Ac Yong

Source of Electrocardiographic ST Changes in Subendocardial Ischemia

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 (r=0.77+/-0.14, P<0.0001), 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.

Epicardial ST Depression in Acute Myocardial Infarction

The presence of electrocardiographic ST depression in acute infarction remains controversial and poorly explained. A combined animal and modeling study was performed to evaluate the source of ST changes in acute infarction. In anaesthetized sheep, small infarcts showed uniform ST elevation over the infarction whereas larger infarcts showed marked ST depression over the normal myocardium in addition to the ST elevation. These findings were replicated by bidomain models of the heart. A hollow sphere was used to model a gradually increasing infarct, and this showed that there was a decrease in the ratio of ST elevation to ST depression as the infarct was increased. The current flowing out of the heart must be identical to the current flowing back into the heart. This means that any infarction will produce ST depression as well as ST elevation, the ratio between the two being related to the size of the infarction. Small infarction is associated with a small region of ST elevation and minor ST depression of the remaining myocardium, and as the infarct region increases, the amplitude of the epicardial ST elevation falls and the amplitude of the ST depression increases. Infarction size is proportional to both the height of the ST depression on the epicardium and the strength of the epicardial ST segment dipole.

Fast Fourier Transform Analysis of Ventricular Fibrillation Intervals to Predict Ventricular Refractoriness and Its Spatial Dispersion

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.

HAEMODYNAMIC CHANGES IN THE MONCADA MODEL OF ATHEROSCLEROSIS

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.

Arrhythmogenicity of Hypothermia – A Large Animal Model of Hypothermia

BACKGROUND Therapeutic hypothermia (TH) is used to mitigate cerebral injury after an out of hospital cardiac arrest. There is a perceived risk of increased arrhythmias with temperatures lower than the current target of 32-34°C for TH. This study sought to develop and investigate the electrophysiological changes in a sheep model of systemic hypothermia regarding the susceptibility to ventricular arrhythmias. METHODS Ten sheep underwent systemic hypothermia using a venous-venous extra-corporeal circuit whilst instrumented with a 12 lead ECG. An epicardial sock recorded potentials to 30°C (N=10) or 26°C (N=6). Activation times (AT) and Activation Recovery Intervals (ARI) were calculated using custom software. RESULTS The AT and ARI were significantly prolonged with increased heterogeneity during hypothermia. This effect was most pronounced between normothermia and 34°C during sinus rhythm (SR). For ventricular pacing (VP) however heterogeneity continued to increase with progressive hypothermia. CONCLUSIONS Hypothermia causes a significant increase in the heterogeneity of depolarisation and repolarisation. There is evidence to suggest that SR is protective with most of the increase in heterogeneity occurring with cooling to 34°C. This raises the possibility that the current target temperatures for therapeutic hypothermia may be safely lowered to provide a gain in cerebral protection.

VALIDATION OF A SUBENDOCARDIAL ISCHAEMIC SHEEP MODEL BY INTRACORONARY FLUORESCENT MICROSPHERES

1. We evaluated the use of non‐radioactive fluorescent‐labelled microspheres (FM) for the measurement of regional myocardial blood flow (RMBF) in an ischaemic sheep model.

ONSET AND OFFSET OF STRUCTURAL ARTERIOLAR CHANGES IN DOCA/SALT HYPERTENSION IN THE RAT

1.Structural changes in resistance vessels were studied sequentially (a) by hind‐quarter perfusion and (b) by planimetry of renal arterioles ≤ 20 μm radius, for 10 weeks during development of DOCA (deoxycorticosterone acetate)/salt hypertension in uninephrectomized rats and 5 weeks after cessation of DOCA treatment.

Effects of Procainamide on Transmural Ventricular Repolarisation

To investigate the pharmacological effect of procainamide on transmural ventricular repolarisation in normal heart, the transmural activation-recovery intervals (ARI) and their responses to procainamide (20 mg/min i.v. for 20 min) were studied in 6 open-chest, pentobarbitone-anaesthetised sheep. ARI was measured from the unipolar ECGs acquired with 4 plunge needles inserted into the basal and apical parts of the left ventricular wall. During sinus rhythm (cycle length 500–700 ms), there was no significant difference in the pooled ARI between the epicardium (266.0 ± 30.5 ms), midmyocardium (265.0 ± 28.9 ms) and endocardium (265.7 ± 28.1 ms) (p > 0.05). Procainamide prolonged ARI in all myocardial layers. The pooled ARI prolongation from the epicardium, midmyocardium and endocardium of the 6 animals was 66.8 ± 18.3, 70.3 ± 14.7 and 65.3 ± 15.7 ms (p > 0.05), respectively. In conclusion, sodium channel blocker procainamide results in a similar repolarisation prolongation in the left ventricular epicardium, midmyocardium and endocardium of a healthy heart.

PREVENTION OF STRUCTURAL ARTERIOLAR CHANGES IN DOCA HYPERTENSION WITH HYDRALLAZINE

1. Structural changes in resistance vessels were studied by (a) hindquarter perfusion; and (b) planimetry of cross‐sections of renal arterioles in uninephrectomized rats treated for 10 weeks with saline and either DOCA (deoxycorticosterone acetate), DOCA plus hydralazine, vehicle plus hydralazine or vehicle only.

The determination of the bidomain conductivity values of heart tissue

A method for determining the bidomain conductivity values was developed. The study was due to the different sets of conductivity values reported in the literature, each producing significantly different bidomain simulation results.The method involves mapping the propagation of the electrical activation of cardiac tissue, initiated by point stimulation, via extracellular electrodes. A time-dependent bidomain model is used to simulate the electrical phenomena. The optimum set of conductivity values is achieved by minimising the difference between the bidomain model output and the measured extracellular potential, by means of inverse techniques in parameter estimation, such as leastsquares (LS) and singular value decomposition (SVD). The method takes a different approach to the conventional four-electrode technique, as it does not require the small electrode separation needed to separate the extracellular current from the intracellular.