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Biomedical subjects

R L Hardesty

Publications and source records attributed to R L Hardesty.

At least 91 records · Page 5Linked to original sources
PubMed1989

Ventilation and breathing pattern during progressive hypercapnia and hypoxia after human heart-lung transplantation.

The effects of human pulmonary denervation on the ventilatory responses to progressive hyperoxic hypercapnia and isocapnic hypoxia as well as the effect on resting breathing pattern were evaluated in nine female heart-lung transplant (H-LT) recipients. The results were compared to those obtained from 10 normal women of comparable age and stature. Testing was performed 2 to 37 months after H-LT (median, 7.5 months). Cardiac function was normal in all H-LT recipients. None of the patients had spirometric evidence of airway obstruction, while six had a restrictive pattern with forced vital capacities less than 80% of predicted values. Resting minute ventilation (VE), tidal volume (VT), and ventilatory drive (VT/TI) in the H-LT recipients were not significantly different from those of the normal subjects. Inspiratory time (TI), however, was significantly shorter in the H-LT patients (1.64 +/- 0.2 versus 2.09 +/- 0.13 s, p = 0.035), and resting breathing frequency (F) tended to be greater in the H-LT recipients (16.27 +/- 2.04 versus 12.82 +/- 0.53 breaths/min, p = 0.052). The overall ventilatory response to hypercapnia was reduced after H-LT (0.91 +/- 0.17 versus 1.5 +/- 0.27 L/min/mm Hg CO2, p less than 0.043), as was the F response (0.2 +/- 0.09 versus 0.65 +/- 0.13 breaths/min/mm Hg CO2, p less than 0.01). The VT and VT/TI responses to hypercapnia did not differ between the H-LT recipients and normal subjects. There were no significant differences between the two groups with respect to the responses to progressive hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Breathing during wakefulness and sleep after human heart-lung transplantation.

To study the effects of pulmonary denervation on breathing during sleep, sleep studies were conducted on seven heart-lung transplant recipients (H-LT) and a comparable number of sex-matched normal subjects of similar age. Four of the H-LT patients had a restrictive pattern on spirometry. The time since transplantation ranged from 45 to 1,102 days. There were no significant differences between the groups with respect to total sleep time or distribution of sleep stages. There were no significant differences between the H-LT recipients and normal subjects with respect to baseline awake oxyhemoglobin saturation (SaO2) or the nadirs of SaO2 during REM and non-REM sleep, the absolute number and frequency (number per hour of sleep) of apneas, hypopneas, desaturation events, both over the whole night of study or separately during non-REM and REM sleep. Across wakefulness and all sleep stages, the H-LT patients tended to have shorter total respiratory cycle times (Ttot) (p = 0.052) and more rapid breathing frequency (F) than the normal subjects. This was associated with significantly shorter inspiratory times (Tl) (p less than 0.001) and smaller duty cycles (Tl/Ttot) (p less than 0.005) in the H-LT recipients. During non-REM and REM sleep, F tended to be higher in the H-LT recipients with pulmonary restriction than in the nonrestricted patients. There were no significant differences between the H-LT recipients and the normal subjects with regard to the periodicity of breathing, either in terms of timing parameters or breath amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pulmonary capillary hemangiomatosis. A report of three cases and a review of the literature.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension. At present, only eleven cases have been reported. This report describes the clinical and pathologic findings in three additional cases who presented to the University of Pittsburgh for heart-lung transplantation and integrates the clinical features of all fourteen cases. Clinically, this disorder should be suspected in a patient who presents with pulmonary hypertension, hemoptysis, a reticulonodular infiltrate on chest radiograph, a lung scan showing inhomogeneously enhanced perfusion (particularly in the lower lobes), and pulmonary angiography showing increased peripheral vascularity corresponding to both the radiographic infiltrate and the areas of enhanced perfusion on lung scan. Histologic features consist of nodular proliferation of capillary-sized vessels that infiltrate the pulmonary interstitium, vascular walls, and lumens as well as the alveolar septa. The vascular invasion results in a secondary veno-occlusive phenomenon that explains the clinical confusion with pulmonary veno-occlusive disease.

Adult↗
PubMed1989

Infections in mortally ill cardiac transplant recipients.

A total of 351 cardiac transplantations performed between June 1, 1980, and Sept. 30, 1987, were reviewed to determine if infectious complications were more frequent in those patients requiring preoperative intravenous inotropic support, placement of an intraaortic balloon pump, or mechanical support with a left ventricular assist device or total artificial heart. One hundred forty-nine transplants (45%) were performed in these mortally ill patients. There was no statistically significant difference between patients with and without infection within each support group for the following: the number of in-patient days awaiting a donor heart, the number of days receiving support, the percent of patients with preoperative tracheal intubation, the length of the operation, and the percent of patients requiring reoperation for bleeding. The need for invasive methods of support (intraaortic balloon pump, left ventricular assist device, or total artificial heart) in patients awaiting heart transplantation increases the prevalence of perioperative nonviral infection. Preoperative mechanical support with a left ventricular assist device or total artificial heart significantly increases the risk of infection-related mortality.

Adult↗
PubMed1989

[New trends in combined transplantation of the heart and lungs].

Heart-lung transplantation is a surgical alternative for patients with end-stage lung disease with associated right heart failure. While the procedure is very promising, the morbidity and mortality remain high. The current understanding of the proper selection of candidates, procurement and preservation of donor organs, operative procedure and postoperative care continues to evolve. At the University of Pittsburgh, 70 heart-lung transplantations have been performed since 1982. Early infection and chronic rejection are the major factors influencing survival. Early (less than 2 weeks) intrathoracic infection occurred in 43% of heart-lung transplant recipients, with pneumonia being the most frequent infection. The incidence of pneumonia in heart-lung transplant recipients is twice that in a comparable group of heart recipients. Subclinical pneumonitis in the donor lung, abnormal muco-ciliary clearance and altered allogenic response in the transplanted lung are significant factors associated with the increased incidence of early infections. Chronic rejection, manifested as bronchiolitis obliterans, has occurred in 54% of heart-lung transplantation recipients. Infection caused by cytomegalovirus, Epstein-Barr virus and Pneumocystis carinii have been shown to increase the incidence of bronchiolitis obliterans, as have episodes of acute rejection. Recent reports of a 61% 2-year survival rate represent a substantial improvement over earlier trials. With a better understanding of the pathogenesis of infection in the transplanted lung as well as improved immunosuppressive agents, further improvements in survival can be expected.

Heart-Lung Transplantation↗
PubMed1988

Evidence of an altered pattern of breathing during exercise in recipients of heart-lung transplants.

Recipients of heart-lung transplants represent an unusual opportunity to study the regulation of ventilation, because the neural pathways between the lungs and the central nervous system are disrupted in these patients. We compared the ventilation response in seven recipients of heart-lung transplants who had normal pulmonary function and seven recipients of heart transplants, all of whom performed incremental bicycle ergometry. The level of ventilation in recipients of heart-lung transplants was similar to that in heart-transplant recipients for equivalent levels of carbon dioxide production. Arterial pH and partial pressure of carbon dioxide at maximal exercise were normal and not significantly different in the two groups, also suggesting that levels of ventilation were appropriate in both groups. However, the rate of the rise in respiratory rate for increasing levels of ventilation was significantly lower in recipients of heart-lung transplants than in heart-transplant recipients, and the initial increase in tidal volume was more rapid in the former group than in the latter. Thus, recipients of heart-lung transplants have an appropriate level of ventilation during exercise as the result of a disproportionate increase in tidal volume at a reduced respiratory rate. We speculate that intrapulmonary receptors are important in regulating the pattern, but not the absolute level, of ventilation during exercise.

Acid-Base Equilibrium↗
PubMed1988

The artificial heart: infection-related morbidity and its effect on transplantation.

Between October, 1985, and September, 1987, a total of 195 patients received cardiac allografts and 15 candidates required mechanical support with the Jarvik-7 total artificial heart. Seven of the 15 died within 60 days of total artificial heart implant. There have been no late deaths, and survivors are unrestricted. Six of 7 deaths were related to infection (mediastinitis, 5; pneumonia and sepsis, 1), and the remaining 1 was due to failure of the transplanted heart. Respiratory tract infection occurred in each of the recipients who died with infection, and the same organisms appeared to be related to subsequent mediastinitis in 3 patients (Serratia marcescens, 2; Pseudomonas, 1) and caused fatal sepsis in another (Enterobacter aerogenes, Candida albicans). One patient died with pneumonia and sepsis prior to transplantation, and another succumbed with mediastinal infection known to be present before transplantation.

Heart Transplantation↗
PubMed1988

Immunologically mediated disease of the airways after pulmonary transplantation.

Obliterative bronchiolitis has occurred in eleven of 30 recipients of cardiopulmonary allografts who survived at least 4 months after transplantation, has caused significant morbidity, and has been associated with four of eleven late deaths in this series. Although some improvement, or at least stability, of pulmonary function has followed augmented immune suppression, it appears that once the process is recognized clinically, much of the damage to the airways is irreversible. The histopathology, response to therapy, and, most important, the response of donor specific alloreactivity in the lymphocytes from the lung (bronchoalveolar lavage and peripheral blood) suggest immune- mediated basis for bronchiolitis obliterans. The presence of donor specific alloreactivity detected by primed lymphocyte testing predicted obliterative bronchiolitis in five of six recipients (83% sensitivity, 91% specificity) was absent in ten of eleven recipients who have not as yet developed the process (negative predicted value of 91%). Currently, the presence of a positive primed lymphocyte test in the bronchoalveolar lavage of the cardiopulmonary recipient is an indication for early treatment by augmented immune suppression.

Bronchiolitis Obliterans↗
PubMed1988

Unexpectedly high incidence of Pneumocystis carinii infection after lung-heart transplantation. Implications for lung defense and allograft survival.

Pneumonia due to Pneumocystis carinii (PCP) is regularly encountered in organ allograft recipients who are immunosuppressed to prevent rejection. Recipients of lung/heart allografts may be particularly prone to pulmonary infection due to systemic immunosuppression and the fact that defense mechanisms in the transplanted lung may be further impaired through tissue incompatibility and the effects of surgery. In this study, we monitored 16 lung transplant recipients for infection with Pneumocystis carinii using serial bronchoalveolar lavage (BAL) and found the prevalence of Pneumocystis infection of the lung to be 88%. Six episodes were associated with the usual symptoms of pneumonia, whereas 10 episodes were associated with minimal or no symptoms. In 3 of the 6 symptomatic episodes, a concurrent bacterial infection was also found. The total number of cells recovered from the lung by BAL, the proportion of T-lymphocytes, and the number of cytotoxic/suppressor and helper/inducer cells were elevated during infection with Pneumocystis compared to before and after. Spontaneous and interleukin-2-induced proliferation of BAL cells in vitro was also higher during infection, suggesting that there was an increased number of activated T-lymphocytes in the airspaces of the infected allograft. BAL cells cultured with irradiated spleen cells from the donor proliferated at higher levels when obtained after Pneumocystis infection than when obtained before or during infection even for subclinical infections. These results indicate that in the absence of prophylaxis, the prevalence of Pneumocystis infestation is very high after lung/heart transplantation. Impaired defense of the transplanted lung does not seem to stem from the inability of activated T-lymphocytes to accumulate in the allograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗
PubMed1988

Role of the antibody to vascular endothelial cells in hyperacute rejection in patients undergoing cardiac transplantation.

Traditionally, the human lymphocyte antigens have been considered to be the major barrier to successful transplantation, and lymphocytes have been used as the target cell in evaluating histocompatibility. The presence in the serum of recipients of preformed antibodies, cytotoxic to donors lymphocytes, is associated with a high probability of hyperacute rejection. We identified 11 patients in whom, despite a compatible direct lymphocytotoxic cross-match, acute failure of the cardiac homograft was associated with histologic and immunologic findings consistent with hyperacute rejection. Direct immunofluorescence and immunohistochemical staining showed the presence of antibodies on the surface of vascular endothelial cells in each of these 11 patients. The serum of these recipients was found to contain antibodies against a panel of endothelial cells. In contrast, cytotoxic antibodies to vascular endothelial cells were not present in a control group of 18 heart transplant recipients who did not experience hyperacute rejection. Thus the presence of antibodies against vascular endothelial cells seems to be related to hyperacute rejection of the cardiac allograft.

Antibodies↗
PubMed1988

Patient selection and results of cardiac transplantation in patients with cardiomyopathy.

Cardiac transplantation for the treatment of end-stage congestive heart failure has been shown to be of benefit regardless of the etiology. With few exceptions, the evaluation of patients with end-stage heart failure is the same, regardless of the etiology. In those with cardiomyopathy not as a result of CAD, special attention must be given to exclude secondary causes of cardiomyopathy such as amyloidosis, hemochromatosis, and sarcoidosis, as well as generalized systemic illnesses that may also involve the heart, either secondary or hereditary, because special consideration must be given to these patients on a case-by-case basis to determine that there is no general systemic involvement of the illness that would preclude satisfactory rehabilitation after transplantation. Before cardiac transplantation becomes widely available, there must be a greater number of donor hearts, the lack of which now severely limits the number of transplants performed in comparison with the estimated need.66 Additionally, more effective and specific immunosuppressive agents must be identified in order to reduce the incidence of rejection, infection, and accelerated atherosclerosis that now limits the longevity of transplant recipients. Furthermore, the ideal immunosuppressive agent should be associated with fewer side effects than those currently available. The emotional and economic burdens placed on the patient, the family, and society must be balanced against the benefits generated by the procedure. Despite these limitations, cardiac transplantation continues to offer hope for the terminally ill patient, which must be tempered by an understanding of the real limitations of transplantation.

Adolescent↗
PubMed1988

Upper gastrointestinal endoscopy after cardiac transplantation.

Three hundred four patients have undergone cardiac transplantation at the University of Pittsburgh since 1980. Twenty patients have required 27 upper gastrointestinal (GI) endoscopic procedures. After heart transplantation the primary indications for endoscopy were epigastric pain (six patients with gastritis, one with multiple shallow gastric ulcers, and one with normal test results), mild upper GI bleeding (four patients with esophagitis, two with gastritis, and two with multiple shallow gastric ulcers), dysphagia and odynophagia (two patients with esophagitis), persistent nausea and vomiting (one with normal test results), lower GI bleeding (one with normal test results), and routine follow-up (one with normal test results). After heart-lung transplantation the primary indications for the endoscopy were massive upper GI bleeding (three patients with actively bleeding duodenal ulcers), dysphagia and odynophagia (one patient with esophagitis), mild upper GI bleeding (one patient with gastritis), and routine follow-up (one patient with normal test results). No complications resulted from endoscopy. The procedures were performed in the GI suite without cardiac monitoring. Prophylactic antibiotics were not routinely administered. No patient had a fungal infection of the upper GI tract--a finding attributed to the prophylactic use of nystatin in all patients. Opportunistic viral infections were identified histologically in six patients, including two patients with actively bleeding duodenal ulcers. The possibility of opportunistic viral infections in this immunosuppressed group required aggressive diagnostic techniques, including endoscopy and biopsy, which can be safely performed after cardiac transplantation.

Adult↗