Abnormal global left ventricular relaxation occurs early during the development of pharmacologically induced ischemia

In animal and human models, left ventricular (LV) diastolic function has been observed to be highly sensitive to myocardial ischemia. The response of LV diastolic parameters to pharmacologically induced ischemia, however, has not been characterized and might be important in the interpretation of dobutamine stress echocardiography. Eight mongrel dogs, in which were inserted a high-fidelity micromanometer LV catheter, coronary sinus sampling catheter, and ultrasonic coronary artery flow probe, underwent intravenous dobutamine infusion at escalating doses both before (control protocol) and after (ischemia protocol) creation of left anterior descending coronary artery stenosis with a hydraulic cuff occluder adjusted to maintain resting coronary artery flow but attenuate reactive hyperemia. At each dobutamine dose, epicardial short-axis 2-dimensional echocardiographic images and hemodynamic measurements were obtained. LV diastolic function was examined by calculation of peak (-)dP/dt and the time constant of isovolumic relaxation (tau). The dobutamine infusion protocol was terminated on the earliest recognition of an anterior wall motion abnormality. Peak (+)dP/dt normalized for developed isovolumetric pressure was calculated as a relatively load-independent index of global LV contractile function. Dobutamine infusion with and without ischemia resulted in comparable changes in heart rate and (+)dP/dt/IP, with no change in LV end-diastolic or -systolic pressure. The magnitude of peak (-)dP/dt increased less during the ischemia (1231 +/- 109 to 1791 +/- 200 mm Hg/sec) versus the control (1390 +/- 154 to 2432 +/- 320 mm Hg/sec) protocol (P <.05). Similarly, the observed decrease in tau was less during the ischemia (53 +/- 3 to 38 +/- 4 msec) than the control (51 +/- 5 to 23 +/- 3 msec) protocol, corresponding to a slower rate of relaxation (P <.05). In addition, the smaller decrease in tau was observed at the dobutamine dose before the dose at which an echocardiographic wall motion abnormality was first recognized. Dobutamine-induced ischemia is associated with abnormal LV diastolic function. In addition, these abnormalities seem to occur early in the development of ischemia. These observations extend to pharmacologically induced ischemia prior findings from other models of ischemia, suggesting the high sensitivity of LV diastolic function to the development of myocardial ischemia.