Skip Navigation

European Journal of Heart Failure 2006 8(8):784-789; doi:10.1016/j.ejheart.2006.02.005
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Stefano, L. M. D.
Right arrow Articles by Matsubara, B. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stefano, L. M. D.
Right arrow Articles by Matsubara, B. B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 European Society of Cardiology

Myocardial dysfunction with increased ventricular compliance in volume overload hypertrophy

Laercio Martins De Stefano, Luiz Shiguero Matsubara and Beatriz Bojikian Matsubara*

Department of Clinical Medicine Botucatu School of Medicine-UNESP, Brazil

* Corresponding author. Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, UNESP 18618-000, SP, Brazil. Tel.: +55 14 68822969; fax: +55 14 68822238. E-mail address: beatrizm{at}fmb.unesp.br


   Abstract
Top
 Abstract
1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 Acknowledgments
 References
 
The aim this study was to evaluate systolic and diastolic function in volume overload induced myocardial hypertrophy in rats.

Volume overload myocardial hypertrophy was induced in thirteen male Wistar rats by creating infrarenal arteriovenous fistula (AVF). The results were compared with a SHAM operated group (n = 11). Eight weeks after surgery, tail-cuff blood pressure was recorded, then rats were sacrificed for isolated heart studies using Langendorff's preparation.

AVF rats presented increased left and right ventricular weights, compared to controls. The increased normalized ventricular volume (V0/LVW, 0.141 ± 0.035 mL/g vs. 0.267±0.071 mL/g, P <0.001) in the AVF group indicated chamber dilation. Myocardial hydroxyproline concentration remained unchanged. There was a significant decrease in +dP/dt (3318±352 mm Hg s–1 vs. 2769±399 mm Hg s –1; P=0,002), end-systolic pressure-volume relation (246±56 mm Hg mL–1 vs. 114±63 mm Hg mL–1; P<0,001), and –dP/dt (1746±240 mm Hg s –1 vs. 1361±217 mm Hg s –1 P<0.001) in the AVF group, which presented increased ventricular compliance ({Delta}V25: SHAM=0.172±0.05 mL vs. AVF=0.321±0.072 mL, P<0.001) with preserved myocardial passive stiffness (Strain25: SHAM=13.5±3.0% vs. AVF=12.3+1.9%, P>0.05).

We conclude that volume-overload induced hypertrophy causes myocardial systolic and diastolic dysfunction with increased ventricular compliance. These haemodynamic features help to explain the long-term compensatory phase of chronic volume overload before transition to overt congestive heart failure.

Key Words: Cardiac hypertrophy • Ventricular dilation • Volume overload • Myocardial contractility

Received April 8, 2005; Revised November 30, 2005; Accepted February 8, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Material and methods
 3. Results
 4. Discussion
 Acknowledgments
 References
 
Myocardial hypertrophy plays a major role in the compensatory response to haemodynamic overload [1]. However, the hypertrophied heart is not just an increased version of the normal heart. There is genome expression, which results in molecular, cellular and interstitial alterations causing changes in heart size, shape and function. This is a very complex process known as cardiac remodelling and it is closely related to heart failure [2]. One of the most remarkable characteristics of this process is the abnormal accumulation of interstitial and perivascular collagen [3-7]. However, several studies have demonstrated that myocardial remodelling following chronic volume overload does not present abnormal increased collagen concentration [5,8-10]. Conversely, Brower and Janicki [11] reported a significant increase in interstitial collagen secondary to long term volume overload and overt heart failure in male rats.

Although the structural and biochemical alterations in hypertrophied muscle induced by chronic volume overload may cause ventricular dysfunction, there is no consensus in the literature on the mechanisms of heart failure. Experimental studies have shown either preserved [12-15] or depressed myocardial contractility [16,17] caused by aortocaval fistula in rats. Brower et al. [17] showed that systolic ventricular dysfunction was related to chamber dilatation and increased compliance. Later, Brower and Janicki [11] provided evidence to support the hypothesis that marked ventricular dilation occurs once myocardial hypertrophic response is exhausted, triggering transition to heart failure.

As ventricular dilatation allows stroke volume to be maintained and ventricular compliance increased, systolic and diastolic myocardial dysfunction can be seen long before the appearance of signs and symptoms of congestive heart failure.

We hypothesized that volume overload myocardial hypertrophy without increased collagen accumulation and no signs of congestive heart failure causes both systolic and diastolic dysfunction as well as increased ventricular compliance.

Therefore, the aim of this study was to analyze ventricular and myocardial function in volume overload-induced myocardial hypertrophy in rats.


   2. Material and methods
Top
 Abstract
 1. Introduction
 2. Material and methods
3. Results
 4. Discussion
 Acknowledgments
 References
 
All experiments were conducted in accordance with our University's Animal Use Committee guidelines and the Guide for the Care and Use of Laboratory Animals (NIH publication 86-23, Revised 1985) and were approved by the Botucatu School of Medicine Animal Research Committee, São Paulo, Brazil.

Volume overload myocardial hypertrophy was induced in thirteen 20-week-old male Wistar rats following surgery to create infrarenal arteriovenous fistula (AVF), according to the method of Garcia and Diebold [18]. Eleven SHAM operated animals were used as controls. All animals were housed in controlled light (12-h cycles) and temperature (25 °C) conditions with standard rat chow diet and water ad libitum. Eight weeks after surgery, tail-cuff blood pressure was recorded and rats were sacrificed for isolated heart studies using Langendorff's preparation.

2.1. Left ventricular function—Langendorff's preparation
Hearts were studied using a modified Langendorff preparation as previously described [19]. Briefly, animals were anaesthetized with thiopental sodium (50 mg/kg, IP) and heparinized (1000 UI, IP). The chest was entered by median sternotomy under artificial ventilation. The ascending aorta was isolated and cannulated for retrograde perfusion with filtered, oxygenated Krebs-Henseleit solution maintained at constant temperature and perfusion pressure (37 °C and 75 mm Hg). The Krebs Henseleit solution, gassed with 95% oxygen 5% carbon dioxide, pH 7.4, had the following composition (in mM): 115 NaCl, 5.4 KCl, 2.5 CaCl, 1.2 MgPO4, 1.15 NaH2PO4, 1.2 Na2SO4, 25 NaHCO3, and 11 glucose. After cannulation, the entire heart was quickly removed from the chest and attached to the perfusion apparatus (model 830 Hugo Sachs Electronic-March-Hugstetten, Germany). The pulmonary artery was cut to vent the right ventricle during systole, and after removal of the left atrial appendage, a latex balloon (12-mm length) was placed into the left ventricle (LV) via the mitral valve orifice. The proximal end of the balloon was attached to a plastic cannula connected to a three way valve through which the balloon was filled with saline solution and ventricular pressure was measured using a P23XL transducer and polygraph (model 40-9800-20 Windograph; Gould). Once stable, isovolumetric contractions were achieved, balloon volume was increased in 20 µl increments over an end-diastolic pressure range of 0-25 mm Hg. Pressure and volume within the balloon were recorded after each increment and corresponded to LV pressure and volume, respectively. Under these experimental conditions, the volume at zero end-diastolic pressure reflects unstressed ventricular volume (V0), which was used as an index of chamber size. Typically, 8-10 pressure-volume points were obtained from each series of measurements; two or three data sets were recorded to ensure preparation stability. All hearts were paced from right atrium at 250 bpm using an artificial pacemaker (model 79232; Hugo Sachs Eletronik). The entire procedure required no more than 20min, thereby minimizing the risk of myocardial oedema.

After haemodynamic data had been recorded, the heart was detached, the atria and large vessels were removed, and the ventricles were separated and weighed.

The ratio of V0 and body weight (V0/BW, mL/g) was used as the parameter for normalized ventricular chamber size and the ratio of V0 and left ventricular weight (V0/LVW, mL/g) was used as an indicator of ventricular geometry.

2.2. Systolic function indices
Systolic function was assessed by: peak isovolumetric pressure (LVP, mm Hg) corresponding to the end diastolic pressure of 25 mm Hg, slope of the linear end systolic pressure-volume relationship (ESPVR, mm Hg mL–1), and maximum rate of ventricular pressure rise (+dP/dt, mm Hg s–1).

2.3. Diastolic function indices
Diastolic function was analyzed by measuring or calculating the following variables: maximal rate of LV pressure fall, as an index of myocardial relaxation (–dP/dt, mm Hg s–1), variation in LV volume required to increase diastolic pressure from 0 to 25 mm Hg, as the index of LV compliance ({Delta}25, mL), and diastolic strain (%) caused by a 25 g cm–2 stress (strain25, index of passive myocardial stiffness). Stress ({sigma}, g cm–2) and strain ({varepsilon}, %) at LV midwall were calculated assuming the LV to be a thick-walled sphere. The equations were as follows [20]:


Formula



Formula

where x is the multiplication sign, LVV is LV volume (mL), V0 is LVV at end-diastolic pressure of 0 mm Hg, LVW is LV weight (g), and LVP is LV diastolic pressure (mm Hg).

2.4. Biochemical and morphometric study
Myocardial hydroxyproline concentration (HOP, µg/mg), a marker for myocardial collagen, was measured in left ventricle apex tissue according to the Switzer method [21].

2.5. Statistical analyses
Data were expressed as means±SD. The differences between groups were assessed by the Student's t test. All statistical analyses were performed using Sigma Stat 2.0 software (Jandel Scientific Software, San Rafael, CA, USA). Differences were considered significant when P<0.05.


   3. Results
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
4. Discussion
 Acknowledgments
 References
 
Table 1 shows morphometric parameters, tail-cuff blood pressures and HOP. SHAM and AVF groups had similar body weights. The AVF group had significantly reduced tail-cuff blood pressure (117±9 mm Hg vs. 154±27 mm Hg, P<0.001), and increased left (1.44±0.21 g vs. 1.02±0.09 g, P<0.001) and right ventricular weights (0.604±0.140 g vs. 0.290±0.048 g, P<0.001) compared to controls. The AVF group also showed significantly increased V0 and V0/LVW (0.388±0.118 mL/g vs. 0.144±0.029 mL/g; P<0.001 and 0.267±0.071 mL/g vs. 0.141±0.035 mL/g; P<0.001, respectively) indicating ventricular dilatation. HOP was similar in both groups indicating normal collagen concentration in AVF.


View this table:
[in this window]
[in a new window]

  		Table 1 Morphometric data, tail-cuff blood pressure (SBP) and myocardial hydroxyproline concentration (HOP) obtained in sham-operated (SHAM) and chronic volume overload (AVF) rats (means±SD)

 
Table 2 shows systolic function indices. Peak isovolumetric pressure, corresponding to zero and 25 mm Hg diastolic pressure, was similar in both groups. In contrast, AVF values for +dP/dt and ESPVR were significantly decreased (2769±399 mm Hg s–1 vs. 3318±352 mm Hg s–1; P=0.002 and 114±63 mm Hg mL–1 vs. 246±56 mm Hg mL–1; P<0.001, respectively).


View this table:
[in this window]
[in a new window]

  		Table 2 Systolic function data in isolated heart from sham-operated (SHAM) and chronic volume overload (AVF) rats (means±SD)

 
Table 3 shows diastolic function data. AVF values of –dP/dt were significantly reduced (1361±217 mm Hg s–1 vs. 1746±240 mm Hg s–1; P<0.001). Ventricular compliance ({Delta}25) was increased in animals with arteriovenous fistula, compared to SHAM group (0.321±0.072 mL vs. 0.172±0.50 mL, P<0.001); there was no difference in myocardial passive stiffness between groups.


View this table:
[in this window]
[in a new window]

  		Table 3 Diastolic function indices in isolated heart from sham-operated (SHAM) and chronic volume overload (AVF) rats (means±SD)

 
Fig. 1 shows the significant inverse relationship between the LV chamber geometry parameter (V0/LVW) and systolic function index (ESPVR) in the AVF (R=–0.614; P=0.026) and SHAM (R=–0.639; P=0.034) groups.


Figure 1
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Assoiation between end systolic pressure volume relationship slope (ESPVR) and normalized ventricular volume (V0/LVW) in sham-operated (SHAM) and aortocaval fistula (AVF) rats.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
Acknowledgments
 References
 
Experimental infra-renal aortocaval fistula induced a fall in systolic blood pressure; this was attributed to reduced peripheral vascular resistance and should not be interpreted as an indicator of decreased myocardial contractility.

Sustained volume overload induced significant increases in right and left ventricular weight without increasing myocardial hydroxyproline concentration suggesting hypertrophy without fibrosis. Our results are comparable with previous studies [9,10,22-27], however, it is important to point out that Brower and Janicki [11] reported myocardial fibrosis in rats with heart failure after 21 weeks of aortocaval fistula.

Decreased +dP/dt and ESPVR in volume overloaded rats suggests impaired myocardial contractility which is in agreement with previous findings [11,28]. It has also been reported that rat hearts subjected to 8 weeks or more of aortocaval fistula do not respond to β-adrenergic stimulus with dobutamine [29], suggesting β-adrenergic receptor down regulation or uncoupling. Moreover, Yamazaki et al. [30] showed that volume overload induces overexpression of the slower myosin heavy chain isozyme, decreasing contraction velocity. These mechanisms would explain the reduced +dP/dt seen in our study, reinforcing the role of myocyte dysfunction in decreased contractility. Other mechanisms, such as fibrosis and ischaemia can be excluded as the experimental model did not show alterations in myocardial collagen, and the in vitro preparation used for ventricular function evaluation prevents hypoxia.

ESPVR reflects the mechanical properties of the LV and its slope corresponds to maximal chamber elastance. However, in a review paper Suga [31] highlights the limitations of ESPVR such as its slight dependency on loading conditions and the inherent complexity of normalization for comparing hearts of different sizes. Later, Sato et al. [32] using a miniaturized conductance catheter showed that ESPVR is useful for evaluating myocardial contractility in rats. Other studies in rats submitted to the same experimental model have shown that this index is useful for detecting alterations in myocardial contractility associated with ventricular dilatation [11,33]. In our study, finding an inverse and significant association between ESPVR and dilatation in both the AVF and control group suggests that in isolated rat heart, this index is influenced by ventricular volume, independently of contractile state.

The varying degrees of ventricular dilatation after 8 weeks of aortocaval fistula demonstrated the inverse association between dilatation and dysfunction, which is in agreement with other studies [11,17,28,34]. Brower et al. [11] reported progressive myocardial hypertrophy without dilatation during the compensatory phase of chronic volume overload. They suggested the existence of an upper limit before the development of congestive heart failure, since there was no difference in LV weight between the compensated and failure groups. Wang et al. [28] described a progressive cardiac mass increase in rats with aortocaval shunt, occurring in two bursts. The initial burst was during the first 2 weeks of fistula, which was followed by a period of compensated hypertrophy when the growth rate was comparable to controls, and a later burst between 8 and 16 weeks of follow up, which was characterized by decompensated hypertrophy or ventricular dysfunction and congestive heart failure. Our follow-up was only 8 weeks, so we are unable to confirm these findings. However, normalized left ventricular weight was the same in rats with marked chamber dilation and in those with compensated hypertrophy (i.e., no ventricular dilation—data not shown), even in the absence of congestive phenomena.

The analysis of diastolic performance requires additional caution, since mechanical properties of the myocardium do not always reflect ventricular chamber characteristics, which will ultimately be implicated in the development of congestive heart failure. Left ventricular diastolic function is determined by chamber size or volume, ventricular wall thickness and physical properties, and by myocardial relaxation [35]. It is well known that under pressure overload, myocardial hypertrophy is associated with increased passive stiffness; which contributes to a left and upwards displacement of the diastolic pressure-volume relationship. Experimental conditions in our study allowed us to distinguish between muscle and ventricle mechanics in chronic volume-overload. Myocardial passive stiffness was the same in AVF and SHAM groups. Since this index is highly influenced by muscle composition [36,37], we attributed this preserved myocardial passive stiffness to the unchanged hydroxyproline concentration in the hypertrophied myocardium. The significant reduction of –dP/dt in the AVF group led us to conclude that the myocardial relaxation impairment was dependent on the hypertrophy itself. This might be explained by changes in calcium homeostasis [38,39], following a myosin heavy chain isozyme expression shift from V1 to V3, as demonstrated by Wang et al. [28]. Since we did not evaluate myosin isozyme composition or intracellular calcium kinetics, we cannot draw any conclusions about the mechanism behind this alteration. However, the preserved passive stiffness associated with eccentric hypertrophy and ventricular dilatation would explain the increased LV compliance.

Another important question is whether or not ventricular dilatation and reduced contractility would be reversible with correction of the fistula. Gerdes et al. [40] described partial cardiac hypertrophy regression after closure of aortocaval fistula in rats. Interestingly, they reported a 28% increase in peak rate of pressure rise induced by the fistula, which was reversed 12 weeks after fistula occlusion. In humans, Unger et al. [41] analyzed 17 kidney transplant recipients and observed decreased LV hypertrophy and chamber diameter 21 weeks after arteriovenous fistula reversal compared to eight other transplant patients with patent fistulas.

The most remarkable pathological implication of these findings is that the dilated ventricle with depressed systolic function is able to hold in higher volumes, preventing congestive phenomena despite myocardial dysfunction. Brower and Janicki [11] described overt heart failure in rats around 21 weeks after fistula creation. They defined heart failure as a significant increase in body weight together with laboured respiration and/or pitting oedema.

We conclude that chronic volume overload causes myocardial dysfunction, hypertrophy and chamber dilatation, which worsen ventricular dysfunction and cardiac overload. Therefore, myocardial dysfunction and alteration in chamber geometry work in a synergic vicious circle, causing progressive cardiac failure. In addition, increased ventricular compliance would explain the prolonged compensatory phase before transition to overt congestive heart failure.


   Acknowledgments
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 Acknowledgments
References
 
The authors thank José Carlos Georgette, Vitor de Souza, and Elenise Jamas for technical assistance.


   References
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 Acknowledgments
 References
 

  1. Colucci W.S., Braunwald E. Pathophysiology of heart failure. In: Heart disease a textbook of cardiovascular medicine—Braunwald E., Ipes D.P., eds. (2001) 6th ed. Philadelphia: WB Saunders. 503–533.
  2. Cohn J., Ferrari R., Sharpe N. Cardiac remodeling—concepts and clinical implications: a consensus paper from an International Forum on Cardiac Remodeling. J Am Coll Cardiol (2000) 35:569–582.[Abstract/Free Full Text]
  3. Marino T.A., Kent R.L., Uboh C.E., Fernadez E., Thompson E.W., Iv G.C. Structural analysis of pressure versus volume overload hypertrophy of cat right ventricle. Am J Physiol (1985) 18:H371–H379.
  4. Eghbali M., Weber K.T. Collagen and the myocardium: fibrilar structure, biosynthesis and degradation in relation to hypertrophy and its regression. Mol Cell Biochem (1990) 96:1–14.[CrossRef][Web of Science][Medline]
  5. Weber K.T., Pick R., Silver M.A., et al. Fibrillar collagen and remodeling of dilated canine left ventricle. Circulation (1990) 82:1387–1401.[Abstract/Free Full Text]
  6. Weber K.T., Brilla C.G. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation (1991) 83:1849–1865.[Abstract/Free Full Text]
  7. Okoshi M.P., Matsubara L.S., Franco M.F., Cicogna A.C., Matsubara B.B. Myocyte necrosis is the basis for fibrosis in renovascular hypertensive rats. Braz J Med Biol Res (1997) 30(9):1135–1144.[Web of Science][Medline]
  8. Michel J.B., Salzmanm J.L., Nlon M.O., Bruneral P., Barres D., Camilleri J.P. Morphometric analysis of collagen network and plasma perfused capillary bed in the myocardium of rats during evolution of cardiac hypertrophy. Basic Res Cardiol (1986) 81:142–154.[CrossRef][Web of Science][Medline]
  9. Ruzicka M., Keeley F.W., Leenen F.H.H. The renin-angiotensin system and volume overload-induced changes in cardiac collagen and elastin. Circulation (1994) 90:1989–1996.[Abstract/Free Full Text]
  10. Ruzicka M., Yuan B., Leenen F.H.H. Effects of enalapril versus losartan on regression of volume overload-induced cardiac hypertrophy in rats. Circulation (1994) 90:484–491.[Abstract/Free Full Text]
  11. Brower G.L., Janicki J.S. Contribution of ventricular remodeling to pathogenesis of heart failure in rats. Am J Physiol Heart Circ Physiol (2001) 280:H674–H683.[Abstract/Free Full Text]
  12. Badke F.R., White F.C., Lewinter M., Covell J.W., Andres J., Bloon C.M. Effects of experimental volume overload hypertrophy on myocardial blood flow and cardiac function. Am J Physiol (1981) 241:H564–H570.[Web of Science][Medline]
  13. Pouleur H., Rousseau M.F., Petein M., Van Mechelen H., Charlier A.A. Effects of chronic volume overload on left ventricular response to tachycardia. Am J Physiol (1983) 245:H218–H228.[Web of Science][Medline]
  14. Noma K., Brändle M., Rupp H., Jacob R. Left ventricular performance in rats with chronic overload due to arterio-venous shunt. Heart Vessels (1990) 5:65–70.[CrossRef][Medline]
  15. Lavandero S., Cartagena G., Guarda E., et al. Changes in cyclic AMP dependent protein kinase and active stiffness in the rat volume overload model of heart hypertrophy. Cardiovasc Res (1993) 27:1634–1638.[Abstract/Free Full Text]
  16. Newman W.H., Webb J.G., Privitera P.J. Persistence of myocardial failure following removal of chronic volume overload. Am J Physiol (1982) 243:H876–H883.[Web of Science][Medline]
  17. Brower G.L., Heneger J.R., Janicki J.S. Temporal evaluation of left ventricular remodelling and function in volume-overload hypertrophy. Am J Physiol (1996) 271:H2071–H2078.[Web of Science][Medline]
  18. Garcia R., Diebold S. Simple, rapide and effective method of producing aortocaval shunts in the rat. Cardiovasc Res (1990) 24:430–432.[Abstract/Free Full Text]
  19. de Leris J., Harding D.P., Pestre S. The isolated perfused rat heart: a model for studying myocardial hypoxia or ischemia. Basic Res Cardiol (1984) 79(3):313–321.[CrossRef][Web of Science][Medline]
  20. Weber K.T., Janicki J.S., Reeves R.C. Factors influencing left ventricular shortening in isolated canine heart. Am J Physiol (1976) 230:419–426.[Abstract/Free Full Text]
  21. Switzer B.R. Determination of hydroxyproline in tissue. J Nutr Biochem (1991) 2:229–231.[CrossRef][Web of Science]
  22. Noma K., Brändle M., Rupp H., Jacob R. Left ventricular performance in rats with chronic overload due to arterio-venous shunt. Heart Vessels (1990) 5:65–70.[CrossRef][Medline]
  23. Huang M., Hester R.L., Guyton A.C. Hemodynamic changes in rats after opening an arteriovenous fistula. Am J Physiol (1992) 262:H846–H851.[Web of Science][Medline]
  24. Ruzicka M., Baoxue Y., Harmsen E., Leenen H.H. The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker. Circulation (1993) 87:921–930.[Abstract/Free Full Text]
  25. Liu Z., Hilbelink D.R., Crockett W.B., Gerdes A.M. Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas: 1. Developing and established hypertrophy. Circ Res (1991) 69:52–58.[Abstract/Free Full Text]
  26. Liu Z., Hilbelink D.R., Crockett W.B., Gerdes A.M. Regional changes in hemodynamics and cardiac myocite size in rats with aortocaval fistulas: 2. Long-term effects. Circ Res (1991) 69:59–65.[Abstract/Free Full Text]
  27. Emery J.L., Omens J.H. Mechanical regulation of myocardial growth during volume-overload hypertrophy in the rat. Am J Physiol (1997) 273:H1198–H1204.[Web of Science][Medline]
  28. Wang X., Ren B., Liu S., Sentex P., Tappia P.S., Dhalla N.S. Characterization of cardiac hypertrophy and heart failure due volume overload in the rat. J Appl Physiol (2003) 94:752–763.[Abstract/Free Full Text]
  29. Bower G.L., Stewart J.A. Jr., Janicki J.S. Beta receptor downregulation in heart failure is protective against angiotensin II mediated myocardial necrosis. Circulation (1998) 98:70. [Abstract].
  30. Yamazaki T., Shiojima I., Komuro I., Nagai R., Yazaki Y. Involvement of the renin-angiotensin system in the development of left ventricular hypertrophy and dysfunction. J Hypertens (1994) 12:S153–S157. [suppl].[Web of Science]
  31. Suga H., Sagawa K. Instantaneous pressure-volume relationships and their ratio in excised, supported canine left ventricle. Circ Res (1974) 35:117–126.[Abstract/Free Full Text]
  32. Sato T., Shishido T., Kawada T., et al. ESPVR of in situ rat left ventricle shows contractility-dependent curve linearity. Am J Physiol (1998) 274:H1429–H1434.[Web of Science][Medline]
  33. De Stefano L.M., Matsubara L.S., Matsubara B.B. Myocardial contractility of the isovolumetrically beating isolated rat heart. Braz J Med Biol Res (2004) 37:1563–1569.[Web of Science][Medline]
  34. Gardner J.D., Brower G.L., Janicki J.S. Gender differences in cardiac remodeling secondary to chronic volume overload. J Card Fail (2002) 8:101–107.[CrossRef][Web of Science][Medline]
  35. Zile M.R., Tomita M., Nakano K., et al. B.A. Effects of left ventricular volume overload produced by mitral regurgitation on diastolic function. Am J Physiol (1991) 261:H1471–H1480.[Web of Science][Medline]
  36. Matsubara L.S., Matsubara B.B., Okoshi M.P., Cicogna A.C., Janicki J.S. Alterations in myocardial collagen content affect rat papillary muscle function. Am J Physiol Heart Circ Physiol (2000) 279:H1534–H1539.[Abstract/Free Full Text]
  37. Janicki J.S., Brower G.L., Gardner J.D., Chancey A.L., Stewart J.A. Jr. The dynamic interaction between matrix metalloproteinase activity and adverse myocardial remodeling. Heart Fail Rev (2004) 9:33–42.[CrossRef][Web of Science][Medline]
  38. Tubau J.F., Wikman-Coffelt J., Massie B.M. Diltiazem prevents hypertrophy progression, preserves systolic function, and normalizes myocardial oxygen utilization in the spontaneously hypertensive rat. Cardiovasc Res (1987) 21:606–614.[Abstract/Free Full Text]
  39. Cooper I.C., Fry C.H., Webb-People M.M. Mechanical restitution of isolated human ventricular myocardium subjected to in vivo pressure and volume overload. Cardiovasc Res (1992) 26:978–982.[Abstract/Free Full Text]
  40. Gerdes A.M., Clark L.C., Capasso J.M. Regression of cardiac hypertrophy after closing an aortocaval fistula in rats. Am J Physiol Heart Circ Physiol (1995) 37:H2345–H2351.
  41. Unger P., Vellez-Roa S., Wissing K.M., Hoang A.D., van de Borne P. Regression of left ventricular hypertrophy after arteriousvenous fistula closure in renal transplant recipients: a long term follow-up. Am J Transplant (2004) 4:2038–2044.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur Heart JHome page
K. Winkler, C. Wanner, C. Drechsler, J. Lilienthal, W. Marz, V. Krane, and for the German Diabetes and Dialysis Study Investi
Change in N-terminal-pro-B-type-natriuretic-peptide and the risk of sudden death, stroke, myocardial infarction, and all-cause mortality in diabetic dialysis patients
Eur. Heart J., September 1, 2008; 29(17): 2092 - 2099.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Stefano, L. M. D.
Right arrow Articles by Matsubara, B. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stefano, L. M. D.
Right arrow Articles by Matsubara, B. B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?