title: Repetitive stretching during low-flow ischemia impairs function in isolated porcine hearts: a model for segmental dyskinesis.
abstract: Myocardial infarction appears after 20 min of regional no-flow ischemia in vivo, but only after a much longer duration of global ischemia in isolated hearts. We tested whether repetitive myocardial stretching (RMS), as occurs in segmental ischemia, is involved in the pathogenesis of myocardial cell injury. Furthermore, we evaluated the role of stretch-activated channels by using Gadolinium (Gd3+). Isolated piglet hearts were perfused with red cell enriched Krebs-Henseleit buffer. RMS was induced by inflating a balloon in the left ventricle, using a control system to provide a pressure of 120 mmHg during one-third of the cycle and 0 mmHg during the rest of the cycle, with a frequency 150 per min. Function and metabolism were compared during 2 h of low-flow ischemia (10% of control), with and without RMS, followed by 1 h of reperfusion. Non-RMS hearts were exposed to saline (Isch), or Gd3+ 25 micromol/l (Gd3+-Isch). During ischemia, left ventricular systolic pressure (LVSP) stabilized in non-RMS hearts, but a further decrease, combined with increased anaerobic metabolism occurred in RMS hearts. After 30 min of reperfusion in the non-stretched hearts, LVSP returned to 77+/-4% of control (mean+/-s.e.) in the Isch group, and to 74+/-2% in the Gd3+-isch group (between groups; P=n.s.). In hearts exposed to RMS, LVSP returned to only 46+/-4% of control (RMS) and to 51+/-3% in the Gd3+-RMS group (both P=0.01 v Isch). The same alterations were seen for LV dP/dt. In RMS hearts, tissue concentrations of ATP were reduced and concentrations of lactate increased. We conclude that stretching of ischemic myocardium severely increases anaerobic metabolism and reduces functional and metabolic recovery. Blockade of stretch activated channels by Gd3+ does not prevent this effect. Thus, the reduced recovery induced by RMS is due to factors other than ion fluxes through stretch-activated channels.
authors.affiliation: Institute for Experimental Medical Research, University of Oslo, Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Offstad
authors.forename: H
authors.initials: H
authors.lastname: Sommerschild
authors.forename: A
authors.initials: A
authors.lastname: Ilebekk
authors.forename: K A
authors.initials: KA
authors.lastname: Kirkebøen
authors.forename: S E
authors.initials: SE
authors.lastname: Downing
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D005682:Gadolinium / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D013314:Stress, Mechanical; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D005682:Gadolinium