Effects of pretreatment with caffeine or ryanodine on the myocardial response to simulated ischaemia.

1. The cytoplasmic calcium concentration ([Ca]c) of rat isolated atrial myocardium was assessed with the dye indo-1. Dye-loaded atria were superfused with physiological salt solution and excited with radiation at 360 nm, while epifluorescence emissions were collected simultaneously at 400 nm and 500 nm. The ratio of these emissions was used as a measure of [Ca]c. 2. Dye-loaded atria showed a phasic rise and fall in [Ca]c with each applied electrical pacing stimulus. The amplitude of these oscillations was reduced by the presence of caffeine (10(-3)-10(-2) M) or of ryanodine (10(-8)-10(-6) M) in a concentration-dependent manner. 3. Atria superfused with a solution the composition of which resembled that found extracellularly in regions of myocardial ischaemia rapidly lost systolic increments in [Ca]c, while end-diastolic [Ca]c values gradually rose. 4. Pretreatment with caffeine (10(-2) M) or ryanodine (10(-7) M) protected atria against the rise in end-diastolic [Ca]c that occurred when the tissue was exposed to conditions of simulated ischaemia.