The indirect alloresponse impairs the induction but not maintenance of tolerance to MHC class I-disparate allografts.

We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney-heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney-heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance.

Comparison of lung and kidney allografts in induction of tolerance by a mixed-chimerism approach in cynomolgus monkeys.

BACKGROUND: We have previously reported the successful induction of renal allograft tolerance in non-human primates using a nonmyeloablative conditioning regimen to produce a mixed-chimeric state in the recipient. In the present study, we applied this same technique to lung allotransplantation in cynomolgus monkeys. METHODS: Nine pairs of fully major histocompatibility complex (MHC)-mismatched cynomolgus monkeys were used. The conditioning regimen consisted of total body irradiation, thymic irradiation, and antithymocyte globulin. The recipients underwent lung and bone marrow transplantation, followed by anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine. The regimen included anti-CD8 mAb in the last 5 recipients and alpha 1-antitripsin in the last 3 recipients. The results were compared with 8 recipients that received kidney allografts using the same regimen. RESULTS: Transient chimerism developed in all lung recipients, as was previously seen in the kidney recipients. Nonetheless, the lung recipients rejected their allografts significant earlier than the kidney recipients (P < .01). CONCLUSIONS: Despite the successful induction of mixed chimerism in recipients of fully MHC-mismatched lung allografts, we have not observed long-term graft survival, as has been seen in an analogous kidney model. Strategies to overcome this problem include organ-specific modifications of the transplant regimen.

Rejection of cardiac xenografts transplanted from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs to baboons.

The use of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL(+) graft cell injury with the infiltration of T cells (including CD3 and TIA-1(+) cytotoxic T cells), CD4(+) cells, CD8(+) cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL(+) dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens.

Effects of tolerance induction on the actions of interferon-gamma on porcine cardiac allografts.

It is well known that interferon-gamma (IFN-gamma) not only plays a critical role in antigen-dependent but also in antigen-independent tissue injury; however, it is not clear how tolerance induction affects the actions of IFN-gamma in the transplant setting. To address this question, we compared the effects of IFN-gamma on porcine recipients of near-syngeneic, rejecting, and tolerant heart transplants. IFN-gamma was infused continuously into the left anterior descending artery of hearts transplanted into 3 groups of major histocompatibility complex (MHC) inbred miniature swine, each treated with a 12-day course of cyclosporine A (CyA). Group 1 recipients received a MHC class I disparate heart, group 2 recipients received a near-syngeneic heart, and group 3 recipients were cotransplanted with a MHC class I disparate heart and kidney, which uniformly induces tolerance to both grafts. An additional group of animals was not transplanted but received intracoronary IFN-gamma infusion into their native hearts. IFN-gamma perfusion not only accelerated the acute rejection of MHC class I disparate hearts (mean survival time = 19 +/- 7.21 vs 38 +/- 8.19 days, P = .025), but caused near-syngeneic heart transplants, which otherwise survive indefinitely, to reject within 35 days (n = 3). In contrast, IFN-gamma perfusion had no demonstrable effects on interstitial rejection, the development of vascular lesions, or graft survival in tolerant heart plus kidney allograft recipients (n = 4) or in autologous hearts (n = 2). These results suggest that tolerance induction mitigates the damaging effects of IFN-gamma itself and that the beneficial effects of tolerance induction on acute and chronic rejection may extend to antigen-independent factors like ischemia/reperfusion injury.

Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts in miniature Swine.

UNLABELLED: We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously reported the importance of the presence of the thymus in the induction of tolerance to isolated heart, kidney, and combined heart-kidney transplants. In this study, we examined the impact of thymectomy on tolerance induction in lung transplantation. METHODS: Orthotopic left lung transplantation was performed using MHC class I-disparate donors. The recipients received a 12-day course of high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the swine 21 days prior to transplantation. Lung grafts were monitored by chest radiography and serial open lung biopsy. RESULTS: All euthymic recipients maintained their grafts for over 1 year. None of the thymectomized recipients has experienced graft loss in the 6 to 10 months following transplantation. Although isolated lesions of obliterative bronchiolitis were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co-culture assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naïve recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with third-party antigens against appropriate targets. CONCLUSIONS: These data suggest that thymus-independent peripheral regulatory mechanisms may be sufficient to induce and maintain long-term acceptance of the lung allografts.

The role of indirect recognition of MHC class I and II allopeptides in a fully mismatched miniature swine model of lung transplantation.

UNLABELLED: Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class II allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine. METHODS: Recipients were immunized with either donor-derived class I or class II peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus. RESULTS: One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over 1 year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays. CONCLUSIONS: Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class II molecules may be less antigenic when presented indirectly.

An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine.

OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. We have induced robust tolerance to class I-disparate lung allografts in miniature swine using an intensive 12-day course of tacrolimus. Here, we tested whether a tolerant state can be induced in swine receiving fully mismatched lung allografts. METHODS: Orthotopic left lung allografts were performed using MHC class I-disparate (group 1: n = 3) or fully disparate (group 2: n = 6) donors. The recipients received a 12-day postoperative course of tacrolimus (continuous intravenous infusion; target level = 35-50 ng/mL) as their only immunosuppression. RESULTS: All swine in group 1 maintained their grafts long term without developing any lesions of chronic rejection (>497, >432, >451 days). These recipients exhibited donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity (CML) and mixed lymphocyte reaction (MLR) assays. In group 2, five of the six recipients maintained their grafts long term (sacrificed on postoperative days 515, 389, 429, 481, and 438 with viable grafts). Isolated lesions of obliterative bronchiolitis were occasionally seen on biopsy, and donor-specific hyporesponsiveness on assays was consistently observed. The remaining recipient rejected its graft on day 103 with histologic findings of obliterative bronchiolitis. CONCLUSIONS: We report long-term graft acceptance without chronic immunosuppression in five of six recipients across a full MHC disparity, albeit with some evidence of obliterative bronchiolitis. These data suggest that the class II disparity inherent in a fully mismatched transplant increases the requirement for tolerance induction.

Long-term acceptance of porcine pulmonary allografts without chronic rejection.

OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. Using a strategy to induce tolerance across strong allogeneic barriers, we have employed a brief, intensive course of immunosuppression to determine whether the induction of donor-specific hyporesponsiveness would prevent allograft rejection in a preclinical model of lung transplantation using MHC-inbred miniature swine. METHODS: Orthotopic left lung allografts were performed using MHC class I-disparate donors. The recipients received a 12-day postoperative course of cyclosporine (n = 6) or a 12-day postoperative course of high-dose tacrolimus (n = 3) as their only immunosuppression. Control animals received no immunosuppression (n = 3). RESULTS: Cyclosporine-treated recipients exhibited graft survival ranging from 67 to >605 days. All six animals developed acute cellular rejection between postoperative days (PODs) 27 and 108. Two animals lost their grafts on PODs 67 and 69, before developing obliterative bronchiolitis (OB). The other four recipients developed OB between PODs 119 and 238. In contrast, all tacrolimus-treated recipients maintained their grafts long term, without developing chronic rejection (>339, >308, and >231). These recipients also exhibited donor-specific hyporesponsiveness in assays of cell-mediated lymphocytotoxity. All untreated control animals lost their grafts to acute rejection by POD 11. CONCLUSIONS: This study demonstrates the ability of a brief course of high-dose tacrolimus to induce long-term graft acceptance with donor-specific hyporesponsiveness in a class I-disparate preclinical lung transplant model.

Potential of aspirin to inhibit thrombotic microangiopathy in alpha1,3-galactosyltransferase gene-knockout pig hearts after transplantation in baboons.

Hearts from alpha1,3-Galactosyltransferase gene-knockout (GaIT-KO) pigs were transplanted heterotopically into 8 baboons that received an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen and heparin. Three baboons died or were euthanized with beating grafts on 16, 23, and 56 days, respectively, and the remaining 5 grafts functioned for 59-179 days. Hyperacute rejection did not occur, and classical features of acute humoral xenograft or acute cellular rejection were rare. However, thrombotic microangiopathy (TM) developed in all cases; its onset was delayed in 2 baboons that received aspirin. Function of a pig organ in a baboon for a period approaching 6 months has not been reported previously and lends encouragement that the barriers to xenotransplantation will be overcome, but TM requires investigation.

Enhancement of the recovery of rat hearts after prolonged cold storage by cyclocreatine phosphate.

The present study determined whether the administration of cyclocreatine phosphate (CCrP) prior to ischemia can enhance the recovery of rat hearts hypothermically preserved for a prolonged period. Rats (n = 6 per group) were injected intravenously with 1 ml saline or CCrP (500 mg/kg). After 2 hr, hearts were excised and arrested by an infusion of University of Wisconsin solution. Saline hearts were then incubated in 40 ml UW, while CCrP hearts were incubated in 40 ml UW containing 100 mg CCrP; a mixture that is now referred to as Hartford Hospital (HH) solution. After 6 hr of storage at 4 degrees C, hearts were reperfused in the Langendorff mode for 15 min and then in the working heart mode for 30 min. Results indicated that the recovery of cardiac function--measured as aortic flow, coronary flow, cardiac output, stroke volume, and stroke work--was significantly better in CCrP group (50-55% baseline) compared with that of saline hearts (20-25%). Although no difference in enzyme leakage (i.e., creatine kinase) or lactate was detected between the two groups, the increase in heart weight after the initial 6-hr storage was significantly higher in saline hearts compared with that of CCrP hearts. Results of this study support the conclusion that CCrP treatment provides improved functional recovery after prolonged hypothermic preservation.

Spleen transplantation in miniature swine: surgical technique and results in major histocompatibility complex-matched donor and recipient pairs.

BACKGROUND: Spleen transplantation (Tx) between some strains of rodents can lead to donor-specific tolerance either spontaneously or after a short course of immunosuppression. This study developed a surgical technique for spleen Tx in miniature swine to investigate its immunologic impact in a large animal model. METHODS: The preferred surgical technique of spleen Tx (n=8) involved excision of the donor spleen with its vascular pedicle to the aorta and portal vein. Carrel patches of donor aorta and portal vein were anastomosed to the abdominal aorta and inferior vena cava, respectively, of the (splenectomized) recipient. The results in four major histocompatibility complex-matched pairs that were mismatched for the porcine allelic antigen are reported. Two recipients were untreated, one received a 12-day course of cyclosporine A (CsA) alone, and one received thymic irradiation (700 cGy) and CsA. Hematopoietic cell chimerism was followed by fluorescence-activated cell sorter, and graft survival was assessed by histology. RESULTS: Spleen Tx was technically successful. In two untreated pigs, chimerism was detected in the blood (maximum 5% for 17 and 25 days) and lymph nodes (maximum 6% for 28 and 56 days), but both grafts showed histologic rejection by day 28. In two treated pigs, chimerism was present in the blood for 47 and 57 days, and rejection was prevented, with follow-up for 57 and 217 days, respectively. CONCLUSION: Spleen Tx in major histocompatibility complex-matched pairs treated with CsA+/-thymic irradiation results in prolonged chimerism and is associated with the development of in vivo unresponsiveness to the transplanted spleen.

Cardiac-derived neutrophil chemotactic factors: detection in coronary sinus effluents of patients undergoing myocardial revascularization.

Recent studies from our laboratory have demonstrated the release of neutrophil chemotactic factors from isolated rabbit hearts perfused with cardioplegic solutions and from ischemic dog hearts after coronary artery occlusion for 1 hour. On the basis of these animal studies, a test is now made of the hypothesis that neutrophil chemotactic factors are released by myocardial tissues of patients who undergo surgical myocardial revascularization. By means of modified Boyden chambers, the levels of neutrophil chemotactic factors were measured in effluent collected from the coronary sinuses of six patients undergoing cardiopulmonary bypass during periods of cold cardioplegia. Plain cardioplegic solutions were also analyzed. The standard formyl-methionyl-leucyl-phenylalanine, a stimulant of neutrophil recruitment, was used as a positive control solution. Results indicated the recovery of significantly high levels of neutrophil chemotactic factors in patient samples (i.e., 128% +/- 19% of formyl-methionyl-leucyl-phenylalanine) compared with control plain cardioplegic solution (less than 5% of formyl-methionyl-leucyl-phenylalanine) (p less than 0.0001). A standard checkerboard analysis indicated that the observed activity is chemotactic (i.e., directed migration) and not chemokinetic (i.e., random migration). This study also showed that these factors are proteins of a molecular weight in excess of 300 kd and exhibit in vivo activity by recruiting neutrophils into rabbit skin. The absence of immune cell-derived chemoattractants such as interleukin-1 and leukotriene B4 in these coronary sinus effluents suggests that the observed chemotactic activity is cardiac derived. Results of this investigation therefore demonstrate the release of neutrophil chemotactic factors by ischemic human hearts during cardiopulmonary bypass.

The impact of cocaine on the donor heart: a case report.

With a limited supply of donor hearts in the United States and a prevalent history of cocaine abuse among potential heart donors, the question of transplanting the hearts of cocaine users presents a dilemma to the surgeon. We report a patient who died of the acute right ventricular failure of a heart from a donor with a history of binge drinking and cocaine abuse and who had sustained traumatic brain death. The donor's serum was positive for cocaine prior to transplantation, and autopsy findings were consistent with cocaine cardiomyopathy. This case illustrates the importance of accurate donor history and toxicologic screen prior to heart transplantation and suggests that hearts of cocaine users should not be transplanted, especially in a setting of traumatic brain death.

Valvular heart disease in patients with hypocomplementemic urticarial vasculitis syndrome associated with Jaccoud's arthropathy.

BACKGROUND: Since 1973, more than 75 patients with hypocomplementemic urticarial vasculitis syndrome (HUVS) were reported, but valvular heart disease does not seem to have been noted in these patients. Since 1993, however, five patients with HUVS accompanied by Jaccoud's arthropathy (JA) were found to have serious valvular heart disease. METHODS: To characterize the cardiac valvulopathy of the third patient with HUVS/JA to have undergone valve replacement, this study included the use of routine and special tissue stains, as well as immunohistochemical staining. We compared gross and histologic findings of this patient's valve to those of two other patients with this complex syndrome who underwent valve replacement. Pathologic findings of these latter two patients were described in separate earlier reports. RESULTS: Histologic examination of the resected valves in all three patients showed an acute necrotizing endocarditis and fibrin deposition on the surface of valve leaflets. Beneath the surfaces of the leaflets, there was evidence of chronic inflammation, consisting of lymphocytes and histiocytes. A fibrocalcific degenerative change was also present in all three valves. Positive staining for IgG, IgA, IgM, and light-chain determinant-bearing proteins was detected primarily at the valve surface in special studies of the aortic valve of the patient described in the current report. CONCLUSION: Patients with HUVS and associated JA should be evaluated for the presence of valvular heart disease. The latter is probably a nonrheumatic, inflammatory, and degenerative process, mediated by immune complex, as well as cellular immune mechanisms.

Serum lipids and arterial plaque load are altered independently with high-dose progesterone in hypercholesterolemic male rabbits.

Antiatherogenic effects of sex steroids in premenopausal women are not well defined. Therefore, we employed an established rabbit model for atherosclerosis to study the effects of exogenous estrogen and a progesterone analogue (P) on serum lipids and aortic plaque load. Serum cholesterol (C) and triglyceride (T) levels and atherosclerotic plaque loads were compared in 5 groups of male New Zealand White rabbits fed a 12-week, C-rich diet: 1 control group (CG) and 4 groups treated with estriol (E), haloperidol (H), low-dose 17-hydroxyprogesterone (LDP), or high-dose 17-hydroxyprogesterone (HDP). Serum P was measured in the LDP and HDP groups. Serial histologic sections (15 each of 27 ascending aortas) were studied by light microscopy and computerized morphometric analysis. Plaque load is defined as the ratio of intimal area to medial area (I/M). Exogenous E (p<0.001), H (P = 0. 02), LDP and HDP (P<0.001, each) were found to be significantly associated with less aortic plaque load than controls. In a multivariate analysis, after controlling for the differences in serum C and T levels, HDP (p = 0.014) was found to be associated with less aortic plaque load than controls, and this association approached statistical significance in the E (p = 0.052) and H (p = 0.069) groups. These data suggest that the mechanism(s) involved with the antiatherogenic effect of HDP in this animal model is, or are, independent of an alteration in serum lipids.

Should the greater saphenous vein be preserved in patients requiring arterial outflow reconstruction in the lower extremity?

Two patient groups were studied to determine the need to preserve the greater saphenous vein during femoral outflow reconstruction for later aortocoronary bypass procedures. First, 74 patients were followed to the time of death or to a minimum of 5 years after femoral outflow reconstruction was performed. Only four patients (5.4%) underwent subsequent aortocoronary bypass. The previous outflow procedures had no adverse effect on the quality of aortocoronary conduit. Risk factors were analyzed to help predict the incidence of later coronary revascularization after femoral outflow reconstruction was performed. The second group that was analyzed included 500 nearly consecutive patients who underwent aortocoronary bypass. In 15 of these patients (3%), there was inadequate saphenous vein for conduit use. In no case was the inadequacy of saphenous vein due to its previous use as outflow conduit in the leg. Only seven patients (1.4%) had had an outflow reconstruction prior to aortocoronary bypass. In conclusion, continued use of adequate greater saphenous vein as femoral outflow conduit is justified despite the high incidence of coronary artery disease in these patients.

Evidence of cardiac inflammation after open heart operations.

In this study, 6 anesthetized dogs underwent global cardiac arrest for 1 hour, followed by reperfusion on bypass for 45 minutes. The hearts were then weaned off cardiopulmonary bypass and monitored for an additional 2 hours. Using modified Boyden chambers, high levels of neutrophil chemotactic activity were detected (using a checkerboard analysis) in the coronary sinus effluents obtained during cardiac arrest. The activity tended to decline during reperfusion. Assay of myeloperoxidase (a marker for neutrophils) revealed an accumulation of large numbers of neutrophils in the right (14 +/- 1.1 x 10(4) cells/g wet weight) and left (16 +/- 1 x 10(4) cells/g wet weight) ventricles after 2 hours of reperfusion. Light microscopy evaluation confirmed the presence of neutrophils, not only in the ventricles, but also in a greater number in the right and left atria. Electron microscopy study of these hearts revealed the presence of mild reversible changes, indicating good preservation of the hearts during arrest. Results of this study provide evidence for an acute inflammatory reaction that takes place after cardiac operations and suggest a role for myocardial tissues in the initiation of such a response through their release of neutrophil chemotactic factors.

Significant atheromatous debris following uncomplicated vein graft direct stenting: evidence supporting routine use of distal protection devices.

We present the case of an angiographically uncomplicated direct stent vein graft intervention in which the Percusurge embolization containment device was used. We performed histological examination of the resulting debris and observed massive particulate atheromatous material. This case illustrates the severity of distal embolization that can go clinically unnoticed after direct stenting and also supports the routine use of distal protection devices for vein graft intervention.

Bronchocentric granulomatosis with mucus impaction due to bronchogenic carcinoma. An association with clinical relevance.

OBJECTIVE: To describe an unexpected inflammatory process associated with malignancy in the lung and to postulate a new mode of pathogenesis. DESIGN: Retrospective review of surgical pathologic findings. SETTING: Academic hospital pathology department. PATIENTS: Four patients, 2 men and 2 women, ranging in age from 45 to 74 years, each of whom had a solitary mass on chest radiographs. INTERVENTIONS: Pulmonary lobectomy. MAIN OUTCOME MEASURE: Histopathologic identification of bronchocentric granulomatosis. RESULTS: Accompanying a bronchogenic carcinoma in each case was a necrotizing chronic granulomatous reaction centered around bronchioles that were plugged with mucus, necrotic detritus from the tumor, lipid, or a combination of these substances. Eosinophils were present in small numbers in one case. The pathologic findings characterize bronchocentric granulomatosis. CONCLUSIONS: The presence of bronchocentric granulomatosis in the biopsy of a mass does not exclude the presence of an accompanying bronchogenic carcinoma associated with obstruction of bronchioles. Bronchocentric granulomatosis in some cases may represent an immunologic response to tumor detritus or lipid, as well as to mucus impaction.

Porcine coronary imaging in vivo by optical coherence tomography.

OBJECTIVE: A high-resolution coronary artery imaging modality has the potential to address important diagnostic and management problems in cardiology. Optical coherence tomography (OCT) is a promising new optical imaging technique with a resolution of approximately 10 microm. The purpose of this study was to use a new OCT catheter to demonstrate the feasibility of performing OCT imaging of normal coronary arteries, intimal dissections, and deployed stents in vivo. METHODS AND RESULTS: Normal coronary arteries, intimal dissections, and stents were imaged in five swine with OCT and compared with intravascular ultrasound (IVUS). In the normal coronary arteries, visualization of all of the layers of the vessel wall was achieved with a saline flush, including the intima which was not identified by IVUS. Following dissection, detailed layered structures including intimal flaps, intimal defects, and disruption of the medial wall were visualized by OCT. IVUS failed to show clear evidence of intimal and medial disruption. Finally, the microanatomic relationships between stents and the vessel walls were clearly identified only by OCT. CONCLUSIONS: In this preliminary experiment, we have demonstrated that in vivo OCT imaging of normal coronary arteries, intimal dissections, and deployed stents is feasible, and allows identification of clinically relevant coronary artery morphology with high-resolution and contrast.