Predictive value of intraoperative in situ radial artery conduit flow assessment prior to harvesting during coronary artery bypass surgery.

OBJECTIVE: Radial artery (RA) is increasingly preferred as the second best conduit in coronary artery bypass grafting (CABG). Harvesting techniques affect the integrity of the RA with implications for the immediate and late outcome. The aim of this study was to describe a simple intra-operative technique that allows the quality of the RA to be assessed prior to its harvesting during CABG. METHODS: The study group consisted of 54 patients who underwent CABG. A 2-cm vertical incision was made over the nondominant RA pulse. A limited pedicle of the RA was positioned inside the metal cradle of the flexible flow probe. Baseline transit-time ultrasonic flow and pulsatility index (PI) were measured. RESULTS: Average IN SITU RA flow was 18.6 ml/min (range 4-51 ml/min). Of 14 IN SITU RAs, all but three RAs were found to have adequate flow characteristics and were used as conduits. In the three unsuitable RAs, one had complete obliteration and no flow; one had visible calcifications and very low flow and the third one had a weak pulse, low flow and high PI. CONCLUSION: Routine assessment of IN SITU RA flow characteristics via a 2-cm incision provides useful information about RA conduit quality prior to its formal harvesting during CABG. Despite considerable skepticism about the use of the radial artery due to its vasospastic potential, this technique may increase utilization rates of the RA as a conduit during CABG, in particular in many young diabetic patients.

Serum lactates are not predictive of heart failure severity in status I cardiac transplant candidates.

BACKGROUND: Blood lactate is an accurate predictor of outcome in clinical shock syndrome patients. However, its usefulness in status I heart transplant candidates with failing myocardium is largely unknown. The purpose of this study was to determine whether serum lactate levels are predictive of congestive heart failure severity in cardiomyopathic status I cardiac transplant candidates. METHODS: Over a 6-month period, serial arterial serum lactate levels in 30 status I heart transplant candidates were measured. Measured serum lactate values (mmol/L) included the initial lactate level upon admission to the intensive care unit and the lactate level at 6-week intervals up to 24-weeks. Surveillance right heart catheterizations were also performed at 6-week intervals to determine pulmonary artery pressures and cardiac index. Baseline measurements were compared with the values obtained at time intervals of 6-, 12-, 18-, and 24-weeks. RESULTS: All status I heart transplant candidates were admitted to the intensive care unit for treatment of worsening heart failure with intravenous inotropic therapy. All patients had severe pulmonary hypertension (greater than two-thirds of systemic arterial pressure, mmHg) and/or severe low cardiac output state (cardiac index less than 2.0 L/min/M(2)). Admission lactate level was normal in all candidates. Intravenous inotropic therapy improved patients' symptoms and cardiopulmonary hemodynamic derangements although lactate levels remained within the normal range until the time of heart transplant operation or up to 24-weeks (p=NS). CONCLUSIONS: Blood lactate remains unaffected by worsening congestive heart failure of cardiomyopathy patients and is not predictive of heart failure severity in status I cardiac transplant candidates.

Reversal of preexisting vasospasm in coronary artery conduits.

BACKGROUND: To reverse preexisting coronary graft spasm, we investigated the vasodilative effect of the average therapeutic plasma concentration of nitroglycerin (NTG) alone and various calcium antagonists in combination with NTG in human arterial and venous conduits. METHODS: Vasodilative effects of 2 x 10(-8) mol/L NTG alone and 10(-8) mol/L NTG in combination with 2.2 x 10(-7) mol/L diltiazem, 2.8 x 10(-7) mol/L nifedipine, 10(-7) mol/L verapamil, or 5.6 x 10(-8) mol/L nicardipine were assessed in human radial artery, internal thoracic artery, and saphenous vein segments precontracted with a mixture of ten times the maximum plasma concentrations of endothelin-1 (8.6 x 10(-13) mol/L), angiotensin II (36 x 10(-11) mol/L), 5-hydroxytryptamine (3.4 x 10(-7) mol/L), and norepinephrine (1.7 x 10(-8) mol/L). The studies were done in organ baths. RESULTS: The therapeutic concentration of NTG alone or nifedipine, verapamil, diltiazem, or nicardipine in combination with NTG caused equal relaxation in a particular group of vascular segments (average vasodilation: radial artery, 83% to 95% [p = 0.7608 by analysis of variancel; saphenous vein, 47% to 70% [p = 0.3142]; internal thoracic artery, 54% to 79% [p = 0.27831). These combinations were not equally effective when compared between different groups of vascular segments (vasodilation; radial artery > internal thoracic artery > saphenous vein [p < 0.0001 by analysis of variance]). Although not significant, in comparison with NTG alone, NTG in combination with a calcium antagonist caused less vasodilation in any group of vascular segments. CONCLUSIONS: Nitroglycerin alone or in combination with nifedipine, verapamil, diltiazem, or nicardipine effectively reverses preexisting vasospasm in coronary artery conduits.

Staged resection of bilateral pleuropulmonary blastoma in a two-month old girl.

Pleuropulmonary blastoma is a rare unilateral intrathoracic tumor of childhood. We report an unusual case of bilateral pleuropulmonary blastoma in a two-month old girl who underwent staged thoracotomies for complete wedge resection of both neoplasm. She remains well and tumor free two years after the operation.

Coronary artery bypass combined with bilateral carotid endarterectomy.

BACKGROUND: Surgical management of patients presenting for coronary artery bypass grafting with significant bilateral carotid artery stenosis has not been well defined. In this study, our preliminary results of coronary artery bypass grafting with concomitant bilateral carotid endarterectomy have been reviewed. METHODS: A retrospective nonrandomized chart review was performed in 33 patients with unstable angina and bilateral carotid artery stenosis, more than 70%, undergoing simultaneous coronary artery bypass grafting and bilateral carotid endarterectomy using an eversion technique. RESULTS: Concomitant coronary artery bypass grafting with bilateral carotid endarterectomy was performed urgently in 24 (73%) and electively in 9 (27%) patients. The average carotid artery cross-clamp and total perfusion times were 14.7 +/- 4.9 minutes and 123 +/- 29.2 minutes, respectively. The average length of stay in the cardiopulmonary intensive care unit was 4.2 +/- 14.2 days and total hospital stay was 16.2 +/- 20.5 days. Postoperative in-hospital stay was 14.9 +/- 20.3 days. There were no postoperative strokes. Twenty-one (64%) patients were discharged before the tenth postoperative day. Nonfatal postoperative complications occurred in 27% (9 of 33) of patients. The overall 30-day mortality was 6.1% (2 of 33) and that was unrelated to primary cardiac or cerebrovascular events. CONCLUSIONS: Favorable outcome supports the justification for performing concomitant coronary artery bypass grafting with bilateral carotid endarterectomies in selected patients.

Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation.

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.

Use of intraoperative hetastarch priming during coronary bypass.

BACKGROUND: The use of hetastarch during coronary bypass surgery has been limited due to its unresolved potential risk for hemorrhage. Therefore, the purpose of this study was to investigate the effects of using 6% hetastarch in priming cardiopulmonary bypass (CPB) circuitry on the need for blood product transfusions and outcome after coronary bypass. MATERIALS AND METHODS: This nonrandomized retrospective study involved 887 patients who underwent isolated primary coronary artery bypass grafting. Based on the type of solution used in priming the CPB circuitry, patients were stratified into the following four different groups: group 1, crystalloid (500 mL; n = 211); group 2, 25% human albumin (50 mL; n = 217); group 3, 6% hetastarch (500 mL; n = 298); and group 4, 25% human albumin (50 mL) and 6% hetastarch (500 mL; n = 161). Patient characteristics and clinical variables were compared among the groups using the Kruskal-Wallis test. Patient survival estimates were compared using log-rank test. RESULTS: Demographic patient characteristics for all groups were similar (p > 0.05). Intraoperative and perioperative variables among groups were comparable (p > 0.05). The use of hetastarch as a part of prime solution in CPB circuitry did not alter the need for banked blood, platelets, or fresh frozen plasma transfusions (p > 0.05). The length of stay in the ICU or in the hospital was unaffected in all groups. The early (ie, 30-day) mortality rate was 1.4% in group 1, 1.8% in group 2, 1.0% in group 3, and 3.1% in group 4. Long-term survival among the groups was unaffected by the type of priming solution. CONCLUSIONS: The use of hetastarch in priming CPB circuitry is devoid of any added hemorrhagic risk after coronary bypass, and the type of prime solution for CPB has no influence on the early or late survival rates of patients undergoing primary coronary bypass.

Neurogenic vasoreactivity of human internal thoracic artery is unaffected by endothelial cell integrity.

BACKGROUND: The role of internal thoracic artery (ITA) nervous supply has not been previously considered as a potential factor influencing excellent long-term patency of an ITA graft. To define the interaction between the primary afferent neurons and endothelial cells of ITA, we investigated the effects of acute capsaicin administration in vitro on the isometric tension of human ITAs. METHODS: Vessels were obtained from patients undergoing coronary bypass or from multi-organ transplant donors. Thirty-three ITA segments (5 mm wide) were suspended as rings between two stainless-steel stir-ups in water-jacketed (37 degrees C) tissue baths. The tissue baths contained 10 ml physiological salt solution (PSS) of the following composition (mM/L): NaCl 119, KCl 4.7, NaH2PO4 1.0, MgCl2 0.5, CaCl2 2.5, NaHCO3 25, and glucose 11, aerated continuously with 95% O2 and 5% CO2. Peptidase inhibitors, phosphoramidon (1 microM) and captopril (1 microM), were added to PSS to decrease peptide degradation. Mechanical responses were measured isometrically and recorded on a polygraph via isometric force transducers. Vessels were preconstricted with submaximal concentrations of norepinephrine. After the tension had stabilized, capsaicin was added cumulatively to the tissue bath. The viability of ITA was verified by its responses to endothelial-dependent (acetylcholine, 1 microM) (n=20) and endothelial-independent (sodium nitroprusside, 10 microM) (n=13) vasodilators. RESULTS: The exposure of capsaicin (3 microM) to human ITA produced varied effects on ITA irrespective of its endothelium. Capsaicin induced contraction of the ITA smooth muscle in 13 endothelium-intact ITA segments while it produced vasoconstriction in 9 endothelium-denuded ITAs (p=0.6437). In response to capsaicin, relaxation of ITA smooth muscle was observed in 7 ITA rings with endothelium, while vasodilation was present in 4 ITA segments without endothelium (p=0.4099). CONCLUSIONS: Capsaicin-sensitive neurons encircling human ITA produce a neurogenic vasoreactive response independent of ITA endothelial cell integrity.

Possible relationship between degenerative cardiac valvular pathology and lyme disease.

We report an unusual clinical presentation of Lyme carditis in a previously healthy 20-year-old black woman without any epidemiologic history of Lyme disease, fulminant in nature, involving a heart valve necessitating emergent mitral valve replacement, and requiring further surgical intervention because of the development of pericardial effusion and tamponade. A dilated right ventricle with normal contractility and severe tricuspid regurgitation with increase in the right atrial size diagnosed later remains under close surveillance.

Association of osteopontin with calcification in human mitral valves.

BACKGROUND: Little is known about the long-standing inflammation leading to calcification within heart valves. Osteopontin, a phosphorylated glycoprotein, is present within atheromatous calcific plagues in response to vascular endothelial injury. The purpose of the study was to investigate whether osteopontin exists in calcific mitral valve leaflets in human beings, and to determine a link between chronic inflammation leading to mitral stenosis and the osteopontin status of mitral valvular tissue. MATERIALS AND METHODS: We reviewed the case histories of 17 patients who underwent mitral valve replacement therapy for mitral stenosis between 1995 and 1997 (8 men and 9 women, mean age 61 years). Hybrid mouse monoclonal immunoglobulin G1 antibodies were used for immunohistochemical detection of osteopontin in the acetone-fixed specimen. The control group consisted of normal mitral valve tissue from cardiomyopathy patients who underwent cardiac transplantation. RESULTS: A weak osteopontin immunoreactivity was present in apparently normal mitral valve tissue obtained from cardiomyopathy patients. All mitral stenosis patients had immunoreactivity (17/17) for osteopontin within calcific deposits of mitral valve tissue. The intensity of osteopontin activity had a strong association with increasing macrophage and calcium aggregations in the mitral valvular tissue. We found no correlation between osteopontin status and clinical features on the prognosis of calcific mitral stenosis. CONCLUSIONS: We conclude that osteopontin coexists with intimal macrophages in calcific human mitral valve tissue. Demonstration of such association between the presence of osteopontin and calcification in human mitral valves is consistent with the hypothesis that calcification in this tissue is, at least in part, an actively mediated phenomenon.

Acute renal failure requiring hemodialysis immediately after heart transplantation portends a poor outcome.

BACKGROUND: Previous studies have not provided a definite clarification for the predictive value of pretransplant renal indices on postcardiac transplant patient outcome. Therefore, the purpose of this study was to investigate the interaction between pretransplant renal function and recovery after heart transplantation. METHODS: The study group consisted of 199 consecutive patients who underwent heart transplantation between 1973 and 1994. For better comparison, patients were arbitrarily divided into three different groups based on the year of the transplant operation: Group I- before 1985 (n=13), Group II- between 1985 and 1989 (n=68) and Group III- between 1990 and 1994 (n=118). Values for serum creatinine (Cr), blood urea nitrogen (BUN), urea/creatinine ratio (U/Cr), creatinine clearance (Cr(cl)), length of hospital stay (LOS), early (30-day) mortality, and survival at 1-year and at 5-year were collected for each patient. The data was analyzed by the use of univariate log-rank test with forward stepwise procedure. RESULTS: Postcardiac transplant LOS in the hospital or survival was unaffected by the pretransplant renal indices except the U/Cr ratio (p>0.05). When adjusted for the time, the U/Cr ratio was also insignificant (p=0.1349). The use of hemodialysis was necessary in 9 patients (4.5%) for treatment of acute renal failure manifested immediately after the transplant operation. Early mortality was 44% for these 9 cardiac transplant recipients who required the use of hemodialysis: 0% (0/3) in the 1985-1989 period and 67% (4/6) in the 1990-1994 period. CONCLUSIONS: Pretransplant renal indices have no predictive value on outcome after a heart transplant operation, however, postcardiac transplant acute renal failure necessitating hemodialysis portends a poor outcome.

Milrinone for long-term pharmacologic support of the status 1 heart transplant candidates.

BACKGROUND: We determined the efficacy of long-term therapy with milrinone alone or in combination with inotropic agents in status 1 heart transplant candidates as a pharmacological support until heart transplantation. METHODS: Hemodynamic and biochemical variables were recorded in 29 status 1 men with symptoms of severe congestive heart failure, who received continuous intravenous milrinone alone (group 1, n = 21) or in combination with inotropic agents (group 2, n = 8) while awaiting heart transplantation. RESULTS: Symptomatic relief was noted in all patients of both groups without any preoperative deaths. One patient (4.8%) of group 1 died on the second day and 1 patient of group 2 died 16.4 months after transplantation. Although pulmonary capillary wedge pressure (group 1, p = 0.021; group 2, p = 0.0002), mean pulmonary artery pressure (group 1, p = 0.051; group 2, p = 0.004), and pulmonary vascular resistance (group 1, p = 0.0026; group 2, p = 0.056) were reduced by 1 hour after the onset of treatment and maintained unchanged until transplantation, the changes in mean pulmonary artery pressure in group 1 and pulmonary vascular resistance in group 2 were statistically insignificant except in the posttransplantation period. CONCLUSIONS: Long-term therapy with milrinone in combination with inotropic agents is safe and effective when only milrinone infusion is inadequate for pharmacologic support in status 1 candidates.

Prevention of radial artery graft vasospasm after coronary bypass.

BACKGROUND: Pharmacologic prophylaxis for prevention of notorious radial artery (RA) spasm is critical because of the increasingly routine use of the RA conduit during coronary bypass. Therefore, we investigated the vasodilatory effect of calcium antagonist in combination with nitroglycerin (NTG) RA segments. METHODS: We evaluated the vasodilatory effect of nifedipine alone, verapamil alone, diltiazem alone, NTG alone, and calcium antagonist in combination with in endothelin-1 (ET-1)-, angiotensin II (AII)-, 5-hydroxytryptamine (5-HT)-, and norepinephrine (NE)-precontracted human RA rings mounted in organ baths. RESULTS: Nifedipine (10(-5) M) alone, diltiazem (10(-5) M) alone, verapamil (10(-5) M) alone, and NTG (10(-5) M) alone showed maximum vasodilatory effect in either 10(-7) M ET-1-, 10(-7) M AII-, 10(-5) M NE-, or 10(-4) M 5-HT-precontracted RA segments. The 10(-5) M NTG alone-induced vasodilation (88.5% +/- 7.7%) in ET-1-precontracted segments was the highest vasodilation (ANOVA, p = 0.0008) among NTG alone-induced vasodilatory effects in RA. The relaxing effect of any of the calcium antagonists alone varied from 32.7% +/- 13.2% to 76.5% +/- 20.5% in RA precontracted with different vasoconstrictors. Nearly 200% vasodilation was observed with calcium antagonist in combination with NTG in AII-precontracted vessels. Nonetheless, the vasodilatory effect of calcium antagonist in combination with NTG in RA segments precontracted with different vasoconstrictors other than AII was nearly 100%. CONCLUSIONS: A calcium antagonist in combination with NTG is more potent than calcium antagonist alone or NTG alone in prevention of human RA vasospasm after coronary bypass.

Transit-lime Ultrasound Flowmetry in CABG.

Intraoperative measurement of flow allows functional evaluation of coronary bypass grafts and may be predictive of a patient's immediate and late outcome after myocardial revascularization as it permits early detection of technical errors. Many different methods have been used to assess the quality of the anastomosis intraoperatively. Angiography is considered the gold standard technique to which all other methods should be compared. However, it is invasive, costly, time consuming, and not always readily accessible in the operating room.

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Does University of Wisconsin solution harm the transplanted heart?

BACKGROUND: University of Wisconsin solution (UW) has been shown to be an effective preservative for the cardiac allograft. Recently, the high potassium content of UW has been implicated in causing coronary endothelial damage, allegedly contributing to development of cardiac allograft vasculopathy (CAV) and eventually to poorer survival. METHODS: We examined our experience using UW for preservation of cardiac allografts between 1990 and 1994 (n = 94), and compared these to hearts preserved with the lower potassium-containing Stanford solution used at our center between 1986 and 1990 (n = 65). Indices of graft function, ischemic injury, CAV incidence, CAV severity, and survival were evaluated. RESULTS: The 2 groups were similar in age, gender, diagnosis, donor inotropic support, donor-recipient weight ratio, incidence of acute graft failure, and cytomegalovirus seroconversion. UW-preserved hearts came from older donors (30.5 vs 24.1 years, p < .001), and were transplanted into more status 1 recipients (56% vs 22%, p < .001), consistent with current trends. Mean ischemic time of UW-preserved hearts was significantly longer (184 vs 155 minutes, p < .005) although time required to wean from bypass was less (45.5 vs 73.8 minutes, p < .001) and there was a trend towards less inotropic requirement. CPK-MB release was less with UW preservation (63 vs 87 microg/ dL, p = .001). Three years after transplantation, both groups were similar in the incidence of CAV (UW, 27.3%; STNF, 37.5%; p = 0.27), and also the severity of CAV (p = 0.78). Deaths attributed to CAV were equal in each group (UW, 11.4% vs STNF, 10.7%; p = 0.79). Kaplan-Meier survival analysis revealed equivalent survival curves (p = 0.26). CONCLUSIONS: We conclude that UW is a safe and effective myocardial preservative, allowing longer ischemic times with equivalent graft function. Our data suggest that when UW is used for cardiac allograft preservation, both CAV and survival are comparable to the experience with other preservatives containing lower concentrations of potassium.

Efficacy of tacrolimus in the treatment of refractory rejection in heart and lung transplant recipients.

BACKGROUND: Refractory acute cellular rejection may occur despite triple-drug immunosuppression (cyclosporine A, steroids, azathioprine/mycophenolate mofetil). The purpose of this study was to determine the efficacy of tacrolimus rescue therapy in patients maintained on cyclosporine-based immunosuppression (CBI). METHODS: Between December 1993 and October 1996, 208 patients underwent thoracic organ transplantation at the Hospital of the University of Wisconsin at Madison. One hundred forty-nine patients underwent heart replacement; 59 underwent lung transplantation. One hundred thirty-nine of the heart transplant cohort received CBI preceded by induction therapy with OKT3. Forty-six of the lung transplant cohort received CBI without induction cytolytic therapy. Refractory rejection was defined as failure to respond to high-dose steroids (500 mg to 1 g IV methylprednisolone for 3 days) and/or monoclonal antibody therapy (OKT3, 5 to 10 mg IV/day for 7 to 14 days). In patients with refractory rejection, cyclosporine was replaced with tacrolimus. RESULTS: Overall, 16% (30/185) of patients receiving CBI experienced refractory rejection. Thirty-one episodes of grade IIIa or greater rejection occurred in 11% (15/139) of heart transplant recipients. Twenty episodes of grade II to IV rejection occurred in 33% (15/46) of lung transplant recipients. After tacrolimus rescue therapy, 93% (14/15) of patients in the heart transplant group converted to grade II or less rejection. Refractory rejection was reversed in 73% (11/15) of the lung transplant group. Reversal was documented at biopsy in all (8/8) lung recipients in whom it had been histologically identified. FEV1 values of 3 additional patients stabilized. CONCLUSIONS: The incidence of refractory rejection in thoracic organ transplant recipients on CBI is significant. Reversal of refractory rejection follows rescue immunotherapy with tacrolimus.

Impact of University of Wisconsin solution on clinical heart transplantation. A comparison with Stanford solution for extended preservation.

BACKGROUND: The University of Wisconsin Solution (UW) has extended preservation of abdominal organs but has not allowed equally extended preservation of the heart. Therefore, the impact of UW on clinical heart transplantation has remained unclear. METHODS AND RESULTS: Between June 1986 and March 1994, 161 orthotopic heart transplants were performed at our center. Of these, 66 were preserved for > or = 3 hours. Of these, 17 hearts were preserved with Stanford solution (STNF), which was used before 1990, and 49 were preserved with UW. These groups were compared for indexes of ischemic injury, ventricular function, and survival. The UW group contained more status-1 recipients (57% versus 29%, P < 0.05) and a higher mean donor age (30.7 versus 22.1 years, P = 0.008). Mean ischemic time was slightly but not significantly higher with UW (228 versus 205 minutes for UW versus STNF, respectively; P = 0.085). The time to wean from bypass after cross-clamp removal was nearly twice as long with STNF than with UW (80.6 versus 44.3 minutes, P < 0.001). There was no difference in the incidence of primary graft failure (2% for UW versus 6% for STNF, P = 0.43). The average need for inotropic support over the first 8 posttransplant hours was significantly higher with STNF than UW. Neither hospital stay nor survival differed. Nevertheless, the ability to use donor organs from more distant sites was increased. Of all hearts preserved with STNF, 26% were stored for > or = 3 hours, whereas 51% of all hearts preserved in UW were stored for this length of time. Donor use of hearts increased from 20% in 1989 to 63% in 1993, largely because of greater use of more distant donors. CONCLUSIONS: We conclude that heart preservation with UW limits ischemic damage from prolonged storage and improves myocardial function in the early posttransplant period, thus allowing greater use of available donors from distant sites to patients awaiting heart transplantation.

The influence of cardiopulmonary function on outcome of veterans undergoing resectional therapy for lung cancer.

BACKGROUND: The unknown but presumably poor preoperative cardiopulmonary function of U.S. Armed Forces veterans with bronchogenic cancer may dissuade surgeons performing necessary major lung resection. The purpose of this study was to investigate the relationship between preoperative cardiopulmonary risk and the outcome of veterans undergoing pulmonary resection for bronchogenic carcinoma. METHODS: A retrospective chart review was performed on 79 veterans who underwent lung resection for bronchogenic cancer between March 1990 and June 1995. Preoperative cardiac function was assessed by 1) history of heart disease (myocardial infarction, previous open heart surgery, and hypertension), 2) electrocardiogram, EKG, and 3) transthoracic echocardiography, TTE (ejection fraction and left ventricular wall motion abnormalities). Pulmonary reserve was evaluated by 1) history of lung disease (active smoking, known chronic obstructive pulmonary disease, COPD), and 2) spirometry (forced expiratory volume in 1 second, FEV1, and minute ventilation volume, MVV). Resections were performed by standard pulmonary techniques and follow-up data was available in all patients. RESULTS: All patients were males except one, with a mean age of 66+/-1.0 yrs (range=32 to 81 yrs). Fifty-one patients (64.60%) had a history of COPD while one-third of the veterans were smoking and using excessive alcohol just prior to surgery. Twenty-four patients (29%) had abnormal preoperative EKG and only 10 (15%) had prior myocardial infarction. Eleven patients (13.9%) had undergone previous coronary bypass surgery. Average preoperative left ventricular ejection fraction was 63+/-2% (range=41 to 80%) and left ventricular wall motion abnormalities were present in only 6 patients (8%). Mean preoperative FEV1 was 2.2+/-0.1 L (range=0.6-4.1 L) and MW was 87+/-4 L/min (range=26-198 L/min). A lobectomy was performed in 68 patients (86.1%), pneumonectomy in 10 (12.7%), and wedge resection in 1 (1.2%). The most common types of cancer were squamous cell (36 patients) and adenocarcinoma (31 patients). While pulmonary complications (atelectasis, prolonged air leak, pneumonia) occurred in 8 patients (10%), only two (3%) suffered nonpulmonary complications (ischemic bowel disease). For all veterans with bronchogenic cancer, early (30-day) mortality after major lung resection was 3.9% (3/79): 1.5% (1/68) after lobectomy, and 20% (2/10) after pneumonectomy (p=not significant). Overall survival at 5 years was 39.5%. CONCLUSIONS: Preoperative cardiopulmonary risk for veterans with bronchogenic cancer is acceptable and lung resection can be performed with good outcomes in this distinct patient population.