Cardiovascular Research

Cardiovascular Research 2003 58(2):444-450; doi:10.1016/S0008-6363(02)00834-9
© 2003 by European Society of Cardiology

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Copyright © 2003, European Society of Cardiology

Endoventricular porcine autologous myoblast transplantation can be successfully achieved with minor mechanical cell damage

Bénédicte Chazaud^a, Luc Hittinger^b,c,d, Corinne Sonnet^a, Stéphane Champagne^b, Philippe Le Corvoisier^c, Nicole Benhaiem-Sigaux^e, Thierry Unterseeh^f, Jinbo Su^c, Pascal Merlet^g, Alain Rahmouni^h, Jérôme Garot^b,c, Romain Gherardi^a,e and Emmanuel Teiger^f,i,*

^aINSERM E0011, Faculté de Médecine, Créteil, France
^bFédération de Cardiologie, Hôpital Henri Mondor, Créteil, France
^cINSERM U400, Faculté de Médecine, Créteil, France
^dCentre de Recherche Chirurgicales, Hôpital Henri Mondor, Créteil, France
^eService d’Histo-embryologie-cytogénétique, Hôpital Henri Mondor, Créteil, France
^fService des Explorations Fonctionnelles, Hôpital Henri Mondor, 51 Avenue du Maréchal DeLattre de Tassigny, 94010 Créteil Cedex, France
^gService de Médecine Nucléaire, Hôpital Henri Mondor, Créteil, France
^hService de Radiologie et Imagerie Médicale, Hôpital Henri Mondor, Créteil, France
ⁱINSERM U492, Faculté de Médecine, Créteil, France

teiger{at}creteil.inserm.fr

^* Corresponding author. Tel.: +33-1-4981-2677; fax: +33-1-4981-2667.

Received 24 September 2002; accepted 26 November 2002

	Abstract

Top Abstract 1 Introduction 2 Methods 3 Results 4 Discussion Acknowledgments References

 
Objective: Transplantation of skeletal myogenic precursor cells (mpc) into the myocardium using a non-surgical procedure. Methods: Closed-chest mpc transplantation was assessed in pigs using the NOGA-Biosense^® device allowing both electromechanical mapping of the left ventricle (LV), and guided mpc injections through endocardium. Results: We successively established that: (1) adequate preimplantation handling of mpc can be achieved when mpc are kept in 0.1% serum albumin-containing medium until implantation; (2) mpc are neither retained nor destroyed in the catheter or the needle and their passage does not affect their survival, growth and differentiation; (3) large numbers of autologous mpc can be actually transplanted in the LV myocardium by transendocardial route, as assessed by post-mortem examination of pigs injected with iron-loaded mpc; (4) cell injection into the myocardium does not induce conspicuous cell mortality since more than 80% of mpc recovered from LV tissue are alive 15 min after injection; (5) mpc injections can be guided into circumscribed LV targets such as infarcted areas, as assessed by comparison of map injection sites with location of iron-loaded mpc at post-mortem examination of LV myocardium. Conclusion: This new approach may pave the way for a large spectrum of cell therapies targeting myocardial diseases.

KEYWORDS Heart failure; Infarction; Myocytes; Stem cells; Transplantation

	1 Introduction

Top Abstract 1 Introduction 2 Methods 3 Results 4 Discussion Acknowledgments References

 
In contrast to skeletal muscle, cardiac muscle tissue does not regenerate after developmental stages. For 10 years, numerous studies have used muscle cell transplantation to limit post-infarction akinetic fibrous scar formation and subsequent congestive heart failure by replacing missing cardiomyocytes by contractile cells [1,2]. Successful preclinical studies using foetal cardiomyocytes and myogenic cell lines can hardly be transferred to humans. Indeed, foetal cardiomyocytes are poorly available and their use raises ethical problems, and myogenic cell lines are potentially tumorigenic [3–5]. These limitations opened the way to autologous myogenic precursor cells (mpc) transplant [6,7]. In several experimental studies, mpc transplanted in a damaged myocardium have generated functional tissue, although mechanisms by which engrafted mpc improved myocardial contractility remained elusive [6,8]. Feasibility of autologous mpc transplantation within an infarcted myocardium was recently demonstrated in humans by epicardial injections during a coronary artery bypass grafting intervention performed by sternotomy [9].

In the present study we assessed the feasibility of a percutaneous approach for autologous mpc grafting in myocardium using the NOGA-Biosense device (NOGA-STAR^TM, Biosense Webster, Johnson & Johnson), that allows both electromechanical mapping of the left ventricle (LV) [10] and guided microinjections through the endocardium [11]. We used the pig, a large animal model that allows utilization of devices designed for humans. We set up large-scale porcine autologous skeletal muscle-derived mpc cultures. In this study we examined whether the percutaneous device could be used for injection of mpc into contracting LV myocardium under physiological conditions. Emphasis was put on possible mechanical cell damage induced by the procedure, and on targeting accuracy of electromagnetically guided cell injections. We successively determined: (1) an adequate preimplantation handling of mpc for an estimated whole procedure time of 1 h, (2) the influence of catheter injection on mpc viability and myogenic capacities, (3) the effectiveness of mpc transplant procedure in vivo, (4) the viability and myogenic capacities of mpc engrafted into the LV myocardium, and (5) the accuracy of injection guidance into a target area, i.e. an infarcted zone, experimentally induced by coronary artery occlusion.

	2 Methods

Top Abstract 1 Introduction 2 Methods 3 Results 4 Discussion Acknowledgments References

 
2.1 Mpc culture
Mpc were obtained from sternocleidomastoid muscles of the pigs included in the present study and cultured according to Ref. [12]. Briefly, muscles were mechanically minced and incubated in digestion medium (HAM F12–HEPES containing 1.5 mg/ml pronase E (Sigma, St. Louis, MO, USA) and 0.03% EDTA (p:v)) (Invitrogen, Paisley, Scotland, UK) for 40 min at 37°C. Cells were recovered from tissue debris after washes, slow centrifugations and filtering. Cells were seeded in HAM-F12 containing 15% foetal calf serum (FCS) (Invitrogen). Cell expansion was enhanced by addition of human bFGF (10 ng/ml) and IGF-I (50 ng/ml) (Abcys, Paris, France). Culture in the Cell factory^TM device (Nunc, Roskilde, Denmark) allowed the production of about 1x10⁹ cells in 4 weeks.

2.2 Mpc handling
Mpc recovered using a trypsinization procedure were incubated at different cell concentrations (1.5x10⁷ to 7x10⁷ mpc/ml) at room temperature for 1 h. This incubation time was chosen because, in practice, the whole in vivo injection procedure including mpc recovery from the flasks, transfer to the surgical room, and guided injections through the NOGA-Biosense device, can hardly be performed in less than 30 min. The number of dead cells was conventionally estimated using Trypan blue dye exclusion. Mpc mortality index was calculated as the ratio of percent of dead cells at 1 h of incubation versus at the beginning of the incubation. Mortality index was calculated in serum-free medium and in medium containing 0.1% PSA (porcine serum albumin).

2.3 Mpc passage through the NOGA-Biosense catheter
Since the passage through both catheter and needle can damage mpc, the effects of a manual procedure similar to that used for in vivo injection on mpc mortality were examined ex vivo. Mpc were resuspended at different cell concentrations (2x10⁶ to 150x10⁶ mpc/ml) in medium containing 0.1% PSA and injected proximally into the catheter and recovered distally. Cell concentration and mortality were calculated after passage through the catheter and compared with initial values, and cells were classically seeded and further cultured.

2.4 Mpc loading with iron particles
Cultured mpc were incubated with iron oxide particles (Endorem^®, Guerbet, France) at 4 mg iron/10⁶ mpc for 36 h. Under these conditions Endorem^® was not toxic for mpcs as assessed by the WST-1 proliferation kit (Roche Diagnostics, Mannheim, Germany).

2.5 Animal preparation
Twelve farm pigs weighing 28–37 kg each were studied. The animals were used in accordance with the Guide for the Care and Use of Laboratory Animals (DHHS publ. no. (NIH) 85-23, revised 1996, Office of Science and Health Reports, Bethesda, MD 20892, USA). After premedication with ketamine (15 mg/kg, i.m.) and atropine (0.05 mg/kg, i.m.), animals were anaesthetized with a mixture of propofol (0.1 mg/kg/min i.v.) and isofluorane (1–2%). Throughout experimental procedures, anaesthesia was adjusted to maintain heart rate and blood pressure at physiological and stable levels. After completion of the procedure, animals were euthanized with an overdose of pentobarbital sodium and the heart excised for macroscopic and histological analysis.

2.6 Mapping procedure
The NOGA system (Biosense, Johnson & Johnson) of catheter-based mapping and navigation has been previously described in detail [10,13]. A complete electromechanical mapping was performed for each animal with a mean number of points acquired of 82±14.

2.7 Injection procedure
The injection catheter has been previously described [14,15]. Briefly, it consists of a mapping catheter modified to integrate a retractable 27G needle for intramyocardial injection. The catheter ‘dead space’ was 0.1 ml and was flushed with 0.1 ml of mpc suspension before endovascular insertion. The exact catheter-tip location, orientation and the injection sites were indicated in real-time on the LV map, and local electrical and location signal were traced to assure catheter stability and optimal endocardial contact. The needle was extended from 5 to 6 mm deep into the LV myocardium. The same volume of 0.4 ml of mpc suspension (120x10⁶ to 150x10⁶ mpc/ml in HAM-F12 containing 0.1% PSA) was injected per site (3 to 4 sites/animal except for survival measurement experiments).

2.8 Mpc survival in LV myocardium
Four pigs were used for this part of the study. Using an endoventricular route, autologous mpc injections were performed 15 min prior to sacrifice. Then the heart was excised, injection points were visually localized and the surrounding myocardium was quickly dissected. Myocardial samples were then sliced thinly, extensively washed with culture medium to recover all the non-adherent cells, and filtered (70 µm pores) to remove tissue debris. Only large and refringent cells (mpc) present in the suspension were counted. The percentage of dead cells in the same cell suspension, but not injected and kept in the culture room was subtracted from this value to obtain the net mortality due to the transplantation procedure. Mpc recovered from the LV were seeded at 5000 cells/cm² into 24-well plates and further classically cultured. To establish growth curves, cell number was estimated every 4 days using a Malassez haemocytometer, after trypsinization.

For comparison of mpc survival between routes and injection devices, identical procedure was carried out in three of the four pigs using an epicardial route. In these animals, a thoracotomy was performed and the epicardium was injected with the same cell preparation as those used for transendocardial implantation using a 27 gauge needle.

2.9 Infarction model
To produce a targetable lesion, a myocardial infarction was produced in three additional pigs. The infarction model used was derived from a previously described procedure [16]. Briefly a 6F sheath was placed in the right carotid artery and baseline coronary angiography with 6F Judkins guiding catheter was performed to assess coronary patency. Before the beginning of the infarction procedure all animals received intravenous (i.v.), morphine (0.25 mg), heparin (5000 IU), lidocaine (0.5 mg/kg) and propanolol (0.15 mg/kg). After placement of a 0.014-inch guide wire into the left anterior descending coronary artery (LAD), a balloon catheter (balloon/vessel ratio, 1.1 to 1.2) was inflated distal to the first diagonal branch until complete occlusion of the artery was achieved. The balloon was deflated 120 min after ischaemia onset and animals were maintained 90 min under anaesthesia for reperfusion. During the same procedure pieces of both sternocleidomastoid muscles were harvested. After surgery, animals were treated with antibiotics and analgesics and were kept in the animal facility for 4 weeks to allow healing of the infarct. At that time, animals were anaesthetized using the previously described protocol. Then, a completed electromechanical NOGA mapping was performed. Infarcted myocardium was identified as an area of both electrical (unipolar voltage <5 mV) and mechanical (local endocardial shortening <5%) impairment (appearing in red color on NOGA maps) as previously described [17]. Autologous mpc transplantation was performed in the infarcted area using the protocol described above except that the needle was only extended 3 to 4 mm deep into the LV myocardium.

2.10 Statistical evaluation
All experiments were performed at least three times. For in vitro experiments, at least three separate cultures obtained from at least three different animals were used. The data are presented as means±S.D. Comparisons were made using the Mann–Whitney or Wilcoxon matched paired tests. A P-value below 0.05 was considered significant.

	3 Results

Top Abstract 1 Introduction 2 Methods 3 Results 4 Discussion Acknowledgments References

 
3.1 Adequate preimplantation handling of mpc and survival after passage through the catheter
Mortality index determined after 1 h incubation at room temperature was 3.8 in serum-free medium and threefold lower (1.3) in 0.1% porcine serum albumen medium (n = 4, P<0.05) (Fig. 1A).

View larger version (58K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 1 Mpc survival and myogenic capacities. (A) Mortality index (mpc mortality at the end of 1 h incubation/mpc mortality at the beginning of the experiment) of mpc incubated in serum-free medium and medium containing 0.1% PSA. Each symbol represents one separate experiment (n = 4) and bar symbols represent the means. (B) Mpc mortality (% of dead cells) before and after passage through the catheter. Each symbol represents one separate experiment (n = 10). (C) Growth curve of mpc recovered from the heart tissue after transplantation (injected) versus the initial mpc population (control) (n = 3, in duplicate). (D, E) Hematoxylin stain of mpc at day 16 of culture: initial population (D) and mpc recovered from the heart tissue after transplantation (E). Bar=80 µm.

 
Mpc passage through the catheter was not associated with cell loss (percent of cell concentration variation before and after passage was 2.2% maximum), indicating that cells were neither retained nor destroyed in the device (Fig. 1B). In addition, mpc cultured after their passage through the device exhibited the same growth and fusion capacities as the initial population (data not shown).

3.2 Effectiveness of mpc transplant procedure
To assess the effectiveness of the transplant procedure, mpc were first loaded with iron particles. Mpc incubated with Endorem^® presented efficient ingestion of iron particles (Fig. 2A). Injected iron-loaded mpc were retrieved at post-mortem examination of LV, at sites corresponding to those mapped by the NOGA-Biosense device (data not shown). Perls stain for iron [24] allowed detection of huge numbers of injected mpc within LV myocardium, in all injected animals. They formed large sheets of densely packed mononucleated myogenic cells (Fig. 2B).

View larger version (114K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 2 Mpc transplantation into normal myocardium. (A) Perls stain of mpc incubated with Endorem® before injection shows the ingestion of iron particles by mpc. (B) Perls stain of mpc injected into normal LV. Bar=40 µm.

 
3.3 Mpc damage after injection into the myocardium
The net mortality of injected mpc extracted from LV myocardium 15 min after injection was 17.5±3.6%, indicating that a minority of engrafted mpc were damaged by the implantation procedure. Moreover, injected mpc showed the same growth curve (Fig. 1C) and differentiation capacities (Fig. 1E) as the initial population (Fig. 1C and D). Mpc injected by the epicardial route after thoracotomy showed a similar net mortality (13.5±1.5%).

3.4 Guidance of injections into a target area
Injection of iron-loaded mpc into an infarcted LV area showed precise targeting of injections by the NOGA device in all animals. The myocardial region with myocardial infarction were characterized by impairment of regional contractility and a low electrical voltage amplitude (<5 mV) visualised in red on the generated maps (typical example shown in Fig. 3A). Targeting was assessed by histologic examination of LV tissue showing injected cells in both the centre of the scar area (Fig. 3B) and at the margin of the infarcted zone (Fig. 3C and D), as expected from the NOGA-Biosense mapping. The histologic features of these cells were similar to that observed in normal myocardium.

View larger version (154K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 3 Mpc transplantation into infarcted myocardium. (A) Map of the electrical activity of the LV using the NOGA-Biosense device showing the infarcted area (in red) and sites of mpc injection (black dots). (B, C, D) Post-mortem histological examination after Perls coloration of the mapped injection sites: infarcted area (B), border zone of infarction (C and D). Black arrows indicate the limit of the infarcted area. D is a magnification of C. Bar=50 µm.

 
All injected pigs with or without myocardial infarction survived the entire procedure. Neither tamponade nor post-mortem evidence of pericardial effusion was observed.

	4 Discussion

Top Abstract 1 Introduction 2 Methods 3 Results 4 Discussion Acknowledgments References

 
In the present study, endoventricular mpc transplantation was successfully achieved in all animals, including three with experimental myocardial infarction.

Successful epicardial autologous myoblast transplantation into myocardium has been demonstrated in a variety of animal models [2] and was recently shown to be associated with myocardial function improvement in humans [9]. Although the presence of multinucleated myotubes assessing skeletal muscle differentiation of the transplanted myoblast in the myocardium has been repeatedly documented, massive post-implantation cell death, accounting for up to 90% of transplanted myoblasts, constitutes a major limitation of myoblast transfer therapy [18]. This phenomenon remains poorly understood, but is commonly attributed to both mechanical injury caused by pressure variations endured by cells during injection, and environmental biological factors, such as inflammatory mediators, reactive oxygen species and deprivation of cell survival factors [18–20]. In fact, the degree of mechanical injury of transplanted myoblasts has not been previously determined. Admittedly, the endoventricular route of mpc transplantation could be regarded as more prone to produce cell injury, because of the necessary passage through a long catheter, and implantation into the subendocardial myocardium which is subjected to higher mechanical strain than the subepicardium [21]. We demonstrated here that passage of mpc through the catheter induces no cell loss and that endoventricular injection into myocardium per se causes minimal damage to mpc, accounting for less than 20% of injected cells. In addition, the transplantation procedure did not affect in vitro mpc proliferation and differentiation capacities. This is in agreement with a recent in vivo preliminary report, conducted in one pig injected intraventricularly with allogenic myoblasts, which post-mortem heart examination 10 days post-injection showed multinucleated myotube formation [22].

Percutaneous myocardial cell transplantation offers several advantages as compared to the surgical approach. This strategy necessitates an easy to use and adequate device for in situ cell delivery that does not alter cell characteristics and allows precise targeting of definite myocardial areas. The present study demonstrates that the NOGA device is suitable for these purposes. Mpc were precisely injected in the desired target sites, as demonstrated by post-mortem histologic examination. Such an accurate targeting has been previously reported with plasmid [23] or adenoviral injections [15]. The relatively limited number of animals included in each protocol does not allow us to insure that the procedure we used will be successful in every case performed. However, our results do show clearly the feasibility of cell grafting by transendocardial route.

The ischaemia/reperfusion model of myocardial infarction used in the present study seems appropriate to evaluate cell transplantation therapy since it mimics the usual human clinical situation of myocardial infarction in which reperfusion strategy is performed. As demonstrated herein, adequate pharmacological management and tight pig monitoring allow high animal survival rates compatible with preclinical evaluations. At this point, the question of the long-term fate of the transplanted mpc remains to be carefully evaluated in terms of survival, ability to form muscle tissue, and improvement of heart function.

In conclusion, we established that myocardial mpc delivery can be successfully achieved in normal and infarcted myocardium, in a site-specific fashion, via a closed-chest percutaneous procedure. At present mpc transplantation in humans mainly consists of epicardial injection during a coronary bypass grafting intervention that limits indications to a narrow set of patients. The percutaneous approach significantly extends the spectrum of myocardial diseases in which substitutive cell therapy could be proposed for evaluation.

Time for primary review 30 days.

	Acknowledgments

Top Abstract 1 Introduction 2 Methods 3 Results 4 Discussion Acknowledgments References

 
This work was supported by the Association Française contre les Myopathies (DdT 2001, fellowship for B. Chazaud) and by the Assistance Publique-Hôpitaux de Paris, Délégation régionale à la Recherche Clinique (CRCE001002). We thank P. Druelle, W.-Y. Liu, P. Mario, and F. Poron for their technical assistance.

	References

Top Abstract 1 Introduction 2 Methods 3 Results 4 Discussion Acknowledgments References

 

1. Kessler P., Byrne B. Myoblast cell grafting into heart muscle: cellular biology and potential applications. Annu Rev Physiol (1999) 61:219–242.[CrossRef][Web of Science][Medline]
2. El Oakley R., Ooi O., Bongso A., Yacoub M. Myocyte transplantation for myocardial repair: a few good cells can mend a broken heart. Ann Thorac Surg (2001) 71:1724–1733.[Abstract/Free Full Text]
3. Van Meter C., Claycomb W., Delcarpio J., et al. Myoblast transplantation in the porcine model: a potential technique for myocardial repair. J Thorac Cardiovasc Surg (1995) 110:1442–1448.[Abstract/Free Full Text]
4. Li R., Jia Z., Weisel R., et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg (1996) 62:654–661.[Abstract/Free Full Text]
5. Sakai T., Li R., Weisel R., et al. Fetal cell transplantation: a comparison of three cell types. J Thorac Cardiovasc Surg (1999) 118:715–725.[Abstract/Free Full Text]
6. Taylor D., Atkins B., Hungspreugs P., et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med (1998) 8:929–933.
7. Dorfman J., Duong M., Zibaitis A., et al. Myocardial tissue engineering with autologous myoblast implantation. J Thorac Cardiovasc Surg (1998) 116:744–751.[Abstract/Free Full Text]
8. Atkins B., Hueman M., Meuchel J., et al. Myogenic cell transplantation improves in vivo regional performance in infarcted rabbit myocardium. J Heart Lung Transplant (1999) 18:1173–1180.[CrossRef][Web of Science][Medline]
9. Menasché P., Hagege A., Scorsin M., et al. Myoblast transplantation for heart failure. Lancet (2001) 357:279–280.[CrossRef][Web of Science][Medline]
10. Ben-Haim S., Osadchy D., Schuster I., et al. Nonfluoroscopic, in vivo navigation and mapping technology. Nat Med (1996) 2:1393–1395.[CrossRef][Web of Science][Medline]
11. Lessick J., Kornowski R., Fuchs S., Ben-Haim S. Assessment of NOGA catheter stability during the entire cardiac cycle by means of a special needle-tipped catheter. Catheter Cardiovasc Interv (2001) 52:400–406.[CrossRef][Web of Science][Medline]
12. Doumit M., Cook D., Merkel R. Fibroblast growth factor, epidermal growth factor, insulin-like growth factors, and platelet-derived growth factor-BB stimulate proliferation of clonally derived porcine myogenic satellite cells. J Cell Physiol (1993) 157:326–332.[CrossRef][Web of Science][Medline]
13. Gepstein L., Hayam G., Ben-Haim S. A novel method for non fluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results. Circulation (1997) 95:1611–1622.[Abstract/Free Full Text]
14. Kornowski R., Hong M., Gepstein L., et al. Preliminary animal and clinical experiences using an electromechanical endocardial mapping procedure to distinguish infarcted from healthy myocardium. Circulation (1998) 98:1116–1124.[Abstract/Free Full Text]
15. Kornowski R., Leon M., Fuchs S., et al. Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models. J Am Coll Cardiol (2000) 35:1031–1039.[Abstract/Free Full Text]
16. Garot P., Pascal O., Simon M., et al. Usefulness of combined quantitative assessment of myocardial perfusion and velocities by myocardial contrast and Doppler tissue echocardiography during coronary blood flow reduction. J Am Soc Echocardiol (2002) 16:1–8.
17. Gepstein L., Goldin A., Lessick J., et al. Electromechanical characterization of chronic myocardial infarction in the canine coronary occlusion model. Circulation (1998) 98:2055–2064.[Abstract/Free Full Text]
18. Menasché P. Cell transplantation for the treatment of heart failure. Sem Thorac Cardiovasc Surg (2002) 14:157–166.[CrossRef][Medline]
19. Suzuki K., Murtuza B., Smolenski R., et al. Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts. Circulation (2001) 104:I207–I212.[Web of Science][Medline]
20. Qu Z., Balkir L., van Deutekom J., et al. Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol (1998) 142:1257–1267.[Abstract/Free Full Text]
21. Sabbah H., Marzilli M., Stein P. The relative role of subendocardium and subepicardium in left ventricular mechanics. Am J Physiol (1981) 240:H920–H926.[Web of Science][Medline]
22. Dib N., Diethrich E., Campbell A., et al. Endoventricular transplantation of allogenic skeletal myoblasts in a porcine model of myocardial infarction. J Endovasc Ther (2002) 9:313–319.[CrossRef][Web of Science][Medline]
23. Vale P., Losordo D., Tkebuchava T., et al. Catheter-based myocardial gene transfer utilizing nonfluoroscopic electromechanical left ventricular mapping. J Am Coll Cardiol (1999) 34:246–254.[Abstract/Free Full Text]
24. Pearse A.G. Histochemistry theoretical and applied. Pearse A.G., ed. (1972) 3rd ed. London: Churchill Livingstone. 1130–1132.

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