Unusual presentation of nickel allergy requiring explantation of an Amplatzer atrial septal occluder device.

Systemic allergic reaction to a percutaneous patent foramen ovale (PFO) occlusion device is a rare event with only scattered reports in the literature. Serious allergic reactions to these devices have a poorly defined incidence, presentation, and natural history. We present a woman with a previously unknown nickel allergy who developed severe chest pain beginning the morning after percutaneous device closure of the PFO. Despite multiple visits to her cardiologists and primary care physicians, the cause of her chest pain remained unclear. After seeking a second opinion at our medical center, skin testing showed a severe reaction to nickel. These symptoms were refractory to treatment until device explantation 18 mo later. This case highlights the importance of recognizing nickel allergy as a cause of chest pain following implantation of certain types of devices used for closure of PFOs and other heart defects.

Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells.

Transforming growth factor-beta1 (TGF-beta1) is abundantly expressed in pulmonary hypertension, but its effect on the pulmonary circulation remains unsettled. We studied the consequences of TGF-beta1 stimulation on freshly isolated human pulmonary artery smooth muscle cells (HPASMC). TGF-beta1 initially promoted differentiation, with upregulated expression of smooth muscle contractile proteins. TGF-beta1 also induced expression of Nox4, the only NAD(P)H oxidase membrane homolog found in HPASMC, through a signaling pathway involving Smad 2/3 but not mitogen-activated protein (MAP) kinases. TGF-beta1 likewise increased production of reactive oxygen species (ROS), an effect significantly reduced by the NAD(P)H oxidase flavoprotein inhibitor diphenylene iodonium (DPI) and by Nox4 siRNAs. In the absence of TGF-beta1, Nox4 was present in freshly cultured cells but progressively lost with each passage in culture, paralleling a decrease in ROS production by HPASMC over time. At a later time point (72 h), TGF-beta1 promoted HPASMC proliferation in a manner partially inhibited by Nox4 small interfering RNA and dominant negative Smad 2/3, indicating that TGF-beta1 stimulates HPASMC growth in part by a redox-dependent mechanism mediated through induction of Nox4. HPASMC activation of the MAP kinases ERK1/2 was reduced by the NAD(P)H oxidase inhibitors DPI and 4-(2-aminoethyl)benzenesulfonyl fluoride, suggesting that TGF-beta1 may facilitate proliferation by upregulating Nox4 and ROS production, with transient oxidative inactivation of phosphatases and augmentation of growth signaling cascades. These findings suggest that Nox4 is the relevant Nox homolog in HPASMC. This is the first observation that TGF-beta1 regulates Nox4, with important implications for mechanisms of pulmonary vascular remodeling.

Early experience with sirolimus in lung transplant recipients with chronic allograft rejection.

BACKGROUND: Chronic lung allograft rejection, commonly manifest as obliterative bronchiolitis (OB/BOS), hinders long-term survival after lung transplantation (LT). OB/BOS is traditionally treated with augmented immunosuppression and results in short-term stabilization in pulmonary function for most patients. However, peribronchiolar fibroproliferation and airway obstruction usually recur despite initial improvements seen with increases in immunosuppression. In this observational, uncontrolled study, the effect of sirolimus, a novel immunosuppressant with anti-proliferative activity, was assessed in LT patients with OB/BOS. METHODS: Between June 1999 to November 2000, LT recipients with newly diagnosed or progressive OB/BOS received sirolimus in combination with a calcineurin inhibitor (CI) and prednisone. Pulmonary function, laboratory data and adverse effects were monitored for the first 24 weeks of therapy. RESULTS: Sirolimus was utilized in 12 LT recipients with OB/BOS. After drug initiation, 58% of patients required a reduction in CI dose to maintain appropriate CI trough concentrations. Despite CI dose reduction, serum creatinine rose in 75% of patients. Unexpected adverse effects included anemia of chronic disease (100%), edema (50%) and malignancy (17%). For the group, the rate of change in FEV(1) and FEF(25%-75%) was unchanged with sirolimus, but individual responses varied. CONCLUSIONS: For the group, the decline in pulmonary function was not affected by the addition of sirolimus. However, among individuals with rapidly declining pulmonary mechanics, sirolimus resulted in stabilization or improvement in pulmonary function. Significant adverse effects resulted from combination sirolimus plus CI therapy. Until optimal dosing strategies and a more complete adverse effect profile are established, combination therapy should be utilized cautiously in these patients.

Conduits for cerebrovascular bypass and lessons learned from the cardiovascular experience.

Direct cerebral revascularization is an important procedure in the treatment of certain complex aneurysms and skull base tumors when acute sacrifice of the internal carotid artery is required. It likely remains an appropriate treatment in a small subgroup of patients with cerebral ischemia refractory to maximal medical management. Similar to cardiovascular surgery, the choice of a graft conduit is critical for a successful outcome. The standard conduits are interposition vein grafts (usually the greater saphenous vein), free arterial grafts (radial artery), and pedicled arterial grafts (superficial temporal artery). The goal of this review is to summarize the conduits commonly used in cerebral revascularization with emphasis on their patency rates and flow characteristics. Comparisons are made with similar data available in the cardiovascular literature.

Prevention of bone loss and fracture after lung transplantation: a pilot study.

BACKGROUND: Osteoporotic fracture is a significant source of morbidity after lung transplantation. Therapies to prevent posttransplant fracture are largely untested among lung transplant recipients. METHODS: In this prospective uncontrolled study, lung transplant referrals were assessed for bone health with metabolic, radiographic, and bone mineral density measurements. Transplant recipients were treated with an antiresorptive regimen that included a bisphosphonate starting before or after transplantation. One year after transplantation, the fracture rate and bone density of patients in each group were reassessed and compared to historical controls. Between January 1996 and August 1999, 45/50 (90%) lung transplant referrals underwent bone health assessment. Transplant candidates received calcium, vitamin D, and hormone replacement therapy as indicated for hypogonadism. After July 1998, bisphosphonate therapy was added for candidates with osteopenia or osteoporosis (T score <1). After transplantation, all patients received 90 mg of pamidronate i.v. every 12 weeks, regardless of pretransplant bone density. Radiologic evaluation was performed for clinical suspicion of fracture. Bone density was remeasured 1 year after transplantation. RESULTS: Most transplant referrals suffered from osteopenia or osteoporosis, and 29% of transplant referrals had prevalent vertebral compression fractures. Hypogonadism was untreated in 50% of men and 20% of women, and 15% of patients had hypovitaminosis D. Of the 21 patients assessed 1 year after transplantation, new fractures occurred in 4% of these patients. Lateral lumbar spine and hip bone density remained stable or improved in 65% and 86% of patients, respectively. Most of those who lost bone density had started bisphosphonate therapy after transplantation. CONCLUSIONS: Antiresorptive therapy with a bisphosphonate decreases the fracture rate and preserves bone mass 1 year after lung transplantation. In end-stage lung disease patients with osteopenia or osteoporosis, bisphosphonate therapy should be initiated before transplant surgery is contemplated.

Effect of a resident self-study and presentation program on performance on the thoracic surgery in-training examination.

BACKGROUND: In this study we examine whether conversion from a didactic lecture format to a resident self-study and presentation program can improve performance on the Thoracic Surgery In-Training Examination (TSITE). METHODS: During the first 5 years, educational conferences were didactic lectures delivered by the attending thoracic surgery staff (group 1, n = 9 residents). During the second 5 years, residents prepared and delivered reviews from major textbook sources (group 2, n = 9 residents). Scores on the American Board of Surgery In-Training Examination (ABSITE) as a chief resident in general surgery were analyzed using one-way analysis of variance to assess fund of knowledge and test-taking skills prior to thoracic surgery training for the two groups. Scores on the TSITE during the first and second years of thoracic surgery training were recorded for each resident and analyzed using a paired t test. The data are expressed as the mean +/- standard deviation. RESULTS: Eighteen thoracic surgery residents over a 10-year period were involved in the study. ABSITE scores as a chief resident in general surgery did not differ between the two groups. Residents in group 1 improved their percentile rank from the first to the second year by a mean of 11%+/-12%, whereas those in group 2 improved their scores by a mean of 31%+/-21% (P < 0.05). CONCLUSIONS: When compared with a didactic lecture format, a resident self study and presentation program improves performance on the Thoracic Surgery In-Training Examination. This improvement in performance typically manifests during the second year of thoracic surgery training.

Interleukin-18 production following murine cardiac transplantation: correlation with histologic rejection and the induction of INF-gamma.

Interleukin-18 (IL-18) and IL-12 have been shown to play an important role in the induction of interferon-gamma (IFN-gamma). IFN-gamma induces the proliferation of T cells and natural killer (NK) cells and augments the Th1 immune cascade. The role of IL-18 and IL-12 in the induction of IFN-gamma following allogeneic heart transplantation has not been described. We sought to characterize the IL-12 and IL-18 response to murine allogeneic heart transplantation, particularly with respect to IFN-gamma production and histologic transplant rejection. Forty-eight heterotopic heart transplants were performed in two groups of mice: syngeneic C3H/HeN to C3H/HeN mice and allogeneic BALB/C to C3H/HeN mice. Transplants were followed out to 2, 6, 10, and 14 days. Six transplants were performed in each group. Serum and splenic samples were used to evaluate the cytokine response by ELISA. Explanted heart tissue was processed for evidence of histologic rejection, and RT-PCR was performed to evaluate the IL-12, IL-18, and IFN-gamma signal qualitatively. Analysis of variance (ANOVA), Fisher's projected least significant difference (PLSD) was used for statistical analysis. Transplant rejection occurred in the allogeneic group histologically by day 6 and clinically by day 10. Serum IFN-gamma levels rose significantly by day 6 in the allogeneic group and then continued to rise in the splenocyte cultures. Serum IL-18 also rose significantly in the allogeneic group at day 6 compared with syngeneic group. RT-PCR revealed that the allogeneic tissue contained an increased signal for IL-12, IL-18, and IFN-gamma beginning at day 6 and peaking at day 10 after transplant. Beginning 6 days after transplantation, IL-12 and IL-18 appear to play a significant role in the induction of IFN-gamma in allogeneic heart transplants.

Coronary artery bypass grafting with cardiopulmonary bypass versus off-pump cardiopulmonary bypass grafting: does eliminating the pump reduce morbidity and cost?

BACKGROUND: Cardiopulmonary bypass (CPB) may contribute to the complications and cost of coronary artery bypass grafting (CABG). Off-pump CABG (OPCAB) allows coronary revascularization without CPB. We hypothesized that OPCAB provides satisfactory graft patency while reducing complications and cost compared with CABG with CPB. METHODS: We prospectively followed 80 patients undergoing CABG: 40 patients undergoing OPCAB and 40 patients undergoing CABG with CPB. OPCAB patients underwent angiography within 48 hours of surgery to determine early graft patency. Incidence of complications, length of stay, and costs were recorded for each patient. The influence of the number of vessels bypassed was analyzed. RESULTS: OPCAB patients (n = 40) underwent grafting of 2.7 +/- 0.7 vessels per patient compared with 3.6 +/- 0.8 vessels per patient in the CABG with CPB group (n = 40) (p < 0.0001). Angiography demonstrated 105 of 108 (97%) of grafts were patent in the OPCAB group. Incidence of complications, length of stay, and costs did not differ between the OPCAB and CABG with CPB groups. Number of vessels grafted showed a positive correlation to total costs in both groups. CONCLUSIONS: While OPCAB provided satisfactory early graft patency, there was no significant difference between OPCAB and CABG with CPB with regard to cost, length of stay, or incidence of complications. In this study, eliminating CPB did not reduce morbidity or cost after CABG.

Improved biochemical preservation of lung slices during cold storage.

BACKGROUND: Development of lung preservation solutions typically requires whole-organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that lung slices could be used to assess preservation of biochemical function during cold storage. MATERIALS AND METHODS: Whole rat lungs were precision cut into slices with a thickness of 500 microm and preserved at 4 degrees C in the following solutions: University of Wisconsin (UW), Euro-Collins (EC), low-potassium-dextran (LPD), Kyoto (K), normal saline (NS), or a novel lung preservation solution (NPS) developed using this model. Lung biochemical function was assessed by ATP content (etamol ATP/mg wet wt) and capacity for protein synthesis (cpm/mg protein) immediately following slicing (0 h) and at 6, 12, 18, and 24 h of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as means +/- SD. RESULTS: ATP content was significantly higher in the lung slices stored in NPS compared with all other solutions at each time point (P < 0.0001). Protein synthesis was significantly higher in the lung slices stored in NPS compared with all other solutions at 6, 12, and 18 h of preservation (P < 0.05). CONCLUSIONS: This lung slice model allows the rapid and efficient screening of lung preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel solution that improves the biochemical preservation of lung slices during cold storage.

Mitral and tricuspid valve rupture after moderate blunt chest trauma.

We present a patient with rupture of both atrioventricular valves in a previously healthy adult man who sustained a 5-foot fall. The mechanism of injury was such that it would not necessarily raise an adequate index of suspicion for valvular damage had valvular rupture not occurred. The usefulness of perioperative echocardiography is highlighted.

Aprotinin preserves myocardial biochemical function during cold storage through suppression of tumor necrosis factor.

OBJECTIVE: Inflammatory cytokines, particularly tumor necrosis factor, contribute to myocardial dysfunction after ischemia-reperfusion injury. Aprotinin may improve outcomes in cardiac surgery through suppression of inflammatory mediators. We hypothesized that aprotinin may exert its beneficial effects through suppression of tumor necrosis factor alpha. METHODS: Adult rat hearts were precision cut into slices with a thickness of 200 microm and stored in crystalloid cardioplegic solution alone or with one of the following additions: aprotinin or tumor necrosis factor alpha, aprotinin plus tumor necrosis factor alpha, a monoclonal antibody to tumor necrosis factor alpha, or a polyclonal antibody to the tumor necrosis factor alpha receptor. Myocardial biochemical function was assessed by adenosine triphosphate content and capacity for protein synthesis immediately after slicing (0 hours) and after 2, 4, and 6 hours of storage at 4 degrees C. The content of tumor necrosis factor alpha was measured by an enzyme-linked immunosorbent assay. Six slices were assayed at each time point for each solution. The data were analyzed by analysis of variance and are expressed as the mean +/- standard deviation. RESULTS: When stored in cardioplegic solution containing aprotinin, the heart slices demonstrated (1) an increase in adenosine triphosphate content and protein synthesis (P <.0001), (2) a decrease in intramyocardial generation of tumor necrosis factor alpha (P

Improved biochemical preservation of heart slices during cold storage.

BACKGROUND: Development of myocardial preservation solutions requires the use of whole organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that myocardial slices could be used to assess preservation of biochemical function during cold storage. MATERIALS AND METHODS: Whole rat hearts were precision cut into slices with a thickness of 200 microm and preserved at 4 degrees C in one of the following solutions: Columbia University (CU), University of Wisconsin (UW), D5 0.2% normal saline with 20 meq/l KCL (QNS), normal saline (NS), or a novel cardiac preservation solution (NPS) developed using this model. Myocardial biochemical function was assessed by ATP content (etamoles ATP/mg wet weight) and capacity for protein synthesis (counts per minute (cpm)/mg protein) immediately following slicing (0 hours), and at 6, 12, 18, and 24 hours of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as the mean +/- standard deviation. RESULTS: ATP content was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, 18 and 24 hours of cold storage (p < 0.05). Capacity for protein synthesis was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, and 18 hours of cold storage (p < 0.05). CONCLUSIONS This myocardial slice model allows the rapid and efficient screening of cardiac preservation solutions and their components using quantifiable biochemical endpoints. Using this model, we have developed a novel preservation solution which improves the biochemical function of myocardial slices during cold storage.

Functional outcome and survival after pharyngolaryngoesophagectomy for cancer.

BACKGROUND: Surgical resection of the larynx, hypopharynx and cervical esophagus, or pharyngolaryngoesophagectomy (PLE), with pharyngogastric anastomosis (PGA) offers a means of controlling local and regional carcinoma of the upper aerodigestive tract (UADT). We reviewed our experience with PLE for carcinoma of the UADT to evaluate functional outcome and survival. METHODS: Patients undergoing PLE from 1986 through 1999 were reviewed. Survivors completed questionnaires which graded their level of function and voice rehabilitation. Gastric emptying studies were performed with rates compared with normal controls. Survival curves were generated using the Kaplan-Meier method. RESULTS: Thirty-one patients underwent PLE during the study period. Twenty-nine patients had squamous cell carcinoma. Operative mortality was 0%. Thirty-day mortality was 9.6%. There were 2 anastomotic leaks (6.4%). All survivors reported normal ability to complete activities of daily living. Voice rehabilitation was acceptable in 7 of 10 survivors. Positive surgical margins resulted in decreased survival (P = 0.03). No other patient demographic or management variable altered survival. One-year, 5-year, and 10-year survival rates were 67%, 40%, and 18%, respectively. CONCLUSION: PLE with PGA for carcinoma of the UADT may be performed with low morbidity and mortality. Functional patient outcomes including gastric emptying, activities of daily living, and voice rehabilitation are acceptable.

Avoidance of cellular blood product transfusions in LVAD recipients does not prevent HLA allosensitization.

BACKGROUND: Transfusion of cellular blood products during left ventricular assist device (LVAD) implantation has been associated with HLA allosensitization, resulting in the need for a negative prospective cross-match and prolonged transplant waiting times. In order to prevent this risk, we developed a protocol to avoid transfusion of cellular blood products. METHODS: The protocol included preoperative patient stabilization, perioperative recombinant erythropoietin and blood conservation strategies, and postoperative monitoring of mixed venous oxygen saturation (SVO2) to assure adequate peripheral oxygen delivery. Panel reactive antibody (PRA) was measured in all patients pre and post LVAD placement to assess HLA sensitization. RESULTS: Seven consecutive patients underwent LVAD implantation without transfusion of blood or platelets, one of whom expired perioperatively. Mean hematocrit was 35.2% preoperatively, and 21.8% postoperatively, reaching a nadir of 20.2%. Postoperative SVO2 was >60% in all patients. In the six survivors, mean hematocrit reach 24.3%, 27.3%, and 33.0% by postoperative day seven, fourteen, and thirty, respectively. PRA in three patients was 0% preoperatively and remained 0% until transplantation after 33, 34, and 50 days of support. In two patients, preoperative PRA was 7% and 17%, dropped to 3% and 0% after thirty days, then progressively rose to 96% and 100% after 60 and 90 days, respectively. In one other patient, preoperative PRA was 0%, remained at 0% after thirty days, then rose to 96% by 60 days. CONCLUSIONS: Avoiding transfusion of cellular blood products in LVAD recipients is safe and well tolerated, but does not universally protect from HLA allosensitization. Other factors may also produce sensitization, such as immunogenic components of the LVAD, soluble antigen in fresh frozen plasma, or latent sensitization which is not initially evident in critically ill and possibly anergic patients.

ET-1 modulates KCa-channel activity and arterial tension in normoxic and hypoxic human pulmonary vasculature.

The molecular mechanisms by which endothelin (ET)-1 induces pulmonary hypertension are poorly understood. We investigated the effects of ET-1 on outward K+ currents of normoxic and chronically hypoxic human pulmonary arterial (PA) smooth muscle cells (HPSMCs). In normoxic HPSMCs, ET-1 has dual effects. In intact cells, 5 nM ET-1 activates the large-conductance and Ca2+-activated K+ (KCa)-channel current [IK(Ca)] by increasing intracellular Ca2+ concentration, whereas it directly inhibits IK(Ca) in isolated membrane patches. At a higher concentration (10 nM), ET-1-induced IK(Ca) inhibition predominates. In hypoxic HPSMCs, ET-1 at 5 nM significantly reduces IK(Ca). The ETA-receptor antagonist BQ-123 reverses the ET-1-induced decrease in IK(Ca). Chronic BQ-123 treatment also prevents the hypoxia-induced decrease in IK(Ca). In PA rings obtained from human organ donors, ET-1 causes a concentration-dependent increase in tension. The ET-1-mediated increase in tension is reversed by a KCa-channel agonist. The increase in tension at the highest concentration studied (9 nM) was more pronounced in PA rings obtained from patients with chronic obstructive pulmonary disease. These results imply that an ET-1-induced decrease in IK(Ca) contributes to chronic hypoxia-induced pulmonary hypertension.

Effect of chronic hypoxia on K+ channels: regulation in human pulmonary vascular smooth muscle cells.

We investigated the effects of chronic hypoxia on the major outward K+ currents in early cultured human main pulmonary arterial smooth muscle cells (HPSMC). Unitary currents were measured from inside-out, outside-out, and cell-attached patches of HPSMC. Chronic hypoxia depolarized resting membrane potential (Em) and reduced the activity of a charybdotoxin (CTX)- and iberiotoxin-sensitive, Ca2+-dependent K+ channel (KCa). The 4-aminopyridine-sensitive and CTX-insensitive channel or the delayed rectifier K+ channel was unaffected by chronic hypoxia. Chronic hypoxia caused a +33- to +53-mV right shift in voltage-dependent activation of K(Ca) and a decrease in K(Ca) activity at all cytosolic Ca2+ concentrations ([Ca2+]i) in the range of 0.1-10 microM. Thus the hypoxia-induced decrease in K(Ca) activity was most likely due to a decrease in K(Ca) sensitivity to Em and [Ca2+]i. Chronic hypoxia reduced the ability of nitric oxide (NO.) and guanosine 3',5'-cyclic monophosphate (cGMP) to activate K(Ca). The cGMP-dependent protein kinase-induced activation of K(Ca) was also significantly inhibited by chronic hypoxia. In addition, inhibiting channel dephosphorylation with calyculin A caused significantly less increase in K(Ca) activity in membrane patches excised from chronically hypoxic HPSMC compared with normoxic controls. This suggests that the mechanism by which hypoxia modulates NO.-induced K(Ca) activation is by decreasing the NO./cGMP-mediated phosphorylation of the channel.

Improved long-term survival after heart transplantation predicted by successful early withdrawal from maintenance corticosteroid therapy.

BACKGROUND: Short-term studies suggest that cardiac transplant immunosuppression without maintenance corticosteroids is feasible in selected patients. However, concern exists as to the long-term effects, specifically the possibility of increased morbidity and mortality because of late allograft rejection and allograft coronary artery disease. METHODS: We retrospectively reviewed the records from 441 consecutive heart transplantation procedures done in 416 patients with use of an immunosuppressive protocol that attempted corticosteroid withdrawal within 2 months of transplantation. forty-two patients died or underwent retransplantation during the first 3 months and were excluded from further analysis. Analysis focused on demographic and long-term outcome variables (including death, rejection, retransplantation, and infection). RESULTS: Thirty percent (111) of eligible patients (374) met the definition of successful early steroid withdrawal. Only male gender independently predicted successful withdrawal. Mortality, both short and long term, was significantly lower in patients in whom successful early withdrawal from corticosteroids was achieved than in patients in whom the early attempts failed (1.7% per year versus 4.7% per year; p < 0.0001). The prevalence of late acute allograft rejection (more than 1 year after transplantation) was lower in patients successfully withdrawn from steroid therapy early after transplantation (0.07 pt-yr of follow-up versus 0.15 pt-yr; p = 0.002). Multivariate analysis of the entire group identified incidence of infection (p = 0.001), older age (p = 0.001), failed early steroid withdrawal (p = 0.006), and female gender (p = 0.016) as independent predictors of mortality. CONCLUSIONS: Successful early corticosteroid withdrawal identifies a subgroup of "immunologically privileged" patients with a low risk for long-term mortality and is not associated with an increased prevalence of late rejection or clinically significant coronary artery disease.

Potassium currents in cultured human pulmonary arterial smooth muscle cells.

In this study, using whole cell and single-channel configurations of the patch-clamp technique, we characterized K+ currents (IK) in cultured human pulmonary arterial smooth muscle cells. The net whole cell outward membrane current (IKo) was activated at potentials positive to -60 mV. One component of IKo, IK(dr), was inhibited by 4-aminopyridine (4-AP) and high concentrations of tetraethylammonium (TEA) but was Ca2+ and charybdotoxin (CTX) insensitive. The other component of IKo, IK(Ca), was voltage and Ca2+ dependent and was inhibited by CTX and low concentrations of TEA. Activation of IKo in single-channel recordings was voltage dependent and demonstrated a high-conductance channel (245 +/- 2 pS) that was Ca2+ and CTX sensitive [IK(Ca)] and a low-conductance channel (109 +/- 2 pS) that was inhibited by 4-AP [IK(dr)] but was insensitive to low concentrations of TEA or to an increase in intracellular [Ca2+]. In isolated pulmonary arterial rings, TEA and 4-AP caused an additive increase in arterial tension. To our knowledge these data provide the first characterization of the IK in human pulmonary arterial smooth muscle cells and indicate that IK(Ca) and IK(dr) play an important role in maintaining pulmonary vascular tone. The data confirm previous observations in pulmonary smooth muscle cells of animal models.

Long-term results of cardiac transplantation in patients older than sixty years. UTAH Cardiac Transplant Program.

Advanced age has traditionally been a contraindication to cardiac transplantation. We have, however, offered cardiac transplantation to patients older than 60 years with end-stage heart failure if they were otherwise acceptable candidates. From 1985 to 1994, 527 patients underwent cardiac transplantation. Among these patients, 101 were older than 60 years at transplantation. The mean follow-up of this group is 6 years. Patients older than 60 years had significantly fewer rejection episodes per patient than those who were younger than 60 years at transplantation (1.9 +/- 1.3 vs 2.6 +/- 1.8, p = 0.009). No difference in the number of infectious complications per patient was detected between the two groups. Both short-term and long-term survival after transplantation were significantly lower for patients who were older than 60 years at transplantation than for younger patients (p < 0.05). The 6-year actuarial survival after transplantation for patients older than 60 years was 54% compared with 72% for patients younger than 60 years at transplantation (p < 0.05). Patients older than 60 years at transplantation were more likely to die of infectious complications or malignant disease after transplantation (p < 0.05). We believe caution is warranted in offering cardiac transplantation to patients older than 60 years. This group of patients should be carefully observed for the development of potentially life-threatening infectious complications or new malignant tumors after transplantation.