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ORIGINAL ARTICLE

Left ventricular function after plication of the left ventricular free wall in dogs*

James Newton Bizetto Meira de Andrade0; Aparecido Antonio Camacho0; Paulo Sérgio Patto Santos0; Alexandra Pinheiro Fantinatti0; Newton Nunes0; Ângelo João Stopiglia0; João Carlos Leal0; Domingo Marcolino Braile0

DOI: 10.1590/S0102-76382004000200007

INTRODUCTION

Ventricular remodeling, with changes in the geometry and increase in the stress on the ventricular wall and the consumption of oxygen by the myocardium, occurs as a result of the physiopathology and progression of cardiac insufficiency [1,2]. The definitive treatment is heart transplantation however this is not always possible due to the low numbers of donors and other limitations [3].

Recently, a new concept for the treatment of end-stage heart disease was introduced, to reduce the diameter of the remodeled left ventricle (LV) [4]. The operation, named partial ventriculectomy, is based on Laplace's law, in which a reduction of the left ventricle (LV) chamber diminishes the tension on the free wall of the LV and improves its function [4-6]. Although its clinical application is limited by the high rate of mortality during the first postoperative months and high late morbidity [7,8]. An alternative to the resection of a portion of the potentially viable myocardium was suggested, by means of plicature of the papillary muscles, after a small apical incision in the LV. This approach has given good preliminary results [9]. Another technique at LV reduction by plicature of akinetic areas after myocardial infarction induced in rats was described, with an initial improvement in LV function. However, this improvement was not maintained four weeks after the procedure [3]. An apparatus denominated as "myosplint" was also developed to change the shape of the LV, with a reduction of parietal stress and improvement in the LV function in dogs with cardiac insufficiency induced by high frequency pacemakers [2].

Recently, ANDRADE et al. [10] described a technique of plicature of the free wall of the LV (PLVFW) to reduce the LV in dogs, without the necessity of cardiopulmonary bypass (CPB).

The aim of this study was to evaluate the effects of this technique on the ventricular function in dogs with dilated heart disease induced by doxorrubicin.

METHOD

Experimental Groups

Thirteen crossbreed dogs weighing on average 14.3 kg were utilized. Five were submitted to PLVFW without induction of cardiomyopathy (Group I) and eight received intravenous injections of 30 mg/m2 of 0.2% doxorubicin (Adriblastina RD® -Pharmacia & Upjohn Ltda.) every 21 days until the shortened fraction of the LV was less than 20%, corresponding to a cumulative dose of 240 mg/m2. Of these animals, four were submitted to PLVFW (Group II) and two were not operated (Group III). The remaining two dogs died during the induction process and could not be included in the study. The animals received care according to the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council, published by the National Academy Press, revised 1996 (http://www.nap.edu/readingroom/books/labrats/chaps.html).

Clinical Evaluation

A physical examination, blood tests, serum biochemistry, computerized electrocardiogram (ECG) (TEB - ECGPC - Tecnologia Eletrônica Brasileira S.A.) and non-invasive mean blood pressure were performed one day before the operation and at one, two, seven, 15, 21, 30, 60, 90, 120, 150 and 180 days after the procedure. Continuous electrocardiography (Holter System; SpaceLabs - mod. 90208) was performed in the first 24 postoperative hours. Echocardiography (Pie Medical - mod. Pandion Vet) was performed in the same time intervals, except on the first postoperative day. The mean diameter and area of the LV at diastole and systole were obtained and the shortened fraction (EF) was calculated using the following formula: EF = {[(DLVd-DLVs)/DLVd] x 100}, where DLVd = internal diameter of the LV at diastole and DLVs = internal diameter of the LV at systole. The left ventricle volumes at diastole (VLVd) and at systole (VLVs) were obtained using the formula {V = 0.85 x [(A)2/L]} (where V = left ventricle volume, A = area of LV and L = long axis of the LV). The ejection fraction of the left ventricle (EjF) was obtained by the ratio between the diastolic and systolic volumes and the diastolic volume multiplied by 100 [11].

The cardiac output was measured by thermo-dilution [12] before and after the plicature, with the thorax closed.

Anesthetic induction and maintenance

Anesthesia was induced with propofol (Propofol® - Cristália Produtos Químicos e Farmacêuticos Ltda.) (8.0 ± 2.0 mg/kg iv) and maintained with sevoflurane (Sevorane® - Abbott Laboratórios do Brasil Ltda.), diluted with O2 (3.5V%), in a semi-closed anesthetic circuit. After the opening of the thorax the breathing was controlled.

Operative technique

Left lateral thoracotomy in the sixth intercostal space was performed, followed by T-shaped pericardiotomy. Three anchoring U-shaped sutures were made using 2-0 polypropylene thread (Prolene 2-0 agulhado - Ethicon Johnson & Johnson Produtos Profissionais Ltda.), fixed with bovine pericardium strips (Braile Biomédica Indústria, Comércio e Representação S.A) on the free wall of the LV, stretching from the apex to the third dorsal, below the left ventricular marginal branch [10], as can be seen in Figure 1. To avoid an excessive drop in the arterial pressure, the heart was partially dislocated, by lifting the tweezers fixed to the pericardium, only at the moment of making each stitch, repositioning it immediately after each stitch. The pericardium was not sutured and the thorax was closed in the normal manner.



Postoperative care

At the end of the operations, an intercostal block using bupivacaine (Neocaína® - Cristália Produtos Químicos Farmacêuticos Ltda.) (1.5 mg/kg) was performed. The dogs received tramadol (Tramal® - Searle/Monsanto do Brasil Ltda.) (1.5 mg/kg intramuscular at 8 hour intervals for three days), flunixim meglumine (Banamine® - Indústria Química e Farmacêutica Schering Plough S.A. - Divisão Veterinária) (1.1 mg/kg intramuscular at 24 hour intervals for three days) and ampicilina (Optacilin® - Byk Química e Farmacêutica Ltda) (22 mg/kg intramuscular at 24 hour intervals for seven days).

Statistical analysis

Analyses of repeated measurements over time were made for each of the evaluated variables, utilizing the mixed procedure of the SAS ® version 8.0 [13]. For the cardiac outflow, variance analysis with 2x2 factorial rearrangement was performed and for the variables of the Holter system, simple variance analysis was made. A significance level for a p-value of 0.05 was established.

RESULTS

Induction of dilated cardiomyopathy

All the animals in Groups II and III experienced a significant increase of the LV diameter at systole (mean 22.75 ± 1.78 mm to 30.84 ± 3.1 mm - p-value < 0.05) and at diastole (mean 33.53 ± 1.31 mm to 37.9 ± 3.9 mm - p-value < 0.01) after a cumulative dose 240 mg/m2 of doxorubicin. This condition reduced the EF from 31.67 ± 1.65 % to 17.50 ± 1.51% (p-value < 0.01) after induction. However, two dogs died due to congestive heart failure and ventricular arrhythmia during induction (cumulative dose 150 mg/m2).

Clinical evaluation

All the induced dogs demonstrated signs of intolerance to exertion and weak pulses, with a significant improvement after the operation. The operated dogs presented with a very fast rhythm in the immediate postoperative period. The dogs in Group III gradually deteriorated, with death due to acute pulmonary edema at 36 to 48 days after induction of cardiomyopathy.

A trans-operative ECG revealed ventricular extra-systoles during suturing of the myocardium, with one animal from Group I presenting with paroxistic ventricular tachycardia which improved with lidocaine (Lidol® - Hipolabor Farmacêutica Ltda.). A postoperative ECG and the Holter monitoring demonstrated isolated ventricular extra-systoles in pairs in bigeminal pulses and occasional paroxistic ventricular tachycardia, which spontaneously improved 48 hours after the operation. There was also an increase in the amplitude of the T-wave and a reduction in the amplitude of the R-wave in the first postoperative week.

The DLVd and the DLVs reduced significantly 48 hours after the operation. In Group I, the EF did not alter greatly, in Group II it increased significantly and in Group III it reduced drastically (Table 1, Figure 2). The increase in Group II was of about 38% in the immediate postoperative period (from 16.75% to 23.25%) and 114% on the 180th postoperative day (from 16.75% to 35.98%), but within the normal values from the 15th postoperative day.





The area and volume of the LV was significantly diminished in the operated groups and increased in Group III (Figures 3, 4 and 5). There was a significant increase of the EjF after the operation in Group II and gradual drop in Group III, with only slight changes in Group I (Table 2, Figure 6).











The cardiac output increased in Group I but without significance. In Group II however, this increase was significant (from 1,702 ± 0.2 vs. 2,315 ± 0.11 L/min - p-value < 0.1). The arterial pressure did not suffer alterations over the trial period.

COMMENTS

Induction of dilated cardiomyopathy by doxorrubicin was characterized by an increase in the DLVd and DLVs and reduced EF, in agreement to findings reported by TOYODA et al. [14] and MONNET & ORTON [15]. According to these authors the pharmacological therapeutic effects or operative techniques can be studied in experimental models of dilated cardiomyopathy induced by doxorrubicin, whose physiopathologic aspects are similar to idiopathic dilated cardiomyopathy.

Ventricular extra-systoles were observed during the suturing and in the first 48 postoperative hours. This arrhythmia was also observed by ANDRADE et al. [10] in 2001, and is possibly caused by mechanical irritation of the suturing process. The Holter system revealed ventricular extra-systoles and periods of paroxistic ventricular tachycardia, which disappeared after 48 hours, stressing the need of continuous electrocardiographic monitoring in the first 48 postoperative hours.

The increase in the amplitude of the T-wave observed in this study may have been caused by myocardial hypoxia [10,16]. However, this alteration was temporary demonstrating that the PLVFW did not cause irreversible electrocardiographic alterations.

There was a reduction in the left ventricular volume at diastole and systole, which is in agreement to the findings of ANDRADE et al. [10]. In this study, the EjF increased by 60.4% 180 days after the operation (from 37.5 to 60.17%). In humans suffering from dilated cardiomyopathy submitted to partial ventriculectomy, a reduction in the DLVd and DLVs were observed. Also an increase of the EjF was seen, which according to BESTETTI et al. [17] was of about 65% (29.0% before the operation to 48.0% 12 months after), according to GRADINAC et al. [18] this was about 50.1% (23.9% vs. 40.7%), for MOREIRA et al. [19] it was an increase of 33.9% (17.7% vs. 23.7%), according to LUCCHESE et al. [20] it was 39.8% (22.1% vs. 30.9%) and according to POPOVIC et al. [21] it was 70.8% (24.0% vs. 41.0%).

In cases of partial ventriculectomy in humans, medical therapy is not discontinued and, normally, the operation is performed with inotropic support. In this study, the dogs with dilated cardiomyopathy induced by doxorrubicin did not receive any medication for congestive heart insufficiency, not even positive inotropic agents. The EjF of the induced dogs that did not undergo surgery, gradually dropped until the dogs died. Thus, the improvement in the operated dogs was attributed to PLVFW. However, the sample utilized here was small suggesting that further studies are necessary with a greater sample size.

MCCARTHY et al. [2] in 2001 observed an increase in the EjF from 19.0% to 36% in the immediate postoperative period that remained at 39% one month after the implantation of a myosplint, which is an apparatus with three polytetrafluoroethylene pins in the myocardium of dogs with cardiomyopathy induced by high-frequency pacemakers. However, this procedure is more onerous, aggressive and harder work than PLVFW.

According to NAIR et al. [9], a complication of partial ventriculectomy is the resection of a portion of the potentially viable myocardium. With PLVFW no area was removed and the blood supply of the pleated region was guaranteed by the maintenance of the left ventricular marginal branch.

In humans submitted to partial ventriculectomy, cardiac indices obtained from the outflow divided by the body surface area in m2 were reported. According to Gradinac et al. [18], the cardiac index increased from 2.3 to 2.8 L/min/m2, while POPOVIC et al. [22] obtained an increase from 2.27 to 2.85 L/min/m2 and KONERTZ et al. [23] reported an increase from 1.8 to 2.9 L/min/m2. In this study, there was an increase in the outflow after PLVFW, which was significant in the dogs with cardiomyopathy induced by doxorrubicin.

CONCLUSIONS

Plicature of the left ventricle free wall without cardiopulmonary bypass reduced the area and volume of the left ventricle, which remained for a period of six months, both in healthy dogs as in those suffering from dilated cardiomyopathy induced by doxorrubicin. The surgical procedure was fast, with low morbidity and mortality.

ACKNOWLEDGEMENTS

We wish to thank the Foundation for the amplification of research in the State of São Paulo (FAPESP - Fundação de Amparo à Pesquisa no Estado de São Paulo) for the financial support of this research and to Dr. Adalberto Menezes Lorga for the interpretation of the Holter examinations.

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* Project financed Foundation for the amplification of research in the State of São Paulo (FAPESP - Fundação de Amparo à Pesquisa no Estado de São Paulo)

Article receive on Tuesday, April 1, 2003

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