Angiogenesis and surgical or endovascular enhancement of noncoronary collateral circulation: A new research field

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CTSNet classification: 18, 23, 26

To the Editor:

We read with great interest the article by Atluri and colleagues,¹ and we congratulate them for their experiments with myocardial perfusion and contractility improvement using a laser transmyocardial approach. We agree with the authors that the problem with myocardial revascularization in patients who might not benefit from conventional procedures still demands investigative efforts. This was the genesis of a research program we began at Laval University in Quebec and that we are going to start in Europe at Université Paris Sud. This program is aimed at the enhancement of noncoronary collateral circulation (NCCC). Our animal models are dogs (Canada) and pigs (France).

NCCC is a topic that is virtually ignored, with very few publications in existence. This is surprising, considering that it is not rare to find evidence of NCCC, such as during coronary bypass surgery when arterial blood flow comes from the coronary ostia during valve replacement surgery or from the incised coronary artery, despite adequate aortic crossclamping and venting. NCCC consists of a network of small channels that come from mediastinal, bronchial, and pericardial vessels and that enter the heart through the pericardial reflections surrounding the pulmonary and systemic veins, as well as through the vasa vasorum of the aorta and pulmonary artery leading to and from the myocardium. Our studies are premised on the belief that this network is bigger than generally thought and that it might play a role, if adequately enhanced, as an alternative means of myocardial blood supply. We also believe that the normal ventricular function sometimes seen in patients with occlusion of the 3 major coronary vessels can be evidence of myocardial nourishment related to such a collateral source. Previous studies² have shown that vascular connections exist between the internal thoracic arteries (ITAs) and myocardium and that surgical bilateral ligation of the ITAs creates a local hypertensive status, increasing the perfusion pressure within the channels leading to the heart.³

Before cardiopulmonary bypass became widespread, some groups in Italy² and the United States³ performed ligation of the ITAs in canine models and human subjects with ischemic heart disease. Reported results were promising: angina disappeared, correlating with the disappearance of ischemic signs at electrocardiography. We believe that these data should be re-explored with the help of modern technology. Our hypothesis⁴, ⁵ has been that administration of angiogenic growth factors combined with distal occlusion of the ITAs might enhance angiogenesis of NCCC. We performed surgical ligature of the ITAs distally, and vascular endothelial growth factor was administered into the occluded arteries. Intuitively, occlusion by means of endovascular embolization is possible as well. It is known that the ITAs have high plastic potential, being capable of developing major branches that work as the only source of blood in extreme cases of lower limb ischemia.⁶ Hence myocardial ischemia should also be able to stimulate noncoronary collateral blood flow, preferably diverting this to the diseased area rather than to the chest wall.

It will be neither easy nor quick to demonstrate such theories, but our current studies represent a parallel, alternative research field, moving in the same direction of laser transmyocardial revascularization.

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References 

1. Alturi P, Panlilio CM, Liao GP, Suarez EE, McCormick RC, Hiesinger W, et al. Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function. J Thorac Cardiovasc Surg. 2008;135:283–291.e1
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2. Battezzati M, Tagliaferro A, De Marchi G. La legatura delle due arterie mammarie interne nei disturbi di vascolarizzazione del miocardio. Minerva Med. 1955;46:1178–1188
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3. Glover RP, Davila JC, Khyle RH, Beard JC, Trout RG, Kitchell JR. Ligation of the internal mammary arteries as a means of increasing blood supply to the myocardium. J Thorac Surg. 1957;34:661–678
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4. Picichè M, Kingma JG, Fadel E, Dagenais F, Robillard J, Simard D, et al. Enhancement of noncoronary collateral circulation: the hypothesis of an alternative treatment for ischemic heart disease. Med Hypotheses. 2010;74:21–23
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5. Picichè M, Kingma JG, Fadel E, Dagenais F, Mathieu P, Simard D, et al. Enhancement of noncoronary collateral blood flow from the internal thoracic arteries: the theoretical and practical basis of an alternative method of myocardial blood supply. J Cardiovasc Surg. In press.
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