Aaj Adgey

Metabolic changes and mitochondrial dysfunction early following transthoracic countershock in dogs.

TROUTON, T.G., et al.: Metabolic Changes and Mitochondrial Dysfunction Early Following Transthoracic Countershock in Dogs The mechanisms of myocardial injury and necrosis /olloning transfhoracic shocks from a direct current cardiac defibrillator were investigated in adult greyhounds. Myocardial lactate extraction became negative maximally at 1 minute, following two (mean –22%± SEM 23) or five (–193%± 135) shocks and returned to baseline in 6–15 minutes. Myocardial necrosis assessed at 4 hours following the shock period was 0.05 g (± 0.03) after two shocks, 6.69 g (± 1.76) after five shocks and zero in controls. In further experiments, dogs received five or zero (dummy) shocks and mitochondria were isolated from their hearts following excision within 1 minute of receiving the final shock. Maximal oxygen consumption in right ventricular mitochondria was lower than the unshocked controls ivith both giutamate (66.9 ± 9.4 nanoatoms of oxygen/mg per minute, n = 9 vs 86.6 ± 13.6 nanoatoms/mg per minute, n = 7) and succinate (96.2 ± 8.7 nanoatoms/mg per minute, n ‐ 9 vs 119.5 ± 14.4 nanoatoms/mg per minute, n = 7) as substrates. Using electron spin resonance spectroscopy, an increase in a peroxyl‐free radical with g = 2.031 was detected in myocardial tissue after two internal shocks (50 joules stored energy, 0.5‐minute intervals). We conclude that mitochondria) dysfunction and free‐radical generation are likely contributors to cellular injury following multiple countershocks.

BODY-SURFACE MAP MODELS FOR EARLY DIAGNOSIS OF ACUTE MYOCARDIAL INFARCTION

Abstract The standard 12-lead ECG is only 50% sensitive for the detection of acute myocardial infarction (AMI). The majority of leads for optimal classification of AMI probably lie outside the area covered by the 6 precordial leads. Thus, body-surface mapping (BSM) may be more helpful, as a larger thoracic area is sampled. We recorded 64-lead anterior BSMs in 635 patients with chest pain suggestive of AMI and abnormal electrocardiograms (ECGs), and 125 controls without chest pain. Of the 635 patients, 325 had AMI according to World Health Organization (WHO) criteria (203 presenting with ST segment elevation, and 122 with nondiagnostic ECG), and 310 had an “abnormal ECG but not AMI.” QRS and ST-T isointegrals and variables describing map shape were derived. Subjects were randomly allocated to a training set (63 controls, 321 patients) and a validation set (62 controls, 314 patients). Multiple logistic regression was used in the training set to identify which variables gave best discrimination between groups. A model with these variables was then tested prospectively in the validation set. In stage 1 (all subjects), controls were compared with patients. In the training set, a model containing 21 variables classified 58/63 controls (specificity 92%) and 316/321 patients (sensitivity 98%). In the validation set, the model classified 48/62 controls (specificity 77.4%) and 302/314 patients (sensitivity 96%). In stage 2 (studying patients only), patients with AMI were compared with patients who had an abnormal ECG—not AMI. In the training set, a model containing 28 variables classified 132 165 patients (sensitivity 80%) with AMI and 134 156 patients (specificity 86%) with an abnormal ECG—not AMI. In the validation set, the model classified 123/160 patients (sensitivity 77%) with AMI and 131 154 patients (specificity 85%) with an abnormal ECG—not AMI. Combining results of both stages in a two-step algorithm gave an overall classification in the training set of controls 92%, abnormal ECG—not AMI 84%, AMI 80%, and in the validation set of controls 77%, abnormal ECG—not AMI 82%, AMI 74%. Thus, in conclusion, when compared with the 12-lead ECG, BSM models results in higher sensitivity and specificity for detection of AMI, particularly in patients presenting with chest pain and nondiagnostic ECG changes. The use of BSM models in such patients, may lead to the earlier detection of AMI and appropriate administration of fibrinolytic therapy and/or anti-platelet agents.

Body surface ECG potential maps in acute myocardial infarction

An algorithm for the early detection of acute myocardial infarction (MI) using body surface electrocardiographic potential mapping has been developed. The mapping system consists of a 64-hydrogel electrode harness applied rapidly to the anterior chest, from which electrocardiographic signals are stored on a memory card and processed by computer. At each of the 64 points, QRS and ST-T isointegrals and 10 other features of the QRST segment are measured. Using these measurements, new variables are derived that express the shape of the three-dimensional geometric surface of the map. The isointegrals, features, and shape variables are used in a variety of techniques to discriminate between MI and control subjects. Maps were recorded from 69 patients at initial presentation of chest pain suggestive of acute MI and from 80 healthy control subjects. Using a multiple logistic regression technique, 14 variables were identified that correctly classified 79 of the 80 control subjects (specificity, 98.8%) and 65 of the 69 MI patients (sensitivity, 94.2%). The algorithm based on these 14 variables was applied prospectively to maps recorded on a further 48 control subjects and 59 patients with acute MI. Of the MI patients, 31 had inferior, 13 inferoposterior, 10 anterior, 2 posterior, 1 lateral, 1 inferior with right bundle branch block, and 1 anterior non Q wave MI. The algorithm correctly classified all 48 control subjects (specificity, 100%) and 57 of the 59 MI patients (sensitivity, 96.6%). Marked differences in the three-dimensional geometric map surfaces between the control subjects and MI patients were demonstrated. Variables derived from these surfaces form the basis of an algorithm with a high sensitivity and specificity for the automated detection of acute MI. The design of adaptive algorithms and their application to patients with chest pain and atypical electrocardiographic changes, particularly ST depression, may lead to the earlier detection of MI and greater numbers of patients receiving thrombolytic therapy.

An angiographic assessment of alteplase : Double-bolus and front-loaded infusion regimens in myocardial infarction

BACKGROUNDnThis study was designed to investigate the efficacy of alteplase double-bolus dosing compared with the front-loaded 90-minute infusion regimen in patients with acute myocardial infarction. Recent pilot studies have suggested that bolus dosing may provide improved efficacy in establishing early, complete, and sustained patency of the infarct-related artery in the thrombolytic treatment of acute myocardial infarction.nnnMETHODS AND RESULTSnIn this multicenter, randomized, open-label trial, 461 patients with acute myocardial infarction received 100 mg alteplase as a front-loaded 90-minute infusion (15 mg bolus, then 50 mg over a 30-minute period, then 35 mg over a 60-minute period) or double bolus (two 50 mg bolus injections 30 minutes apart). All patients also received intravenous heparin and oral aspirin during and after alteplase treatment. The 90-minute angiographic patency rates were 74.5% in the double-bolus group and 81.4% in the infusion group (p = 0.08). Patency rates were also comparable for the two groups at 60 minutes (76.8% vs 77.5%) and 24 hours (95.5% vs 93.5%) after initiation of treatment. In-hospital mortality rates were 4.5% in the bolus group and 1.3% in the infusion group (p = 0.04); 30-day mortality rates were 4.5% and 1.7%, respectively (p = NS). The two-groups were comparable in frequency of all other adverse events.nnnCONCLUSIONSnDouble-bolus alteplase administration produced reperfusion rates comparable to front-loaded infusion, but in-hospital and 30-day mortality rates were higher in the double-bolus group. These findings are in agreement with those of the COBALT megatrial, which also reported a trend to higher mortality rates with double-bolus dosing.

A Gastroesophageal Electrode for Atrial and Ventricular Pacing

Temporary transvenous cardiac pacing requires technical expertise and access to fluoroscopy. We have developed a gastroesophageal electrode capable of atrial and ventricular pacing. The flexible polythene gastroesophageal electrode is passed into the stomach under light sedation. Five ring electrodes, now positioned in the lower esophagus, are used for atrial pacing. A point source (cathode) on the distal tip of the electrode, now positioned in the gastric fundus. is used for ventricular pacing. Two configurations of atrial and ventricular pacing were compared: unipolar and bipolar. During unipolar ventricular pacing the indifferent electrode (anode) was a high impedance chest pad. For bipolar ventricular pacing the indifferent electrode was a ring electrode placed 2 cm proximal to the tip. Unipolar atrial pacing was performed with 1 of 5 proximal ring electrodes acting as cathode (“cathodic”) or as anode (“anodic”) in conjunction with a chest pad. Bipolar atrial pacing was performed using combinations of 2 of 5 ring electrodes. Atrial capture was obtained in all 55 subjects attempted. When all electrode combinations were compared, atrial capture was significantly more frequent using the bipolar approach (153/210 bipolar, 65/210 unipolar; t = 7.37, P < 0.001). For unipolar atrial pacing, cathodic stimulation (from esophagus) was more successful than anodic stimulation (cathodic 62/105, anodic 20/105; t = 5.81, P < 0.001). In 43 subjects attempted unipolar ventricular pacing resulted in a higher frequency of capture than the bipolar approach (unipolar 41/43 (95.3%), bipolar 19/43 (44.2%); P < 0.001). In conclusion, atrial pacing was optimal using pairs of ring electrodes (“bipolar”) while ventricular pacing was optimal using the distal electrode tip (cathode) in conjunction with a chest pad electrode (“unipolar”). This gastroesophageal electrode may be useful in the emergency management of acute bradyarrhythmias and for elective electrophysiological studies.

Transthoracic defibrillation threshold of sine and trapezoidal waveforms in defibrillation.

The transthoracic defibrillation threshold of trapezoidal (2.5-, 5-, 10-, 15-, 20-, 40-, and 55-msec duration) and damped sine waveforms were established in groups of anesthetized greyhounds. Of the seven trapezoidal waveforms, the threshold current was lowest for the 20-msec pulse but was not significantly different for the 5-20-msec pulses (p greater than 0.05). The threshold delivered energy was not significantly different for the 2.5-20-msec waveforms. The 40- and 55-msec pulses had significantly greater delivered energies than the shorter pulses (p less than 0.01). The transthoracic defibrillation threshold of two trapezoidal (5- and 20-msec) and three damped sine waves (Lown, Edmark, and Belfast) showed that the threshold transthoracic current and energy were not significantly different for the 5-msec trapezoid and three sine waves (p greater than 0.05). The threshold transthoracic energy for the 20-msec trapezoid was significantly greater than that of the four other waveforms. The threshold current for the 20-msec trapezoid was significantly less than that of the Belfast and Edmark waveforms only. Thus, none of the three damped sine waveforms was superior, with the 5-msec trapezoid producing similar results. Although the 20-msec trapezoid had the lowest threshold current, it had the highest delivery energy.

Altered Cardiac Oxygen Extraction, Lactate Production and Coronary Blood Flow After Large Dose Transthoracic DC Countershocks

Although problems such as hypotension and pulmo‐nary edema complicate the use of trunsthorucic DC counlershocks, the mechanisms are not clear. In anesthetized dogs at 1 minute after only two defibrillator shocks there was a brief rise in coronary sinus lactate. exceeding arteriol concentrations. Larger rises in lactale were seen after five shocks, indicating myocardial production of lactate. By contrast in eight animals given dummy shocks the heart always extracted lactate. At 2 minutes after five shocks mean myocardial oxygen extraction (6.5 ± 0.6 mL/100 mL blood; n = 5) was significantly lower than in controls (11.1 ± 0.6 mL/100 mL blood: n = 4; P < 0.0001), and remained so until 3 minutes after shocks, without significant increase in the lipid pevoxidation product malondiaidehyde in coronary sinus or arterial blood. Great cardiac venous blood flow, measured hy thermodiiution, rose after five shocks, and the heart rate pressure product also increased at 1–2 minutes. This transient failure of oxygen extraction, in the presence of arterial normoxia. hyperemia, and increased cardiac work, is best accounted for by a central effect of countershocks on myocardial ceiluiar respiration.

Discriminant function analysis of body surface potential maps in acute myocardial infarction

Using a newly developed 64-electrode portable mapping device, QRS and ST-T isointegral maps were compared in 194 control subjects and 101 patients. One hundred ninety-four control subjects (mean age, 48 years; 120 men) with no history of cardiac disease were selected randomly and mapped. One hundred one patients (mean age, 62 years; 77 men) were mapped at presentation of chest pain suggestive of first myocardial infarction (MI); all patients had classic 12-lead electrocardiographic findings--46 with anterior and 55 with inferior MI. The diagnosis was confirmed in all cases by a significant rise in serial cardiac enzymes. The mean delay between onset of chest pain to map recording was 163 minutes. Of the 101 patients, 78 were first mapped outside the hospital. Applying discriminant function analysis to the isointegral measurements made on the control subjects and on the first map of MI patients achieved a correct classification of 97% of the control subjects (189 of 194) and 72% of the anterior (33 of 46) and 76% of the inferior (42 of 55) MI groups. This preliminary study suggests that discriminant function analysis, based on isointegral maps, not only provides a method of separating control subjects from MI patients but that it can also differentiate between types of infarct. Further studies are required to improve the predictive values of discriminant function and to extend the methodology to assess both the site and size of MI.

Frequency Analysis of Atrial Fibrillation Predicts Success for Low Energy Intracardiac Cardioversion

The aim of this study was to evaluate the relation between atrial fibrillatory frequency (AFF) and the probability of successful internal cardioversion of atrial fibrillation (AF). Thirty consecutive patients suggested for DC cardioversion at the Royal Victoria Hospital in Belfast, were included in the study. Two catheters were positioned in the right atrial appendage (RAA) and the coronary sinus (CS), for delivering a biphasic shock waveform, 6/6 msec, synchronized with the Rwave on the ECG signal. The atrial fibrillatory activity was derived from 60 seconds of surface ECG from the defibrillator pads, prior to shock delivery, by bandpass filtering and ventricular activity (QRST) cancellation. QRST complexes subtraction was implemented by means of a template matching and signal averaging algorithm. FFT was applied to the residual atrial fibrillatory signal. Atrial fibrillatory frequency was estimated from the dominant frequency in the 3–12Hz band of the power spectrum. Eighteen patients were successfully cardioverted using a voltage step up protocol beginning from 50V up to 300V (biphasic pulse amplitude). Twelve of the cases were not successfully cardioverted to sinus rhythm. The AFF was 5.42±1.03 Hz (within the range of 3.69 – 7.38 Hz) in patients successfully cardioverted vs. 6.5 ± 0.68 Hz (within the range of 5.38–7.56 Hz) in patients which failed cardioversion, P < 0.004. AFF was < 6.26 Hz in 15 of the 18 patients with successful cardioversion. AF cardioversion was predicted with a specificity of 83.33% in the best cases, and with an acceptable sensitivity of 75%. Also, there was a positive correlation (ρ = 0.624 and P < 0.01) between the minimal defibrillation energy and the fibrillatory frequency in cardioverted patients. In conclusion, calculated AFF from the surface ECG, may predict the success of internal low energy cardioversion of patients with atrial fibrillation.

A method for the ECG inverse problem in the frequency domain

The Inverse ECG problem is ill-conditioned and its solution requires a relatively high computing effort. Additional constraints are required in order to obtain a stable solution. A method is proposed in which the solution of the inverse ECG problem is approached in the frequency domain, taking advantage of the assumption that propagation delays may be ignored and the quasi-periodicity of ECG. In this method usual Tikhonov zero-order constraints are applied to the amplitudes of the signals for a selected frequency domain. This method ensures faster solutions that are spatially and temporally well behaved. Calculation of epicardial electrograms is compared to a basic method.