitation efforts after 10 minutes.

Table 1 Comparison of ROSC and time from CPR to ROSC

among 3 groups

The rate of ROSC was observed in only 1 (10%) of 10 and the time

from CPR to ROSC was 200 seconds in Sal-gro. However, the rates of ROSC were observed in 7 (70%) and 8 (80%) of 10, respectively, in Epi-gro and Pac-gro, which were significantly higher than that in Sal- gro ( P = .02 and .005, respectively). However, no significant difference was indicated between Epi-gro and Pac-gro. In reference to the time from CPR to ROSC, Epi-gro showed a faster tendency than Pac-gro but statistically was insignificant.

* P b .05 vs Sal-gro.

** P b .01 vs Sal-gro.

Table 2 Comparison study of the changes in respiration within 60 minutes after ROSC between Epi-gro and Pac-gro

Appearance of spontaneous breathing was found in some of Resuscitated animals; only a small percentile could be withdrawn from the ventilator within

60 minutes after ROSC. In Epi-gro, AOSB was found in 5 (71.4%) of 7, but only 1 (14.3%) of 7 could withdraw from ventilation, which took 55 minutes. In Pac-gro, AOSB was found in 8 (100%), and 100% could withdraw from ventilation within 60 minutes, which took 33 F 12 minutes. There was a significant difference between 2 groups with regard to the rate of ventilator withdrawal within 60 minutes ( P = .001). Time from CPR to ROSB showed no difference between 2 groups. Time of ventilation withdrawal cannot be compared because of the low rate of ventilation withdrawal in Epi-gro. Sal-gro data was excluded because of the low survival rate.

* P b .01 vs Epi-gro.

Transesophageal cardiac pacing protocol

A 5F pacing catheter with four 1-mm ring electrodes and an inter-electrode distance of 5 mm was inserted orally into the esophagus of the subjects in 3 groups before CPR at about 7 cm depth. The pacing catheter was connected to a cardiac electrophysiologic stimulus apparatus (DF-5A, Suzhou DongFang Electric Apparatus Factory, Suzhou, China). In addition to transmitting electric stimuli, the stimulus appara- tus can emit acoustic audio tones at a frequency of 180 per minute to guide the investigator in performing chest compression consistently for the rats of 3 groups. Only animals in the pacing group received pacing stimuli. Cardiac pacing was performed using 2 poles (distal electrode and its adjacent electrode) on the pacing catheter (stimulus duration width, 10 milliseconds and 25 V). Stimulation at a rate of 180 stimuli per minute was performed continuously in early CPR. With the ROSC of the rats, the pacing frequency was altered to the rate of 20 to 30 per minute, higher than the rate of intrinsic rhythm of the rats correspondingly, and stimulate the left atrium intermittently (20 seconds for stimulation and 10 seconds for pause alternately) for 20 to 30 minutes so as to provoke the increasing heart response with the intent of quickening the heart rate (HR) and improve the cardiac output of the animal.

Post resuscitation care

Hemodynamics and HR monitoring previously men- tioned were continued for 1 hour. Mechanical ventilation was continued for 1 hour or less after successful re- suscitation depending on the condition of the animal’s respiration. The appearance of spontaneous breathing (AOSB) of the animals was observed closely and imme- diately recorded by the investigators. Appearance of spontaneous breathing was defined as the return of spontaneous breathing with more than 5 breaths per minute under the circumstances of mechanical ventilation. If spontaneous breathing presented with z40 breaths per minute for z5 minute within 1 hour after ROSC and blood pressure remained stable or increased gradually, mechanic ventilation could be withdrawn. After 1 hour of intensified

Groups

ROSC (n)

AOSB, n (%)

Withdrawal from ventilator, n (%)

Time from CPR to ROSB (min)

Time of withdrawal from ventilator (min)

Epi-gro

7

5 (71.4)

1 (14.3)

14 F 5

55

Pac-gro

8

8 (100)

8 (100)*

14 F 6

33 F 12

Groups

ROSC (n)

1-h Survival, n (%)

2-h Survival, n (%)

Mean survival time (h)

Longest survival time (h)

Epi-gro

7

7 (100)

1 (14.3)

1 (1.1)

9

Pac-gro

8

8 (100)

7 (87.5)*

3.5 (1.75, 21.75)

24

observation, all catheters were removed with tracheal tube left in place. The wound was sutured. The animals were then returned to their cages and allowed to recover without further interventions. The investigators observed the animals until their spontaneous breathing stopped. The survival time was defined as the time from ROSC to the cessation of spon- taneous breathing.

Table 3 Comparison of the survival time after resuscitation between Epi-gro and Pac-gro

Survival time was presented as median (25th, 75th percentile). Although 1-hour survival rate between Epi-gro and Pac-gro had no difference, 2-hour

survival rate in Pac-gro was significantly higher than that in Epi-gro ( P = .01). Mean survival time showed an increased tendency in Pac-gro compared with Epi-gro after resuscitation. Sal-gro data were excluded because of the low survival rate.

* P b .05 vs Epi-gro.

Necropsy was routinely performed after death, in both resuscitated and unresuscitated animals. Thoracic and abdo- minal organs were examined for gross evidence of traumatic injures that followed intraperitoneal injection of anesthesia, airway management, vascular cannulation, or precordial compression. The position of catheters was documented.

Statistical analysis

Data were presented as mean (FSD) for normally distributed variables and alternately as median (25th, 75th percentiles). One-way analysis of variance was used to determine statistical significance among the 3 groups. Concerning the data after CPR, Student t tests were applied to examine the difference between the epinephrine and pacing groups with regard to blood pressure and HR. Mann- Whitney U test was used to determine differences for variables not normally distributed between the groups. Using Fisher exact test, we tested discrete variables such as ROSC, and 1- and 2-hour survival. A 2-tailed value of P b .05 was considered statistically significant.

Results

Experimental variables

Before asphyxia, no significant differences were ob- served among the 3 groups with regard to body weight, HR, systolic blood pressure, diastolic blood pressure, MAP, central venous pressure, and body temperature. Time from the initiation of asphyxia to CA was not significantly different among the 3 groups. Time from the initiation of asphyxia to termination of spontaneous breathing was not significantly different among the 3 groups.

Results of CPR in each group

The rates of ROSC in Epi-gro and Pac-gro were significantly higher than that in Sal-gro ( P = .02 and .005, respectively), but no difference was noted between Epi-gro and Pac-gro (Table 1). The appearance of spontaneous

breathing was seen in both Epi-gro and Pac-gro, but the rate of ventilator withdrawal within 60 minutes after resuscitation in Pac-gro was much higher than that in Epi-gro ( P = .001) (Table 2); 2-hour survival rate in Pac-gro was significantly higher than that in Epi-gro ( P = .01); mean survival time showed a longer tendency in Pac-gro compared with Epi-gro after resuscitation, but not to a statistically significant degree (Table 3).

Coronary perfusion pressure changes during resuscitation among 3 groups

Coronary perfusion pressure in Sal-gro was the lowest among the 3 groups during the earliest 10-minute resusci- tated phase (Fig. 1). The changes of CPP coincided with the rate of ROSC among the 3 groups.

Changes in MAP during 60 minutes of monitoring after CPR

Mean aortic pressure in Pac-gro remained stable unlike the Epi-gro, which indicated a dropping tendency during 60-minute monitoring after CPR (Fig. 2).

Fig. 1 Changes in CPP during the earliest 10 minutes of resuscitation after 10 minutes of untreated asphyxiation. Variables were expressed as mean FSEM. Coronary perfusion pressure in Sal-gro was lower than those in Pac-gro and Epi-gro from 1.5 to 10 minutes ( P = .039-.01 compared with Pac-gro and P = .029-

.008 compared with Epi-gro, respectively). The changes of CPP were consistent with the rate of ROSC among the 3 groups. The lowest CPP in Sal-gro resulted in the lowest rate of ROSC during the earliest 10-minute resuscitation phase.

Fig. 2 Changes in MAP during 60 minutes of monitoring after CPR. Variables were expressed as mean F S.D. Mean aortic pressure in Epi-gro was higher than that in Pac-gro from 4 to 20 minutes ( P = .000, .000, .000, .003, .006, and .012, respec- tively), although there was no significant difference between the 2 groups from 25 to 60 minutes. In the Pac-gro, MAP maintained a stable status 15 minutes later. In contrast, the Epi-gro MAP showed a rapidly decreasing tendency and considerably lower MAP from 35 to 60 minutes compared with 15 minutes ( P = .007, .016, .001,

.001, .000, and .000, respectively).

Changes in HR during 60 minutes of monitoring after CPR

Heart rate in the Pac-gro was higher than that of Epi-gro and maintained a stable status; alternately, HR in the Epi-gro showed a decreasing tendency 15 minutes later during 60 minutes of monitoring after CPR (Fig. 3).

Necropsy results

Correct placement of catheters was confirmed in all of the animals. No adverse effects of invasive procedures or other traumatic injures were found.

Discussion

In the present study, investigations were conducted into the effectiveness of epinephrine and transoesophageal cardiac pacing for 10 minutes of asphyxia in rats. The rate of ROSC was seen in 7 (70%) and 8 (80%) of 10, respectively, in Epi-gro and Pac-gro, which is significantly higher than that in Sal-gro ( P b .05 and b.01 respectively), although did not present a significant difference between Epi-gro and Pac-gro. Therefore, the conclusion is that both epinephrine as well as transoesophageal cardiac pacing are effective within 10 minutes of asphyxia in rats.

Epinephrine administered during CPR is known to increase aortic diastolic and myocardial perfusion pressures, while enhancing myocardial blood flow. However, published results of dose-response effects of epinephrine vary so much between studies because of differences in animal models and

duration of ischemia before drug administration that opti- mal dosing of epinephrine during CPR is less certain. As a preliminary study, relatively Large doses of epinephrine were administered to facilitate examination during 6 and 14 minutes of asphyxiation. In the case of 6 minutes of asphyxiation, all of the animals could be resuscitated. In the case of 14 minutes of asphyxiation, most of the animals failed to resuscitate. Ten minutes of asphyxiation was chosen for this experiment to compare the effects of transoesopha- geal cardiac pacing with epinephrine during the CPR.

Although the pharmacodynamics of epinephrine admin- istered during CPR is generally well known, the therapeutic mechanisms of transoesophageal cardiac pacing for the CA is complicated, multifactorial, and remains unclear at the present time. In the present study, during the earliest 10 minutes of resuscitation, CPP in Pac-gro was higher than that in Sal-gro. In addition, higher CPP resulted in a higher resuscitated rate in Pac-gro compared with that in Sal-gro.

Although the exact mechanisms of the rise in CPP in Pac-gro cannot be ascertained with the present study design, given that no other medications were administered in both groups with the exception of a saline solution, it is therefore reasonable to assume that the higher CPP may have been caused by transoesophageal cardiac pacing. In 1986, Murdock et al [27] described a patient in cardiogenic shock and Complete heart block in whom the associated vigorous abdominal and chest muscle contractions caused by transthoracic cardiac pacing resulted in a marked augmen- tation of cardiac output and systemic blood pressure via a bCPRQ effect. Transthoracic cardiac pacing is frequently associated with simultaneous stimulation of skeletal muscle

Fig. 3 Changes in heart rate during 60 minutes of monitoring after CPR. Variables were expressed as mean F S.D. Heart rate showed no significant difference between the 2 groups from 0 to 10 minutes. However, 15 minutes later, HR in the Pac-gro was higher than that of Epi-gro ( P b .01) and maintained a stable status. Alternately, HR in the Epi-gro animals demonstrated a decreasing tendency. Lower HR from 30 to 60 minutes was observed compared with 15 minutes ( P = .044, .004, .002, .001, .001,

.000, and .004, respectively). Sal-gro data were excluded because of the low survival rate.

and nerves, which is beneficial to patients. Transoesopha- geal cardiac pacing always shares the similar reaction in the experimented rats. It is presumed that artificial stimulation may influence neurohumoral regulation of the animal and cause endogenic vasoconstrictive substances or an alterna- tive chemical to be released, including catecholamines, which result in contractive reaction of systemic vessel, increase of CPP, and improvement of resuscitation.

According to this preliminary study, consideration of the stimulation of higher voltage output may be beneficial in capturing heart rate and enhancing the survival rate. Under the circumstance of CA, the position of electrodes could only be placed experientially. Higher voltage could possibly offset the potential pacing threshold rising resulting from inaccurate placement of the electrode. The pacing voltage was fixed at 20 to 25 V during early CPR. After ROSC, the voltage was reduced by 3 to 5 V to lessen abdominal and chest muscle contractions caused by transoesophageal cardiac pacing.

It is also important to keep chest compression to be consistent with pacing frequency during CPR. The electro- physiologic features of cardiac muscle cells are susceptible to ischemia. At the resuscitation phase, resting membrane potential of cardiac muscle cells had not completely recovered from CA. Under such circumstances, irregular stimulation is apt to form unidirectional conduction blocks and conduction delays, which are well-documented patho- physiologic conditions for the development of tachyarrhyth- mias, based on the reentrant phenomena. Manual external (cardiac percussion) pacing is 1 of 3 emergency pacing modalities [28,29]. Precordial compression is comparable to manual external pacing (one kind of mechanic stimulation) to the heart; this could cause cardiac muscle excitability to change regularly, just as an electrical stimulation does. If cardiac muscle received different kinds of stimulation at different times, it would be possible to stroke in vulnerable periods of cardiac muscle cells and cause tachyarrhythmias, which may attenuate the effects of cardiac pacing or even induce serious iatrogenic adverse results. However, pacing at 180 stimuli per minute combined with compression at the same frequency could simulate a physiologic state and might at least avoid or decrease such potential disadvan- tages. During the present study, chest compression was always performed by the same investigator who was blinded from access to hemodynamic monitor tracings, but guided by acoustic audio tones emitted from the cardiac stimulus apparatus. This ensured the synchronization of compression and pacing in Pac-gro as well as eliminated the inves- tigator’s bias as much as possible.

After ROSC, artificial stimulation modality should be changed from continuous pacing to intermittent pacing (20 seconds for stimulation pause for 10 seconds alternate- ly). Pacing frequency should be altered to the rate of 20 to 30 per minute higher than the intrinsic heart rate of the rats correspondingly to provoke the increasing reaction of the heart muscle in the animals. Cardiac output was not

measured owning to the difficult procedure of advancing the catheter to the left ventricular cavity without damnification of the heart during CPR. It is believed that a little faster heart rate could enhance the cardiac output, improve perfusion pressure of vital organ, and rectify metabolic turbulence of the animals.

Results clearly show that cardiac pacing helps to resume spontaneous breathing of resuscitated animals. In Pac-gro, AOSB was found in 8 (100%), and 100% could withdraw the ventilator within 60 minutes. The rate of ventilator withdrawal was much higher than that of Epi-gro. The improved respiratory effort in Pac-gro as opposed to Epi-gro might be attributed to electric stimulation. Respiratory effects of electrical stimulation of the phrenic nerve in anesthetized cats indicate that the phrenic nerve itself may affect respiratory output and play a role in the control of breathing [30]. Langou et al [31] reported that diaphragm pacing caused pulmonary arteriolar resistance to decrease and normalized the arterial blood gases. The mechanism for these changes was improved with alveolar ventilation.

Electrical stimulation has been used for more than 35 years to restore breathing to patients with high quadri- plegia resulting in respiratory paralysis and patients with central alveolar hypoventilation. Up to 1996, approximately 1000 people worldwide had received phrenic pacing de- vices, most with substantially positive results [32]. Electric stimulation of the diaphragm essentially improved ven- tilation volume and regularity, as well as pulmonary Gas exchanges [33].

Because diaphragm pacing has so many advantages for improvement in respiratory efficiency, it is speculated that transoesophageal cardiac pacing might share the same function, accounting for a positive trend toward better result with respiration in Pac-gro.

A longer survival time after resuscitation was found in Pac-gro compared with that of Epi-gro. A proposed explanation for the beneficial effect could be the result of 1 of 4 mechanisms. First, because of shorter half-life of exogenic catecholamines, the pharmacologic effect of epinephrine administered initially during CPR attenuates rapidly over time, which results in induced heart rate and MAP decreasing gradually and leading to a shorter duration of survival in Epi-gro.

Secondly, although large doses of epinephrine increase CPP and flow during CPR, epinephrine also increases myocardial oxygen consumption because of its b-adrenergic actions, including inotropic and chronotropic effects. This consequently increases oxygen demand and exceeds the increase in oxygen delivery produced by augmentation of CPP and myocardial blood flow [34]. Accordingly, epinephrine significantly increased the severity of postre- suscitation myocardial dysfunction and decreased duration of survival [35].

Thirdly, as suggested above, artificial stimulation may influence the neurohumoral regulation of the animal and cause endogenic vasoconstrictive substances to release,

which resulted in contractive reaction of systemic vessels. Perhaps the pharmacologic effect of endogenic vasocon- strictive substances may last longer and cause a relatively stable heart rate and MAP, which in turn assure the Blood supply of the vital organs and help to rectify the metabolic disturbance of the animals in Pac-gro after CPR.

Finally, transoesophageal cardiac pacing is comparable to diaphragm pacing, which helps to improve respiratory efficiency and prolong survival time.

A limitation of the present study is the fact that this is bradyasystole in the setting of asphyxial arrest and that this mechanism is an uncommon cause of bradyasystolic arrest in adults (although likely much more common in children). Therefore, the benefit for treating CA with cardiac pacing during CPR may be restricted. We caution against direct extrapolation of the present findings to human victims of CA in the clinical setting.

Conclusion

Both epinephrine and transoesophageal cardiac pacing are effective in 10 minutes of asphyxia in rats. However, transoesophageal cardiac pacing produced a better outcome with respiration, more stable MAP and HR, and conse- quently, prolonged survival time compared with epinephrine after ROSC.

A major new finding of this study is that cardiac pacing is now proven to be effective for CPR in a rat of asphyxial model and has a better outcome than epinephrine.

Acknowledgment

The authors express their gratitude to the staff of the Department of Physiology for excellent technical help, suggestions, and expert input.

References

  1. Zoll PM. Resuscitation of the heart in ventricular standstill by external electric stimulation. N Engl J Med 1952;247(20):768 – 71.
  2. Zoll PM, Linenthal AJ, Norman LR. Treatment of Stokes-Adams disease by external electric stimulation of the heart. Circulation 1954;9(4):482 – 93.
  3. Zoll PM, Linenthal AJ, Norman LR, et al. Treatment of unexpected cardiac arrest by external electric stimulation of the heart. N Engl J Med 1956;254(12):541 – 6.
  4. Zoll PM, Linenthal AJ, Norman LR, et al. External electric stimulation of the heart in cardiac arrest: Stokes-Adams disease, reflex vagal standstill, drug-induced standstill, and unexpected circulatory arrest. AMA Arch Intern Med 1955;96(5):639 – 53.
  5. Austin JL, Preis LK, Crampton RS, et al. Analysis of pacemaker malfunction and complications of temporary pacing in the coronary care unit. Am J Cardiol 1982;49(2):301 – 6.
  6. Hynes JK, Holmes Jr DR, Harrison CE. Five-year experience with Temporary pacemaker therapy in the coronary care unit. Mayo Clin Proc 1983;58(2):122 – 6.
  7. Clinton JE, Zoll PM, Zoll R, et al. Emergency noninvasive external cardiac pacing. J Emerg Med 1985;2(3):155 – 62.
  8. White JD, Brown CG. Immediate transthoracic pacing for cardiac asystole in an emergency department setting. Am J Emerg Med 1985;3(2):125 – 8.
  9. Olson CM, Jastremski MS, Smith RW, et al. External cardiac pacing for out-of-hospital bradyasystolic arrest. Am J Emerg Med 1985;3(2): 129 – 31.
  10. Zoll PM, Zoll RH, Falk RH, et al. External noninvasive temporary cardiac pacing: clinical trials. Circulation 1985;71(5): 937 – 44.
  11. O’Toole KS, Paris PM, Heller MB, et al. Emergency transcutaneous pacing in the management of patients with bradyasystolic rhythms. J Emerg Med 1987;5(4):267 – 73.
  12. Tachakra SS, Jepson E, Beckett MW, et al. Successful transcutaneous external pacing for asystole following cardiac arrest. Arch Emerg Med 1988;5(3):184 – 5.
  13. Falk RH, Zoll PM, Zoll RH. Safety and efficacy of noninvasive cardiac pacing. A preliminary report. N Engl J Med 1983;309(19): 1166 – 8.
  14. Eitel DR, Guzzardi LJ, Stein SE, et al. Noninvasive transcutaneous cardiac pacing in prehospital cardiac arrest. Ann Emerg Med 1987;16(5):531 – 4.
  15. Falk RH, Jacobs L, Sinclair A, Madigan-McNeil C. External noninvasive cardiac pacing in out-of-hospital cardiac arrest. Crit Care Med 1983;11(10):779 – 82.
  16. Knowlton AA, Falk RH. External cardiac pacing during in-hospital cardiac arrest. Am J Cardiol 1986;57(15):1295 – 8.
  17. Quan L, Graves JR, Kinder DR, Horan S, Cummins RO. Transcu- taneous cardiac pacing in the treatment of out-of-hospital Pediatric cardiac arrests. Ann Emerg Med 1992;21(8):905 – 9.
  18. Cummins RO, Graves JR, Larsen MP, et al. Out-of-hospital transcutaneous pacing by emergency medical technicians in patients with asystolic cardiac arrest. N Engl J Med 1993;328(19): 1377 – 82.
  19. Voorhees III WD, Foster KS, Geddes LA, et al. Safety factor for precordial pacing: minimum current thresholds for pacing and for ventricular fibrillation by vulnerable-period stimulation. Pacing Clin Electrophysiol 1984;7(3 Pt 1):356 – 60.
  20. Niemann JT, Adomian GE, Garner D, et al. Endocardial and transcutaneous cardiac pacing, calcium chloride, and epinephrine in postcountershock asystole and bradycardias. Crit Care Med 1985; 13(9):699 – 704.
  21. Niemann JT, Haynes KS, Garner D, et al. Postcountershock pulseless rhythms: response to CPR, artificial cardiac pacing, and adrenergic agonists. Ann Emerg Med 1986;15(2):112 – 20.
  22. Song F-Q, Xie L, Chen M-H. Transoesophageal cardiac pacing is effective for cardiopulmonary resuscitation in a rat of asphyxial model. Resuscitation 2006 [in press].
  23. Paradis NA, Martin GB, Rosenberg J, et al. The effect of standard- and high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation. JAMA 1991;265(9): 1139 – 44.
  24. Chase PB, Kern KB, Sanders AB, et al. Effects of graded doses of epinephrine on both noninvasive and invasive measures of myocardial perfusion and blood flow during cardiopulmonary resuscitation. Crit Care Med 1993;21(3):413 – 9.
  25. Callaham M, Barton CW, Kayser S. potential complications of high- dose epinephrine therapy in patients resuscitated from cardiac arrest. JAMA 1991;265(9):1117 – 22.
  26. Ebmeyer U, Keilhoff G, Wolf G, et al. Strain specific differences in a cardio-pulmonary resuscitation rat model. Resuscitation 2002;53(2): 189 – 200.
  27. Murdock DK, Moran JF, Speranza D, et al. Augmentation of cardiac output by external cardiac pacing: pacemaker-induced CPR. Pacing Clin Electrophysiol 1986;9(1 Pt 1):127 – 9.
  28. Chan L, Reid C, Taylor B. Effect of three emergency pacing modalities on cardiac output in cardiac arrest due to ventricular asystole. Resuscitation 2002;52(1):117 – 9.
  29. Tucker KJ, Shaburihvili TS, Gedevanishvili AT. Manual external (fist) pacing during high-degree atrioventricular block: a lifesaving inter- vention. Am J Emerg Med 1995;13(1):53 – 4.
  30. Marlot D, Macron JM, Duron B. Inhibitory and excitatory effects on respiration by phrenic nerve afferent stimulation in cats. Respir Physiol 1987;69(3):321 – 33.
  31. Langou RA, Cohen LS, Sheps D, et al. Ondine’s curse: Hemodynamic response to diaphragm pacing (electrophrenic respiration). Am Heart J 1978;95(3):295 – 300.
  32. Creasey G, Elefteriades J, DiMarco A, et al. Electrical stimulation to restore respiration. J Rehabil Res Dev 1996;33(2):123 – 32.
  33. Klimov AG, Levshankov AI. Optimization of external respiration in patients during surgery with different types of anesthesia using transcutaneous electric stimulation of the diaphragm. Anesteziol Reanimatol 1993;(4):3 – 7.
  34. Ditchey RV, Lindenfeld J. Failure of epinephrine to improve the balance between myocardial oxygen Supply and demand during closed-chest resuscitation in dogs. Circulation 1988;78(2):382 – 9.
  35. Tang W, Weil MH, Sun S, et al. Epinephrine increases the severity of postresuscitation myocardial dysfunction. Circulation 1995;92(10): 3089 – 93.

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