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Biomedical subjects

R L Hardesty

Publications and source records attributed to R L Hardesty.

At least 55 records · Page 3Linked to original sources
PubMed1992

Lung transplantation at the University of Pittsburgh.

Lung transplantation appears to be a therapeutic alternative for selected patients with end-stage pulmonary vascular and/or parenchymal disease. The greatest impediment to transplantation remains the availability of donor organs. This has become more significant as additional transplant centers become operational. The primary cause of death has been infection, and this most frequently occurs in the early post-transplant period. Significant progress has been made in curbing the morbidity and mortality from bacterial pneumonia and CMV infection, and this is the primary reason for improved survival rates. If the recipient survives the initial hospital stay, the likelihood of survival at 5 years is approximately 80%. The primary long-term complication is obliterative bronchiolitis which is poorly understood and difficult to treat. Nevertheless, the improvement in survival provides impetus to refine and improve the procedure so that survival can reach that attained by recipients of other major organ allografts.

Academic Medical Centers↗
PubMed1992

Right ventricular/arterial coupling in the patient with left ventricular assistance.

BACKGROUND: Improvements are known to occur in right ventricular (RV) ejection fraction after the use of a left ventricular assist device (LVAD); less is known, however, about the mechanism of this improvement. The concept of ventricular/arterial coupling was applied to investigate whether systolic pump function or afterload reduction was the major contributing factor leading to the improvement in RV ejection fraction. METHODS AND RESULTS: Eight consecutive patients who underwent Novacor LVAD implantation as a bridge to transplantation were studied intraoperatively with transesophageal echocardiogram and a catheter-tip manometer to examine the RV end-systolic pressure-area relation (ESPAR) before and after LVAD implantation. Fractional area change (FAC) obtained by echocardiogram was used as an approximation of ejection fraction. End-systolic elastance (Ees), area axis intercept of ESPAR (A0), maximal area (Amax), and pulmonary effective arterial elastance (Ea) were obtained. RV FAC improved from 0.20 +/- 0.09 to 0.29 +/- 0.13 (p < 0.05). There was a decrease in Ea from 12.06 +/- 5.79 to 4.92 +/- 2.51 mm Hg/cm2 (p < 0.01), which indicated a reduction in RV afterload. A0 increased from -0.14 +/- 7.81 to 6.83 +/- 9.42 cm2 (p < 0.05), which implied impaired systolic pump function. There was no difference in Ees and Amax. CONCLUSIONS: The concept of ventricular/arterial coupling predicts that an increase of A0 (reduced RV systolic mechanics) decreases FAC, whereas a reduction in Ea improves FAC. The improvement in RV FAC (improved RV pump performance) may result from the effect of reduced Ea (afterload reduction) overwhelming the effect of increased A0. Afterload reduction is the most likely mechanism by which RV ejection fraction improves after LVAD implantation.

Adolescent↗
PubMed1992

Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model.

Lazaroids are a class of novel 21 aminosteroids. They have been reported to be potent inhibitors of lipid peroxidation, which is a major contributing factor to ischemia-reperfusion injury in the lung. A Lewis rat orthotopic left lung isotransplant model was used to investigate the effects of the lazaroid U74500A on pulmonary preservation. The heart-lung blocks of donor rats were flushed with and then stored in either standard University of Wisconsin solution or University of Wisconsin solution with 30 mumol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0 degrees C, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as a thiobarbituric acid-reactive substance. Although arterial oxygen and carbon dioxide pressures and water content after 6 hours of preservation followed by reperfusion were similar in both the lazaroid and dexamethasone groups, lipid peroxide concentration was significantly higher in the dexamethasone group (0.88 +/- 0.07 mumol/gm) than in the lazaroid group (0.54 +/- 0.07 mumol/gm) (p < 0.01). After 12 hours of preservation, there were significant differences between the lazaroid and dexamethasone groups in arterial oxygen pressure (339 +/- 70 vs 27 +/- 3 mm Hg, p < 0.01), arterial carbon dioxide pressure (24.3 +/- 2.7 vs 47.7 +/- 7.0 mm Hg, p < 0.001), and lipid peroxide concentrations (0.69 +/- 0.07 vs 1.30 +/- 0.09 mumol/gm, p < 0.001). We conclude that addition of U74500A to the flush and storage solution enhances the preservation of the pulmonary graft in this transplant model.

Adenosine↗
PubMed1992

Donor-transmitted pneumonia in experimental lung allografts. Successful prevention with donor antibiotic therapy.

Bacterial pneumonia is the most common cause of early morbidity and mortality (less than 2 weeks) after heart-lung transplantation. The majority (76%) of cultures taken from human donor tracheas at the time of explant grew bacteria. The abnormal immune response of the lung allograft and the common finding of bacterial contamination of lung donors led us to hypothesize that clinically silent bacterial contamination of the donor lung progresses to pneumonia in the recipient and that antibiotic treatment of donors will prevent the development of pneumonia in the recipient. Inocula of Streptococcus pneumoniae were instilled into the left middle lobe of normal and donor dogs to identify the number of bacteria that would result in pneumonia in a normal animal and the amount that, when given to a donor, would result in pneumonia in the recipient. Initial studies established that inocula of 10(4) colony-forming units of S. pneumoniae did not result in pneumonia in normal or immunosuppressed animals. When 10(4) colony-forming units or as few as 10(2) were instilled into the left middle lobe of donors 24 hours before explantation and use of the lung for transplantation, severe acute bronchopneumonia developed in all 18 recipients. Treatment of donors with aerosol and intravenous antibiotics, but not with either alone, prevented pneumonia in the recipients. We conclude that bacterial contamination of the donor lung leads to pneumonia in recipients. Intravenous and aerosol antibiotic treatment of donors with bacterial contamination prevents pneumonia in canine lung recipients. Treatment of human donors with this antibiotic regimen may decrease the prevalence of early bacterial pneumonia.

Administration, Inhalation↗
PubMed1991

Evolving experience with mechanical circulatory support.

Since 1985 total mechanical circulatory support for mortally ill transplant candidates has been progressively integrated into the authors' program. During this period 379 patients underwent transplantation. Of this group of patients, 62 required some form of mechanical support other than the intra-aortic balloon pump. Because intra-aortic balloon pump assist was limited in therapeutic effect and was associated with patient immobility and line-related sepsis, the next logical step toward support was the artificial heart. Of 20 patients implanted with the Jarvik heart, 17 underwent transplantation, but only 9 of these survived to discharge. In 1988, the authors abandoned the preferential use of the total artificial heart because of excessive cumulative probability of death from wound infection. They began to use the Novacor electrical assist device with the percutaneous power cord because they believed that univentricular support would be adequate for most patients, because its heterotopic position would reduce the likelihood of infection, and because it had the potential for chronic implantation. Twenty-three patients with biventricular failure (right ventricular ejection fraction less than 20%, 18/23) received the electrical assist device for an average of 50.4 days (range 1-193 days). All 17 transplanted patients survived until discharge. Only one of the five deaths that occurred after implantation, but without transplantation, was due to infection (candidiasis). Remarkably, all patients who survived the perioperative period ultimately survived with univentricular support alone. Based on this experience, survival of mechanically supported patients is now comparable to that of those less mortally ill.

Adolescent↗
PubMed1991

Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation.

Twenty-seven patients received pulmonary transplants during the period since we began routine use of cytomegalovirus-seronegative blood products for CMV-seronegative recipients. Preoperative serologic status of the recipient and the occurrence of cytomegalovirus infection in the postoperative period were correlated with development of obliterative bronchiolitis (OB) as diagnosed by transbronchial biopsy (TBB). Patients included 20 heart-lung and 7 double-lung recipients. OB occurred in 18 of 27 patients. All 3 CMV seronegative recipients receiving lungs from a seropositive donor and 9 of 10 CMV recipients seropositive at the time of transplantation developed OB compared with only 6 of 14 CMV seronegative patients receiving seronegative grafts (P = 0.018). CMV infection occurred in 10/27 patients, of whom 5 were asymptomatic; 90% of these patients developed OB. Donor-specific alloreactivity, based on primed lymphocyte testing (PLT) of bronchoalveolar lavage cells was found at the time of diagnosis of OB in 23 of 27 patients. A positive PLT was significantly associated with the presence of OB (P = 0.017). We conclude that preoperative seropositive status for CMV, grafting of organs from seropositive donors, and postoperative CMV infection are significant risk factors for developing OB. That OB is, in part, an immunologically mediated form of injury and represents chronic rejection is supported by the presence of donor-specific alloreactivity in BAL lymphocytes from all recipients with OB.

Antibodies, Viral↗
PubMed1991

Histocompatibility and other risk factors for histological rejection of human cardiac allografts during the first three months following transplantation.

A histological analysis of 2564 endomyocardial biopsies was conducted in 349 cardiac transplant patients to determine potential risk factors for acute cellular rejection during the first three months following transplantation. This analysis dealt with the frequency, time of onset, and duration of cellular rejection. Patients on perioperative RATG experienced significantly less rejection than patients on OKT3 or without antilymphocyte antibody immunoprophylaxis. A trend was noted toward increased rejection in recipients diagnosed originally with chronic myocarditis compared with patients in other disease categories including ischemic heart disease and dilated cardiomyopathy. No significant differences were seen in histological rejection between male and female recipients. On the other hand, patients over 55 years of age were found at lower risk of histological rejection. The results of this analysis have demonstrated quite clearly, but not unexpectedly, that a greater degree of HLA mismatching correlates with increased cellular rejection. This effect was noted not only for the HLA-A,B and DR antigens, but also HLA-DQ and HLA-DRw52/53 antigens. In multivariate analysis, the highest level of statistical significance was obtained for the combined HLA-A,B,DR and DQ group. Sensitized patients with panel-reactive lymphocytotoxic antibodies of greater than 10% experienced more histological rejection than nonsensitized patients. On the other hand, a positive lymphocytotoxic crossmatch did not appear to influence cellular rejection of cardiac allografts. Also, no differences were seen in histological rejection between ABO-identical and compatible heart transplants. These findings further support the concept that donor HLA compatibility and pretransplant sensitization represent significant risk factors for cellular rejection in cardiac transplantation.

Adolescent↗
PubMed1991

Alveolar macrophage migration after lung transplantation.

Pulmonary infection is a major source of morbidity and mortality in recipients of lung allografts. The alveolar macrophage plays an important role in pulmonary host defense, and to fulfill this role it must have the ability to orient and migrate in the direction of a stimulus. Thus migratory activity was measured in cells recovered from lung transplant recipients by bronchoalveolar lavage. The primary patient group consisted of recipients who had no evidence of infection or rejection at the time of bronchoalveolar lavage. These patients were further subdivided into an early postoperative group (less than 6 wk posttransplant) and a late postoperative group (greater than 6 wk posttransplant). Other categories included patients with chronic rejection and a small group of patients with Pneumocystis carinii pneumonia. Alveolar macrophages recovered by bronchoalveolar lavage were assayed for migratory response to N-formylmethlonylphenylalanine and endotoxin-activated human serum. Stimulated migration of cells from healthy recipients obtained in the late postoperative course was similar to that of normal control subjects, but stimulated migration of cells from healthy recipients in the early postoperative period and those undergoing chronic rejection was greater than expected. Spontaneous migration was similar in all groups except those with P. carinii pneumonia, in whom it was greatly increased. We conclude that alveolar macrophage migration is not impaired in lung allograft recipients without apparent signs of infection or rejection and is in fact increased during periods of possible macrophage activation (shortly after transplantation and during chronic rejection).

Bronchoalveolar Lavage Fluid↗
PubMed1991

Interim use of Jarvik-7 and Novacor artificial heart: blood rheology and transient ischemic attacks (TIA's).

The rheological properties of blood were studied in patients supported by both the Jarvik-7 total artificial heart (TAH) and Novacor left ventricular assist device (LVAD) as a bridge to cardiac transplantation. Both groups of patients had abnormalities in blood rheology which differed according to the type of device implanted as well as on the clinical state of the patient. The rheology of individual patients correlated well with their clinical status and outcome, with incidences of TIA's and/or stroke being accompanied by marked increases in relative blood viscosity, erythrocyte rigidity, fibrinogen concentration and platelet aggregation in varying combination. Observed abnormalities in blood rheology were also crucial to thrombus formation on artificial heart valves as well. Our results show that the therapeutic management of rheological parameters should prove to be a unique and clinically rewarding approach to these patients.

Adult↗
PubMed1991

Cardiac transplantation at the University of Pittsburgh: 1980 to 1991.

When examining survival rates following cardiac transplantation, it is important to examine the risk factors for both early (30-day) and late (greater than 30-day) survival as they may well be different. Factors affecting early survival appear related more to the preoperative condition of the patient (including degree of pulmonary hypertension) as well as advances that have been made in postoperative care. It is not immediately obvious why gender has such a profound effect on early survival and why primary graft failure rates appear higher in this group. Donor organ factors did not appear to relate to this difference. On the other hand, late survival appears to be influenced mainly by immunologic factors such as panel reactive antibody level and immunosuppressive protocol. A less dramatic effect of transpulmonary gradient appears to have a lasting effect on recipients even when they survive the initial 30-day period. Thus, pulmonary hypertension may have prolonged effects on the cardiac allograft which as yet we do not understand completely. The majority of late mortality is still due to graft atherosclerosis, infection, and acute cellular rejection, the latter 2 occurring most frequently within the first year after transplantation whereas death from graft atherosclerosis becomes most prominent beyond 5 years. Despite persistent improvements in 30-day survival, late survival following cardiac transplantation will only improve with the advent of better tissue matching and improved immunosuppression. The results with FK506, for example, are promising.

Adult↗
PubMed1990

Experience with univentricular support in mortally ill cardiac transplant candidates.

Between July 1987 and March 1989, 11 patients underwent left ventricular support with the Novacor left ventricular assist system irrespective of apparent degree of right ventricular failure. The first 2 patients died of multisystem organ failure while on support. All the remaining patients survived the support period, and actuarial survival after transplantation was 100% at 6 months and 89% at 1 year. In no patient did bacterial infection develop during support or after transplantation. Right ventricular ejection fraction before implantation of the left ventricular assist system was lower than 15% in 6 of 8 patients, yet it increased twofold during left ventricular support. The need for excessive inotropic support (2 patients) or temporary (four days) mechanical right ventricular support (2 patients) while on the left ventricular support system appeared to be related to elevated pulmonary vascular resistance during support in association with large preimplantation ventricular volumes. It appears that even patients with compromised right ventricular performance can be supported long term with a left ventricular assist device. Patients with elevated pulmonary vascular resistance may require temporary right ventricular support.

Adult↗
PubMed1990

Disruption of the aortic anastomosis after heart-lung transplantation.

Disruption of the aorta at the anastomotic site occurred in 4 of 66 consecutive heart-lung transplant recipients and was associated with a 100% mortality. In 3 of these patients, Candida either was cultured from the suture line or was seen in the wall of the aorta at postmortem examination. In 2 of these 3 patients, cultures of material from the donor trachea taken at the time of explanation grew Candida species. Two patients were seen with sudden massive hemorrhage on postoperative day 26 and postoperative day 28. One patient experienced acute decompensation due to right ventricular outflow tract obstruction on postoperative day 30, and the remaining patient was seen 7 months postoperatively with obstruction of both the left main bronchus and the right pulmonary artery caused by extrinsic compression by an aortic pseudoaneurysm. A high index of suspicion should be maintained when transplanting lungs containing Candida species, as we believe there is substantial evidence of donor transmission of the fungal agents. We now include amphotericin B in our antibiotic prophylactic regimen in an attempt to prevent fungal infection because previous treatment has been uniformly unsuccessful. Furthermore, we wrap both the trachea and the aorta with omentum to lessen the likelihood of mediastinal spread of infection to the aortic suture line.

Adolescent↗
PubMed1990

Clinical experience with the Medtronic-Hall valve prosthesis.

Medtronic-Hall valves were implanted during 204 procedures performed between 1982 and 1988. Mean population age was 54.4 years; 96% of patients were in New York Heart Association functional class III or greater. Emergency operations constituted 16% of the procedures. Rheumatic heart disease was the single most common indication for valve replacement. In 18% of patients, operation was performed to replace a previous prosthetic valve. The mean follow-up was 3.2 years. Overall operative mortality was 10.3%, the highest mortality being for double-valve replacements (24%). Valve-related mortality, by position, was 5.3% for aortic valves, 6.0% for mitral valves, and 4.0% for multiple-valve replacements. Actuarial 5-year freedom from events were: survival, 68%; thromboembolism, 90%; prosthetic valve endocarditis, 98%; paravalvular leak, 95%; and reoperation, 92%. Complications with the highest mortality were thromboembolism (36%) and endocarditis (33%). The complication rates in this series are high but the patients were more severely ill than in other reports, and operative survivors experienced a considerable improvement in New York Heart Association functional class.

Aortic Valve↗
PubMed1990

Propagation of infiltrating lymphocytes and graft coronary disease in cardiac transplant recipients.

The pattern of lymphocyte growth from endomyocardial biopsies in 55 heart transplant recipients was shown to be correlated with the subsequent development of graft coronary disease. Persistent lymphocyte growth was observed in 39 patients, and 15 of these growers (or 41%) developed graft coronary disease. In contrast, only 1 of 15 patients (or 6%) with nongrower biopsies showed subsequent graft coronary disease. Thus, biopsy growth was associated with a higher incidence of subsequent GCD (p = 0.02). A comparison between the group of 15 growers with subsequent graft coronary disease and the 24 growers without subsequent graft coronary disease did not show any differences with respect to patient age, presence of coronary artery disease in the native heart, biopsy histology, donor alloreactivity of biopsy grown lymphocytes, and immunosuppressive drug regimen. On the other hand, the number of treated rejection episodes was significantly lower in the grower group with subsequent graft coronary disease (p = 0.04). These data support the concept that graft coronary disease may involve rejection and that more immunosuppression may lower its incidence. This concept is strengthened by findings showing that alloreactive T cells can be propagated from coronary arteries of cardiac allografts with graft coronary disease.

Biopsy↗
PubMed1990

Acute myocardial dysfunction and recovery: a common occurrence after coronary bypass surgery.

To evaluate whether acute myocardial dysfunction was common in the early postoperative period, serial hemodynamic measurements and radionuclide evaluation of ventricular function were performed before and after operation in 24 patients undergoing elective coronary bypass surgery. All patients had uncomplicated surgery, and no patient sustained an intraoperative infarction. In 96% of patients, significant depression in right and left ventricular ejection fraction was seen postoperatively, reaching a nadir at 262 +/- 116 min after coronary bypass. Left ventricular ejection fraction was 58 +/- 12% preoperatively and 37 +/- 10% at trough. Right ventricular function displayed a similar pattern. These findings were also associated with depressed cardiac and left ventricular stroke work index despite maintenance of adequate ventricular filling pressures and mean arterial pressure. The depression in ventricular function was partially reversible within 8 to 10 h after surgery. Left ventricular ejection fraction had increased to 55 +/- 13% at 426 +/- 77 min after coronary bypass and showed complete recovery within 48 h. Left ventricular end-systolic and end-diastolic volume index increased significantly postoperatively, but recovery in left ventricular ejection fraction was mostly due to decreases in end-systolic volume index (50 +/- 22 ml at trough and 32 +/- 16 ml at recovery). Depressed myocardial function was independent of bypass time, number of grafts placed, preoperative medications or core temperatures postoperatively. Postoperative therapy with pressors or inotropic agents delayed but did not prevent the occurrence of postoperative ventricular dysfunction. Despite improvements in operative techniques and methods of myocardial protection, postoperative left ventricular dysfunction continues to be common in patients undergoing cardiopulmonary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗