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Failure mechanisms of ventricular tissue due to deep penetration
ARTICLE IN PRESS Journal of Biomechanics 42 (2009) 626–633
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Failure mechanisms of ventricular tissue due to deep penetration T. Christian Gasser a,, Peter Gudmundson a, Gottfried Dohr b a b
Department of Solid Mechanics, Royal Institute of Technology (KTH), Osquars Backe 1, SE–100 44 Stockholm, Sweden Histology and Embryology and Center of Molecular Medicine, Institute of Cell Biology, Medical University of Graz, Harrachgasse 21, A–8010 Graz, Austria
a r t i c l e in f o
a b s t r a c t
Article history: Accepted 10 December 2008
Lead perforation is a rare but serious complication of pacemaker implantations, and in the present study the associated tissue failure was investigated by means of in-vitro penetration of porcine and bovine ventricular tissue. Rectangular patches from the right ventricular free wall and the interventricular septum were separated, bi-axially stretched and immersed in physiological salt solution at 37 C before load displacement curves of in total 891 penetrations were recorded. To this end flat-bottomed cylindrical punches of different diameters were used, and following mechanical testing the penetration sites were histological analyzed using light and electron microscopes. Penetration pressure, i.e. penetration force divided by punch cross-sectional area decreased slightly from 2.27(SD 0.66) to 1:76ðSD0:46Þ N=mm2 for punches of 1.32 to 2.30 mm in diameter, respectively. Deep penetration formed cleavages aligned with the local fiber orientation of the tissue, and hence, a mode-I crack developed, where the crack faces were wedged open by the advancing punch. The performed study derived novel failure data from ventricular tissue due to deep penetration and uncovered associated failure mechanisms. This provides information to derive mechanical failure models, which are essential to enrich our current understanding of failure of soft biological tissues and to guide medical device development. & 2008 Elsevier Ltd. All rights reserved.
Keywords: Deep penetration Ventricular tissue In-vitro experiment Lead perforation Tissue splitting
1. Introduction Acute or delayed lead perforation is a rare but serious complication of pacemaker implantation with numerous case reports and case series known (Khan et al., 2005). Design parameters, e.g., diameter (Khan et al., 2005) and positioning of the lead are thought to be associated risk factors (Vlay, 2003). It is recognized that the constitution of ventricular tissue intrinsic to the patient, i.e. its elastic and failure properties might also be critically important to the design of the lead, which, however, has not been attracted much attention in the literature. Although experimental studies to characterize failure properties of vascular tissue under tensile (Mohan and Melvin, 1982; Vorp et al., 1996; MacLean et al., 1999; Vorp et al., 2003; Sommer et al., 2008), tearing (Purslow, 1983), dissection (Carson and Roach, 1990; Tiessen and Roach, 1993; Roach and Song, 1994; Tam et al., 1998; Roach et al., 1999), biaxial (Mohan and Melvin, 1983) and peeling (Sommer et al., 2008) loads have been reported, no studies have investigated failure of ventricular tissue due to deep penetration. Deep penetration of soft biological tissues has mainly be studied towards needle insertion (Abolhassani et al., 2007), where phenomenological models based on experimental data
(Okamura et al., 2004; DiMaio and Salcudean, 2005) have been developed but less attention has been spent to the failure characteristics of the underlying material. To the authors knowledge the involved fracture mechanisms of deep penetration in soft biological tissues has only been discussed with application to skin (Shergold and Fleck, 2004), where shearing and tensile modes of failure have been related to flat-bottomed and sharp-tipped punches (penetrators), respectively. Failure mechanisms of ventricular tissue have not yet been investigated from a mechanical perspective, which, however, is a prerequisite to develop strategies against acute or delayed lead perforation. Likewise, a fundamental mechanical understanding of soft tissue failure in general is critical to develop numerical fracture models (Gasser and Holzapfel, 2006, 2007; Ferrara and Pandolfi, 2008), which then allows guided devices development and fast prototyping. Within this work we propose an in-vitro mechanical test to explore the resistance of bi-axially stretched ventricular tissue against deep penetration. The mechanical experiment has been performed with cylindrical punches of different diameters and the introduced tissue failure has been studied.
2. Methods Corresponding author. Tel.: +46 8 790 7793; fax: +46 8 411 2418.
E-mail addresses: [email protected] (T.C. Gasser), [email protected] (P. Gudmundson), [email protected] (G. Dohr). URL: http://www.hallf.kth/tg (T.C. Gasser). 0021-9290/$ - see front matter & 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.jbiomech.2008.12.016
A novel mechanical testing device has been developed to characterize the penetration properties of right ventricular tissue at fixed biaxial stretches. The basic experimental principle is illustrated in Fig. 1, whereas the device is described
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F
1
u
λy
1
λx
Fig. 1. Basic principle of the penetration experiment. Ventricular tissue specimens were bi-axially stretched by the principal stretches lx and ly . This state of deformation was kept fixed during the tissue was penetrated, where the displacement, u, was prescribed and the penetration force, F, was recorded.
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and lower position plates, which allowed a defined distribution of penetrations. Grips and position plates were made of polyvinyl chloride (PVC) while a stainless steel container stored the PSS. The punch was mounted in the punch holder, which was connected to the 100.0 N FCTA load cell (VETEK AB) and fixed to the testing system with a magnet. This design allowed a fast and easy positioning (defined by the position plates) of the punch. The inherent stiffness of the testing device was investigated at different positions of the punch, and found to be several magnitudes higher than the stiffness of the investigated ventricular specimens. Likewise, the ability to reproduce test results with the developed experimental equipment has been ensured due to preliminary penetration of man-made materials. For illustrative purposes, Fig. 4 is included, which shows results from validation experiments with silicon gel in air at 18:0 C and a penetration velocity of 5.0 mm/min. The diagram presents results from five penetrations with a punch of 1.32 mm in diameter. As can be seen from the data, the deviation of the particular load displacement curves remains acceptable, an hence, the experimental principle and device have been found to be suitable to identify penetration properties of the underlying material. Finally, it is worth noting that similar curves, as shown in Fig. 4, have been presented earlier (Shergold and Fleck, 2005).
2.2. Specimen preparation for the penetration test Intact hearts have been provided by Swedish Meats AB, Uppsala and specimen preparation started within less than 4 hours post mortem. To this end the heart was opened at the base, right ventricular free wall and interventricular septum were separated and rectangular specimens of about 70:0 70:0 mm were prepared from these two anatomical sites. Due to geometrical limitations porcine test specimens could only be obtained from the right ventricular free wall. Since the ventricular wall is anisotropic, i.e. it has directional dependent mechanical properties, the specimen’s orientation with respect to the ventricular wall needed to be considered. In details, the edges of the rectangular specimen should coincide with the material axes, i.e. the principal directions of material anisotropy. Naturally, the material axes are not homogeneous over the (big) specimens, and hence, this requirement could only be fulfilled in an average sense. Within this work, the epicardial and myocardial fiber directions were used to define the orientations of the specimens from the right ventricular free wall and the interventricular septum, respectively. To this end the fiber orientation was detected from visual inspection with a low magnifying loupe, where the tissue was partly stained with blue ink to highlight its fibrous structure. Note that the fiber orientation of the interventricular septum was much more coherent, which simplified the characterization of the specimen orientation. To mount the specimen in the testing device it had to be thinner than 12.0 mm, and hence, if required the epicardial layers was sliced off. In details, this preparation step affected mainly the bovine specimens and aimed at getting about the same specimen thickness over the testing area. In contrast, the endocardial site was always kept intact to provide equivalent conditions to the onset of lead perforation. Thereafter, the specimen was stored in PSS at 4 C until testing.
Fig. 2. Experimental device for ventricular tissue penetration integrated in a conventional testing system (100.0 kN MTS load-frame updated with an INSTRON digital controler 8500þ). in detail in Section 2.1. In total nine rectangular specimens harvested from three cows and three pigs were prepared, and 891 penetrations were performed; specimen preparation and testing protocol are outlined in Sections 2.2 and 2.3, respectively. Penetrations are performed with flat-bottomed cylindrical punches of 2.30, 1.98, 1.65 and 1.32 mm in diameter, with a rounded edge (radius of 0.13 mm). Note that the penetrator size is in the range of commonly used pacemaker leads. During the experiment penetration forces and displacements were recorded and thereafter the tissue was fixated in 4.0% zinc formaldehyde solution for 24 hours and stored in 70% alcohol. Tissue failure of selected penetrations were histologically analyzed, where in total four sub-specimens were prepared; details are given in Section 2.4.
2.1. Design of the mechanical testing device The especially developed experimental device for ventricular tissue penetration has been integrated in a conventional testing system (100.0 kN MTS loadframe updated with an INSTRON digital controler 8500þ); see Fig. 2 of the installation and the schematic drawing of the experimental device in Fig. 3. During testing the ventricular tissue specimens remained entirely in physiological salt solution (PSS) at 37 1 C, which was controlled by a THERMAC 6000 D30 micro controller (research incorporated). Stretching screws, to be controlled independently from each other, allowed a biaxial stretching of the specimen, where specially designed grips (four on each side of the specimen) transferred the load into it. The location of the penetration was defined by upper
2.3. Protocol for the penetration test The ventricular specimen was equilibrated in PSS at 37 1 C for about 30 minutes prior the grips were applied by use of fixation nails, see Fig. 5(a). The stainless steel container was filled with PSS and the heating system was activated, such that the stable testing temperature of 37 1 C was reached after about 20 minutes. Thereafter, the specimen was mounted in the experimental device (described in Section 2.1) and bi-axially stretched to its testing conditions, see Fig. 5(b), which were defined by the principal stretches of lx ¼ 1:128 and ly ¼ 1:084. This state of deformation, which corresponds to the anterior midventricle deformation of the dog heart at 75% filling (McCulloch et al., 1989), was applied by the four stretching screws (see Fig. 3) and controlled by measuring the (average) distance between the fixation nails. Note that edge effects, i.e. strain inhomogeneities at the fixation were negligible because of the large specimen size. Once the upper position plate was mounted and the punch was positioned, a displacement controlled penetration at a velocity of 5.0 mm/min was performed, where the bi-axially stretch state was kept constant. Preliminary experiments with ventricular tissue at penetration velocities ranging from 1.0 to 15.0 mm/min showed that rate effects are negligible compared to regional variations of the test results. For convenience, the penetration velocity was set to 5.0 mm/min, and in view of the observed rate independence the experiment could be regarded as quasi-static. Note that similar (Frick et al., 2001) and contradictory (Brett et al., 1997) statements regarding rate effects of deep penetration of skin tissue have been reported earlier. The penetration force and the displacement were recorded with a sampling rate of 2.0 Hz and each specimen was 25 times penetrated with punches of 2.30, 1.98, 1.65 mm in diameter and 24 times with the punch of 1.32 mm in diameter. The locations of the penetrations with the different punches were homogeneously distributed over the specimen, such that regional variations of the tissue
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Stretching screw Upper and lower position plates
Magnet Load cell (100.0 N) Punch holder Punch Stretched ventricular specimen
Grip
Heating system
Container filled with PSS
Fig. 3. Schematic drawing of the experimental device to penetrate bi-axially stretched specimens of ventricular tissue.
Penetration Force N
1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 0.0
2.5
5.0
7.5 10.0 12.5 Displacement mm
15.0
17.5
Fig. 4. Validation experiment illustrating the force displacement response of silicon gel penetration, where a punch of 1.32 mm in diameter and a penetration velocity of 5.0 mm/min were used.
properties were compensated and the achieved results could be compared amongst the different punches.
2.4. Specimen preparation for the histological analysis Light microscopy. Heart tissue was fixed in Zenker’s fluid, which was made by mixing distilled water (950 ml), potassium dichromate (25 g), mercuric chloride (50 g) and glacial acetic acid (50 g). The tissue was then transferred into 70% ethanol and embedded in paraffin using an overnight standard protocol and an automatic tissue processor (Shandon Citadel). Sections at a thickness of 5 mm were taken with a sledge type microtome, routinely stained with the haematoxylin and eosin method and thereafter cover-slipped with a xylen based mounting medium. Scanning electron microscopy. Heart tissue samples were dehydrated in a graded series of ethanol and dried in a critical-point drying apparatus (Balzers CPD 020; Balzers, Liechtenstein). Thereafter, samples were mounted on aluminum stubs, sputter-coated with gold palladium and investigated with a scanning electron microscope (DSM 950; Zeiss, Oberkochen, FRG).
3. Results 3.1. Observed penetration characteristics According to the anatomy of the right ventricular wall, different types of tissues fail during deep penetration, which was to some extent visible from the recorded force displacement curves, see Fig. 6. As long as the tissue deformed elastically, the
penetration force increased progressively with respect to the punch displacement, and at the elastic limit, irreversible deformation developed, i.e. the tissue failed and the specimen got (irreversible) penetrated. Clearly, the mechanical penetration properties of the involved tissues defined the recorded mechanical signal, as illustrated in Fig. 6, where the signals from penetration of (a) the myocardium, (b) endocardium and myocardium and (c) the intact wall, i.e. endocardium, myocardium and epicardium are illustrated. While Fig. 6(a) is characterized by a single (scattered) force plateau of about 1.1 N defining myocardial’s resistance against penetration, Fig. 6(b) exhibits a load peak of about 7.5 N associated with endocardium penetration prior the myocardium failed at a load level of about 1.5 N. Finally, Fig. 6(c) shows load peaks of about 8.0 and 12.0 N denoting penetrations of endo- and epicardium, respectively. Once the punch went through the whole tissue a decrease of the force was recorded, and thereafter, friction between tissue and punch defined the force level. Naturally, the force required to penetrate endo- and epicardium will strongly depend on the thicknesses of these layers, which themselves vary significantly over the anatomical site of the right ventricle (LeGrice et al., 1995), and hence, the definition of a ‘typically force displacement curve’ for the right ventricular wall failed. In order to discuss tissue failure mechanisms a particular penetration is considered, where a punch of 2.30 mm in diameter went through endocardium and parts of the myocardium. In particular, the recorded force displacement curve and the induced ‘channel of tissue failure’ are illustrated, see Fig. 7. It can be seen that the tissue failure remained localized and did not spread extensively away from the site of the penetration, i.e. inelastic deformation is limited to the site of the penetration. Likewise, a cylindrical channel as it is supposed to develop by the hypothized mode-II crack propagation associated with flat-bottomed punches (Shergold and Fleck, 2004), cannot be observed. Although visual inspections of the penetrated specimens exhibited a few cylindrical holes at the entrance of the punch, the majority of penetrations formed cleavages aligned with the local fiber orientation of the tissue, see Fig. 8(a). Hence, a splitting mode (mode-I crack), where the crack faces are wedged open by the advancing punch defines the primary penetration mechanism; the idealized situation is illustrated in Fig. 9. In addition to the splitting mode, secondary dissections in planes parallel to the layers of the ventricular wall, see Fig. 10(a),
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Fig. 5. Porcine specimen from the right ventricular free wall. (a) Specimen fixed to the grips and (b) specimen bi-axially stretched to its testing conditions.
Irreversible deformation
Elastic deformation
Penetration Force N
1.40 1.12 0.84 0.56 0.28 0.00 0
0.2
0.4 0.6 Relative Thickness
Elastic deformation
0.8
1.0
Irreversible deformation
Penetration Force N
10.0 8.0 6.0 4.0 2.0 0.0 0
0.2
0.4 0.6 Relative Thickness
Elastic deformation
0.8
1.0
Irreversible deformation
Penetration Force N
14.0 11.2 8.4 5.6 2.8 0.0 0
0.2
0.4 0.6 Relative Thickness
0.8
1.0
Fig. 6. Particular force displacement curves recorded with a punch of 1.98 mm in diameter. Penetration through (a) the myocardium, (b) endocardium and myocardium and (c) the intact wall, i.e. endocardium, myocardium and epicardium.
and rupture (tearing) of myocardial fibers (heart muscle cells) with associated pull-out of sarcomeres, see Fig. 10(b), have been identified from the histological investigation. Although substantial reversible deformation were observed when the punch was removed, (locally) large remaining deformations are shown by the
electron microscopical images taken at the entrance and exit of the punch in Fig. 8 (or alternatively in the Fig. 7). Failure of ventricular tissue due to deep penetration involves complex crack formations and, in particular, a sharp crack tip does not exist. This is also illustrated by the electron microscopical
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Elastic deformation
Irreversible deformation
Penetration Force N
10.0 8.0 6.0 4.0 2.0 0.0 0.4 0.6 Relative Thickness
0.2
0.8
1.0
Penetration exit
Penetration entrance
0
Endocardium
Myocardium
C hannel of tissue failure
Fig. 7. Particular results from penetrating the endocardium and myocardium of right ventricular wall of a porcine specimen with a punch of diameter 2.30 mm. (a) Recorded force displacement curve. (b) Picrosirius red stain illustrating tissue failure through the different layers of the ventricular tissue.
© Inst.f.Zellbiologie,Histologie
u.Embryologie
© Inst.f.Zellbiologie,Histologie
u.Embryologie
Fig. 8. Electron microscopical images taken at the (a) entrance and (b) exit of the punch illustrating a splitting mode (mode-I) failure and the presence of remaining deformations, respectively.
image shown in Fig. 10(c), which was taken at the exit of the punch and shows multiple (partly cross-bridged) dissections. Finally, it is emphasized that the electron microscopical images taken from the disrupted endocardium Fig. 10(d) exhibits long bundles of collagen fibers, and hence, collagen pull-out rather than rupture of collagen bundles might determine the failure thereat.
3.2. Statistical analysis Due to the irregular results from the endo- and epicardial layers, probably caused by the varying thicknesses of them, we limit the analysis to quantify the penetration properties of myocardial tissue. In details, only the recorded penetration force
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Circular penetrator
631
Fibrous tissue Penetration Force N
15.0 12.5 10.0 7.5 5.0 2.5 0.6
0.65
0.7 0.75 0.8 Relative Thickness
0.85
0.9
Fig. 11. Filtered force penetration characteristics from pig specimen P2, where 25 penetrations with a punch of 2.30 mm in diameter were recorded. The data reflects myocardium’s resistance against deep penetration and was used to define average penetration forces in a least square sense. Fig. 9. Idealized failure mode of ventricular tissue due to deep penetration, where crack faces are wedged open by the advancing punch defining a splitting mode (mode-I) failure.
20µm
20µm
Endocard
Fig. 10. Tissue failure mechanisms due to penetrating right ventricular tissue. Picrosirius red stains from the penetrated myocardium illustrate myocardium fiber (a) dissection and (b) rupture as indicated by arrows. Electron microscopical image illustrating dissection type of failure at the exit of the punch (c) pull-out of bundles of collagen of the sub-endocardial layer at the entrance of the punch (d).
between 60% and 90% punch displacement has been used in the following, i.e. data from the elastic deformation and from penetrating endo- and epicardium layers were filtered out. As a representative example, Fig. 11 shows the filtered data from 25 penetrations of pig specimen P2 using a punch of 2.30 mm in diameter. Subsequently, the average penetration force for each penetration was quantified in a least square sense, which finally defined the data in Table 1. In details, mean value and standard deviation (SD) of penetration forces with respect to the punch
Table 1 Force in Newton to penetrate the myocardium of six bovine (B1–B6) and three porcine (P1–P3) specimens with punches of different diameters. Specimen
Punch diameter (mm) 2.30
1.98
1.65
B2 B3 B4 B5 B6
6.19(SD 1.53) 8.82(SD 2.58) 9.43(SD 3.13) 8.43(SD 3.45) 9.69(SD 3.34)
5.06(SD 7.05(SD 6.99(SD 5.24(SD 6.82(SD
P1 P2 P3
7.27(SD 2.35) 6.60(SD 2.05) 4.76(SD 2.03)
5.94(SD 1.74) 4.52(SD 1.48) 3.74(SD 1.98)
1.19) 1.88) 1.99) 2.17) 2.20)
4.67(SD 4.88(SD 5.01(SD 5.09(SD 5.34(SD
1.32 1.14) 1.14) 1.65) 1.94) 1.70)
3.16(SD 0.67) 3.95(SD 1.23) 3.38(SD 0.85) 4.02(SD 1.78) 4.11(SD 1.48)
4.85(SD 1.73) 3.39(SD 1.11) 2.68(SD 1.56)
3.25(SD 1.49) 2.50(SD 0.83) 1.85(SD 0.87)
diameters of six bovine and three porcine specimens are given. It is emphasized that the applied method gives analyst independent results and that the applied least square fitting, which can also be seen as an integration of the experimental data, reduces the impact of spurious load peaks if present. Table 1 exhibits no significant difference between bovine and porcine specimens, and hence, the mean values of the penetration forces were pooled, which, finally, lead to the plot of the penetration pressure with respect to the punch diameter in Fig. 12. A slight decrease of the penetration pressure towards thicker punches is observed (similar results apply to skin tissue (Shergold and Fleck, 2004), however, it appears that this parameter remains fairly insensitive within the considered domain of punch diameters.
4. Discussion We introduced a novel experimental setup to investigate the penetration properties of ventricular tissue under controlled mechanical boundary conditions. To this end bi-axially stretched specimens were penetrated, force displacement properties were recorded and the induced tissue failure was histologically analyzed using light and electron microscopes. Throughout this study the bi-axial state of stretch according to data from anterior mid-ventricle deformation of the dog heart at 75% filling (McCulloch et al., 1989) has been applied, which was also found to be in the transition zone between the soft (low-strain) and the stiff (high-strain) passive properties of the
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Penetration pressure N/mm2
3.0 2.5 2.0 1.5 1.0 0.5 0.0 1.2
1.4
1.6 1.8 2.0 Punch diameter mm
2.2
2.4
Fig. 12. Penetration characteristics of the right ventricular myocardium. Penetration pressure (penetration force divided by punch cross section) with respect to the punch diameter. Results are in qualitative agreement with findings from skin tissue (Shergold and Fleck, 2004).
right ventricular free wall (Sacks and Chuong, 1993). This indicates that the considered state of deformation appears during the cyclic in-vivo stretching of the ventricular free wall, and hence, our experiment mimicked at least a single physiologically relevant deformation. To the authors’ knowledge the in-vivo deformation of the interventricular septum has not been reported in the literature, and hence, the same bi-axially state of stretch was applied to the interventricular specimens. The rectangular tissue specimens were prepared, such that the material axes coincided with the stretching directions, and hence, no shear deformation develops during bi-axial stretching. Since the fiber orientation of the ventricular free wall is inhomogeneous, this could only be satisfied in average, i.e. the fiber orientations were in average aligned with the stretching direction but not locally. Consequently, local strain inhomogeneities were present in the bi-axially stretched tissue. It needs to be emphasized that ventricular tissue is fairly heterogeneous (as indicated by the complex topology of the endocardium), and hence, strain (stress) inhomogeneities might reflect the in-vivo deformation of ventricular tissue (McCulloch et al., 1989). The identified failure of ventricular tissue due to deep penetration exhibited complex crack formations and a sharp crack tip could not be observed, thus theories associated with sharp crack tips will fail to describe the problem satisfying. Although the present study used flat-bottomed punches, a splitting mode, where the crack faces were wedged open by the advancing punch seems to be the primary penetration mechanism. Hence, a mode-I crack develops in parallel to the myocardial fibers and a splitting like failure mechanism applies. This is in clear contradiction to the development of a mode-II (shear) failure, as it has been postulated for flat-bottomed punches (Shergold and Fleck, 2004). This discrepancy might be a direct consequence of the fibrous ventricular tissue considered herein. Likewise, secondary dissections, tearing of myocardial fibers (muscle cells) and large remaining deformations were found to be characteristic for deep penetration of ventricular tissue. These secondary phenomena might be of minor importance to the mechanics of deep penetration, which, however, could not be further investigated by the present study. The penetration resistance of the myocardial tissue was quantified, where experimental data between 60% and 90% penetration displacement was considered, which aims at cutting off results from elastic deformations and endo- and epicardial penetration. These limits were selected after inspecting the collected experimental data. To quantify myocardium’s penetra-
tion resistance the recorded penetration forces were averaged between these limits. Naturally, the derived penetration forces include frictional resistance from the (already penetrated) endocardial layer, and hence, this approach might be slightly overestimating the strength of the myocardium in case a thick endocardial layer is present. The analysis of the experimental results showed that the pressure required penetrating ventricular tissue (slightly) decreased with increasing punch diameters. Most interestingly, this tendency could not be observed for punches of larger diameters, where the penetration pressure remained insensitive with respect to the punch diameter. Perhaps the observed change in characteristics indicates the activation of different failure mechanisms for larger and smaller punches. Passive ventricular tissue was used for the penetration experiments although this tissue is cyclic activation in-vivo. Activated ventricular tissue would at least cause a higher frictional resistance against deep penetration, thus an increase of the penetration force is expected. However, cyclic activation might also activate fatigue-like failure mechanisms (Suresh, 1998), which in a long term might decrease the tissue’s resistance against penetration. It is emphasized that the proposed experimental setup might also be used to penetrate (cyclic) activated ventricular tissue to explore this question further. In conclusion, the performed study provided novel information regarding the mechanisms of deep penetration of soft biological tissues, and the presented data might be used to develop analytical and/or numerical models to gain further insight in failure of soft biological tissues and/or to improve clinical devices.
Conflict of interest statement None declared.
Acknowledgments This work has been supported by St. Jude Medical and by the Young Faculty Grant no. 2006-7568 from the Swedish Research Council, VINNOVA, and the Swedish Foundation for Strategic Research. Likewise, contributions by Bengt Mo¨llerberg and Hans ¨ berg (design and manufacture the experimental device) and by O Astrid Blaschitz and Rudolf Schmied (preparation of specimens for the histological analysis) are gratefully acknowledged. References Abolhassani, N., Patel, R., Moallema, M., 2007. Needle insertion into soft tissue: a survey. Med. Eng. Phys. 29, 413–431. Brett, P.N., Parker, T.J., Harrison, A.J., Thomas, T.A., Carr, A., 1997. Simulation of resistance forces acting on surgical needles. Proc. Inst. Mech. Eng. H211, 335–347. Carson, M.W., Roach, M.R., 1990. The strength of the aortic media and its role in the propagation of aortic dissection. J. Biomech. 23, 579–588. DiMaio, S.P., Salcudean, S.E., 2005. Interactive simulation of needle insertion models. IEEE Trans. Biomed. Eng. 52, 1167–1179. Ferrara, A., Pandolfi, A. 2008. Numerical modeling of fracture in human arteries. Comput. Methods Biomech. Biomed. Eng. 27(1), in press. Frick, T.B., Marucci, D.D., Cartmill, J.A., Martin, C.J., Walsh, W.R., 2001. Resistance forces acting on suture needles. J. Biomech. 34, 1335–1340. Gasser, T.C., Holzapfel, G.A., 2006. Modeling dissection propagation in soft biological tissues. Eur. J. Mech. A/Solids 25, 617–633. Gasser, T.C., Holzapfel, G.A., 2007. Modeling dissection failure during balloon angioplasty. Ann. Biomed. Eng. 35, 711–723. Khan, M.N., Joseph, G., Khaykin, Y., Ziada, K.M., Wilkoff, B.L., 2005. Delayed lead perforation: a disturbing trend. Pacing Clin. Electrophysiology 28, 251–253. LeGrice, I.J., Smaill, B.H., Chai, L.Z., Edgar, S.G., Gavin, J.B., Hunter, P.J., 1995. Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog. Am. J. Physiol. Heart Circ. Physiol. 269, H571–H582.
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Shergold, O.A., Fleck, N.A., 2005. Experimental investigation into the deep penetration of soft solids by sharp and blunt punches, with application to the piercing of skin. J. Biomed. Eng. 127, 838–848. Sommer, G., Gasser, T.C., Regitnig, P., Auer, M., Holzapfel, G.A., 2008. Dissection of the human aortic media: an experimental study. J. Biomech. Eng. 130 (2), 021007. Suresh, S., 1998. Fatigue of Materials, second ed. Cambridge University Press, Cambridge. Tam, A.S.M., Sapp, M.C., Roach, M.R., 1998. The effect of tear depth on the propagation of aortic dissections in isolated porcine thoracic aorta. J. Biomech. 31, 673–676. Tiessen, I.M., Roach, M.R., 1993. Factors in the initiation and propagation of aortic dissections in human autopsy aortas. J. Biomech. Eng. 115, 123–125. Vlay, S.C., 2003. Complications of active-fixation electrodes. Pacing Clin. Electrophysiology 25, 1153–1154. Vorp, D.A., Raghavan, M.L., Muluk, S.C., Makaroun, M.S., Steed, D.L., Shapiro, R., Webster, M.W., 1996. Wall strength and stiffness of aneurysmal and nonaneurysmal abdominal aorta. Ann. N.Y. Acad. Sci. 800, 274–276. Vorp, D.A., Schiro, B.J., Ehrlich, M.P., Juvonen, T.S., Ergin, M.A., Griffith, B.P., 2003. Effect of aneurysm on the tensile strength and biomechanical behavior of the ascending thoracic aorta. Ann. Thora. Surg. 800, 1210–1214.
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Journal of Biomechanics journal homepage: www.elsevier.com/locate/jbiomech www.JBiomech.com
Failure mechanisms of ventricular tissue due to deep penetration T. Christian Gasser a,, Peter Gudmundson a, Gottfried Dohr b a b
Department of Solid Mechanics, Royal Institute of Technology (KTH), Osquars Backe 1, SE–100 44 Stockholm, Sweden Histology and Embryology and Center of Molecular Medicine, Institute of Cell Biology, Medical University of Graz, Harrachgasse 21, A–8010 Graz, Austria
a r t i c l e in f o
a b s t r a c t
Article history: Accepted 10 December 2008
Lead perforation is a rare but serious complication of pacemaker implantations, and in the present study the associated tissue failure was investigated by means of in-vitro penetration of porcine and bovine ventricular tissue. Rectangular patches from the right ventricular free wall and the interventricular septum were separated, bi-axially stretched and immersed in physiological salt solution at 37 C before load displacement curves of in total 891 penetrations were recorded. To this end flat-bottomed cylindrical punches of different diameters were used, and following mechanical testing the penetration sites were histological analyzed using light and electron microscopes. Penetration pressure, i.e. penetration force divided by punch cross-sectional area decreased slightly from 2.27(SD 0.66) to 1:76ðSD0:46Þ N=mm2 for punches of 1.32 to 2.30 mm in diameter, respectively. Deep penetration formed cleavages aligned with the local fiber orientation of the tissue, and hence, a mode-I crack developed, where the crack faces were wedged open by the advancing punch. The performed study derived novel failure data from ventricular tissue due to deep penetration and uncovered associated failure mechanisms. This provides information to derive mechanical failure models, which are essential to enrich our current understanding of failure of soft biological tissues and to guide medical device development. & 2008 Elsevier Ltd. All rights reserved.
Keywords: Deep penetration Ventricular tissue In-vitro experiment Lead perforation Tissue splitting
1. Introduction Acute or delayed lead perforation is a rare but serious complication of pacemaker implantation with numerous case reports and case series known (Khan et al., 2005). Design parameters, e.g., diameter (Khan et al., 2005) and positioning of the lead are thought to be associated risk factors (Vlay, 2003). It is recognized that the constitution of ventricular tissue intrinsic to the patient, i.e. its elastic and failure properties might also be critically important to the design of the lead, which, however, has not been attracted much attention in the literature. Although experimental studies to characterize failure properties of vascular tissue under tensile (Mohan and Melvin, 1982; Vorp et al., 1996; MacLean et al., 1999; Vorp et al., 2003; Sommer et al., 2008), tearing (Purslow, 1983), dissection (Carson and Roach, 1990; Tiessen and Roach, 1993; Roach and Song, 1994; Tam et al., 1998; Roach et al., 1999), biaxial (Mohan and Melvin, 1983) and peeling (Sommer et al., 2008) loads have been reported, no studies have investigated failure of ventricular tissue due to deep penetration. Deep penetration of soft biological tissues has mainly be studied towards needle insertion (Abolhassani et al., 2007), where phenomenological models based on experimental data
(Okamura et al., 2004; DiMaio and Salcudean, 2005) have been developed but less attention has been spent to the failure characteristics of the underlying material. To the authors knowledge the involved fracture mechanisms of deep penetration in soft biological tissues has only been discussed with application to skin (Shergold and Fleck, 2004), where shearing and tensile modes of failure have been related to flat-bottomed and sharp-tipped punches (penetrators), respectively. Failure mechanisms of ventricular tissue have not yet been investigated from a mechanical perspective, which, however, is a prerequisite to develop strategies against acute or delayed lead perforation. Likewise, a fundamental mechanical understanding of soft tissue failure in general is critical to develop numerical fracture models (Gasser and Holzapfel, 2006, 2007; Ferrara and Pandolfi, 2008), which then allows guided devices development and fast prototyping. Within this work we propose an in-vitro mechanical test to explore the resistance of bi-axially stretched ventricular tissue against deep penetration. The mechanical experiment has been performed with cylindrical punches of different diameters and the introduced tissue failure has been studied.
2. Methods Corresponding author. Tel.: +46 8 790 7793; fax: +46 8 411 2418.
E-mail addresses: [email protected] (T.C. Gasser), [email protected] (P. Gudmundson), [email protected] (G. Dohr). URL: http://www.hallf.kth/tg (T.C. Gasser). 0021-9290/$ - see front matter & 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.jbiomech.2008.12.016
A novel mechanical testing device has been developed to characterize the penetration properties of right ventricular tissue at fixed biaxial stretches. The basic experimental principle is illustrated in Fig. 1, whereas the device is described
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F
1
u
λy
1
λx
Fig. 1. Basic principle of the penetration experiment. Ventricular tissue specimens were bi-axially stretched by the principal stretches lx and ly . This state of deformation was kept fixed during the tissue was penetrated, where the displacement, u, was prescribed and the penetration force, F, was recorded.
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and lower position plates, which allowed a defined distribution of penetrations. Grips and position plates were made of polyvinyl chloride (PVC) while a stainless steel container stored the PSS. The punch was mounted in the punch holder, which was connected to the 100.0 N FCTA load cell (VETEK AB) and fixed to the testing system with a magnet. This design allowed a fast and easy positioning (defined by the position plates) of the punch. The inherent stiffness of the testing device was investigated at different positions of the punch, and found to be several magnitudes higher than the stiffness of the investigated ventricular specimens. Likewise, the ability to reproduce test results with the developed experimental equipment has been ensured due to preliminary penetration of man-made materials. For illustrative purposes, Fig. 4 is included, which shows results from validation experiments with silicon gel in air at 18:0 C and a penetration velocity of 5.0 mm/min. The diagram presents results from five penetrations with a punch of 1.32 mm in diameter. As can be seen from the data, the deviation of the particular load displacement curves remains acceptable, an hence, the experimental principle and device have been found to be suitable to identify penetration properties of the underlying material. Finally, it is worth noting that similar curves, as shown in Fig. 4, have been presented earlier (Shergold and Fleck, 2005).
2.2. Specimen preparation for the penetration test Intact hearts have been provided by Swedish Meats AB, Uppsala and specimen preparation started within less than 4 hours post mortem. To this end the heart was opened at the base, right ventricular free wall and interventricular septum were separated and rectangular specimens of about 70:0 70:0 mm were prepared from these two anatomical sites. Due to geometrical limitations porcine test specimens could only be obtained from the right ventricular free wall. Since the ventricular wall is anisotropic, i.e. it has directional dependent mechanical properties, the specimen’s orientation with respect to the ventricular wall needed to be considered. In details, the edges of the rectangular specimen should coincide with the material axes, i.e. the principal directions of material anisotropy. Naturally, the material axes are not homogeneous over the (big) specimens, and hence, this requirement could only be fulfilled in an average sense. Within this work, the epicardial and myocardial fiber directions were used to define the orientations of the specimens from the right ventricular free wall and the interventricular septum, respectively. To this end the fiber orientation was detected from visual inspection with a low magnifying loupe, where the tissue was partly stained with blue ink to highlight its fibrous structure. Note that the fiber orientation of the interventricular septum was much more coherent, which simplified the characterization of the specimen orientation. To mount the specimen in the testing device it had to be thinner than 12.0 mm, and hence, if required the epicardial layers was sliced off. In details, this preparation step affected mainly the bovine specimens and aimed at getting about the same specimen thickness over the testing area. In contrast, the endocardial site was always kept intact to provide equivalent conditions to the onset of lead perforation. Thereafter, the specimen was stored in PSS at 4 C until testing.
Fig. 2. Experimental device for ventricular tissue penetration integrated in a conventional testing system (100.0 kN MTS load-frame updated with an INSTRON digital controler 8500þ). in detail in Section 2.1. In total nine rectangular specimens harvested from three cows and three pigs were prepared, and 891 penetrations were performed; specimen preparation and testing protocol are outlined in Sections 2.2 and 2.3, respectively. Penetrations are performed with flat-bottomed cylindrical punches of 2.30, 1.98, 1.65 and 1.32 mm in diameter, with a rounded edge (radius of 0.13 mm). Note that the penetrator size is in the range of commonly used pacemaker leads. During the experiment penetration forces and displacements were recorded and thereafter the tissue was fixated in 4.0% zinc formaldehyde solution for 24 hours and stored in 70% alcohol. Tissue failure of selected penetrations were histologically analyzed, where in total four sub-specimens were prepared; details are given in Section 2.4.
2.1. Design of the mechanical testing device The especially developed experimental device for ventricular tissue penetration has been integrated in a conventional testing system (100.0 kN MTS loadframe updated with an INSTRON digital controler 8500þ); see Fig. 2 of the installation and the schematic drawing of the experimental device in Fig. 3. During testing the ventricular tissue specimens remained entirely in physiological salt solution (PSS) at 37 1 C, which was controlled by a THERMAC 6000 D30 micro controller (research incorporated). Stretching screws, to be controlled independently from each other, allowed a biaxial stretching of the specimen, where specially designed grips (four on each side of the specimen) transferred the load into it. The location of the penetration was defined by upper
2.3. Protocol for the penetration test The ventricular specimen was equilibrated in PSS at 37 1 C for about 30 minutes prior the grips were applied by use of fixation nails, see Fig. 5(a). The stainless steel container was filled with PSS and the heating system was activated, such that the stable testing temperature of 37 1 C was reached after about 20 minutes. Thereafter, the specimen was mounted in the experimental device (described in Section 2.1) and bi-axially stretched to its testing conditions, see Fig. 5(b), which were defined by the principal stretches of lx ¼ 1:128 and ly ¼ 1:084. This state of deformation, which corresponds to the anterior midventricle deformation of the dog heart at 75% filling (McCulloch et al., 1989), was applied by the four stretching screws (see Fig. 3) and controlled by measuring the (average) distance between the fixation nails. Note that edge effects, i.e. strain inhomogeneities at the fixation were negligible because of the large specimen size. Once the upper position plate was mounted and the punch was positioned, a displacement controlled penetration at a velocity of 5.0 mm/min was performed, where the bi-axially stretch state was kept constant. Preliminary experiments with ventricular tissue at penetration velocities ranging from 1.0 to 15.0 mm/min showed that rate effects are negligible compared to regional variations of the test results. For convenience, the penetration velocity was set to 5.0 mm/min, and in view of the observed rate independence the experiment could be regarded as quasi-static. Note that similar (Frick et al., 2001) and contradictory (Brett et al., 1997) statements regarding rate effects of deep penetration of skin tissue have been reported earlier. The penetration force and the displacement were recorded with a sampling rate of 2.0 Hz and each specimen was 25 times penetrated with punches of 2.30, 1.98, 1.65 mm in diameter and 24 times with the punch of 1.32 mm in diameter. The locations of the penetrations with the different punches were homogeneously distributed over the specimen, such that regional variations of the tissue
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Stretching screw Upper and lower position plates
Magnet Load cell (100.0 N) Punch holder Punch Stretched ventricular specimen
Grip
Heating system
Container filled with PSS
Fig. 3. Schematic drawing of the experimental device to penetrate bi-axially stretched specimens of ventricular tissue.
Penetration Force N
1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 0.0
2.5
5.0
7.5 10.0 12.5 Displacement mm
15.0
17.5
Fig. 4. Validation experiment illustrating the force displacement response of silicon gel penetration, where a punch of 1.32 mm in diameter and a penetration velocity of 5.0 mm/min were used.
properties were compensated and the achieved results could be compared amongst the different punches.
2.4. Specimen preparation for the histological analysis Light microscopy. Heart tissue was fixed in Zenker’s fluid, which was made by mixing distilled water (950 ml), potassium dichromate (25 g), mercuric chloride (50 g) and glacial acetic acid (50 g). The tissue was then transferred into 70% ethanol and embedded in paraffin using an overnight standard protocol and an automatic tissue processor (Shandon Citadel). Sections at a thickness of 5 mm were taken with a sledge type microtome, routinely stained with the haematoxylin and eosin method and thereafter cover-slipped with a xylen based mounting medium. Scanning electron microscopy. Heart tissue samples were dehydrated in a graded series of ethanol and dried in a critical-point drying apparatus (Balzers CPD 020; Balzers, Liechtenstein). Thereafter, samples were mounted on aluminum stubs, sputter-coated with gold palladium and investigated with a scanning electron microscope (DSM 950; Zeiss, Oberkochen, FRG).
3. Results 3.1. Observed penetration characteristics According to the anatomy of the right ventricular wall, different types of tissues fail during deep penetration, which was to some extent visible from the recorded force displacement curves, see Fig. 6. As long as the tissue deformed elastically, the
penetration force increased progressively with respect to the punch displacement, and at the elastic limit, irreversible deformation developed, i.e. the tissue failed and the specimen got (irreversible) penetrated. Clearly, the mechanical penetration properties of the involved tissues defined the recorded mechanical signal, as illustrated in Fig. 6, where the signals from penetration of (a) the myocardium, (b) endocardium and myocardium and (c) the intact wall, i.e. endocardium, myocardium and epicardium are illustrated. While Fig. 6(a) is characterized by a single (scattered) force plateau of about 1.1 N defining myocardial’s resistance against penetration, Fig. 6(b) exhibits a load peak of about 7.5 N associated with endocardium penetration prior the myocardium failed at a load level of about 1.5 N. Finally, Fig. 6(c) shows load peaks of about 8.0 and 12.0 N denoting penetrations of endo- and epicardium, respectively. Once the punch went through the whole tissue a decrease of the force was recorded, and thereafter, friction between tissue and punch defined the force level. Naturally, the force required to penetrate endo- and epicardium will strongly depend on the thicknesses of these layers, which themselves vary significantly over the anatomical site of the right ventricle (LeGrice et al., 1995), and hence, the definition of a ‘typically force displacement curve’ for the right ventricular wall failed. In order to discuss tissue failure mechanisms a particular penetration is considered, where a punch of 2.30 mm in diameter went through endocardium and parts of the myocardium. In particular, the recorded force displacement curve and the induced ‘channel of tissue failure’ are illustrated, see Fig. 7. It can be seen that the tissue failure remained localized and did not spread extensively away from the site of the penetration, i.e. inelastic deformation is limited to the site of the penetration. Likewise, a cylindrical channel as it is supposed to develop by the hypothized mode-II crack propagation associated with flat-bottomed punches (Shergold and Fleck, 2004), cannot be observed. Although visual inspections of the penetrated specimens exhibited a few cylindrical holes at the entrance of the punch, the majority of penetrations formed cleavages aligned with the local fiber orientation of the tissue, see Fig. 8(a). Hence, a splitting mode (mode-I crack), where the crack faces are wedged open by the advancing punch defines the primary penetration mechanism; the idealized situation is illustrated in Fig. 9. In addition to the splitting mode, secondary dissections in planes parallel to the layers of the ventricular wall, see Fig. 10(a),
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Fig. 5. Porcine specimen from the right ventricular free wall. (a) Specimen fixed to the grips and (b) specimen bi-axially stretched to its testing conditions.
Irreversible deformation
Elastic deformation
Penetration Force N
1.40 1.12 0.84 0.56 0.28 0.00 0
0.2
0.4 0.6 Relative Thickness
Elastic deformation
0.8
1.0
Irreversible deformation
Penetration Force N
10.0 8.0 6.0 4.0 2.0 0.0 0
0.2
0.4 0.6 Relative Thickness
Elastic deformation
0.8
1.0
Irreversible deformation
Penetration Force N
14.0 11.2 8.4 5.6 2.8 0.0 0
0.2
0.4 0.6 Relative Thickness
0.8
1.0
Fig. 6. Particular force displacement curves recorded with a punch of 1.98 mm in diameter. Penetration through (a) the myocardium, (b) endocardium and myocardium and (c) the intact wall, i.e. endocardium, myocardium and epicardium.
and rupture (tearing) of myocardial fibers (heart muscle cells) with associated pull-out of sarcomeres, see Fig. 10(b), have been identified from the histological investigation. Although substantial reversible deformation were observed when the punch was removed, (locally) large remaining deformations are shown by the
electron microscopical images taken at the entrance and exit of the punch in Fig. 8 (or alternatively in the Fig. 7). Failure of ventricular tissue due to deep penetration involves complex crack formations and, in particular, a sharp crack tip does not exist. This is also illustrated by the electron microscopical
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Elastic deformation
Irreversible deformation
Penetration Force N
10.0 8.0 6.0 4.0 2.0 0.0 0.4 0.6 Relative Thickness
0.2
0.8
1.0
Penetration exit
Penetration entrance
0
Endocardium
Myocardium
C hannel of tissue failure
Fig. 7. Particular results from penetrating the endocardium and myocardium of right ventricular wall of a porcine specimen with a punch of diameter 2.30 mm. (a) Recorded force displacement curve. (b) Picrosirius red stain illustrating tissue failure through the different layers of the ventricular tissue.
© Inst.f.Zellbiologie,Histologie
u.Embryologie
© Inst.f.Zellbiologie,Histologie
u.Embryologie
Fig. 8. Electron microscopical images taken at the (a) entrance and (b) exit of the punch illustrating a splitting mode (mode-I) failure and the presence of remaining deformations, respectively.
image shown in Fig. 10(c), which was taken at the exit of the punch and shows multiple (partly cross-bridged) dissections. Finally, it is emphasized that the electron microscopical images taken from the disrupted endocardium Fig. 10(d) exhibits long bundles of collagen fibers, and hence, collagen pull-out rather than rupture of collagen bundles might determine the failure thereat.
3.2. Statistical analysis Due to the irregular results from the endo- and epicardial layers, probably caused by the varying thicknesses of them, we limit the analysis to quantify the penetration properties of myocardial tissue. In details, only the recorded penetration force
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Circular penetrator
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Fibrous tissue Penetration Force N
15.0 12.5 10.0 7.5 5.0 2.5 0.6
0.65
0.7 0.75 0.8 Relative Thickness
0.85
0.9
Fig. 11. Filtered force penetration characteristics from pig specimen P2, where 25 penetrations with a punch of 2.30 mm in diameter were recorded. The data reflects myocardium’s resistance against deep penetration and was used to define average penetration forces in a least square sense. Fig. 9. Idealized failure mode of ventricular tissue due to deep penetration, where crack faces are wedged open by the advancing punch defining a splitting mode (mode-I) failure.
20µm
20µm
Endocard
Fig. 10. Tissue failure mechanisms due to penetrating right ventricular tissue. Picrosirius red stains from the penetrated myocardium illustrate myocardium fiber (a) dissection and (b) rupture as indicated by arrows. Electron microscopical image illustrating dissection type of failure at the exit of the punch (c) pull-out of bundles of collagen of the sub-endocardial layer at the entrance of the punch (d).
between 60% and 90% punch displacement has been used in the following, i.e. data from the elastic deformation and from penetrating endo- and epicardium layers were filtered out. As a representative example, Fig. 11 shows the filtered data from 25 penetrations of pig specimen P2 using a punch of 2.30 mm in diameter. Subsequently, the average penetration force for each penetration was quantified in a least square sense, which finally defined the data in Table 1. In details, mean value and standard deviation (SD) of penetration forces with respect to the punch
Table 1 Force in Newton to penetrate the myocardium of six bovine (B1–B6) and three porcine (P1–P3) specimens with punches of different diameters. Specimen
Punch diameter (mm) 2.30
1.98
1.65
B2 B3 B4 B5 B6
6.19(SD 1.53) 8.82(SD 2.58) 9.43(SD 3.13) 8.43(SD 3.45) 9.69(SD 3.34)
5.06(SD 7.05(SD 6.99(SD 5.24(SD 6.82(SD
P1 P2 P3
7.27(SD 2.35) 6.60(SD 2.05) 4.76(SD 2.03)
5.94(SD 1.74) 4.52(SD 1.48) 3.74(SD 1.98)
1.19) 1.88) 1.99) 2.17) 2.20)
4.67(SD 4.88(SD 5.01(SD 5.09(SD 5.34(SD
1.32 1.14) 1.14) 1.65) 1.94) 1.70)
3.16(SD 0.67) 3.95(SD 1.23) 3.38(SD 0.85) 4.02(SD 1.78) 4.11(SD 1.48)
4.85(SD 1.73) 3.39(SD 1.11) 2.68(SD 1.56)
3.25(SD 1.49) 2.50(SD 0.83) 1.85(SD 0.87)
diameters of six bovine and three porcine specimens are given. It is emphasized that the applied method gives analyst independent results and that the applied least square fitting, which can also be seen as an integration of the experimental data, reduces the impact of spurious load peaks if present. Table 1 exhibits no significant difference between bovine and porcine specimens, and hence, the mean values of the penetration forces were pooled, which, finally, lead to the plot of the penetration pressure with respect to the punch diameter in Fig. 12. A slight decrease of the penetration pressure towards thicker punches is observed (similar results apply to skin tissue (Shergold and Fleck, 2004), however, it appears that this parameter remains fairly insensitive within the considered domain of punch diameters.
4. Discussion We introduced a novel experimental setup to investigate the penetration properties of ventricular tissue under controlled mechanical boundary conditions. To this end bi-axially stretched specimens were penetrated, force displacement properties were recorded and the induced tissue failure was histologically analyzed using light and electron microscopes. Throughout this study the bi-axial state of stretch according to data from anterior mid-ventricle deformation of the dog heart at 75% filling (McCulloch et al., 1989) has been applied, which was also found to be in the transition zone between the soft (low-strain) and the stiff (high-strain) passive properties of the
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Penetration pressure N/mm2
3.0 2.5 2.0 1.5 1.0 0.5 0.0 1.2
1.4
1.6 1.8 2.0 Punch diameter mm
2.2
2.4
Fig. 12. Penetration characteristics of the right ventricular myocardium. Penetration pressure (penetration force divided by punch cross section) with respect to the punch diameter. Results are in qualitative agreement with findings from skin tissue (Shergold and Fleck, 2004).
right ventricular free wall (Sacks and Chuong, 1993). This indicates that the considered state of deformation appears during the cyclic in-vivo stretching of the ventricular free wall, and hence, our experiment mimicked at least a single physiologically relevant deformation. To the authors’ knowledge the in-vivo deformation of the interventricular septum has not been reported in the literature, and hence, the same bi-axially state of stretch was applied to the interventricular specimens. The rectangular tissue specimens were prepared, such that the material axes coincided with the stretching directions, and hence, no shear deformation develops during bi-axial stretching. Since the fiber orientation of the ventricular free wall is inhomogeneous, this could only be satisfied in average, i.e. the fiber orientations were in average aligned with the stretching direction but not locally. Consequently, local strain inhomogeneities were present in the bi-axially stretched tissue. It needs to be emphasized that ventricular tissue is fairly heterogeneous (as indicated by the complex topology of the endocardium), and hence, strain (stress) inhomogeneities might reflect the in-vivo deformation of ventricular tissue (McCulloch et al., 1989). The identified failure of ventricular tissue due to deep penetration exhibited complex crack formations and a sharp crack tip could not be observed, thus theories associated with sharp crack tips will fail to describe the problem satisfying. Although the present study used flat-bottomed punches, a splitting mode, where the crack faces were wedged open by the advancing punch seems to be the primary penetration mechanism. Hence, a mode-I crack develops in parallel to the myocardial fibers and a splitting like failure mechanism applies. This is in clear contradiction to the development of a mode-II (shear) failure, as it has been postulated for flat-bottomed punches (Shergold and Fleck, 2004). This discrepancy might be a direct consequence of the fibrous ventricular tissue considered herein. Likewise, secondary dissections, tearing of myocardial fibers (muscle cells) and large remaining deformations were found to be characteristic for deep penetration of ventricular tissue. These secondary phenomena might be of minor importance to the mechanics of deep penetration, which, however, could not be further investigated by the present study. The penetration resistance of the myocardial tissue was quantified, where experimental data between 60% and 90% penetration displacement was considered, which aims at cutting off results from elastic deformations and endo- and epicardial penetration. These limits were selected after inspecting the collected experimental data. To quantify myocardium’s penetra-
tion resistance the recorded penetration forces were averaged between these limits. Naturally, the derived penetration forces include frictional resistance from the (already penetrated) endocardial layer, and hence, this approach might be slightly overestimating the strength of the myocardium in case a thick endocardial layer is present. The analysis of the experimental results showed that the pressure required penetrating ventricular tissue (slightly) decreased with increasing punch diameters. Most interestingly, this tendency could not be observed for punches of larger diameters, where the penetration pressure remained insensitive with respect to the punch diameter. Perhaps the observed change in characteristics indicates the activation of different failure mechanisms for larger and smaller punches. Passive ventricular tissue was used for the penetration experiments although this tissue is cyclic activation in-vivo. Activated ventricular tissue would at least cause a higher frictional resistance against deep penetration, thus an increase of the penetration force is expected. However, cyclic activation might also activate fatigue-like failure mechanisms (Suresh, 1998), which in a long term might decrease the tissue’s resistance against penetration. It is emphasized that the proposed experimental setup might also be used to penetrate (cyclic) activated ventricular tissue to explore this question further. In conclusion, the performed study provided novel information regarding the mechanisms of deep penetration of soft biological tissues, and the presented data might be used to develop analytical and/or numerical models to gain further insight in failure of soft biological tissues and/or to improve clinical devices.
Conflict of interest statement None declared.
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