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Biomedical subjects

D B Doty

Publications and source records attributed to D B Doty.

At least 19 recordsLinked to original sources
PubMed1992

Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation.

To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (< 6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infection was similar in first and second transplant recipients. Second transplant recipients had a higher level of sensitization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repetition in the second donor of mismatched HLA antigens present in the first donor did not adversely affect survival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant.

Actuarial Analysis↗
PubMed1990

The surgeon's response to a low-output state after cardiopulmonary bypass: etiologies and remedies.

Following cardiopulmonary bypass, a series of steps can usually be used to restore function to the heart. A low postbypass cardiac output can be countered with a response checklist that includes adjusting heart rate, correcting cardiac arrhythmia, ensuring adequate hematocrit, adjusting preload and afterload, and stimulating cardiac contractility. It is the surgeon's responsibility to make a thorough investigation of any structural abnormality that may contribute to the low-output state; adequate repair of cardiac defects will often result in an improved hemodynamic state. Hemorrhage is an important cause of poor cardiac performance. Tamponade of the heart is usually due to retained clots associated with hemorrhage after operation and is indicated by a low-output state with equalization and elevation of atrial pressures. In a low-output, postsurgical state, the possibility of residual shunts and obstructions, inadequate valve repair, and closure or inadequate flow through a graft may need to be investigated. Once that has been achieved, the appropriate steps can be taken to improve cardiac performance.

Arrhythmias, Cardiac↗
PubMed1990

Cardiac transplantation in situs inversus.

Transplantation of the heart was successfully performed in a patient with situs inversus of the viscera and atria. Anatomic constants common to all patients allowed the left atrium, pulmonary artery, and aorta to be joined as usual in the transplant operation. Systemic venous reconstruction was the crux of the operation. A composite superior vena cava was reconstructed on the right side from the recipient translocated superior vena cava, donor superior vena cava and innominate vein, and recipient in situ pericardium. The inferior vena cava was rerouted from the left side across the midline to the right through a composite conduit consisting of the recipient night atrium and in situ pericardium over the diaphragm. These reconstructed venous passageways have remained patent and unobstructed for 1 1/2 years after the operation.

Anastomosis, Surgical↗
PubMed1990

Bypass of superior vena cava. Fifteen years' experience with spiral vein graft for obstruction of superior vena cava caused by benign disease.

Nine patients had operations for obstruction of the superior vena cava with superior vena caval syndrome caused by benign disease. Three patients had fibrosing mediastinitis, four had fibrosing mediastinitis with caseous necrosis, one had thrombosis of the superior vena cava around a pacemaker electrode, and one had spontaneous thrombosis of the superior vena cava. Patients ranged in age from 25 to 68 years. All bypass operations were performed with a composite spiral vein graft constructed from the patient's own saphenous vein, split longitudinally and wrapped around a stent in spiral fashion. The edges of the vein were sutured together to form a large conduit ranging in diameter from 9.5 to 15.0 mm. Six grafts were from the left innominate vein and three grafts were from the internal jugular vein. The grafts were placed into the right atrial appendage in all except one case, in which the graft was to the distal superior vena cava. Follow-up extends from 1 to 15 years. One patient required reoperation at 4 days for thrombosis at the innominate vein-graft anastomosis. Resection of the anastomosis and reconstruction of the graft rendered the patient symptom free. Two grafts closed during the first year after operation. One patient had advancing fibrosing mediastinitis, and a second bypass graft from the external jugular veins remain patent. Another patient had recurrence of spontaneous venous thrombosis. Thus seven of nine grafts remain patent for up to nearly 15 years and all but one patient is free of superior vena caval syndrome. These data show that bypass of the obstructed superior vena cava with a spiral vein graft relieves superior vena caval syndrome and demonstrate long-term patency of the graft.

Adult↗
PubMed1990

Influence of corticosteroid-free maintenance immunosuppression on allograft coronary artery disease after cardiac transplantation.

Although the etiology of allograft coronary artery disease, a major limiting factor in long-term survival after cardiac transplantation, is poorly understood, it is undoubtedly in part immune mediated and not detected by routine endomyocardial biopsy. Therefore it is possible that withdrawal of maintenance corticosteroids, although providing other short- and long-term benefits, could increase the prevalence of allograft coronary artery disease by permitting undetected immune-mediated vascular injury to occur. To assess whether corticosteroid-free maintenance immunosuppression increased the prevalence of allograft coronary artery disease, we reviewed serial angiograms of 102 patients (49% not receiving corticosteroid maintenance therapy) who underwent heart transplantation after March 7, 1985. Multiple variables including serum cholesterol, recipient and donor age, sex, blood pressure, rejection frequency and severity, early rejection prophylaxis protocol (polyclonal versus monoclonal T-cell agents), and corticosteroid use were examined in relation to allograft coronary artery disease by univariate and multivariate analyses. Allograft coronary artery disease was identified in 21 patients (seven severe, four moderate, and 10 mild). The prevalence by Kaplan-Meier life-table analysis was 17% at 1 year and 25% at 2 years. No further allograft coronary artery disease was detected among patients undergoing angiography at three years. Increased allograft coronary artery disease was not noted in patients withdrawn from maintenance corticosteroids when compared with their corticosteroid-requiring counterparts. In fact, with each 1 gm increment in cumulative corticosteroid use, a slightly increased risk (1.04, p less than 0.05) of allograft coronary artery disease was noted (Cox regression model). None of the other variables correlated with the prevalence of allograft coronary artery disease. Thus withdrawal of maintenance corticosteroids is not associated with an increased risk of early allograft coronary artery disease and minimization of corticosteroids may lead to a decreased long-term incidence of coronary artery disease in cardiac transplant recipients.

Adrenal Cortex Hormones↗
PubMed1989

Efficacy of OKT3 retreatment for refractory cardiac allograft rejection.

Although OKT3 monoclonal antibody is a useful therapy for refractory cardiac allograft rejection, the use of OKT3 for prophylaxis may be limited by the potential of sensitization and subsequent loss of efficacy on retreatment. OKT3 was required for refractory rejection in 21 of 165 recipients transplanted between March 1985 and August 1988. Twelve of these patients had previously been exposed to OKT3, and the retreatment efficacy was evaluated. The study population averaged 42.1 +/- 15.3 years of age (mean +/- SEM) and had experienced 2 +/- 1 previous episodes of rejection. The prior episodes of rejection had been treated with pulse methylprednisolone and antithymocyte globulin, and in addition 3 patients (25%) also required a course of antilymphoblast globulin. Retreatment OKT3 for refractory rejection was required 120 +/- 94 days following transplantation. CD3+ lymphocytes were eliminated from the circulation within 24-48 hr in 11 of 12 patients, all of whom showed histologic improvement within the first week. Total resolution on the initial follow-up biopsy was noted in 9 (75%) during the course of therapy. Subsequent rejection episodes occurred in 9 (82%) of the survivors at 71 +/- 64 days. One-year survival was 83% in this vigorously rejecting patient population. Serious infections occurred within 3 months of therapy in 4 (36%). The side effects of OKT3 retreatment were similar to those seen with first exposure and did not require OKT3 discontinuation. Thus OKT3 may be administered with success in most patients who have previously been exposed to it.

Adult↗
PubMed1989

A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3.

To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.

Antibodies, Monoclonal↗
PubMed1988

The effects of cardiopulmonary bypass and cold cardioplegia on coronary flow velocity and the reactive hyperemic response in patients and dogs.

In normal coronary arteries, reactive hyperemic responses to a 20-second occlusion, an index of coronary reserve, usually demonstrate a peak-to-resting flow velocity ratio of 4:1 or more. Most intraoperative studies that have assessed reactive hyperemic responses in bypassed vessels have reported peak-to-resting flow velocity ratios of 2:1 or less following a 20-second occlusion. These decreased reactive hyperemic responses could be due to coronary vasodilatation after cardiopulmonary bypass or to an inadequate physiological result of the surgical procedure. In 14 patients with angiographically normal coronary arteries, the peak-to-resting flow velocity ratio following a 20-second coronary occlusion decreased significantly (p less than 0.05) from 4.4 +/- 0.2 (mean +/- standard error) before bypass to 3.0 +/- 0.3 after bypass. In a similar dog model, the peak-to-resting flow velocity ratio decreased by 36 to 52% during the first hour following one hour of cardiopulmonary bypass and cardioplegia. During the same period, left ventricular perfusion increased 21 to 30%, mean arterial pressure and coronary vascular resistance decreased, and myocardial oxygen consumption was unchanged. In a second group of dogs studied for the effects of duration (200 to 240 minutes) of anesthesia and thoracotomy alone, peak-to-resting flow velocity ratio was significantly lower. These clinical and experimental studies suggest that major coronary vasodilatation occurs early following cardiopulmonary bypass and cold cardioplegia, and may contribute to the blunted coronary reactive hyperemic responses reported during this time. Consequently, an intraoperative peak-to-resting flow velocity ratio of 3:1 for bypassed coronary arteries may represent an excellent physiological result.

Adolescent↗
PubMed1987

Age-associated decline in cardiac allograft rejection.

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.

Actuarial Analysis↗
PubMed1987

Replacement of the aortic valve with cryopreserved aortic valve allograft: considerations and techniques in children.

Normal structure and function of the aortic valve requires not only the basic three-cusp architecture but also the dynamic action and shape of the aortic sinuses and correct diameter relationships at the left ventricular outlet and at the aortic sinus rim. Congenital malformation of the aortic valve implies abnormality of the aortic cusps and, additionally, there may be deformity of the aortic sinuses or the subvalvular left ventricular outflow tract or the supravalvular aorta. Aortic valve replacement in children using an aortic valve allograft often requires enlargement of the left ventricular outflow tract or restoration of aortic sinus configuration. Careful consideration of the malformations of the aortic root and planning of reconstructive operation is required lest the malformation be recreated in the allograft valve replacement. Even the best execution of known aortic root reconstructive or left ventricular outflow tract enlarging operations has limitations in restoration of normal structure and compliance of the aortic root. Consequently, there remain many unknown factors that could affect late results of aortic valve allograft operations in children compared to those results observed in adult patients.

Aorta↗
PubMed1987

Pulmonic valve.

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Heart Valve Diseases↗
PubMed1986

Cerebral infarction complicating Fontan surgery for cyanotic congenital heart disease.

We report on four children who had cerebral vascular events in the first three months after the Fontan procedure for complex cyanotic congenital heart disease. Potential risk factors in these children included congestive heart failure, postoperative thrombocytosis, and cardiac arrhythmias. These cases suggest that children who undergo Fontan surgery may be at increased risk for cerebral infarction.

Adolescent↗
PubMed1986

Morphologic characteristics of aortic atresia: implications for fetal hemodynamics.

We studied hearts with aortic atresia to determine the relationship between cardiac morphology and fetal cardiac blood flow. We compared measurements of aortic, pulmonary, and tricuspid valve circumference and right ventricular wall thickness among 37 hearts with aortic atresia and mitral hypoplasia, 14 hearts with aortic atresia together with mitral atresia and 24 normal hearts. Right ventricular free wall thickness and tricuspid and pulmonary valve annular circumferences were greater and aortic circumferences were smaller in hearts with aortic atresia than in normal hearts (P less than 0.05). Between the subgroups of aortic atresia, the aortic circumference was 5 +/- 1 mm in those with mitral atresia compared to 7 +/- 2 mm in association with mitral hypoplasia (P less than 0.05). The morphologic differences between the subgroups of aortic atresia are consistent with differences in fetal blood flow. Left heart blood flow was likely to be greater during development in those hearts with aortic atresia and mitral hypoplasia than in those with the combination of aortic and mitral atresia.

Aorta↗
PubMed1986

The role of venography and surgery in the management of patients with superior vena cava obstruction.

Venacavography proved to be an excellent guide for the design of patient management programs. Type 1 patients with incomplete obstruction of the superior vena cava (SVC) are best managed by irradiation and chemotherapy regimens and usually do not require operation to bypass the SVC. Types II and IV patients are treated by operation when symptoms of airway obstruction or cerebral venous hypertension are present. Type III patients should be considered for SVC bypass as an initial therapeutic intervention. This group is more likely to have cerebral or airway symptoms and would benefit most from the bypass operation. In terms of operative considerations, type III patients are ideal for operation because the left brachiocephalic vein is usually available for bypass. Type IV patients may also be considered, but operation is more difficult and may require venous thrombectomy or extension of the bypass graft above the thoracic inlet to obtain head and neck decompression.

Adult↗
PubMed1986

Coronary obstructive lesions: assessing their physiological significance in humans.

For more than two decades cardiologists and cardiac surgeons have estimated the physiologic significance of coronary lesions by measuring percent stenosis of the obstructive vascular segment from coronary angiograms. Such measurements, when performed without computer-based analysis, are associated with substantial variability between observers, as well as within a single observer. In addition, recent intraoperative measurements of coronary reserve in individual obstructed vessels of patients with multivessel coronary disease performed with a suction Doppler probe indicate that, in the intermediate range (10% to 90% diameter stenosis), percent stenosis measurements of coronary lesions by angiography correlates poorly with coronary reserve. These studies suggest that the physiologic significance of coronary obstructions cannot be accurately assessed by visual interpretation of coronary angiograms. More sophisticated and accurate approaches are needed for assessing the physiologic significance of coronary obstructions preoperatively.

Coronary Disease↗