Experimental myocardial hypertrophy induced by a minimally invasive ascending aorta coarctation

Braz J Med Biol Res, March 2001, Volume 34(3) 413-415 (Short Communication)

Experimental myocardial hypertrophy induced by a minimally invasive ascending aorta coarctation

A.S. Martins¹, N.W. Aguilera¹, B.B. Matsubara² and E.A. Bregagnollo²

¹Departamento de Cirurgia e Ortopedia, and ²Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil

^Text

References

^{Correspondence and Footnotes}

Abstract

Ascending aorta coarctation was produced by a minimally invasive technique in rabbits. Animal mortality was 5%. Morphometric and hemodynamic parameters were evaluated. A parabiotically isolated heart model was used to assess the hemodynamic parameters. Left ventricular weight/body weight ratio and muscle area showed clear evidence of hypertrophy when compared to control. The hemodynamic changes in the isolated heart model suggested decreased diastolic and systolic function in the coarcted group. The present model produced hypertrophy with low mortality rates as a result of its less invasive nature.

Key words: ventricular hypertrophy, ventricular function, experimental model

Experimental models producing myocardial hypertrophy and ventricular dysfunction are of interest in heart research. These models permit the evaluation of drug effects, of myocardial protection methods, and of stunned myocardium recovery methods, among other possibilities. Several models have been proposed and different animals have been used. Several authors have described cardiac hypertrophy induced by drugs, coarctation of aorta or coarctation of the pulmonary artery (1-6). Aorta coarctation is frequently used in either the ascending or descending position. Ascending aorta coarctation is more similar to clinical conditions such as supravalvar congenital aortic stenosis. This technique, however, requires full sternotomy which is associated with up to 20% animal mortality (7,8). Minimally invasive methods are those which use small incisions by the endovascular technique or assisted video, and allow complex procedures to be carried out with less trauma (9). Our objective was to standardize a minimally invasive technique for ascending aorta coarctation in order to induce left ventricular anatomic and functional changes in rabbit hearts, with low surgical mortality.

For the proposed technique, after sodium pentobarbital anesthesia, a small transverse cervical incision is made above the sternal bone. After retrosternal dissection, the ascending aorta and its branches are identified and, under pericardiotomy, aorta coarctation is carried out according to the classic technique of Bregagnollo et al. (4). This technique was applied to 10 animals and the results were compared with those for age-matched, sham-operated rabbits (N = 10). After 5 weeks, the animals were euthanized with an anesthetic overdose for morphometric and functional study of the left ventricle according to the parabiotic model (use of a support animal). After the functional study, the atria were discarded and the right and left ventricles (including the septum) were separated and weighed. A 3-mm thick coronal section of the left ventricle was obtained, corresponding to the median portion of the chamber at the papillary muscle level. The transverse section area occuppied by the myocardium was obtained by scanning, using the Sigma Scan Pro^® software. The following functional parameters were analyzed: dP/dt+, defined as the maximum rate of systolic pressure increase; Dpmax, defined as maximum developed pressure, corresponding to the difference between systolic pressure and a diastolic pressure of 30 mmHg; Dstress, defined as developed stress, corresponding to the difference between systolic and diastolic stress, calculated when diastolic pressure was 30 mmHg; Kmyo, defined as the passive myocardial stiffness constant, which was determined for each animal by fitting the diastole stress (sd)-strain (e) data to an exponential relation, and DV, defined as the balloon volume required to increase diastolic pressure from zero to 30 mmHg, which is used as an index of ventricular compliance (10). All of these indexes are often used in similar preparations reported in the literature (11,12). The Student t-test was used for comparison of the two groups, with the level of significance set at 5%.

A mortality rate of 5% for the animals undergoing ascending aorta coarctation by this minimally invasive technique was considered low enough to demonstrate a technical advantage when compared to the traditional surgical approach (7,8).

The 5-week period of coarctation allowed the development of significant left ventricular concentric hypertrophy, which showed a mass increase of 50% compared to the sham-operated group. Myocardial growth was partially due to the reduction of the ventricular chamber (Table 1).

[print this table in landscape]

 

The objective of induced myocardial hypertrophy with ventricular dysfunction was reached as demonstrated by the results shown in Table 1. The studies performed on the isolated heart permitted the identification of systolic and diastolic function impairment.

Dpmax and dP/dt+ were maintained and Dstress was decreased in the hypertrophied ventricle. Although these results may seem conflicting, two factors should be taken into consideration: first of all, it has been reported that compensatory myocardial hypertrophy increases systolic function rates (13). Therefore, the findings of systolic function compared to control might indicate early decompensation. Secondly, left ventricular concentric hypertrophy provides favorable geometric conditions for the development of high isovolumetric pressure, overestimating the actual contractile condition of the myocardium (14). In this case, the most adequate contractility index would be Dstress. Therefore, we conclude that the coarcted animals presented ventricular systolic dysfunction. Moreover, diastolic function, evaluated by the ventricular compliance index (DV), was decreased and the passive myocardial stiffness constant (Kmyo) was abnormal, although with a significance level of 10%. This means a statistical trend to higher myocardial passive stiffness in this experimental model, indicating a biological significance which agrees with several studies of pressure-overload myocardial hypertrophy (15). The major cause of diastolic impairment is reported to be myocardial fibrosis (13), which was not evaluated in the present study. The decreased ventricular compliance might be caused by either the increased myocardial stiffness or the altered ventricular geometry. Thus, the decreased cavity surrounded by a thick wall is less capable of accommodating a given diastolic volume.

In conclusion, ascending aorta coarctation by a minimally invasive technique was effective in producing myocardial hypertrophy and ventricular dysfunction. In addition, the technique is easily performed and may become an optional method for surgical ascending aorta coarctation.

Address for correspondence: A.S. Martins, Departamento de Cirurgia e Ortopedia, Faculdade de Medicina de Botucatu, UNESP, 18618-000 Botucatu, SP, Brasil. E-mail: [e-mail]

Publication supported by FAPESP. Received January 7, 2000. Accepted January 3, 2001.

• 1. Taylor PB & Tang Q (1984). Development of isoproterenol-induced cardiac hypertrophy. Canadian Journal of Physiology and Pharmacology, 62: 384-389.
• 2. Taylor Q, Taylor PB & Helbing RK (1987). Catecholamine induced hypertrophy. Canadian Journal of Cardiology, 3: 311-316.
• 3. Hasenfuss G (1998). Animal models of human cardiovascular disease, heart failure and hypertrophy. Cardiovascular Research, 39: 60-76.
• 4. Bregagnollo EA, Rodrigues MAM, Montenegro MR, Curi PR & Tucci PJF (1986). Temporal evolution of structural and functional parameters of cardiac hypertrophy induced in Wistar rats by abdominal aorta constriction. Arquivos Brasileiros de Cardiologia, 46: 9-17.
• 5. Bing OHL, Matsushita S, Fanburg BL & Levine HJ (1971). Mechanical properties of rat cardiac muscle during experimental hypertrophy. Circulation Research, 28: 234-245.
• 6. Schlensak C, Sarai K, Gilden HP & Beyersdorf F (1997). Pulmonary banding with a novel percutaneously, bidirectionally adjustable device. European Journal of Cardiothoracic Surgery, 12: 931-933.
• 7. Bregagnollo EA, Cicogna AC, Spadadro J, Saiki OS & Tucci PJF (1981). Standardization of an experimental model of arterial hypertension capable to develop cardiac hypertrophy. Arquivos Brasileiros de Cardiologia, 36: 91-94.
• 8. Malhota A, Siri FM & Aronson R (1992). Cardiac contractile in hypertrophied and failing guinea pig heart. Cardiovascular Research, 26: 153-161.
• 9. Vanermem H (1998). What is minimally invasive cardiac surgery? Journal of Cardiovascular Surgery, 13: 268-274.
• 10. Shintani H & Glantz AS (1994). The left ventricular diastolic pressure-volume relation, relaxation, and filling. In: Gaasch WH & LeWinter MM (Editors), Left Ventricular Diastolic Dysfunction and Heart Failure. Lea & Febiger, Philadelphia, 57-88.
• 11. Gilson N, Houda BN, Corsin A & Crozatier B (1990). Left ventricular function and beta-adrenoceptors in rabbit failing heart. American Journal of Physiology, 258: H634-H641.
• 12. Ezzaher A, Houda BN, Su JB, Hittinger L & Crozatier B (1991). Increased negative inotropic effect of calcium-channel blockers in hypertrophied and failing rabbit heart. Journal of Pharmacology and Experimental Therapeutics, 257: 466-471.
• 13. Bing OHL, Sem S, Conrad CH & Brooks WW (1984). Myocardial function structure and collagen in the spontaneously hypertensive rat: progression from compensated hypertrophy to haemodynamic impairment. European Heart Journal, 5 (Suppl F): 43-52.
• 14. De Simone G, Deveraux RB, Volpe M, Camargo MJ, Wallerson DC & Laragh JH (1992). Relation of left ventricular hypertrophy afterload, and contractility to left ventricular performance in Goldblatt hypertension. American Journal of Hypertension, 5: 292-301.
• 15. Noma MP, Brandle M, Rupp H & Jacob R (1990). Left ventricular performance in rats with chronic overload due to arterio-venous shunt. Heart Vessels, 5: 65-70.

Correspondence and Footnotes

Publication Dates

• Publication in this collection
  16 Mar 2001
• Date of issue
  Mar 2001

History

• Accepted
  03 Jan 2001
• Received
  07 Jan 2000