ATP release by cardiac myocytes in a simulated ischaemia model: inhibition by a connexin mimetic and enhancement by an antiarrhythmic peptide.

We studied the role of connexin hemichannels in the release of ATP by neonatal cardiac myocytes subject to ischaemic stress. Mechanical, osmotic and oxidative stress and changes in extracellular or intracellular Ca(2+) levels induce connexin hemichannels located in the plasma membrane to open and release small ions and molecules with signaling potential such as ATP. Since ATP release has been implicated in adaptation to oxygen deprivation, we studied its release by cardiac myocytes incubated in a custom-built hypoxia chamber for various periods. In a simulated ischaemia model (0.5% oxygen and 0.2 g/l glucose) a peak of ATP release occurred at 80 min followed by a return to steady state levels for a further 200 min. This peak of ATP release was not observed in myocytes subject to hypoxia (0.5% oxygen, 3.0 g/l glucose). ATP release in ischaemia was influenced by two classes of reagents that target connexins, the channel forming proteins of gap junctions. First, the connexin hemichannel inhibitors Gap 26 and 18a glycyrrhetinic acid abolished the ATP peak of release. Second, the AAP10, a peptide with antiarrhythmic properties markedly increased the peak of ATP release observed at 80 min of ischaemia and also induced a second smaller peak at 180-240 min. ATP content of the myocytes and Cx43 phosphorylation were monitored. Since the release of ATP in ischaemia was abolished by connexin channel inhibitors and stimulated by a peptide developed to target connexins in the context of cardiac arrhythmia, the results suggest that nucleotide release by connexin hemichannels is likely to feature in the response of myocytes to ischaemic stress in the heart.

Holotropic Breathwork: the potential role of a prolonged, voluntary hyperventilation procedure as an adjunct to psychotherapy.

OBJECTIVES: To pose the question of whether Holotropic Breathwork (HB), a prolonged, voluntary hyperventilation procedure, might be useful in treatment of common psychiatric conditions such as anxiety and depressive disorders. DESIGN: This is a hypothesis-posing paper pertaining to a potential novel treatment. SUMMARY: The neurophysiology and psychology of hyperventilation are reviewed, including findings demonstrating that hyperventilation leads to significant changes in central nervous system activity as measured by various technological means. Preliminary evidence suggesting efficacy for HB is reviewed. A tentative biopsychologic hypothesis is offered, suggesting a potential mechanism that may underlie putative therapeutic effects of HB. Specifically, when HB is used in the context of ongoing psychotherapy, hyperventilation may facilitate generalized extinction of avoidance behaviors, resulting in therapeutic progress. Individuals high in trait absorption and social desirability who have failed to respond adequately to psychotherapy might be those most likely to respond to HB. Recommendations for future research directions examining the therapeutic potential of HB are offered. CONCLUSIONS: Further research using more sophisticated methodologies than have been used to date will be necessary in order to confirm or refute the hypothesis that HB may be useful in treatment of psychiatric disorders.