Does Patent Foramen Ovale Size Matter in Men and Women

Study Overview
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Brief Summary
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A patent foramen ovale (PFO) is present in  30% of the general population. The PFO has historically been considered to be trivial. However, recent work by the investigator's group and others has identified that, compared to individuals without a PFO, those with a PFO have worse pulmonary gas exchange efficiency, have a higher core body temperature, blunted ventilatory responses to chronic hypoxia and acute carbon dioxide and increased susceptibility to altitude illnesses such as acute mountain sickness, and high altitude pulmonary edema (Lovering, Elliott & Davis J Appl Physiol 2016). Specific to this application,subjects with a PFO may have worse pulmonary gas exchange efficiency because a PFO is a potential source of right-to-left shunt that will make pulmonary gas exchange efficiency worse. If true, then this may negatively impact exercise capacity and/or exercise tolerance. Further, in those with a PFO compared to those without, preliminary work from the investigator's lab indicates that there may be an effect of PFO size on pulmonary gas exchange efficiency. This is such that those with a large PFO (grade 3 or higher) display significantly worse gas exchange efficiency compared to those with a small (grade 2 or lower) or no PFO,even at low exercise workloads. Additionally, the investigators were curious as to whether there would be a sex effect, but due to logistical constraints, the investigators were unable to recruit an equal number of female and male subjects. Thus, in addition to the potential size effect on the investigators outcome measures, the investigators would like to build on this work by examining the potential effect of biological sex. Although a PFO has been traditionally considered to have a minimal impact of physiology and pathophysiology, emerging evidence suggests this may not be the case. The investigator's lab is focused on understanding how and why a relatively small hole in the heart (PFO) can have a relatively large impact on cardiopulmonary and respiratory physiology, and how these impacts may be based on the size of the PFO.

Official Title
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Does Patent Foramen Ovale Size Matter in Men and Women

Conditions
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Patent Foramen Ovale

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18-40 Known to have/not have a PFO. Exclusion Criteria: Previous history of coronary artery disease(ischemic heart disease such as angina, heart attack, myocardial infarction). Failure of Modified Allen's Test in both hands. Currently taking medications or herbal supplements for any heart or respiratory disease that they cannot stop taking for 48 hrsprior to testing (seasonal allergy medication not included in exclusion medications). Lidocaine, nitroglycerine or heparin allergy. Women who are pregnant or trying to become pregnant. Previous history of any condition that would prevent the subject from performing cycle ergometer exercise (for exercise study only).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No PFO<br>Research subjects who present no evidence of PFO - IE no appearance of saline contrast microbubbles within 3 cardiac cycles | |
| Small PFO<br>Research subjects who present evidence of having a small PFO or ASD - IE appearance of 1-11 saline contrast microbubbles within 3 cardiac cycles | |
| Large PFO<br>Research subjects who present evidence of having a large PFO - IE appearance of 12+ saline contrast microbubbles within 3 cardiac cycles. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alveolar-arterial difference in oxygen | difference in the partial pressure of oxygen between the alveoli (calculated) and arterial blood (direct measure) | Baseline | 
| aerobic exercise capacity | ability to utilize oxygen while exercising, AKA Vo2MAX | Baseline | 
| six-minute walk test | distance covered in 6 minutes of walking | Baseline | 
| minute flow of intrapulmonary areterio-venous anastamoses (QIPAVA) | minute flow through intrapulmonary arteriovenous anastamoses | Baseline | 
| core body temperature | subject's core body temperature as measured through an ingestible pill | Baseline | 
| level of tumor necrosis factor alpha | inflammatory marker | Baseline | 
| level of C-C motif cytokine 2 | inflammatory marker | Baseline | 
| level of interferon alpha 2 | inflammatory marker | Baseline | 
| level of interferon gamma | inflammatory marker | Baseline | 
| level of interleukin 1 beta | inflammatory marker | Baseline | 
| level of interleukin 6 | inflammatory marker | Baseline | 
| level of interleukin 8 | inflammatory marker | Baseline | 
| level of interleukin 10 | inflammatory marker | Baseline | 
| level of interleukin 12p70 | inflammatory marker | Baseline | 
| level of interleukin 17 alpha | inflammatory marker | Baseline | 
| level of interleukin 18 | inflammatory marker | Baseline | 
| level of interleukin 23 | inflammatory marker | Baseline | 
| level of interleukin 33 | inflammatory marker | Baseline | 
| level of myoglobin | inflammatory marker | Baseline | 
| level of myeloid-related protein 8/14 | inflammatory marker | Baseline | 
| level of neutrophil gelatinase-associated lipocalin | inflammatory marker | Baseline and 3 months post percutaneous closure | 
| level of c-reactive protein | inflammatory marker | Baseline | 
| matrix metallopeptidase 2 | inflammatory marker | Baseline and 3 months post percutaneous closure | 
| level of osteopontin | inflammatory marker | Baseline | 
| level of myloperoxidase | inflammatory marker | Baseline | 
| level of Serum amyloid A | inflammatory marker | Baseline | 
| level of insulin like growth factor binding protein 4 | inflammatory marker | Baseline | 
| level of intracellular adhesion molecule 1 | inflammatory marker | Baseline | 
| level of vascular cell adhesion protein 1 | inflammatory marker | Baseline | 
| level of metallopeptidase 9 | inflammatory marker | Baseline | 
| level of Cystatin C | inflammatory marker | Baseline |