REPETITIVE STRETCHING DURING LOW-FLOW ISCHEMIA IMPAIRS FUNCTION IN ISOLATED PORCINE HEARTS - A MODEL FOR SEGMENTAL DYSKINESIS

Myocardial infarction appears after 20 min of regional no-flow ischemi a 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 stre tch-activated channels by using Gadolinium (Gd3+). Isolated piglet hea rts were perfused with red cell enriched Krebs-Henseleit buffer. RMS w as induced by inflating a balloon in the left ventricle, using a contr ol system to provide a pressure of 120 mmHg during one-third of the cy cle 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 isch emia (10% of control), with and without RMS, followed by 1 h of reperf usion. Non-RMS hearts were exposed to saline (Isch), or Gd3+ 25 mu mol /l (Gd3+-Isch). During ischemia, left ventricular systolic pressure (L VSP) stabilized in non-RMS hearts, but a further decrease, combined wi th 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 th e 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 t he Gd3+-RMS group (both P=0.01 nu Isch). The same alterations were see n for LV dP/dt. In RMS hearts, tissue concentrations of ATP were reduc ed and concentrations of lactate increased, We conclude that stretchin g of ischemic myocardium severely increases anaerobic metabolism and r educes functional and metabolic recovery Blockade of stretch activated channels by Gd3+ does not prevent this effect. Thus, the reduced reco very induced by RMS is due to factors other than ion fluxes through st retch-activated channels. (C) 1997 Academic Press Limited.