To determine whether sudden cardiac death exhibits a circadian rhythm similar to that recently demonstrated for nonfatal myocardial infarction, we analyzed the time of day of sudden cardiac death as indicated by death certificates of 2203 individuals dying out of the hospital in Massachusetts in 1983. The data reveal a prominent circadian variation of sudden cardiac death, with a low incidence during the night and an increased incidence from 7 to 11 A.M. The pattern is remarkably similar to that reported for nonfatal myocardial infarction and episodes of myocardial ischemia. The finding that the frequency of sudden cardiac death is increased in the morning is compatible with hypotheses that sudden cardiac death results from ischemia or from a primary arrhythmic event. Further study of the physiologic changes occurring in the morning may provide new information supporting or refuting these hypotheses, thereby leading to increased understanding and possible prevention of sudden cardiac death.

Circadian variation in the frequency of sudden cardiac death.

To investigate the pathogenesis of myocardial infarction we undertook a systematic study of patients with angina at rest, a syndrome known to evolve frequently into infarction. Among 187 consecutive patients, 37 had infarction, all in the area that showed electrocardiographic changes during angina. In all 76 patients who underwent hemodynamic monitoring, 201thallium myocardial scintigraphy or angiography during angina, a vasospastic origin of the attacks was documented. In six patients with infarction shortly after these studies and in two in whom the infarction developed during hemodynamic monitoring or during angiography the onset of infarction was indistinguishable from the onset of anginal attacks. One patient in whom spasm was observed at the onset of infarction died six hours later; at post-mortem examination, a fresh laminar thrombus was found at the site of the spasm. After infarction, complete thrombotic occlusion of the branch shown to undergo vasospasm was documented in two patients by...

Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of "preinfarction" angina.

https://journal.chestnet.org/article/S0012-3692(16)61834-2/pdf

The Histopathologic Evolution of Myocardial Infarction

Ischemic contracture of the left ventricle (“stone heart”) occurs in the rat heart after a period of global ischemia at 37° C. The time of onset of contracture can be delayed by various interventions that reduce myocardial energy demand, increase myocardial energy supply or reduce cellular calcium influx. Conversely, the time of onset of contracture may be advanced by interventions that reduce the energy supply. Analysis of myocardial energy metabolism, and particularly of adenosine triphosphate (ATP) availability in relation to the onset and duration of contracture suggests that contracture is initiated when the cellular ATP content decreases to approximately 12 μmoles/g dry weight. Furthermore, the progression of contracture is characterized by an acceleration in the rate of ATP degradation and the completion of contracture coincides with the reduction of ATP to 3 to 4 μmoles/g dry weight. The results of this study suggest that the development of ischemic contracture represents the accumulation of rigor complexes arising as a result of an ATP deficiency. These rigor complexes are able to exacerbate the contracture by promoting uncontrolled ATP hydrolysis. Although the development of these complexes and the onset of contracture is calcium-insensitive the results indicate that calcium availability may influence the magnitude of the developed contracture.

Ischemic contracture of the myocardium: mechanisms and prevention.

The cardiomyopathic Syrian hamster develops focal myocardial necrosis beginning at 1 month of age, which leads to eventual ventricular failure within 1 year. The pathogenesis of this myocytolytic necrosis is unknown. Based on the nature of the cell necrosis, cytochemical evidence of vascular alterations, and the sensitivity of the hamsters to catecholamines and other vasoactive substances, we believe that the cardiomyopathy may be mediated by abnormalities of the microcirculation. Nonetheless, until the present study, no significant changes have been observed in these vessels. To elucidate the pathogenesis of this disease, we perfused living cardiomyopathic hamsters with silicone rubber solutions, which revealed numerous areas of microvascular constriction, diffuse vessel narrowing and luminal irregularity. Fixed structural lesions in these vessels could not be demonstrated. Pretreatment of young hamsters with verapamil during the period when they normally develop myocardial necrosis prevented myocytolytic lesions and abolished microvascular hyperreactivity. We believe that focal, transient spasm of small blood vessels, probably secondary to vasoactive substances, may cause myocytolytic necrosis (a form of reperfusion injury) in this model. This may also be a multifactorial disease with myocellular as well as vascular abnormalities leading to myocardial degeneration. The similarity of this disease to human and experimental cardiomyopathy suggests that microvascular spasm may be a common denominator of many different cardiomyopathic syndromes.

Giorgio Baroldi

Papers

Different types of myocardial necrosis in coronary heart disease: a pathophysiologic review of their functional significance.

Letter: Myocardial necrosis: the need for definition.

Myocardial cell damage in “stone hearts”

Coronary stenosis: Ischemic or non-ischemic factor?