Oxygen reperfusion is limited in the postischemic hypertrophic myocardium

Abstract

Chung, Youngran. Oxygen reperfusion is limited in the postischemic hypertrophic myocardium. Am J Physiol Heart Circ Physiol 290: H2075-H2084, 2006; doi:10.1152/ajpheart.00619.2005.-Studies have shown that hypertrophied hearts are unusually vulnerable to ischemia. Compromised O 2 supply has been postulated as a possible explanation for this phenomenon on the basis of elongated O 2 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.1 H/ 31 P 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 O 2 was severely deprived in the SHR hearts compared with the normal hearts. Depressed postischemic O 2 reperfusion correlated well with depressed energetic and functional recovery. The results from the current study thus demonstrate a critical relationship between reperfused O 2 level and functional recovery in hypertrophic myocardium. The role of reperfused O 2, however, is time dependent. During early reperfusion, factor(s) other than O 2 appear to limit functional recovery. It is when the mechanical function of the heart approaches a new steady state that O 2 becomes a dominant factor. Meanwhile, the finding of a normal O 2 level in preischemic SHR hearts defies the notion of preexisting hypoxia as a primer of ischemic damage. left ventricular hypertrophy; myocardial ischemia; spontaneously hypertensive rat; nuclear magnetic resonance HYPERTROPHIED HEARTS show an increased susceptibility to ischemia (1,9,15, 31,39,53,55). The concentric left ventricular (LV) hypertrophy (LVH) is an adaptive response to chronic pressure overload, which involves multistep signaling pathways. After a period of compensated hypertrophic state, the hemodynamics of hypertrophic hearts gradually deteriorate and often culminate in heart failure. However, even before it develops overt hemodynamic failures, hypertrophic myocardium frequently displays signs of abnormalities, including an increased susceptibility to ischemia. Consequently, LVH is an independent risk factor for patients undergoing heart surgery. LVH is also characterized by diminished mechanical and energetic responses to the functionally ischemic conditions induced by high-workload challenges (6).Inflammatory and oxidative signals, including TNF-␣ or oxygen free radicals, might contribute to the increased susceptibility of hypertrophic myocardium to ischemia (31, 55). Yet many studies have also demonstrated an altered energy metabolism in LVH and have suggested a cellular hypoxia (15,41,61,64). Consistent with possible O 2 limitation, a depressed O 2 consumption in the hypertrophic myocardium, especially under low perfusion pressure, has...

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