| INSIGHTS FROM MYOGLOBIN KNOCKOUT MICE
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| Access to embryonic stem cells and complementary DNA fragments permits selected gene disruption in whole animals. With deletion of exon 2 in the gene encoding mouse Mb, three genotypes could be compared: wild-type, heterozygous, and homozygous null (or knockout). Quite unexpectedly, mice lacking Mb exhibited no obvious phenotypic abnormalities under normal conditions or even during exercise or hypoxia. Thus, Mb does not appear to be essential for normal cardiovascular, musculoskeletal, and reproductive function. However, this 'normal' phenotype was the result of numerous compensatory mechanisms, all of which contributed to a steeper pO2 gradient between the capillary and the mitochondrion. Some of the adaptations were increased capillary density, more rapid coronary flow, transition to fast-twitch myofibers, and elevated Hb concentration.
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These findings have prompted a reappraisal of the function of Mb in muscle tissues. In the knockout animals the development of broad compensatory measures strongly suggests that Mb is normally important in facilitating O2 diffusion and maintaining mitochondrial electron transport, particularly in muscles that produce slow, repetitive, and forceful activity. In the fast-twitch muscles of Mb-deficient mice, however, there is a significant increase in nitric oxide (NO), a potent vasodilator and an inhibitor of electron transport. This has led to the intriguing idea that Mb, with a recognized capacity to convert NO to nitrate, may be a key mediator of O2 delivery and a regulator of O2 utilization.
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| HYPERVENTILATION, NUMBNESS, AND DIZZINESS |
| A college student with severe muscle spasms in her arms, numbness in her extremities, some dizziness, and respiratory difficulty was brought to the student health center. The patient had been vigorously exercising in an attempt to relieve the stress of forthcoming examinations when she suddenly began to experience forced, rapid breathing. Suspecting hyperventilation, a health care worker began to reassure the student and helped her recover by getting her to breathe into a paper bag. After 20 minutes the spasms ceased, feeling returned to her fingers, and the lightheadedness resolved. |
| Comment. Alveolar hyperventilation is an abnormally rapid, deep, and prolonged breathing pattern that leads to respiratory alkalosis, i.e. a profound decrease in pCO2 and an increase in blood pH that can be attributed to the increased loss of CO2 from the body. With decreased [CO2] and [H+], two allosteric effectors of O2 binding and release, the affinity of Hb for O2 increases sufficiently to reduce the efficiency of delivery of O2 to peripheral tissues, including the central nervous system. Another characteristic of alkalosis is a decreased level of ionized calcium in plasma, a situation that contributes to muscle spasms and cramps. In general, hyperventilation may be triggered by hypoxemia, pulmonary and cardiac diseases, metabolic disorders, pharmacologic agents, and anxiety. |
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