Coronary vasodilation by isoflurane. Abrupt versus gradual administration

Under certain circumstances, isoflurane is associated with coronary artery vasodilation. The objective of the current study was to ascertain whether the rate of administration of isoflurane influences its vasodilating effect in the coronary circulation.

Seven open-chest dogs anesthetized with fentanyl and midazolam were studied. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs; reservoir 1 (control) was supplied with arterial blood free of isoflurane, and reservoir 2 was supplied with blood from an extracorporeal oxygenator, which was provided with 95% O2/5% CO2 gas that passed through calibrated vaporizer. Coronary blood flow (CBF) was measured with Doppler flow transducer. In each dog, isoflurane was administered according to two protocols; abrupt (isoflurane-A) or gradual (isoflurane-G). In isoflurane-A, the left anterior descending coronary artery was switched from reservoir 1 to reservoir 2 after the latter was filled with blood previously equilibrated with 1.4% (1 MAC) isoflurane. In isoflurane-G, the left anterior descending coronary artery was switched to reservoir 2 with vaporizer set at 0% isoflurane; then the vaporizer was adjusted to 1.4% isoflurane, which produced a gradual increase in isoflurane concentration within reservoir 2 that reached a level equivalent to that in isoflurane-A (as evaluated by gas chromatography) by 30 min. CBF during maximally dilating, intracoronary infusion of adenosine served as a reference to assess effects of isoflurane.

Isoflurane-A caused marked increases in CBF, which, at constant perfusion pressure, reflected pronounced reductions in vascular resistance. These increases in CBF were 80% of those with adenosine. Although isoflurane-G also caused increases in CBF, the increases were only 45% of those caused by isoflurane-A.

The current findings demonstrate that the extent of coronary vasodilation by isoflurane was not dependent only on its blood concentration but also on the rate at which this blood concentration was achieved; a gradual increase in blood concentration blunted the vasodilator effect. Differences in the rate of administration of isoflurane likely contributed to its widely variable coronary vasodilating effects in previous studies.