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Ann Thorac Surg 2004;77:2011
© 2004 The Society of Thoracic Surgeons

Invited commentary

UC Clinical Centre of Serbia, Institute for Cardiovascular Diseases, Clinic for Cardiac Surgery, 8th Kosta Todorovic St 11000 Belgrade, Serbia and Montenegro, Slovak Republic

e-mail: kocica{at}sezampro.yu

In their paper, Friehs and colleagues show that performance of hypertrophied myocardium can be preserved by inducing therapeutic angiogenesis, with a single dose of VEGF-165, given into the pericardial sac. Their previous results have demonstrated numerous deleterious effects that accompany the concentric hypertrophic response of the rabbit heart, exposed to pressure overload.

In this study, 10-day-old rabbits, divided into two experimental groups (VEGF treated and untreated) were exposed to pressure overload for 4 weeks. The control group consisted of age-matched, nonhypertrophied, untreated animals. Progression and extent of myocardial hypertrophy (LV mass to volume and LV to body weight ratio), and in-vivo functional parameters (midwall contractility) were followed echocardiographically. In order to test their hypothesis, that therapeutic angiogenesis could increase vascular density and thus ensure further benefits to the hypertrophied heart (increased substrate availability, increased tolerance to ischemic-reperfusion injury, and later onset of dilatation and failure), they performed a series of additional and elegant morphometric, metabolic, and isolated functional and perfusion measurements.

In this series of generally well-thought-out and well-structured experimental studies, several burning questions, spanning "from cell to bedside", deserve emphasis.

1. Is it possible to match the compensatory myocardial hypertrophy and blood vessel density? According to the reported morphometric analyses in different groups of experimental animals, Friehs and colleagues proved such possibility. Similarly, the capillary-to-myocyte ratios, in control and VEGF treated hypertrophied groups, emphasize the necessity of enhancing the natural angiogenic potential in pressure overloaded hearts, to maintain homeostasis of myocardial tissue units (ie, to raise the nautural equilibrium between capillaries and myocytes to a higher level).

2. What is the crucial change in a complex array of interactive events that is responsible for the transition from compensatory cardiac hypertrophy to heart failure? Although a single answer is difficult, the authors focused their attention mainly on the metabolic arena. Both structural (increased diffusion distance) and functional changes (impaired glucose transport) proved responsible for ischemic-reperfusion vulnerability and consecutive contractile dysfunction of the hypertrophied myocardium. Applied VEGF treatment, again, showed similar changes in control and VEGF treated hypertrophied groups.

3. Could the knowledge, gained from this particular study, be easily transformed into everyday clinical practice? This may be the most important question. The experimental model and design of this study was meant to simulate a population of pediatric cardiac surgical patients. It is well-known that pressure-overload myocardial hypertrophy in children (and thus, probably, in 10-day-old rabbits, as well) demonstrates a proportional angiogenic response, whereas in adults, hypertrophy appears to be associated with failure of compensatory angiogenesis. Also, we must bear in mind completely different mechanisms of short- and long-term adjustments in myocardial growth in response to functional load. These are points that may be considered in future reports. Apart from that, this study verifies the pharmacokinetic advantages and possible clinical benefits of intrapericardial administration of angiogenic cytokines. And finally, a very important lesson of wider scope and direct application to clinical practice, is that all compensatory mechanisms inevitably become insufficient and deleterious.

Friehs and colleagues merit praise for their contributions to this important and very difficult area of research.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Mladen J. Kocica Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kocica, M. J. Search for Related Content PubMed Articles by Kocica, M. J. Related Collections Cardiac - other