Glucose Is Arrhythmogenic in the Anoxic-Reoxygenated Embryonic Chick Heart

Abstract

Unlike in adult heart, embryonic myocardium works at low PO2 and depends preferentially on glucose. Therefore, activity of the embryonic heart during anoxia and reoxygenation should be particularly affected by changes in glucose availability. Hearts excised from 4-d-old chick embryos were submitted in vitro to strictly controlled anoxia-reoxygenation transitions at glucose concentrations varying from 0 to 20 mmol/L. Spontaneous and regular heart contractions were detected optically as movements of the ventricle wall and instantaneous heart rate, amplitude of contraction, and velocities of contraction and relaxation were determined. Anoxia induced transient tachycardia and rapidly depressed contractile activity, whereas reoxygenation provoked a temporary and complete cardioplegia (oxygen paradox). In the presence of glucose, atrial rhythm became irregular during anoxia and chaotic-periodic during reoxygenation. The incidence of these arrhythmias depended on duration of anoxia, and no ventricular ectopic beats were observed. Removal of glucose or blockade of glycolysis suppressed arrhythmias. These results show similarities but also differences with respect to the adult heart. Indeed, glucose 1) delayed and anoxic contractile failure, shortened the reoxygenation-induced cardiac arrest, and improved the recovery of contractile activity; 2) attenuated stunning at 20 mmol/L but worsened it at 8 mmol/L; and 3) paradoxically, was arrhythmogenic during anoxia and reoxygenation, especially when present at the physiologic concentration of 8 mmol/L. The last named phenomenon seems to be characteristic of the young embryonic heart, and our findings underscore that fluctuations of glycolytic activity may play a role in the reactivity of the embryonic myocardium to anoxiareoxygenation transitions.

Oxidative and Glycogenolytic Capacities within the Developing Chick Heart

“…The findings that normalized glycogen content and glycogenolytic rate were the highest in atria clearly indicate that sinoatrial tissue could better tolerate combined O 2 /substrates deprivation. This is supported by the observations that sinoatrial spontaneous pacemaking activity can persist under anoxia, whereas ventricle and conotruncus stop (12,33,38). Thus, rhythmic activity of the sinoatrial region could be related to glycogenolytic metabolism, whereas myocardial contractility could depend preferentially on oxidative phosphorylation because mechanical loading increased O 2 consumption without modifying glycogenolysis and lactate production.…”

“…The embryonic myocardium (7-9) displays also a glycogen concentration 10 -20-fold higher than in the adult (3) and can tolerate a transient depletion of exogenous substrates in normoxia (10) or even recover rapidly from substrate-free anoxic episodes (11,12). Similar characteristics are found in fetal and neonatal hearts (13)(14)(15).…”

“…In such a heart, by contrast with the adult, mitochondria convert fatty acids to energy at a very low rate (1), whereas glycolysis contributes significantly to ATP production (2, 3) and glycogen turnover is rapid (4). Such metabolic features confer a benefit to the developing heart, because glucose requires less O 2 than fatty acids to produce a given amount of ATP, which is advantageous specially when O 2 availability is limited (5, 6).The embryonic myocardium (7-9) displays also a glycogen concentration 10 -20-fold higher than in the adult (3) and can tolerate a transient depletion of exogenous substrates in normoxia (10) or even recover rapidly from substrate-free anoxic episodes (11,12). Similar characteristics are found in fetal and neonatal hearts (13)(14)(15).…”

Differential contribution of mitochondria, NADPH oxidases, and glycolysis to region-specific oxidant stress in the anoxic-reoxygenated embryonic heart

“…Furthermore, the facts that glucose worsens ROS production (Fig. 5) and is arrhythmogenic at reoxygenation (85) and that the duration of ventricular arrhythmias was shortened by the antioxidant vitamin C at 10 mM (unpublished data) clearly indicate that transient oxidative stress contributes to the temporary reoxygenation-induced dysrhythmias. Endogenous vitamin C is present in the yolk sac membrane early during development of the chick (77) and may afford protection for the embryo against oxidant stress.…”

“…Glucose, which is known to prolong activity of the embryonic heart under anoxia but to be arrhythmogenic at reoxygenation (85), worsened oxidative stress during reoxygenation with no effect under normoxia (Fig. 5).…”