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NONINVASIVE COlHuntsman et al.perfusion imaging using surfactant stabilized microbubbles. (abstr) Circulation 64 (suppl IV): IV-203, 1981 infarctions are not recognizable by standard clinical criteria. ' Current criteria for the clinical evaluation of circulation in myocardial infarction are often timeconsuming, subjective and prone to error. Clinicians are urged to rely on "monitoring of heart rate and rhythm, measurement of systemic and arterial pressure by cuff, obtaining chest roentgenograms to detect heart failure, careful and repeated auscultation of lung fields for pulmonary congestion and edema, measurement of urine flow, examination of the skin and mucous membranes for evidence of the adequacy of perfusion, and arterial sampling of Po2, Pco2, and pH when hypoxemia or metabolic acidosis is suspected."3 Physicians are often reluctant to use invasive CO determinations, except in selected patients, because they cause discomfort and may result in complications.4 I Given the importance of CO assessment, a noninvasive, easily

How an atherosclerotic plaque evolves from minimal diffuse intimal hyperplasia to a critical lesion is not well understood. Cellular proliferation is a relatively infrequent and modest event in both primary and restenotic coronary atherectomy specimens, leading us to believe that other processes, such as the formation of extracellular matrix, cell migration, neovascularization, and calcification might be more important for lesion formation. The investigation of proteins that are overexpressed in plaque compared with the normal vessel wall may provide clues that will help determine which of these processes are key to lesion pathogenesis. One such molecule, osteopontin (OPN), is an arginine-glycine-aspartate-containing acidic phosphoprotein recently shown to be a novel component of human atherosclerotic plaques and selectively expressed in the rat neointima following balloon angioplasty. Using in situ hybridization and immunohistochemical I dentifying the processes and molecular mediators of atherosclerotic plaque formation are currently areas of intense investigation. While focal smooth muscle cell (SMC) accumulations have been considered a hallmark of atherosclerosis and restenosis, 15 recent data suggest that the frequency of SMC replication in plaques is low. 6 -7 Thus, smooth muscle proliferation may not be a dominant event in lesion progression. Instead, other processes, such as cell migration, extracellular matrix formation, neovascularization, and calcification may be important pathophysiological events that are possibly linked to the expression of genes unique to atherosclerotic plaque and not found in the normal vessel wall. Examples of molecules that are overexpressed in the plaque compared with the normal vessel wall include platelet-derived growth factor-A, 8 bone morphogenetic protein-2a, 9 the major histocompatibility complex class II (la) antigen, 10 and the focus of the current study, osteopontin (OPN)." Although the mechanisms by which these genes are regulated are unknown, it is plausible to consider that SMC diversity plays a role, since plaque SMCs show a spectrum of phenotypes ranging from well differentiated (ie, containing abundant smooth muscle contractile proteins) to relatively undifferentiated (ie, containing little contractile apparatus but increased protein synthetic machinery), with the latter being present in the greatest numbers and commonly implicated in lesion progression. 12Using a differential cloning strategy, we have identified OPN, as well as several other genes (eg, collagen 1 [o-l], elastin), that are overexpressed in the rat neointima in vivo and that distinguish rat vascular SMC phenotypes in vitro.1314 OPN is an arginine-glycineaspartate-containing acidic phosphoprotein normally restricted to bone matrix, kidney, and epithelial lining cells and has been implicated in bone morphogenesis, tumor metastasis, bacterial resistance, immune function, and renal physiology. 15 In vitro, OPN serves as an adhesive substrate for both vascular smooth muscle and endothelial...

Chlamydia pneumoniae TWAR has been associated with coronary heart disease by seroepidemiologic studies and direct detection of the organism in atheromatous lesions of coronary arteries and aorta. In this study, 38 fresh tissue specimens from patients with coronary artery lesions that were treated by directional coronary atherectomy were tested for C. pneumoniae. Twenty-three specimens were from patients with primary lesions and 15 were from patients with restenoses. C. pneumoniae was detected by polymerase chain reaction (PCR), immunocytochemical stain (ICC), or both in 20 of 38 specimens. Using cell identity markers, the organism was localized to macrophages. Ultrastructural evidence of the organism was found in the 2 specimens examined by transmission electron microscopy, which were also positive by both ICC and PCR. C. pneumoniae was found more frequently in tissues from restenoses than in primary lesions (P = .17). There was no relation between the frequency of detection of the organism and C. pneumoniae-specific antibody titers.

On the basis of animal models of arterial injury, smooth muscle cell proliferation has been posited as a dominant event in restenosis. Unfortunately, little is known about this proliferation in the human restenotic lesion. The purpose of this study was to determine the extent and time course of proliferation in primary and restenotic coronary atherectomy-derived tissue. Primary (n = 118) and restenotic (n = 100) coronary atherectomy specimens were obtained from 211 nonconsecutive patients. Immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to gauge proliferation in the atherectomy specimens. The identity of PCNA-positive cells was then determined using immunohistochemical cell-specific markers. Eighty-two percent of primary specimens and 74% of restenotic specimens had no evidence of PCNA labeling. The majority of the remaining specimens had only a modest number of PCNA-positive cells per slide (typically < 50 cells per slide). In the restenotic specimens, PCNA labeling was detected over a wide time interval after the initial procedure (eg, 1 to 390 days), with no obvious proliferative peak. Cell-specific immunohistochemical markers identified primary and restenotic PCNA-positive cells as smooth muscle cells, macrophages, and endothelial cells. In conclusion, the findings were as follows: (1) Proliferation in primary and restenotic coronary atherectomy specimens, as indicated by PCNA labeling, occurs infrequently and at low levels. (2) The response to injury in existing animal models of angioplasty may follow a very different course of events from the clinical reality in human atherosclerotic coronary arteries and may help explain why current approaches to restenosis therapy have been ineffective.