Stenting unprotected left main coronary artery stenosis in heart transplant patients--the good, bad, and the ugly.

The major cause of late death following orthotopic heart transplantation is coronary artery vasculopathy. Approximately 50% of heart transplant patients have coronary artery vasculopathy 5 years post-transplantation. With advances in interventional cardiology technology, heart transplant patients with selected lesions are now undergoing intravascular stenting with acute-gain and late-loss rates similar to stenting in non-transplanted patients. We describe 3 consecutive cases of stenting unprotected left main coronary artery disease in orthotropic heart transplant patients. With follow-up to 3 years and no evidence of restenosis, these results suggest that stenting unprotected left main coronary artery lesions in heart transplant patients can be performed with excellent immediate and long-term results.

Total myocardial revascularization without cardiopulmonary bypass utilizing computer-processed monitoring to assess cerebral perfusion.

BACKGROUND: Total myocardial revascularization without the use of cardiopulmonary bypass (CPB) has been easily achieved using a combination of: a) deep pericardial sutures, b) right pleural herniation, and c) controlled intermittent hypotension. METHODS: Five hundred fifty patients underwent revascularization off CPB, with 344 patients having three-vessel disease, 150 two-vessel disease, and 54 one-vessel disease. The use of controlled intermittent hypotension, administering esmolol and nitroglycerine during anesthesia greatly facilitated access to the marginal territory. The reduction of the systemic arterial blood pressure and the heart rate resulted in decrease ventricular wall stress. The heart was pliable, easy to manipulate, herniated into the right pleural cavity, and thus epicardial stabilization was achieved without inducing hemodynamic instability. To avoid the potential detrimental effects of intermittent hypotension we used two continuous brain-monitoring techniques: a) cortical brain oxymetry (cerebro-venous oxygen saturation (CVOS)) and b) electroencephalographic spectral array (EEG). Brain oxymetry changes of more than 20% from baseline value were observed in 15% of patients and preceded the EEG changes observed in 6% of patients. A reduction of CVOS, more than 20% for one to two minutes from baseline values required pharmacological intervention with alpha agents. The combination of both CVOS and EEG required temporary placement of the heart back into the pericardial cavity. Normalization of CVOS and EEG to baseline values was always restored. Following recovery the addition of alpha agents and reduction of drug dosage allowed successful cardiac herniation. RESULTS: We performed a total of 1,579 grafts on 1,389 VD, obtaining a ratio of 1.13 grafts for VD. In the entire group, there were 411 patients with circumflex disease who underwent 456 bypass grafts (ratio of 1.1). The stroke incidence was not significantly different than patients operated on using CPB. CONCLUSION: We conclude that using CVOS and EEG monitoring during off CPB, CABG complete coronary revascularization including the obtuse marginal artery is routinely achieved.

Laceration of a saphenous vein graft by an epicardial pacemaker wire.

The use of temporary pacing wires has become wide-spread in cardiac surgery. Complications related to their use are rare. We report a case of cardiac tamponade following removal of an atrial pacing wire.

Ultrastructure changes associated with brain death in the human donor heart.

Electromicroscopic examinations were carried out on 30 myocardial biopsies taken from 22 human donor hearts immediately after excision (prestorage) or immediately before transplantation (poststorage). All electron micrographs were independently examined by two morphologists. Eleven structures were examined in each micrograph, and each structure was scored according to the degree of injury. A good interobserver correlation was obtained in 84% of the structures scored. In the prestorage left ventricular biopsies (n = 11), approximately 20%-25% showed moderate to severe ultrastructural injury. The ultrastructural injury observed in the poststorage left ventricular biopsies (n = 15) was no different from that in the prestorage group, particularly injury to the sarcomere and mitochondria. A similar degree and pattern of injury was seen in the right ventricle (n = 4). There was no evidence that an ischemic storage period of less than 6 h increased the degree of injury seen. However, there was a higher incidence of moderate to severe injury in those hearts excised from donors initially dependent on high inotropic support.

Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery.

Experimental and clinical studies have shown the beneficial effects of triiodothyronine (T3) following myocardial revascularization on cardiopulmonary bypass (CPB). In this study, open-label T3 was administered to 68 high-risk patients undergoing open heart surgery. The New Jersey Risk Assessment was used to calculate the preoperative estimated surgical mortality. A loading dose of T3 was administered: (a) at release of the aortic cross-clamp, (b) whenever the patient became CPB dependent, (c) if the patient exhibited low cardiac output after discontinuing CPB and (d) as pretreatment before initiating CPB. All therapeutic modalities were followed by a continuous T3 infusion. Following T3 therapy, CPB was discontinued in all patients. Based upon discriminant analysis, a total of 26 deaths were expected from the entire group, but only 7 patients died, therefore, the observed mortality was reduced by 72% (p < 0.007). The use of T3 had a major impact on reducing surgical mortality, and may be advocated as a new therapeutic modality in patients with high estimated mortality undergoing open heart surgery.

Novel actions of thyroid hormone: the role of triiodothyronine in cardiac transplantation.

In clinical heart transplantation, the heart is procured from brain dead (BD) organ donors who acutely experienced a variety of critical illnesses. In all of these conditions, a profound derangement of the thyroid profile has been observed. Although the plasma levels of thyroid stimulating hormone (TSH) remain unchanged, there is a rapid decline in free triiodothyronine (FT3) levels (p < 0.0001) as well as an elevation of reverse triiodothyronine (rT3) (p < 0.001). Following induction of experimental brain death, the heart exhibits a progressive significant hemodynamic-biochemical deterioration (reduction of cardiac contractility, depletion of high energy phosphates, glycogen, and accumulation of tissue lactate). The administration of T3 to BD animals resulted in rapid reversal of the hemodynamic and metabolic derangements. The impact of T3 therapy to unstable human brain dead organ donors has resulted in rapid hemodynamic stability allowing significant reduction of inotropic support (p < 0.001). These hearts, following cardiac transplantation, exhibited excellent hemodynamic function in the recipients. The low FT3 state has also been observed during and following open heart surgery on cardiopulmonary bypass (CPB). Therefore, at the completion of the heart transplant procedure, T3 was also administered to the recipient to prevent relapse of the hemodynamic-metabolic abnormality observed in the donor. The impact of T3 therapy to initially unstable donors allowed for rapid inotropic reduction and recovery of the heart, thus enlarging the donor organ pool and improving the outcome of the recipients following cardiac transplantation.

Selection and management of cardiac allograft donors.

The selection of suitable donor hearts is essential for successful recipient outcome. Early allograft failure accounts for approximately 25% of deaths in heart transplantation recipients. The pool of donor organs that become available is inadequate to meet the ever increasing demand. Almost 30% of patients awaiting cardiac transplantation die before a suitable donor heart becomes available. The development of strategies aimed at expanding the donor pool are critically needed. To accomplish this goal it is important to improve donor management, prevent tissue injury following brain death, and attempt to correct donor organ dysfunction.

Beneficial effect of initial warm crystalloid reperfusion in 6-hour lung preservation.

BACKGROUND: To achieve successful lung transplantation, it is essential to minimize reperfusion injury occurring as a result of metabolite accumulation during the preservation period or at the time of initial interaction of blood with constricted pulmonary vasculature. Initial reperfusion with warm crystalloid solution may be advantageous in preventing this injury. METHODS: This study was designed to evaluate the effect of low-potassium (4 mmol/L) dextran (1%) solution as the initial warming solution after 6 hours of hypothermic storage. In 23 New Zealand White rabbits the lungs were flushed with low-potassium dextran solution (10 degrees C, 40 ml/kg, 600 cm H2O), excised, inflated with room air, and stored in a low-potassium dextran solution (10 degrees C) for 6 hours. After storage, the lungs were divided into two groups. Group 1 (n = 8) was reperfused with warm low potassium dextran for 4 minutes, at 37 degrees C followed by blood reperfusion for 30 minutes at 37 degrees C. Group II (n = 15) was reperfused only with blood for 30 minutes at 37 C. The mean pulmonary vascular resistance measured during cold flush and prior to storage was similar in both groups (group I = 20.0 +/- 5.9 mm Hg.sec/ml, group II = 19.3 +/- 1.9 mm Hg.sec/ml). RESULTS: During reperfusion, only 4 of the 15 lungs in group II maintained an acceptable (< 80 mm Hg) mean pulmonary artery pressure; six failed immediately. All eight lungs in group I completed the 30-minute reperfusion (p < 0.005). The mean pulmonary artery pressure was significantly less, and effluent oxygen tension was significantly greater in group I during reperfusion. CONCLUSIONS: In this experimental model, initial warm reperfusion with low-potassium dextran ameliorated the deleterious effects of reperfusion, thus providing an environment to improve lung preservation.

Preservation of competent rabbit lung function after 30 hours of storage with a low-potassium dextran solution.

BACKGROUND: The goal of organ preservation is maintenance of physiologic functions during extended extracorporeal storage. METHODS: This study was designed to evaluate the efficacy of using low-potassium (4 mmol/L) dextran (1%) solution on lung function after 30 hours hypothermic (10 degrees C) storage and to compare this with lung function after no storage. With low-potassium dextran solution rabbit lungs were flushed (10 degrees C, 40 ml/kg, 60 cm H2O), excised, inflated (with room air), and either not stored (control; no preservation; n = 9) or stored in low-potassium dextran solution (10 degrees C) 30 hours (experimental group; n = 9). RESULTS: During the flush the infusion pressure and pulmonary vascular resistance for the two groups did not differ (17.56 +/- 1.3 versus 16.74 +/- 1.5 mm Hg/ml/sec). After either no preservation or after 30 hours of storage, the lungs were first reperfused with low-potassium dextran solution (37 degrees C) for 4 minutes and then with blood (37 degrees C) for 30 minutes at 100 ml/min. During the reperfusion period the mean pulmonary artery pressure and end-inspiratory airway pressure for the control and experimental groups did not differ. After reperfusion the wet and dry weights of the left lung were determined. The wet/dry ratio for the two groups did not differ (5.32 +/- 2.20 versus 4.70 +/- 2.70, respectively). CONCLUSIONS: These data suggest that cold flush, cold storage, and initial warm perfusion with low-potassium dextran solution crystalloid preserve lung function after 30 hours of storage.

Effects of allopurinol pretreatment with pulmonary flush on lung preservation.

This study was designed to test whether use of allopurinol could improve lung preservation after 6 hours of cold storage. Thirty-two rabbits were divided into four groups (n = 8 each group): (1) the control group received no flush or storage, (2) the EC group received Euro-Collins (EC) solution for both flush and storage, (3) the Allo-F group received Euro-Collins solution with allopurinol (1 mmol/L) for both flush and storage, and (4) the Allo-R group received Euro-Collins solution to which allopurinol (1 mmol/L) was added only to the reperfused blood. For groups 2 through 4, the lungs were flushed (40 ml/kg) in situ, excised, and then stored at 4 degrees C. After storage, the lungs were reperfused for 1 hour with an in vitro blood-perfused ventilated model. Lung function was measured during reperfusion with mean pulmonary arterial pressure, end-inspiratory airway pressure, and blood gas data. The lung wet/dry weight ratio was used to measure lung edema. The lungs in the EC group had a significant increase in mean pulmonary arterial pressure, airway pressure, and wet/dry weight ratio when compared with the control group. The mean pulmonary arterial pressure in either of the groups receiving allopurinol was consistently lower than that in the EC group. The airway pressure in the Allo-R group also significantly decreased compared with the EC group.(ABSTRACT TRUNCATED AT 250 WORDS)

Facilitated recovery of cardiac performance by triiodothyronine following a transient ischemic insult.

Reperfusion following a transient ischemic insult has been shown to result in a delayed recovery of myocardial function. A reduction in plasma triiodothyronine (T3) has been reported in these acute cardiovascular challenges. To test whether the replacement of T3 can facilitate the recovery of myocardial function following a transient regional ischemia, we investigated cardiac performance for 3 h after a 15-min, left anterior descending coronary artery occlusion in a canine model. Three groups of dogs were studied: I--control (n = 10); II--receiving T3 (0.25 micrograms/kg i.v. and 0.25 micrograms/kg/h for 3 h, n = 9), and III--receiving T3 (0.25 micrograms/kg i.v. and 0.5 micrograms/kg/h for 3 h, n = 9). Three hours following reperfusion, the T3 level in blood was significantly decreased in group I. Concomitantly, local segmental shortening was reduced from preocclusion control levels in group I (15.2 to 5.1%, p < 0.05), but recovered in both treated groups. The endsystolic elastance (Ees) and the external work (EW) efficiency (EW/PVA) in group I were depressed from preocclusion control (Ees = 95.5 +/- 0.8%; EW/PVA = 90.2 +/- 1.8%, both p < 0.05), the effective arterial elastance (Ea) and ventriculoarterial coupling (Ea/Ees) in group I were still elevated from preocclusion control (Ea = 122.5 +/- 5.1%; Ea/Ees = 128.3 +/- 5.3%, both p < 0.05). But these measures of global cardiac performance in the treated groups recovered following reperfusion, and the extent of recovery was dose dependent. These data suggest that T3 facilitates recovery of the stunned myocardium by improvement in local and global contractile function, in ventriculoarterial coupling, and in the energy efficiency.

Acute inotropic response of rabbit papillary muscle to triiodothyronine.

The effects of triiodothyronine (T3) on the force frequency responses of isometrically contracting rabbit papillary muscles were studied in the presence of d-glucose, pyruvate or butyrate. The stimulation frequency was varied from 0.1 to 0.5 Hz, and the maximum developed tension and its maximum (Tmx) and minimum (Tmn) time derivative were measured. T3 concentrations ranged from 0.1 to 4.0 ng/ml. The addition of T3 resulted in a substrate-dependent increase in twitch tension; with the largest increases being: d-glucose 118 +/- 7%, pyruvate 143 +/- 6%, butyrate 123 +/- 11%; Tmx:d-glucose 121 +/- 8%, pyruvate 157 +/- 5%, butyrate 138 +/- 12%, and Tmn:d-glucose 150 +/- 10%, pyruvate 159 +/- 6%, butyrate 163 +/- 14%. All three measures of contractility showed a dose-dependent increase reaching a maximum value at a T3 concentration between 1 and 2 ng/ml. These data show that T3 induces an inotropic response in rabbit papillary muscles which is manifested within, approximately 30 min, and that the greatest increase is seen in Tmn.

Successful management of symptomatic cytomegalovirus disease with ganciclovir after heart transplantation.

In the 30-month period from January 1987 through June 1989, 57 patients underwent heart transplantation. Immunosuppressive therapy consisted of a combination of cyclosporine, azathioprine, low-dose methylprednisolone, and antilymphoblast globulin. Clinically significant, proven cytomegalovirus (CMV) disease has developed in no fewer than 22 patients (39%), involving the lung (n = 11), colon (n = 8), stomach (n = 4), and retina (n = 1). The diagnosis was confirmed by direct fluorescent antibody (DFA) (n = 14), histologic study (n = 6), and culture (n = 6) in all cases. The onset of CMV infection occurred at a mean of 5.7 months after heart transplantation (range, 3 weeks to 18 months). All patients were treated with ganciclovir until no sign of active CMV disease could be found. The length of treatment required varied from 2 to 8 weeks (mean, 3.5 weeks). Recurrence has occurred in only one patient, necessitating a further 26-week course of therapy. There were no deaths attributed definitely to CMV disease. There was a higher incidence of acute rejection in the first 3 posttransplant months (0.68 episodes/patient) in the CMV group than in those in whom CMV disease did not develop (0.34 episodes/patient; p less than 0.02). Of the CMV patients, 25% had significant features of graft atherosclerosis during the first posttransplant year, compared with only 8% of the non-CMV patients. In conclusion, (1) there was a high incidence of CMV disease with this immunosuppressive regimen, and we have subsequently discontinued routine antilymphoblast globulin therapy and instituted a triple therapy immunosuppressive protocol with prophylactic immunoglobulin and acyclovir; (2) CMV disease was successfully treated in all cases with ganciclovir alone; and (3) there was a trend toward an increased incidence of both acute rejection and accelerated graft atherosclerosis in the CMV group of patients.