Correlation of cardiac performance with cellular energetic components in the oxygen-deprived turtle heart

Abstract

The relationship between cardiac energy metabolism and the depression of myocardial performance during oxygen deprivation has remained enigmatic. Here, we combine in vivo (31)P-NMR spectroscopy and MRI to provide the first temporal profile of in vivo cardiac energetics and cardiac performance of an anoxia-tolerant vertebrate, the freshwater turtle (Trachemys scripta) during long-term anoxia exposure (approximately 3 h at 21 degrees C and 11 days at 5 degrees C). During anoxia, phosphocreatine (PCr), unbound levels of inorganic phosphate (effective P(i)(2-)), intracellular pH (pH(i)), and free energy of ATP hydrolysis (dG/dxi) exhibited asymptotic patterns of change, indicating that turtle myocardial high-energy phosphate metabolism and energetic state are reset to new, reduced steady states during long-term anoxia exposure. At 21 degrees C, anoxia caused a reduction in pH(i) from 7.40 to 7.01, a 69% decrease in PCr and a doubling of effective P(i)(2-). ATP content remained unchanged, but the free energy of ATP hydrolysis (dG/dxi) decreased from -59.6 to -52.5 kJ/mol. Even so, none of these cellular changes correlated with the anoxic depression of cardiac performance, suggesting that autonomic cardiac regulation may override putative cellular feedback mechanisms. In contrast, during anoxia at 5 degrees C, when autonomic cardiac control is severely blunted, the decrease of pH(i) from 7.66 to 7.12, 1.9-fold increase of effective P(i)(2-), and 6.4 kJ/mol decrease of dG/dxi from -53.8 to -47.4 kJ/mol were significantly correlated to the anoxic depression of cardiac performance. Our results provide the first evidence for a close, long-term coordination of functional cardiac changes with cellular energy status in a vertebrate, with a potential for autonomic control to override these immediate relationships.

Beating oxygen: chronic anoxia exposure reduces mitochondrial F1FO-ATPase activity in turtle (Trachemys scripta) heart

“…Indeed, during anoxia at 5°C, heart rate and cardiac power output of T. scripta decreases progressively over the first 3days and stabilises at values that are 5 and 20% of normoxic values, respectively (Stecyk et al, 2004). The exact mechanisms behind the downregulation of cardiac function are still being elucidated (Stecyk et al, 2009) Normoxia-(black circles, N=5) and anoxia-exposed (white circles, N=5) turtle heart mitochondria were subjected to stepwise changes in respiration rate and membrane potential by injecting increasing amounts of malonate (1mmoll −1 steps with a final concentration of 16mmoll…”

“…to be contributing factors in the anoxic decline in heart rate and aortic blood flow (Stecyk et al, 2009). Elevated P i , intracellular acidosis and a reduction in ∆fG′ ATP are known to depress cardiac function directly through a reduction in Ca 2+ sensitivity, a diminished activation of actin-myosin cross-bridges, and a lowering of the phosphorylation potential (Bers, 2001).…”

“…Free (Golding et al, 1995;Teague et al, 1996) (Pörtner et al, 1996;Stecyk et al, 2009). Tissue P i concentrations were taken directly from Stecyk et al (Stecyk et al, 2009), who exposed T. scripta to a similar anoxic treatment.…”

“…Tissue P i concentrations were taken directly from Stecyk et al (Stecyk et al, 2009), who exposed T. scripta to a similar anoxic treatment. ∆fG′ ATP values are expressed as kJmol −1 (more negative values indicate greater free energy available from the hydrolysis of ATP).…”

Temperature dependence of 1H NMR chemical shifts and its influence on estimated metabolite concentrations

“…Recently, the use of alternative animal models for in vivo MR studies in experimental medicine or in comparative physiology have gained increasing interest, including those that use birds [25], lower vertebrates such as amphibians [26], fishes [27], and invertebrates [28]. The body temperatures of these organisms are usually far away from 37 °C or depend on their environmental temperature (ectothermic animals) that can range from very low temperatures around the freezing point of water [29] up to 40 °C and higher in insects [30].…”