In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 18 ( 1999-08-31), p. 10495-10500
Abstract:
Myoglobin may serve a variety of functions in muscular oxygen supply, such as O 2 storage, facilitated O 2 diffusion, and myoglobin-mediated oxidative phosphorylation. We studied the functional consequences of a myoglobin deficiency on cardiac function by producing myoglobin-knockout (myo −/− ) mice. To genetically inactivate the myoglobin gene, exon 2 encoding the heme binding site was deleted in embryonic stem cells via homologous recombination. Myo −/− mice are viable, fertile, and without any obvious signs of functional limitations. Hemoglobin concentrations were significantly elevated in myo −/− mice. Cardiac function and energetics were analyzed in isolated perfused hearts under resting conditions and during β-adrenergic stimulation with dobutamine. Myo −/− hearts showed no alteration in contractile parameters either under basal conditions or after maximal β-adrenergic stimulation (200 nM dobutamine). Tissue levels of ATP, phosphocreatine ( 31 P-NMR), and myocardial O 2 consumption were not altered. However, coronary flow {6.4 ± 1.3 ml⋅min −1 ⋅g −1 [wild-type (WT)] vs. 8.5 ± 2.4 ml⋅min −1 ⋅g −1 [myo −/− ]} and coronary reserve [17.1 ± 2.1 (WT) vs. 20.8 ± 1.1 (myo −/− ) ml⋅min −1 ⋅g −1 were significantly elevated in myo −/− hearts. Histological examination revealed that capillary density also was increased in myo −/− hearts [3,111 ± 400 mm −2 (WT) vs. 4,140 ± 140 mm −2 (Myo −/− )]. These data demonstrate that disruption of myoglobin results in the activation of multiple compensatory mechanisms that steepen the pO 2 gradient and reduce the diffusion path length for O 2 between capillary and the mitochondria; this suggests that myoglobin normally is important for the delivery of oxygen.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.96.18.10495
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1999
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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