Altered left ventricular diastolic properties during pacing-induced ischemia in dogs with coronary stenoses. Potentiation by caffeine.

Publisher Website
Google Scholar
Abstract
An upward shift of the left ventricular (LV) diastolic pressure-volume relation was observed during angina in humans and was recently induced by pacing tachycardia in dogs with coronary stenoses. To assess the mechanism of this phenomenon, the effects of caffeine (an agent known to prolong intracellular Ca availability) were studied on the upward shift of the LV diastolic pressure-volume relation induced by pacing tachycardia in dogs with coronary stenoses. Severe (90%) coronary artery stenoses were produced on both the left anterior descending and circumflex coronary arteries in 14 chloralose-anesthetized, .beta.-blocked dogs with chest and pericardium open. In 6 dogs, 2 pairs of ultrasonic crystals were implanted subendocardially in the ischemic areas. The left atrium was paced at a rate of 1.5 times the resting heart rate for 3 min. In the immediate post-pacing period there was a rise of the left ventricular end-diastolic pressure (LVEDP) from 9 .+-. 1 to 15 .+-. 1 mm Hg (P < 0.005) at comparable peak-systolic pressures and slightly increased end-diastolic segment lengths (16.8 .+-. 0.9 mm to 17.5 .+-. 0.9 mm) (P < 0.005). After the return of LV hemodynamics to baseline values, atrial pacing was repeated at a rate and blood pressure comparable to the 1st pacing run but with the administration of caffeine (20 .+-. 4 mg/kg, i.v.) in the last 30 s of pacing. In the post-pacing period the LVEDP rose from 9 .+-. 1 to 27 .+-. 2 mm Hg (P < 0.005) at comparable peak systolic pressures and slightly increased end-diastolic segment lengths (16.8 .+-. 0.9 mm to 17.3 .+-. 1.0 mm) (P < 0.05). The increased LV filling pressure persisted 3 times longer than in the control pacing run and was associated with a marked upward shift of the LV diastolic pressure-segment length and pressure-volume relation. The same dose of caffeine, when given in the non-ischemic (control) setting, produced a transient (< 1 min) fall in LV peak systolic pressure (112 .+-. 6 to 97 .+-. 3 mm Hg, P < 0.005), LVEDP (9 .+-. 1 to 7 .+-. 1 mm Hg, P < 0.01) and end-systolic segment length (14.8 .+-. 0.9 to 14.3 .+-. 0.9 mm, P < 0.005) consistent with a peripheral vasodilatory effect of caffeine. Caffeine potentiates the ischemia-induced changes in LV diastolic stiffness. These findings could be explained by sustained intracellular Ca availability with persistent contractile element interaction in diastole.