Shapur Naimi

Distinctive time course of ventricular vulnerability to fibrillation during and after release of coronary ligation

Abstract Release of left anterior descending coronary artery ligature was performed in 32 dogs after periods of ligation ranging from 3 to 45 minutes. Spontaneous ventricular tachycardia or fibrillation occurred during occlusion in 9 of 20 dogs, developing during the first 8 minutes of occlusion in 8 of the 9. Ventricular tachycardia or fibrillation was evoked by release of occlusion in 3 of 7 dogs after a short-term occlusion of 3 to 6 minutes, and in 9 of 13 dogs after release of a long-term occlusion of 15 to 45 minutes. Thresholds for induced ventricular tachycardia or fibrillation were obtained using a train of gated stimuli (100 Hz for 250 msec). During short-term occlusions, average thresholds for ventricular tachycardia or fibrillation were reduced from 32.4 ma (control) to 3.4 ma ( P Our data suggest the following conclusions: (1) The time course of spontaneous ventricular vulnerability to fibrillation during coronary occlusion differs from that of ligature release, the former diminishing and the latter increasing with the duration of occlusion. (2) This observation and the lack of correlation between thresholds of induced ventricular tachycardia or fibrillation and spontaneous vulnerability to fibrillation after ligature release suggest different electrophysiologic mechanisms for ventricular tachyarrhythmias during and after release of coronary ligation.

Differential diagnosis generation from a causal network with probabilities

One of the problems with building expert systems for medical domains is handling the uncertainty that exists in almost every task. The authors solve this problem, in the context of a system for diagnosing and managing patients with cardiovascular disease, by developing a heuristic method for generating likely causal hypotheses for a set of clinical findings. The method uses the potential causal pathways to determine sets of primary causes that could produce the findings. From each set it builds a hypothesis by determining the most probable explanation for each finding and adding that explanation to the hypothesis. Hypotheses are compared by computing the overall probability of each as an explanation for the findings. The most likely hypotheses are presented to the user as a detailed differential list. The method has been tested in a network with 150 physiological nodes and about 280 potential findings. It produces differential diagnoses for cases with 10 to 15 abnormal findings in a few minutes. Each hypothesis contains 20 to 30 physiological nodes which can be displayed with their interconnections, showing the user how the findings can be accounted for by the possible causes.<<ETX>>

Multifocal Atrial Tachycardia (Chaotic Atrial Tachycardia) Clinical Associations and Significance

Multifocal atrial tachycardia, also designated “chaotic atrial tachycardia,” was identified in the records of 31 patients. It was particularly noted that the arrhythmia progressed to atrial fibrillation or flutter in 17 cases (55%). Unifocal or multifocal premature atrial contractions preceded the arrhythmia in 20 cases (64%). The arrhythmia developed during an acute illness in 18 cases (58%). However, it occasionally occurred in paroxysms without an apparent cause in patients with chronic disease. Significant acute or chronic pulmonary disease was present in 12 cases (39%). The arrhythmia was not associated with digitalis toxicity or with rhythm disturbances known to occur in digitalis intoxication such as paroxysmal atrial tachycardia with block. In general, digitalis therapy seemed to have little effect on the course of the arrhythmia, but in some cases it appeared to be beneficial, especially if atrial fibrillation supervened. In several patients there seemed to be a transition from multifocal premature atrial contractions through chaotic atrial tachycardia to atrial fibrillation. These observations suggested that chaotic atrial tachycardia might be a forewarning of atrial fibrillation and that the two arrhythmias may have a similar mechanism.

Dispersion of effective refractory period during abrupt reperfusion of ischemic myocardium in dogs

Dispersion of the effective refractory period was measured in anesthetized dogs using a computerized system and bipolar epicardial electrodes or, alternatively, transmural plunge electrodes. Measurements were made at 1 minute intervals during short (5 minute) and long (15 minute) periods of coronary arterial ligation and for 3 to 5 minutes after release of the ligatures. Both transepicardial and transmural temporal dispersion of refractoriness correlated well with the increased vulnerability to spontaneous ventricular fibrillation during short periods of ligation and the relative electrical stability observed toward the end of the longer periods of ligation. During reperfusion, transmural dispersion increased somewhat after ligature release in the longer-term experiments but the increase did not appear adequate to explain the associated large incidence of spontaneous arrhythmias after release. Effective refractory periods measured at one nonischemic and five ischemic electrode sites at intervals as short as 20 seconds revealed abrupt shortening of the refractory period at all ischemic sites during the 1st minute of reperfusion, resulting in a large but short-lived electrical gradient between the ischemic and nonischemic myocardium. This increased dispersion between the ischemic and nonischemic myocardium occurred at a time of maximal vulnerability to reperfusion arrhythmias. However, this increased dispersion was greater after the 5 minute than after the 15 minute periods of ligation and thus does not fully explain the greater incidence of reperfusion arrhythmias after ligature release in the longer-term studies. Although arrhythmias of acute ischemia are associated with increased dispersion of refractoriness within theischemic segment and reperfusion arrhythmias with dispersion between ischemic and nonischemic segments, other electrophysiologic alterations probably play an important role in the genesis of the arrhythmias of reperfusion.

Studies of Coagulation and Fibrinolysis of the Arterial and Venous Blood in Normal Subjects and Patients with Atherosclerosis

In studies of coagulation of the arterial and venous blood of relatively young normal subjects, there were statistically significant arteriovenous differences in some of the tests employed. These differences, however, were not all in the same direction, in that some indicated increased and some decreased coagulation activity of the arterial blood. In patients with coronary heart disease, these arteriovenous differences were absent or less marked. It was suggested that this change in arteriovenous difference in such patients could possibly be attributed to the surface effect of the diseased arterial wall on the coagulation mechanism. It was recognized, however, that a number of other factors could contribute to, or entirely account for, this phenomenon.There was some evidence of increased coagulation activity in the venous blood of patients with coronary heart disease as compared to matched controls. This was indicated by a more rapid generation of thromboplastin with the addition of inosithin (platelet substitute), and a more rapid generation as well as a greater yield of thromboplastin without the addition of inosithin.Fibrinolytic activity was significantly lower in the arterial blood compared to the venous in both the normal subjects and patients with atherosclerosis. This arteriovenous difference was greater in the atherosclerotic group and it was widely variable. Because of this variability, venous fibrinolysis determinations could not be taken as an indicator of the level of fibrinolytic activity in the arterial blood. Hence, it was suggested that in studies of fibrinolysis as related to atherosclerosis, arterial blood samples should be routinely used.Fibrinolytic activity of the blood in the atherosclerotic group as a whole was lower than that in the normal group on both the arterial and the venous sides. The difference between the two groups was greater in the arterial than the venous blood. In the group with atherosclerosis, the subgroup with coronary heart disease and that with occlusive disease of the peripheral arteries were separately analyzed. The subgroup with coronary heart disease exhibited a significantly lower fibrinolytic activity compared to normal subjects only in the arterial blood, whereas the subgroup with occlusive disease of the peripheral arteries showed a lower fibrinolytic activity in both the arterial and the venous blood. In the subgroup with occlusive disease of the peripheral arteries, it was particularly note-worthy that the younger patients had a very low fibrinolytic activity. It was thought that one could only speculate as to whether this low fibrinolytic activity in such young patients is in any way causally related to the disease process.It appeared that in patients with coronary heart disease the delicate balance of coagulation and fibrinolysis was tipped in the direction of clot formation. It was not clear, however, whether the changes in blood coagulation and fibrinolysis observed in such patients were etiologic in the pathogenesis of the disease process, associated with it, or simply a secondary phenomenon. Moreover, it was recognized that in vitro demonstration of such changes in blood coagulation and fibrinolysis does not necessarily imply in vivo hypercoagulability.No correlation was found between the level of serum cholesterol and plasma fibrinolytic activity.

Reasoning requirements for diagnosis of heart disease

Over the past dozen years, the Heart Disease Program (HDP) has been developed to assist physicians in reasoning about cardiovascular disorders. Driven by several evaluations, the inference mechanism has progressed from a logic based model, to a Bayesian Probability Network (BPN) and finally a pseudo-Bayesian network with temporal and severity reasoning. Though aspects of cardiovascular reasoning are handled well by BPNs, temporal reasoning, homeostatic feedback mechanisms and effects of disease severities require additional inference strategies. This article discusses how these reasoning problems are handled, and deals with closely linked issues in building the user interface to collect detailed cardiovascular data and provide clear explanations of diagnoses.

Development of a knowledge base for diagnostic reasoning in cardiology

This paper reports on a formative evaluation of the diagnostic capabilities of the Heart Failure Program, which uses a probability network and a heuristic hypothesis generator. Using 242 cardiac cases collected from discharge summaries at a tertiary care hospital, we compared the diagnoses of the program to diagnoses collected from cardiologists using the same information as was available to the program. With some adjustments to the knowledge base, the Heart Failure Program produces appropriate diagnoses about 90% of the time on this training set. The main reasons for the inappropriate diagnoses of the remaining 10% include inadequate reasoning with temporal relations between cause and effect, severity relations, and independence of acute and chronic diseases.

Sequential unipolar strength-interval curves and conduction times during myocardial ischemia and reperfusion in the dog.

Computerized techniques were employed to generate alternating anodal and cathodal or sequential anodal strength-interval curves during and following 15-minute coronary artery ligations in 14 anesthetized dogs. The right atrium was paced at 2.5 Hz, and unipolar ventricular strengthinterval curves with simultaneous conduction times were recorded every 45-120 seconds during ischemia and reperfusion. Within 1-2 minutes of ligation, anodal midcurve and late diastolic thresholds fell sharply, and cathodal thresholds fell slightly or changed little. After 5 minutes of ischemia, anodal thresholds remained low, cathodal thresholds rose, and conduction times increased. At 10–15 minutes of ligation, if the ischemic zone was small, anodal thresholds were low, often approaching cathodal values, and conduction returned toward control values. When the ischemic zone was large, unipolar thresholds and conduction times increased late during the ligation period. Throughout the course of ischemia, the falling limb of the strength-interval curve shifted progressively to the left indicating shorter refractory periods. Following abrupt reperfusion, anodal phase 3 dips promptly reappeared; refractory periods returned toward control, and supernormal conduction was noted. By 3-5 minutes of reperfusion, the falling limb of the strength-interval curve had shifted to the right of control and conduction times increased. Thus, vulnerability to arrhythmias during early ischemia (i.e., 5 minutes) is characterized by low anodal midcurves and late diastolic thresholds, short refractory periods, and slow conduction. During the first minute of reperfusion, anodal excitability is increased during the early dip and conduction times are supernormal. Increases in anodal excitability correlate better with the peak incidence of early ligation and reperfusion arrhythmias than do changes in cathodal excitability.

The Development and Use of a Causal Model for Reasoning about Heart Failure

The investigation of causal models as a paradigm of automated reasoning has blossomed. However, there are a wide variety of views of what a causal model is. The causal models that have appeared in the literature range from the qualitative simulation models of Kuipers and Kassirer1 to the probabilistic organization schemes of Pearl.2 Investigation of a particular problem of medical diagnosis or management usually leads to the realization that there is some truth in all of the camps. The problem becomes how to cast the various aspects of the problem into the appropriate causal framework and how to integrate the divergent aspects of the problem into a coherent whole.

Evaluation of a New Method for Cardiovascular Reasoning

OBJECTIVE Evaluate the accuracy of the detailed diagnostic reasoning of the Heart Failure Program incorporating a new mechanism to handle temporal relationships and severity constraints. DESIGN Tools were developed to summarize diagnoses and automatically generate evaluation forms. Five expert cardiologists were asked to review the reasoning of the program, with two analyzing each case. Cases were gathered retrospectively for diversity and difficulty and 26 randomly selected cases were evaluated. The underlying issues were identified and classified. RESULTS Both reviewers rated the first diagnosis correct in 25% of the cases and at least one rated it wrong in 10%. Analyzing the detailed reasoning, 137 issues were raised, about 5.3 per case. Of these, 53% were possible concerns raised by one reviewer. Of the 5.3 issues per case, 2.5 were attributable to controversies, misunderstandings, or mistakes; 1 was due to the overly simplistic representation of the summaries; and 1.8 were issues related to the program. CONCLUSION Overall, the program is capable of providing high-quality detailed diagnostic hypotheses for complex cardiovascular cases. The results highlight several issues: 1) the difficulty of effectively summarizing hypotheses, 2) the nature of a physicians causal explanation, and 3) some problems in evaluating detailed diagnostic reasoning. The mistakes the program made imply that some additional refinement is needed but that the reasoning mechanisms developed can support the appropriate reasoning. The appropriate next step is a prospective evaluation addressing the programs usefulness.