The rationale of using calcium antagonists in the treatment of ischaemic heart disease
Approximately one-third of patients dying suddenly exhibit occlusive coronary artery thrombi, in contrast to the high frequency (90%) associated with transmural myocardial infarction. Such a discrepancy, along with other considerations, indicates that not all cases of sudden cardiac death are simply the result of myocardial ischemia or infarction in the traditional sense, and does, we believe, justify a rigorous search for alternative pathophysiological mechanisms. Some alternative mechanisms have been discussed, including disturbances in the cardiac conducting system, and the potentially very important role of platelet microembolism or microthrombosis in the genesis of focal ischemia and the lethal arrhythmias. Additionally, not all disturbances leading to the development of lethal arrhythmias may be reflected in light microscopic changes. There is a need for more sophisticated methodological approaches to the detection of early ischemia or other changes at a subcellular level. Although existing studies have provided a useful initial approach to an understanding of the pathology of sudden cardiac death, more questions remain unanswered than answered. In particular, no definitive comparison of deaths occurring in or out of hospital is currently possible, while much more information is necessary in relationship to the clinical status of patients dying suddenly. For example, one needs to know whether there are fundamental pathological differences in patients dying instantaneously relative to those surviving minutes or hours after the onset of terminal symptoms or signs; to what extent the pathologic findings are modified by therapy; whether there are any terminal symptoms specifically associated with particular pathological findings; what differences, if any, exist between patients with myocardial injury who die suddenly and those who do not; and how one can ensure a reasonable degree of comparability between different studies. Answers to these and many other questions will not, we believe, be forthcoming if we continue to be preoccupied with the epicardial arteries and light microscopy alone, but rather from well-conceived studies employing the collective resources of clinical cardiology, epidemiology, pathology, and experimental biology.