Microvascular and collateral adaptation in swine hearts following progressive coronary artery stenosis

Abstract

We chronically implanted hygroscopic occluders around the left circumflex coronary artery in 49 anesthetized young male domestic pigs and we studied the development of a collateral circulation at 4, 8, 12, and 26 weeks after implantation. At these time intervals groups of animals were again anesthetized, the hearts were explanted and perfused in Langendorff-fashion with leucocyte-filtered pig blood. Maximal coronary vasodilation was induced with adenosine and global (electromagnetic), and regional (tracer microspheres) blood flow was measured at 40, 60, 80, and 100 mm Hg of perfusion pressure. At 4 weeks after occluder implantation maximal left circumflex collateral blood flow was about 20% of normal maximal flow. Collateral flow rose to 60% of maximal normal flow between 4 and 8 weeks and did not improve further with longer time intervals. In contrast to the canine heart numerous small vessels develop in response to ischemia in the pig heart. These vessels develop throughout the entire risk region with a slight preference for the subendocardium. They appear on tomographic angiograms as a dense "blush". The study of the relationship between peripheral coronary pressure vs collateral flow showed a relationship much steeper than that of normal maximal flow vs aortic perfusion pressure which indicates that the minimal resistance of the risk region was decreased as part of the mechanism to ensure adequate blood supply in a situation of progressive coronary narrowing.

Elevated Fluid Shear Stress Enhances Postocclusive Collateral Artery Growth and Gene Expression in the Pig Hind Limb

“…That capillary sprouting is able to reduce minimal resistance was shown by us previously in the pig heart. 20 We had also shown previously that ischemia is not a requirement for arteriogenesis from experiments in the rabbit 10,21 and mouse hind leg. We therefore conclude that also under the conditions of venous drainage of collateral flow, ischemia had not influenced the development of collateral vessels in the upper leg.…”

Reactive hyperemia and BOLD MRI demonstrate that VEGF inhibition, age, and atherosclerosis adversely affect functional recovery in a murine model of peripheral artery disease

“…5B; or by atherosclerosis, Fig. 5C), mitigates the initial reduction in outflow peripheral resistance that can occur via capillary sprouting (31). This may secondarily alter the hemodynamics through the collateral pathway such that we shorten the time during which wall shear stress (WSS) is elevated and, therefore, able to induce complete large-vessel remodeling proximally.…”

“Flow and Rate”: Concept and Clinical Applications of a New Hemodynamic Theory

“…However several conditions supported the role of microcirculation, as the subendocardial resistance vessels are more sensitive to mediators of vasodilatation and endothelium dependent dilators (Pelc, 1987). In consideration of the short biological lifetime of NO (Doherty et al, 1998), and the maintained coronary ligation, the chosen model is known for poor coronary collaterals, in addition to the immature myocardium in young pig model (Gorge, et al 1989). This may be explained by an undiscovered endothelial mediator(s) that improved myocardial microcirculation in the group P. in group P. v. Reperfusion injury syndrome to be deleted, interestingly the study results showed that immediate myocardial reperfusion might be unnecessary.…”