ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Erwin P. Bauer
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bauer, E. P.
Right arrow Articles by Schaper, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bauer, E. P.
Right arrow Articles by Schaper, W.

Ann Thorac Surg 1998;66:527-531
© 1998 The Society of Thoracic Surgeons

Original articles: cardiovascular

Upregulated and downregulated transcription of myocardial genes after pulmonary artery banding in pigs

Erwin P. Bauer, MDa, Satoru Kuki, MDb, Rene Zimmermann, PhDb, Wolfgang Schaper, MD, PhDb

a Division of Thoracic and Cardiovascular Surgery, Max-Planck-Institute, Kerckhoff-Clinic, Bad Nauheim, Germany
b Division of Experimental Cardiology, Max-Planck-Institute, Kerckhoff-Clinic, Bad Nauheim, Germany

Accepted for publication March 18, 1998.

Address reprint requests to Dr Bauer, Division of Thoracic and Cardiovascular Surgery, Max-Planck-Institute, Kerckhoff-Clinic, Benekestrasse 2-8, 61231 Bad Nauheim, Germany
e-mail: (erwin.p.bauer{at}kerckhoff.med.uni-giessen.de)


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 References
 
Background. Acute or chronic pressure overload may occur during or after cardiac surgical procedures. Typical examples are aortic cross-clamping and pulmonary artery banding. It is well known that mechanical stress induces transcription of different myocardial genes. However, these results were mainly obtained from in vitro studies and experiments with rodents. This experiment was carried out to investigate molecular alterations after pressure overload in porcine hearts.

Methods. The study was performed with 35 Landrace pigs with a mean weight of 32 ± 1.2 kg. The five groups consisted of 7 pigs each, 3 sham-operated pigs and 4 banded pigs. The hearts were exised after different time intervals. We investigated messenger RNA expression of sarcoplasmic reticulum adenosine triphosphatase, phospholamban, {alpha}-/ß-myosin heavy chain, and atrial natriuretic factor by Northern blot analysis.

Results. The ratio of right ventricular weight to body weight increased significantly after 7 and 24 days in banded pigs (p < 0.05). Atrial natriuretic factor messenger RNA was significantly upregulated in banded pigs versus sham-operated pigs after 1 day (240% ± 7% versus 100% ± 6%; p < 0.01) and 3 days (520% ± 8% versus 100% ± 8%; p < 0.01). There was insignificant downregulation of sarcoplasmic reticulum adenosine triphosphatase and phospholamban after 1, 3, and 7 days. Myosin heavy chain messenger RNA expression remained unchanged.

Conclusions. Pulmonary artery banding results in hypertrophic response of the porcine right ventricle; however, the weight increase is not the result of myosin heavy chain messenger RNA upregulation. Atrial natriuretic factor messenger RNA is locally expressed in mechanically stressed myocytes. Furthermore, pressure overload downregulates transcription of calcium-binding proteins that can influence ventricular contractility. These results may have an impact on cardiac surgical procedures.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 References
 
Mechanical stress is known to induce transcription of different genes in myocardial cells [1, 2]. However, these findings were mainly obtained from in vitro experiments or experiments with rodents. For this reason, we investigated gene transcription in stressed porcine myocardium, which is comparable with human myocardium with respect to gross and cellular anatomy and biochemistry [3, 4].

Acute mechanical stress on the left ventricle is induced after aortic cross-clamping, whereas chronic overload on the right ventricle is produced after pulmonary artery banding. Because pulmonary artery banding is still a common pediatric cardiac operation, we wanted to investigate molecular alterations within the right ventricular myocardium after this specific procedure. If such alterations are beneficial, they could have several clinical implications, including preparation of the left ventricle in patients with transposition of the great arteries.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 References
 
Animal preparation
The experimental protocol described in this study was approved by the bioethics committee of the District of Darmstadt, Germany. All animals were handled in accordance with the American Physiological Society guidelines for animal welfare, and the investigation conformed with the "Guide for the Care and Use of Laboratory Animals" (NIH publication 85-23, revised 1985).

Experimental protocol and instrumentation
Experiments were performed in 35 young German Landrace pigs with a mean weight of 32 ± 1.2 kg (range, 25 to 44 kg). There were five randomized groups, each group consisting of 7 animals (3 sham-operated [S pigs] and 4 banded pigs [B pigs]). The animals of each group were sacrified after different time intervals. Surgical anesthesia was achieved with intravenous metomidate hydrochloride (Hypnomidate; Janssen, Neuss, Germany), 5 mg/kg, and piritramide (Dipidolor, Janssen), 22 mg. After orotracheal intubation lungs were ventilated with an air (80%)–oxygen (20%) mixture (Stephan Respirator ABV; Stephan GmbH, Germany). A left lateral fifth intercostal space thoracotomy was performed on the occasion of the first operation. The pulmonary artery was exposed and encircled with a polyester band (Deknatel Inc, Fall River, MA). In B-pigs the band was constricted, but in sham animals it was not. When arterial blood pressure and oxygen saturation declined or ventricular arrhythmias occurred, the band was released and tightened again. Pressure measurements were made by direct puncture of aorta and pulmonary artery (before and after banding) and recorded continuously (Graphtec Linearcoder Mark VII, Graphtec Corp, Kanagawa, Japan). The thoracotomy was closed and the animals were allowed to recover. The final experiment was performed after 2 or 24 hours or 3, 7, or 24 days with a median sternotomy approach. The animals were killed with an overdose of KCl and anesthetics. The hearts were exised, weighed, and prepared for further investigation. Samples were snap-frozen in liquid nitrogen and stored at -80°C.

Northern blot analysis
Total RNA from frozen heart tissue was isolated according to the method of Chomczynski and Sacchi [5]. Fifteen micrograms of total RNA from control and experimental tissue of the same time group was fractioned by size as pairs on a 1% agarose gel containing 0.66 mol/L formaldehyde and vacuum transferred to Hybond-N nylon membrane (Amersham, Arlington Heights, IL) using 10 x SSC as transfer buffer. Fixation was carried out with an ultraviolet crosslinker (Stratagene, La Jolla, CA). The integrity of the RNA was judged under ultraviolet light.

The blots were prehybridized for 4 to 6 hours at 42°C in a buffer. Subsequent hybridization was carried out for about 16 hours at 42°C in the same buffer containing 1 x 106 cpm · mL-1 of the labeled probe. After washing to a final stringency of 0.2x SSC/0.1% SDS at 60°C, filters were exposed for up to 3 days. For control purposes, filters were rehybridized with an 18S complementary DNA probe [6].

Quantification
After hybridization, the signals were quantified with a PhosphorImager (Molecular Dynamics, Sunnyvale, CA) using ImageQuant software. For normalization, the data of each hybridization signal were divided by the values for the matching 18S signal. The data obtained for the cardiac control tissue of the S-pigs were standardized at 100%.

Statistical analysis
All data are presented as mean ± standard error of the mean. Analysis of variance was used to compare the differences between the groups. Values of p less than 0.05 were considered significant.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 References
 
Baseline data
Mean transbanding gradient in B pigs was 29 ± 2.5 mm Hg. Hemodynamic and laboratory data before death are presented in Table 1. Baseline data were identical in B pigs and S pigs. Thus, pulmonary artery banding did not influence hemodynamics and blood gas exchange at rest.


View this table:
[in this window]
[in a new window]
  		Table 1. Hemodynamic and Laboratory Data of Banded and Sham-Operated Pigs Before Deatha

 
Right ventricular weight
The ratio of right ventricular weight (g) to body weight (kg) is an indicator for the increase in the size of the ventricle. The following ratios were measured (B pigs versus S pigs): 0.9 ± 0.07 versus 0.89 ± 0.01 after 2 hours (not significant [NS]); 1.2 ± 0.04 versus 1.3 ± 0.14 after 24 hours (NS); 1.5 ± 0.08 versus 1.12 ± 0.10 after 3 days (NS); 2.3 ± 0.23 versus 1.12 ± 0.04 after 7 days (p < 0.05); and 2.2 ± 0.15 versus 1.27 ± 0.03 after 24 days (p < 0.05) (Fig 1). To preclude mycardial edema, the tissue was completely dried and reweighed to calculate the water content. The water content of the right ventricle was as follows (B pigs versus S pigs): 78% ± 0.7% versus 78% ± 1.3% after 2 hours (NS); 78% ± 1.0% versus 81% ± 1.3% after 24 hours (NS); 77% ± 1.0% versus 78% ± 0.3% after 3 days (NS); 79% ± 0.7% versus 79% ± 0.4% after 7 days (NS); and 78% ± 0.4% versus 78% ± 0.6% after 24 days (NS). These data suggest that edema was not a contributing factor to the increase of right ventricular weight.



View larger version (18K):
[in this window]
[in a new window]
  		Fig 1. Ratio of right ventricular weight (g) to body weight (kg) in banded (n = 20) and sham-operated (Sham, n = 15) pigs. (*p < 0.05.)

 
Sarcoplasmic reticulum adenosine triphosphatase
Sarcoplasmic reticulum adenosine triphosphatase (SERCA) is an enzyme that is responsible for reuptake of calcium by the sarcoplasmic reticulum [7]. Any alteration to SERCA will modify the contraction or the relaxation velocity of myocytes [8]. The values of SERCA messenger RNA (mRNA) were as follows (B pigs versus S pigs): 131% ± 9% versus 100% ± 15% (NS) after 2 hours; 57% ± 10% versus 100% ± 39% after 24 hours (NS); 90% ± 19% versus 100% ± 33% after 3 days (NS); 75% ± 27% versus 100% ± 40% after 7 days (NS); and 136% ± 49% versus 100% ± 20% after 24 days (NS). Although not significant, there was downregulation of SERCA during the first 7 days in B pigs (Fig 2).



View larger version (20K):
[in this window]
[in a new window]
  		Fig 2. Expression of sarcoplasmic reticulum adenosine triphosphatase (SERCA) messenger RNA in banded (n = 20) and sham-operated (Sham, n = 15) pigs after different time intervals.

 
Phospholamban
Phospholamban is the regulator protein of SERCA. There appears to be a coordinate association of phospholamban expression and SERCA [9]. The following values for phospholamban mRNA were measured (B pigs versus S pigs): 140% ± 33% versus 100% ± 16% after 2 hours (NS); 58% ± 16% versus 100% ± 14% after 24 hours (NS); 76% ± 18% versus 100% ± 44% after 3 days (NS); 75% ± 14% versus 100% ± 43% after 7 days (NS); and 111% ± 35% versus 100% ± 12% after 24 days (NS). Like SERCA, phospholamban mRNA was downregulated during the first 7 days (Fig 3).



View larger version (19K):
[in this window]
[in a new window]
  		Fig 3. Expression of phospholamban messenger RNA (mRNA) in banded (n = 20) and sham-operated (Sham, n = 15) pigs after different time intervals.

 
Atrial natriuretic factor
Atrial natriuretic factor (ANF) is one of the natriuretic peptides released by the atria. However, ANF is known to be expressed in ventricular myocardium after pressure overload [10, 11]. The following values for ANF mRNA were observed (B pigs versus S pigs): 110% ± 10% versus 100% ± 2% after 2 hours (NS); 240% ± 7% versus 100% ± 6% after 24 hours (p < 0.01); 520% ± 8% versus 100% ± 8% after 3 days (p < 0.01); 160% ± 20% versus 100% ± 13% after 7 days (NS); and 110% ± 20% versus 100% ± 7% after 24 days (NS) (Fig 4).



View larger version (16K):
[in this window]
[in a new window]
  		Fig 4. Expression of atrial natriuretic factor (ANF) messenger RNA (mRNA) in banded (n = 20) and sham-operated (Sham, n = 15) pigs after different time intervals. (**p < 0.01.)

 
{alpha}-/ß-myosin heavy chains
Each myosin molecule is composed of two myosin heavy chains (MHCs) and four myosin light chains. Myosin heavy chains of the ventricular myocardium consist of three isoforms, V1 through V3 [12]. These isoforms are composed of {alpha}- and ß-MHCs. The values for ß-MHC mRNA were as follows (B pigs versus S pigs): 135% ± 12% versus 100% ± 0.9% after 2 hours (NS); 72% ± 14% versus 100% ± 18% after 24 hours (NS); 115% ± 12% versus 100% ± 18% after 3 days (NS); 82% ± 24% versus 100% ± 13% after 7 days (NS); and 77% ± 10% versus 100% ± 20% after 24 days (NS) (Fig 5). There was also no significant upregulation for {alpha}-MHC mRNA in B pigs (data not shown).



View larger version (19K):
[in this window]
[in a new window]
  		Fig 5. Expression of ß-myosin heavy chain (ß-MHC) messenger RNA (mRNA) in banded (n = 20) and sham-operated (Sham, n = 15) pigs after different time intervals.

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
References
 
Right ventricular weight
As expected, the ratio of right ventricular weight to body weight increased significantly after 7 and 24 days in B pigs, whereas it remained nearly unchanged in S pigs. As shown by others, pulmonary artery banding in rats results in a 60% increase of right ventricular weight after 2 days and 85% after 14 days [13]. White and associates [14] found an increase of the ratio up to 117% in mini pigs. However, between day 7 and day 24 there was no further increase of the ratio in B pigs (Fig 1). A similar result was found in feline hearts after pulmonary artery banding [15]. If we look at mRNA expression in the mechanically stressed pig ventricles, we notice an upregulation and a downregulation of genes within the first 7 days. After this time, mRNA expression returns to normal levels.

Transcription of calcium-regulating proteins
Phospholamban mRNA and SERCA mRNA were downregulated after pulmonary artery banding. Although the values in B pigs were not significantly different from those in S pigs because of high standard deviations, we assume that pressure overload influences transcription of these genes. Similar observations were made in experiments with rabbits [16]. It is proposed that downregulation of SERCA may decrease the maximal velocity of shortening and power output [7]. Although we could not demonstrate any hemodynamic alterations in our animals at rest, we would expect such alterations during exercise. Interestingly, expression of SERCA mRNA and phospholamban mRNA was normalized after 24 days although pressure overload persisted. Obviously, the myocytes were able to regenerate, at least with regard to transcription of calcium-regulating proteins.

Atrial natriuretic factor
Pressure overload produced by pulmonary artery banding significantly upregulated transcription of ANF in right ventricular myocardium after 1 and 3 days (Fig 4). Similar results were found by Carroll and colleagues [17]. These data suggest that mechanical stress caused by pressure overload may trigger ANF mRNA expression. Because upregulation of ANF mRNA was not observed in left ventricles, a hormonal stimulation of this factor can be excluded. This experiment shows that local mechanical stress is able to change the gene program of myocytes.

Myosin heavy chain
Human myocardium is mainly composed of ß-MHC (V3 isoform). This is in contrast to rodent myocardium, which contains {alpha}-MHC (V1 isoform) preponderantly. Pressure overload on rat ventricles results in an isoform switch from {alpha}-MHC to the embryonic ß-MHC [18]. However, an isoform switch is not possible in humans and large mammals [19]. We can confirm this observation, as ß-MHC mRNA was not upregulated in mechanically stressed porcine right ventricle. But why could we observe an increase of the ratio of right ventricular weight to body weight after pulmonary artery banding (Fig 1)? Our morphologic examinations showed that neither vessels nor fibrotic tissue was increased in hypertrophic right ventricles. Furthermore, myocardial edema was not observed. The only morphologic alteration was seen in myocytes in that the ratio of myocyte width to myocyte length increased significantly after 7 and 24 days in mechanically stressed right ventricles (data not shown). These results suggest that the hypertrophic response of the right ventricle is not caused by myosin accumulation. On the contrary, we suggest that there is only an unspecific increase of several intracellular structures. Similar observations were made in patients with aortic stenosis resulting in left ventricular hypertrophy [20].

In another study, we found an increased transcription of proto-oncogenes, vascular endothelial growth factor, and transforming growth factor-ß1 in right ventricles after pulmonary artery banding [21]. As in the present study, expression of these mRNAs was returned to baseline after 7 days, although pressure overload persisted. This means that mechanical stress is able to trigger a cascade of mRNA but only for a limited time. If this interval could be expanded experimentally, we would probably find useful trophic alterations such as neoangiogenesis and an increase of myosin. Such alterations would potentially have a great impact on cardiac surgical procedures.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. Cody R.J. Hypertensive heart disease and heart failure. Curr Opin Cardiol 1995;10:450-457.[Medline]
  2. Sadoshima J., Izumo S. Mechanotransduction in stretch-induced hypertrophy of cardiac myocytes. J Recept Res 1993;13:777-794.[Medline]
  3. Barth E., Stämmler G., Speiser B., Schaper J. Ultrastructural quantification of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man. J Mol Cell Cardiol 1992;24:669-681.[Medline]
  4. Schaper W., Jageneau A., Xhonneux R. The development of collateral circulation in the pig and dog heart. Cardiologia 1967;51:321-335.
  5. Chomczynski P., Sacchi Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156-159.[Medline]
  6. Oberbäumer I. Retroposons do jump: a B2 element recently integrated in an 18S rDNA gene. Nucleic Acids Res 1992;20:671-677.[Abstract/Free Full Text]
  7. Alpert N.R., Hasenfuss G., Mulieri L.A., Blanchard E.M., Leavitt B.J., Ittleman F. The reorganisation of the human and rabbit heart in response to hemodynamic overload. Eur Heart J 1995;13(Suppl D):9-16.
  8. Swyngedauw B., Delcayre C., Cheav S.L., Callens-El Amrani F. Biological basis of diastolic dysfunction of the hypertensive heart. Eur Heart J 1992;13(Suppl D):2-8.
  9. Nagai R., Zarain-Herzberg A., Brandl C.J., et al. Regulation of myocardial Ca 2+-ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. Proc Natl Acad Sci USA 1989;86:2966-2970.[Abstract/Free Full Text]
  10. Adachi S., Hiroshi I., Ohta Y., et al. Distribution of mRNAs for natriuretic peptides in RV hypertrophy after pulmonary arterial banding. Am J Physiol 1995;268:H162-H169.
  11. Izumo S., Mahdavi V., Nadal-Ginard B. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA 1988;85:339-343.[Abstract/Free Full Text]
  12. Morkin E. Regulation of myosin heavy chain genes in the heart. Circulation 1993;87:1451-1460.[Abstract/Free Full Text]
  13. Bishop J.E., Rhodes S., Laurent G.J., Low R.B., Stirewalt W.S. Increased collagen synthesis and decreased collagen degradation in right ventricular hypertrophy induced by pressure overload. Cardiovasc Res 1994;28:1581-1585.[Medline]
  14. White F.C., Nakatani Y., Nimmo L., Bloor C.M. Compensatory angiogenesis during progressive right ventricular hypertrophy. Am J Cardiovasc Pathol 1992;4:51-68.[Medline]
  15. Tagawa H., Rozich J.D., Tsutsui H., et al. Basis for increased microtubules in pressure-hypertrophied cardiocytes. Circulation 1996;93:1230-1243.[Abstract/Free Full Text]
  16. Matsui H., MacLennan D.H., Alpert N.R., Periasamy M. Sarcoplasmic reticulum gene expression in pressure overload-induced cardiac hypertrophy in rabbit. Am J Physiol 1995;268:C252-C258.
  17. Carroll S.M., Nimmo L.E., Knoepfler P.S., White F.C., Bloor C.M. Gene expression in a swine model of right ventricular hypertrophy: intercellular adhesion molecule, vascular endothelial growth factor and plasminogen activators are upregulated during pressure overload. J Mol Cell Cardiol 1995;27:1427-1441.[Medline]
  18. Chevalier B., Callens F., Charlemagne D., et al. Signal and adaptational changes in gene expression during cardiac overload. J Mol Cell Cardiol 1989;21(Suppl 5):71-77.
  19. Swyngedauw B., Lelievre L., Charlemagne D., et al. Adaptational changes of sarcomere and sarcolemma during chronic cardiac overloading in rats and humans. J Cardiovasc Pharmacol 1987;10(Suppl 6):S13-S19.
  20. Schaper J., Schaper W. Ultrastructural correlates of reduced cardiac function in human hearts. Eur Heart J 1983;4(Suppl A):35-42.
  21. Bauer E.P., Kuki S., Arras M., Zimmermann R., Schaper W. Growth factor release after pulmonary artery banding. Eur J Cardiothorac Surg 1997;11:818-823.[Abstract]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. Urashima, M. Zhao, R. Wagner, G. Fajardo, S. Farahani, T. Quertermous, and D. Bernstein
Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis
Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1351 - H1368.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. Li, G. Zhang, L. Benson, H. Holtby, S. Cai, T. Humpl, G. S. Van Arsdell, A. N. Redington, and C. A. Caldarone
Comparison of the Profiles of Postoperative Systemic Hemodynamics and Oxygen Transport in Neonates After the Hybrid or the Norwood Procedure: A Pilot Study
Circulation, September 11, 2007; 116(11_suppl): I-179 - I-187.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
E. Le Bret, J. M. Lupoglazoff, N. Borenstein, G. Fromont, F. Laborde, J. Bachet, and P. Vouhe
Cardiac "Fitness" Training: An Experimental Comparative Study of Three Methods of Pulmonary Artery Banding for Ventricular Training
Ann. Thorac. Surg., January 1, 2005; 79(1): 198 - 203.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
N. Sekarski, P. Fridez, A. F. Corno, L. K. von Segesser, and E. J. Meijboom
Doppler-guided regulation of a telemetrically operated adjustable pulmonary banding system
J. Am. Coll. Cardiol., September 1, 2004; 44(5): 1087 - 1094.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
B. Kaynak, A. von Heydebreck, S. Mebus, D. Seelow, S. Hennig, J. Vogel, H.-P. Sperling, R. Pregla, V. Alexi-Meskishvili, R. Hetzer, et al.
Genome-Wide Array Analysis of Normal and Malformed Human Hearts
Circulation, May 20, 2003; 107(19): 2467 - 2474.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. Clauss and W. Schaper
Vascular Endothelial Growth Factor : A Jack-of-All-Trades or a Nonspecific Stress Gene?
Circ. Res., February 18, 2000; 86(3): 251 - 252.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Erwin P. Bauer
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bauer, E. P.
Right arrow Articles by Schaper, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bauer, E. P.
Right arrow Articles by Schaper, W.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS