Extracardiac to coronary anastomoses support regional left ventricular function in dogs

Abstract

Intramyocardial implantation of a systemic artery [the internal mammary artery (IMA)] causes angiogenesis, with formation of systemic to coronary anastomoses. In dogs, we assessed the magnitude of IMA-derived nutritive flow and determined its influence on regional contraction. We also sought to determine whether acidic fibroblast growth factor (FGF), an angiogenic peptide, could enhance myocardial neovascularization. Ameroid constrictors and hydraulic balloon occluders were placed on the left anterior descending coronary artery (LAD) of 23 dogs, and the left IMA was implanted in the LAD territory. Dogs were randomized to receive continuous infusions of acidic FGF with heparin, heparin alone, or placebo directly into the IMA for 8 wk. Regional myocardial blood flow was assessed in the conscious state 3 days and 8 wk after operation. Left ventricular function was determined in the anesthetized state at the 8-wk conclusion of treatment. In all dogs, IMA occlusion reduced mean maximal LAD zone perfusion by 28% (P < 0.001), without influencing regional contraction. When IMA occlusion was superimposed on left circumflex coronary artery (LCX) occlusion, LAD zone perfusion declined by 34% (relative to LCX occlusion alone), significantly impairing regional contraction. Treatment with either acidic FGF plus heparin or heparin alone improved IMA-derived collateral flow; however, addition of acidic FGF to heparin afforded no additional advantage over heparin by itself. We conclude that acidic FGF did not enhance myocardial angiogenesis in this model. IMA-derived collateral flow has significant functional importance; however, it is evident in the dog only when other sources of collateral flow are compromised.

Extracardiac coronary arterial anastomoses

“…They also noted that myocardial ischemia was the most important factor providing a stimulus for the proliferation of the collateral arteries during the angiogenic treatment. In a later study, they concluded that the extracardiac anastomoses were capable of providing significant support for the improvement of left ventricular function (Unger et al, 1993). This research highlights the therapeutic possibilities for controlled vascular development and angiogenesis (Unger et al, 1990).…”

Untitled

“…Although therapeutic angiogenesis has been studied intensively as an alternative treatment for ischemic vascular diseases using growth factors such as VEGF, aFGF, bFGF or PDGF, these factors take a period of approximately 3 days to 3 weeks to act (1)(2)(3)(4)(5)(6)(7)(8), while myocardial necrosis in the acute severe coronary occlusion area occurs very rapidly within a matter of hours (4,(9)(10). The consequence is that fibrous tissue grows rapidly despite the relative ischemic condition, which replaces the infarcted heart tissues and also blocks the space for any newly-regenerated myocyte replacement.…”

Noncoronary Collateral Myocardial Blood Flow: The Human Heart’s Forgotten Blood Supply

“…More recently (1993), Unger et al confirmed in canine models that implanting ITAs in intramyocardial tunnels improved ITA-derived collateral blood flow, provided nutritive supply, and improved left ventricular function. Also, continuous infusion of heparin, rather than acid fibroblast growth factor, promoted new ITA-related collateral anastomoses [ 74 - 76 ]. Another example of the ITAs’ potential for collateralization was seen following imperfect coronary surgery, where blood flow was impeded by stenosis at the ITA-to-coronary artery anastomotic site, and eventually by graft occlusion in its middle-distal portion.…”