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Antithrombotic activity of inogatran, a new low-molecular-weight inhibitor of thrombin, in a closed-chest porcine model of coronary artery thrombosis.

OBJECTIVE: To characterize the antithrombotic activity of inogatran per se in a porcine model of copper-coil-induced coronary artery thrombosis and to compare its effect with that of heparin and ASA. METHODS: Forty-eight pigs were assigned to one of the following groups: (1) saline; (2) heparin, (a) 75 and (b) 150 IU/kg/h; (3) acetylsalicylic acid (ASA), 12.5 mg/kg; (4) ASA 12.5 mg/kg + inogatran, 0.06 mg/kg/h; (5) ASA 12.5 mg/kg + inogatran, 0.30 mg/kg/h; (6) inogatran, 0.30 mg/kg/h; (7) inogatran, 0.60 mg/kg/h; (8) inogatran, 1.5 mg/kg/h. Computerized vectorcardiography was applied to monitor coronary occlusion and reperfusion. RESULTS: Cumulative time in which coronary arteries were patent, expressed as a percentage of the treatment time (i.e., 90 min) in heparin- and ASA-treated pigs, was 8 +/- 6 and 14 +/- 7%, respectively. This is not significantly different from placebo-treated pigs. Inogatran-treated pigs showed a dose-dependent antithrombotic effect, and the average patency rates were 34 +/- 39, 54 +/- 37 and 80 +/- 32%, in groups 6, 7 and 8, respectively. Combined treatment with inogatran and ASA did not significantly improve the antithrombotic effect. A partial antithrombotic effect of inogatran was maintained for, on average, at least 150 min after the end of treatment, as evidenced by patency rates of 31 +/- 43, 52 +/- 48 and 62% +/- 44, in groups 6, 7, and 8, respectively. CONCLUSION: Inogatran inhibits the formation of arterial thrombosis more effectively than heparin or ASA. Inhibition of clot-bound thrombin and thrombin-induced platelet activation may be the mechanisms behind this effect. Our findings also suggest that a thrombus formed in the presence of inogatran is more susceptible to spontaneous endogenous fibrinolysis.

Animals↗

Advances in the diagnostic management of arrhythmogenic right ventricular dysplasia-cardiomyopathy.

Latest advances in the diagnostic management of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) confirm that ARVD/C is not a rare disease (one affected in 1000-1250 inhabitants) and is of familial origin in 50-80% of cases. Diagnostic criteria defined in 1994 lead to low rates in the diagnosis of ARVD/C. Progress was made in the definition of diagnostic markers. New criteria of localised right precordial QRS prolongation could be identified. The detection of epsilon potentials could be enhanced by highly amplified and modified recording techniques. Vectorcardiography, signal averaging per lead and electroanatomic voltage mapping might become more important in the future. Cardiac MRI does not represent the single diagnostic test to make the diagnosis of ARVD/C. It remains a promising noninvasive imaging technique with advantages in the evaluation of the right ventricle. After the characterisation of mutations in the plakophilin-2 gene, molecular genetics is going to become an important diagnostic tool. Up to now, unsolved problems exist in the differentiation of ARVD/C and other conditions with ventricular arrhythmias evolving from the right ventricle such as Brugada syndrome and right ventricular outflow tract tachycardia. These problems can be overcome by distinct ECG analysis and the use of imaging techniques. With the help of corrected and modified diagnostic criteria it seems to be possible to identify symptomatic and asymptomatic affected by ARVD/C with predominantly major criteria and only in a minority of cases minor criteria.

Arrhythmogenic Right Ventricular Dysplasia↗

Cardiac involvement in myotonic muscular dystrophy (Steinert's disease): a prospective study of 25 patients.

The presence, degree and frequency of disorders of cardiac conduction and rhythm and of regional or global myocardial dystrophy or myotonia have not previously been studied prospectively and systematically in the same population of patients with myotonic dystrophy. Accordingly, 25 adults with classic Steinert's disease underwent electrocardiography, 24-hour ambulatory electrocardiography, vectorcardiography, chest x-rays, echocardiography, electrophysiologic studies, and technetium-99m angiography. Clinically important cardiac manifestations of myotonic dystrophy reside in specialized tissues rather than in myocardium. Involvement is relatively specific, primarily assigned to the His-Purkinje system. The cardiac muscle disorder takes the form of dystrophy rather than myotonia, and is not selective, appearing with approximately equal distribution in all 4 chambers. Myocardial dystrophy seldom results in clinically overt ventricular failure, but may be responsible for atrial and ventricular arrhythmias. Since myotonic dystrophy is genetically transmitted, a primary biochemical defect has been proposed with complete expression of the gene toward striated muscle tissue, whether skeletal or cardiac. Specialized cardiac tissue and myocardium have close, if not identical, embryologic origins, so it is not surprising that the genetic marker affects both. Cardiac involvement is therefore an integral part of myotonic dystrophy, targeting particularly the infranodal conduction system, to a lesser extent the sinus node, and still less specifically, the myocardium.

Adult↗

Factors predictive of perioperative myocardial infarction during coronary operations.

The diagnosis of perioperative myocardial infarction (PMI) in our patients was based upon electrocardiography, vectorcardiography, and postoperative enzyme changes. A group of 303 patients operated on between January and September, 1972, formed the basis of this study. Three groups were identified from among these patients. Group A was composed of 90 consecutive patients in whom MI was excluded by all criteria. Group B comprised 25 patients with proved MI and yielded the 8% incidence of MI among our patients. Group C included 34 patients with triple-vessel disease who did not sustain MI. Significantly more patients sustaining MI had preinfarction angina and severe coronary artery disease. The incidence of MI was also higher in patients with diffuse disease and those in whom the lesions could not be totally bypassed. A statistical correlation with longer pump runs and periods of anoxia was obtained. There was some suggestion that the preoperative location of the hypokinetic segment determined the site of MI in patients.

Angina Pectoris↗

Continuous multilead ST-monitoring identifies patients with unstable coronary artery disease who benefit from extended antithrombotic treatment.

AIMS: Prolongation of anticoagulant treatment might reduce subsequent cardiac events in patients with unstable coronary artery disease. Multilead ST-segment monitoring identifies patients with a high risk of adverse outcome. The aim was to assess the value of multilead ST-monitoring in prospectively identifying patients who respond to extended anticoagulant treatment with low-molecular weight heparin when treated by a primarily non-invasive strategy. METHODS AND RESULTS: In this substudy of the FRISC II trial, ST-monitoring with a continuous 12-lead ECG or vectorcardiography was performed for 24 h in 629 patients with unstable coronary artery disease randomized to receive either the low-molecular weight heparin dalteparin, or placebo for 3 months after at least 5 days' dalteparin treatment in all patients. Ischaemic episodes were detected in 34% during ST-monitoring. In the group with ischaemic episodes, the extended dalteparin treatment was associated with a lower rate of death, myocardial infarction, or revascularization (35.2% vs 53.4%, relative risk reduction: 34%, P=0.01). In patients without ischaemic episodes, long-term dalteparin treatment had no effect. CONCLUSIONS: In patients with unstable coronary artery disease treated primarily with a non-invasive strategy, ischaemic episodes revealed while on multilead ST-monitoring identifies patients who benefit most from extended treatment with anticoagulants.

Adult↗

Improved EASI coefficients: their derivation, values, and performance.

The EASI lead system, which is based on the dipole hypothesis of vectorcardiography, offers the possibility of deriving the standard 12-lead electrocardiogram (ECG) and other desired leads from ECGs recorded at only 4 sites; it uses the Frank E, A, and I electrode locations, a fourth electrode location (S) at the manubrium, and a reference electrode. Accordingly, the electrodes of this system can be applied rapidly on easy-to-locate, stable anatomical sites that leave the precordium free for other diagnostic procedures. In early EASI implementations, the derived leads differed from actual leads by more than some clinicians found acceptable. As these differences were thought to be caused by the fact that the coefficients that were used had been derived from a limited data set, we have calculated a new set of EASI coefficients for the standard 12 leads, and several other leads, by using a data set of 983 adult subjects with 120-lead ECGs and well-documented diagnoses. This database is a concatenation of 2 previously described ones: one consisting of 892 persons (normal subjects, postmyocardial-infarction patients with and without arrhythmias, and patients with ventricular arrhythmias but no history of myocardial infarction) and the other consisting of 91 patients with single-vessel coronary artery disease who underwent coronary balloon-inflation angioplasty. In addition to the coefficients for the standard 12 leads (derived for standard limb leads as well as for Mason-Likar leads), we derived coefficients for six additional unipolar leads (posterior V(7)-V(9), and right-sided V(3)R-V(5)R), the Frank orthogonal leads, and three bipolar, vessel-specific leads that have been previously shown to exhibit optimal sensitivity for acute myocardial ischemia. We also derived coefficients for the modified electrode locations of the EASI system that must be used with patients who have undergone a midline sternotomy. Optimal coefficients for lead transformations were determined by maximizing the ensemble average (over the entire data set) of the correlation between the derived and the true lead for the chosen interval of the averaged complex. For derived standard limb leads, the amplitude was adjusted to give the best root-mean-square fit over the entire PQRST interval, whereas for derived Mason-Likar leads it was adjusted to give the best ST-segment fit. The entire set of coefficients and their corresponding goodness-of-fit measures are presented.

Adult↗

Potassium and myoglobin release and ST and QRS vector changes during acute myocardial infarction.

Thirty-three consecutive patients aged 39 to 77 years with signs of myocardial infarction with a duration of symptoms of less than 4 h took part in the study. Serial blood sampling was done for the determination of myoglobin (MG), creatine-kinase (CK) and potassium (K). Continuous vectorcardiography was monitored. Peak rates of K and MG release occurred 7.0 +/- 3.7 and 6.5 +/- 3.9 hours, respectively, after the onset of symptoms not different from the end of ST vector change that occurred after 7.6 +/- 2.8 h. Following the end of ST vector change there was a 4-hour delay until the end of QRS vector change and another 8-hour delay to the end of MG release occurring about 20 h after the onset of symptoms. At the time for peak rate of MG release 48 +/- 17% of total MG release had occurred. In conclusion, the physiologically different indicators of myocardial damage showed signs of maximum release within the same time range, 6-8 h after the onset symptoms and 8-10 h before signs of completed infarction.

Adult↗

Effect of aging alone on mechanical properties of the normal adult human lung.

For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25-75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were alpha1-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25-35, 36-64, and 65-75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly.

Adult↗

False-negative and false-positive ECG diagnoses of Q wave myocardial infarction in the presence of right bundle-branch block.

Right bundle-branch block (RBBB) has not traditionally been seen as an obstacle to ECG diagnosis of Q wave myocardial infarction (MI)--in clinical electrocardiography and vectorcardiography--because this conduction disturbance is not believed to cause significant alterations in the spatial orientation of initial excitation wavefronts. In the era of large-scale clinical trials, however, where serial ECG analysis is among the major diagnostic tools in MI classification, both false-positive and false-negative diagnoses of MI in the presence of RBBB have become increasingly evident. Because of the limited detectability of Q wave MI by ECG in the presence of RBBB, the electrocardiographic finding of Q wave MI should not be regarded as an independent diagnostic tool. It is best to utilize independent corroboration to establish the diagnosis of transmural infarction when RBBB is present. Further investigations are warranted to better delineate sensitivity, specificity, and predictive value of Q wave MI in the presence of RBBB.

Atrial Function, Right↗

Anterior infarctional changes occurring during mid and late ventricular activation detectable by surface mapping techniques.

This is a comparative body surface potential map study of 26 patients with a recent acute anterior myocardial infarction. The mean plus or minus two standard deviations (+/- 2 SD) for the voltage distribution was established at 5 msec intervals throughout the cardiac cycle in 30 normal subjects at each of 142 recording sites. Instances in which a patient's potential distribution fell outside the normal range were analyzed as to location, duration and intensity against the expected time course of ventricular activation. Only four patients had departures from the normal distribution confined to the Q time zone. Twenty patients had not only Q time zone abnormalities, but had areas of both positivity and negativity exceeding +/- 2 SD, which occurred well after 30 msec. Two patients with clearly documented diagnostic Q waves during the first few days of hospitalization had lost these findings by the date of body surface mapping. They did retain, however, departure map findings demonstrating significant abnormalities occurring between 30 and 60 msec after onset of ventricular activation. These changes occurring in the mid and late time zones of the activation sequence are not detectable by conventional electrocardiography or vectorcardiography, yet present a strikingly apparent finding by this technique of analysis and display.

Action Potentials↗

Delineation of premature P waves on four-dimensional electrocardiography, a new display of electrical forces by computer techniques.

This study investigated the feasibility of four-dimensional electrocardiography (4-D ECG), a new display in which the vector loop was rotated and scanned along a timed axis to overcome the shortcomings of vectorcardiography (VCG). The subjects consisted of 38 patients with premature atrial complexes and 30 controls. The orthogonal Frank electrocardiograms were rotated three-dimensionally according to the right-hand rectangular coordinate system and scanned along a timed axis. The P wave delineation score, signifying good agreement with the intraobserver and interobserver variability, was significantly higher in 4-D ECG than those in the orthogonal leads or those on the transverse and frontal projections (P < 0.001). The authors measured the premature P loop areas as viewed from 361 directions. P loop areas were best delineated when viewed from cranial directions of 42.6 +/- 34.0 degrees and from rightward directions of 11.3 +/- 30.7 degrees. Adequate cranial rotation followed by scanning along a timed axis will maximally delineate premature atrial signals and provide comprehensive visualization of electrical forces.

Atrial Premature Complexes↗

Hereditary carnitine deficiency of muscle.

An eight-year-old boy with slowly progressive muscle weakness was found to have Oil red O positive vacuoles in predominanty type i muscle fibers. Subsequent studies demonstrated markedly reduced skeletal muscle carnitine (0.24 mumoles per gram; normal 1.64 to 3.34). Serum carnitine was normal. Although both parents were clinically normal, muscle carnitine levels were low in both (mother 0.60; father 0.90 mumoles). There was no clinical evidence of cardiac disease but the patient had ventricular hypertrophy by electrocardiography, vectorcardiography, and echocardiography. Treatment with prednisone resulted in clinical improvement but no change in muscle histology. Our studies suggest that the carnitine deficiency of muscle in this case may be due to impaired carnitine entry into muscle and that this form of disease can be inherited as an autosomal recessive disorder.

Aspartate Aminotransferases↗

Experimental and clinical study of the pre-excitation syndrome.

Ventricular pre-excitation was experimentally produced in mongrel dogs. Their ECG and epicardial maps were analyzed. Forty-two cases of W-P-W syndrome were operated on between 1969 and May, 1980. The relationship between ECG, particularly the delta wave and localization and meaning of pre-operative examinations such as vectorcardiography, echocardiography, body surface mapping, intracavitary potential study, and cardiac pacing, were presented and discussed. As an intraoperative study, epicardial mapping was indispensable and was the most accurate method in determining the ACP. Endocardial potential study was another meaningful method in certain cases. Detachment of the atrium from the ventricle with an incision along the annulus and at the opposite of the pre-excitation area resulted in complete correction in 32 out of 34 cases between 1973 and May, 1980. Six cases of multiple ACPs were also corrected, although 4 needed a second operation. Indications for surgery of the W-P-W syndrome should be extended further in view of the high success and safety rate of the surgery.

Animals↗

[Clinical and instrumental characteristics of primary high altitude arterial pulmonary hypertension].

The clinical pattern of primary high altitude pulmonary arterial hypertension observed in permanent residents of mountain regions is described. The diagnostic value of some non-invasive instrumental methods in primary high altitude pulmonary artery hypertension is analysed: electro- and vectorcardiography, rheopulmonography, and indirect pulmonary artery pressure determination. It is suggested to distinguish the labile, stable and decompensated forms of the disease on the basis of its clinical and functional peculiarities. The criterion for the initial two forms consists in the persistence of the pulmonary artery pressure elevation, while the latter form is established when the high altitude cor pulmonale gets decompensated. Functional vasoconstriction of the pulmonary resistive vessels was shown to play an important role in the genesis of the disease: the administration of 0.5 mg of nitroglycerine and a 5-minute oxygen inhalation caused a positive dynamics in the indices of the pulmonary rheogramme and a reduction of the pulmonary artery pressure, which did not reach the level of the plane inhabitants, though.

Adult↗

Transient Increase in ST-segment Changes at Time of Reperfusion in Acute Myocardial Infarction Treated by Coronary Angioplasty.

PURPOSE: The clinical significance of early ST-segment re-elevation, a so called Òreperfusion peakÓ in patients with acute myocardial infarction (AMI) treated with thrombolysis is unclear. We examined the incidence and significance of early ST-segment re-elevation immediately upon reperfusion in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) where the time of reperfusion can be precisely established. METHODS: Thirty-two patients (6 women, 26 men, age 61.5 +/- 10.2 years) with an AMI, admitted less than four hours after the onset of chest pain, were included. Twenty-four patients were treated with primary PTCA and eight with rescue PTCA. Computerized on-line vectorcardiography was used for continuous ischemia monitoring. A reperfusion peak was defined as an increase in ST-vector magnitude (ST-VM) of > 50 µV, starting within two minutes after the re-opening of the infarct-related coronary artery and followed by an immediate decrease in the ST segment. RESULTS: Primary success was achieved in all treated patients. Twenty of the patients (63%) developed a reperfusion peak. ST-VM before coronary angiography was significantly larger (p = 0.004) and peak enzyme levels were higher (p = 0.014) in patients who developed a reperfusion peak. Thrombolytic treatment prior to rescue angioplasty, time to reperfusion, target vessel, presence of collaterals or medication on admission did not differ significantly between the groups. CONCLUSION: The occurrence of a reperfusion peak during the minutes after the onset of reperfusion is a common finding in patients with AMI treated at an early stage with angioplasty. There is a relationship with the occurrence of a reperfusion peak and the extent of the initial ST deviation (presumably reflecting the myocardium at risk) and peak enzyme levels. The importance of a reperfusion peak for clinical outcome and prognosis is so far not known.

Journal Article↗

[A history of the electrocardiogram].

The discoveries by Galvani and Volta of electricity and its effects fascinated the intellectual world, but it was not until 1856 that Köllicker and Müller discovered that the heart muscle could produce electric activity. Muirhead in London recorded the first electrocardiogram (ECG) in man in 1869 or 1870 with a siphon instrument and Waller in 1887 with a capillary electrometer. Einthoven's string galvanometer was a breakthrough. As early as five years after his publication Einthoven introduced "Le Télecardiograme" in 1906 by which a cable connected his instrument to a hospital one and a half kilometres away. The string galvanometer produced precise ECG recordings but it was like the opera primadonnas of the time, voluminous and unpredictable. Rune Elmqvist developed the direct-writing inkjet recorder, first demonstrated at the Congress of Cardiology in Paris, 1950. Ohnell's studies of preexcitation, to which the WPW-syndrome belongs, were important. After the initial focus on arrhythmias, ECG became more and more used in the diagnosis of myocardial ischaemia and coronary heart disease. To refine this diagnosis the hypoxaemia (breathing air with low oxygen content) test, as well as the exercise test and other stress tests were introduced. Vectorcardiography displays the spatial movements of the electrical forces generated by the heart. Long-term ECG registration with a portable tape recorder is important both for the diagnosis of arrhythmias and myocardial ischaemia. Foetal and comparative ECG have provided important clinical and scientific information.

Electrocardiography↗

[Pathways in the development of electrocardiography].

Electrocardiography celebrates hundred years of its existence. The historical article on the cornerstones of its development was written on request of the editorial board of Vnitrní lékarství (Internal Medicine) and the Czech Society of Internal Medicine. After summarizing the beginnings of the discovery of bioelectric current and attempts of its registration the author describes the construction of the string galvanometer by Willem Einthoven. In 1901 and 1903 he published the first findings on the application of electrocardiography in man. Therefore that years are considered the years when clinical electrocardiography was born. Next we deal with the development of lead systems and modern electrocardiographs, incl. the discovery of the Braun tube, the construction of monitors, vectorcardiography and spatiocardiography. The author summarizes the principles of rational interpretation of the surface electrocardiogram and analyzes further modifications such as the use of leads from the right hemithorax, oesophageal leads, stress electrocardiography. Classical surface electrocardiography is probably a completed discipline. It will remain also in future a basic auxiliary examination method in internal medicine and allied disciplines. Due to its importance however classical electrocardiographic examination should be shifted into primary care where it may be a great enrichment and acceleration of the diagnostic process. Further development of electrocardiology is focused on non-invasive and invasive examinations and in particular treatment of arrhythmias where surface electrocardiography will be also in future important as a reference signal for the time localization of electric potentials of the intracardial electrocardiogram and programmed electrical stimulation.

Electrocardiography↗

[Orthogonal electrocardiography].

The orthogonal electrocardiography was a further development of Einthovens conception of electrocardiography. It eliminates the redundancy of the 12-lead ECG and offers a more precise and illustrative image of the model of an equivalent dipole. It was the prerequisite of the development of vectorcardiography. It improves the diagnostic performance of electrocardiology, especially by decreasing the spread of parameters used to characterize normal cardiac electrogenesis. It may be assumed that clinical electrocardiography will not petrify its standard 12-lead system but will utilize the possibilities offered by the more rational lead systems of orthogonal electrocardiography, as well as its enrichment by vectorcardiographic presentation of the cardiac electric field.

Electrocardiography↗