Patients with chronic left ventricular (LV) dysfunction are assumed to have a lower chance of successful CPR and lower likelihood of ultimate survival. However, these assumptions have rarely been documented. Therefore, we investigated the outcome of prolonged ventricular fibrillation (VF) and CPR in a rat model of chronic LV dysfunction. Sprague-Dawley rats were randomized to (1) chronic LV dysfunction: animals underwent left coronary artery ligation; and (2) sham control. Echocardiography was used to measure cardiac performance before surgery and 4 weeks after surgery. Four weeks after surgical intervention, 8 min of VF was induced and defibrillation was delivered after 8 min of CPR. LV dilation and low ejection fraction were observed 4 weeks after coronary ligation. With optimal chest compressions, coronary perfusion pressure values during CPR were well maintained and indistinguishable between groups. There were no differences in resuscitability and numbers of shock required for successful resuscitation between groups. Despite the significantly decreased cardiac index in LV dysfunction animals before induction of VF, no differences in cardiac index were observed between groups following resuscitation, which was associated with the insignificant difference in postresuscitation survival. In conclusion, the outcomes of CPR were not compromised by the preexisting chronic LV dysfunction.
A majority of episodes of sudden cardiac deaths occur in victims with ischemic heart disease. Ischemic heart disease may develop over a lengthy span of time and is often associated with left ventricular (LV) remodeling. This ultimately leads to chronic ischemic LV dysfunction with subsequent congestive heart failure. Lower ejection fraction (EF) has been consistently demonstrated to be the strongest independent predictor of sudden cardiac death [
The goals of the present study were therefore to obtain prognostic information on the outcome of prolonged ventricular fibrillation (VF) and CPR in the chronic ischemic LV dysfunction due to complete left coronary artery ligation in Sprague-Dawley rats. We hypothesized that when undergoing prolonged VF/CPR, chronic ischemic LV dysfunction animals would be less likely to be resuscitated. If resuscitated, such animals would be likely to have more severe postresuscitation myocardial dysfunction and decreased duration of postresuscitation survival.
This study was approved by the Institutional Animal Care and Use Committee of the Weil Institute of Critical Care Medicine. All animals received humane care in compliance with the
Fourteen male Sprague-Dawley rats weighing
The animals were fasted overnight except for free access to water. They were anesthetized by intraperitoneal injection of pentobarbital (45 mg/kg). The animals were then orally intubated and mechanically ventilated with room air. Electrocardiogram (ECG) was continuously monitored. After measurements of baseline myocardial function using noninvasive transthoracic echocardiography, a thoracotomy via the third left intercostal space was performed. The atrial appendage was elevated and the left coronary artery near its origin was ligated. Successful ligation was confirmed by the ST segment elevation. The chests were then closed, and the animals were returned to their cages. Postsurgical pain was controlled with intramuscular injection of ketorolac (0.4 mg/kg). Control rats were prepared similarly except that the coronary artery was not ligated.
Four weeks after surgical intervention, the animals were reanesthetized and intubated. Cardiac geometry and function were assessed by echocardiography. A PE-50 catheter (Becton Dickinson) was advanced from the right carotid artery into the left ventricle for measurement of LV pressure. A PE-50 catheter was advanced through the left external jugular vein into the right atrium for measurement of right atrial pressure. For electrical induction of VF, a 4 French PE catheter was advanced through the right external jugular vein into the right atrium, and through its lumen a precurved guide wire was then advanced into the right ventricle for electrically inducing VF. A PE-50 catheter was advanced through the left femoral artery into the thoracic aorta for measurement of mean aortic pressure (MAP). A thermocouple microprobe (9030-12-D-34, Columbus Instruments; Columbus, OH) was advanced from the right femoral artery into the descending thoracic aorta for measurement of blood temperature. ECG was recorded. A heat lamp was used to maintain body temperature at 36.8°C (±0.2%).
The animals were mechanically ventilated with room air at a tidal volume of 0.55 mL/100 g and a frequency of 100 breaths/min. A progressive increase in 60 Hz current to a maximum of 4 mA was then delivered to the right ventricular endocardium. The current flow was continued for 3 min to preclude spontaneous reversal of VF. Mechanical ventilation was discontinued after onset of VF. Precordial compression was then begun and mechanical ventilation with 100% O2 was resumed 8 min after the onset of VF. Precordial compression at a rate of 200 min−1 was synchronized to provide a compression/ventilation ratio of 2 : 1. The depth of compression was adjusted to maintain a coronary perfusion pressure (CPP) at
Following ROSC, the animals were monitored for 4 hours. All catheters were then removed. The animals were observed for an additional 68 hours after which they were euthanized with an intraperitoneal injection of pentobarbital sodium (150 mg/kg). An autopsy was performed to confirm the complete ligation of left coronary artery, and organs were inspected for gross abnormalities, including evidence of traumatic injuries consequent to cannulation, airway management, or precordial compression.
LV geometry and cardiac function prior to and 4 weeks after ligation was quantitated with a Sonos 2500 echocardiographic system utilizing a 7.5 Hz transducer (Model 21363A, Hewlett-Packard Co., Medical Products Group, Andover, MA). The animal hearts were imaged in the parasternal short-axis plane through the anterior chest. At two-dimensional imaging of short-axis view, left ventricular end-systolic volumes (LVESV) and left ventricular end-diastolic volumes (LVEDV) were calculated by the method of discs (Acoustic Quantification Technology, Hewlett-Packard, Andover, MA). From these, EF was computed.
Aortic, LV, right atrial pressures, and ECG were recorded via a WinDaqdata-acquisition system (DataQ; Akron, OH). CPP was calculated as the difference between aortic and time-coincident right atrial pressures in the interval between chest compressions.
Myocardial function during VF/CPR experimental phase was assessed from measurements of LV pressure and cardiac output. The rate of LV pressure increase at 40 mmHg (
Measurements are reported as means ± SD. Comparisons between groups before surgical operation and 4 weeks after coronary ligation were performed by using Student’s
Before surgical operations, there were no differences in baseline values of echocardiographically measured LVEDV, LVESV, and EF between groups (Figure
Echocardiographic measurements at baseline (BL) and 4 weeks after left coronary artery ligation. Values are means ± SD. LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; EF: ejection fraction.
CPP values were maintained at
Effects of intervention on ROSC, number of 72-hour survival, and number of defibrillations.
Group | ROSC | 72-hour survival | Number of shocks |
---|---|---|---|
Chronic LV dysfunction | 6/7 | 3/6 |
|
Control | 5/7 | 3/5 |
|
Values are means ± SD. ROSC: return of spontaneous circulation.
Before induction of VF and following ROSC, there were no significant differences in both MAP and heart rate in heart failed animals when compared with control animals (Figure
Mean aortic pressure and heart rate before onset of cardiac arrest and following resuscitation. Values are means ± SD. MAP: mean aortic pressure; BL: baseline; VF: ventricular fibrillation; PC: precordial compression; DF: defibrillation.
Myocardial function, as measured by
LV end-diastolic pressure (LVDP) before onset of cardiac arrest and following resuscitation. Values are means ± SD;
Cardiac index before onset of cardiac arrest and following resuscitation. Values are means ± SD;
Kaplan-Meier survival curves.
At autopsy, transmural scar formation of the LV anterior wall was observed in LV dysfunction animals. No gross abnormalities were observed at autopsy in any animals.
In this study, CPR was performed effectively after prolonged VF in a rat model of chronic ischemic LV dysfunction. With optimal chest compressions, the ease of defibrillation and cardiac resuscitability were not compromised by the preexisting chronic LV dysfunction. Furthermore, this study revealed that it was the systemic blood that flows through the circulation following ROSC, rather than the preexisting chronic LV dysfunction, which was the predominant determinant of postresuscitation survival.
Fewer studies have directly evaluated the influence of preexisting chronic ischemic LV dysfunction on the likelihood of resuscitability and ultimate postresuscitation survival. Previously we have demonstrated the feasibility of applying CPR in a rat model of chronic nonocclusive left coronary artery constriction [
Overt LV dysfunction and extensive ventricular remodeling were observed in left coronary artery ligation animals. Myocardial function as assessed by EF, CI,
In the current study, the number of defibrillations and resuscitability in LV dysfunction animals did not differ from thoat in control. It is well known that the myocardial blood flow is the overriding determinant for the success of resuscitation effort, especially when the duration of untreated cardiac arrest is prolonged [
Following ROSC, the primary goal of patient care is to ensure that the patient has adequate spontaneous circulation, such that the whole-body ischemia/reperfusion injury can be prevented, minimized, or reversed; subsequently, the ultimate postresuscitation survival with intact organ function might be improved. Reversible myocardial dysfunction has been observed after ROSC in experimental models [
It is interesting to notice that no difference in CI following ROSC was observed between groups regardless of the significant difference before induction of VF. Previously the phenomenon of adaptive process of chronic hypoxia conferring myocardial tolerance to subsequent acute severe hypoxia/reoxygenation or ischemia/reperfusion injury has been observed in cardiac myocytes models [
There are limitations that need to be acknowledged and addressed regarding the present study. Clinically, most episodes of VF are caused by ischemic heart disease rather than electric shock. We recognized that despite the minimal level of current flow, the potential electrical injury to the myocardium would likely compromise the clinical relevance of this rat model of VF/CPR. Regardless of this potential shortcoming, this, however, did not alter our conclusion since all the animals receive the same procedure. In this preliminary study, CPP is adopted as a reflection of myocardial blood flow. We admitted that ideally myocardial blood flow should be measured by real-time techniques during CPR and following resuscitation. However, aiming to observe the effect of chronic ischemic LV dysfunction on the duration of postresuscitation survival and the technical difficulties of directly measuring myocardial blood flow during chest compressions do not enable us to perform such measurement in real time. Nevertheless, based on the current data, we cautiously draw the conclusion that the extent of levels of CPP can, in part, reflect myocardial blood flow. In addition, we admit that our current studies lack direct evidence about the underlying mechanisms responsible for the phenomenon of “myocardial ischemic tolerance to insult of cardiac arrest and CPR.” This relatively preserved postresuscitation myocardial function in the chronic ischemic heart deserves further investigation. Finally, we admit that LVEF values before induction of VF are greater than those we usually observed in patients with chronic heart failure. Nevertheless, we do observe that the outcomes of CPR were not compromised by preexisting chronic ischemic LV dysfunction. The appropriate animal model and optimal experimental design will be considered in our future investigations, so that the effect of more depressed LVEF on the outcome of CPR can be further revealed.
Our findings may have potential clinical implications. First, our work indicates that efficacy of chest compressions during CPR overrides the detrimental effect of preexisting chronic heart failure in determining the likelihood of successful resuscitation. Second, since postresuscitation outcome was largely determined by the systemic blood flow, the postresuscitation patient care should be focused on maintaining and improving global blood flow following resuscitation, such that the ultimate postresuscitation survival with intact organ function might be improved.
Cardiac index
Coronary perfusion pressure
Cardiopulmonary resuscitation
Ejection fraction
Left ventricular
Left ventricular end-diastolic pressure
Left ventricular end-systolic volume
Left ventricular end-diastolic volume
Mean aortic pressure
Return of spontaneous circulation
Ventricular fibrillation.
The authors declare that there is no conflict of interests regarding the publication of this paper.
This research was supported by the National Natural Science Foundation of China (81272061), the Fundamental Research Funds for the Central Universities (11ykpy26), and Yat-Sen Scholarship for Young Scientists. Lisa Luna assisted with the editing of this paper.