BACKGROUND: Several nonischemic stimuli have been shown to precondition myocardium. We investigated cardioprotective effects and underlying mechanisms of brief pressure overload of the left ventricle in this study. METHODS: Brief pressure overload of the left ventricle was achieved by two 10-minute partial snaring of the ascending aorta so that systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. Ten minutes after different pretreatments, myocardial infarction was induced by a 60-minute coronary artery occlusion followed by 3-hour reperfusion. Area at risk and myocardial infarct was determined by blue dye injection and triphenyl tetrazolium chloride staining. RESULTS: The myocardial infarct size, expressed as percentage of area at risk, was significantly reduced in the pressure overload group (15.9% +/- 2.9%, p < 0.001, n = 9) as well as in the ischemic preconditioning group (14.9% +/- 1.9%, p < 0.001, n = 9) versus the control group (30.0% +/- 6.9%, n = 10). Pretreatment with a blocker of stretch-activated ion channels (gadolinium, 40 micromol/kg, intravenous) abolished the protection induced by pressure overload and ischemic preconditioning. Gadolinium itself did not alter the extent of infarct. There was no significant difference in hemodynamics, area at risk, and mortality among all groups of animals. CONCLUSIONS: Brief pressure overload of the left ventricle by partial snaring of the ascending aorta preconditioned rabbit myocardium against infarction. The underlying mechanism might be related to activation of stretch-activated ion channels.
BACKGROUND: Several nonischemic stimuli have been shown to precondition myocardium. We investigated cardioprotective effects and underlying mechanisms of brief pressure overload of the left ventricle in this study. METHODS: Brief pressure overload of the left ventricle was achieved by two 10-minute partial snaring of the ascending aorta so that systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. Ten minutes after different pretreatments, myocardial infarction was induced by a 60-minute coronary artery occlusion followed by 3-hour reperfusion. Area at risk and myocardial infarct was determined by blue dye injection and triphenyl tetrazolium chloride staining. RESULTS: The myocardial infarct size, expressed as percentage of area at risk, was significantly reduced in the pressure overload group (15.9% +/- 2.9%, p < 0.001, n = 9) as well as in the ischemic preconditioning group (14.9% +/- 1.9%, p < 0.001, n = 9) versus the control group (30.0% +/- 6.9%, n = 10). Pretreatment with a blocker of stretch-activated ion channels (gadolinium, 40 micromol/kg, intravenous) abolished the protection induced by pressure overload and ischemic preconditioning. Gadolinium itself did not alter the extent of infarct. There was no significant difference in hemodynamics, area at risk, and mortality among all groups of animals. CONCLUSIONS: Brief pressure overload of the left ventricle by partial snaring of the ascending aorta preconditioned rabbit myocardium against infarction. The underlying mechanism might be related to activation of stretch-activated ion channels.
Authors: André Uitterdijk; Tirza Springeling; Kevin C M Hermans; Daphne Merkus; Vincent J de Beer; Charlotte Gorsse-Bakker; Eric Mokelke; Evangelos P Daskalopoulos; Piotr A Wielopolski; Jack P M Cleutjens; W Matthijs Blankesteijn; Frits W Prinzen; Willem J van der Giessen; Robert-Jan M van Geuns; Dirk J Duncker Journal: Basic Res Cardiol Date: 2017-04-06 Impact factor: 17.165