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

In animal and human models, left ventricular (EV) diastolic function has be en 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 dob utamine stress echocardiography. Eight mongrel dogs, in which were inserted a high-fidelity micromanometer LV catheter, coronary sinus sampling cathet er, and ultrasonic coronary artery flow probe, underwent intravenous dobuta mine infusion at escalating doses both before (control protocol) and after (ischemia protocol) creation of left anterior descending coronary artery st enosis with hydraulic cuff occluder adjusted to maintain resting coronary a rtery flow but attenuate reactive hyperemia, At each dobutamine dose, epica rdial short-axis 2-dimensional echocardiographic images and hemodynamic mea surements 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 ind ex 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) prot ocol (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 ? was observed at the dobutamine dose bef ore the dose at which an echocardiographic wall motion abnormality was firs t recognized. Dobutamine-induced ischemia is associated with abnormal LV di astolic function. In addition, these abnormalities seem to occur early in t he development of ischemia. These observations extend to pharmacologically induced ischemia prior findings from other models of ischemia, suggesting t he high sensitivity of LV diastolic function to the development of myocardi al ischemia.