The findings of this study demonstrate that epicardial and endocardial activation can be discordant in specific regions and that discordance increases with abnormal activation sequences. Many of the differences in the epicardial and endocardial activation can be correlated with the heterogeneity of the anatomic architecture of the right atrium. The study also demonstrates that reentry can occur in a three-dimensional plane using the epicardial and endocardial surfaces connected by transmural muscle fibers.

Activation sequence maps derived during normal sinus rhythm from extracellular potentials in the canine right atrium exhibit widely separated sites of origin. The objectives of this study were to characterize the distribution of pacemakers within the right atrium and to determine the relationship of pacemaker action potentials to sites of earliest surface activation as well as to local extracellular electrograms. The right atria of six adult mongrel dogs were rapidly excised under deep pentobarbital sodium anesthesia and perfused with 95% O2-5% CO2 Krebs-Henseleit solution. Action potentials from the epicardial surface were recorded throughout the region bounded by the crista terminalis laterally and the atrial septum medially. Simultaneously, unipolar extracellular electrograms were recorded from 250 endocardial sites. The earliest pacemakers preceded the earliest electrogram by 63 +/- 34 ms; the latest pacemakers followed the earliest electrogram by 71 +/- 40 ms. Primary negativity in the extracellular electro gram did not predict the site of the earliest or dominant pace maker and in some cases was associated with the latest pace makers. We conclude that primary negativity and/or the sites of earliest activation reflect the point at which the impulse engages atrial myocardium, not the site of earliest pacemaker activity. As such, early extracellular activation appears to represent sites of exit from a relatively insulated sinus node.

The site of earliest extracellular electrical activation in the sinoatrial node (SAN) is known to shift in response to autonomic stimuli, but the mechanisms underlying this phenomenon and the determinants of the location of dominant pacemaker activity have not been elucidated. The present study was designed to characterize the spatial distribution of muscarinic cholinergic and β-adrenergic receptors in the canine SAN and to determine whether a consistent relationship exists between autonomic receptor densities and the site of dominant pacemaker activity. We used quantitative light-microscopic autoradiography of radioligand binding sites to characterize the spatial distribution of muscarinic cholinergic and β-adrenergic receptor subtypes in tissue sections containing the SAN and adjacent right atrial muscle from 18 canine hearts. Muscarinic receptor density was 5.4 times greater in SAN cells than in atrial myocytes ( P <.01). Total β-adrenergic receptor density was more than 3 times greater in SAN cells than in atrial myocytes ( P <.0001), due entirely to the significantly greater number of β 1 -adrenergic receptors in the SAN. The region of dominant pacemaker activity, localized in 4 hearts with in vitro mapping, consistently exhibited greater densities of muscarinic and β 1 -adrenergic receptors than other SAN regions. Muscarinic receptor density in the dominant pacemaker region was 18±2% and 29±7% higher than in adjacent superior and inferior regions, respectively. β 1 -Receptor density in the dominant site was 53±5% and 26±4% higher than in adjacent superior and inferior SAN regions, respectively. Thus, the SAN is richly endowed with both muscarinic cholinergic and β 1 -adrenergic receptors. Differential responsiveness to autonomic inputs, related perhaps to regional differences in receptor density, may help determine the spatial localization of pacemaker activity.

Gottliebson WM, Effat MA. Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model. Am J Physiol Heart Circ Physiol 300: H382-H387, 2011. First published October 8, 2010 doi:10.1152/ajpheart.00412.2010.-A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDPe, ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR Ͻ 120 and HR Ͼ 120 beats/min, in the presence of epicardial coronary lesions of Ͻ50% AS and Ͼ50% AS. The mean values of FFR, CDPe, and LFC were significantly different (P Ͻ 0.05) for lesions of Ͻ50% AS and Ͼ50% AS (0.88 Ϯ 0.04, 0.76 Ϯ 0.04; 62 Ϯ 30, 151 Ϯ 35, and 0.10 Ϯ 0.02 and 0.16 Ϯ 0.01, respectively). The mean values of FFR and CDPe were not significantly different (P Ͼ 0.05) for variable HR conditions of HR Ͻ 120 and HR Ͼ 120 beats/min (FFR, 0.81 Ϯ 0.04 and 0.82 Ϯ 0.04; and CDPe, 95 Ϯ 33 and 118 Ϯ 36). The mean values of LFC do somewhat vary with HR (0.14 Ϯ 0.01 and 0.12 Ϯ 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP e and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting. coronary disease; hemodynamics; catheterization CORONARY ANGIOGRAPHY is the current gold standard for detecting epicardial coronary artery disease. Augmenting this anatomical data with coronary functional parameters (pressure, flow, and/or velocity) provides unique information that facilitates fully informed therapeutic decision making in the catheterization laboratory. Several invasive functional approaches have been used for the past several years within the cardiac catheterization laboratory that allow for a determination of the functional significance of epicardial coronary stenoses. These methods include measurement of coronary flow reserve [CFR, the ratio of hyperemic flow to basal flow (10) (9), an advanced func...

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