Platelets are postulated to have an important role in acute and chronic cardiovascular events. Clinical events may result during the sequence of platelet activation reactions of adhesion, aggregate formation, release of granular constituents, thromboxane A2 formation, microembolization and platelet vascular occlusion. For example, sudden death may occur in patients with increased platelet sensitivity to catecholamine stimulation, platelet aggregate formation and thromboxane A2 generation resulting in ischemic ventricular arrhythmia induced by small-vessel platelet microembolization and local thromboxane A2 vasoconstriction. Whereas angina might be manifest if the microemboli disaggregated and vasospasm were transient, myocardial infarction would follow extensive permanent occlusion of small vessels or localized narrowing by vasospasm and extension of platelet thrombus formation at the site of intimal thickening. Platelets may also have an important role in atherogenesis through the mediation of the platelet-derived growth factor in the proliferative smooth muscle cell intimal lesion. Direct experimental and indirect clinical studies support the concept that platelets are important in cardiovascular events, but the relationship to spasm and to other possibly even more important mechanisms is not clear. Acute myocardial infarction and mural thrombogenesis appear to have the greatest evidence of being platelet-related.

Case-control and prospective epidemiologic studies have found a striking, consistently negative association between high-density lipoprotein (HDL) levels and coronary vascular events. As a result, the genetic and environmental determinants of HDL levels are being studied intensively. These investigations and their potential clinical applications require a fundamental understanding of the structure, function and metabolism of HDL and its components. Of special interest are the means by which HDL exerts its apparently protective effect. In this report we characterize the structure of HDL and describe its components, particularly the protein component. We discuss HDL metabolism in light of the relationship of HDL to the other lipoprotein classes, and relate what little is known of the functions of HDL. We also review the biochemical mechanisms by which HDL may protect against cardiovascular disease and discuss further biochemical research that will be necessary for a better understanding of HDL.

Available estimates of the ratio of wall thickness to luminal radius of human coronary arteries and certain geometrical assumptions were used to calculate the amounts of vascular smooth muscle shortening required to produce specific changes in luminal diameter for hypothetical "normal" and stenotic arteries. The results indicate that even modest mural thickening due to disease may act as a "lever" in translating physiologic degrees of medial smooth muscle shortening into critical luminal obstructions, providing the diseased segment maintains some pliability. The possibility of acute luminal occlusion occurring at stenotic sites as the result of "normal" vasomotion is illustrated. The appropriate use of the term coronary arterial "spasm" is discussed in light of these observations.

The history of vascular surgery and the developments that made it possible are briefly traced. Approaches to the treatment of arterial lesions are considered in terms of the characteristic anatomic, pathologic and clinical patterns of arteriosclerosis or atherosclerosis, the basic underlying lesion in most aneurysmal and occlusive diseases of the aorta and major arteries. The importance of appreciating the various patterns and rates of progression of atherosclerosis is emphasized.

Altered regional mechanical myocardial performance is an early, sensitive marker of myocardial ischemia, and can be estimated in man with reasonable accuracy. Identification, localization and quantification of abnormalities in mechanical performance can be used to predict the presence of coronary artery disease. Testing techniques that have little or no effect on diagnostic efficiency must be replaced with more sensitive indicators of ischemia. If experimental data are validated by findings in human subjects, accurate identification of regional wall motion changes during test conditions should prove to be a powerful marker of ischemia. To be of value, a diagnostic test must strongly increase the frequency of identification of subjects with a high probabilty for the presence of coronary artery disease in an otherwise low-prevalence population, and of those with known disease who are at the highest risk for complications including myocardial infarction or death.

In the past three decades, techniques that permit noninvasive quantitation of the function of the heart have been developed. Exercise electrocardiography has been widely used to determine the presence or absence of ischemic heart disease. Echocardiography permits detection of valvular, congenital and arteriosclerotic disease and quantitation of its severity. Selective use of isotopes allows nuclear angiogarphy, myocardial perfusion studies and detection of damage to cellular myocardium. New techniques such as computerized axial tomography, magnetometry, focused pulsed Doppler, and wider application of computer-enhanced image processing are important future directions for noninvasive monitoring.

The number of patients with cerebral infarctions increases as the population ages, despite campaigns against hypertension, the greatest risk factor. Cerebral ischemia initiates events that are presumed to defer the stage of irreversible injury. These events cause an increase of perfusion around the central ischemic zone and trigger the Bohr effect, both of which preserve tissue viability. Almost simultaneously, mitochondrial function fails, resulting in insufficient energy for the enzyme systems to control Na and K ion equilibrium. At the same time, protein synthesis slows and cellular respiratory enzymes decrease their activity, initiating an irreversible state of tissue change. Tissue fatty acids increase as a result of dissolution of cell membrane lipoprotein structure. Barbiturates reduce the extent of experimental infarction. Resperine and aminophylline are also effective, but there are no corroborative clinical trials. That ischemic brain damage may be the result of toxic substances in the ischemic tissue represents a new concept.

1) While it is possible only one type of second-degree AV block exists electrophysiologically, the available data do not justify such a conclusion and it would seem more appropriate to remain a "splitter," and advocate separation and definition of multiple mechanisms, than to be a "lumper," and embrace a unitary concept. 2) The clinical classification of type I and type II AV block, based on present scalar electrocardiographic criteria, for the most part accurately differentiates clinically important categories of patients. Such a classification is descriptive, but serves a useful function and should be preserved, taking into account the caveats mentioned above. The site of block generally determines the clinical course for the patient. For most examples of AV block, the type I and type II classification in present use is based on the site of block. Because block in the His-Purkinje system is preceded by small or nonmeasurable increments, it is called type II AV block; but the very fact that it is preceded by small increments is because it occurs in the His-Purkinje system. Similar logic can be applied to type I AV block in the AV node. Exceptions do occur. If the site of AV block cannot be distinguished with certainity from the scalar ECG, an electrophysiologic study will generally reveal the answer.

The Starling relationship in the normal human ventricle may be different than usually portrayed. In normal, resting, supine man the ventricular function curve is at its peak at a left ventricular end-diastolic pressure of approximately 10 mm Hg. Below this point is a strong direct relation between filling pressure and stroke work, while at higher filling pressures, a plateau occurs. Limitation of ventricular response is related to a sharply rising ventricular pressure-volume curve at a normal level of filling pressure. Thus, in the supine position, the normal heart is not on the active portion of the ventricular function curve, but is in a unique position in which cardiac output is probably controlled by factors other than ventricular filling pressure. In ventricular failure, the peak of the ventricular function curve is displaced to a higher level.

This report deals with the ramifications of the concept of left axis deviation. In early life, the leftward shift of the frontal plane QRS axis is determined chiefly, if not solely, by the relative weights of the ventricles. Once adult ventricular weight ratios are reached, there is a long period of axis stability, then a gradual leftward drift of the QRS, governed principally by left anterior fascicular conduction. Thus, the normal QRS axis is age-dependent, and left axis deviation must be considered accordingly.

Changes in cardiac metabolism in myocardial failure and after alcohol ingestion are discussed. The main effect of alcohol ingestion is loss of cardiac contractility. Since heart muscle does not contain alcohol dehydrogenase, its toxicity is probably the result of a direct toxic effect of ethanol and acetaldehyde on the myocardial cell, possibly involving various membrane systems. Alcohol inhibits mitochondrial respiration and the activity of enzymes in the tricarboxylic acid cycle, and its interferes with both mitochondrial calcium uptake and binding. Ethanol profoundly affects myocardial lipid metabolism. Acetaldehyde diminishes myocardial protein synthesis and inhibits Ca++-activated myofibrillar ATPase. In myocardial failure, a series of possibilities may be responsible for the loss of contractility. Excitation-contraction coupling could be disturbed at the level of the sarcolemma, at the sarcoplasmic reticulum, at the mitochondria, and between calcium and the regulatory proteins. Deficiencies in Ca++ delivery systems of excitation-contraction coupling on the myosin ATPase activity could be responsible for the dimunition in cardiac contractility. Mitochondrial function may also be involved, since mitochondria from failing human hearts are defective with respect to respiratory control and calcium accumulation. Under certain conditions, the relationship of mitochondria to calcium sequestration is very important in influencing contractility. The involvement of contractile and regulatory proteins in myocardial failure cannot be excluded.