Triggering of the Bezold Jarisch Reflex by Reperfusion during Primary PCI with Maintenance of Consciousness by Cough CPR

A Case Report and Review of Pathophysiology

Author Affiliations: From Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada. The authors report no conflicts of interest regarding the content herein. Manuscript submitted January 14, 2008, provisional acceptance given May 5, 2008, and accepted May 8, 2008. Address for correspondence: Dr. Wiliam Keeble, Mazankowski Alberta Heart Institute, 8440-112 Street, Edmonton, Alberta, Canada. T6G 2B7. E-mail: williamkeeble@doctors.org.uk

_______________________________________________ ABSTRACT: This report documents a case of hemodynamic collapse during primary angioplasty (PCI) for acute inferior ST-segment elevation myocardial infarction (STEMI). The patient had stable vital signs during the initial angiogram which had demonstrated an occluded mid right coronary artery (RCA). There was no evidence of right ventricular infarction or heart block. Reperfusion arrhythmia did not occur. The case illustrates triggering of the Bezold Jarisch Reflex (BJR) not by occlusion but reperfusion. In addition, this report illustrates the use of cough cardiopulmonary resuscitation (cough-CPR) to maintain consciousness during the BJR. Cough-CPR has previously been reported as a temporizing mechanism during ventricular arrhythmia prior to electrical cardioversion. This primary PCI case puts into clinical context the findings of historical animal studies and compares with clinical observations made during trials of intracoronary thrombolytic therapy.

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J INVASIVE CARDIOL 2008;20:E239–E242 Case Report. A 50 year-old-male awoke at 2:00 am with diaphoresis and shortness of breath. He experienced vomiting and involuntary defecation. Diffuse retrosternal chest pain radiated into the left shoulder. He delayed seeking medical attention until the pain escalated. The first electrocardiogram (ECG) performed at 6:30 am in the emergency department demonstrated inferoposterior ST-elevation myocardial infarction (STEMI) criteria (Figure 1). He was in sinus arrhythmia with an approximate rate of 70 beats per minute and a blood pressure of 140/90 mmHg. There was no evidence of pulmonary edema or mechanical complication of MI. The patient was referred for primary percutaneous coronary intervention (PCI) and received aspirin 325 mg orally, clopidogrel 600 mg orally, and 5,000 units of unfractionated heparin bolus intravenously. Selective coronary angiography demonstrated right coronary artery (RCA) dominance with complete occlusion of the RCA in mid vessel (Figure 2A). No significant disease was found in the left coronary artery. Intravenous abciximab was administered. The vessel was wired and the lesion was dilated using a 2.5 mm balloon (Figure 2B; 8:16 am). Profound bradycardia occurred with a concomitant fall in systolic pressure from 105 to 40 mmHg (Figure 2D). The patient became presyncopal and was instructed to cough. Figure 2E shows salvos of coughing with pauses for inspiration. The increases in intrathoracic pressure generated arterial pressures of almost 200 mmHg. He maintained consciousness and cooperated with instructions. The first contrast injection following this demonstrated prompt filling of the distal vessel (Figure 2C). Despite a return of electrical activity and improvement in his heart rate following atropine administration, the patient’s blood pressure response was significantly delayed. Pressures only approached pre-PCI levels 10 minutes later despite 1,000 ml of fluid loading. A 3 x 33 mm Cypher drug-eluting stent (Cordis Corp., Miami Lakes, Florida) was subsequently deployed with 20 atm of pressure (between asterixes in Figure 2C), yielding a good result. Transthoracic echocardiography 1 day later revealed minimal inferior wall hypokinesis and an estimated left ventricular ejection fraction of 60%. Discussion. The Bezold Jarisch Reflex (BJR) was a physiological observation reported by von Bezold and Hirt in 1867, when injecting cats with intravenous veratrum alkaloids. A profound decrease in blood pressure occurred, associated with apnea. The reflex nature of the response was substantiated in the 1930s by serial studies before and after the interruption of cardiac branches of the vagus nerve. Jarisch established the receptors to be localized in the left ventricle of the heart rather than the lung. Apnea was later removed from the definition when Dawes et al determined that it was related to an alternative mechanism.1,2 This is pertinent to our case in which the patient performed cough-cardiopulmonary resuscitation (CPR). The generation of pressures of 200 mmHg overrode the initial hemodynamic collapse caused by the reflex and allowed the patient to maintain consciousness. Zucker and Cornish studied 22 conscious and instrumented dogs, stimulating the BJR with veratidine injections into the circumflex coronary artery.3 With the use of atropine, pacing and phentolamine, they demonstrated chemical stimulation of left ventricular (LV) receptors to mediate bradycardia, hypotension and a reduction in total peripheral vascular resistance.3 Interestingly, this was produced by sympathetic withdrawal as well as cholinergic-mediated vasodilatation. Veratrum alkaloid is not present naturally in animals or humans. As such, the pharmacological trigger of the BJR appeared to have no relevance to clinical cardiology until observed during the study of acute MI. Occlusion of coronary vessels, most notably the RCA when supplying the inferior left ventricular wall, was noted to cause transient hypotension and sinus bradycardia. This became most evident when mobile cardiac units attended patients in the first hour of acute MI.4 In health, the cardiovascular reflexes maintaining blood pressure principally include the cardio-inhibitory BJR, the baroreflex (with stretch receptors in the walls of the arteries, carotid and aortic bodies) and low-pressure atrial stretch receptors. These are sensitive to changes in blood volume, which may trigger the release of atrial natiuretic factor, inhibit antidiuretic hormone secretion from the pituitary and decrease renin activity.5 Vasomotor tone is maintained by holding blood vessels partially vasoconstricted by the sympathetic nervous system. Feedback on the medullary vasomotor center ensures hemodynamic stability.5 A common transient imbalance of this system also occurs during vasovagal syncope. This is described as being neurally mediated when triggers such as intense emotional upset or the sight of blood stimulate the higher neural centers. This leads to variable expression of either cardio-inhibitory syncope or vasodepressor syncope. This contrasts with the mechanism occurring after prolonged standing or moving to a warm environment. In this situation, mechanoreceptors are triggered by reduced preload to the ventricle due to venous pooling. Animal studies of hypovolemic insult have shown that the interaction of baroreceptor and BJR reflexes maintain blood pressure. The cardio-inhibitory activity of the BJR falls and the vasomotor output is correspondingly augmented. Other than resulting mild tachycardia, the sole manifestation of the reflex adaptations is an increase in renin activity.6 Sudden occlusion of the RCA may trigger the BJR, inducing syncope.4 However, early studies of intracoronary thrombolysis revealed not only that occlusion, but reperfusion, of a coronary artery may trigger the BJR.7 Wei et al studied the hemodynamic changes occurring in 43 patients undergoing intracoronary thrombolysis using streptokinase as the principle agent.7 Successful reperfusion occurred in 27 patients. Of these, the Bezold Jarisch reflex occurred in 17. Spontaneous resolution occurred in 6 cases, and 11 were administered atropine. Patients having unsuccessful intracoronary thrombolytic therapy acted as a control arm. No reflex cardiovascular changes occurred in this group.7 Time to reperfusion in the study ranged between 180 to 460 minutes. No relation between time to reperfusion and extent of hemodynamic changes was found. This suggests that triggering of the BJR is causally related to reperfusion and is not time-dependent on the duration of ischemia. In our patient, the BJR occurred dramatically during angioplasty 7 hours from symptom onset. Wei et al also studied the significance of the infarct-related vessel. They concluded that it was not the artery per se, but the dominant vessel supplying the inferior wall that most likely triggered the BJR when reperfused.7 This confirmed the experimental evidence that the cardiac reflex results from the activation of inhibitory cardiac receptors with vagal afferents located predominantly in the inferoposterior wall of the left ventricle.3,8 This case report demonstrates the BJR phenomenon occurring with primary PCI in a similar way to successful thrombolysis: an overwhelming imbalance in autonomic control occurred with late reperfusion of ischemic myocardium. Profound firing of cardio-inhibitory receptors within the inferior wall likely inhibited the vasomotor center of the medulla. This triggered the BJR reflex. Loss of sympathetic tone occurred, the vasodepressor response predominated and total peripheral vascular resistance precipitously fell. We administered atropine as the first-line drug for acute symptomatic bradycardia.9 One liter of saline was subsequently given. A partial response to bradycardia occurred with atropine, but there was delayed compensation by the baroreceptor reflex in restoring blood pressure (Figure 2E). This is in keeping with animal studies.10 The bradycardia induced by veratidine in dogs is abolished by atropine, but the decrease in blood pressure is only partially attenuated. This implies that the BJR inhibits vasomotor output independent of heart rate modulation.10 The immediate intervention in this case, employed before staff had time to respond to drug and fluid orders, was the use of cough-CPR. Cough-induced cardiac compressions have been an established technique since the 1970s to briefly maintain consciousness should ventricular fibrillation (VF) occur during coronary angiography. In this regard, the procedure is also termed cough-CPR. There are reports of patients remaining conscious for up to 60 seconds before receiving formal electrical cardioversion.11–13 In 8 patients, this self-administered cough CPR notably accomplished much greater mean systolic pressures when compared to external CPR (140 vs. 60 mmHg).11 As a modified Valsalva maneuver, cough generates intrathoracic pressures of up to 300 mmHg and expiratory velocities of 280 m/second. Awareness of the contribution of intrathoracic pressure changes on venous return to the heart has lead to improvements in resuscitation equipment. In an instrumented pig model of cardiac arrest, an intrathoracic pressure regulator (ITPR) device attached to an endotracheal tube allows continuous negative pressure (-9 mmHg) while allowing for positive pressure ventilation. Coronary perfusion pressure was calculated as diastolic aortic pressure minus right atrial pressure. Cerebral perfusion pressure was calculated as mean arterial pressure minus intracranial pressure. Compared with standard CPR, ITPR-CPR commenced 8 minutes into untreated ventricular fibrillation arrest was found to have beneficial hemodynamic effects that were sustained for at least 15 minutes without any compromise in oxygenation.15 American Heart Association (AHA) guidelines for pulseless arrest due to ventricular arrhythmia are for basic life support, immediate DC shock, 5 cycles of CPR, then a further shock if the rhythm is appropriate. This is coupled with the use of intravenous vasopressors.16 In the catheterization laboratory, the onset of cardiac arrest is promptly recognized by continuous ECG and hemodynamic data. Immediate resuscitation equipment is available to experienced staff. Cough-CPR has a place in maintaining partial hemodynamic stability while defibrillation equipment is applied.11–13 There may be no need to withdraw the image intensifier completely, and the attempt to reopen the occluded vessel to relieve ischemia can progress. In the environment of the emergency department with ECG monitoring, but without the benefit of intra-arterial blood pressure monitoring provided in the catheterization laboratory, witnessed malignant ventricular arrythmias have been briefly managed by cough-CPR prior to defibrillation.17 In the context of STEMI, this avoids potential chest trauma due to external CPR and reduces the risk of bleeding complication if thrombolytic therapy were to be given.17 Outside of the hospital, a report suggests that patients experiencing symptoms that they attribute to cardiac arrest may abort them by coughing.18 However, this report is limited by a lack of documented ECG evidence of ventricular arrhythmia that might exclude nonarrhythmic causes of syncope. The AHA does not endorse cough-CPR or teach it in any part of the core curriculum of any course. Current guidelines emphasize the need to establish unresponsiveness, call for help and commence basic life support. Chest compressions are “hard and fast” (100/minute) ensuring full chest recoil and minimizing interruptions.16 Summary. This report highlights several aspects regarding the BJR and cough-CPR specific to interventional cardiology practice within the catheterization laboratory: in trials of intracoronary thrombolysis, signs of successful reperfusion included ST-segment resolution and idioventricular rhythm. Sudden hypotension and bradycardia reflecting activation of the BJR also signaled reopening of an occluded artery.7 In our patient, the BJR reflex was the first sign of reperfusion, even before a post-balloon inflation angiogram could be taken. The restoration of flow triggering the BJR suggests that the receptors in the inferior wall reside in noninfarcted myocardium. Evidence of the reflex occurring implies that viable myocardium may be salvaged. A greater awareness of the BJR being due to successful reperfusion avoids the unnecessary and potentially hazardous administration of vasoconstrictors. A conservative approach is possible with fluid, atropine and, in this case, cough-CPR. The literature focuses on using cough-CPR during arrhythmias. We report a case of cough-CPR during the BJR. Cyclical cough-CPR for the patient is not traumatic, avoids rib fracture and is a self-sustaining method to maintain consciousness. This is advocated only in the context of complete hemodynamic monitoring in the cardiac catheterization laboratory. A practical consideration is to disengage the guiding catheter if at all possible. Both cardiac compressions and cough-CPR may cause catheter-induced dissection of a coronary artery ostium, which must be actively excluded before ending the procedure.

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