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Ann Thorac Surg 1997;64:81-85
© 1997 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Cardiac Binding in Experimental Heart Failure

Divisions of Cardiothoracic Surgery and Cardiology, State University of New York-Health Science Center at Brooklyn, Brooklyn, New York

Accepted for publication January 10, 1997.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
Background. Cardiomyoplasty is a potential therapy for heart failure. Its benefits are attributed to systolic augmentation (dynamic cardiomyoplasty) and prevention of cardiac dilatation (static cardiomyoplasty). To evaluate the static component, we used an artificial membrane for cardiac binding in a canine model of heart failure.

Methods. Intracoronary doxorubicin was administered weekly for 4 weeks to induce heart failure in 10 dogs, each of which was assigned to one of two treatment groups: (1) no treatment, or (2) cardiac binding. Hemodynamic data were obtained at operation and at 7 weeks after operation. Echocardiography was performed weekly.

Results. Left ventricular end-diastolic pressure and diameter, and right ventricular end-diastolic diameter increased in group 1 (from 9.6 ± 6.1 to 19.6 ± 2.3 mm Hg, p = 0.009; from 3.9 ± 0.4 to 5 ± 0.3 cm, p = 0.0013; and from 1.6 ± 0.2 to 1.9 ± 0.3 cm, p = 0.0036, respectively). Ejection fraction fell in group 1 from 0.60 ± 0.10 to 0.40 ± 0.04 (p = 0.0009) and in group 2 from 0.56 ± 0.02 to 0.40 ± 0.04 (p = 0.0001), but the difference between groups was not significant.

Conclusion. Cardiac binding reduces the ventricular dilatation associated with heart failure without exacerbating left ventricular dysfunction.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
See also page 85.

Dynamic cardiomyoplasty is not an established treatment modality for chronic heart failure despite its clinical introduction almost a decade ago [1]. Various studies have been performed to investigate its mechanisms of action [2–4]. Its beneficial effects have been attributed to two mechanisms: (1) systolic augmentation from the stimulated muscle wrap (dynamic component), and (2) limitation of progressive cardiac dilatation (static component). Improvement in patient functional status and survival have been reported [5, 6]. However, objective evidence of enhanced ventricular performance has not been produced consistently.

The constraining or girdling effect of the muscle wrap has received attention recently. Few studies have shown that cardiomyoplasty increases contractility while unloading the ventricle through a reduction of end-diastolic volume [7, 8]. This mechanism may be a major benefit after cardiomyoplasty. The muscle wrap is not stimulated in currently used transformation protocols for at least 2 weeks after cardiomyoplasty (the "vascular delay" period). Several weeks then are necessary to train the muscle and obtain the full advantage of an effective transformation. During this period, further deterioration may occur as a consequence of the additional burden provided by the thick, heavy latissimus dorsi muscle that is wrapped around the heart and is not contributing any significant contractile work.

We used a canine model of chronic heart failure caused by multidose intracoronary infusions of doxorubicin to test the potential benefit of wrapping the heart with a thin synthetic membrane in the hope of attenuating cardiac dilatation and preserving ventricular function [9].

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
Ten adult male mongrel dogs weighing 20 to 34 kg (mean, 27.4 ± 3.5 kg) were randomly assigned to two groups: untreated heart failure (group 1), or heart failure treated by cardiac binding (group 2) with a Gore-Tex surgical membrane (expanded polytetrafluoroethylene, 0.1 mm; W.L. Gore & Associates Inc, Flagstaff, AZ). All animals received humane care in accordance with the "Guide for the Care and Use of Laboratory Animals," National Institutes of Health publication 86-23, revised 1985. The animals were premedicated with acepromazine maleate (Aveco Co, Inc, Fort Dodge Laboratories, Inc, Fort Dodge, IA) and were anesthetized with an intravenous injection of 15 mg/kg of sodium thiopental (Abbott Laboratories, North Chicago, IL). Anesthesia was maintained after endotracheal intubation with oxygen and halothane (0.5% to 1%).

The animals were positioned in the supine position and a bilateral anterior thoracotomy was made through the fifth intercostal space (a "clamshell" incision). A percutaneous vascular access port (model GPV; Access Technologies, Skokie, IL) was positioned in the subcutaneous tissue in the posterior aspect of the incision. The pericardium was opened and the heart was suspended in a cradle. After the coronary vasculature was examined, the first or second diagonal branch was identified and mobilized. A 4F catheter was introduced into it retrogradely until the tip was in the left main coronary artery. The catheter immediately was flushed with 1 mL of heparin (1,000 U/mL) and then secured to the epicardium with several sutures. The incision was closed and postoperative pain was controlled with intramuscular butorphanol tartrate (0.4 mg/kg; Aveco Co, Inc, Fort Dodge Laboratories, Inc).

In group 2 animals, cardiac wrapping was performed after placement of the intracoronary catheter. A surgical membrane was shaped and sized according to the animal's heart. The heart was lifted gently and the membrane was wrapped around both ventricles and atria up to the pericardial reflection. The cephalad edges of the membrane were anchored to the pericardium to prevent slippage. The wrap was made tight enough to follow the contour of the heart without altering hemodynamic parameters, and the anterior edges were sutured with interrupted 3-0 silk sutures.

All animals received weekly infusions of doxorubicin (Adria Laboratories, Columbus, OH) for 4 weeks. Doxorubicin (10 mg) was diluted in 60 mL of 0.9% NaCl solution and infused (0.25 mg/kg) through the catheter at a rate of 1 mL/min. After each infusion and every other day, the catheter was flushed with 1 mL of heparin (1,000 U/mL). Doxorubicin administration was started 1 week after operation.

	Cardiac Hemodynamics

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
Right and left cardiac catheterization was carried out before operation (baseline) and repeated at 7 weeks of follow-up. A Swan-Ganz catheter (Arrow International, Inc, Reading, PA) was inserted into the external jugular vein, and the right atrial, right ventricular, pulmonary artery, and pulmonary capillary wedge pressures were measured. Cardiac output was measured in triplicate using the thermodilution method (model 9520A; American Edwards Laboratories, Irvine, CA). Left ventricular pressure was obtained by insertion of a pigtail catheter (Cordis Corporation, Miami, FL) into a femoral or carotid artery. After instrumentation, arterial and mixed venous blood gas levels were obtained. Hemodynamic and oximetric parameters were calculated using standard formulas for cardiac and stroke volume indices, oxygen delivery and consumption, systemic and pulmonary vascular resistance indices, left and right ventricular stroke work indices, and left ventricular minute work index.

	Echocardiography

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
Two-dimensional echocardiographic studies were performed using a 1500 echocardiographic system (Hewlett-Packard, Andover, MA) with a 2.5-MHz transducer. All animals were anesthetized with intravenous sodium thiopental (10 mg/kg) and placed in the right lateral decubitus position. Long- and short-axis views were obtained at the apex, left sternal border, and subcostal margin. Three sets of repeated measurements were made in each echocardiographic view at baseline and then weekly for 7 weeks in both groups of animals. The mean value of the three repeated measurements then was used to describe the quantitative data for each dog at each of the seven data points. All images were analyzed by the same echocardiographer. The calculated parameters included left ventricular end-diastolic diameter and length, endocardial area and volume, right ventricular end-diastolic diameter, left ventricular end-systolic length, endocardial area and volume, and ejection fraction.

	Statistical Analysis

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
Data were expressed as means plus or minus standard deviations, and were analyzed by repeated-measures analysis of variance with multiple comparisons (Scheffé's procedure). A p value of 0.05 or less was considered to represent statistical significance.

	Results

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
Hemodynamic Parameters
No significant differences were observed in indices of systolic function (Table 1). Cardiac index fell from 4.2 ± 1.8 to 3.2 ± 1 L•min^-1•m^-2 in group 1 and from 4.7 ± 1.4 to 3.1 ± 0.6 L•min^-1•m^-2 in group 2; stroke volume index decreased from 43.6 ± 11.9 to 29.7 ± 11.9 mL•beat•m^-2 in group 1 and from 45.22 ± 15.3 to 24.8 ± 6.6 mL•beat•m^-2 in group 2; left ventricular stroke work index declined from 62.7 ± 16.1 to 40.9 ± 9 g•m/m² in group 1 and from 63.2 ± 29.8 to 30 ± 12.1 g•m/m² in group 2. Heart rate and mean systemic arterial pressure did not change significantly in either group. Left ventricular peak systolic pressure and systemic and pulmonary vascular resistance indices increased comparably in both groups, but these changes did not reach statistical significance. Left ventricular end-diastolic pressure increased significantly in group 1 (from 9.6 ± 6.1 to 19.6 ± 2.3 mm Hg; p = 0.009), but not in group 2 (Fig 1).

View larger version (15K): [in this window] [in a new window]   Fig 1. . Experimental data from all animals comparing mean change in left ventricular end-diastolic pressure in the control and cardiac binding groups at baseline (white bars) and at 7 weeks (black bars). Bars indicate standard deviation. The asterisk indicates p = 0.009 from baseline.

	Echocardiographic Parameters

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

View larger version (17K): [in this window] [in a new window]   Fig 2. . Time course of left ventricular dilatation with (squares) and without (circles) cardiac binding. Bars indicate standard deviation. The asterisk indicates p = 0.0013 from baseline.

View larger version (17K): [in this window] [in a new window]   Fig 3. . Time course of right ventricular dilatation with (squares) and without (circles) cardiac binding. Bars indicate standard deviation. The asterisk indicates p = 0.0036 from baseline.

View larger version (17K): [in this window] [in a new window]   Fig 4. . Time course of ejection fraction with (squares) and without (circles) cardiac binding. Bars indicate standard deviation.

	Comment

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

Cardiomyoplasty improved left ventricular diastolic function in several studies. Increased contractility (end-systolic elastance) and decreased end-diastolic volume without an increase in cardiac output, ejection fraction, or stroke volume were described [7]. Jondeau and colleagues [12] could not document, by hemodynamic evaluation or exercise stress test variables, a benefit from muscle stimulation 6 months after cardiomyoplasty, and they suggested that prevention of cardiac dilatation is the main effect of the procedure. Stimulation of the wrap provided no objective benefit, and passive constraint by the wrap was considered to be the most important mechanism of cardiomyoplasty [8]. Preservation of cardiac function and reduced enlargement of the left ventricle after unstimulated muscle wrap were obtained in a model of chronic heart failure [13].

Progressive muscle damage and fibrosis after cardiomyoplasty was documented [14]. Structural muscle damage resulted from the combined effects of chronic electrical stimulation, muscle ischemia, and loss of resting tension [11].

A negative effect of muscle wrapping could appear in the early postoperative period. Application of the unstimulated muscle wrap to the failing heart decreased the ejection fraction from 0.34 to 0.18 in dogs [4]. The unstimulated muscle wrap significantly decreased cardiac output [3, 15]. These findings could account for the prohibitively high early morbidity and mortality after cardiomyoplasty in patients with New York Heart Association class IV disease [7, 11].

The idea of using an artificial cardiac constraint or girdle is appealing. This could avoid some of the negative aspects of cardiomyoplasty, such as the burden and inertia of the muscle, the fibrosis of the muscle flap, and the prolonged operative procedure in patients with heart failure. Cardiac binding, as designed in our study, does not appear to alter the progression of systolic deterioration in the course of heart failure. All the systolic function parameters were comparable in the untreated heart failure group and the cardiac binding group. The analysis of diastolic function showed significantly increased left ventricular end-diastolic pressure associated with significant dilatation of both ventricles in the control group. Cardiac binding prevented biventricular dilatation and significantly attenuated the increase in left ventricular end-diastolic pressure.

An obvious limitation of our study is the performance of cardiac binding before the development of heart failure. Further studies will define its role in established heart failure. Another limitation of our study is the use of echocardiography and hemodynamic evaluation to study changes in systolic and diastolic function, as is commonly done in clinical practice.

Our study did not demonstrate an improvement in cardiac function as evaluated by clinical hemodynamic measurements. Interestingly, cardiac binding did not appear to have deleterious effects on cardiac performance, which could be expected in an animal model of rapidly progressive heart failure. If further studies are unable to demonstrate a significant advantage of an appropriate muscle stimulation, and the efficacy of cardiomyoplasty is attributed largely to the "girdling effect," then a skeletal muscle wrap may not be necessary because an equivalent result could be achieved by wrapping the heart with an artificial membrane.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
This study was supported by The Foundation for Surgical Education and Investigation, Inc, State University of New York Health Science Center at Brooklyn, and The Maimonides Research and Development Foundation.

We thank the Adria Laboratories of Columbus, OH, for graciously providing our laboratory with doxorubicin, and W. L. Gore & Associates, Inc of Flagstaff, AZ, for providing our laboratory with a generous supply of surgical membrane.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 
Address reprint requests to Dr Chiavarelli, State University of New York-Health Science Center at Brooklyn, 450 Clarkson Ave, Box 40, Brooklyn, NY 11203.

	References

Top Footnotes Abstract Introduction Material and Methods Cardiac Hemodynamics Echocardiography Statistical Analysis Results Echocardiographic Parameters Comment Acknowledgments References

 

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