Abstract-To clarify the source of electrocardiographic ST depression associated with ischemia, a sheep model of subendocardial ischemia was developed in which simultaneous epicardial and endocardial ST potentials were mapped, and a computer model using the bidomain technique was developed to explain the results. To produce ischemia in different territories of the myocardium in the same animal, the left anterior descending coronary artery and left circumflex coronary artery were partially constricted in sequence. Results from 36 sheep and the computer simulation are reported. The distributions of epicardial potentials from either ischemic source were very similar (rϭ0.77Ϯ0.14, PϽ0.0001), with both showing ST depression on the free wall of the left ventricle and no association between the ST depression and the ischemic region. However, endocardial potentials showed that ST elevation was directly associated with the region of reduced blood flow. Insulating the heart from the surrounding tissue with plastic increased the magnitude of epicardial ST potentials, which was consistent with an intramyocardial source. Increasing the percent stenosis of a coronary artery increased epicardial ST depression at the lateral boundary and resulted in ST elevation starting from the ischemic center as ischemia became transmural. Computer simulation using the bidomain model reproduced the epicardial ST patterns and suggested that the ST depression was generated at the lateral boundary between ischemic and normal territories. ST depression on the epicardium reflected the position of this lateral boundary. The boundaries of ischemic territories are shared, and only those appearing on the free wall contribute to external ST potential fields. These effects explain why body surface ST depression does not localize cardiac ischemia in humans.(Circ Res. 1998;82;957-970.)Key Words: ST depression Ⅲ potential mapping Ⅲ bidomain model Ⅲ subendocardial ischemia Ⅲ regional myocardial blood flow E lectrocardiographic ST-segment depression has long been recognized as a sign of ischemia, 1,2 but the explanations of the responsible mechanisms have been controversial. [3][4][5][6] Much of the current opinion regarding the genesis of ST-segment depression is derived from interpretations based on certain theoretical considerations 7,8 and indirect evidence from animal experiments. 1,2 Ischemic muscle generates intracellular currents, which effectively cause TQ depression and ST elevation over the ischemic area 9,10 and which conventional electrocardiography with AC-coupled amplifiers reflects as ST elevation. ST-segment depression recorded at the epicardium has been considered to be secondary to an injury current in the underlying subendocardium. [11][12][13][14] In conventional stress testing, as myocardial demand exceeds the ability of the narrowed coronary arterial bed to increase blood flow, the ischemic threshold is exceeded, and reversible ST-segment depression is produced. However, the location of this ST depression does not enable us to localize...

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The aim of this study was to re-evaluate wave reflection in the healthy pulmonary arteries of sheep utilizing the time-domain-based method of wave intensity analysis. A thorough understanding of patterns of wave reflection during health and disease may provide future sensitive markers of early pulmonary vascular disease. Wave intensity was calculated from the simultaneous acquisition of proximal pulmonary arterial pressure and velocity in 12 anesthetized open-chest sheep. Normal pulmonary arterial wave speed was 2.1 ± 0.3 m s(-1). The incident forward compression wave generated by right ventricular systole was reflected in an open-end manner as a backward expansion wave from a site 3 cm downstream, corresponding to the main pulmonary bifurcation, and in a closed-end manner as a backward compression wave from a site 21 cm downstream, corresponding to the pulmonary microcirculation. The proximal open-end reflection site was not present throughout the entire cardiac cycle. Wave reflection was minimal with only 1% of the incident forward compression wave energy reflected as a backward expansion wave and 2% as a backward compression wave. The normal pulmonary artery in open-chest sheep is characterized by variable proximal open-end reflection from the main pulmonary bifurcation and fixed closed-end reflection from the microcirculation, generating backward-travelling waves of minimal intensity.

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A technique of fast Fourier transform analysis has been used to derive mean ventricular fibrillation (VF) intervals, and to confirm that these VF intervals predict ventricular refractory periods. Twenty episodes of VF were induced by a rapid ventricular pacing in 12 sheep. VF activations in a 10-second period were simultaneously acquired from 64 epicardial sites with an electrode sock. The VF electrograms were analyzed by a fast Fourier transform analysis. The dominant peak frequency of the VF spectrum in each epicardial site was converted into milliseconds and served as a mean VF interval. The dominant peak frequency of VF electrograms ranged from 8.1 to 11.5 Hz, and the corresponding mean VF intervals were 87 to 124 ms. In five sheep, the mean VF intervals and the effective refractory periods were determined by the extrastimulus technique obtained from 29 epicardial sites. There was a very good correlation between the two parameters when the effective refractory periods were determined at a basic cycle length of 300 ms (r = 0.89, P < 0.001) and 400 ms (r = 0.87, P < 0.001), respectively. VF was induced twice in eight sheep. The maximum difference in the mean VF intervals between the two VF episodes in the same sheep was 3 ms (P > 0.05). In conclusion, mean VF intervals determined by the fast Fourier transform analysis have a good reproducibility and a good correlation with ventricular refractory periods measured by the classic extrastimulus technique. The mean VF intervals could serve as an index of ventricular refractoriness.

1. The application of a non-constricting silastic cuff to the rabbit common carotid artery (CCA; n = 5) results in intimal thickening within 7 days. 2. Ultrasonography showed kinking of the CCA at the cuff edges, as well as a 13% arterial narrowing (P less than 0.02) within the cuffed segment, both at days 1 and 7. Correspondingly, the time averaged diastolic Doppler velocity (TAV) was 68.8 +/- 12.8% higher (P less than 0.025) in the cuffed region in comparison with that 1 cm proximal (P 1 cm) on day 1, and 54.2 +/- 11.5% higher at day 7 (P less than 0.05). TAV values along control silastic strips were not significantly changed. 3. There was a significant increase (P less than 0.025) in intimal area within the cuffed region (0.098 +/- 0.024 mm3) compared with both the proximal control (0.014 +/- 0.001 mm3) and with that over control silastic strips (0.021 +/- 0.004 mm3, P less than 0.01). 4. Medial area within the cuff (0.433 +/- 0.017 mm3) was decreased (P less than 0.005) compared with P 1 cm control (0.602 +/- 0.069 mm3). 5. There was gross peri-arteritic thickening involving the adventitia along the non-constricted cuffed segment. Importantly, it was also noted alongside the control silastic strip. 6. Kinking of the CCA and associated vasoconstriction cause changes in blood flow velocity along even a non-constricting cuff, and this may explain the intimal thickening previously noted in this experimental model. The peri-arteritic changes, on the other hand, appear to be a reaction to the silastic itself.

1. Liver and kidney glutathione are depleted in rats and mice following administration of N-hydroxyparacetamol. 2. Centrilobular hepatic necrosis and necrosis of renal proximal convoluted tubules were also found, the liver lesion predominantly in mice and the renal lesion predominantly in rats. Glutathione depletion was not responsible for this species difference. 3. These results indicate that N-hydroxyparacetamol is the metabolic precursor of the reactive toxic intermediate of paracetamol. They are also relevant to the pathogenesis of the renal damage associated with long term abuse of phenacetin containing compound analgesics.