We have reviewed the literature and supplemented it with our own experience to provide a current viewpoint on emergency coronary bypass in three settings in which cardiogenic shock did not exist preoperatively. Acute failure of coronary angioplasty led to emergency operation in 701 patients with 25 (3.6%) deaths. There was a 37.6% incidence of perioperative infarction. Thrombolytic therapy for acute myocardial infarction, sometimes followed by angioplasty, led to emergency operation within 8 hours in 145 instances with four (2.1%) deaths. Emergency coronary bypass was primary therapy for 1,051 patients with acute myocardial infarction with 51 (4.9%) hospital deaths. Emergency operation for failed angioplasty is frequently mandated in the setting of surgical standby and iatrogenic ischemia although some operations could be postponed to an elective status. Emergency operation after thrombolytic therapy has been used for unsuccessful angioplasty of the infarct vessel, left main stenosis of greater than 50%, left main equivalent, multivessel disease with complex lesions not amenable to angioplasty, or failure to restore patency of the infarct vessel with thrombolysis. Operation within 12 hours of thrombolytic therapy is associated with a coagulopathy causing increased bleeding, the need for transfusion, and a greater incidence of reoperation for perioperative bleeding.

Restenosis after successful PTCA remains a major problem limiting the efficacy of the procedure. The pathophysiologic mechanism of restenosis has been enigmatic so far, but accumulated evidence strongly suggests that intimal hyperplasia is the major mechanism. Based on current understanding of the process of intimal hyperplasia, one unifying concept may be that there are at least two major local biologic determinants influencing this process, lesion characteristics and regional flow dynamics. Lesion characteristics include the plaque structure and the quantity of smooth muscle. These may provide the anatomic substrate that determines the extent of injury and the degree of smooth muscle cell proliferation. The amount of smooth muscle cells in the stenotic lesion activated by injury to undergo proliferation may determine the eventual bulk of the restenotic lesion. In addition, low wall shear stress could promote intimal hyperplasia and cause structural change of vessels to decrease the lumen, whereas high wall shear stress exerts the opposite effects. Intimal hyperplasia after balloon injury is a complex process involving platelets, growth factors, endothelial cells, smooth muscle cells, mechanical injury, wall shear stress, and probably other unknown factors. Platelets not only contribute growth factors such as PDGF but also cause organized thrombus. Different growth factors may be involved in initiating smooth muscle cell proliferation and may come from many different sources, including smooth muscle cells, endothelial cells, and macrophages. Intact confluent endothelial cells may produce heparin sulfates and inhibit intimal proliferation; however, regenerating endothelial cells may have the opposite effect. Thus, the proliferative potential of smooth muscle cells, endothelial recovery, extent of injury, wall shear stress, and other unknown factors may all influence this process. Based on these concepts concerning the biology of restenosis, some research directions concerning potential forms of therapy are proposed.

At this time, endomyocardial biopsy has proven validity as a diagnostic method in few circumstances. However, it is overused. In the near term, the extent of its use should be modified by knowledge of its therapeutic relevance in patients with myocarditis. In the long term, numerous new techniques for studying pathophysiology at the subcellular and molecular levels will demand a central role for endomyocardial biopsy in the diagnosis, treatment and fundamental understanding of myocardial diseases. We believe that endomyocardial biopsy will serve as an indispensible link between basic scientists and clinicians in the effort to describe disease mechanisms.

Information obtained during the past decade suggests the need to reexamine the possibility that the onset of myocardial infarction and sudden cardiac death is frequently triggered by daily activities. The importance of physical or mental stress in triggering onset of coronary thrombosis is supported by the findings that 1) the frequencies of onset of myocardial infarction, sudden cardiac death, and stroke show marked circadian variations with parallel increases in the period from 6:00 AM to noon, 2) transient myocardial ischemia shows a similar morning increase, and episodes are often preceded by mental or physical triggers, 3) a ruptured atherosclerotic plaque, often nonobstructive by itself, lies at the base of most coronary thrombi, 4) a number of physiologic processes that could lead to plaque rupture, a hypercoagulable state or coronary vasoconstriction, are accentuated in the morning, and 5) aspirin and beta-adrenergic blocking agents, which block certain of these processes, have been shown to prevent disease onset. The hypothesis is presented that occlusive coronary thrombosis occurs when 1) an atherosclerotic plaque becomes vulnerable to rupture, 2) mental or physical stress causes the plaque to rupture, and 3) increases in coagulability or vasoconstriction, triggered by daily activities, contribute to complete occlusion of the coronary artery lumen. Recognition of the circadian variation--and the possibility of frequent triggering--of onset of acute disease suggests the need for pharmacologic protection of patients during vulnerable periods, and provides clues to mechanism, the investigations of which may lead to improved methods of prevention.

In 1904, Marchand recognized the consistent association of fatty degeneration and vessel stiffening and introduced the term "atherosclerosis" to indicate this combination. Current research is focused principally on the lipid component, but there is evidence that both aspects are reversible. Atheromatous lipids add significantly to the volume of lesions and thus contribute to vascular obstruction and end-organ damage. Reversal of atherosis has been observed in all the major species used in atherosclerosis research; rabbits, swine, dogs, chicks, pigeons, and subhuman primates. Direct evidence for reversal in humans is based on angiographic trials and is less extensive. One femoral artery and one coronary artery trial indicate that the lesions can be stabilized. CLAS, the largest angiographic trial to date, indicates that coronary lesion reversal is possible. Clinical effects of sclerosis are more subtle, and there is little evidence that sclerosis alone leads to end-organ damage. However, it should be noted that atherosclerotic lesions producing end-organ damage invariably have a major fibrous component. Sclerotic vessels have reduced systolic expansion and abnormally rapid pulse wave propagation, which can be measured noninvasively. Primate studies indicate that sclerosis is induced by hypercholesterolemic diets and is reversible when these diets are withdrawn. Changes in sclerosis may be another useful indicator of the formation and reversal of lesions and may involve changes in EDRF. Future studies of atherosclerosis reversal should use a combination of measures to evaluate both atherosis and sclerosis.

Myocardial dysfunction eventuating in systolic and diastolic pump function abnormalities is a consequence of a wide variety of cardiac diseases. The symptoms that develop in this syndrome appear to be related as much to peripheral and neurohormonal mechanisms as to the underlying pathological and cardiac functional abnormality. Relief of symptoms, slowing of the progression of the cardiac functional abnormality, and prolongation of life provide the major agenda for the physician faced with the management of these patients. Judicious use of vasodilators, diuretics, digoxin, dietary therapy, and exercise therapy can relieve symptoms and improve the quality of life in most patients suffering from this syndrome. Recent evidence that vasodilator drugs can prolong life now provides the physician with further justification for routine use of this class of compounds. The eventual solution to the high mortality in this common disease process may be prevention of the development of overt heart failure by more prompt recognition and early treatment of the signs of ventricular dysfunction. This possibility must await the completion of current and proposed clinical trials.

In recent years, there has been a renewed interest in surgical reconstruction of the insufficient mitral valve because of reconfirmation of the limitations of existing prosthetic and bioprosthetic valves. A follow-up study, including late functional data, of 148 patients who underwent mitral valve reconstruction at our institution was combined with a review of the literature to assess the current status of mitral reconstruction. The results indicate that mitral reconstruction by Carpentier techniques is widely applicable, durable, and relatively free of complication. Freedom from late thromboembolic and anticoagulant complications is particularly notable. These factors could prove to justify earlier operative intervention in patients with mitral insufficiency before permanent myocardial damage evolves. As mitral valve reconstruction techniques become more familiar and widely used, mitral reconstruction may become the operative procedure of choice for mitral insufficiency, especially insufficiency due to degenerative disease.

Positron emission tomography offers the possibility of evaluating and quantifying regional myocardial blood flow and metabolism. Used in patients with coronary artery disease, positron emission tomography has demonstrated sustained metabolic activity in regions with reduced blood flow and impaired contractile function, and it thereby enables differentiation between viable myocardium and myocardium that has succumbed to necrosis and scar formation. Viable myocardial regions identified by metabolic rather than functional or blood-flow criteria are frequently observed in patients after an acute coronary event and in patients with stable coronary artery disease. Positron emission tomography reflects either acute myocardial ischemia, "hibernation," as well as "myocardial stunning." Findings from metabolic imaging have proved useful in characterizing more accurately coronary artery disease and its functional consequences. These findings have been found equally useful for clinical management.

Converting-enzyme inhibition, whether teprotide, captopril, or enalapril is used, produces a larger increase in renal blood flow in patients with essential hypertension than in normal subjects when they are on a low-salt diet, a quantitative difference. When studies were performed in individuals on a high-salt diet, normal subjects showed little or no response, whereas a substantial number of patients with essential hypertension displayed an increase in renal blood flow with these agents, a qualitative difference. The individuals that show this potentiated response we now are coming to recognize, have a number of features that suggest a distinct subgroup, the "nonmodulators." Normotensive offspring of hypertensive patients show a directionally similar but smaller renal vascular response to converting-enzyme inhibition. These hypertensive patients also show a blunted natriuresis in response to a sodium loading, which is corrected by converting-enzyme inhibition. Several lines of evidence suggest that the locus of action is intrarenal rather than systemic. Plasma renin activity and plasma angiotensin II concentration are not higher in these subjects, and thus cannot account for their potentiated response to converting-enzyme inhibition. Moreover, the infusion of captopril directly into the renal artery in doses far too low to induce a systemic effect increases renal blood flow specifically in these subjects. They also show a blunted rate of renin suppression after a sodium load, although plasma renin activity falls to the same low level at steady state.(ABSTRACT TRUNCATED AT 250 WORDS)

The presence of the renin-angiotensin system (RAS) in extrarenal tissues, namely the vascular wall and brain tissue, is well established. The availability of effective blocking agents, converting-enzyme inhibitors, has made it possible to further elucidate important functions of the extrarenal RAS. We have found that the angiotensin converting-enzyme inhibitor captopril shifts the limits of cerebral blood flow autoregulation to lower blood pressure levels in normotensive and in spontaneously hypertensive rats. This effect may explain our finding of a remarkable preservation of cerebral blood flow, despite significant blood pressure reduction, in patients with chronic heart failure. We suggest that the effect of angiotensin converting-enzyme inhibition on autoregulation of cerebral blood flow is mediated by a dilatation of larger cerebral arteries, which results from inhibition of the vascular tone normally maintained by locally produced angiotensin II.

The renin-angiotensin system has traditionally been viewed as an endocrine system. Recent data demonstrate that renin and angiotensinogen genes and their products are expressed at many local tissue sites. The concept that multiple tissues synthesize angiotensin has changed our understanding of the physiology of the renin-angiotensin system. These potential autocrine-paracrine systems may be important in the regulation of local tissue functions in addition to the circulating endocrine system. The activity of the tissue system under different conditions can influence the pharmacologic response to inhibitors of the renin-angiotensin system. For example, evidence suggests that tissue angiotensin-converting enzyme (ACE) may be the primary site of action of ACE inhibitors. Consequently, the duration of action of an ACE inhibitor may be more dependent on the duration of tissue ACE inhibition than on the drug's serum half-life. The differential effects of these pharmacologic inhibitors on the tissue renin-angiotensin systems may form the basis of differentiation between the various ACE inhibitors.