Microembolization in pigs: effects on coronary blood flow and myocardial ischemic tolerance

Abstract

Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0–40 × 106, 15 μm in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 ± 1.5 (SE) + (5.8 ± 0.7 × 10−7 × number of injected microspheres). Because injection of 40 × 106 microspheres induced a long-lasting hyperemic response, which could be blocked by 8- p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 × 106microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 ± 3% of area at risk in control animals to 84 ± 6% ( P< 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.

Effect of metoprolol on myocardial apoptosis after coronary microembolization in rats

“…It has been reported that the microembolized myocardium is characterized by perfusion-contraction mismatch, reduced contractile function and unchanged or possibly elevated blood flow. [17,18] Since cardiomyocytes are non-renewable cells, the loss of cardiomyocytes via apoptosis may play an important role in the progression of myocardial contractile dysfunction. The mechanisms of myocyte cell death include apoptosis and necrosis, with early research confirming that myocyte cell death by apoptosis is likely in the beginning hours of ischemia, and that myocyte cell death by necrosis is evident after long-term ischemia.…”

Koronare Mikroembolisation: Perfusions-Kontraktions-Mismatch durch inflammatorische Reaktion des Myokards

“…Wiederholte intrakoronare Injektionen (Enddosis 3 000 Mikrosphären pro ml/min koronaren Einstroms) bewirken unmittelbar nach jeder Injektion eine transiente Reduktion der Koronardurchblutung, der eine länger andauernde reaktive Durchblutungserhöhung folgt (Abbildung 1). Grund für die Zunahme der Koronardurchblutung nach Mikroembolisation, trotz mechanischer Verlegung des Gefäßbetts durch Embolisationspartikel, ist die Freisetzung vasodilatatorischer Mediatoren, die in benachbarten Gefäßen eine Vasodilatation bewirkt [19,26]. Im Gegensatz zur Koronardurchblutung erholt sich die myokardiale Funktion nach jeder Injektion nur teilweise und wird mit jeder erneuten Mikroembolisation immer mehr reduziert (Abbildung 1) [35].…”

Coronary microembolization does not induce acute preconditioning against infarction in pigs?the role of adenosine

“…Subsequently, myocardial function is progressively reduced whereas coronary blood flow remains unchanged or is even increased (perfusion -contraction mismatch) [2,3]. The increase in coronary blood flow is attributed to vasodilation of adjacent nonembolized vessels in response to adenosine release from the ischemic microembolized myocardium [4,5]. The progressive myocardial contractile dysfunction in the presence of normal or increased blood flow following microembolization is associated with an inflammatory response, characterized by increased leukocyte infiltration and increased tumor necrosis factor-a (TNFa) concentration within the myocardium [2].…”

“…This adenosine dilates vessels in the adjacent non-embolized myocardium and increases myocardial blood flow [4,5]. Adenosine is an important trigger of ischemic preconditioning (IP) in many species including pigs [8] and also humans [9].…”