HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Brian D. Mott Yoshio Misawa Joe Helou Vinay Badhwar Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mott, B. D. Articles by Chiu, R. C.-J. Search for Related Content PubMed PubMed Citation Articles by Mott, B. D. Articles by Chiu, R. C.-J.

Ann Thorac Surg 1998;65:1039-1044
© 1998 The Society of Thoracic Surgeons

Mechanisms of Cardiomyoplasty: Comparative Effects of Adynamic Versus Dynamic Cardiomyoplasty

^a Division of Cardiothoracic Surgery, McGill University, Montreal, Quebec, Canada

Accepted for publication November 4, 1997.

Address reprint requests to Dr Chiu, Division of Cardiothoracic Surgery, The Montreal General Hospital, 1650 Cedar Ave, Room C9-169, Montreal, PQ, Canada H3G 1A4
e-mail: (mdiu{at}musica.mcgill.ca)

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. The apparent paradox seen in patients who have undergone dynamic cardiomyoplasty and shown substantial clinical and functional improvements with only modest hemodynamic changes may be due to inappropriate end points chosen for study, a result of incomplete understanding of mechanisms involved. The purpose of this study was to compare the relative role of the passive "girdling effect" and the dynamic "systolic squeezing effect" of the wrapped muscle in cardiomyoplasty.

Methods. The control group of 6 dogs underwent 4 weeks of rapid pacing (250 beats/min) to induce severe heart failure followed by 8 weeks of observation without rapid pacing. The trajectory of recovery in hemodynamics and cardiac dimensions was followed with echocardiography and Swan-Ganz catheters. In the "adynamic" cardiomyoplasty group (n = 4), the left latissimus dorsi muscle was wrapped around the ventricles and allowed to stabilize and mature for 4 weeks. This was followed by rapid pacing and recovery as in the control group. In the "dynamic" cardiomyoplasty group (n = 3), the same protocol for the adynamic group was followed except that a synchronizable cardiomyostimulator was attached to the thoracodorsal nerve of the muscle wrap. This allowed the latter to be transformed during the rapid-pacing phase and permitted dynamic squeezing of the muscle wrap to be generated by burst stimulation synchronized with cardiac contraction in a 1:2 ratio.

Results. Baseline data were comparable in all groups prior to rapid pacing. After 4 weeks of rapid pacing, the left ventricular ejection fraction was higher in the adynamic (27.0% ± 3.9%; p < 0.05) and dynamic (33.3% ± 2.3%; p < 0.02) cardiomyoplasty groups compared with controls (18.8% ± 8.3%). Similarly, ventricular dilatation in both systole and diastole was less in the adynamic (51.8 ± 8.7 mL, [p < 0.002] and 38.2 ± 7.2 mL [p < 0.001], respectively) and dynamic (62.0 ± 7.2 [p < 0.02] and 41.3 ± 3.5 mL [p < 0.005], respectively) cardiomyoplasty groups compared with controls. In the dynamic group, on and off studies were carried out after cessation of rapid pacing while the heart was still in severe failure, and they demonstrated a systolic squeezing effect in stimulated beats. Only this group recovered fully to baseline after 8 weeks.

Conclusions. By reducing myocardial stress, both the passive girdling effect and the dynamic systolic squeezing effect have complementary roles in the mechanisms of dynamic cardiomyoplasty.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Dynamic cardiomyoplasty has undergone phase I and phase II clinical trials, and a phase III prospective, randomized trial is in progress in North America [1]. Clinical follow-up results to date indicate that in more than 80% of patients who have undergone cardiomyoplasty, considerable subjective and functional improvements have occurred even when hemodynamic changes have been rather modest [2]. In the meantime, both clinical and experimental studies continue to indicate that the mechanisms of dynamic cardiomyoplasty are much more complex than previously thought; initially, it was believed to be simply a synchronized systolic squeeze of the failing heart by the wrapped muscle [3]. Of considerable interest is the so-called girdling effect, which indicates that the passive presence of a skeletal muscle wrap around the ventricles per se could modulate the remodeling process of the failing heart [4]. Because the latissimus dorsi muscle used to wrap the patient’s heart is always stimulated with a synchronized-burst cardiomyostimulator, it is difficult to separate the passive girdling effect from effects derived from the dynamic squeeze of the muscle wrap during cardiac systole [5]. The experimental studies have used different animal models to observe either of these two effects, which makes interpretation of the results difficult because of the many confounding factors associated with the different experimental animal species, heart failure models, and experimental protocols employed [4, 6].

The purpose of this study was to examine the relative contributions of the "adynamic" girdling effect and the "dynamic" systolic squeezing effect in cardiomyoplasty using the same animal species, the same heart failure model, and a comparable experimental protocol to further elucidate the mechanisms involved in dynamic cardiomyoplasty.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Nineteen mongrel dogs weighting 21 to 26 kg were used in this study in accordance with the Guidelines of the Canadian Council for Animal Care. Six dogs were eliminated from the final data analysis because of various technical complications ranging from anesthesia-related death to mediastinitis. The other 13 dogs survived the operation and follow-up.

Study groups
The dogs were divided into three groups: control, adynamic cardiomyoplasty, and dynamic cardiomyoplasty (Fig 1). The control group (n = 6) had a rapid-pacing pacemaker inserted, underwent induction of rapid-pacing heart failure for 4 weeks, and were observed for 8 weeks of recovery after the cessation of rapid pacing.

View larger version (16K): [in this window] [in a new window]   Fig 1. Experimental design. (ACMP = adynamic cardiomyoplasty; DCMP = dynamic cardiomyoplasty; E = echocardiography; S-G = Swan-Ganz study.)

In the dynamic cardiomyoplasty group (n = 3), the protocol was identical to that of the adynamic group except that the muscle wrap underwent transformation during the 4 weeks of rapid pacing and during the 8 weeks of recovery, synchronized contraction of the latissimus dorsi muscle wrapped around the heart was generated by burst stimulation of the muscle wrap.

Induction of heart failure
Heart failure was induced during the 4 weeks of continuous rapid pacing using a modified Medtronic pacemaker model 8329. The pacemaker power pack was placed in a subcutaneous pocket in the anterior abdominal wall, and a Medtronic myocardial lead model 5071 was positioned near the apex of the left ventricle. These pacemakers were programmed transcutaneously by telemetry to a rate of 250 beats/min using a Medtronic programmer model 9710. Termination of rapid pacing was also achieved by telemetry.

Cardiomyoplasty procedures
Anesthesia was induced with sodium pentobarbital (30 mg/kg) and maintained with 1% isoflurane and oxygen delivered by a mechanical ventilator (Muffield anesthesia ventilator series 200; Intermed, Penlon, UK). The left latissimus dorsi muscle was harvested with the animal in the right lateral decubitus position. The distal and proximal muscular tendinous attachments were divided, and the thoracodorsal pedicle was preserved. In the adynamic cardiomyoplasty group, no cardiomyostimulator was implanted. In the dynamic cardiomyoplasty group, on the other hand, Medtronic intramuscular leads model 4750 were sewn near the trifurcation of the thoracodorsal nerve as previously described [8]. The muscle and leads were then placed into the left pleural cavity through a minithoracotomy created by resection of the second rib anteriorly. The proximal tendon was reattached to the periosteum of the resected rib to anchor it in place, with care taken not to compromise the thoracodorsal pedicle. The incision was closed in layers.

The dog was repositioned in the supine position, and a median sternotomy was performed. A wide pericardiotomy was done, and the left latissimus dorsi muscle, retrieved from the pleural space, was wrapped in a posterior clockwise direction around both ventricular surfaces snugly, but without excessive tension. The muscle was sewn to the pericardium along the posterior atrioventricular groove and then sewn to itself anteriorly to complete the wrap. The epicardial sensing and pacing leads were placed near the apices of the ventricles, and then tunneled subcutaneously to pockets created on each side of the abdominal wall. The pacing electrode was used for rapid pacing (described later), and the sensing electrode as well as the intramuscular electrodes for the latissimus dorsi muscle were connected to a Medtronic transform cardiomyostimulator model 4710, which was used for both skeletal muscle transformation and burst stimulation of the muscle wrap. The mediastinum was drained and the sternum closed with wires.

Pacing protocols for dynamic cardiomyoplasty group
During the rapid-pacing period, the latissimus dorsi muscle wrapped around the ventricles was subjected to a transformation protocol to alter the muscle phenotype into type I fibers to confer fatigue resistance. This was carried out with the modification of a previously published protocol [8]. During the first week, the latissimus dorsi muscle received one stimulating pulse 50 times a minute from the cardiomyostimulator. The number of pulses within a burst increased by one a week until the fourth week, namely, at the end of the rapid-pacing phase, at which time the latissimus dorsi muscle received bursts comprising four pulses each. After the cessation of the rapid-pacing phase, with the heart in normal sinus rhythm, the latissimus dorsi muscle was stimulated in synchrony with cardiac systole at a ratio of 1:2 (stimulation to heart rate) throughout the 8-week recovery period. The standard electric burst stimulation protocol used to induce dynamic contraction of the muscle wrap was as follows: amplitude, 5 V; pulse width, 210 µs; pulse interval, 31 ms; and synchronization delay, 50 msec.

Data collection
Indices of left ventricular function and dimension were measured weekly with two-dimensional echocardiography (model 77020 AC; Hewlett-Packard, Andover, MA) with the animal under general anesthesia (see Fig 1). Left ventricular ejection fraction (LVEF), left ventricular end-systolic volume, and left ventricular end-diastolic volume (LVEDV) were measured. Hemodynamic data were obtained using Swan-Ganz pulmonary artery catheters (Arrow International, Inc, Reading, PA). Cardiac output was measured by the thermodilution method (model 90303A; Space Labs Inc, Redmond, WA). Other variables measured or calculated included stroke volume, pulmonary capillary wedge pressure, central venous pressure, right ventricular pressure, and pulmonary artery pressure. The Swan-Ganz catheter measurements were repeated at 4-week intervals with the dogs under anesthesia. In addition, a femoral artery catheter was inserted to measure systemic arterial pressure, and heart rate was recorded by monitoring the electrocardiogram. All measurements by echocardiography and Swan-Ganz catheter were repeated three times. The data are represented as the mean ± standard deviation.

Statistical analysis
Group means were compared with Student’s unpaired t tests using Statview version 3.0 software (Abacus Concepts, Berkeley, CA). Analysis of variance with repeated measures followed by the multiple comparison of Student-Neuman-Keuls was also used.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Echocardiographic measurements of LVEDV and LVEF are shown in Figures 2 and 3, respectively. As described, the cardiomyoplasty groups had a 4-week stabilization and conformation period prior to the initiation of rapid pacing (see Fig 1). All three groups had similar baseline values at 4 weeks, just prior to the start of rapid pacing with cardiac contractions of 250 beats/min. Four weeks of such rapid pacing resulted in severe heart failure, with decreases in LVEF and enlargement of ventricular volumes in both systole and diastole in all three groups. However, the degree of ventricular dysfunction induced by rapid pacing, as reflected in the reduction in LVEF, was less in both the adynamic and dynamic cardiomyoplasty groups. At the end of 4 weeks of rapid pacing, LVEFs in the adynamic and dynamic cardiomyoplasty groups were 27.0% ± 3.9% (p < 0.05) and 33.3% ± 2.3% (p < 0.03), respectively, versus 18.8% ± 8.3% in the control group. The degree of ventricular dilatation at the end of the rapid-pacing phase was also less in the cardiomyoplasty groups. In the adynamic cardiomyoplasty group, LVEDV and left ventricular end-systolic volume were 51.8 ± 8.7 mL (p < 0.002) and 38.2 ± 7.2 mL (p < 0.001), respectively, compared with 94.8 ± 17.6 mL and 76.2 ± 14.2 mL, respectively, in the control group. Similarly, in the dynamic cardiomyoplasty group, LVEDV and left ventricular end-systolic volume were 62.0 ± 7.2 mL (p < 0.02) and 41.3 ± 3.5 mL (p < 0.005), respectively.

View larger version (15K): [in this window] [in a new window]   Fig 2. After rapid pacing, all groups showed ventricular dilatation, but the adynamic cardiomyoplasty (ACMP) and dynamic cardiomyoplasty (DCMP) groups had less enlargement than the control group. (*p < 0.02; **p < 0.002.)

View larger version (16K): [in this window] [in a new window]   Fig 3. The degree of ventricular dysfunction during rapid pacing was less in the adynamic cardiomyoplasty (ACMP) and dynamic cardiomyoplasty (DCMP) groups than in the controls. During the recovery period, ejection fractions were higher in the DCMP group compared with the control group. (*p < 0.05; **p < 0.005.)

View larger version (18K): [in this window] [in a new window]   Fig 4. At the end of induction of heart failure, the control group had a higher pulmonary capillary wedge pressure than the adynamic cardiomyoplasty (ACMP) and dynamic cardiomyoplasty (DCMP) groups. (*p < 0.05.)

View larger version (10K): [in this window] [in a new window]   Fig 5. In the dynamic cardiomyoplasty group there was a trend toward higher left ventricular ejection fractions (LVEF) with the stimulator on compared with off throughout the entire recovery period, but it was not significant except at week 9 (*p < 0.05).

View larger version (93K): [in this window] [in a new window]   Fig 6. Two-dimensional echocardiograms (apical view) after rapid-pacing period (week 9) during cardiomyostimulator studies: stimulator "off" at (A) end-diastole and (B) end-systole and stimulator "on" at (C) end-diastole and (D) end-systole, where the left ventricle (LV) looks smaller because of systolic assist of skeletal muscle. (LA = left atrium.)

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

Recently, a number of articles have synthesized data obtained in both clinical and laboratory studies, and a more complex picture of mechanisms involved in dynamic cardiomyoplasty is emerging [3, 7]. The central effect appears to be the reduction in myocardial stress, achieved primarily in two ways. The first is the passive constraint provided by the muscle around the heart to restrain continued ventricular dilatation, a well-known remodeling process in heart failure. Clinical and experimental evidence indicates that "adynamic cardiomyoplasty," namely, a latissimus dorsi muscle flap wrapped around the heart without being stimulated, can provide such a constraint [4]. Prevention of progressive ventricular dilatation can forestall a further increase in myocardial tension associated with a larger radius of the ventricular cavity in accordance with Laplace’s law.

Another way myocardial stress can be reduced is by systolic compression in "dynamic cardiomyoplasty" [10]. It has been shown by direct measurement that the transmyocardial pressure gradient can be significantly reduced by contraction of the muscle wrapped around the ventricle during systole [11]. Thus, one can postulate that dynamic compression of the myocardium provides a measure of relief in myocardial stress during systole and that the girdling effect may prevent progressive increases in myocardial tension during diastole by limiting cardiac dilatation [9]. In the clinical study, all patients received dynamic cardiomyoplasty, and therefore it was difficult to distinguish the relative contributions of these two components, ie, adynamic girdling effect and dynamic systolic compression. In animal studies, in contrast, simply wrapping the skeletal muscle around the heart without stimulation was carried out [4]. However, the results were often compared with effects of dynamic cardiomyoplasty in different animal and heart failure models [6]. In a number of other investigations, acute on/off studies had been done to discern the role of muscle stimulation. However, because any effects on the remodeling process take time, such acute on/off studies are unlikely to uncover the true consequences of long-term systolic compression. Our study is of interest in that we used an identical animal species and heart failure model to observe the effects of these two mechanisms for a substantially longer period than in acute on/off studies. Our results are consistent with the hypothesis that these two effects are complementary and possibly additive.

Many heart failure models have been used to study therapeutic interventions in heart failure, but there is no ideal experimental model that truly represents human heart failure. Rapid pacing is a well-defined heart failure model that leads to severe dilated cardiomyopathy and heart failure in 3 to 4 weeks [12]. At a heart rate of 250 beats/min in the rapid-pacing phase, it is not possible to observe the effects of dynamic compression of the muscle wrap, as the skeletal muscle cannot be stimulated at such a rapid rate without fatigue and serious damage, even after transformation. Therefore we elected to observe the effects of dynamic cardiomyoplasty only after the cessation of rapid pacing. At this point, the heart is in severe heart failure, but without continued rapid pacing, it tends to gradually improve in function and decrease in size. We performed acute on/off studies in the early phase of the recovery period when the heart is still in severe failure but in sinus rhythm [13] and then examined the long-term effects by comparing the trajectory of recovery in ventricular function and dimension for 8 weeks. As all three study groups underwent an identical insult for an identical period of time, these observations allowed us to minimize confounding factors so that direct comparisons could be made.

In clinical cardiomyoplasty, of course, the cardiomyoplasty procedure is not done before the onset of heart failure as it was here. As explained earlier, however, in this study our goal was to examine the mechanism of cardiomyoplasty after the cardiomyoplasty has "matured." By doing the muscle wrap 4 weeks before the onset of rapid pacing in the cardiomyoplasty groups, we eliminated the effects of a major surgical intervention and allowed the skeletal muscle wrap to conform to the new dimension [14]. The fact that the baseline values of these groups were not significantly different from those of the control group (at 4 weeks) allowed us to compare the effects of rapid pacing per se. The transformation protocol used for the dynamic group does not greatly affect the variables measured.

The combined effects of systolic compression and girdling can stabilize the remodeling process of the heart, which in itself is beneficial for patients with heart failure, as the natural history of a failing heart is progressive ventricular dilatation associated with an increase in severity in heart failure. Of great interest are the clinical reports of "reverse remodeling" in which the cardiac sizes not only stabilized but, in fact, decreased. This has been demonstrated by follow-up roentgenograms [7], echocardiograms, and ventricular pressure–volume loops obtained by conductance catheters [15]. Recently, histologic evidence of improved myocardial viability after afterload reduction by prolonged left ventricular assist devices has been reported [16]. We speculate that sustained reduction in myocardial stress by cardiomyoplasty, like that achieved with left ventricular assist devices, may allow the hibernating myocardium to recover or reduce apoptosis, which is thought to contribute to the progressive deterioration of myocardial function in heart failure [17]. This may explain why "reverse remodeling" can take place. However, such intriguing possibilities need to be further investigated and confirmed.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
This work was supported by a grant from the Medical Research Council of Canada.

Mr Francischelli is affiliated with Medtronic Inc, Minneapolis, MN.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. Chiu R.C.-J. Dynamic cardiomyoplasty for heart failure. Br Heart J 1995;73:1-3.[Free Full Text]
2. Furnary A.P., Jessup M., Moreira L.F.P. Multicenter trial of dynamic cardiomyoplasty for chronic heart failure. The American Cardiomyoplasty Group. J Am Coll Cardiol 1995;28:1175-1180.
3. Oh J.H., Badhwar V., Chiu R.C.-J. Mechanisms of dynamic cardiomyoplasty: current concepts. J Cardiac Surg 1996;11:194-199.[Medline]
4. Capouya E.R., Gerber R.S., Drinkwater D.C., Jr, et al. Girdling effect of nonstimulated cardiomyoplasty on left ventricular function. Ann Thorac Surg 1993;56:867-871.[Abstract/Free Full Text]
5. Carpentier A., Chachques J.C., Acar C., et al. Dynamic cardiomyoplasty at seven years. J Thorac Cardiovasc Surg 1993;106:42-53.[Abstract]
6. Lucas C.H.B., van der Veen F., Cheriex E.C., et al. Long-term follow-up (12 to 35 weeks) after dynamic cardiomyoplasty. J Am Coll Cardiol 1993;22:758-767.[Medline]
7. Li C.M., Chiu R.C.-J. Dynamic cardiomyoplasty: the mechanisms and optimization of programming. In: Stephenson L.W., Brachmann J., eds. Current clinical practices in dynamic cardiomyoplasty. Mt. Kisco, NY: Futura, 1997.
8. Chiu R.C.-J. Cardiomyoplasty. In: Edmunds H., ed. Adult cardiac surgery. New York: McGraw-Hill, 1996:1491-1504.
9. El Oakley R.M., Jarfis J.C. Cardiomyoplasty. A critical review of experimental and clinical results. Circulation 1994;90:2085-2090.[Free Full Text]
10. Lee K.F., Dignan R.J., Parmar J.M., et al. Effect of dynamic cardiomyoplasty on left ventricular performance and myocardial mechanics in dilated cardiomyoplasty. J Thorac Cardiovasc Surg 1991;102:124-131.[Abstract]
11. Chen F.Y., Aklog L., Guzman B.J., et al. de. New technique measures decreased transmural myocardial pressure in cardiomyoplasty. Ann Thorac Surg 1995;60:1678-1682.[Abstract/Free Full Text]
12. Wilson J.R., Douglas P., Hickey W.F., et al. Experimental congestive heart failure produced by rapid ventricular pacing in the dog. Cardiac effects. Circulation 1987;75:857-867.[Abstract/Free Full Text]
13. Schreuder J.J., van der Veen F.H., van der Velde E.T., et al. Beat to beat analysis of left ventricular pressure volume relation and stroke volume by conductance catheter and aortic modelflow in cardiomyoplasty patients. Circulation 1995;91:2010-2017.[Abstract/Free Full Text]
14. Gealow K.K., Solien E.E., Bianco R.W., Chiu R.C.-J., Shumway S.J. Conformational adaptation of muscle: implications in cardiomyoplasty and skeletal muscle ventricles. Ann Thorac Surg 1993;56:520-526.[Abstract/Free Full Text]
15. Kass D., Baughman K.L., Pak P.H., et al. Reverse remodelling from cardiomyoplasty in human heart failure. External constraint versus active assist. Circulation 1995;91:2314-2318.[Abstract/Free Full Text]
16. Tayama E., Nose Y. Can we treat dilated cardiomyopathy using a left ventricular assist device? [editorial]. Artif Organs 1996;20:197-201.[Medline]
17. Olivetti G., Abbi R., Quaini F., et al. Apoptosis in the failing human heart. N Engl J Med 1997;336:1131-1142.[Medline]

This article has been cited by other articles:

				E. Monnet and J. C. Chachques Animal Models of Heart Failure: What Is New? Ann. Thorac. Surg., April 1, 2005; 79(4): 1445 - 1453. [Abstract] [Full Text] [PDF]

				Y. Misawa and K. Fuse Dynamic cardiomyoplasty reduces myocardial oxygen consumption Ann. Thorac. Surg., September 1, 2003; 76(3): 977. [Full Text] [PDF]

				W. B. Dobkowski Myocardial Protection During Minimally Invasive Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2002; 6(4): 319 - 324. [Abstract] [PDF]

				H. G. Kaulbach, R. Lorusso, G. Bolotin, J. J. Schreuder, and F. H. van der Veen Effects of chronic cardiomyoplasty on ventricular remodeling in a goat model of chronic cardiac dilatation: part 2 Ann. Thorac. Surg., August 1, 2002; 74(2): 514 - 521. [Abstract] [Full Text] [PDF]

				K. Shirota, Y. Huang, O. Kawaguchi, T. Yuasa, P. W. Brady, Y. Ueda, and S. N. Hunyor Functional recovery of the native heart after cardiomyoplasty in sheep with heart failure: passive and dynamic effects of volume loading Ann. Thorac. Surg., March 1, 2002; 73(3): 849 - 854. [Abstract] [Full Text] [PDF]

				K. Shirota, O. Kawaguchi, Y. Huang, T. Yuasa, R. Carrington, P. W. Brady, and S. N. Hunyor Ventricular remodeling after cardiomyoplasty in heart failure sheep: passive and dynamic effects Ann. Thorac. Surg., December 1, 2000; 70(6): 2102 - 2106. [Abstract] [Full Text] [PDF]

				J.M Power, J Raman, A Dornom, S.J Farish, L.M Burrell, A.M Tonkin, B Buxton, and C.A Alferness Passive ventricular constraint amends the course of heart failure: a study in an ovine model of dilated cardiomyopathy Cardiovasc Res, December 1, 1999; 44(3): 549 - 555. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Brian D. Mott Yoshio Misawa Joe Helou Vinay Badhwar Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mott, B. D. Articles by Chiu, R. C.-J. Search for Related Content PubMed PubMed Citation Articles by Mott, B. D. Articles by Chiu, R. C.-J.