Regional pulmonary perfusion following human heart-lung transplantation.

Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

Prolonged survival after heart-lung transplantation in systemic lupus erythematosus.

Patients with multisystem involvement of connective tissue disorders are generally excluded from consideration for heart-lung and lung transplantation because of profound donor organ shortages. A 23-year-old woman with systemic lupus erythematosus (SLE) was referred for evaluation of severe, progressive pulmonary hypertension. She underwent an uneventful heart-lung transplant and received cyclosporine A, azathioprine, and prednisone on a long-term basis. Bronchiolitis obliterans resulted in the development of moderate airflow obstruction 18 months after transplantation, but the process was stabilized with augmented immunosuppression consisting of high-dose parenterally administered corticosteroids, and subsequently a course of antithymocyte globulin. Four years after transplant, despite the persistence of reduced complement levels, the patient remains functionally well without clinical manifestations of SLE. This patient's long-term successful outcome indicates that connective tissue disorders such as SLE do not necessarily represent absolute contraindications to heart-lung and lung transplantation.

Successful orthotopic canine heart transplantation after 24 hours of in vitro preservation.

A protocol was developed to provide continuous, hypothermic, low-pressure perfusion for 24 hours' preservation of the isolated canine heart prior to orthotopic transplantation. Donor cardiectomy included coronary vasodilatation with diltiazem, potassium arrest, and rapid cooling of the heart. The graft was perfused at a pressure of 18 to 22 cm H2O and at an average flow of 0.743 cc/min/gm of tissue. The septal temperature was 5 degrees to 7 degrees C and perfusate pH was 7.25 to 7.4. Two groups of mongrel dogs were studied after orthotopic transplantation: Group I (n = 15) received hearts perfused for 24 hours. Group II (n = 9) received hearts removed by the same cardiectomy technique, but transplanted immediately. All grafts were able to support the recipient circulation after cardiopulmonary bypass. These was no significant difference in survival or in graft function when hemodynamic studies were done in five animals of each group, between 5 and 10 days after operation. We conclude that a reliable and reproducible method of 24 hours' in vitro perfusion of the canine heart has been obtained and should be applicable in clinical cardiac transplantation when prolonged periods of preservation are required.

Noninvasive detection of transplant coronary artery disease by dobutamine stress echocardiography.

Coronary artery disease has emerged as the leading cause of late morbidity and mortality in heart transplant recipients. The incidence of allograft coronary artery disease has been reported to be as high as 40% to 50% by 5 years. Coronary angiography remains the standard approach for surveillance of coronary artery disease in this patient population. However, the detection and surveillance of allograft coronary disease by noninvasive methods remains a challenge. The purpose of this study was to determine the value of dobutamine stress echocardiography as a noninvasive screening test to rule out the presence of anatomically significant allograft coronary artery disease and to assess its prognostic power. Dobutamine stress echocardiography was carried out according to a standard protocol in which dobutamine was infused at 5, 10, 20, 30, and 40 micrograms/kg/min intravenously at 5-minute stages with 12-lead electrocardiogram and blood pressure monitoring. Left ventricular wall motion was analyzed at baseline and at peak dobutamine dose. Mean age (+/- standard error of the mean) of the study population was 50.5 +/- 1.5 years, and mean duration (+/- standard error of the mean) since transplantation was 57 +/- 5 months. The sensitivity, specificity, and positive and negative predictive accuracy of dobutamine stress echocardiography were 95%, 55%, 69%, and 92%, respectively. In the 12-month follow-up study 12 patients with abnormal dobutamine stress echocardiographic findings had 15 major cardiac events whereas no event occurred in patients with normal dobutamine stress echocardiograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of costal and crural diaphragm during progressive hypoxia or hypercapnia.

Because costal and crural diaphragm segments have different functional characteristics, ventilatory stimulation with hypoxia or hypercapnia may elicit differential segmental function. We report measurements of diaphragm segmental length, shortening, and electromyogram (EMG) activity from 11 canines that were chronically implanted with sonomicrometry transducers and EMG electrodes and then studied a mean of 18 days postimplantation while awake and breathing spontaneously during CO2 rebreathing and progressive isocapnic hypoxia. Ventilatory responses to hypercapnia and progressive hypoxia were moderate at 1.13 +/- 0.31 (SD) 1. min-1. mm-1 arterial Pco2 and -0.98 +/- 0.51 l. min-1.%arterial O2 saturation-1. When tidal values for breathing pattern and segmental function were compared at matching tidal volumes that correspond to mean CO2 of 49.4 arterial Pco2 and 77% arterial O2 saturation, there was no significant difference in resting length, tidal shortening, or tidal EMG of costal or crural segments. Intrabreath profiles of flow, shortening, and EMG activity at matched tidal volumes showed that 1) inspiratory flow during hypoxia was significantly greater during early inspiration, 2) crural EMG activity preceded costal EMG activity in early inspiration during both hypercapnia and hypoxia, 3) both segments showed increased postinspiratory inspiratory activity with stimulated ventilation, and 4) postinspiratory shortening and EMG were greatest for the crural segment during hypoxia. These results suggest that costal and crural diaphragm segments exhibit differential function during chemical stimulation, especially during postinspiration.

Costal and crural diaphragm function during panting in awake canines.

During natural panting for thermal regulation, the pattern of activation of the major respiratory muscles, including costal and crural diaphragm segments, is not known. We measured diaphragm segmental length, shortening, and electromyographic (EMG) activity in five chronically implanted canines awake and breathing spontaneously at rest and during a mild dry heat stress. During panting, minute ventilation increased fourfold from 5.07 l/min and respiratory rate increased from 16.9 to 192.8 breaths/min or 3.2 Hz. During panting, end-expiratory length of both costal and crural segments decreased, concurrent with significant increases in end-expiratory EMG. With the onset of panting, tidal costal shortening decreased significantly from 6.29% of end-expiratory length to 3.54%, whereas crural shortening decreased from 6.04 to 2.46%. Meanwhile, segmental EMG tended to increase during panting. During panting, intrabreath costal and crural segmental function revealed differential activation; the costal segment shortened in concert with inspiratory flow, whereas peak crural shortening occurred in expiration, almost 180 degrees out of phase with costal. The divergence in segmental shortening during panting was accompanied by a lesser shift in timing of segmental EMG. In the awake spontaneously panting canine, asynchronous costal and crural shortening may enhance gas mixing in a manner analogous to high-frequency ventilation.

Costal and crural diaphragm function during CO2 rebreathing in awake dogs.

If costal and crural diaphragm segments can perform as separate muscles, then CO2-stimulated ventilation may elicit differential segmental function. We studied diaphragm segmental length, shortening, and electromyogram (EMG) activity in 10 awake dogs chronically implanted with sonomicrometer transducers and EMG electrodes. During CO2 rebreathing, segmental shortening and EMG activity per whole tidal breath progressively increased, but segmental responses could not be differentiated at any level of CO2. With increasing CO2, resting end-expiratory length of both diaphragm segments increased. During the complete intrabreath inspiratory-expiratory cycle, costal and crural diaphragm revealed distinctive segmental function. At rest, crural shortening exceeded costal shortening in earliest inspiration, costal and especially crural shortening persisted into early expiration, and EMG activity of the crural segment was greater than that of the costal segment in earliest inspiration and showed more end-inspiratory/early expiratory [post-inspiratory inspiratory activity (PIIA)] activity. During CO2-stimulated breathing, neither segment shortened during the inspiratory flow of earliest inspiration. During CO2 rebreathing, shortening of the crural segment exceeded that of the costal segment during early inspiration and outlasted costal shortening during expiration; for both segments, shortening persisted after termination of inspiratory airflow. With increased CO2, EMG activity of the crural segment preceded that of the costal segment in earliest inspiration and was dominant into expiration, whereas costal EMG activity terminated abruptly with inspiratory flow. Thus, costal EMG PIIA was not evident during hypercapnia, whereas crural EMG PIIA was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of diaphragm function after laparotomy and chronic sonomicrometer implantation.

If sonomicrometry transducers could be implanted permanently into the diaphragm, direct measurements of costal and crural length and shortening could be made during recovery from the laparotomy and then indefinitely in an awake, non-anesthetized mammal. We report results from six canines in which we successfully implanted transducers onto the left hemidiaphragm through a midline laparotomy and measured segmental shortening and ventilation at intervals through 22 days of postoperative recovery. After laparotomy, breathing pattern, including tidal volume, respiratory rate and mean inspiratory flow, stabilized by the 4th postoperative day (POD). Tidal shortening of costal and crural segments increased from 1.82 and 1.45% of end-expiratory length (%LFRC) on the 2nd POD to 5.32 and 8.56% LFRC, respectively, after a mean of 22 POD. Segmental shortening did not stabilize until 10 POD, and the recovery process displayed a sequence of segmental motions: lengthening, biphasic inspiratory lengthening-shortening, and increasing simple shortening. Three weeks after implantation, costal and crural segments were stable and shortening 5.32 and 8.56% LFRC, respectively, and capable of shortening 49% LFRC with maximal phrenic stimulation. In a pair of recovered animals, the initial postoperative dysfunction did not recur after a subsequent, simple laparotomy. At postmortem examination, the chronically implanted sonomicrometer transducers were found to have evoked only a thin fibrotic capsule within the diaphragm.

Diaphragm length adjustments with body position changes in the awake dog.

Sonomicrometry was used to measure end-expiratory length and tidal shortening of the costal and crural diaphragm in awake chronically instrumented dogs in the right lateral decubitus, standing, and sitting postures. End-expiratory length did not change significantly in standing but fell by 11.5% for the costal and by 14.4% for the crural segment in sitting, when compared with decubitus position. Tidal shortening of both segments did not change significantly in the three postures. From decubitus to sitting, diaphragmatic electromyogram (EMG) activity increased only in some dogs, not significantly for the group. The inspiratory swing of abdominal pressure was always positive in decubitus and negative in standing and sitting. In the latter two postures, abdominal pressure increased gradually during expiration and fell in inspiration, suggesting a phasic expiratory contraction of abdominal muscles. We conclude that diaphragmatic tidal shortening is maintained in the different postures assumed by the awake dog during resting breathing. It seems that the main compensatory mechanism for changes in diaphragmatic operational length is a phasic expiratory contraction of the abdominal muscles rather than an increase in diaphragmatic EMG activity.

Circulatory assistance with a cardiac allograft after exclusion of the canine left ventricle.

Cardiogenic shock after myocardial infarction still carries a high mortality despite use of intraaortic counterpulsation and early surgical revascularization. An experimental canine model of left ventricular exclusion and circulation support was developed by closing the mitral valve and by interposing "in series" a cardiac allograft between pulmonary and systemic circulations. This preparation was able to support the recipient circulation after cardiopulmonary bypass in 25 animals. In 16 dogs the graft sustained life for from 1 to 32 days. It is hypothesized that such left ventricular assistance could be used to maintain the life of patients in cardiogenic shock after myocardial infarction. By providing maximal left ventricular decompression and improvement of the native coronary perfusion, this method may reverse the metabolic imbalance responsible for extension of the infarction, thereby salvaging muscle that is in jeopardy but still viable.

Cardiac transplantation with corticosteroid-free immunosuppression: long-term results.

To assess the long-term safety of an immunosuppressive regimen without corticosteroids, we retrospectively evaluated 42 long-term (greater than 1 year) survivors of orthotopic cardiac transplantation. We determined the incidence of (1) conversion of the immunosuppressive regimen from cyclosporine and azathioprine alone (group I) to cyclosporine, azathioprine, and prednisone (group II), (2) late acute graft rejection (defined as occurring at greater than 1 postoperative year), and (3) major postoperative complications related to corticosteroids. Of the 42 patients who were started on cyclosporine and azathioprine, 48% remained in group I, and 52% converted to group II. Forty-five percent of group II patients were able to taper and discontinue prednisone in 15.6 +/- 2.2 months. Among the patients on long-term corticosteroid-free immunosuppression, the incidence of late rejection was 2.1% per endomyocardial biopsy. The incidence of late infectious episodes was not significantly different between the two groups of patients, although diabetes mellitus and hypercholesterolemia were more prevalent in group II than in group I. These data suggest that cardiac transplant recipients who chronically remain on corticosteroid-free immunosuppression represent a select group of patients with an acceptably low risk of late graft rejection and associated reduction of potential risk factors of accelerated coronary artery disease.

Atrioventricular fistula: an unusual complication of endomyocardial biopsy in a heart transplant recipient.

Endomyocardial biopsy remains the primary method for diagnosis of cardiac allograft rejection. Generally, endomyocardial biopsy is considered a relatively safe procedure in heart transplant recipients. Complications that have been reported are related to catheter insertion and include carotid arterial puncture, prolonged bleeding, vasovagal reaction, ventricular tachyarrhythmias, and transient conduction abnormalities. Serious complications such as right ventricular perforation with cardiac tamponade may also occur. Most complications are usually without significant long-term sequelae. This report describes an unusual case of atrioventricular fistula between the right atrium and left ventricle that occurred during a routine endomyocardial biopsy in a heart transplant recipient. Sudden hemodynamic compromise developed in this patient soon after heart biopsy associated with hemodynamic picture of high-output heart failure. Right heart catheterization, including oximetry, peripheral venous contrast echocardiography, color flow Doppler studies, and transesophageal echocardiography confirmed the diagnosis of fistulous communication between the right atrium and left ventricle, most likely through the membranous interventricular septum. Conservative medical management resulted in striking clinical improvement within 48 hours commensurate with spontaneous closure of the right atrium-to-left ventricle fistula documented by hemodynamic and echocardiographic studies.

Coronary artery bypass profile in Canada and the United States.

This study compares computer registry data on coronary bypass surgery from several centres in Canada and the United States to assess current trends in patient profile, and looks at demand and resources available for this form of treatment. A computerized registry established at the Royal Victoria Hospital in 1982 was used to document the profile of patients undergoing coronary artery bypass graft. Comparing 1988 to the previous six years (1982-87), a significant increase was found in patients with unstable angina (P less than 0.001) and abnormal left ventricular function (P less than 0.015) among those operated. The incidence of emergency operations also increased (P less than 0.001). The patient profile was similar to that of the Toronto university hospital population and many major United States university hospitals. The incidence of coronary artery bypass graft per 100,000 population, however, is much greater in the United States than in Canada (120 versus 56). Resources in many Canadian centres appear to be insufficient to meet demand for this type of surgical intervention.

Use of the omentum in the management of sternal wound infection after cardiac transplantation.

Seven patients with deep sternal wound infection after orthotopic cardiac transplantation were treated at the Medical College of Virginia-McGuire Veterans Administration Hospitals over a 3-year period. Six patients had mediastinitis with pericardial abscess, and one patient had only sternal osteomyelitis. All patients underwent prompt sternal debridement. In the six patients with mediastinitis, the transplanted heart was surrounded by a large dead space after debridement. This space appeared to result from a size mismatch between the remaining enlarged pericardial sac and the new normal-sized transplanted heart. Wound closure was done at the time of debridement in all patients except one who was closed 3 days later. A pedicled omental flap based on the right gastroepiploic artery was used in five of the six patients with mediastinitis, and these five patients healed their wounds and resolved their infection. Three of these patients are alive and well and two died of later complications other than sternal infection. The patient with only sternal osteomyelitis healed uneventfully. When mediastinitis and intrapericardial infection is present after cardiac transplantation, the omentum appears to provide adequate bulk for obliteration of the large dead space that remains after debridement. This surgery, combined with antibiotic therapy and temporary reduction of immunosuppression, can treat sternal wound infection successfully after cardiac transplantation. Mortality from other complications can occur, however, and not all patients survive.

Echocardiographic evaluation of patients with a left ventricular device.

Limited donor heart availability is primarily responsible for the renewal of interest in mechanical left ventricular assist devices (LVADs) as a bridge to transplantation. Donor availability is unlikely to increase significantly in the near future. Experience to date has shown that many patients can be maintained long enough to undergo transplantation, and LVADs may be acceptable as alternate therapy in some who may not be candidates for transplantation. However, criteria for noninvasive evaluation of patients on LVADs have not been developed. In a prospective study using serial echocardiography, we found that aortic valve opening, aortic forward flow, nonlaminar flow in the left ventricle, and mismatch of Doppler derived cardiac output at the pulmonic valve and device output are associated with device malfunction. Echocardiography was diagnostic in five of six patients with clinical instability unrelated to the device. These findings suggest that echocardiography is helpful in the routine evaluation of patients on LVADs.