| Abstract: | Aftercontractions, delayed afterdepolarizations, and automaticity occurred in guinea pig papillary muscles that were reoxygenated after hypoxic conditioning. The emergence of dysfunction was dependent on the severity of hypoxic conditioning and on stimulation during reoxygenation. After 60 minutes of substrate-free hypoxia, reoxygenation induced automaticity in a high proportion of stimulated muscles; the automaticity appeared within 1 minute and lasted for 10-20 minutes. After similar conditioning, muscles reoxygenated for 7-15 minutes were stimulated at various cycle lengths. The incidence of automaticity and the amplitudes of delayed events had W-shaped dependencies on cycle length (200-1,000 msec), whereas coupling intervals had M-shaped dependencies. In ventricular myocytes that displayed automaticity after reoxygenation, extrasystolic upstrokes arose smoothly from delayed afterdepolarizations that reached threshold. In tissue, extrasystolic upstrokes usually rose sharply from delayed afterdepolarizations that were distinctly subthreshold. Thus, threshold was reached elsewhere in the tissue. Further evidence of electrical heterogeneity was obtained from surface mapping of delayed-afterdepolarization amplitude in reoxygenated muscle. There were no detectable aftercontractions, delayed afterdepolarizations, or signs of automaticity in quiescent reoxygenated muscles or in stimulated reoxygenated muscles that were treated with 1 microM ryanodine. We conclude that the dysfunction precipitated by reoxygenation is due to synchronized spontaneous releases of calcium from overloaded sarcoplasmic reticulum. |
