Background: Inverse electrocardiographic mapping reconstructs cardiac electrical activity from recorded body surface potentials. This noninvasive technique has been used to identify potential ablation targets. Despite this, there has been little systematic evaluation of its reliability. Methods: Torso and ventricular epicardial potentials were recorded simultaneously in anesthetized, closed-chest pigs (n=5), during sinus rhythm, epicardial, and endocardial ventricular pacing (70 records in total). Body surface and cardiac electrode positions were determined and registered using magnetic resonance imaging. Epicardial potentials were reconstructed during ventricular activation using experiment-specific magnetic resonance imaging–based thorax models, with homogeneous or inhomogeneous (lungs, skeletal muscle, fat) electrical properties. Coupled finite/boundary element methods and a meshless approach based on the method of fundamental solutions were compared. Inverse mapping underestimated epicardial potentials >2-fold ( P <0.0001). RESULTS: Mean correlation coefficients for reconstructed epicardial potential distributions ranged from 0.60±0.08 to 0.64±0.07 across all methods. Epicardial electrograms were recovered with reasonable fidelity at ≈50% of sites (median correlation coefficient, 0.69–0.72), but variation was substantial. General activation spread was reproduced (median correlation coefficient, 0.72–0.78 for activation time maps after spatio-temporal smoothing). Epicardial foci were identified with a median location error ≈16 mm (interquartile range, 9–29 mm). Inverse mapping with meshless method of fundamental solutions was better than with finite/boundary element methods, and the latter were not improved by inclusion of inhomogeneous torso electrical properties. Conclusions: Inverse potential mapping provides useful information on the origin and spread of epicardial activation. However the spatio-temporal variability of recovered electrograms limit resolution and must constrain the accuracy with which arrhythmia circuits can be identified independently using this approach.
We tested the hypothesis that 21 days of intermittent hypoxia (IH) increases the tolerance of the spontaneously beating guinea‐pig double atria preparation to acute in‐vitro hypoxia, and reduces cardiac stress protein expression. A total of 28 guinea‐pigs were divided into four groups: (i) IH; (ii) IH + in‐vitro hypoxia (IH + IV); (iii) control (CON); (iv) control + in‐vitro hypoxia (CON + IV). The IH animals were exposed to 8% O 2 /0.3% CO 2 for 12 h day –1 for 21 days. Normoxic controls were exposed to room air for the same duration. Acute in‐vitro hypoxia (20, 10, 5 and 0% O 2 in 5% CO 2 ) was introduced into the atrial preparation. Heat shock protein (Hsp) 70 and Hsp90 content were determined by Western blotting. Intermittent hypoxia groups demonstrated typical responses to chronic hypoxic exposure, characterized by significantly ( P < 0.05) lower body weights, reduced growth rates and increased heart weight/body weight ratios. In the CON + IV group, in‐vitro hypoxia reduced heart rate (20% O 2 , –30 ± 8 beats min –1 ; 10% O 2 , –34 ± 8 beats min –1 ; 5% O 2 , –37 ± 9 beats min –1 and 0% O 2 , –51 ± 9* beats min –1 : * P < 0.05 vs. 20% O 2 ). At 0% O 2, the decrease in the rate response was significantly attenuated in the IH + IV (–30 ± 8 beats min –1 ; n =10) compared with the CON + IV (–51 ± 9 beats min –1 ; n =10). IH significantly reduced atrial Hsp70 and Hsp90 expression, however, levels of both proteins were unchanged in the ventricle. Furthermore, Hsp90 and to a lesser degree Hsp70 in the atria remained suppressed following in‐vitro hypoxia in the IH group. Our results show that the increased resistance of the isolated atria to anoxia following IH may contribute to the concomitant reductions in basal and hypoxia‐induced Hsp expression as the overall stress response is reduced.
Recent studies have shown a decrease in the amplitude and an increase in the threshold of the cat's auditory brainstem evoked response (ABER) during severe hypoxia (PaO2 of 20 to 30Torr). In this study we have examined the effects of euoxia (end tidal PO2 100 Torr) and mild hypoxia (end tidal PO2 of 45 to 50 Torr) on the latency of the ABER in 6 human subjects. Hypoxia resulted in a blood O2 saturation of between 75 to 85% and caused a significant prolongation of the latency of wave V of the ABER by 0.185 ± 0.045 ms (Mean ± S.D; p <0.01). The prolongation of the ABER during severe hypoxia has previously been attributed to a change in peripheral sensitivity. Using the stimulus level/response latency relationship obtained for each subject under normal breathing conditions, the change in latency produced by mild hypoxia can be interpreted as a mean shift in auditory sensitivity of 5.1 ± 3.4 dB. These results suggest that the auditory system is sensitive to much smaller changes in blood O2 saturation than previously thought.
One hundred years ago in this journal, Krogh and Lindhard published a seminal paper highlighting the importance of the brain in the control of breathing during exercise. This symposium report reviews the historical developments that have taken place since 1913, and attempts to place the detailed neurocircuitry thought to underpin exercise hyperpnoea into context by focusing on key structures that might form the command network. With the advent of enhanced neuroimaging and functional neurosurgical techniques, a unique window of opportunity has recently arisen to target potential circuits in humans. Animal studies have identified a priori sites of interest in mid-brain structures, in particular the subthalamic locomotor region (subthalamic nucleus, STN) and the periaqueductal grey (PAG), which have now been recorded from in humans during exercise. When all data are viewed in an integrative manner, the PAG, in particular the lateral PAG, and aspects of the dorsal lateral PAG, appear to be key communicating circuitry for 'central command'. Moreover, the PAG also fulfils many requirements of a command centre. It has functional connectivity to higher centres (dorsal lateral prefrontal cortex) and the basal ganglia (in particular, the STN), and receives a sensory input from contracting muscle, but, importantly, it sends efferent information to brainstem nuclei involved in cardiorespiratory control.
Hypertension is associated with abnormal neurohumoral activation. We tested the hypothesis that beta-adrenergic hyperresponsiveness in the sinoatrial node (SAN) of the spontaneously hypertensive rat occurs at the level of the L-type calcium current because of altered cyclic nucleotide-dependent signaling. Furthermore, we hypothesized that NO, a modulator of cGMP and cAMP, would normalize the beta-adrenergic phenotype in the hypertensive rat. Chronotropic responsiveness to norepinephrine (NE), together with production of cAMP and cGMP, was assessed in isolated atrial preparations from age-matched hypertensive and normotensive rats. Right atrial/SAN pacemaking tissue was injected with adenovirus encoding enhanced green fluorescent protein (control vector) or neuronal NO synthase (nNOS). In addition, L-type calcium current was measured in cells isolated from the SAN of transfected animals. Basal levels of cGMP were lower in hypertensive rat atria. These atria were hyperresponsive to NE at all of the concentrations tested, with elevated production of cAMP. This was accompanied by increased basal and norepinephrine-stimulated L-type calcium current. Using enhanced green fluorescent protein, we observed transgene expression within both tissue sections and isolated pacemaking cells. Adenoviral nNOS increased right atrial nNOS protein expression and cGMP content. NE-stimulated cAMP concentration and L-type calcium current were also attenuated by adenoviral nNOS, along with the chronotropic responsiveness to NE in hypertensive rat atria. Decreased calcium current after cardiac nNOS gene transfer contributes to the normalization of beta-adrenergic hyperresponsiveness in the SAN from hypertensive rats by modulating cyclic nucleotide signaling.
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