Management of the sensitized cardiac recipient: the use of plasmapheresis and intravenous immunoglobulin.

Previously, we reported that the combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg) allow sensitized patients to undergo orthotopic heart transplantation (OHT), even across a positive crossmatch. In the current study, the effect of that combination, PP+IVIg, on survival of a larger group of such recipients is investigated. The latter group (I) consisted of 35 sensitized patients who received PP+IVIG together with standard immunosuppressive drugs. Rejection was seen in 11 patients, findings strongly suggestive of a vascular (humoral) being identified in five of those cases. Four deaths occurred, two of them in the immediate post-operative period, one after almost six months, and one after almost two yr post-OHT. Follow-up range 4.5 months to 7.8 yr post-OHT (average=1.1 yr). Patient survival was analyzed after generation of a Kaplan-Meier plot. Comparison with a control OHT group (II) given standard immunosuppressive drugs only (N=276) showed enhanced survival of group I (p=0.0414 by log-rank test). We conclude that the combination of PP and IVIG (i) is associated with declines in T- and B-percent-reactive antibody and in crossmatch positivity, and (ii) is very useful in the management of the sensitized cardiac patient undergoing OHT, often allowing a successful outcome to transplantation in the face of a positive crossmatch.

Direct effects of triiodothyronine on human internal mammary artery and saphenous veins.

OBJECTIVE: Thyroid hormone (3,5,3'-triiodo-L-thyronine is under investigation as a positive inotrope and vasodilator for patients undergoing cardiac surgery. This study determined the direct effects of triiodothyronine on human blood vessels. DESIGN: Prospective, controlled, in vitro study. SETTING: Laboratory facility in a university teaching hospital. PARTICIPANTS: Small excess segments of internal mammary arteries or saphenous veins were obtained from patients undergoing coronary artery bypass surgery. INTERVENTIONS: Vessel segments were cut into rings to measure isometric tension development in isolated tissue baths containing Krebs-Ringer bicarbonate solution at 37 degrees C. Rings were prestretched in vitro to resting tensions analogous to mean arterial or central venous pressures in vivo and then constricted with potassium or phenylephrine. Rings were exposed to increasing concentrations of triiodothyronine (4 x 10(-12) to 1 x 10(-4) mol/L) to obtain dose-response curves. MEASUREMENTS AND MAIN RESULTS: High concentrations (> or = 3.3 x 10(-5) mol/L) of trilodothyronine produced dose-dependent relaxation of preconstricted rings. The relaxation was not selective for arteries or veins at arterial resting tensions, and with either potassium or phenylephrine as a vasoconstrictor. Propranolol had little effect on subsequent triiodothyronine-induced relaxation of potassium-constricted rings at resting arterial tensions. CONCLUSIONS: Triiodothyronine, in supraphysiological and suprapharmacological concentrations, dilates preconstricted rings of human blood vessels in vitro; however, triiodothyronine had no demonstrable vasomotor effects on human internal mammary artery or saphenous vein in clinically relevant concentrations (10(-9) to 10(-8) mol/L). Triiodothyronine administration in vivo most likely has little direct effect on the tone of human vascular smooth muscle, particularly coronary artery bypass conduits.

Intravenous vitamin K1 prior to orthotopic heart transplantation: effects in vivo and in vitro.

BACKGROUND: Vitamin K1 is used to reverse warfarin's anticoagulant action. It is unclear whether intravenous vitamin K1 is safe or efficacious prior to urgent cardiac surgery. METHODS: We retrospectively and prospectively examined the effects of preoperative intravenous vitamin K1 in vivo (administered for warfarin reversal immediately before heart transplantation) on intraoperative blood product utilization, hemodynamics and coagulation parameters. We also determined the direct effects of vitamin K1 in vitro on rings of human saphenous vein and internal mammary artery. RESULTS: In the retrospective limb, 29 of 67 patients were administered vitamin K1 preoperatively via slow intravenous infusion. Vitamin K1 administration produced no adverse outcome but did not affect subsequent perioperative use of blood products. In the prospective limb (n = 10), vitamin K1 significantly (P < or = 0.01, Student t-test) altered mean arterial pressure (from 85 +/- 15 to 76 +/- 16 mmHg), systemic vascular resistance (from 1364 +/- 308 to 1078 +/- 252 dyn.s.cm-5), and cardiac index (from 2.3 +/- 0.3 to 2.7 +/- 0.3 L/min/m2) (mean +/- SD). Significant decreases in prothrombin time (19.8 +/- 2.7 to 17.7 +/- 1.8 s) and activated clotting time (164 +/- 26 to 137 +/- 24 s) were observed at 60 min. In vitro vitamin K1 (10(-7) to 10(-4) M) had no effect on the tone of noradrenaline-constricted rings. CONCLUSIONS: Vitamin K1, administered by intravenous infusion prior to heart transplantation, did not alter subsequent perioperative blood product administration. Vitamin K1 rapidly reversed the anticoagulant effect of warfarin and produced modest hemodynamic changes. The decrease in systemic vascular resistance is probably not due to a direct effect of vitamin K1 on vascular smooth muscle.

Standard criteria for an acceptable donor heart are restricting heart transplantation.

BACKGROUND: The lack of satisfactory donor organs limits heart transplantation. The purpose of this study was to determine whether the criteria for suitability of donors may be safely expanded. METHODS: One hundred ninety-six heart transplantations were performed on 192 patients at our institution from January 1992 to 1995 and were divided into two groups. Group A donors (n = 113) conformed to the standard criteria. Group B donors (n = 83) deviated by at least one factor and consisted of the following: 16 hearts from donors greater than 50 years of age, 33 with myocardial dysfunction (echocardiographic ejection fraction = 0.35 +/- 0.10, dopamine level exceeding 20 micrograms.kg-1.min-1, and resuscitation with triiodothyronine), 33 undersized donors with donor to recipient weight ratios of 0.45 +/- 0.04, 48 with extended ischemic times of 297.4 +/- 53.6 minutes, 25 with positive blood cultures, 16 with positive hepatitis C antibody titers, and 7 with conduction abnormalities (Wolff-Parkinson-White syndrome, prolonged QT interval, bifascicular block). RESULTS: Thirty-day mortality was 6.2% (7/113) in group A and 6.0% (5/83) in group B. Mortality in group A was attributed to 3 patients with myocardial dysfunction, 2 with infection, 1 with acute rejection, and 1 with pancreatitis; group B had 2 with myocardial dysfunction, 1 with infection, 1 with aspiration, and 1 with bowel infarction. At 12 months, survival and hemodynamic indices were similar between the groups. Of the 16 recipients with hepatitis C-positive hearts, 5 have become hepatitis C positive with mild hepatitis (follow up, 6 to 30 months). CONCLUSIONS: Expanding the criteria for suitability of donor hearts dramatically increases the number of transplantations without compromising recipient outcome.

Increased activation of the coagulation and fibrinolytic systems leads to hemorrhagic complications during left ventricular assist implantation.

BACKGROUND: Left ventricular assist devices (LVADs) have provided a new therapeutic option for patients with end-stage heart failure. Despite advances in device design, there remains an apparent bleeding diathesis, which leads to increased transfusion requirements and reoperative rates. The purpose of our study was to examine the abnormalities that might contribute to these clinical sequelae. METHODS AND RESULTS: To separate the effects of cardiopulmonary bypass (CPB), eight patients undergoing coronary revascularization (CABG) were compared with seven LVAD (TCI HeartMate) recipients intraoperatively and 2 hours postoperatively. We evaluated several well-characterized indexes of platelet activation: platelet count, platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), and thromboxane B2 (TXB2). We also measured activation of thrombin: thrombin-antithrombin III (TAT), prothrombin fragment 1 + 2 (F1 + 2), and fibrinopeptide A (FPA) as well as markers of fibrinolysis: plasmin-alpha 2-antiplasmin (PAP) and D-dimer. Patterns of intraoperative platelet adhesion and activation were not statistically different in the CABG control and LVAD groups. In the immediate postoperative period, however, there was significant release of PF4 and beta-TG and generation of TXB2. Compared with the CABG controls (TAT, 26 +/- 8 micrograms/L; F1 + 2, 4 +/- 1 nmol/L; mean +/- SEM), there was a significant increase in TAT (380 +/- 112 micrograms/L) and F1 + 2 (23 +/- 4 nmol/L) in LVAD patients 2 hours after surgery. Furthermore, a sharp rise in FPA was noted 20 minutes after LVAD initiation (CABG, 8 +/- 4 ng/mL; LVAD, 235 +/- 63 ng/mL; P < .05). A concomitant increase in both PAP (CABG, 987 +/- 129 micrograms/L; LVAD 3456 +/- 721 micrograms/L; P < .05) and D-dimer (CABG, 1678 +/- 416 ng/mL; LVAD, 15243 +/- 4682 ng/mL; P < .05) was observed. CONCLUSIONS: The additive effects of CPB and LVAD lead to platelet activation as well as elevation of markers of in vivo thrombin generation, fibrinogen cleavage, and fibrinolytic activity. The etiology of these findings may be secondary to the LVAD surface, flow characteristics, and/or operative procedure. Nevertheless, platelet alterations and exaggerated activation of the coagulation and fibrinolytic systems may contribute to the clinically observed hemostatic defect.

Defining the role of aprotinin in heart transplantation.

BACKGROUND: Heart transplantation is associated with excessive bleeding due to recipient coagulopathy, frequent need for reoperative median sternotomy, and prolonged cardiopulmonary bypass. Aprotinin reduces bleeding and the inflammatory response after cardiopulmonary bypass, but there are concerns about efficacy and side effects. METHODS: To determine the role of aprotinin in primary and reoperative sternotomy heart transplantation, we studied 70 patients undergoing heart transplantation between August 1993 and October 1994. Thirty-eight undergoing primary sternotomy for heart transplantation and receiving no aprotinin were randomized to group A (n = 20); patients in group B (n = 18) received the full recommended dose. Similarly, 32 patients undergoing reoperative heart transplantation were randomized to group C (n = 16), receiving no aprotinin, and to group D (n = 16), receiving aprotinin at the full recommended dose. All patients received the same immunosuppression regimen. Similarities in the groups included recipient age, weight, preoperative hemodynamic indices, creatinine, creatinine clearance, platelet count, hemoglobin, percentage receiving warfarin, prothrombin time, partial thromboplastin time, cardiopulmonary bypass time, and creatinine level at 48 hours. RESULTS: There were no significant differences postoperatively between groups A and B. Differences (p < 0.05) 24 hours postoperatively between groups C and D, respectively, included: total blood product requirement (5.9 +/- 3.8 versus 3.6 +/- 2.0 U), total fluid balance (+752 +/- 300 versus -250 +/- 185 mL), chest tube drainage (894 +/- 120 versus 526 +/- 95 mL), alveolar-arterial O2 difference (120.4 +/- 45.9 versus 95.5 +/- 33.5), and pulmonary artery mean pressures (28.2 +/- 4.6 versus 21.1 +/- 3.5 mm Hg). CONCLUSIONS: Aprotinin decreases bleeding after reoperative heart transplantation without renal dysfunction. Decreased inflammation is manifested as reduced fluid requirement and improved pulmonary and right heart function, which benefit patients during the posttransplantation period. Aprotinin at recommended doses is effective and safe for patients undergoing reoperative heart transplantation.

Isradipine for treatment of acute hypertension after myocardial revascularization.

OBJECTIVE: To evaluate the efficacy and duration of action of iv isradipine in the control of postoperative hypertension immediately after myocardial revascularization. DESIGN: Prospective, phase 2 trial. SETTING: Surgical ICU, university hospital. PATIENTS: Twenty-one (15 male, six female) patients, ages 49 to 75 yr (mean 65 +/- 5), undergoing elective myocardial revascularization. INTERVENTIONS: Twenty-one patients with postoperative hypertension after coronary artery bypass graft surgery received iv isradipine, a new dihydropyridine calcium-channel antagonist. Mean duration of the isradipine infusion was 96.9 +/- 29 min. Mean dose of isradipine, indexed to weight, was 16.63 +/- 6.66 micrograms/kg (n = 20). MEASUREMENTS AND MAIN RESULTS: Twenty of the 21 patients achieved satisfactory BP control. The reduction in mean arterial pressure (MAP), first noted at the 15-min point, was maximal at 1 hr when MAP decreased from 102 +/- 9 mm Hg baseline to 81 +/- 5 mm Hg (p less than .01), accompanied by a significant (p less than .01) decrease in systemic vascular resistance from 1753 +/- 339 baseline to 1180 +/- 229 dyne.sec/cm5. The CVP, pulmonary artery diastolic pressure, and pulmonary artery occlusion pressure did not change significantly. Heart rate and cardiac index increased; however, stroke volume index did not change. CONCLUSIONS: Isradipine is an acceptable agent for the treatment of hypertension in this setting.

Endomyocardial biopsy: variations in venous access for endomyocardial biopsy in cardiac transplantation.

With the increasing number of cardiac transplantation procedures performed worldwide, a strategy for endomyocardial biopsy techniques has evolved at our institution. Specific approaches for venous access for biopsy purposes are described. These include approaches via the right internal jugular vein, right external jugular vein, left subclavian vein, and the femoral veins. Particular emphasis is placed on the technical nuances of each approach. In approximately 2,000 endomyocardial biopsies performed on 155 transplant patients from 1984-1989, only two major complications occurred, only one of which required operative intervention. This was a perforated right ventricle, and the patient recovered after repair without further sequelae. No pneumothoraces or infection occurred during this time period. With proper understanding of regional anatomy, fluoroscopic appearance, and experience, endomyocardial biopsies can be performed with an extremely low incidence of major or minor complications.

Successful heart transplantation in recipients with recent preoperative pulmonary emboli.

Acute pulmonary embolus (less than 6 weeks old) has been considered an absolute contraindication to heart transplantation for fear of the potential problems of lung abscess, empyema, bronchopleural fistula, and systemic sepsis in an immunosuppressed patient. It is difficult to adhere to this principle because 30% to 50% of patients with dilated cardiomyopathy may have an acute pulmonary embolus and would be excluded from transplantation. Several centers have considered such patients for heart transplantation if they are young, on maximal medical therapy, and in extremis. The surgical management of the postoperative pulmonary problems can include bronchoscopy, antibiotics, surgical drainage, decortication, and pulmonary resection with or without muscle flaps. We describe our approach to two such patients who were managed successfully with lobectomies and latissimus dorsi muscle flaps to seal the bronchus and fill the pleural space.

Sternotomy closure with Parham bands.

The closure of a median sternotomy incision requires secure bony approximation to prevent postoperative pain, sternal click, and/or nonunion of bone. The standard technique of sternotomy closure involves the use of stainless steel wires for reapproximation of the sternum. These wires occasionally break or pull through bone, resulting in instability of either a portion of the sternum or the entire sternum. Presented here is our technique for sternotomy closure that provides secure closure with reduced postoperative morbidity.

Bran-induced small-intestinal obstruction in a patient with no history of abdominal operation.

An infrequently reported cause of small-bowel obstruction, but one with increasingly important implications in today's diet-conscious society, is bran. This report describes a patient with no history of abdominal operation who developed complete obstruction of the small bowel after the ingestion of two bowls of bran cereal. The obstructing mass of bran was removed by enterotomy and found to be an inspissated, toothpastelike plug. The patient recovered fully.

Antithymocyte gamma globulin, low-dosage cyclosporine, and tapering steroids as an immunosuppressive regimen to avoid early kidney failure in heart transplantation.

Cyclosporine is a powerful immunosuppressive agent that unfortunately has significant renal toxicity. Two risk factors associated with a high incidence of kidney failure in patients receiving cyclosporine have been described in the literature. In an effort to decrease the possibility of renal toxicity with the use of cyclosporine, we use low-dosage cyclosporine, antithymocyte gamma globulin, and tapering dosages of steroids as an immunosuppressive regimen. Twenty-one patients had orthotopic heart transplants from January 1985 to January 1986. Sixteen of 21 patients or 70% had at least one high risk factor for kidney failure. There were no episodes of acute kidney failure, and the blood urea nitrogen and creatinine levels that were recorded over an average of 8.5 months per patient did not increase significantly from preoperative values. Seventeen of 21 or 81% of the patients are alive and functioning fully. The incidence of rejection per patient was 0.9, and there were no biopsy-proven severe rejections. One patient died at 5 months; the autopsy showed generalized moderate rejection. There were 0.24 episodes of infection per patient, with one patient who died from Pneumocystis pneumonia. With this immunosuppression protocol, early postoperative kidney dysfunction was avoided. The incidences of rejection and infection were within acceptable range, and the quality of life in the 17 survivors is excellent.