Characterization of blood flow through intrapulmonary arteriovenous anastomoses and patent foramen ovale at rest and during exercise in stroke and transient ischemic attack patients.
OBJECTIVE
We determined whether stroke and/or TIA subjects have exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) and/or patent foramen ovale (QPFO) and a genetic predisposition for ischemic stroke.


METHODS
Twenty-eight stroke and/or TIA subjects (33-63 years old) underwent transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect QIPAVAand QPFOat rest and during supine exercise with and without breathing 100% O2. We also examined genetic polymorphisms in FV Leiden (G1691A; rs6025), factor II (FII) prothrombin (G20210A; rs1799963), methylene tetrahydfropholate reductase (C677T, rs1801133), and plasminogen-activator inhibitor-1 (PAI-1) (4G/5G; rs1799889) and angiotensin-converting enzyme (ACE; I/D, rs4646994) in 24/28 subjects.


RESULTS
No subject without PFO had QIPAVAat rest (n=17), but 12/17 did with exercise. All PFO subjects had QPFOat rest (n=11) and 7/11 had either QIPAVAor QPFOwith exercise. Breathing 100% O2during exercise reduced or eliminated left heart contrast in all subjects. Gene analyses revealed that 15/24 patients were either heterozygous or homozygous for methylenetetrahydrofolate reductase gene polymorphism; 4G/4G and 4G/5G genotypes of plasminogen-activator inhibitor-1 were present in 7/24 and 13/24 patients, respectively; polymorphisms of ACE D/D genotype were present in 6/24 and I/D in 14/24 patients. Having both I/D and 4G/4G genotypes was more prevalent in PFO+ subjects (P=.03), and there was a trend (P=.06) for PFO- subjects to have a greater D/D genotype prevalence.


CONCLUSIONS
Novel genetic predispositions reported here in PFO subjects should be investigated further in larger stroke and/or TIA patient datasets.
Department of Neurology, University Hospital Center Split, Split, Croatia.
Rinaldo
R
Romac
Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.|Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Otto
O
Barak
Division of Cardiology, Department of Internal Medicine, University Hospital Center Split, Split, Croatia.
Duska
D
Glavas
Division of Cardiology, Department of Internal Medicine, University Hospital Center Split, Split, Croatia.
Zora
Z
Susilovic Grabovac
Division of Cardiology, Department of Internal Medicine, University Hospital Center Split, Split, Croatia.
Petar
P
Lozo
Department of Neurology, University Hospital Center Split, Split, Croatia.
Igor
I
Roje
Department of Anesthesiology, University Hospital Center Split, Split, Croatia.
Kresimir
K
Caljkusic
Department of Pathology, Forensic Medicine and Cytology, University Hospital Center Split, Split, Croatia.|Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia.
Irena
I
Drmic-Hofman
Department of Kinesiology, Recreation and Sport, Indiana State University, Terre Haute, IN, USA.
James T
JT
Davis
Department of Integrative Physiology, University of Split School of Medicine, Split, Croatia.
Zeljko
Z
Dujic
Department of Human Physiology, University of Oregon, Eugene, OR, USA.
Andrew T
http://orcid.org/0000-0001-7826-4290
AT
Lovering
D000328:Adult; D001164:Arteriovenous Fistula / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001783:Blood Flow Velocity; D025401:Echocardiography, Stress / Q000379:methods*; D005260:Female; D054092:Foramen Ovale, Patent / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D011652:Pulmonary Circulation; D011667:Pulmonary Veins / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D020521:Stroke / Q000000981:diagnostic imaging / Q000503:physiopathology*
D005819:Genetic Markers
exercise; polymorphisms; shunt; stroke; transient ischemic attack