Biomedical subjects

Youngran Chung

Publications and source records attributed to Youngran Chung.

4 recordsLinked to original sources

PubMed2006

Implication of CO inactivation on myoglobin function.

Myoglobin (Mb) has a purported role in facilitating O2 diffusion in tissue, especially as cellular PO2 drops or the respiration demand increases. Inhibiting Mb with CO under conditions that accentuate the facilitated diffusion role should then elicit a significant physiological response. In one set of experiments, the perfused myocardium received buffer with decreasing PO2 (225, 129, and 64 mmHg). Intracellular PO2 declined, as reflected in the 1H NMR Val E11 signal of MbO2 (67%, 32%, and 18%). The addition of 6% CO further reduced the available MbO2 (11%, 9%, and 7%), as evidenced by the decline of the MbO2 Val E11 signal intensity at -2.76 ppm. In a second set of experiments, electrical stimulation increased the heart rate (300, 450, and 540 beats/min) and correspondingly the O2 consumption rate (MVO2). Intracellular PO2 also declined, as reflected in the slight drop in the MbO2 signal (100%, 96%, and 82%). MVO2 increased (100%, 114%, 165%). The addition of 3% CO in the stimulated hearts further decreased the available MbO2 (46%, 44%, and 29%). In all cases, CO inactivation of Mb does not induce any change in the respiration rate, contractile function, and high-energy phosphate levels. Moreover, the MbCO/MbO2 partition coefficient shifts dramatically from its in vitro value during hypoxia and increased work. The observation suggests a modulation of an intracellular O2 gradient. Overall, the experimental observations provide no evidence of a facilitated diffusion role for Mb in perfused myocardium and implicate a physiologically responsive intracellular O2 gradient.

Animals↗

PubMed2006

Oxygen reperfusion is limited in the postischemic hypertrophic myocardium.

Studies have shown that hypertrophied hearts are unusually vulnerable to ischemia. Compromised O2 supply has been postulated as a possible explanation for this phenomenon on the basis of elongated O2 diffusion distance and altered coronary vasculature found in hypertrophied myocardium. To examine the postulate, perfused heart experiments followed the metabolic and functional responses of hypertrophic myocardium to ischemia. 1H/31P NMR was used to measure cellular oxygenation and energy level during ischemia-reperfusion. The left ventricles from spontaneously hypertensive rats (SHR) were enlarged by 48%. With this moderate degree of hypertrophy, cellular O2 and energy levels were normal during baseline perfusion. After an ischemic episode, however, cellular O2 was severely deprived in the SHR hearts compared with the normal hearts. Depressed postischemic O2 reperfusion correlated well with depressed energetic and functional recovery. The results from the current study thus demonstrate a critical relationship between reperfused O2 level and functional recovery in hypertrophic myocardium. The role of reperfused O2, however, is time dependent. During early reperfusion, factor(s) other than O2 appear to limit functional recovery. It is when the mechanical function of the heart approaches a new steady state that O2 becomes a dominant factor. Meanwhile, the finding of a normal O2 level in preischemic SHR hearts defies the notion of preexisting hypoxia as a primer of ischemic damage.

Animals↗

PubMed2004

Control of respiration and bioenergetics during muscle contraction.

(1)H-NMR experiments have determined intracellular O(2) consumption (Vo(2)) with oxymyoglobin (MbO(2)) desaturation kinetics in human calf muscle during plantar flexion exercise at 0.75, 0.92, and 1.17 Hz with a constant load. At the onset of muscle contraction, myoglobin (Mb) desaturates rapidly. The desaturation rate constant of approximately 30 s reflects the intracellular Vo(2). Although Mb desaturates quickly with a similar time constant at all workload levels, its final steady-state level differs. As work increases, the final steady-state cellular Po(2) decreases progressively. After Mb desaturation has reached a steady state, however, Vo(2) continues to rise. On the basis of current respiratory control models, the analysis in the present report reveals two distinct Vo(2) phases: an ADP-independent phase at the onset of contraction and an ADP-dependent phase after Mb has reached a steady state. In contrast to the accepted view, the initial intracellular Vo(2) shows that oxidative phosphorylation can support up to 36% of the energy cost, a significantly higher fraction than expected. Partitioning of the energy flux shows that a 31% nonoxidative component exists and responds to the dynamic energy utilization-restoration cycle (which lasts for only milliseconds) as postulated in the glycogen shunt theory. The present study offers perspectives on the regulation of respiration, bioenergetics, and Mb function during muscle contraction.

Adenosine Diphosphate↗

PubMed2003

Role of myoglobin in regulating respiration.

The 1H NMR Val E11 signal provides a unique opportunity to observe carbon monoxide (CO) inhibition of Mb in the in vivo myocardium and to assess the functional role of Mb in regulating respiration. Upon carbon monoxide infusion, the MbO2 Val E11 signal at -2.76 ppm gradually disappears, and a new signal at -2.26 ppm, corresponding to MbCO, emerges. These signals yield the intracellular partial pressure of both O2 and CO and the extent of Mb inactivation, since CO binds more tightly to Mb than O2. Although contractile function decreases slightly to a steady state level, it shows no dose dependence on pCO. Up to 80% MbCO saturation, the contractile function remains at the steady state level. Neither the PCr concentration nor the oxygen consumption rate is significantly perturbed. Above 80% MbCO saturation, the oxygen consumption rate starts to decline. The experimental observations raise provocative questions about the functional role of Mb in the cell.

Animals↗