Coronary smooth muscle reactivity to muscarinic stimulation after ischemia-reperfusion in porcine myocardial infarction

Abstract

This study tested whether ischemia-reperfusion alters coronary smooth muscle reactivity to vasoconstrictor stimuli such as those elicited by an adventitial stimulation with methacholine. In vitro studies were performed to assess the reactivity of endothelium-denuded infarct-related coronary arteries to methacholine (n = 18). In addition, the vasoconstrictor effects of adventitial application of methacholine to left anterior descending (LAD) coronary artery was assessed in vivo in pigs submitted to 2 h of LAD occlusion followed by reperfusion (n = 12), LAD deendothelization (n = 11), or a sham operation (n = 6). Endothelial-dependent vasodilator capacity of infarct-related LAD was assessed by intracoronary injection of bradykinin (n = 13). In vitro, smooth muscle reactivity to methacholine was unaffected by ischemia-reperfusion. In vivo, baseline methacholine administration induced a transient and reversible drop in coronary blood flow (9.6 +/- 4.6 to 1.9 +/- 2.6 ml/min, P < 0.01), accompanied by severe left ventricular dysfunction. After ischemia-reperfusion, methacholine induced a prolonged and severe coronary blood flow drop (9.7 +/- 7.0 to 3.4 +/- 3.9 ml/min), with a significant delay in recovery (P < 0.001). Endothelial denudation mimics in part the effects of methacholine after ischemia-reperfusion, and intracoronary bradykinin confirmed the existence of endothelial dysfunction. Infarct-related epicardial coronary artery shows a delayed recovery after vasoconstrictor stimuli, because of appropriate smooth muscle reactivity and impairment of endothelial-dependent vasodilator capacity.

Single Intracoronary Injection of Encapsulated Antagomir‐92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling

“…To investigate the potential myocardial toxicity and the safety range of therapeutic dosage, the 2 injections of 30 mg fluorescently labeled ME (Figures and ) and 2 progressively higher doses ( Figures and ) in successive injections (120 and 240 mg fluorescently labeled ME, n=2) were administered in the LAD of healthy pigs. Two pairs of piezoelectric crystals were implanted in anterior and posterior myocardium, respectively . Injections caused minor and rapidly reversible depressions of segment shortening in the LAD territory as measured with the piezoelectric crystals.…”

“…When the anterior left ventricular contraction is completely dissipated, EDL=ESL and SS=0. The normal values range between 0.2±0.1 . Coronary flow in LAD and hemodynamic parameters such as aortic pressure (Ao pressure), heart rate (HR), left ventricle pressure (LV pressure), and its derivative left ventricular dP / dT (LV dP / dT ) obtained with a 1.4 F micromanometer tipped conductance catheter (Millar Instruments Inc, Houston, TX) were simultaneously monitored and recorded with a multiple recording system (Chart 5 program for Windows).…”

“…Two pairs of piezoelectric crystals were implanted in anterior and posterior myocardium, respectively. 23 Injections caused minor and rapidly reversible depressions of segment shortening in the LAD territory as measured with the piezoelectric crystals. Segment shortening and LAD flow remained stable after the last injection.…”

“…The normal values range between 0.2AE0.1. 23 Coronary flow in LAD and hemodynamic parameters such as aortic pressure (Ao pressure), heart rate (HR), left ventricle pressure (LV pressure), and its derivative left ventricular dP/dT (LV dP/dT) obtained with a 1.4 F micromanometer tipped conductance catheter (Millar Instruments Inc, Houston, TX) were simultaneously monitored and recorded with a multiple recording system (Chart 5 program for Windows). The graphics show minimal and transitory separation of ischemic pair of crystals lasting a few seconds with any prolonged or irreversible ischemic effect after the first intracoronary injection of 15 mg of fluorescein isothiocyanate albumin-PLGA microspheres.…”

Estudo anatômico das artérias coronárias de suínos Landrace

“…Deste modo, pesquisas utilizando artérias coronárias de suínos em experiências para observar a ação de substâncias são freqüentes na literatura especializada, Cinca et al (1996) com a metacolina; Horstick et al (1997) com C1 esterase; Nakayama (2001) com a tripsina; Dogne et al (2005) com trombose induzida pelo cloreto férrico. Também são citadas na literatura observações em coronárias de suínos sobre isquemia e reperfusão (Koichi et al 2003, Rodriguez-Sinovas et al 2003 bem como a utilização das coronárias de suínos em cirurgias (Paul et al 1997, Donias et al 2003, Scheule et al 2004, Melchior et al 2005) ou ainda como parte importante nos xenotransplantes, (McGregor et al 2004, Cox & Zhong 2005, McGregor 2005.…”