Patent foramen ovale (PFO) is implicated in platypnea-orthodeoxia, stroke and decompression sickness (DCS) in divers and astronauts. However, PFO size in relation to clinical illness is largely unknown since few studies evaluate PFO, either functionally or anatomically. The autopsy incidence of PFO is approximately 27% and 6% for a large defect (0.6 cm to 1.0 cm). A PFO is often associated with atrial septal aneurysm and Chiari network, although these anatomic variations are uncommon. Methodologies for diagnosis and anatomic and functional sizing of a PFO include transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) and transcranial Doppler (TCD), with saline contrast. Saline injection via the right femoral vein appears to have a higher diagnostic yield for PFO than via the right antecubital vein. Saline contrast with TTE using native tissue harmonics or transmitral pulsed wave Doppler have quantitated PFO functional size, while TEE is presently the reference standard. The platypnea-orthodeoxia syndrome is associated with a large resting PFO shunt. Transthoracic echocardiography, TEE and TCD have been used in an attempt to quantitate PFO in patients with cryptogenic stroke. The larger PFOs (approximately > or =4 mm size) or those with significant resting shunts appear to be clinically significant. Approximately two-thirds of divers with unexplained DCS have a PFO that may be responsible and may be related to PFO size. Limited data are available on the incidence of PFO in high altitude aviators with DCS, but there appears to be a relationship. A large decompression stress is associated with extra vehicular activity (EVA) from spacecraft. After four cases of serious DCS in EVA simulations, a resting PFO was detected by contrast TTE in three cases. Patent foramen ovales vary in both anatomical and functional size, and the clinical impact of a particular PFO in various situations (platypnea-orthodeoxia, thromboembolism, DCS in underwater divers, DCS in high-altitude aviators and astronauts) may be different.

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Oxidative stress plays an important role in the pathophysiology of cardiovascular disease. Recent evidence suggests that cytokines induce oxidative stress and contribute to cardiac dysfunction. In this study, we investigated whether increased circulating and tissue levels of tumor necrosis factor (TNF)-alpha in congestive heart failure (CHF) modulate the expression of NAD(P)H oxidase subunits, Nox2 and its isoforms, in the paraventricular nucleus (PVN) of the hypothalamus and contribute to exaggerated sympathetic drive in CHF. Heart failure was induced in Sprague-Dawly rats by coronary artery ligation and was confirmed using echocardiography. Pentoxifylline (PTX) was used to block the production of cytokines for a period of 5 wk. CHF induced a significant increase in the production of reactive oxygen species (ROS) in the left ventricle (LV) and in the PVN. The mRNA and protein expression of TNF-alpha, Nox1, Nox2, and Nox4 was significantly increased in the LV and PVN of CHF rats. CHF also decreased ejection fraction, increased Tei index, and increased circulating catecholamines (epinephrine and norepinephrine) and renal sympathetic activity (RSNA). In contrast, treatment with PTX in CHF rats completely blocked oxidative stress and decreased the production of TNF-alpha and Nox2 isoforms both in the LV and PVN. PTX treatment also decreased catecholamines and RSNA and prevented further decrease in cardiac function. In summary, TNF-alpha blockade attenuates ROS and sympathoexcitation in CHF. This study unveils new mechanisms by which cytokines play a role in the pathogenesis of CHF, thus underscoring the importance of targeting cytokines in heart failure.

Systolic and diastolic ventricular dysfunction frequently coexist. Both are important determinants of prognosis; consequently, a clinical measurement that assesses both systolic and diastolic function may be more useful than one that addresses only one aspect of ventricular function. Recently, a Doppler-derived index (referred to as the Tei index, or myocardial performance index) that combines systolic and diastolic time intervals has been developed to assess global cardiac function. 1 In this brief review we will discuss the measurement and utility of the Tei index.The Tei index, which may be used to assess either left or right ventricular function, is equal to the sum of the isovolumic contraction time (ICT) and isovolumic relaxation time (IRT) divided by ejection time (ET). As originally described by Tei, 1 the time intervals used to calculate the index are measured using pulsed-wave Doppler velocity spectra of ventricular inflow and outflow. Mitral or tricuspid flow velocity spectra are obtained by positioning the pulsed-wave Doppler sample volume at the tips of the mitral or tricuspid valve leaflets in the apical four-chamber view. Left ventricular outflow velocity spectra may be obtained from either the apical five-chamber or the long-axis view, by positioning the pulsed-wave Doppler sample volume at the level of the aorAddress for correspondence and reprint requests: tic annulus. Right ventricular outflow velocity spectra are obtained from the parasternal short-axis view, with the pulsed-wave Doppler sample volume positioned at the pulmonic annulus. Calculation of the Tei index ( Fig. 1) involves measuring the time interval a, extending from the cessation of mitral or tricuspid inflow to its subsequent onset, and ejection time b, which is the duration of the left or right Figure 1. Schema of Doppler flow velocity spectra representing the time intervals used for calculation of the Tei index. Interval 'a' extends from the cessation to the onset of mitral or tricuspid inflow. It includes the isovolumic contraction time, ejection time, and isovolumic relaxation time. Interval 'b' is the duration of left or right ventricular outflow (ejection time). The Tei index is equal to (a − b)/b. ET, ejection time; ICT, isovolumic contraction time; IRT, isovolumic relaxation time.