John P. Rosborough

Pressure-synchronized cineangiography during experimental cardiopulmonary resuscitation.

Cardiopulmonary resuscitation (CPR) has been thought to produce blood flow by compression of the heart between the sternum and spine, termed “external cardiac massage,” but there has been-no direct experimental documentation of this proposed mechanism.Micromanometric pressure recordings were synchronized with cineangiograms during mechanical CPR in 17 dogs with induced ventricular fibrillation. Chest compression produced equivalent pressure increases in the aorta (Ao) and right atrium (RA) (Ao 32 + 14 mm Hg, RA 30 ± 14 mm Hg; NS), a linear relationship between aortic and intrapleural pressures (r = 0.87, p < 0.001) over a wide range of induced pressures, cineangiographic blood flow through both left-heart chambers, and a pressure gradient (21 ± 14 mm Hg) between all intrathoracic cardiovascular compartments and the jugular veins that resulted from closure of venous valves at the thoracic inlets. Simultaneous chest compression and lung inflation significantly increased all intrathoracic vascular pressures, the aortojugular venous gradient (42 ± 13 mm Hg, p < 0.05 vs chest compression alone), electromagnetically determined carotid arterial blood flow (1.75 ± 0.81 ml/min/kg vs 0.51 ± 0.27 mI/min/kg during chest compression alone, p < 0.005), and angiographic left-heart flow.We conclude that blood flow during CPR results principally from an increased intrathoracic pressure and that there is selective flow to the brachiocephalic vascular bed because of the arteriovepous gradient produced by venous valves at the thoracic inlets. Greater intrathoracic pressure resulting from simultaneous inflation and compression improves left-heart flow. The left heart is therefore a conduit, not a pump, during CPR.

Cough-CPR: documentation of systemic perfusion in man and in an experimental model: a "window" to the mechanism of blood flow in external CPR.

Maintenance of arterial pressure and consciousness by vigorous coughing during ventricular fibrillation has been previously documented. Observations in 4 additional patients with unstable rhythms and in fibrillating dogs confirm that coughing: (1) produces an arterial pulse; (2) produces opening of the aortic valve; (3) generates forward blood flow; and (4) can maintain consciousness during circulatory arrest. The authors speculate that cough-induced systemic perfusion results from compression of the pulmonary vascular beds by a rise in intrathoracic pressure, the left heart acting only as a one-way conduit to the lower pressure extrathoracic vascular outlets. Receht data suggest that conventional CPR likewise produces blood flow by compression of the pulmonary vascular blood pool, and not by cardiac compression as previously thought.

Mechanical “cough” cardiopulmonary resuscitation during cardiac arrest in dogs

Hemodynamic findings during ventricular fibrillation (VF) and closed-chest cardiopulmonary resuscitation (CPR) are similar to those described during VF and vigorous coughing. Interventions during CPR that mimic the physiologic events of coughing (high intrathoracic pressure and high intraabdominal pressure) improve perfusion during VF and CPR. An external circulatory assist apparatus was devised to emulate cough physiology, i.e., simultaneous pulsatile increases in intrathoracic pressure (pneumatic vest), intraabdominal pressure (abdominal binder) and airway pressure (high-pressure airway inflation). In this study, vest/binder CPR was compared with conventional CPR during 30 minutes of VF and artificial support in 18 randomized dogs. Defibrillation and long-term (more than 24 hours) survival were chosen as end points. During VF and artificial support, aortic and right atrial (RA) pressures, the instantaneous aortic-RA pressure difference (coronary perfusion pressure) and blood gas levels were measured. After 30 minutes of VF and administration of 1 mg of epinephrine, countershock was attempted. Systolic aortic and RA pressures, mean aortic-RA pressure difference and blood gas levels were not significantly different between dogs that were successfully resuscitated and those that were not. However, peak diastolic coronary perfusion pressure (peak diastolic aortic-RA pressure) for survivors averaged 23 +/- 6 mm Hg, but only 6 +/- 10 mm Hg for nonsurvivors (p less than 0.001). A peak diastolic coronary perfusion pressure 16 mm Hg or greater had a positive and negative predictive value for a successful outcome of 1.00. Only 1 of 9 conventional CPR dogs survived 24 hours; 7 of 9 dogs supported with the vest/binder device were alive and neurologically normal at 24 hours (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Endocardial and transcutaneous cardiac pacing, calcium chloride, and epinephrine in postcountershock asystole and bradycardias

Clinically, asystole or a bradyarrhythmia may follow countershock of ventricular fibrillation (VF) in up to 40% of attempts. This study evaluated the effects of artificial cardiac pacing, calcium chloride (CaCl2), and epinephrine in postcountershock asystole/bradycardia. Micromanometer catheters were positioned in the aorta (Ao) and right atrium (RA) of ten dogs and VF induced by right ventricular (RV) stimulation. After 2 min of VF, a 400-J countershock was given. In six animals, asystole or a pulseless bradyarrhythmia followed one countershock. In four animals, up to three countershocks were needed to terminate VF and resulted in asystole or a pulseless bradyarrhythmia. Thirty seconds after termination of VF, cardiac pacing was begun in all animals using conventional RV endocardial pacing (RVEP) or a transcutaneous transthoracic pacing (TTP) technique. RVEP and TTP produced ventricular depolarizations, but electrical capture was never associated with Ao pressure fluctuations. After 2 min of pacing, CaCI2 was given and chest compressions and artificial ventilations (CPR) initiated. CaCl2 had no effect on CPR pressures. After 2 min of CPR, RVEP and TTP were again studied; capture without Ao pressure fluctuations was seen in all animals. Epinephrine was then given and CPR reinstituted. Epinephrine produced a significant increase in CPR Ao systolic pressure (58 ± 13 to 84 ± 24 mm Hg, p < .001) and end-diastolic coronary perfusion pressure (Ao-RA) (9 ± 4 to 34 ± 8 mm Hg, p < .001). Within 94 ± 53 sec after epinephrine, spontaneous circulation was restored in eight animals. Of the remaining two animals, one succumbed to a pulseless bradyarrhythmia after one countershock and the other to asystole after multiple countershocks for recurrent VF. Electron microscopic changes in myocardial sections were largely consistent with the duration of ischemia, and there was no intracellular calcium accumulation. Dehiscence of the myocardial intercalated discs was seen in the animal that received multiple countershocks. It is concluded that: (a) pacing in postcountershock asystole/bradycardia may produce electrical capture but not effective cardiac contraction, (b) CaCl2 is of limited value in asystole/bradycardia after countershock and does not facilitate electrical-mechanical coupling during pacing, (c) epinephrine is effective in the management of postcountershock asystole/bradycardia, and (d) asystole after multiple countershocks may be of structural origin and not amenable to therapy.

Is all ventricular fibrillation the same? A comparison of ischemically induced with electrically induced ventricular fibrillation in a porcine cardiac arrest and resuscitation model.

Objectives:The standard porcine cardiac arrest model uses electrical induction of ventricular fibrillation. Reported restoration of spontaneous circulation and survival rates in this model are as high as 90% for ventricular fibrillation durations of 7–10 mins, values substantially greater than rates in the clinical population (i.e., 20% to 30%). A high first shock success rate, infrequent refibrillation, and short times for restoration of spontaneous circulation are typical of the model. The purpose of this study was to determine whether ischemic induction of ventricular fibrillation in swine followed by standard advanced cardiac life support would result in short-term outcomes approximating those observed in human victims of out-of-hospital ventricular fibrillation. Design:Randomized comparative trial. Setting:Translational research laboratory. Subjects:Domestic swine (n = 40, mean weight 40 ± 4 kg, range 34–47 kg) of both genders. Interventions:Swine were instrumented and randomized to either electrical ventricular fibrillation induction or ischemic ventricular fibrillation, produced by balloon occlusion of the mid-left anterior descending coronary artery (n = 20 per group). Transthoracic impedance was measured and 30 &OHgr; added in series for all animals. The balloon remained inflated during resuscitation efforts in ischemic ventricular fibrillation animals. After 7 mins of ventricular fibrillation, cardiopulmonary resuscitation was initiated and defibrillation was attempted 1 min later. Epinephrine and antiarrhythmics were administered as per guidelines. Resuscitation was terminated if restoration of spontaneous circulation had not occurred after 15 mins of advanced cardiac life support. Measurements and Main Results:Although the number of countershocks required to initially terminate ventricular fibrillation was not different (electrical ventricular fibrillation 1.9 ± 1.6, ischemic ventricular fibrillation 2.4 ± 2.0), the refibrillation rate was higher in the ischemic ventricular fibrillation group (4.9 ± 4 vs. 0.8 ± 1 episodes/animal, p < .001), resulting in a greater number of shocks before restoration of spontaneous circulation (total shocks for ischemic ventricular fibrillation 9.4 ± 5.6 vs. electrical ventricular fibrillation 2.7 ± 2.2, p < .001). Time to restoration of spontaneous circulation was longer in the ischemic ventricular fibrillation group (430 ± 234 secs vs. 149 ± 120 secs, p < .001). Restoration of spontaneous circulation rates were not different (electrical ventricular fibrillation 90% vs. ischemic ventricular fibrillation 65%). However, survival to 6 hrs was greater in the electrical ventricular fibrillation group (18 of 20, 90%) than in the ischemic ventricular fibrillation group (8 of 20, 40%, p = .002). Conclusions:Resuscitation from ischemic ventricular fibrillation is more difficult than electrical ventricular fibrillation and is characterized by greater time to restoration of spontaneous circulation, frequent refibrillation, greater number of countershocks, higher epinephrine dose during resuscitation efforts, profound cardiac dysfunction, and a short-term survival rate approaching clinical experience. Ischemically induced ventricular fibrillation is a more clinically relevant model for the evaluation of resuscitation interventions.

Hemodynamic effects of continuous abdominal binding during cardiac arrest and resuscitation

Abdominal binding improves arterial pressure and flow during cardiopulmonary resuscitation (CPR). This study was undertaken to assess the mechanisms of improved hemodynamics during cardiac arrest and CPR with continuous abdominal binding in a canine model (n = 8). Carotid and inferior vena caval (IVC) flow probes and cineangiography were used to observe magnitude and direction of blood flow. CPR with binding significantly increased (p < 0.001) systolic aortic (Ao) (49 ± 11 vs 34± 12mm Hg), right atrial (RA) (49 ± 11 vs 31 ± 10 mm Hg) and IVC pressure (50 ± 7 versus 31 ± 11 mm Hg) and common carotid flow (1.1 ± 0.4 vs 0.7 ± 0.4 ml/min/kg, p < 0.05) compared with CPR without binding. Aortic, RA and IVC diastolic pressures increased similarly. Binding decreased the diastolic Ao-IVC pressure difference by 8 ± 12 mm Hg and decreased net IVC flow (0.5 ± 1.4 vs 1.4 ± 1.2 ml/min/kg, p < 0.05). Binding also decreased coronary perfusion pressure (Ao-RA) in 5 of 8 dogs. Cineangiograms showed tricuspid incompetence and reflux from the right atrium to the inferior vena cava during chest compression and IVC-to-right heart inflow during relaxation, which was confirmed by the flowmeter data. Abdominal binding during CPR decreased the size of the perfused vascular bed by inhibiting subdiaphragmatic flow and increased intrathoracic pressure for a given chest compression force, leading to preferential cephalad flow. However, coronary perfusion pressure was often adversely affected. Further studies should be undertaken before the widespread clinical application of continuous abdominal binding during CPR.

Is the tumour necrosis factor-alpha response following resuscitation gender dependent in the swine model?

INTRODUCTION Reperfusion results in a proinflammatory cytokine response, as has been observed following resuscitation from cardiac arrest. Variations in the inflammatory response have been shown to be gender dependent and mediated by steroid hormones. The purpose of this study was to determine whether the tumour necrosis factor-alpha response following resuscitation was gender dependent. METHODS Anaesthetized swine (15 males and 15 females, weighs 32-47 kg) underwent 7 min of electrically induced cardiac arrest, followed by conventional resuscitation and then measurement of tumour necrosis factor-alpha by enzyme-linked immunosorbent assay at intervals for up to 3h. Testosterone and 17-estradiol were measured in 8 males and 8 females. RESULTS In all animals 17-estradiol was undetectable. Testosterone exceeded the lower limit of detection in 3 females and 1 male. Levels of tumour necrosis factor-alpha were higher in males than females, from 30 min after resuscitation to 3h. In females, tumour necrosis factor-alpha levels were significantly higher than control values only at 15 min following restoration of circulation; the levels in males demonstrated marked inter-animal variation. CONCLUSIONS In this swine model, males demonstrated an augmented post-resuscitation tumour necrosis factor-alpha response when compared with females. This difference was not related to steroid hormone levels.

Cardiac Function and the Proinflammatory Cytokine Response After Recovery From Cardiac Arrest in Swine

Increased levels of cytokines have been reported after resuscitation from cardiac arrest. We hypothesized that proinflammatory cytokines, released in response to ischemia/reperfusion, increase following resuscitation and play a role in post-cardiac arrest myocardial dysfunction. Ventricular fibrillation (VF) was induced by coronary occlusion in 20 swine. After 7 min of VF, resuscitation was performed as per guidelines. Plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were measured 15 min after the start of resuscitation in all animals and at intervals of 6 h in resuscitated animals. Intravascular pressures and cardiac output (CO) were also recorded. TNF-alpha abruptly increased after resuscitation, peaking at 15 min following return of spontaneous circulation, and declined to baseline levels after 3 h. IL-1beta increased more slowly, reaching a maximum 2 h after reperfusion. IL-6 concentrations were not significantly different from control values at any time point. Males demonstrated greater elevations of TNF-alpha and IL-1beta than females. Stroke work was significantly depressed at all time points with a nadir at 15-30 min after reperfusion, corresponding to the peak TNF-alpha values. The anti-TNF-alpha antibody infliximab attenuated the decrease in myocardial function observed 30 min after reperfusion. TNF-alpha increases during recovery from cardiac arrest are associated with depression of left ventricle (LV) function. The effect of TNF-alpha can be attenuated by anti-TNF-alpha antibodies.

The central nervous system cytokine response to global ischemia following resuscitation from ventricular fibrillation in a porcine model

AIM OF THE STUDY Pro-inflammatory cytokines have been implicated as culprits in neurotoxicity following ischemia in small animal models of stroke. The aim of this study was to measure the central nervous system (CNS) cytokine response following resuscitation from ventricular fibrillation (VF) in a porcine model of cardiac arrest and global hypoxic ischemia. METHODS VF was induced electrically in 11 anesthetized swine. Following 7 min of untreated VF, animals were resuscitated. Cerebrospinal fluid (CSF) and serum was sampled prior to VF and at 60, 120, and 180 min post-resuscitation from which levels of TNF-alpha, IL-1 beta, and IL-6 were measured. Levels were also drawn in three sham pigs, instrumented but not fibrillated. RESULTS CSF levels of TNF-alpha rose following resuscitation and were associated with CSF levels of IL-1 beta (p=0.0002). CSF levels of all cytokines except TNF-alpha were associated with their serum counterparts. CONCLUSIONS Measurable increases in pro-inflammatory cytokines in the CSF follow resuscitation from cardiac arrest in this porcine model. The CNS response TNF-alpha and IL-1 beta are associated. However, serum levels of TNF-alpha did not seem to predict CSF levels in this study, consistent with the concept of immune privilege of the CNS.

Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model.

Objective:Left ventricular dysfunction after successful cardiopulmonary resuscitation contributes to early death after resuscitation. Proinflammatory cytokines are known to decrease myocardial function, and tumor necrosis factor-&agr; has been shown to increase after successful resuscitation. We hypothesized that blocking the effects of tumor necrosis factor-&agr; with infliximab would prevent or minimize postresuscitation cardiac dysfunction. Design:Randomized, placebo-controlled comparative study. Setting:Large animal research laboratory. Subjects:Twenty-eight anesthetized and instrumented domestic male swine (Yorkshire and Yorkshire/Hampshire mix; weight, 35-45 kg). Interventions:Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from ventricular fibrillation cardiac arrest. Measurements and Main Results:Hemodynamic variables, indices of left ventricular function, and tumor necrosis factor-&agr; were measured before and after 8 mins of cardiac arrest during the early postresuscitation period (3 hrs). Within 5 mins of restoration of spontaneous circulation, 14 animals received infliximab, 5 mg/kg, infused over 30 mins. Fourteen animals received an infusion of normal saline. Inotropes and vasopressors were not administered to either group after resuscitation. Tumor necrosis factor-&agr; increased after restoration of circulation and remained elevated throughout the observation period. Differences between groups were not significant. Interleukin-1&bgr; concentration did not change significantly during the observation period in either study group. Mean arterial pressure and stroke work were significantly greater in the infliximab group within 30 mins of resuscitation, and these differences were sustained throughout the 3-hr postresuscitation period. The effect of tumor necrosis factor-&agr; blockade was evident only in animals with a significant increase (doubling) in plasma tumor necrosis factor-&agr; at 30 mins after arrest. Conclusion:Tumor necrosis factor-&agr; plays a role in cardiac dysfunction after arrest and infliximab may attenuate or prevent postresuscitation myocardial dysfunction when administered immediately after resuscitation.