Polyether polyurethanes for implantable

pacemaker leads
I( Stokes and I( Cobian
Medtronic, Inc., 3055 Old Highway Eigh t, Minneapolis, MN 55418, USA
(Received 9 April 1981; revised 1 March 1982)

Two variations of a commercially available polyether polyurethane were evaluated for certain physical properties
and the changes in those properties as a result of plasticization by absorbed moisture. Appropriate tests were done
to establish biocompatibility. A two-year rat implant study evaluated chronic biocompatibility and biostability.
Ten tumours were found in 34 animals, of which eight were considered unrelated to the materials. Two fibrosarcomas
were presumed to be the result of solid-state carcinogenesis, not related to the material p e r se. Material testing
included analysis of density, tensile strength, elongation, molecular weight, intrinsic viscosity, scanning electron
microscopy, differential scanning calorimetry, and infrared spectrum changes. The polyether polyurethane was
considered to be biocompatible and biostable for long-term implant.

Keywords: Cardiology, pacemaker, lead, polyether polyurethane, biocompatibility, biostability

The transvenous cardiac pacing lead was introduced in 1967 M E T H O D S AND M A T E R I A L S

by Furman and Robinson 1. With only very few exceptions,
Softer (80A durometer*) and harder (55D durometert)
transvenous leads have been insulated with silicone rubber.
versions of a commercially available polymer were evaluated.
But safe and reliable silicone leads have some size-related
A typical commercially available silicone rubbers was used
design constraints due to the low tear and tensile strength
for comparison. This polymer has been used successfully
of silicone rubber. Thin tough leads with special properties
for over 20 years in permanent implantable pacemakers.
needed for dual chamber pacing require the use of elastomers
Polyurethane specimens were prepared by various
that are stiffer and tougher as well as permanently implant-
techniques. Materials were vacuum dried at 80°C for eight
able and stable. The polymer must be processible by state
to fourteen hours. Compression moulded specimens were
of the art fabricating techniques so that 100 000 devices per
die cut from slabs which were pressed at 193 ° to 216°C
year can be made with very high reliability.
and cooled in situ. Injection moulded specimens were made
Polyurethanes have long been considered for use in
on a ram machine with 204°C nozzle, 204-238°C barrel.
implantable devices 2-5. Polyurethane is a generic word
Tubing and rod samples for some plant tests were
describing a large number of polymers but very few are
processed with a 1.9 cm (0.75 in.), 24 : 1 L/D extruder
suitable for long-term implants. Even fewer implantable
using 210°C die, 182-215°C zones. Tubing for human use
polyurethanes lend themselves to suitable mass production
leads was purchased from qualified vendors. Specimens
techniques. Polyester polyurethanes, such as those
were conditioned at ambient for at least 7 days although
frequently used in coronary catheters or temporary pacing
additional steps were frequently called for depending on
leads, exhibit excellent physical properties but are not
the test. Prior to implant or mutagenicity testing, for
hydrolytically stable. Thus, they can degrade in vivo e.
example, specimens were thoroughly cleaned, ethylene
Certain polyether polyurethanes are hydrolytically stable
oxide sterilized, and appropriately aerated.
at neutral and basic pH 7. At least one* has been demon-
All silicone specimens except tubing were prepared
strated to be biocompatible and stable in long-term (3
by transfer moulding with cure at 12t°C. Post-cure was
year) implants 8 but we do not find it readily usable for our
achieved in a forced air oven at 149°C for 16 h. Extruded
mass production lead assembly techniques. This study was
tubing was purchased from a qualified vendor.
done to qualify an extrudable and injection mouldable
polyether polyurethane for permanent human implant in
cardiac and neurologic pacing leads. *Peltethane® 2363-80A; Upjohn, Inc.
t"Pellethane® 2363-55D; Upjohn, Inc.
*Biomer ®, Ethicon, Inc. $Silastic® MDX 4-4515; Dow Coming

© 1982 Butterworth & Co (Publishers) Ltd. 0142-9612/82/040225-07 $03.00

Biomaterials 1982, Vol 3 October 225

Pacemaker leads: K. Stokes and K. Cobian

Stress-strain analyses were done on an Instron Universal Standards were polystyrenes of various molecular
Testing Machine. Tensile tests followed ASTM D-1708 or weights from Waters Associates.
D-412 except for miniaturized implant specimens. These (e) Morphological and other physical changes were
resembled ASTM D-349. but were only 21 mm long and assessed by differential scanning calorimetry (DSC)
4.9 mm in diameter with an 8.8 by 1.6 mm dia necked using a Perkin-Elmer Model DSC-2 instrument.
down portion.
Tear strength tests were done at a rate of 50 cm per
minute on extruded tubing cut 1/3 to 1/4 through with
RESULTS
sharp dykes.
Volume resistivity tests were done on compression
Mechanical tests
moulded polyurethane and silicone slabs, following ASTM
D-257. Mean dry tensile properties of the polyurethane and silicone
The effects of moisture permeation were measured are shown in Table 1. The polyurethanes have 6 to 33 times
after accelerated and real time tests. Accelerated conditions greater elastic modulus. Tensile strength, elongation, and
were: 7 days reflux in pseudo extra cellular fluid (PEF) tear strength are all also significantly greater for the
at pH 7.4. Real time conditions used 37°C or ambient PEF polyurethanes compared to silicone.
or Ringers solution. In some cases, leads explanted from Stress-strain data following 7 days reflux in PEF are
dogs after 12 weeks implant were stored in 37°C test tanks shown in Table 2. Both polyurethanes show decreased
for later evaluation. When necessary, specimens were tensile strength but increased elongation. Silicone does not
patted dry with lintless towels before evaluation. Other change appreciably as a result of moisture absorption.
specimens, such as those used in stress-strain measurements, Tear strength tests were done on extruded tubing.
were tested wet. 8 0 A polyurethane leads were implanted in dogs for three
The effects of the polymer on tissue were evaluated in months. After termination of the experiment the leads
acute and chronic tests. Tissue culture tests were done by were placed in PEF. Twenty-three months later, leads
the method of Guess9 et al. U.S.P. tests were used to assure were removed from the test tank and the tubing
that the polymers contained no pyrogenic materials, were (2.16 mm OD x 1.01 mm ID) stripped off. Notched
not haemolytic, and to evaluate the systemic effects of specimens 7.6 cm long (2.5 cm gauge length) tore at
extracts 1°. Mutagenicity tests followed the procedures 1.4 + 0.9 kg with 100% elongation (N = 10). Fresh tubing
described by Ames et al. 11,12. Extruded rods were of the same size required up to 1.6-+ 0.2 kg with 90%
implanted in rabbit paravertebral muscles per U.S.P. 13 elongation (N = 9) to tear. In contrast, silicone tubing of
Animals were sacrificed for histopathologic analysis at 1, 2, the same size tore at 0.23 kg (N = 5). In a later test (31
3, 4, 8 and 12 weeks. Histopathologic analyses have been months immersion) precise measurement of tubing cross-
done on tissues adjacent to several hundred canine trans- sectional area gave notched 80 A specimen tensile strength
venour atrial and ventricular cardiac leads with implant of 65-76 kg/cm 2 (N = 6). Fresh silicone tubing had only
times ranging from 12 weeks to 18 months. Subcutaneous about 8.1 kg/cm 2 tensile strength when notched.
tissues surrounding miniature tensile specimens in rats Some electrical data before and after 7 day saline
were also evaluated. reflux are shown in Table 3 . Silicone has the highest volume
Biostability was evaluated in a two year in vivo study. resistivity with little change as a result of moisture
Miniature polyurethane tensile specimens resembling absorption. Polyether polyurethane shows greater changes.
ASTM d-349 were injection molded. These were implanted
subcutaneously in Sprague-Dawley rats. Controls were Table 1 Dry tensile properties (large specimens)
stored in 37°C Ringer's solution and under dry nitrogen at Property ASTM D Meanvalues-+standard deviations
ambient temperature. Animals were sacrificed to recover
specimens at approximately 0.1,1, 3, 6, 12, 18, and 24 Urethane Urethane Silicone
months. Specimens were used for many tests including 80 A 55 D
the following:
Young's modulus
(a) Density as measured by the gradient method, A S T M - (kg/cm2) 412 245-+ 16 1430,+96 43-+5
D-1505. Tear strength
(kg/cm2)* 640 Die C /> 33 ~>46 ;) 5.3
(b) Stress-strain tests were done at 1.0 cm per minute
crosshead speed and 2.5 cm per minute chart speed. Tensile strength
(kg/cm2) 1708 440 -+77 600 -+60 65 -+6.5
(c) Surface observations were made by scanning electron
Elongation (%) 1708 650-+35 440-+20 335-+ 19
microscopy used carbon/gold coated specimens with
an AMR Model 9000 instrument. *Manufacturer's data.
(d) Chemical (changes) were monitored by infrared
Table 2 Moisture saturated tensile properties (large specimens)
spectroscopy and molecular weight determinations.
Two methods were used for the latter, gel permeation Property ASTM D Mean values,+standard deviations
chromatography (g.p.c.)14 and intrinsic viscosity 15.
Samples were dissolved in HPLC grade tetrahydrofuran Urethane Urethane Silicone
80A 55D
at concentrations of 0.05-0.1 percent (weight to volume)
and injected into a Micromeritics 750 HPLC pump. Weight change (%) 1708 1.8+0.28 1.6-+0.22 0.8,+0.15
Separation was effected by a pair of Shodex g.p.c, columns Tensile strength
and detection by a Perkin-Elmer LC-55 Ultraviolet (kg/cm2) 1708 2 9 0 - + 2 7 495-+39 67-+13
detector at 254 nm. The distributions were calculated Elongation (%) 1708 810-+30 650-+35 365-+23
using a Spectra-Physics SP-4000 data system.

226 Biomaterials 1982, Vol 3 October

 Pacemaker leads: K. Stokes and K. Cobian

Table 3 Volume resistivity A S T M 0-257

Condition Typical values (ohm-centimeters)

80A 55D Silicone

Dry 4X1012 6X1013 2X1017

7 days reflux in saline 8X 1010 1012 1017

Biocompatibility
All biocompatibility tests (tissue culture, pyrogens,
haemolysis, systemic extracts, mutagenicity, 12 week
intermuscular implants) yielded acceptable results. In two
year subcutaneous rat implants, ten tumours were found in
84 animals, but eight were completely unrelated to the
material and the two others were believed to be related
to solid-state carcinogenesis. No tumours or other untoward
results were observed in tissues surrounding 55D (two-
year) subcutaneous rat implants. One fibrosarcoma was
found around an 80A specimen after 18 months, and one
after two years (43 subjects). No other untoward material
related results were observed. Negative mutagenicity results Figure 1 Canine heart with urethane transvenous ventricular
on control tensile specimens were obtained. Tissues adjacent lead (Medtron ic ® 6971) 12 weeks postimplantation. Fibrous tissue
to several hundred polyurethane cardiac lead implants in encapsulates only the area surrounding the tines, 4-S mm proximal
canines for time periods ranging from 3 to 18 months from the tip
yielded no untoward histopathological results. It must be The same behaviour was observed for the 55D poly-
noted here, however, that one series of canine lead urethane. A t implantation, the tensile strength was
implants early in the study resulted in borderline histo- 471 + 34 kg/cm 2. In three months, this dropped to
pathological data. The questionable results were 316 + 52 kg/cm 2. After two years, tensile strength was
apparently caused by improperly processed or con- 313 + 31 kg/cm 2. Elongation dropped from 315 + 20 at
taminated tubing. As a result, that material was disqualified implantation to 255 + 40% after three months. The two
for our use. year value was 260 + 30%. The one and two year explants
A t necropsy after 12 weeks implant, tined* were desiccated in vacuo having tensile strength of
ventriculart polyurethane leads typically have a thin trans- 444 + 30 kg/cm 2 and elongation of 2 7 0 -+ 24%. Ether and
lucent fibrotic sheath covering the tines and the lead body acetone extracted specimens gave similar results.
for a length of 5 mm. Silicone tined leads typically are Accelerated PEF immersion test results on 80 A
ensheathed for about 2-4 centimeters or more proximal polyurethane miniature tensile specimens are summarized
from the tip. Some examples are shown in Figures I a n d 2. in Table 4. A decrease in tensile strength with slightly
More fibrosis is found around atrial$ leads but in about the increased elongation are shown on moisture saturated
same proportions, more for silicone, less for urethane. specimens. Removal of the water yields a return toward
original tensile strength within one standard deviation,
but a still higher elongation.
Biostability Swanson and Lebeau 16 conducted similar experiments
Specimens from long-term rat implants showed a significant with silicone using miniaturized tensile specimens
drop in tensile strength and elongation in the first months resembling ASTM D412. These were implanted sub-
for both polyurethanes. But the values attained stability cutaneously in dogs. Initial tensile strength was
thereafter. 80 A polyurethane tensile strength dropped from 97 + 2.3 kg/cm 2 with 377 -+ 20 percent elongation. A t
370-+ 34 kg/cm 2 to 193 + 32 kg/cm 2 in one month. After
two years, the tensile strength was 221 + 33 kg/cm 2. Elonga-
tion dropped from 595 + 25% to 480 + 70% in one month
after implantation. After two years, 527 + 55% elongation
was obtained. Specimens from 1 and 2 year implants were
desiccated in a vacuum oven at ambient for 2 and 4 weeks.
A tensile strength of 303 + 42 kg/cm 2 and elongation of
545 + 40% were obtained for the vacuum dried 2 year
implants. Similar results were observed with acetone and
ether extracted specimens from explants after one and two
year intervals. Infrared patterns on the extract residues
showed no other components than low molecular weight
polyurethane which was also extracted from non-
implanted samples.

*Short projections close to the electrode, designed to anchor the Figure 2 Canine heart with silicone transvenous ventricular lead
lead. (Medtronic® 6901) 12 weeks postimplantation. Fibrous tissue
tMedtronic Models 6971 (unipolar) and 6972 (bipolar) encapsulates the distal portion o f the lead, nearly to the valve,
~Meditronic Models 6991U (unipolar) and 6990 (bipolar). roughly 6 cm in this case

Biomaterials 1982, Vol 3 October 227

Pacemaker leads: K. Stokes and K. Cobian

Table 4 Effect of accelerated moisture saturation on miniature

80A tensile specimens

Condition Mean values_+standard deviations

Tensile strength Elongation

(kg/cm2) (%)

Dry 370 +_34 600 -+25

7 day reflux 205-+ 17 335-+ 17
7 day reflux -- )
4 days desiccator I 335 -+17 720 -+30

termination of their studies 7.4 months later, the tensile

strength was 91 + 0.9 kg/cm 2 with 354 + 6 percent elongation.
There was no appreciable change in density for the
polyurethane as a result of two years implant. The 80 A
polymer's density after 24 months implant was 1.120 versus
1.121 initially. The harder polyurethane had the same
density before and after implant (1.162). Scanning electron Figure 4 55D urethane surface. After 18 months implantation
micrographs (Figures 3 and 4) show no changes in poly- 375 X
urethane surface structure as a result of implant. Specimens
stored in saline tanks and under dry nitrogen had the same accelerate morphological changes that will not ordinarily
surface features. Mean values for weight average molecular be seen at 37°C. Hydrolytic degradation follows Arrhenius'
weight (Mw) and number average molecular weight (Mn) Law (the rate of reaction doubles for each 10°C increase).
are shown in Table 5 for both the 55D and 80A poly- Thus, seven days reflux are equivalent to 26 or 64 weeks
urethanes after 24 months conditioning. As another check, implant with respect to degradation by moisture. It is very
intrinsic viscosity was run on the 18-month conditioned important, therefore, that such accelerated tests be
specimens (Table 6). Infrared patterns on the polyurethanes evaluated with great care, limiting interpretation only to
at all implant intervals, stored in 37 ° Ringer's solution or the relevant parameters.
under dry nitrogen, showed no appreciable differences. In seven day boil tests using relatively large specimens,
DSC scans were done on 24-month explants, with test the tensile strength of the polyurethane dropped by nearly
tank specimens and controls stored under dry nitrogen. No 35 percent but the elongation increased by 25 percent so
appreciable differences were observed. at the area under the stress strain curve changed only
slightly from 3580 (cm-kg)/cm 2 to 3040 (cm-kg)/cm 2.
Silicone absorbed little water, thus, no appreciable change in
DISCUSSION stress-strain properties were observed. Note, however, that
the area under silicone's stress-strain curve is roughly
Physical properties 540 (cm-kg)/cm 2, an order of magnitude less than that of
Polyurethane absorbs significant amounts of water from the polyurethane. Tear strength is directly related to the
the body as do most organic polymers. This absorbed water area under the stress-strain curve. Thus, one does not expect
acts as a plasticizer, decreasing elastic modulus and tensile a significant decrease in this parameter for the polyurethane
strength while increasing elongation. The seven day reflux after long-term immersion or implant even though other
test in PEF is designed to simulate the effect of chronic Table 5 Molecular weight (g.p.c.)
implant only with respect to water absorption. The
specimen may even be supersaturated when cooled to Urethane 24 month Typical values
ambient. The heat involved in this test can also induce or conditions
~w ~n ~w/Mn
80A Implant 252000 64000 3.93
80A Ringer's 216000 55200 3.92
solution
80 A Dry 263 000 63 300 4.15
55 D Implant 308 000 62 300 4.95
55 D Ringer's 300 000 41 500 7.22
solution
55D Dry 313000 60400 5.18

Table 6 Intrinsic viscosity

18-month conditions Typical values

80A 55D

I replant 0.993 1.035

Ringer's solution 0.991 1.11
Figure 3 80A urethane surface. After 18 months implantation
750 X
Dry nitrogen 1.00 1.14

228 Biomaterials 1982, Vol 3 October


properties may change. Tubing tear tests after implantation
and long-term immersion verify that this is indeed the case.
Changes in volume resistivity also occur as water
saturates the polymer. Even so, the lowest wet value,
1 0 1 ° ~ c m , is well within our design constraints for
implantable pacing leads.
Biocompatibility
Biocompatibility test results for polymer specimens made
under perfectly controlled conditions may not be realistic.
It is important that the process used in device manufacture
be carefully considered. This is particularly true with
organic polymers such as polyurethane. Silicone, a
thermosetting polymer, is relatively unaffected by high
temperatures. This is a manufacturing advantage. Polyure-
thane, a thermoplastic, is on the other hand, sensitive to
thermal degradation during processing, especially in the
presence of moisture. For example, linear polyurethanes
are made by addition of a diisocyanate ( O = C = N - R - N
= C - - O ) to a diol ( H O - R - O H ) which, in this case, is a
polyether diol. The resultant urethane - R - N H - C O - - O
- R ) - can be safely extruded or injection moulded on
appropriate screw machines at low temperatures with
short residence times if first adequately dried. If overheated,
the urethane linkage can depolymerize to form isocyanate
- ( R - N C O ) and hydroxyl - (R - O H ) . Isocyanates are in
general a highly reactive species. Once depolymerization
begins, many uncontrolled reactions can occur. One of the
many such reactions will be combination with moisture to
form the amine - ( R - N = C = O + H20-> R - N H 2 + C02) ,
which is biologically unacceptable. The most obvious
manifestation of thermal degradation is a severe discolora-
tion of the polymer 3-4 days after processing. Degradation
also produces very significant changes in tensile strength
and in solution viscosity. Polyether polyurethanes are
somewhat hygroscopic as the accelerated reflux test data
demonstrate. The polymer pellets before extrusion or
moulding can absorb atmospheric moisture. If this is not
removed by correct drying techniques prior to extrusion
or moulding, the reaction to form the amine can occur in
s i t u . Since recombination of isocyanate and hydroxyl is
then prevented, degradation is accelerated. Thus, manu-
facturing process controls are critical. Several quality control
tests are available for the device manufacturer to assure that
thermal degradation has not occurred. These include colour,
stress-strain, viscosity, and chemical analysis. Appropriate
process controls are absolutely required to assure continuing
biocompatibility.
Mutagenicity has become a point of concern for certain
polyurethanes 17'18. In our studies, we evaluated extruded
tubing with various degrees of thermal degradation ranging
from none ('implantable quality') to moderate (some
discoloration). Since extractable amine from degraded (or
improperly polymerized) urethane is known to be
mutagenic 18, it is highly significant that no mutagenicity
was observed for any of the specimens.
In our study 10 tumours were found in 84 rats for a
incidence of less than 12% although eight were unrelated
to the implants. Fibrosarcomas were found at the 80A
polyurethane implant site in 2 out of 43 animals, representing
a tumour incidence of 4.7%. Spontaneous tumours in
Sprague-Dawley rats has been reported in four separate
studies. Thompson reported occurrence of tumours in 52
of 125 rats (41.6%) in a study to determine the effects of
an irradiated food diet 19. Schardein reviewed studies on
Pacemaker leads: K. Stokes and K. Cobian
5,086 rats and found only 218 tumours, an incidence of
4.2% 2°. MacKenzie and Garner observed 749 tumours in
2,082 rats for an incidence of nearly 36% and Prejean
found 219 tumours in 360 Sprague-Dawley rats, an
incidence of 60%21'22" The highest incidence of
spontaneously occurring fibrosarcomas in Sprague-Dawley
rats was 1.6% in the study of MacKenzie and Garner 21,22.
In 1941, Turner reported the occurrence of sarcomas at
the sites of subcutaneously implanted Bakelite discs in rats 23.
Subsequently, Oppenheimer induced sarcomas in rats by
implanting cellophane24. These findings resulted in
numerous studies to ascertain the etiology of the malign-
ancies induced by implantation. While some studies
incriminated components or contaminants of the implants
as actual carcinogens, the induction of malignancies in rats
by the presence of foreign bodies became an accepted
fact 25. Additional studies indicated that the physical, not
the chemical, properties of the foreign body were
responsible for tumorigenicity 26. Many test materials lost
their tumorigenicity when implanted in pulverized, finely
shredded or woven form or when their surfaces were
interrupted with multiple perforations 25. It was observed
that there was a quantitative correlation between tumour
incidence and the surface area of the implants 27. Button-
like implants caused more tumours because of the extensive
fibrosis needed to fill in the indentations. Stanton observed
a relationship between foreign body size and tumour
incidence28.
Since the materials which we implanted in rats were
negative on mutagenic screening (Ames test) and are of the
size and shape that cause increased foreign body tumori-
genesis in rodents, our conclusion is that the increased
incidence of subcutaneous fibrosarcoma is a direct result
of foreign body tumorigenesis rather than being induced
by chemicals or contaminants in the polyurethane.
Biostability
We believe that only long-term implants can verify the
biostability of polymers. In order to obtain all necessary
physical data, miniature tensile specimens were used.
Because certain data, such as stress-strain results, are
dependent on specimen shape and strain rate, one must
avoid the temptation to compare the implant data with
results from larger specimens. Clearly, results from larger
specimens as discussed above (Table 1, for example) are
both more accurate and more precise.
Stress-strain studies versus time are a practical means
of establishing the stability of a polymer. The precipitous
drop in tensile strength observed over the first few months
was at first cause for concern. But remember that absorbed
moisture is expected to cause reversible changes. The
straight line behaviour observed for the next two years is
typical of a stable polymer. If chain scission had occurred,
the tensile strength and elongation would have continued
to decrease. Cross-linking and embrittlement would have
revealed increasing tensile strength and decreasing
elongation. These and other signs of degradation were not
observed. If, on the other hand, the observed changes were
the result of moisture absorption or morphological reorgani-
zation they should be reversible for the most part. This
reversibility was indeed demonstrated by the return
toward initial values after vacuum drying or solvent extraction
of one and two year implant interval specimens. Virtually
identical behaviour was demonstrated in test tank studies.
Again, the evidence points to polymer stability after an
Biomaterials 1982, Vol 3 October 229
Pacemaker leads: K. Stokes and K. Cobian
initial change due (primarily) to moisture absorption.
Note that moisture absorption occurs at an exponential
rate so it is reasonable to expect the biggest change in the
first months. In contrast, Swanson and Lebeau 16 showed
that silicone remains virtually unchanged for up to 32
weeks canine implant. Silicone absorbs less than one percent
moisture. Again, one of the key issues is that the toughness
of polyurethane at its worst is superior to silicone at its
best for pacing lead use.
Scanning electron microscopy revealed no changes in
polyurethane surfaces with,~time. In the presence of some
form of external biological attack one would certainly
expect to see surface erosion, cracking, pitting, etc. While
not relevant to this discussion the rippled polyurethane
surface is interesting, it is probably the result of mould
shrinkage.
Molecular weight analyses are also sensitive means to
establish the stability or degradation of a polymer. G.p.c.
molecular weight distribution and intrinsic viscosity results
support the conclusion that the chronically implanted
polymers are stable. The lack of visible infrared spectrum
changes is also strong evidence of biostability.
Differential scanning calorimetry is a very sensitive
technique used to characterize polymers. Changes in
polymer morphology or degradation resulting from thermal
treatment (processing), moisture absorption, and other
environmental factors are readily detectable. T h e r m a l
scans showed no significant differences between explant,
control and tank stored specimens. This supports the
conclusion that no significant degradation occurred. It
also suggests that no appreciable morphological changes
occurred as a result of implant. Changes in tensile strength
shortly after implant, therefore, must be due primarily
to moisture absorption.
CONCLUSION
The dry physical properties of certain polyether poly-
urethane thermoplastics makes them attractive candidates
for use in permanently implantable cardiac and
neurologic leads. Most polyurethanes, however, are
neither adequately stable nor readily processible. Several
polyether polyurethanes were evaluated for permanent
implant. Their physical properties change as the result of
moisture absorption, while those of silicone do not. The
moisture saturated polyurethane tensile strength, stiffness
and toughness values are superior to the traditionally used
silicone for the devices in question. Several in v i t r o and
in vivo tests verified that early changes in stress-strain data
shortly after implantation are the result of reversible processes,
primarily moisture plasticization. Linear tensile strength
and elongation data obtained from specimens after one
month to two years implantation, reversibility of the acute
changes w i t h extraction or desiccation, and studies on
density, infrared absorption, g.p.c, molecular weight, intrinsic
viscosity, differential scanning calorimetry, and scanning
electron microscopy as a function of implant time, verifies
that these moisture plasticized polyurethanes are stable
implantable materials. Biocompatibility data were fewer
and mutagenicity tests were negative. No evidence of
tumours or other untoward results were found on or near the
55D rat implants. Two tumours around 8 0 A specimens in
rats were determined to be related to solid-state carcino-
genesis 29 and not of clinical significance. This conclusion
is based in part on favourable mutagenicity test results and
230 Biomaterials 1982, Vol 3 October
the well known tendency for these animals to develop
tumours about relatively large subcutaneous implants. The
polymers per se are therefore, biologically stable,
permanently implantable and meet our physical property
requirements for permanent pacing leads. Nonetheless,
this conclusion can be rendered invalid simply by inexpert
polymer processing. A thorough knowledge of the chemistry
of polymers, appropriate processing controls, and
continuing quality control testing by the device manu-
facturer are critical in maintaining the validity of the
above conclusions.
ACKNOWLEDGEMENTS
The authors wish to express their sincere appreciation to
the many scientists and technicians who contributed to
this study. Special thanks to Kathy Burford, A r t Coury,
John Doring, Dennis Elsberry, Kay Loucks, Mike
Schollmeyer, Steve Skorich, Peter Urbanski, and Kent Van
Kampen for their dedicated assistance.
REFERENCES
1 Furman, S. and Robinson, G., The caseof an intracardiac
pacemaker in the correction of total heart block, Surgery
Forum 1958, 9,245-248
2 Mandarino, M.P. and Salvatore, J.E., Ostamer: A polyurethane
polymer: Its usesin fractures and diseasedbones. Report of
thirty-five cases,J. Bone Jt. Surg. 1959,41A, 1542 (abstract)
3 Boretos, J.W. and Pierce, W.S., Segmented polyurethane: A
new elastomer for biomedical applications, Science 1967,
158, 1481-1482
4 Brash,J.L., Fritzinger, B.K. and Bruck, S.D., Development of
block copolyether-urethane intra*aortic balloons and other
medical devices, J. Biomed. Mater. Res. 1973, 7, 313-334
5 Boretos, J.W., Pierce, W.S., Baier, R .E., LeRoy, A.F. and
Donachy, H .J., Surface and bulk characteristics of a
polyether urethane for artificial hearts, J. Biomed. Mater.
Res, 1975, 9,327-340
6 Mirkovitch, V., Akutsu, T. and Kolff, W., Polyurethane
aortas in dogs, three-year results, Trans. Amer. Soc. Artif.
Intern. Organs 1962, 8, 79-84
7 Schollenberger, C.S. and Stewart, F.D., Thermoplastic
polyurethane hydrolysis stability,J. Elastoplast. 1971,3,
28 -56
8 Boretos, J.W., Tissue pathology and physical stability of a
polyether elastomer on three year implantations, J, Biomed.
Mater. Res. 1972, 6,473-476
9 Guess,W.L., Rosenbluth, S.A., Schmidt, 8. and Autian, J.,
Agar diffusion method for toxicity screening of plastics on
cultured cell monolayers, J. Pharm. Sci. 1965, 54, 1545-1547
10 United States Pharmacopia, 19th Rev. 1975, 613 and 644
11 Ames, B.N., Durston, W.E., Yamasaki, E. and Lee, F.D.,
Carcinogens are mutagens: A simple test system combining
liver homogenates for activation and bacteria for detection,
Proc, Nat. Acad. Sci. U.S.A. 1973, 70, 2281-2285
12 Ames, B.N., McCann, J. and Yamasaki, E., Methods for
detecting carcinogens and mutagens with salmonella/mammalian
microsomal mutagenicity test, Mutat., Res., 1975, 31,
347-374
13 United States Pharmacopia, 19th Rev., 1975, 646
14 Schollenberger, C.S. and Dinbergs, K., Thermoplastic
polyurethane molecular weight-property relations,J.
Elastoplast. 1973, 5, 222-251
15 Schollenberger, C.S. and Dinbergs, K., Thermoplastic
polyurethane elastomer molecular weight-property relations,
further studies, J. o f Elastomers and Plast. 1979, 11, 58-91
16 Swanson,J.W. and Lebeau, J.E., The effect of implantation
on the physical properties of silicone rubber,J. Biomed.
Mater. Res. 1974, 8,357-367
17 Autian, J., Singh, A .R., Turner, J .E., Hung, G .W.C., Nunez,
L.J. and Lawrence, W.H., Carcinogenesisfrom polyurethane,
Cancer Research 1975, 35, 1591-1596
18 Darby, T.D., Johnson, H .J. and Northrup, S .J., An evaluation

of a polyurethane for use as a medical grade plastic, Toxicol.
Appl. Pharmacol. 1978, 46,449-453
19 Thompson, S.W., Huseby, R .A., Fox, M .A., Davis, C.L. and
Hunt, R.D., Spontaneous tumors in the Sprague-Dawley rat,
J. NCI 1961,27, 1037-1051
20 Schardein, J.L., Fitzgerald, J.E. and Kaump, D.H.,
Sponteneous tumors in Haltzman source rats of various ages,
Path. Vet. 1968, 5,238-252
21 MacKenzie, W.F. and Garner, F.M., Comparison of neoplasms
in six sources of rats, J. NCI 1973, 50, 1243-1257
22 Prejean, J.D., Peckham, J.C. and Casey, A.E., Sponteneous
tumors in Sprague-Dawley rats and Swiss mice, Cancer Research
1973, 33, 2768-2773
23 Turner, F.C., Sarcomas at the site of subcutaneously implanted
bakelite disks in rats, J. NC/1941,2, 81-83
24 Oppenheimer, B.S., Oppenheimer, E.T. and Stout, A.P.,
Pacemaker leads: K. Stokes and K. Cobian
Sarcomas induced in rats by implanting cellophane, Proc. Soc.
Exp. Biol. Med. 1948,67, 33-34
25 Brand, K.G., Johnson, K.H. and Buoen, L.C., Foreign body
tumorigenesis, CRC, Critical Reviews in Toxicoloty, 1976,
2,353-394
26 Brand, K.G., Buoen, L .C. and Brand, I., Foreign body
tumorigenesis in mice -- most probable number of originator
cells, J. NCl 1973, 51, 1071-1074
27 Nothdurft, H., Tumorerzeugung durch Fremdkorper
Implantation, Abh. Dtsch, Akad, Wiss. Berlin KI. Med. 1960,
3, 80
28 Stanton, M.F., Fiber carcinogenesis: Is asbestos the only
hazard? (Editorial), J. NCl 1974, 52, 633-634
29 Oppenheimer, B~S., Oppenheimer, E.T. and Stout, A.P.,
Carcinogenic effect of imbedding various plastic films in
rats and mice, Surg. Forum 1953, 4,672-676
Biomaterials 1982, Vol 3 October 231