IPAVA are large diameter 15-500 μm (up to 1000 μm) vascular conduits, present in >95% of healthy humans, while PFO is present in ~ 1/3 of general population and both represent possible source of right to left shunt. In Study I we investigated the effects of nitroglicerine, norepinephrine and aminophylline on opening and recruitment of intrapulmonary arteriovenous anastomoses in healty humans at rest. We found that these drugs applied in above named doses did not seem to modify the filtering capability of the lung in healthy humans at rest which speakes in fovour that drugs are not affecting the large-diameter inducible intrapulmonary arteriovenous anastomoses by direct effect on opening and recruitment of the IPAVA (via receptors) nor indirect (via increase in pressure and flow). Despite their various vasoactive and hemodynamic effects, none of the drugs caused a substantial increase in QT and/or PASP, stimuli previously shown to passively open IPAVA. Finally, application of these drugs, in named doses, does not open the pathway for systemic micro/embolization of vital organs. However, further research is needed to examine their effect on IPAVA during physical activity intensities required for ordinary daily activities or in moderate and strenuous exercise as well as in others than healthy subjects. In Study II we examined the potential contributions of blood flow through IPAVA and PFO to arterial hypoxaemia in subjects with CHF with and without pulmonary hypertension. We found that arterial hypoxaemia at rest was present in CHF PH+ subjects with PFO. Given that blood flow through IPAVA was absent or insignificant, even in those subjects with pulmonary hypertension, we conclude that blood flow through IPAVA is not influenced by increased pulmonary pressures and does not contribute to arterial hypoxaemia in these subjects. Whether or not PFO contributes to exercise-induced arterial hypoxaemia in subjects with CHF remains unknown. Data from our study and previous data indicate that aging process may negatively affect IPAVA, assuming that blood flow through IPAVA is reduced with increasing age. We still need to investigate what consequences, if any, are associated with this decline. Also, in this study we have shown excellent correlation between detection and quantification of right to left shunt (blood flow through IPAVA and /or PFO) using transthoracic contrast echocardiography and transcranial Doppler. Thus, both methods can be used for the same purpose which is especially important when performing one of them is not suitable or possible. Surgical closure of the PFO may be undertaken for various reasons, such as history of stroke or transient ischaemic attack, yet PFO closure for this purpose remains controversial. However, because PFO contributes to arterial hypoxaemia in subjects with CHF and pulmonary hypertension, these specific subjects may also benefit from PFO closure as an intervention to improve oxygenation, particularly in those subjects with more severe levels of hypoxaemia. IPAVA have been known to exist for over 50 years, but their physiological and clinical significance are still being established; although, currently suggested roles for IPAVA include allowing emboli to reach the systemic circulation, also serve as a parallel vascular network that under certain conditions open to divert potentially damaging hydrodynamic energy from fragile pulmonary capillaries thus creating the right to left shunt which could adversely affect the pulmonary gas exchange. Studying blood flow through IPAVA, as well as through PFO, is an important area of research and as the suggested roles become better established, detecting and quantifying flow throug IPAVA and PFO may become significantly more important in the clinic.