[2] The functional significance of the coronary collateral vessels is a matter of continuing experimental investigation although their existence has been known for over three centuries and been documented repeatedly in man and beast over the past seven decades.
Although a now-classic series of experiments by Schaper[3] in the late 1960s and '70s expanded our understanding of the mechanisms by which these usually redundant, microscopic (40-10 um in diameter in their native state) ur-arterioles are transformed by ischemia or stenosis into vessels with life-preserving blood capacity,[4] equally as many studies[5] have denied the function of these vessels to preserve myocardium by salvaging tissue perfusion and maintaining blood pressure as have documented this.
The native collaterals are small vessels, with a narrow endothelial lining, a layer or two of smooth muscle, and a variable amount of elastic tissue.
They are rarely if ever observed during angiography in the absence of severe ischemia (vessels less than 200 micrometers are not visible, generally), and only coronary stenosis, anemia, and exercise have experimentally been shown to cause transformation.
Schaper summarizes the status-2009 knowledge of coronary collateral transformation in a recent review:[10] "Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells.
The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one.
A key role in this concerted action, which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human), are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the mitogen activated kinases ERK-1 and -2.
In spite of the enormous increase in tissue mass (up to 50-fold), the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal coronary conductance and 40% in the vascular periphery.
Rentrop did not generalize about the functional significance of these collaterals, which he said was "unknown," but their existence suggests that they may exert a preemptive, protective effect.
Subsequently, Rentrop's associate Cohen prospectively evaluated 23 patients undergoing PTCA and observed that during balloon inflation, the mean grade of collateral filling increased dramatically.
In another often-cited study,[9] Freedman focused on the issue of MI prevention by selecting 121 patients with severe single vessel disease.
Spasm resulted in mild angina associated with slight elevation of pulmonary artery end diastolic pressure and ST depression when collaterals were present rather than elevation and lower cardiac lactate production, suggesting strongly that collaterals do salvage myocardium when ischemia is produced by spasm.