This review defines the substantial pediatric morbidity from tobacco use, including health effects on the cardiovascular system, the respiratory system, the fetus and newborn, and risk-taking behaviors of adolescents. More recent research suggests effects may extend to other areas, including reports that cigarette smoking decreases breast milk production in mothers, byproducts of tobacco use are transmitted in breast milk, exposure to passive smoking may alter children's intelligence and behavior, and passive smoke exposure in childhood may be a risk factor for developing lung cancer as an adult. Primary prevention is the most effective strategy to decrease the prevalence of smoking. Those who never smoke never become addicted to nicotine and never have to quit. Secondary prevention must also be emphasized, because children whose parents smoke are exposed to health risks and are themselves more likely to smoke in the future. Parental health can be improved by smoking cessation. To accomplish the goals of primary and secondary prevention, the aggressive public health strategy directed at both parents and children should be expanded. This strategy requires the strong support of physicians, with emphasis on prevention in practice, support of public health initiatives, medical and public policy, and the conduct of high-quality research.

Congestive heart failure is a common, highly lethal cardiovascular disorder claiming over 200,000 lives a year in the United States alone. Some 50% of the deaths in heart failure patients are sudden, and most of these are probably the result of ventricular tachyarrhythmias. Methods designed to identify patients at risk have been remarkably unrewarding, as have attempts to intervene and prevent sudden death in these patients. The failure to impact favorably on the incidence of sudden death in heart failure patients stems largely from a lack of understanding of the underlying mechanisms of arrhythmogenesis. This article explores the role of abnormalities of ventricular repolarization in heart failure patients. We will examine evidence for the hypothesis that alteration of repolarizing K+ channel expression in failing myocardium predisposes to abnormalities in repolarization that are arrhythmogenic. The possible utility of novel electrophysiological and ECG measures of altered ventricular repolarization will be explored. Understanding the mechanism of sudden death in heart failure may lead to effective therapy and more accurate identification of patients at greatest risk.

Exercise testing of children differs from adult exercise testing in many ways beyond the technical issues related to test performance that are addressed in this report. Disease processes that produce myocardial ischemia are relatively rare in children compared with adults. Exercise testing may be useful in these cases, but the use of testing to assess functional capacity or cardiac rhythms will be encountered more often. Although the precise role of exercise testing in patient evaluation or long-term management of the cardiac patient will vary somewhat from center to center, exercise testing is often essential to diagnose and to direct treatment in a wide variety of clinical problems. An understanding of the role of exercise testing for children with known or suspected heart abnormalities is an essential part of the training of pediatric cardiologists. The staff of the pediatric exercise laboratory should be available to discuss with the clinician when a test might be of value in a specific case in addition to providing advice about the specifics of the performance of the test and offering age- and size-appropriate normal data from the laboratory with test interpretation.

Myocardial infarction is the most frequent cause of mortality in the United States as well as in most western countries. In this review, the processes leading to myocardial infarction are described based on the most recent studies of vascular biology; in addition, evolving strategies for prevention are outlined. The following was specifically discussed. (1) Five phases of the progression of coronary atherosclerosis (phases 1 to 5) and eight morphologically different lesions (types I, II, III, IV, Va, Vb, Vc, and VI) in the various phases are defined. (2) The present understanding of the pathogenesis of each of the phases of progression and of the various lesion types preceding myocardial infarction is described; particular emphasis is placed on the physical, structural, cellular, and chemical characteristics of the "vulnerable or unstable plaques" prone to disruption (types IV and Va lesions). (3) The fate of plaque disruption (type VI lesion) in the genesis of the various coronary syndromes and especially acute myocardial infarction is defined; particular emphasis is placed on the combination of plaque disruption and a high thrombogenic risk profile--local factors (ie, degree of plaque disruption, exposure of lipid-macrophage-rich plaque, etc) and systemic factors (ie, catecholamines, RAS, fibrinogen, etc)--in the genesis of myocardial infarction. (4) Strategies of regression or stabilization of "vulnerable or unstable plaques" for prevention of myocardial infarction are presented within the context of recent favorable experience with risk factor modification and lipid-modifying angiographic trials, beta-blockade and angiotensin-converting enzyme inhibition, antithrombotic strategies, and the possible role of estrogens. The recent past has been very fruitful in yielding a better understanding of the processes leading to myocardial infarction, and the near future appears very promising in terms of preventing the number 1 killer in the western world.

Currently used antithrombotics such as heparin have a number of potential limitations that may be overcome by the new class of agents that directly inhibit thrombin. These agents variously block the active catalytic and/or the anion binding exosites of the thrombin molecule and are potent and specific inhibitors of thrombin's many biological actions, as demonstrated by in vitro and animal models of thrombosis. Preliminary data indicate that the direct antithrombins are safe and efficacious in humans, and their use in acute coronary syndromes and coronary angioplasty in place of heparin has yielded promising early results. Phase III trials in these clinical settings are currently under way. Newer antithrombotics that inhibit thrombin generation and thrombin activity at various strategic points within the coagulation cascade are also in the early stages of development.

Numerous reports suggest that coronary artery disease can regress with lipoprotein manipulation. Many of these reports lack control groups and contain relatively small numbers.

Although intracoronary ultrasonography allows detailed tomographic imaging of the arterial wall, it fails to provide data on the structural architecture and longitudinal extent of arterial disease. This information is essential for decision making during therapeutic interventions. Three-dimensional reconstruction techniques offer visualization of the complex longitudinal architecture of atherosclerotic plaques in composite display. Progress in computer hardware and software technology have shortened the reconstruction process and reduced operator interaction considerably, generating three-dimensional images with delineation of mural anatomy and pathology. The indications for intravascular ultrasonography will grow as the technique offers the unique capability of providing ultrasonic histology of the arterial wall, and the need for a three-dimensional display format for comprehensive analysis is increasingly recognized. Consequently, three-dimensional imaging is being rapidly implemented in the catheterization laboratories for guidance of intracoronary interventions and detailed assessment of their results. However exciting the prospects may be, three-dimensional reconstructions at present remain partially artificial because the true spatial position of the imaging catheter tip is not recorded, and shifts in its location and curves of the arterial lumen result in pseudoreconstructions rather than true reconstructions. In this report, we address the principles of three-dimensional reconstruction with a critical review of its limitations. Potential solutions for refinement of this exciting imaging modality are presented.

Rupture of the lipid-rich atheromatous plaque, intraplaque hemorrhage, and intraluminal thrombus are three pathological hallmarks most commonly recognized in the infarct-related coronary artery at the site of acute myocardial infarction. Rupture of the atheromatous plaque is closely related to but does not fully explain the genesis of occlusive intracoronary thrombus formation and thus the development of acute myocardial infarction. Besides a variety of hematologic disorders, one should emphasize the role of the platelet-derived mediators that promote an environment where thrombosis and vasoconstriction occur, including TXA2, serotonin, ADP, platelet-derived growth factor, tissue factor, and the diminished availability of those natural endogenous substances that inhibit platelet aggregation, such as EDRF, tissue plasminogen activator, and PGI2. PGI2 released from vascular endothelial cells is extremely unstable. Our group provided the first evidence that HDL stabilizes PGI2 through the newly discovered function of Apo A-I, which is associated with the surface of HDL particles and identified as PGI2 stabilizing factor. Decrease in HDL-associated Apo A-I in patients with unstable angina and during the acute phase of myocardial infarction indicates that HDL plays an important role in preventing coronary atherosclerosis and intracoronary thrombus formation by stabilizing PGI2 in addition to the generally accepted biochemical property of HDL to prevent the accumulation of cholesterol by mobilizing free cholesterol from tissues or macrophages. There is also a PGI2 synthesis-stimulating factor in serum that has not yet been identified chemically. EDRF or nitric oxide provides another important regulating system in the vessel wall. Lipoproteins are inhibitors of endothelium-dependent relaxation of rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)