B-cell depletion extends the survival of GTKO.hCD46Tg pig heart xenografts in baboons for up to 8 months.

Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Rejection in Gal knockout (GTKO) pigs due to elicited non-Gal antibody response required further genetic modifications of donor pigs and better control of the B-cell response to xenoantigens. We report significant prolongation of heterotopic alpha Galactosyl transferase "knock-out" and human CD46 transgenic (GTKO.hCD46Tg) pig cardiac xenografts survival in specific pathogen free baboons. Peritransplant B-cell depletion using 4 weekly doses of anti-CD20 antibody in the context of an established ATG, anti-CD154 and MMF-based immunosuppressive regimen prolonged GTKO.hCD46Tg graft survival for up to 236 days (n = 9, median survival 71 days and mean survival 94 days). B-cell depletion persisted for over 2 months, and elicited anti-non-Gal antibody production remained suppressed for the duration of graft follow-up. This result identifies a critical role for B cells in the mechanisms of elicited anti-non-Gal antibody and delayed xenograft rejection. Model-related morbidity due to variety of causes was seen in these experiments, suggesting that further therapeutic interventions, including candidate genetic modifications of donor pigs, may be necessary to reduce late morbidity in this model to a clinically manageable level.

Computer aided minimally invasive cardiac procedures.

Minimally invasive cardiac procedures have been investigated to reduce the risks associated with open heart surgery. With the assistance of improvements in engineering technologies such as medical imaging, surgical navigation, and robotic devices, more cardiac surgeries can be performed in a minimally invasive fashion. We have surveyed these state-of-the-art engineering technologies and the minimally invasive cardiac procedures that are benefited from these technologies.

Rapamycin promotes the enrichment of CD4(+)CD25(hi)FoxP3(+) T regulatory cells from naïve CD4(+) T cells of baboon that suppress antiporcine xenogenic response in vitro.

The CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells play an important role in regulating the immune response. These Treg cells are present in peripheral blood and lymphoid organs and have a high potential for immunotherapy in clinics. Adoptive cell transfer therapy using CD4(+)CD25(+) cells has been shown to prevent autoimmune diseases and has also induced transplant tolerance in mice. Treg cells low frequency in peripheral blood will necessitate its ex vivo expansion to enable adaptive immunotherapy. Recently, it has been reported that rapamycin, an immunosuppressive agent, inhibits T-cell proliferation while selectively increasing the number of Treg cells. Based on this additional mode of action, rapamycin can be used to expand Treg cells for ex vivo cellular therapy in T-cell-mediated diseases and in transplantation. We have reported the ex vivo expansion of baboon Treg cells, using irradiated pig peripheral blood mononuclear cell (PBMC) and interleukin (IL)-2, and have demonstrated the suppression of autologus CD4(+)CD25(neg) T-cell proliferation in response to pig PBMCs. In the present study, we have expanded baboon CD4(+) T cells in the presence or absence of rapamycin (0.1-10 nmol/L) using irradiated pig PBMCs and IL-2 to enrich the regulatory T cells. CD4(+)CD25(+)FoxP3(+) Treg cells were increased up to 2 times in the presence of rapamycin versus without rapamycin in vitro. However, a higher dose of rapamycin (> or = 10 nmol/L) considerably decreases the number of Treg cells. Furthermore, purified CD4(+)CD25(+) Treg cells enriched from CD4(+) cells in the presence of rapamycin were able to suppress the baboon anti-porcine xenogeneic immune responses in vitro up to 93% at a 1:1 ratio (Treg cells:T effector cells) and suppression ability exists even at a 1:256 ratio, whereas freshly isolated natural Treg cells suppress only 70% at 1:1 and lose their suppressive ability (>50%) at 1:16. Our results demonstrate that the addition of rapamycin to the culture enriches the Treg phenotype and induces functional regulatory T cells. This method may allow the production of large numbers of regulatory cells for the preclinical testing of Treg cell therapy in a non-human primate model.

Sustained angina relief 5 years after transmyocardial laser revascularization with a CO(2) laser.

BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided symptomatic relief of angina over the short term, the long-term efficacy of the procedure is unknown. Angina symptoms as assessed independently by angina class and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7 years after TMR. METHODS: Seventy-eight patients with severe angina not amenable to conventional revascularization were treated with a CO(2) laser. Their mean age was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42% had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III. Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5 years (and up to 7 years) of follow-up, the average angina class was significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1 average angina class at 1 year postoperatively (P=NS). There was a marked redistribution according to angina class, with 81% of the patients in class II or better, and 17% of the patients had no angina 5 years after TMR. A decrease of >/=2 angina classes was considered significant, and by this criterion, 68% of the patients had successful long-term angina relief. The angina class results were further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe disabling angina provides significant long-term angina relief.

Surgical treatment of adult atrial septal defect: early and long-term results.

OBJECTIVES: The purpose of this study is to determine the early and late results of the surgical repair of atrial septal defect in adults. BACKGROUND: Progressively limiting, untreated atrial septal defect can lead to the early death of middle-aged adults. Recently it has been suggested that the closure of atrial septal defects might be accomplished with interventional cardiac techniques. Although the long-term results of the transcatheter closure are as yet unknown, the outcome of surgical therapy has been shown to be beneficial for almost 40 years. METHODS: Between 1971 and 1991, 166 consecutive patients underwent surgical repair of a secundum or sinus venosus atrial septal defect, or both, at the Brigham and Women's Hospital, Boston. There were 120 women and 46 men in this group; the mean age was 44 years and 58 (35%) of the patients were > or = 50 years old. The average pulmonary to systemic flow ratio was 3.0, and 57 patients had a peak systolic pulmonary artery pressure > 30 mm Hg. RESULTS: There were two operative deaths (early mortality rate 1.2%), and 13% of the patients had a perioperative complication. One hundred fifty-three of the 164 survivors were followed up for a mean of 90 months (range 2 to 247). There were eight late deaths (late mortality rate 4.9%) and a late morbidity rate of 12.4% (in most cases due to arrhythmias). The 5- and 10-year survival rates are 98% and 94%, respectively, and the probability of event-free survival (with no morbidity or mortality) at 5 years is 97% and at 10 years is 92%. CONCLUSIONS: The results indicate that the surgical correction of atrial septal defect in adults is safe and efficacious as confirmed by 20 years of follow-up.

Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization.

OBJECTIVES: The short- and long-term effectiveness of transmyocardial laser revascularization was evaluated in the setting of an acute myocardial infarction. BACKGROUND: Theoretically, transmyocardial laser revascularization allows direct perfusion of the ischemic area as ventricular blood flows through the channels to the myocardium. METHODS: Infarcts were created by coronary occlusion in 30 sheep. Eighteen of these sheep were studied to assess short-term efficacy. The infarct was reperfused after 1 h by either removing the occlusion or by laser drilling using a high power carbon dioxide laser. The occlusions were left in place for the control group. To monitor regional recovery, percent systolic shortening was measured. To evaluate long-term effectiveness, 12 additional sheep underwent creation of an infarct. Six were treated with the laser, and six were untreated. The animals were restudied 30 days later. RESULTS: In the short-term experiment, the control and reperfusion groups exhibited no recovery of regional contractility. The laser group demonstrated improvement throughout the recovery period. There was a significant difference in the area of necrosis within the same area at risk (reperfusion group 44 +/- 6% and control group 39 +/- 5% vs. laser group 6 +/- 2%). After 30 days, none of the control animals showed evidence of contraction in the infarct, whereas the laser-treated animals did. Histologic analysis of the laser-treated infarcts revealed patent channels surrounded by viable myocardium. The control-group infarcts were necrotic and scarred. CONCLUSIONS: On the basis of both short- and long-term improved contractility, as well as diminished necrosis in the area at risk, these results indicate that transmyocardial laser revascularization may be an alternative method of treating ischemic heart disease.

Intraoperative myocardial ischemia detection with laser-induced fluorescence.

Myocardial ischemia can be detected at the mitochondrial level by measuring shifts in nicotinamide adenine dinucleotide and its reduced form. Using a pulsed nitrogen laser and an optical multichannel analyzer, we monitored myocardial metabolism by measuring laser-induced nicotinamide adenine dinucleotide (reduced form) fluorescence in a large animal model of acute ischemia. Eight opened-chest sheep underwent occlusion of branches of the left anterior descending coronary artery, establishing a 15% infarct of the left ventricle. For the simulation of the clinical scenario, after 60 minutes of occlusion, the animals were supported by cardiopulmonary bypass, the aorta was crossclamped, and cold crystalloid cardioplegic solution was administered. The occlusion was removed after 10 minutes, and two additional doses of cardioplegic solution were delivered at 10-minute intervals. The aortic crossclamp was released, and a 30-minute period of reperfusion on bypass ensued. The hearts were then weaned off bypass and allowed to recover. Laser-induced fluorescence was measured inside, outside, and along the border of the infarct. Baseline measurements were made before occlusion, immediately after occlusion, and then at 5, 10, and 20 minutes after occlusion. The results show that immediately after occlusion there is a 200% +/- 30% (mean +/- standard deviation) increase in laser-induced fluorescence in the infarct zone, a 110% +/- 30% increase along the border, and no significant change in the area outside the infarct. The fluorescence in the infarct reaches a plateau in 5 minutes at 270% +/- 30%, whereas along the border it reaches a peak near end ischemia of 110% +/- 40%. With the first dose of cardioplegic solution, fluorescence increases outside the infarct and decreases inside the infarct and along the border to 120% +/- 30%, where it remains for all areas until the aortic crossclamp is removed. Fluorescence then drops to 70% +/- 20% and finally returns to baseline after 5 minutes of recovery. All of these shifts in laser-induced fluorescence were statistically significant (p < 0.01). The changes noted with doses of cardioplegic solution reflect the hypothermic and hyperkalemic effects on the myocardium. Laser-induced fluorescence provides a sensitive and specific method of monitoring myocardial ischemia during the operation. It also provides instantaneous feedback of metabolic changes that may be useful in evaluating the effects of different cardioplegic regimens and in monitoring reperfusion injury.

Transmyocardial laser revascularization: operative techniques and clinical results at two years.

OBJECTIVES: A new technique, transmyocardial laser revascularization, provides direct perfusion of ischemic myocardium via laser-created transmural channels. From 1993 to 1995, we have treated 20 patients (mean age 61 years, four women and 16 men) with transmyocardial laser revascularization. Preoperatively, the average angina class was 3.7. The patients were screened before the operation by a technetium sestamibi perfusion scan to identify the location and extent of their reversible ischemia. METHODS: Operative exposure is gained via a left anterior thoracotomy. With the use of a 850-watt carbon dioxide laser, an average of 21 +/- 4 channels were created in 22 minutes with a total operative time of less than 2 hours. RESULTS: The in-hospital mortality was two of 20 patients. Three additional patients died after discharge. After an accumulated 172 patient-months (mean follow-up 11 +/- 8 months, range 1 to 26 months), the mean angina class is I (p = 0.01). Postoperative sestamibi scans were obtained at 3, 6, and 12 months. Using the septum as a control and comparing the postoperative results with the preoperative baseline, we noted a significant improvement in perfusion particularly in the areas of reversible ischemia. CONCLUSION: These early results indicate that transmyocardial laser revascularization is a simple operative technique that may improve myocardial perfusion and provide angina relief for patients in whom standard methods of revascularization is contraindicated.

Favorable results of coronary artery bypass grafting in patients older than 75 years.

There is controversy whether the short-term and long-term results of coronary artery bypass grafting in elderly patients justify performing the procedure. Between January 1977 and December 1986, 4580 patients underwent coronary artery bypass grafting, of whom 222 (4.9%) were 75 years old or older (mean 77 years). There were 143 men and 79 women and 139 (63%) were in New York Heart Association class IV. One hundred forty-six patients (66%) had had at least one preoperative myocardial infarction. Myocardial revascularization was performed under emergency conditions in 17 patients (18%). The mammary artery was used in 43%, 96% of the patients received two or more grafts. The mean number of bypass grafts was 3.1 per patient. The overall hospital mortality rate was 10.8% (24/222), 3.6% for elective procedures, 14.9% in urgent cases, and 35% in emergencies. In contrast, the overall early mortality rate was 3.1% in 4358 patients less than 75 years old. Complications occurred in 83 patients (37%). Of the patients discharged from the hospital, 198 were followed up for a mean of 48 months (1 to 130). Actuarial probability of survival was 75% at 48 months. Postoperatively 70% were in New York Heart Association class I or II and only 21% were rehospitalized for cardiac problems. During the follow-up period 77% of the patients were free from angina, and of those experiencing angina the mean time from operation to the first episode was 75 months. Although elderly patients have a somewhat increased operative mortality rate, particularly if operated on urgently or emergently, long-term survival and freedom from angina are excellent and justify continued performance of coronary bypass grafting in selected patients over 75 years of age.

Transmyocardial laser revascularization: results of a multicenter trial with transmyocardial laser revascularization used as sole therapy for end-stage coronary artery disease.

BACKGROUND: Transmyocardial laser revascularization was used as the sole therapy for patients with ischemic heart disease not amenable to percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. This technique uses a carbon dioxide laser to create transmyocardial channels for direct perfusion of the ischemic heart. METHODS: Since 1992, 200 patients, at eight hospitals in the United States, have undergone transmyocardial laser revascularization. The patients have a combined 1560 months of follow-up for an average of 10 +/- 3 months per patient. Their age was 63 +/- 10 years and their ejection fraction was 47% +/- 12%. Eighty-two percent had at least one previous bypass graft operation and 38% had a prior angioplasty. Preoperatively, the patients underwent nuclear single photon emission computed tomography perfusion scans to identify the extent and severity of their ischemia. These scans were repeated at 3, 6, and 12 months. Angina class, admissions for angina, and medications were recorded. RESULTS: The perioperative mortality was 9%. Angina class decreased significantly from before treatment to 3, 6, and 12 months (p < 0.001). Likewise, there was a significant decrease in the number of perfusion defects in the treated left ventricular free wall. Concomitantly, there was a significant decrease in the number of admissions for angina in the year after the procedure when compared with the year before treatment (2.5 vs 0.5 admissions per patient-year). CONCLUSION: These combined results indicate that transmyocardial laser revascularization provides angina relief, decreases hospital admissions, and improves perfusion in patients with severe coronary artery disease.

Massive intra-abdominal hemorrhage from a hepatic laceration caused by vomiting.

We present a case report of a previously undocumented incident of massive hemoperitoneum from a liver laceration secondary to vomiting. The patient presented with the complaint of vomiting and abdominal pain. Computed tomography revealed perihepatic and perisplenic fluid collections. With this evidence and a rapidly falling hematocrit, she underwent emergency laparotomy. Intraoperative findings included 3 L of blood in the abdomen and a liver laceration at the juncture of the liver and the falciform ligament.

Thoracoscopic transmyocardial laser revascularization.

Transmyocardial laser revascularization has been used to treat patients with end-stage coronary artery disease and severe disabling angina. Typically, the operative approach is through a left anterior thoracotomy. I report a case of transmyocardial laser revascularization performed thoracoscopically.

Left ventricular functional improvement after transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization has been used to treat patients with end-stage coronary artery disease that is not amenable to standard revascularization. Although there is evidence of angina relief and quality of life enhancement, there is little information concerning improvement in myocardial contractility. The purpose of this study was to determine whether transmyocardial laser revascularization improves myocardial function in chronically ischemic myocardium. METHODS: In a model of chronic ischemia by Ameroid occlusion of the circumflex artery, domestic pigs (n = 8) were treated with transmyocardial laser revascularization. Before laser treatment, segmental contraction was assessed at rest and with dobutamine stress echocardiography. Myocardium subtended by the occlusion was compared with that remote from the occlusion. Six weeks after transmyocardial laser revascularization, the animals were restudied at rest and with stress, and then sacrificed. Sham-treated control animals (n = 4) underwent the same procedures but were not treated with transmyocardial laser revascularization. Control animals did not demonstrate significant recovery of function. RESULTS: Transmyocardial laser revascularization improved resting function in chronically ischemic myocardium by 100%. CONCLUSIONS: Transmyocardial laser revascularization significantly improves the function of chronically ischemic myocardium. These data may help explain the mechanisms by which transmyocardial laser revascularization is clinically effective.

Up-regulation of vascular endothelial growth factor mRNA and angiogenesis after transmyocardial laser revascularization.

BACKGROUND: Angiogenesis has been proposed as a potential mechanism whereby transmyocardial laser revascularization (TMLR) has provided clinical relief of angina. Experimental work has found histologic evidence supporting this, as well as an improved response when angiogenic growth factors have been added to TMLR. The purpose of this study was to demonstrate that the molecular response to TMLR was an increase in the production of endogenous vascular endothelial growth factor to promote angiogenesis. METHODS: Ameroid constrictors were placed on the proximal circumflex artery in 12 domestic pigs. After a chronic ischemic zone was established the animals were randomly divided into two groups. In the TMLR group the ischemic zone was treated with carbon dioxide laser. In the control group the ischemic zone was untreated. Six weeks later the animals were sacrificed, and sections from the ischemic zone and the nonischemic zone were submitted for immunohistochemical, histologic, and molecular analysis. Messenger RNA was obtained from northern blot analysis after being probed with vascular endothelial growth factor. RESULTS: There was a twofold increase in the vascular endothelial growth factor messenger RNA in the ischemic zone of the TMLR group compared with the control group. Additionally, there was a threefold increase in the number of new blood vessels in the ischemic zone of the TMLR group compared with the control group. CONCLUSIONS: Transmyocardial laser revascularization promotes angiogenesis by upregulation of vascular endothelial growth factor. The resulting angiogenesis could be the principle mechanism for the clinical efficacy of TMLR.

Functional comparison of transmyocardial revascularization by mechanical and laser means.

BACKGROUND: As a result of the clinical benefit observed in angina patients treated by transmyocardial revascularization (TMR) with a laser, interest in mechanical TMR has been renewed. Although the injury induced by mechanical TMR is similar to laser TMR, the resultant impact on myocardial contractility is unknown. The purpose of this study was to determine whether mechanical TMR improves ventricular function as compared with laser TMR in chronically ischemic myocardium. METHODS: After establishing an area of chronic myocardial ischemia, 25 domestic pigs were randomized to treatment by: excimer laser (group I), a hot needle (50 degrees C) (group II), a normothermic needle (group III), an ultrasonic needle (40 KHz) (group IV), or no treatment (group V). All devices create a transmural channel of the same diameter; 22 +/- 1 transmural channels were created in each animal. Regional myocardial contractility was assessed by measuring ventricular wall thickening at rest and with dobutamine stress echocardiography. Six weeks after revascularization, the animals were restudied at rest and with stress. Postsacrifice and histologic analysis of angiogenesis and TMR effects was then assessed. RESULTS: Laser TMR provided significant recovery of ischemic myocardial function. This improvement in contractility after laser TMR was a 75% increase over the baseline function of the ischemic zone (p < 0.01). Mechanical TMR provided no significant improvement in function posttreatment. In fact, TMR achieved with an ultrasonic needle demonstrated a 40% worsening of the contractility versus the pretreatment baseline (p < 0.05). Histologic analysis demonstrated a significant increase in new blood vessels in the ischemic zone after laser TMR, which was not demonstrated for any of the other groups (p < 0.05). Additionally, evaluation of the mechanical TMR channels demonstrated significant scarring, which correlated with the functional results. CONCLUSIONS: Using devices to create an injury analogous to the laser, mechanical TMR failed to improve the function of chronically ischemic myocardium. Only laser TMR significantly improved myocardial function.

Thoracoscopic transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization is a promising surgical technique used to treat nonreconstructable ischemic heart disease. Recent clinical data show that this technique improves the regional perfusion of ischemic myocardium and reduces angina. Presently, transmyocardial laser revascularization requires an open, lateral thoracotomy. We report here the use of thoracoscopic techniques to perform transmyocardial laser revascularization in a closed chest fashion. METHODS: Five Yorkshire farm pigs underwent left chest thoracoscopic exploration and pericardiotomy. A specialized laser handpiece then was introduced into the chest and thoracoscopic transmyocardial laser revascularization was performed (one channel per square centimeter) using an 800-W CO2 laser. RESULTS: Video analysis and gross pathology revealed that the anatomic area accessible to thoracoscopic transmyocardial laser revascularization included the entire left ventricular free wall distributions of the left anterior descending, left circumflex, and posterior descending arteries, from base to apex. Standard hematoxylin and eosin staining confirmed the creation of complete and patent 1-mm-diameter transmural channels throughout these distributions. CONCLUSION: We have shown that transmyocardial laser revascularization can be performed effectively and safely by thoracoscopy, and that this less invasive technique may reduce morbidity and provide a more cost-effective alternative therapy for nonreconstructable ischemic heart disease.

HLA histocompatibility affects cardiac transplant rejection and may provide one basis for organ allocation.

Prospective human lymphocyte antigen (HLA) typing is not performed for heart transplantation, and the relation between HLA matching and cardiac graft rejection is unclear. Recipient and donor HLA matching were analyzed retrospectively in 51 patients undergoing orthotopic cardiac transplantation. Immunosuppression was based on cyclosporine and prednisone. During the mean follow-up of 34 months (range, 16 to 63 months), the 46 operative survivors had an average of 3.95 rejection episodes (range, zero to 11 episodes). Twenty-one patients had steroid-resistant rejection requiring treatment with polyclonal or monoclonal antithymocyte globulin. Human lymphocyte antigen typing was available for 44 patients, and antigens were grouped in broad specificities. Patients with two or more HLA-A or HLA-B matches had a reduced number of rejection episodes (3/10 versus 19/34) and a lower incidence of steroid-resistant rejection (1/10 versus 18/34; p = 0.01). Inclusion of HLA-DR matches did not alter the findings. There was a strong correlation between the increased frequency of rejection and the incidence of steroid-resistant rejection (p less than 0.0001). Four of six late deaths occurred in patients with steroid-resistant rejection; four were due to acute rejection and two to graft atherosclerosis. Although not currently done, prospective HLA matching is feasible with present typing methods. Our results suggest a rationale for prospective histocompatibility testing in cardiac transplantation with allocation of donor hearts to patients with two or more HLA matches.

Transmyocardial laser revascularization in the patient with unmanageable unstable angina.

BACKGROUND: Transmyocardial laser revascularization (TMR) provides relief for patients with chronic angina, nonamenable to direct coronary revascularization. Unmanageable, unstable angina (UUA) defines a subset of patients with refractory angina who are at high risk for myocardial infarction and death. Patients were classified in the UUA group when they had been admitted to the critical care unit with unstable angina for 7 days with three failed attempts at weaning them off intravenous antianginal medications. METHODS: Seventy-six treated patients were analyzed to determine if TMR is a viable option for patients with unmanageable unstable angina. These patients were compared with 91 routine protocol patients (protocol group [PG]) undergoing TMR for chronic angina not amenable to standard revascularization. The procedure was performed through a left thoracotomy without cardiopulmonary bypass. These patients were followed for 12 months after the TMR procedure. Both unmanageable and chronic angina patients had a high incidence of at least one prior surgical revascularization (87% and 91%, respectively). RESULTS: Perioperative mortality (< or = 30 days post-TMR) was higher in the UUAG versus PG (16% vs 3%, p = 0.005). Late mortality, up to 1 year of follow-up, was similar (13% vs 11%, UUAG vs PG; p = 0.83). A majority of the adverse events in the UUAG occurred within the first 3 months post-TMR, and patients surviving this interval did well, with reduced angina of at least two classes occurring in 69%, 82%, and 82% of patients at 3, 6, and 12 months, respectively. The percent improvement in angina class from baseline was statistically significant at 3, 6, and 12 months. A comparable improvement in angina was found in the protocol group of patients. CONCLUSIONS: TMR carried a significantly higher risk in unmanageable, unstable angina than in patients with chronic angina. In the later follow-up intervals, however, both groups demonstrated similar and persistent improvement in their angina up to 12 months after the procedure. TMR may be considered in the therapy of patients with unmanageable, unstable angina who otherwise have no recourse to effective therapy in the control of their disabling angina.

Postoperative troponin I values: insult or injury?

BACKGROUND: Troponin I (TnI) is increasingly employed as a highly specific marker of acute myocardial ischemia. The value of this marker after cardiac surgery is unclear. HYPOTHESIS: The purpose of this study was to measure serum TnI levels prospectively at 1, 6, and 72 h after elective cardiac operations. In addition, TnI levels were measured from the shed mediastinal blood at 1 and 6 h postoperatively. Serum values were correlated with cross clamp time, type of operation, incidence of perioperative myocardial infarction, as assessed by postoperative electrocardiograms (ECG) and regional wall motion, as documented by intraoperative transesophageal echocardiography (TEE). METHODS: Sixty patients underwent the following types of surgery: coronary artery bypass graft (CABG) (n = 45), valve repair/replacement (n = 10), and combination valve and coronary surgery (n = 5). Myocardial protection consisted of moderate systemic hypothermia (30-32 degrees C), cold blood cardioplegia, and topical cooling for all patients. RESULTS: Of 60 patients, 57 (95%) had elevated TnI levels, consistent with myocardial injury, 1 h postoperatively. This incidence increased to 98% (59/60) at 6 h postoperatively. There was a positive correlation between the length of cross clamp time and initial postoperative serum TnI (r = 0.70). There was no difference in the serum TnI values whether or not surgery was for ischemic heart disease (CABG or CABG + valve versus valve). There were no postoperative myocardial infarctions as assessed by serial ECGs. There was no evidence of diminished regional wall motion by TEE. Levels of TnI in the mediastinal shed blood were greater than assay in 58% (35/60) of the patients at 1 h and in 88% (53/60) at 6 h postoperatively. Patients who received an autotransfusion of mediastinal shed blood (n = 22) had on average a 10-fold postoperative increase in serum TnI levels between 1 and 6 h. Patients who did not receive autotransfusion average less than doubled their TnI levels over the same interval. At 72 h, TnI levels were below the initial postoperative levels but still indicative of myocardial injury. CONCLUSION: Postoperative TnI levels are elevated after all types of cardiac surgery. There is a strong correlation between intraoperative ischemic time and postoperative TnI level. Further elevation of TnI is significantly enhanced by reinfusion of mediastinal shed blood. Despite these postoperative increases in TnI, there was no evidence of myocardial infarction by ECG or TEE. The postoperative TnI value is even less meaningful after autotransfusion of shed mediastinal blood.