Table of Contents
See Also:Biography of Paul Zoll
| August 28, 1952 Paul Zoll performs the first human clinical cardiac pacing in Boston, Massachusetts. (see "Transthoracic Cardiac Pacing" below) 
Dr. Zoll's Patient - 1952
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| Transthoracic Cardiac Pacing 
The first transthoracic cardiac pacing was accomplished with a Thyratron physiologic stimulator designed for laboratory use. The "stimulating electrodes were attached to needles placed subcutaneously in the chest wall at points in a line transversing the ventricles." "Electric shocks 2 milliseconds in duration were given at frequencies from 25 to 600 per minute. The intensity of the shocks was increased until ventricular responses were observed." "…On August 28, 1952, because of 2 severe Stokes-Adams attacks," a 75 year old man was the "first time it was possible to keep a patient alive during a ventricular asystole…" In the discussion Dr. Zoll speculates that a simplified pulse generator might be better suited for clinical purposes and that an additional circuit permitting bursts of alternating current might possibly be able "to defibrillate the human heart across the unopened chest initially and then to arouse it from ventricular standstill by pacing." In the accompanying editorial, this article is described as "an exceedingly promising report…" Zoll PM. Resuscitation of the Heart in Ventricular Standstill by External Electric Stimulation. New Eng J Med 1952; 247: 768-771 Back to Top |
Letter to Dwight E. Harken
In a letter to Dwight E. Harken dated March 7, 1990:
"First, I would like to be known as the one who introduced the modern era of cardiac pacing with a noninvasive cardiac pacemaker to resuscitate patients from ventricular standstill. Then, in 1956 I first applied transthoracic electric shocks to terminate ventricular fibrillation in man, and also in the same year developed the first cardiac monitors for clinical use."
Photo: Paul M. Zoll with long time surgical collaborator Howard Frank.
Lasker Award
After several unsuccessful attempts to build a pulse generator, I followed Callaghan's lead and obtained a standard laboratory model of a physiologic pacemaker (Grass physiological thyratron pulse generator), which was provided through the kindness of Professor Otto Krayer, head of the pharmacology department at the Harvard Medical School. With a long wire electrode in the esophagus and a second electrode over the precordium in a dog, we were able to demonstrate that an electric stimulus would indeed arouse atrial or ventricular electrical responses and effective myocardial contractions with which cardiac arrest could be reversed and the circulation maintained.
Zoll PM. Development of Electric Control of Cardiac Rhythm. Lasker Awards. JAMA 1973; 226:881-882.
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Vitamin B1 Deficiency in Rats
Vitamin B1 deficiency in rats and pigeons has been found to be associated with bradycardia. Because of the discrepancy between electrocardiographic findings in deficiency states attributed to vitamin B in man (beriberi, pellagra, polyneuritis) and in animals, a study was undertaken on the electrocardiographic effect of vitamin B1 deficiency on the rat heart. Nine rats were placed on diets deficient in B1. Standardized ECGs were obtained. After 3 weeks the animals exhibited marked loss of weight, neurologic, bradychardia and ECG complex changes. The heart rate gradually fell from a normal level of from 564 to 666 per minute (average 581) to from 354 to 134 (average 286). In 5 of the rats' T wave changes of high origin were observed. Increase in T wave amplitude developed in 2 animals. T wave inversion occurred in one, and questionable inversion in another. Administration of crystalline vitamin B1 abolished both the bradycardia and the ECG changes when the rate was 300 or over, but usually failed to save the animals when the rate was below this level. That changes in the ECG complexes could be abolished with crystalline vitamin B1 in animals kept in a fasting state indicates that the cardiac changes are directly related to B1 deficiency rather than to malnutrition. The results of the experiments were reported and the character of the ECG changes are consistent with those observed in human deficiency states (pellagra, polyneuritis, beriberi). The essential difference is that in man tachycardia is present in vitamin B deficiency.
Zoll PM, Weiss, S. Electrocardiographic changes in rats deficient in vitamin B1. Proc Soc Exper Biol Med 1936; 35: 259-262
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Foreign Bodies In and Around the Heart
1. A series of 78 foreign bodies that have been removed from within, or in relation to, the thoracic great vessels is discussed. Three of these were embolic.
2. A series of 56 foreign bodies that have been removed from within or on the heart is discussed. Thirteen of these were removed from the chambers of the heart…in our series of 134 patients who have had foreign bodies removed, there have been no deaths and the men are clinically well."
Foreign bodies, shrapnel, bullets and other detritus were first routinely removed from within and about the heart during the Second World War. At war's end the heart, previously considered inviolate and too dangerous to be operated upon, was demonstrated to be approachable. The intellectual climate changed and led to the cardiac procedures of the post-war era.
Zoll later wrote: "I became interested in electrical stimulation of the heart shortly after World War II, after I had observed much of the pioneering cardiac surgery done by Dr. Dwight Harken for the removal of foreign bodies in and about the heart. The heart appeared, indeed, to be a very sensitive organ that responded readily with ventricular contractions to stimuli; arousal from ventricular standstill by appropriate stimulation should, therefore, not be difficult."
Harken DE, Zoll PM. Foreign bodies in and in relation to the thoracic blood vessels and heart. III Indications for the removal of intracardiac foreign bodies and the behavior of the heart during manipulation. Amer Heart J 1946; 32: 1-19.
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Coronary Artery Visualization
Zoll spent 50% of his time in clinical practice. His early work with Monroe Schlesinger in injecting coronary arteries of cadaveric hearts with different colors of lead-agar mass under a pressure of 150 to 200 mm Hg, yielded useful clinical pathological correlations with untoward outcomes of coronary artery disease. The hearts were then dissected and unrolled with the coronary arteries in one plane, x-rayed and then coronary arteries dissected again. The report included 177 patients with angina pectoris and 671 controls without cardiac pain were reported. (Fig. 1: X-ray of normal control.) The authors discussed the importance of ventricular hypertrophy and spasm in provoking angina as well as the importance of collateral circulation in diminishing ischemia (Fig 2: Diagram of a heart with coronary pathology.) We should note that the Shlesinger technique was a forerunner of coronary angiography. H.L. Blumgart, a co-author in this study and Chief of Medicine at Beth Israel Hospital, Boston, encouraged and supported Zoll's interest in electrical methods of resuscitating the heart.
| Fig. 1 |
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| Fig. 2 |
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Zoll PM, Wessler S, Blumgart HL. Angina Pectoris. A Clinical and Pathological Correlation. Amer J Med 1951; 9: 331-357.
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External Stimulation for Stokes-Adams Disease
Two years following the initial report of successful transthoracic cardiac pacing, Zoll and coworkers reported their results in 14 additional cases. Most patients had Stokes-Adams attacks. Nine patients required prolonged periods of stimulation which was defined as 25 minutes to 108 hours. Case #1 required long periods of pacing for asystole for complete heart block on two occasions. The first period was for 96 consecutive hours and the second for 108 consecutive hours. Overall, mortality was high. Yet, some patients survived for many months.
This paper contains several important observations. #1) "external cardiac pacing appears to be the method of choice for the immediate treatment of patients with unexpected circulatory arrest from cardiac standstill." #2) Chest pain and muscle twitch intensity varied from patient to patient. In two patients it was intolerable. Discomfort was reduced with meperidine hydrochloride or paraldehyde. Curare-like drugs and local anesthetics were not helpful. There is a recognition that a better method should be developed to diminish discomfort. (Zoll achieved this goal 29 years later.) #3) An algorithm is presented for response to cardiac arrest based upon success or failure of transthoracic pacing. Zoll predicts that closed chest defibrillation will be possible (he achieved this goal two years later). #4) There was the implied need for a method to continuously pace patients (permanently) following acute resuscitation. Zoll and his team accomplished this goal six years later with his implantable pacemaker. Zoll PM, Linenthal AJ, Norman LR, Belgard AH. Treatment of Stokes-Adams Disease by External Electric Stimulation of the Heart. Circulation 1954; 9:482-493
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Transthoracic Defibrillation
The figure is from a landmark paper demonstrating that ventricular fibrillation can be interrupted by transthoracic countershock. Four cases with ventricular fibrillation are described. The etiologies were acute myocardial infarction, idiopathic, digitalis intoxication and Stokes-Adams attacks. Only the last patient survived. The alternating current defibrillator was built by Dr. Zoll's team. One episode of ventricular tachycardia was corrected by countershock. Dr. Zoll comments that the procedure should be effective for supraventricular arrhythmias including atrial fibrillation, based upon his laboratory experiments with animals. In his first description of successful clinical transthoracic defibrillation, Dr. Zoll points out that "successful defibrillation depends on immediate recognition of the emergency and prompt application of the external defibrillator". Today, 44 years later, smart compact defibrillators have been positioned into public places. Dr. Zoll preferred the term "countershock" in deference to Carl Wiggers' historic description of electrically shocking the heart of animals into ventricular fibrillation during the vulnerable phase and then countershocking the heart back to normal sinus rhythm with a second discharge.
Zoll PM, Linenthal AJ, Gibson W, Paul M, Norman LR. Termination of Ventricular Fibrillation in Man by Externally Applied Electrical Countershock. New Eng J Med 1956; 254: 727-732.
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Treatment of Unexpected Cardiac Arrest by External Electric Stimulation of the Heart
Cardiac arrest may occur unexpectedly during various diagnostic and therapeutic procedures, particularly under anesthesia. Though infrequent (1 in every 500 to 5000 operations), each accident is a catastrophe, current therapy is too often unsuccessful. The commonly recognized mechanisms of cardiac arrest are ventricular standstill and ventricular fibrillation; standstill is the usual cause. In a compilation of 1200 cases of cardiac arrest, the occurrence of standstill was 88 percent. Eight successful cases of cardiac resuscitation from unexpected arrest by electric stimulation of the heart are reported here. The cases occurred during various procedures - 7 during surgery, and 1 during pericardiocentesis. The cardiac arrest was terminated in each case by the electric pacemaker so that thoracotomy and cardiac massage were not necessary. Five patients recovered completely, 2 died of unsuccessful cardiac surgery, and 1 died eight hours after operation. A practical monitoring device to signal immediately the cessation of the heart beat would obviate crucial delay in recognizing the onset of arrest. Ideally, such an alarm system should register the electric activity of the ventricles by an audible signal of each heart beat and sound an alarm upon the onset of cardiac arrest. In 1 well documented case with such a monitor, thoracotomy was performed and cardiac massage begun eighteen seconds after the onset of arrest. The routine application of a cardiac monitor to all patients under anesthesia would give greatest assurance of immediate recognition of cardiac arrest. Ventricular standstill may persist despite effective massage, may recur after massage or may follow defibrillation. Electric stimulation may then be applied directly to the heart, preferably by needle electrodes a few millimeters apart. Epinephrine hydrochloride (0.2 ml. If 1:1000 aqueous solution) or calcium gluconate (4 ml. Of a 10 per cent aqueous solution) may be injected into a cardiac chamber.
Zoll PM, Linenthal AJ, Norman LR, Paul MH, Gibson W. Treatment of Unexpected Cardiac Arrest by External Electric Stimulation of the Heart. New Eng J Med 1956; 254: 541-546.
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Ventricular Fibrillation: Treatment and Prevention by External Electric Currents
Ventricular fibrillation, usually a rapidly fatal arrhythmia, occurs most commonly in coronary-artery disease, in patients with atrioventricular block and in toxic reactions to digitalis, quinidine and procaine amide. Occasionally, it succeeds ventricular tachycardia. This paper presents additional experiences confirming the clinical value of external countershock in terminating ventricular tachycardia and fibrillation and of external electric stimulation in preventing these arrhythmias. Alternating current (60 cycle, 0.15 second, 150 to 450 volts) was applied to the unopened chest with large electrodes. A cardiac pacemaker providing monophasic rounded impulses of 2 milliseconds duration over wide ranges of rate and amplitude was used to stimulate the heart externally. Ventricular tachycardia and fibrillation were terminated by externally applied electric countershock more than five hundred and thirty-two times in 8 patients; 5 have survived for one month to two and a half years. The technique is immediately effective, clinically feasible and safe. Prevention of recurrent ventricular tachycardia and fibrillation in patients with complete heart block remains an unsolved problem. Drugs are largely ineffective; external electric cardiac stimulation at rates above the basic idioventricular rate has been effective in preventing these recurrent ventricular arrhythmias, but long-term stimulation is difficult.
Zoll PM, Linenthal AJ, Normal Zarsky LR. Ventricular Fibrillation: Treatment and Prevention by External Electric Currents. New Eng J Med 1960; 262:105-112.
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Supernormal Periods in Man
| Zoll and his team member, Arthur Linenthal, performed electrophysiological studies in both animals and mad. The methodological tools were the electrocardiogram and both endocardial and epicardial pacemakers. They studied timing in P wave and electrical stimuli on ventricular excitation. Figure 2 defines the phases of ventricular excitability. Figure 3 defines the absolute and relative refractory periods of the ventricle with greater relative refractoriness determined by the interval between the stimulus and conduction. Figure 5 demonstrates the supernormal period of ventricular excitability. The phases of cardiac excitability were also studied to understand the mechanism of A-V block. The other electrophysiological observations were made regarding features of retrograde atrio-ventricular conduction and fusion beats. | Fig. 2 |
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| Fig. 5 | Fig. 3 |
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Linenthal AJ, Zoll PM. Quantitative studies of ventricular refractory and supernormal periods in man. Tr A A Physicians, 1962; 75: 285-292.
Linenthal AJ, Zoll PM. Ventricular fusion beats during electrical stimulation in man. Application to conduction. Circulation 1965; 36: 651-660.
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Zoll - Electrodyne Implanted Pacemaker
The table depicts Drs. Zoll and Frank's four-year experience with implanted pacemakers. They analyzed 103 patients grouped in three phases of surgical/technological development. There was one advance in pacemaker/model and two advances in electrode design. The pacemaker mode was VOO without capacity for rate or any other adjustment. The factory rate was set at 70 or 75 bpm. The authors addressed alternative technology such as rate adjustability, maintaining atrio-ventricular sequencing, potential problems created by competitive ventricular pacing (R on T phenomenon), controlling heart action during the operative procedures prior to placement of the fully implantable unit and self contained power sources versus rechargeable power sources. The Electrodyne manufactured pacemaker is depicted. In a published discussion which followed the presentation of this paper, Dr. Elliot S. Hurwitt commented that Dr. Seymour Furman had satisfactorily managed 82 patients with severe heart block with temporary transvenous pacemakers and an external pulse generator. Dr. Hurwitt commented that he believed that the catheter pacemaker was the preferred approach to temporarily maintain a patient awaiting a permanent pacemaker and for control during anesthesia and operation. In regard to each of the aforementioned issues, Drs. Zoll and Frank opted for simplicity, security and instrument longevity. In time, each of the innovations discussed gained full acceptance except for the rechargeable battery.
Table 1: Electrical Failure and Sepsis
| Period of
Implantation | Pacemaker
Unit | Electrodes
and Wires | Number of
Patients
in Each
Phase* | Patients with Pace-
maker Failure | Patients with
Wire or Electrode Break | Patients with Sepsis |
| July 1960–May 1961 | Early (metal-encased) | Platinum-solid | 12 | 4 | 3 | 4 |
| June 1961–March 1962 | | | 23 | 1 | 11 | 2 |
| April 1962–September 1963 | Present (epoxy-
encased) | Platinum-plated
49-strand wires | 44 | 0 | 6 | 0 |
| September 1963–April 1964 | | Platinum-plated
77-strand wires | 24 | 0 | 0 | 1 |
*26 patients in more than one phase of the method.
Zoll PM, Frank HA, Linenthal AJ. Four-year Experience with an Implantable Cardiac Pacemaker. Annals of Surgery 1964; 160: 351-365. Back to Top
An Individual Implant History
Paul Zoll deservedly had a premier reputation as a clinical cardiologist and developed a strong bond with his pacemaker patients. He and Howard Frank were constantly available, avoiding vacations, so that patients would travel long distances, on short notice, to return to their care. He often stated that it was the patients and their problems who energized his work in the laboratory. The table depicts sequential pacemaker procedures in a man from the Midwest with Stokes-Adams attacks. After the second pacemaker implantation failed, he was referred to the care of Paul Zoll and Howard Frank who directed his care from 1964 until their retirement. Frank performed 13 operative procedures with Zoll assisting at each to maintain a continuous effective heart rate. The evolution of pacemaker and electrode technology is evident with ultimate realization of reliability and longevity. Although the patient's residence remained in the Midwest, the bond with Zoll and Frank caused him to return to Boston for each pacemaker procedure including the last which was performed by their former trainees. The patient has survived almost 38 years with cardiac pacing.
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Cardiac Monitor Pacemaker
Early recognition and a rapid prearranged response to life-threatening arrhythmias was Dr. Zoll's constant theme. He and Alan Belgard, his engineer, developed oscilloscopic continuous cardiac monitors which visually and audibly recorded cardiac activity and alarmed when predetermined rate limits were violated. Some of their machines were capable of automatically externally pacing the asystolic or extremely bradycardic patient. In time, the monitors had a hard copy ECG printout and retrievable memory. Dr. Zoll's monitors, transthoracic pacemakers, and transthoracic defibrillators were essentially prerequisites for the early coronary care units.
Nicholson MJ, Orr RB, Eversole UH, Crehan JP. A cardiac monitor-pacemaker: Use during and after anesthesia. Anesthesia and Analgesia. 1969; 38: 355-347.
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Wolf Creek Conference on Cardiopulmonary Resuscitation
"The science of resuscitation stems from the demonstration of Zoll and others that the human heart can be defibrillated by a shock administered across the chest."* Zoll's primary research and clinical interests were in managing heart disease with the potential for arrhythmic crisis. he developed algorithms to resuscitate and stabilize these hearts. His works provided the platform for Advanced Cardio-Pulmonary Resuscitation. Zoll was a recognized expert in these matters. As a member of Boston's Beth Israel Hospital's Resuscitation Committee, he responded to many in-house cardiac arrests. He was the Chairman of the Massachusetts Heart Association's Committee on Cardiac Arrest, published on the subject, and participated in national programs on cardiopulmonary collapse. Zoll was among the "first generation" of resuscitation researchers at the first Wolf Creek Conference on cardiopulmonary resuscitation which was a think tank for the initiators of modern CPR.
*Kravitz AE, Killip R. Cardiopulmonary resuscitation status report. NEJM 1972;286:1000-1001.
Zoll PM, Linenthal AJ. External and internal electric cardiac pacemakers. Circulation 1963;28:455-466. Back to Top
Mechanical Cardiac Stimulation
While cardiologist and Chief of Medicine at the U.S. Army Station Hospital, United Kingdom, Zoll observed Dr. Dwight Harken extract bullets, shrapnel and shell fragments from in and about the heart. He noted that the mere contact of a finger or a medical instrument to the surface of the heart evoked a cardiac contraction. He later incorporated the principle of the mechanical stimulus, such as a chest thump or repetitive chest thumps, to cause an asystolic heart in cardiac standstill arrest to beat into an external mechanical cardiac stimulator which could deliver a mechanical precordial chest thump timed to the nonvulnerable phase of the cardiac cycle. Ten human subjects were used in his trial. The thump evoked an electrical stimulus in eight of ten. The experience was somewhat unpleasant for all conscious patients and was tolerated without complaint in four patients. Zoll hoped that the "mechanical pacemaker" would provide a noninvasive means of stimulating a heart during an emergency or for any purpose. In a moment of reflection, Zoll recalled showing the prototype model to an engineer patient who offered to restructure the prototype. Modification was made in one day. The modified model was returned one week later. The prototype had taken years to develop. The engineer-patient's offer was "straight from the goodness of his heart." The external mechanical cardiac stimulator has also been used in clinical experimentation with idiopathic hypertrophic subaortic stenosis.
Zoll PM, Belgard AH, Weintraub MJ, Frank HA. New Eng J Med 1978; 294: 1274-1275.
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The Self-Retaining Myocardial Electrode
Ten years after implanting their first pacemaker, Drs. Zoll and Frank began development of a new epicardial electrode, to be placed securely in the myocardium with a small well tolerated procedure. An "arrow head" implantation tip evolved into a "hook". Two hundred twenty seven experiments were performed with the hook electrode in 27 laboratory animals before the electrode was implanted into four patients who had failed transvenous endocardial electrode placement. The electrode (Model 6919) did not gain acceptance in clinical trials. Medtronic totally redesigned the electrode, maintaining the "hook principle" (Model 4951). It is especially well suited for atrial placement and is in current production.
Zoll RH, Zoll PM, Frank HA, Belgard A. A New Self-Retaining Myocardial Electrode. Cardiac Pacing. Piccin Medical Books. P1125-1128. 1983
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External Noninvasive Temporary Cardiac Pacing: Clinical Trials
An external cardiac pacemaker-monitor has been developed that provides safe, effective noninvasive ventricular stimulation that is well tolerated in conscious patients and allows clear recognition of electrocardiography response. The noninvasive temporary pacemaker (NTP) has now been applied in 134 patients in five hospitals. Stimulation was tolerated well in 73 of 82 conscious patients, and nine found it intolerable. The NTP was effective in evoking electrocardiographic responses in 105 patients; the 29 failures were in the presence of prolonged hypoxia or severe discomfort. The NTP was clinically useful in 82 patients: 43 of 86 were resuscitated from emergency or expected arrest, 38 of 40 were maintained in standby readiness for up to 1 month but did not require stimulation, and one of the eight patients with tachycardia obtained some clinical benefit. The NTP was especially useful in 25 patients with complications or contraindications to endocardial pacing and in 57 patients in whom insertion of an endocardial electrode was avoided.
Zoll PM, Zoll RH, Falk RH, Clinton JE, Eitel DR, Antman EM. External noninvasive temporary cardiac pacing: clinical trials. Circulation 1985; 71: 937-944. Back to Top
Paul Zoll and His Collaborators
Dr. Zoll's curriculum vitae lists 96 publications between 1934-1989 which include 53 separate co-authors. The eleven collaborators represent those who joined Dr. Zoll in more than two efforts and are listed by the number of joint efforts in each category with the exception of Alan Belgard. We regret any exclusions, for Dr. Zoll was not comprehensive in listing the totality of his publications.
Collaborators in Arrhythmia Investigations
Arthur J. Linenthal, M.D., Professor of Medicine, Harvard
Alan Belgard, B.S.E.E., Associate in Medical Research, Beth Israel Hospital
Leona Norman Zarsky, M.D., Associate in Medical Research, Harvard
Howard A. Frank, M. D., Clinical Professor of Surgery, Harvard
Ross H. Zoll, PhD, M.D., Associate in Medical Research, Beth Israel Hospital
Research Fellows
Milton Paul, M.D., Research Fellow in Medicine, Harvard
William Gibson, M.D., Research Fellow in Medicine, Harvard
Collaborators in Cardiac & Clinical/Pathological Investigations
Herman L. Blumgart, M.D., Professor of Medicine, Harvard
Monroe J. Schlesinger, M.D., Clinical Professor of Pathology, Harvard
A. Stone Freedberg, M.D., Professor of Medicine, Harvard
Stanford Wessler, M.D., Assistant Professor of Medicine, Harvard
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