Computer-based analysis of preoperative and postoperative prognostic factors in 100 patients with combined aortic and mitral valve replacement.
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Adult↗
Biomedical subjects
D B Melvin
Publications and source records attributed to D B Melvin.
Cardiac performance and myocardial contractility after experimental mechanical ventricular assistance.
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Animals↗
Simple technique for venous coronary artery bypass in the dog.
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Animals↗
Ventricular radius reduction without resection: a computational analysis.
Reducing a dilated left ventricle's radius by wedge resection lowers wall stress, improving performance. However, compliance falls, stroke volume improvement is limited, and, later, both functional deterioration and serious dysrhythmias are frequent. These all may result from loss of circumference, loss of contractile mass, and myocardial trauma, none of which would occur in geometric remodeling. One specific technique is bimeridianal restraint, which uses two indenting bars to remodel the left ventricle (LV) as two widely communicating "lobes" of reduced radius. Computational analysis of this technique, applied to the dilated ventricular dimensions of four pretransplant patients, showed that 20% radius reduction would be accomplished by two < or =18 mm wide bars, indenting the epicardium < or =8.3 mm with < or =6.4 mm greatest outward displacement. Projected stroke volume (SV) for the subject ventricles was then modeled and compared with projections for resected ventricles. Assuming that equally improved contractile fraction will follow equal radius reduction, however that reduction is accomplished, improvement is dramatic: if postresection remodeling SV were 1.0, 1.2, or 1.5 times baseline, then postgeometric remodeling SV would be 1.36+/-0.06, 1.66+/-0.05, or 2.14+/-0.04 times baseline, respectively. These results, preservation of contractile mass and circumferential length, complete reversibility, and minimal operative trauma, warrant study of implementing mechanical designs.
Cardiac Surgical Procedures↗
Miniature circulatory support power transformer.
Direct power delivery to intracorporeal circulatory support devices risks infection. Electrical transformers spanning the integument (skin or mucosa) have long been attractive means of circumventing this risk. Yet all existing skin surface transformers leak substantial magnetic flux, with an intrinsic risk of battery draining cross-coupling by any nearby conductor, requiring strict control of surroundings. In a progression of designs, we have used the walls of a small pouch, surgically formed from ileum, rather than skin, as a barrier. Previously, we reported a torroidal design with complete magnetic circuits, having zero flux leakage and unmatched heat dissipation in a 2 week canine trial. This work was in three parts: (1) Devices were placed in eight dogs for 9-12 weeks to document performance of the existing design. (2) Based on these results, the device was further miniaturized. Iterative computational modeling was applied to material selection and design. Simultaneously, practical techniques for surgically constructing tiny accommodating ileal pouches were explored in cadavers, by using polymer "mock-ups" of potential designs. (3) The final design was tested by acute implantation in a live 52 kg goat and by in vitro testing of electrical transfer function. IN VIVO TRIALS: The earlier design demonstrated 97.2% AC/AC and 84.2% DC/DC efficiency with contiguous tissue warming of 0.1 degrees C. DESIGN AND PERFORMANCE: A transformer with a Square Permalloy torroidal core (6 cm3, 23 grams, both coils eight turns) was designed, by using human cadaver trials to optimize geometry. Input and output were 6 V, 12W at 9.2 kHz with AC-AC efficiency 96%. OPERATIVE PLACEMENT TRIAL: The primary coil easily fit into an isolated, vascularized, but otherwise disconnected "blind" ileal pouch < 2 cm long with a slender extension to a miniature stoma. With secondary turns, the pouch and transformer fit easily into the abdominal wall. This tiny system seems compatible with near "forgettable" power delivery allowing unprecedented freedom of environment and activity in circulatory support dependent people.
Animals↗
Device-induced ventricular geometric remodeling: appraisal of critical issues.
BACKGROUND AND AIMS: Devices to therapeutically alter the shape of failing left ventricles are being developed by at least two laboratories. This review attempts to assess potential for benefit and possible negative consequences of the device concepts. METHODS AND RESULTS: Data from all known publications and scientific presentations were reviewed. Findings address four key issues: (1) Predictions, based on physical computations, of direct beneficial reduction in myocardial afterload are indeed computationally realistic and supported by effects reported experimentally. (2) Concerns that remodeling might necessitate unacceptably high epicardial contact pressure appear unfounded. Computational force modeling indicates that with optimization of contact area and contour, the expected degree of remodeling (approximately 20% effective radius reduction) might be achieved by epicardial pressures very near existing endocardial pressures, and in diastole, well below arterial perfusion pressures. Reported augmentation of systolic function suggests that there is no significant compromise of regional perfusion in acute (< or = 4 weeks) preclinical studies. (3) If intramural tangential shear stresses were sustained by local bending, detrimental tensile/compressive stresses might be introduced. However, microstructure predicts and reported evidence confirms rapid shear-stress relaxation. (4) The same reduction in wall-stress/chamber-pressure ratios that produces benefit during systole would simultaneously worsen diastolic same-volume stiffness. However, if better systolic contraction effects more complete emptying, operational volume range should become incrementally lower, at least compensating. This is supported by early published data. CONCLUSIONS: There appears to be solid computational and early experimental support for the concept of geometric ventricular remodeling. If one or more of the devices being tested should prove to be safe and effective, left ventricular geometric remodeling will be of substantial benefit in heart failure treatment.
Animals↗
Electric power induction through an isolated intestinal pouch.
A new transintegumental power transformer uses the walls of an isolated intestinal pouch to separate primary and secondary coils. It may surpass transcutaneous devices in heat dissipation potential and in comfort. It was acutely tested in 13 dogs. Corrections in geometry and insulation were suggested by the nine initial trials. In the remaining four animals, up to 14.1 W were delivered, incrementing over 90 to 395 min. Three pouch and two remote thermistors recorded temperature (T) at 10 min intervals. Thirty sets of data were taken at 4 W or less (Group A), 31 at 4-8 W (Group B), and 16 at more than 8 W (Group C). T elevations above reference drift were 0.096 + 0.062 degrees C, 0.468 + 0.234 degrees C, and 0.876 + 0.156 degrees C for groups A, B, and C, respectively. These were significant by t-tests (p less than 0.001 for Group A vs. B; p less than 0.05 for Group B vs. C). The concept appears to be feasible, and longer term implantation trials seem justified.
Animals↗
Home intravenous dobutamine therapy in patients awaiting heart transplantation.
Lack of donor availability has heightened our awareness of the need for suitable long-term management of heart failure in patients awaiting heart transplantation. Frequently patients become dependent on intravenous inotropic agents despite attempts to discontinue these agents. This can lead to prolonged hospitalizations, separation anxiety and depression in families, high hospitalization costs, and poor quality of life. Between June 1987 and April 1988 three patients awaiting heart transplantation at the University of Cincinnati Hospital were sent home while receiving constant intravenous infusion of dobutamine. All three patients had had prolonged hospitalizations and were unable to be weaned from dobutamine without clinical compromise. The patients were New York Heart Association functional class III to IV, had cardiac indices between 1.5 to 2.13 L/min/m2, cardiac output less than 4.0 L/min, pulmonary capillary wedge pressures 17 to 27 mm Hg, and left ventricular ejection fraction less than 20% in two of the patients (idiopathic cardiomyopathy), and 30% in the third patient who was awaiting retransplantation (refractory repeated acute rejections). Dobutamine was infused by means of a constant-rate portable cassette pump at 3.17 micrograms/kg/min in patient 1, 10 micrograms/kg/min in patient 2, and 5 micrograms/kg/min in patient 3. A critical care home health nursing agency was used for follow-up home care. All three patients had central lines placed before discharge from the hospital. Each patient was instructed in proper care of the central line and infusion pump and was able to demonstrate accurate technique before being discharged home. Complications were minimal and were related to central line placement. No patient required rehospitalization for complications. No wound infections were reported.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Immunologic monitoring with Orthoclone OKT3 therapy.
Muromonab-CD3 monoclonal antibody (Orthoclone OKT3) was used 146 times in 123 transplant recipients to treat or prevent rejection. Reversal and prevention of rejection were evaluated 1 week and 1 year after OKT3 therapy. Eighty-one percent (73 of 90) of the rejection episodes in kidney transplant patients were reversed with 67% of these grafts functioning at 1 year. Eighteen of 20 (90%) rejection episodes in liver transplant recipients were reversed, as were 11 of 13 (85%) heart transplant rejection episodes. Only one of five pancreas transplant episodes were reversed. OKT3 was used prophylactically in 18 transplant recipients (13 kidney, four heart, one liver). Immunologic monitoring (lymphocyte subsets, serum OKT3 levels, and antimurine antibodies) was performed during and after OKT3 therapy. Antimurine antibody formation rate was 28% (26 of 94 patients monitored). OKT3 therapy resulted in a rapid depletion of CD3+ cells from the peripheral circulation (less than 20/mm3) and trough serum OKT3 levels of greater than 800 ng/ml by the third day of therapy in all transplant types. Twenty-three patients (14 kidney, five liver, three heart, and one pancreas) were retreated with OKT3; reversal of rejection occurred in 87% of patients (13 of 15) with no antimurine antibodies and in 83% of patients (five of six) with a low antibody titer but did not occur in the two patients with a high antibody titer. Retreatment of patients with no anti-OKT3 antibody resulted in a depletion of CD3+ cells from the peripheral blood, but it took longer than in patients treated with OKT3 for the first time. Similarly, serum OKT3 levels increased slower in retreated patients compared with first treatment. In retreatment patients with a low titer antimurine antibody, often it was necessary to increase the dose of OKT3 to achieve adequate serum OKT3 levels and to deplete CD3+ cells. Antimurine antibody developed de novo in four of the 15 antibody negative patients (27%) who were retreated. Overall, OKT3 was an effective agent in reversing and preventing rejection in solid organ transplantation with few severe side effects and a low mortality. Retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low titer antibodies does not preclude successful retreatment with OKT3. Alternate antirejection therapy, however, should be used in patients with high titer antimurine responses.
Antibodies, Anti-Idiotypic↗
Efficacy and safety of constant-rate intravenous cyclosporine infusion immediately after heart transplantation.
Oral cyclosporine therapy immediately after heart transplantation is erratic and difficult to predict. The purpose of this study was to evaluate the relative efficacy and safety of cyclosporine when administered by constant-rate infusion immediately after transplantation. Nineteen patients (17 men and two women) aged 50 years (range 25 to 61 years) who weighed 71 +/- 9 kg, participated in the study and received cyclosporine, 7 to 10 mg/hr (117 +/- 15 micrograms/kg/hr). The infusions were initially maintained for 26 +/- 5 hours (range 18 to 42 hours) without adjustments in dosage. Whole blood samples were obtained at hourly intervals for the first 8 to 12 hours and then daily throughout the 7-day study period and were analyzed by high-performance liquid chromatography. Constant-rate cyclosporine infusion resulted in therapeutic blood levels (350 to 450 ng/ml) at 6 hours. These levels remained relatively steady throughout the 7-day infusion, requiring only minimal dosage adjustments. Kidney function was not altered significantly after 7 days of intravenous cyclosporine therapy as evidenced by a mean serum creatinine level of 1.3 mg/dl before therapy and 1.4 mg/dl after therapy. There, however, was a transient rise in serum creatinine level in most patients on the second or third day after transplantation that resolved without a reduction in cyclosporine dosage. The mean endomyocardial biopsy score at 1 week after transplantation was 0.1, and only four of the patients required additional immunosuppressive therapy to treat rejection during the first 6 weeks after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Use of cyclosporine and ketoconazole without nephrotoxicity in two heart transplant recipients.
A cyclosporine-ketoconazole drug interaction was first described in 1981. It has been suggested that the two drugs should not be used concomitantly because of the danger of severe nephrotoxicity. Two reported cases indicate that cyclosporine and ketoconazole can be safely coadministered, provided that the dosage of cyclosporine is reduced appropriately. Two patients were initially given 8 mg/kg/day of cyclosporine at the time of heart transplantation, and the dosage was tapered to meet appropriate blood levels (250 to 350 ng/ml by whole blood high-performance liquid chromatography). During ketoconazole therapy (400 mg daily for 4 weeks), patient 1 received 80 to 100 mg/day of cyclosporine, which is equal to approximately 1 mg/kg/day, and patient 2 received between 40 and 80 mg/day of cyclosporine, which is equivalent to 0.4 to 0.8 mg/kg/day. Neither patient exhibited a creatinine value above 1.4 mg/dl while on combined therapy, and there were no problems with allograft rejection. Both patients had inappropriately high cyclosporine blood levels even with this marked reduction in dosage (patient 1, 520 to 1310 ng/ml and patient 2, 320 to 600 ng/ml). Thus it appears that cyclosporine and ketoconazole can be administered together safely, provided that there is an appropriate reduction in the dosage of cyclosporine; this results in the maintenance of adequate immunosuppression without development of nephrotoxicity.
Cyclosporins↗
Coupling of skeletal muscle to a prosthesis for circulatory support.
A durable bond between the end of skeletal muscles and prosthetic structures could, with appropriate linkage, allow circulatory support power by synchronous and/or sequential contraction of several in situ conditioned muscles. Potential advantages relative to a myoplasty wrap involve 1) less traumatic dissection, 2) efficient linear force development, 3) selectable contraction rate, 4) greater stroke work, 5) independent control of muscle pre-load and end diastolic pressure, and 6) independent control of duration of muscle tension and ejection time. However, no existing means of tissue-prosthetic bonding appears adequate. Practicality would demand that full tension bearing capacity by the bond take no longer than muscle conditioning. A prosthesis was developed to achieve those goals. As scaled for this study, it is made of 7,200-7,800 unspun, unplaited, 22 to 26 microns diameter polyester fibers swaged into four taper needles for weaving through distal muscle. The other end is formed into a polyurethane sheathed kernmantel cord for distal fixation. Devices were implanted in six 3 to 4 kg rabbits (unilateral posterior tibial tendon replacement, random side selection with contralateral dissection/closure controls), and their tensile strength was tested at 30 days. All healed well; leg movements were normal after 1 week. Limbs were frozen at -70 degrees C between death and testing. Control failure occurred at 243 +/- 94 N and experimental at 163 +/- 44 N (p = 0.065, t-test); highest estimated requirement was 17.2 N. Interface strength was adequate by 30 days. Continued investigations, addressing other questions, are warranted.
Achilles Tendon↗