This study was designed to determine whether the end-systolic pressure-length relationship (ESPLR) reflects changes in regional contractility during the imposition of graded ischemia, and whether it is modified by diltiazem during propofol anesthesia. Seven beagles were anesthetized and instrumented to measure left ventricular pressure and subendocardial segment lengths (sonomicrometry) in the region of the left anterior descending (LAD) and circumflex (LC) arteries. Afterload was increased by the tightening of a snare around the descending thoracic aorta. Pressure-length loops were constructed and the slope of the ESPLR and the x-axis intercept, Lo, were calculated. Graded ischemia of the apical myocardium only was accomplished by the tightening of a micrometer-controlled snare around the LAD to produce Critical Constriction (CC), Ischemia 1 and 2 (I1, I2), and Total Occlusion (TO). In the basal LC region, LAD ischemia had no effect on either the ESPLR slope or Lo. In contrast, the ESPLR slope in the LAD area was decreased by ischemia at I1 (-40%), increased at TO (+69%), and unchanged at CC and I2, and was reduced by diltiazem at CC and I2 (-31% and -36%, respectively). The LAD ESPLR Lo was increased by ischemia by 64% and 61% at I2, and 91% and 122% at TO, before and after diltiazem, respectively. In the LC region, diltiazem decreased systolic shortening and the ESPLR slope. These results indicate that diltiazem has negative inotropic properties in both ischemic and nonischemic areas. Also, Lo is not a constant and must always be redetermined for every intervention. In the absence of ischemia, the ESPLR may be a reliable measure of myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)