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Abstract
The first implantable cardiac pacemaker is one of the momentous
achievements in history of cardiac surgery. Attempts to pace
erratic heartbeats or revitalize a fibrillating heart from
outside of the body had been mainspring of treatment for long by
cardiologists and cardiac surgeons for conduction
malfunctioning, may it be congenital or acquired or even
iatrogenic. Nonetheless, initial devices invariably lead to
infection development and had undependable energy sources.
Moreover, surgeons were restricted from tempering with heart by
religious dominance also. Research on this ‘tool of choice’
for rhythm disturbances management was possible due to untiring
efforts of many scientists simultaneously at far away places and
with variety of patients that lead to further refinements in
pacemaker technology. A branch of cardiology better known as
Cardiac Electrophysiology developed during the renaissance of
for a better pacemaker. It helped in designing a standard
version of the instrument by combining individual technological
innovations. Creation of pacemaker is not idea of any one brain
but rather a team effort by scientists – surgeons, physicians
and engineers. Developing pacemaker also needed support from
technical expertise as well as from private firms, which gave
birth to a pacemaker industry. Of course, the industrial
collaboration with medicine in this field has provided fruits of
success of years of research to those who were virtually,
‘dying for it’.
Key Words: pacemaker,
artificial, implantable, history, cardiac,
electrostimulation
Citation:
Baxi MV.First Artificial Pacemaker: A milestone in history
of cardiac electrostimulation. Asian Stud Med J 2003:2;5
Introduction
“The farther backward you can look,
the farther forward you are likely to see.”
- Sir Winston Churchill
Heart has been a center of attraction for anatomists,
physiologists, physicians and surgeons for long besides being
the subject of art, love and literature! Primitive man as early
as circa 30,000 years ago was almost certainly aware of the life
driving force of the heart. In 1908, Abbe‘ Breuil, the father
of the study of prehistoric art, sketched in red chalk the
mammoth drawn by Auriganacian man in the cave of Pindal in
northern Spain. This 16.75 X 17.5 inch drawing was noted by
Breuil to have “A broad, almost heart shaped spot, placed in
the middle of the body.” [1] It was probably the first
anatomical drawing of heart. [2] In ancient Indian medicine, it
is stated in Rig Veda,” heart is the seat of intelligence and
the vital spirit”. Chinese medicine describes heart as
“Prince of the body.” [3] William Harvey (1578 – 1657) “
the Columbus of Blood Circulation” described blood circulation
& motion of heart in his book ’Exrcitatio Anatomica de
motu cordis et sanguinis in Animalibus’ (Anatomical exercise
concerning the motion of the heart and blood in animals) in 1628
AD.[4]
After establishment of the fact that heart is the imperative
organ for keeping the person alive, scientist started working in
direction of reviving a dead person by applying some external
artificial maneuver to the heart. When Luigi Galvani made it
clear that a muscle could be made to contract by an electric
current in 1759[5], it was expected by many that the principal
can be exercised for cardiac muscles also.
Early
Developments
De facto cardiac electrostimulation began in the mid-eighteenth
century with the use of currents from the Leyden jar or Voltaic
Pile (Allessandra Volta, 1799) to stimulate cardiac nerves and
muscles in animals and to attempt resuscitation of intact dead
animals.[6] Dr. William Hawes in London established The Humane
Society of London in 1774 AD - A fraternity devoted to salvaging
persons seemingly dead - motivated by similar such society in
Paris. Later on it became The Royal Humane Society of London.
Squires, Henley and Fothergill suggested Electrostimulation for
resuscitation in a number of communications to the Society
between 1774 and 1748.[7] Such an incidence is described by
Charles Kite in his “An Essay upon the Recovery of the
Apparently Dead.” (London, 1788) The 3-year old child was
taken up for dead after falling out of a window. An
“apothecary” was sent for, who could nothing; then
electrical resuscitation by an electrostatic generator with a
Leyden jar capacitor was used. (Fig.1) Squires described,
“With the consent of the parents, very humanely tried the
effects of electricity. Twenty minutes had at least elapsed
before I could apply the shock, which I gave to various, part of
the body without any apparent success; but at length, on
transmitting a few shocks through thorax, I perceived a small
pulsation; soon after that child began to breath, through with
great difficulty. In about 10 minutes she vomited. A kind of
stupor remained for some days, but the child was restored to
perfect health and spirits in about a week.”[8]
 |
| Fig1.Apparatus
as shown in Kite’s ‘An Essay upon the Recovery of
the Apparently Dead’ (1788) [Reproduced with
permission of The Bakken Library and Museum of
electricity in Life, MN, USA] |
Charles Kite commented on this,
“Do (these incidences) not plainly point out that
electricity is the most powerful stimulus we can apply, and we
not justified in assuming, that if it is able so powerfully to
excite the action of the external muscles, that it will be
capable of reproducing the motion of the heart which is
infinitely more irritable, and by that means accomplish our
great desideratum, the renewal of the circulation.”8
However, it is noteworthy that we have almost matching
description of resuscitation by electricity, this time by two
Danish Scientist Herboldt and Rasn (1796) in their small booklet
“Life saving measures for drowning persons and information of
the best means by which they can be brought back to life.”[9]
Similarly, Dr.DeSanctis used “Re-animation Chair.”(Fig.2) as
described by Richmond Reece in his The Medical Guide (1820). It
had 3 pertinent features: a bellows to give forced ventilation,
a metallic tube to be inserted into the esophagus and a voltaic
pile attached at one pole to the esophageal tube and at the
other to an electrode. The electrode was to be successively
touched to “the regions of the heart, the diaphragm and the
stomach…”[10] These reports may have lead John Hunter to
recommend in 1776 that electrostimulation be tried as the as the
resort in the resuscitation of drawing victims.[11]
 |
|
| Fig2.The
Re-animation chair of Dr.DeSanctis (1820)
[Reproduced
with permission of The Bakken Library and Museum of
electricity in Life, MN, USA] |
|
In 1802, Nysten used a human cadaver shortly following death by
execution to demonstrate that the ability to reactivate the
heart electrically was lost earlier for the left ventricle,
later for the right ventricle, still later for the left atrium
and last for right atrium.12 Later in the nineteenth century,
Walshe (1862) and Duchenne (1870) advocated electrostimulation
for cardiac standstill.[13],[14] During the same period, Althaus
(1864) reported successful resuscitation of cardiac arrest
victims by electrical currents applied through transthoracic
needle.[15]
In 1882, Von Ziemssen described a case of a 42-year-old lady
named Catherina Sarafin who had a huge defect in the anterior
left chest wall following resection of an enchondroma. The heart
was covered by a thin layer of skin and was visible and
palpable. Von Ziemssen noted that application of electrodes to
the heart resulted in rhythmic stimulation only it the rate of
stimulation was greater than that of the spontaneous heart rate.
Slower stimulation produced erratic and sometimes slower heart
rate. He also noted while placing his electrodes that the most
sensitive area for stimulation was in the region of
atrioventricular groove. [16] Interestingly this observation was
made more than a decade before the description by Kent and His
of the location of the atrioventricular node and bundle of His,
respectively [17],[18]
In 1899, Prevost and Battelli demonstrated that electrical
currents could cause ventricular fibrillation that often could
be reversed by another powerful stimulus of either alternating
or direct current.[19] Robinvitch in a series of reports from
1907 through 1909 confirmed this work and designed the first
portable electrical resuscitative apparatus for ambulances.[20]
MacWilliam, in many publications beginning in 1899 and extending
to World War I, further elucidated the pathophysiology of
ventricular fibrillation and described deterioration of cardiac
pump function by tachyarrhythmias as well as bradarrythmias.
[21]
Interestingly, the experimental and clinical experiences just
described did not lead to immediate clinical trials of either
cardiac pacing or electrical defibrillation. It was not until
the efforts of Kounwenhowen (1932) and Beck (1947) that
electrical defibrillation became widely used
clinically.[22],[23] Studies in Europe by Marmrostein in 1927,
using both transvenous and transthoracic electrodes to pace
right atrium, right ventricle and left ventricle in dogs were
essentially unnoticed in United States.24 This is evident from
the reports in 1950 by Wilfred Bigelow, John A. Callaghan and
Jack Hopps who independently described similar studies using
transcutaneous electrodes to pace right atrium of dogs.[25] In
1949 during an experimental operation, a dog’s heart suddenly
stopped at 21 ºC. “Out of interest and desperation,”
recalls Dr.Bigelow, “I gave the left ventricle a good poke
with a probe I was holding.”[25]All the four chambers of heart
responded to it and further pokes clearly indicated that the
heart was beating normally with good blood pressure. He
immediately discussed it with Dr. Callaghan. Using dogs and
rabbits, they again collected the data, studying the most
effective and safe electric current and made movies of their key
experiments to present before the Annual Surgical Congress of
the American College of Surgeon’s meeting at Boston in October
1950. As Dr.Callaghan had done a “Lion’s share of work,
particularly in the normal body temperature studies, “he made
a ten minutes presentation.” Which was one of the scientific
highlights of the day with great interest from the media.”[25]
chuckles Dr.Bigelow. Co-incidentally their Co-worker Jack Hopps
also later became a pacemaker recipient.
Developments
leading to Modern Pacemaker
Albert Hyman’s “Artificial Cardiac
Pacemaker”
In 1932, Albert Hyman developed a machine for controlled
repetitive electrostimulation of heart and named his device the
“artificial cardiac pacemaker.” [26] (Fig.3) In Hyman’s
Words:
“Finally on April 6,1930, I received Grant No. 30-2 from the
Witkin Foundation to explore the possibility of developing a
practical machine, to be used as an artificial pacemaker in
experimental animals. Reduced to its simplest blueprint from
such an apparatus would include,
i. A small source of electric current, i.e. a common flashlight
battery.
ii. An interrupter mechanism
iii. A timing device
iv. A method of regulating the duration of the injected current;
and
v. A suitable insulated needle to carry the current only to the
right atrium of heart.
The instrument would, of course be easily portable and small
enough to fit into a doctor’s bag.
The next 10 months were devoted to the assembly of such an
apparatus…
By March 1, 1932 the artificial pacemaker has been used 43 times
with a successful outcome in 14 cases.”[27]
 |
|
| Fig3.A
model of Albert Hyman’s Pacemaker (1931) [Reproduced
with permission of The Bakken Library and Museum of
electricity in Life, MN, USA] |
|
However, Hyman was much subjected to abusive correspondence and
even lawsuits from people who regarded his resuscitation or
electro –pacing attempts as tempering with divine
providence.[28] It was largely forgotten, but Hyman brought the
concept to the United States Navy in which he served during the
Second World War. The Navy did not believe it to be useful and
lost a golden opportunity. An industrial version of his device
was built in Nurnberg but was destroyed in a bombing raid.[29]
“PM – 65” By Paul M.Zoll
in 1952, Paul Zoll first reported clinical, external
transthoracic pacing and brought it to world it to word
attention.[30] The initial impulse generator was a gross
stimulator called PM – 65. (Fig.4) It was line powered and
heavy. A cart was needed which could go only as far as the
extension cord could allow. This was acceptable as long as
pacemaker was considered emergency apparatus for post - surgical
care, mainly in surgically crated heart blocks. Other
disadvantages included skin burns when inadequate amount of
electrode jelly was applied, painful chest muscle contractions
in some patients and inability to pace in thick- chested &
emphysematous patients. Dr. Rodney Starke, Medical Director of
American Heart Association, who used the device during his
training, recalls:
“We would put terrible, frightful electrodes on. They would
stimulate all of the chest muscles and were kind of painful. But
people who would otherwise have died were brought along. That
was kind of miraculous.”[31]
 |
|
Fig4.PM-65
by Paul Zoll allowed the patient to ambulate (1955)
[Reproduced with permission of The Bakken Library and
Museum of electricity in Life, MN, USA]
|
|
Douglas Zipes of the Indiana University school of Medicine, has
his own recollections of a crude prototype device with leads
that penetrated to the heart,
“I remember staying up all night with one patient when I was
an intern at Duke (University). His connection was faulty, and
his heart rate would go to zero. I stayed up all night wiggling
the wires to keep heart going.”[31]
Zoll’s continued work and many publications convinced the
medical fraternity as well as general public that cardiac pacing
was both feasible and life – saving. Even the ethical concerns
were less harsh 20 years after human.
Clarence Walton Lillehei: The father of
Cardiac Surgery
Development of surgery of heart has been one of the most
dramatic phenomena of the 20th century. Indeed, C.Walten
Lillehei played a heroic character on stage for more than 40
years. Dr. Denton Cooley describes him as “Role model for
investigators.”32 One such example is found from his speech
delivered at the Bakken Library and Museum, MN, USA June 18,
1996 where there is a mention of an experimental pacing
technique (Fig.5) for patients with heart blocks due to surgical
correction of septal defects. Lillehei started suturing
insulated stainless steel wires to the heart before closing the
chest. Pacing impulses could be delivered through this wire for
a week or so until the heart healed. Then the wire could be
withdrawn with a simple pull.[33]First such operation was
performed on a girl with post-surgical heart block on 30th
January 1957.[34],[35] This method was universally adopted by
cardiac surgeons, till Lillehei introduced transistor pacemaker
later that year. The prototype model was “Compact, being only
slightly larger than a package of cigarettes.”[36] The
electrodes were insulated silver plated copper wires with
exposed tips supplied by Mr.C.W.Norman. The intramyocardial
electrodes were connected to a self-contained external pacemaker
having a transistor and a mercury battery of 9.4 volts. The
disadvantage of this techniques included dislodgement of the
lead and steadily rising threshold of the myocardial wire
electrodes.36 For their pioneering of pacemakers, Dr. Lillehei
and Earl Bakken, along with Wilson Greatbach were recognized by
the National Society of Professional Engineers on the occasion
of the Society’s 50th anniversary as making one of the 10
outstanding engineering advances in 20th century.[37]
 |
|
fig5.The
battery operated pacemaker by Lillehei and Bakken (1957)
[Reproduced with permission of The Bakken Library and
Museum of electricity in Life, MN, USA]
|
|
Other
Contributions
In 1956, Brockmann, Webb and Bohnson used a wire electrode to
successfully pace the heart of an infant who developed complete
heart block following closure of ventricular septal defect.[38]
Although the patient died, effective, uninterrupted pacing was
accomplished for 10 hours.
In August 1958 Furman and Schwedel used a right ventricular
endocardial wire electrode connected to an external pacemaker to
successfully pace for 96 hours in a 76 years old patient with
complete heart block.[39-40] This experience demonstrated that
prolonged cardiac pacing with low voltages could be accomplished
with an endocardial right ventricular electrode with connection
to external pacemaker.
In 1959, Glenn, Mauro, Longo, Lavietes and Mackay developed a
method of cardiac pacing using radio frequency transmission. The
method had an advantage of leaving the skin intact but it needed
an external pulse generator.[41]
Arne
Larson – A living history of pacemakers
Arne Larson, a Swedish engineer and founder of MarinémÖtage.AB,
will be remembered as the first patient to receive a completely
implantable pacemaker. The surgeon was Dr. Ake Senning, the
technical specialist was Rune Elmquist, from the Swedish firm
Elema SchÖnander, and the indication for pacing was
Stokes-Adams Syndrome following a Hepatitis A induced viral
myocarditis. The operation was undertaken at the Karolinska
Institute in Stockholm, Sweden on October 8, 1958 at 9:00 PM.
The first pacemaker (Fig.6) was implanted without incidence, but
8 hours later it failed when battery acid leaked into the epoxy
casing. According to Else Marie, wife of the patient, Dr.
Senning phoned Elmquist and said: “This damned thing you made
doesn’t work. Do you have another one?”[42] Thankfully
Elmquist had another piece of same model, which was put in place
of the first and it worked for next 6 weeks. The first two
pacemakers had pulse amplitude of 2 volts and pulse width 1.5
milliseconds. There were two Silicone transistors and two Ni–Cd
batteries encapsulated in epoxy resin. The diameter was approx.
55 mm and thickness16 mm. Leads were made up of stainless steel
and encapsulated in a polyethylene coat.[41],[42]
 |
|
Fig6.Replica
of first totally implantable pacemaker by Senning (1958)
[Reproduced with permission of The Bakken Library and
Museum of electricity in Life, MN, USA]
|
|
After these dramatic implantations Arne Larson has survived 26
pacemakers and living active and prosperous at age of 83.
Wilson
Greatbach – pacemaker or penicillin?
In 1960, Chardak, Gage and Greatbach developed a transistorized,
self-contained implantable pacemaker connected to modified
Hunter-Roth epicardial electrodes.[43], [44] It has an
interesting history: Greatbach knew about Stock Adams Syndrome
in 1951 from two neurosurgeons while working at Cornell
University Animal Behavior Farm. “When they described it, I
knew I could fix it.”[45] Recalls Greatbach, a radio engineer
at that time. Around 1956, when he was working for Chronic
Disease Research Institute at Buffalo, a doctor asked him to
design a circuit to record fast heart sounds. By mistake he took
a wrong transistor and plugged it into the circuit he was
making. The circuit pulsed. Greatbach recognized the rhythm. He
contacted Dr.William C. Chardack, Chief of Surgery at
Buffalo’s Veterans Administration hospital. He encouraged
Greatbach to make a practical model. Three weeks later, on May
7, 1958, Greatbach brought the pacemaker with two Texas
Instrument transistors to Chardak. There Chardak and another
surgeon, Andrew Gage, had exposed the heart of a dog, to which
Greatbach touched the two pacemaker wires. The device took
control of heartbeat and put the team into a race.[45],[46]
Chardak performed the first operation on April 15, 1960. One of
the patients was 77 years old Frank Henefelt suffering from
Stokes-Adams syndrome. He had so many attacks in a day that he
customarily wore a football helmet. After the pacemaker
implantation, he was free from the aliment and lived for more 21
years of moderately active life.47 However, mercury batteries
used at that time were short lived and required frequent
recharging, as Greatbach says, “The objective was simply to
drive the heart without much regard for economy of battery
life.”[45]
Greatbach is an example how a simple engineer can turn into a
famous inventor, just like Alexander Flaming who discovered
penicillin and salvaged the earth from deadly bacteria. In
1970s, Greatbach again came up with a longer- lasting pacemaker
battery that would not be affected by corrosive salts in human
body. He adapted Lithium - Iodine power source for the demands
of pacemaker, usually lasting 10 years or more. Then he created
a company to made the special batteries, which still sales or
licenses more than 90% of the world’s pacemaker batteries.[48]
Current
Trends in pacing
The initial implantable permanents pacemakers were all fixed
rate asynchronous devices that delivered their impulse
independent of underlying cardiac rate. The progress in field of
this ‘tool of choice’ for heart rhythm management possible
only because of diligent efforts put in by different scientists
at far away places at different times. In words of Albert
Einstein,
“The efforts of most human beings are consumed in the struggle
for their daily bread, but most of these who are, either through
fortune or some special gift, relived of this struggle are
largely absorbed in further improving their worldly lot. Beneath
the effort directed toward the accumulation of worldly good lies
all frequently the illusion that this is the most substantial
and desirable end to be achieved; but there is fortunately, a
minority composed of those who recognize early in their lives
that the most beautiful and satisfying experiences open to
humankind are not derived from outside, but are bound up with
the development of the individual’s own feeling, thinking and
acting. The genuine artists, investigators and thinkers have
always been persons of this kind. However inconspicuously the
life of these individuals rune its course, none the less the
fruits of their endeavors are the most valuable contributions
which one generation can make to its successors.”[49]
Americans are the most operated upon people in the world. Each
year almost 25 million Americans undergo some type of
surgery.[50] As in number of surgeries, same way in number and
type of pacemakers – a technological explosion - has occurred
in complexity and capacity. Today transvenous pacing has become
routine therapy not only for treating syncope but also for
controlling other non-life threatening symptoms such as
bradyarrhythmias. They have evolved from single asynchronous
circuit to multilead, multiprogrammable devices capable of
maintaining atrioventricular synchrony. Concept of physiological
pacing has provided capacity to pace the heart over a wide range
of cardiac rates as well as responding to physiology of body
such as temperature and movements. Simultaneously these years
have also seen origins of Nuclear powered, Solar powered
pacemakers as well as Steroid lead electrodes. The fast
development in pacing field gave birth to a science of
electrophysiology. It also created a booming pacemaker industry
that has provided fruits of long research to hands of poor in
developing countries also. They cover a wide population
regardless of age, sex or race. The Associate Professor of
Pharmacology at Medical College, Baroda, India, Dr. A.P.Rajani
says,
“Yesterday I talked with Dr. Girish Vaishnav (A Baroda base
Physician) and he informed me about a 100 years old patient in
whom he had advised a pacemaker implementation. I asked him\,
the fellow is 100 years old and still you advised him? He said
the patient wants to live and I have a treatment for him, so why
not to go for it?”*
Conclusion
Clearly, the idea for the
implantable pacemaker was not exclusive property of any one
brain but credit goes to all teams of researchers for pacemaker
who have saved and still saving millions of life. These
sophisticated, computerized rhythm control system arte expanding
to a great extent. Thus series of events of tremors in
scientific research, error and their remedy, accidents and
sparkles of light, a series full of excitement have paved the
way to excite the normal rhythm of heart in a disturbed case
through a most convenient instrument. This is a short summery of
history of searching for nature’s curious phenomenon and to
help it to function naturally when it is disturbed.
Acknowledgement
I would like to express my feeling of gratitude to those who
have helped me preparing for the paper. I am thankful to
Dr.Devang Jhala, MD (Pediatrics) Professor & Head,
Department of Pediatrics, Government Medical College & Sir
Takhtasinhji Civil Hospital, Bhavnagar (Bhavnagar University),
India for his indispensable suggestions for the paper. I am
indebted to Dr.R.K.Baxi, MD, DCH, DPH, Diplomat in MCH,
Associate Professor, Department of Preventive and Social
Medicine, Medical College, Baroda (The Maharaja Sayajirao
University of Baroda) Baroda, India who has been a friend,
philosopher and guide throughout. I thank Dr.Ellen R.Kuhfeld,
PhD, Curator of artifacts at The Bakken Library and Museum of
Electricity in Life, MN, USA for helping me out in searching the
references. I cannot forget to mention my parents without whose
supports this works would have remained a dream.
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