Anoxic energy production and contractile activity in mammalian cardiac muscle.

Contractile activity of electrically driven left atria of guinea pigs was measured auxotonically under normoxic and anoxic conditions at various frequencies and temperatures in Krebs-Henseleit solution containing 15 mM glucose. At 35 degrees C, a frequency of 0.5 Hz and anoxia ("anoxia test") reduced contractile activity was observed, lasting 6.6 +/- 1.55 hr. Under normoxic conditions at 0.5 Hz and 35 degrees C the contractile work per beat (cwb) amounts to 35% of the maximum reached at 1.5 Hz, according to the force-frequency relationship. The total contractile work per hr only comes up to 5% of the maximum reached at 4.0 Hz. The oxygen consumption at 0.5 Hz only exceeds the value of resting atria by 10%. A positive inotropic peak of short duration observed directly after acute anoxia can be antagonized by beta-receptor blockade. Then contractile activity decreases during the first half hr of anoxia to around 20%-30% of the initial value under oxygen. In the second phase, the reduced contractile activity recovers and is stabilized at a level between 50%-80% of the control value during the first and second hour of anoxia and then decreases slowly during the following hours. The recovery period of anoxic contractile activity coincides with the time-dependent increase of the lactic acid production rate which reaches a maximum after around 1 hr of anoxia. This can also explain why the rapid decrease of ATP (30%) and creatine phosphate (CP) (90%) during the first 20 min is stabilized at this reduced value during the 2 hr of anoxia studied. Related to the measured oxygen consumption during normoxia, the glucose consumption increases during anoxia in resting atria approximately 300% and, in beating atria, approximately 650%, representing an ATP production rate of approximately 20% and approximately 50%, respectively, related to aerobic conditions. G-strophanthin enhances anoxic contractile activity up to 200% of the aerobic initial control value and prolongs the anoxic tolerance from 6.6 +/- 1.55 to 21.2 +/- 3.3 hr without significant additional increase of glycolysis or a further decrease of energy-rich phosphates. Addition of adenine and ribose as precursors of the adenine nucleotide pool during the first and second hours of anoxia increases anoxic contractile activity and avoids loss of ATP, ADP, and CP, without enhancemnt of glycolysis. The importance of these findings for anoxic survival of cardiac tissue is discussed. This "anoxia test" can be used to check influence on: 1) force and duration of anoxic contractile activity as well as anoxic arrhythmias (anoxic energy consumption), 2) the rate of anaerobic glycolysis (anoxic energy production), and 3) the concentration of energy-rich phosphates (energy storage).