Effect of Olprinone, Phosphodiesterase III Inhibitor, on Cerebral Blood Flow Assessed with Technetium-99m-ECD SPECT

Abstract

Few clinical reports exist regarding the effects of phosphodiesterase III inhibitors on cerebral arteries. Therefore we used a [99mTc]-ECD brain SPECT and an ultrasound method to quantitatively evaluate cerebral and systemic flow dynamics after the administration of olprinone, a phosphodiesterase III inhibitor. In 15 patients (65 +/- 8 years, M/F = 13/2) with no abnormalities on a brain computed tomography (CT), cerebral blood flow and cardiac output were measured using [99mTc]-ECD brain SPECT and Doppler echocardiography, respectively. Measurements were repeated at baseline and after the administration of olprinone. Significant increases in cerebral blood flow (p = 0.0007) and cardiac output (p = 0.001) were observed, and systolic blood pressure (p = 0.02) and systemic vascular resistance (p = 0.002) significantly decreased. No significant correlation between the increase in cerebral blood flow and the increase in cardiac output was observed. The data indicate that olprinone has a direct vasodilator effect on the cerebral artery, which was little related to the increase in cardiac output in patients who had not experienced stroke.

Olprinone: A Phosphodiesterase III Inhibitor with Positive Inotropic and Vasodilator Effects

“…Although olprinone increased cardiac output due to the positive inotropic action (2 to 48% increase in cardiac output), systemic vascular resistance decreased due to the vasorelaxant effect of the drug. There was no significant correlation between percentage change in CBF and cardiac output (50) (Fig. 3).…”

“…Previous studies have shown that rCBF is significantly reduced in patients with cerebral infarct areas, as compared to patients without lesions, because cerebrovascular resistance due to advanced arteriosclerosis or excessive vasoconstriction may have been increased in patients with cerebral infarction (27). The effect of olprinone on rCBF has little relation to hemodynamic changes, including cardiac output or systemic blood pressure (6,50). We considered that the effect of olprinone on rCBF is likely to be due to a direct action of the drug on the smooth muscle of small cerebral vessels (7,26,39).…”

“…It is also known to augment CBF of a normal cerebral cortex (50,51). We evaluated the effects of olprinone (0.2 ìg/kg/min) on CBF in heart failure.…”

Improvement of Cerebral Blood Flow by Olprinone, a Phosphodiesterase-3 Inhibitor, in Mild Heart Failure

“…In our previous study, the augmentation effect of olprinone on CBF showed no significant correlation with cardiac output measured by Doppler echocardiography in normal elderly subjects [7]. This may suggest that the acute increase in cardiac output due to the improvement in cardiac function is not important for an increase in CBF [2, 7]. In addition, we concluded that excessively fast responses of hormonal systems and cerebral vessels to the hemodynamic changes 15 min after the initiation of olprinone infusion were unlikely.…”

“…Olprinone, a phosphodiesterase-3 inhibitor, has been used to treat acute heart failure due to its positive inotropic and vasodilation effects, and it also augments CBF of the normal cerebral cortex [6, 7]. However, little data exist on the effects of olprinone on CBF in heart failure patients.…”