Coronary collateral reserve during exercise induced ischemia in swine

Abstract

We determined coronary collateral vasodilator reserve during exercise-induced ischemia in 17 mini-swine. We induced coronary collateral development in the left circumflex bed by placing an ameroid occluder on that artery. Four weeks later we studied the animals at rest and during exercise (EX) eliciting heart rates (HR) of 240 and 265 beats/min. We measured myocardial blood flow with microspheres and myocardial function by wall thickness sonomicrometry gauges. At matched exercise HRs we treated the animals with nifedipine (10 micrograms/kg IV) (EXN 10), nifedipine (100 micrograms/kg IV), (EXN 100), and adenosine infusion (1.2 mg/min/kg) EXAD. EXN 10 did not significantly alter hemodynamics compared to EX but EXN 100 and EXAD both decreased blood pressure significantly (p less than 0.05). Ischemic endocardial/nonischemic endocardial flow ratios and collateral resistance served as indices of vasodilator reserve. In the ischemic zone exercise reduced vasodilator reserve to 24 +/- 3% in the endocardium and 64 +/- 7% in the epicardium. Neither EXN 10 nor EXAD improved exercise-induced ischemia measured either as flow or function. However EXN 100 improved function during exercise-induced ischemia without improving coronary collateral flow. We conclude there is no additional coronary flow reserve during exercise-induced ischemia in the collateral dependent bed of the pig a few days after occlusion that can be recruited. Large doses of nifedipine improve function by direct action on the myocardium or by reducing afterload. The lack of development and deep myocardial distribution of the coronary collateral vessels in the pig may be an important factor of why these nifedipine responses differ from those reported in species which have primarily large epicardial coronary collaterals.

A minimally invasive method for induction of myocardial infarction in an animal model using tungsten spirals

“…The coronary artery system closely resembles the human situation, as does the ratio of heart weight to body weight [18,40]. However, existing collaterals in pig hearts are always open and no additional collaterals can be recruited during an ischemic episode [18,39]. That is why cardiac ischemia is poorly tolerated by pigs and relatively short ischemic periods often lead to fatal arrhythmias and rapid development of necrosis [41].…”

“…Although pigs are extremely susceptible to preoperative stress and therefore require efficient premedication to reduce the risk of arrhythmia [39], pig hearts have several properties that are of particular interest for the study of myocardial ischemia or infarction. The coronary artery system closely resembles the human situation, as does the ratio of heart weight to body weight [18,40]. However, existing collaterals in pig hearts are always open and no additional collaterals can be recruited during an ischemic episode [18,39].…”

“…Pigs appear to be superior to dogs as models of myocardial infarction because they are anatomically closer to humans in that each coronary artery only supplies a specific cardiac region and adequate collaterals are lacking [18,19]. The aim of our study is to present a minimally invasive, closed-chest model of acute myocardial infarction in pigs induced by placement of tungsten spirals for occlusion of the left circumflex artery (LCX).…”

Endothelium-Mediated Relaxation of Porcine Collateral-Dependent Arterioles Is Improved by Exercise Training

“…Similarly, exercise training enhances collateral development and regional myocardial perfusion in the porcine model of chronic coronary occlusion. 2,3,25,26 Furthermore, exercise training has been shown to improve myocardial function in patients with ischemic cardiomyopathy 27 and to stimulate blood flow to the myocardium via native and developing collaterals. 3 Therefore, exercise training may act as a nonpharmacological therapeutic strategy 20,21 to enhance collateral development and/or stimulate cellular pathways (ie, flow-and shear stress-dependent signaling mechanisms) involved in ecNOS regulation and induce beneficial adaptations of collateral-dependent microvascular endothelium.…”

Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts.

“…Using this technique, O'Konski et al (16) demonstrated that after 3-4 wk of gradual coronary artery occlusion, pigs develop a significant increase in coronary collateral blood flow to the compromised area reaching almost same level as the flow in the normal area at rest. However, the territory supplied by the ameroid-constricted artery is clearly ischemic during exercise or pharmacological vasodilation (17). The nature of this limitation remains unclear and it has been variously ascribed to new collaterals possessing less smooth muscle than normal arterioles (12), having impaired function (18) or simply to an insufficient number of collaterals forming in the ischemic territory.…”