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Biomedical subjects

J G Copeland

Publications and source records attributed to J G Copeland.

At least 19 recordsLinked to original sources

Left ventricular function after extended hypothermic preservation of the heart is dependent on functional coronary capillarity.

BACKGROUND: A growing body of knowledge has led to the hypothesis that injury to the microcirculation during hypothermic myocardial preservation may result in decreased contractility of hearts upon reperfusion. METHODS AND RESULTS: To test this hypothesis, we examined the relationship between no-reflow and left ventricular function after hypothermic cardiac preservation after reperfusion with solutions containing dilute whole blood (DWB) or washed red blood cells (K2RBC). Rat hearts were arrested with high-potassium cardioplegia, then flushed and stored for 6 hours in low-potassium cardioplegia at 4 degrees C. Hearts were reperfused at a constant flow rate (4 mL/min) with K2RBC for 60 minutes (group 1, n = 5) or DWB for 7 minutes followed by 53 minutes of K2RBC (group 2, n = 5). Left ventricular developed pressure (LVDP) was measured with an intraventricular balloon. Immediately after functional assessment, hearts were perfused with an india ink solution to mark flow, then glutaraldehyde. Morphometric techniques were used to determine the degree of capillary compression [delta d(c)], perfused capillary number per fiber area [QA(0)P], and perfused capillary surface area per fiber volume [Sv(c,f)P]. Capillaries were moderately compressed in both groups after reperfusion (group 1, 19 +/- 1%; group 2, 20 +/- 1%). QA(0)P and Sv(c,f)P were highly correlated with delta d(c) in hearts reperfused with K2RBC (r = .92 and r = .92; P < .01). Although statistically significant, the correlation was not as strong in DWB-reperfused hearts (r = .66 and r = .67; P < .05). LVDP was correlated to QA(0)P and Sv(c,f)P (r = .86 and r = .87, respectively) for groups 1 and 2. CONCLUSIONS: The weaker correlation between capillary perfusion and capillary compression in DWB-reperfused hearts suggests that factors other than compression contribute to no-reflow after hypothermic preservation. Regardless of the composition of the reperfusate, recovery of left ventricular function after hypothermic ischemia is directly related to coronary capillary perfusion upon reperfusion.

Animals

Peripheral vascular disease in heart transplant recipients.

The improved longevity of heart transplant recipients demands heightened awareness of the long-term complications of the procedure. Between 1979 and 1990, 232 patients received 241 heart transplants at our institution. Accelerated coronary atherosclerosis occurred in 45 (19%) of the 232 patients, typically appearing within 2 years of transplantation, whereas peripheral vascular disease (PVD) appeared in 23 (10%) of the 232 patients, usually within 3 years of transplantation. In the patients with PVD, 13 had occlusive disease, nine had aneurysms, and one patient suffered a vertebral artery dissection. Accelerated coronary atherosclerosis afflicted 12 (52%) of the 23 patients affected by PVD (p < 0.05) and preceded the development of PVD in all 12. Logistic regression analysis revealed risk factors predictive of the development of PVD after transplantation to be a pretransplant history of ischemic cardiomyopathy and posttransplant hypertension and hypertriglyceridemia (p < 0.05), with the presence of more than one risk factor increasing the probability of development of PVD. Those patients thus identified as at risk should be closely monitored for the development of PVD. Aggressive medical management of hypertension and hyperlipidemia in this subpopulation may forestall or prevent the development of peripheral vascular disease after heart transplantation.

Adult

Lipid peroxidation results in compromised functional recovery of isolated rabbit hearts after low-pressure, hypothermic, perfused preservation for 24 hours.

Low-pressure, hypothermic perfusion of isolated rabbit hearts for 24 hours compromises contractile function. This occurs despite continuous recirculation of an oxygenated solution. This investigation tested the hypothesis that such functional impairment results from irreversible tissue damage consequent to ischemia-induced lipid peroxidation. Decreases in coronary flow were measured during preservation and related to concentrations of thiobarbituric acid reactive species (TBA+, primarily malondialdehyde, a by-product of lipid peroxidation) in the tissue after preservation. The concentration of TBA+ species and the percent decrease in coronary flow rates at 30 minutes and 24 hours were positively correlated (r = 0.591 and r = 0.646, respectively). India ink was used as a marker of microvascular perfusion. Hearts showing the greatest magnitude of ischemia (evidenced by decreased percentages of perfused microvessels) had the highest levels of TBA+ species (r = 0.924). Moreover, hearts that had the highest levels of TBA+ species in the tissue exhibited the lowest levels of left ventricular function (as measured on a modified Langendorff apparatus; r = 0.767). We conclude that impaired coronary flow rates during perfused preservation portend compromised myocardial contractility. Furthermore, these changes occur largely within the first 30 minutes of perfusion. It is likely that early decrements in microvascular perfusion and consequent tissue injury owing to lipid peroxidation underlie impaired myocardial function after preservation.

Animals

Futility of yearly heart biopsies in patients undergoing heart transplantation.

Three hundred thirty-eight endomyocardial biopsies, performed as part of the routine annual evaluation at 1 or more years after transplantation in 211 patients, were reviewed. In only two instances (0.6%) were the histologic findings suggestive, but not pathognomonic, of acute rejection. Both patients were treated for rejection and are doing well at 4 and 6 years postoperatively. On the basis of the results of this study, we believe that routine yearly heart biopsies in asymptomatic patients are not necessary for long-term care of patients after heart transplantation, and we believe they should be performed only if there is clinical suspicion of rejection or as part of a research protocol.

Actuarial Analysis

Mitral valve replacement six years after cardiac transplantation.

A 33-year-old man found to have increasing mitral regurgitation and decreasing exercise tolerance 6 years after cardiac transplantation received a mitral bioprosthesis. For 8 months he has been without complications from the valve replacement and is clinically and hemodynamically considerably improved.

Adult

Long-term bridge to transplantation with the Symbion acute ventricular assist device system.

A 48-year-old man was supported for 164 days with Symbion biventricular assist devices. During that time, his cytotoxic antibody screen fell from 97% positivity to less than 10%, enabling cardiac transplantation. Complications during the implantation included a 3-minute episode of amaurosis fugax, one positive blood culture, and anemia, which responded to decreased frequency of blood drawing. He is now alive 7 months after transplantation.

Coronary Artery Bypass

Pneumocystis carinii pneumonia after heart transplantation.

Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation.

Adolescent

Comparison of postoperative complications between saphenous vein and IMA grafts to left anterior descending coronary artery.

Considerable controversy exists regarding relative morbidity associated with the saphenous vein graft (SVG) and internal mammary artery (IMA) graft in patients undergoing myocardial revascularization. As a part of the cooperative study on use of antiplatelet drugs for graft patency, operative and postoperative data were prospectively collected on 1,150 patients who underwent either SVG (n = 656) or IMA anastomosis (n = 494) to the left anterior descending coronary artery. There were no differences in baseline characteristics of patients, distribution of randomization among treatment groups, and total number of distal anastomoses performed between the two groups. The aortic cross-clamp time, cardiopulmonary bypass duration, operative time, and chest tube drainage were greater (p = 0.0001) in the patients with IMA grafts compared with SVG. However, there was no difference in the operative mortality rate, the amount of blood and blood products received, the reoperation rate for control of postoperative bleeding, and incidence of wound complications between the two groups. The early and 1-year patency rates for the IMA were slightly but not significantly better than the SVG patency rates (92.8% versus 90.1% for 1-year patency; p = 0.309). In conclusion, use of IMA is associated with a longer operative time as well as increased postoperative bleeding compared with the SVG. It, however, does not increase operative mortality or postoperative morbidity.

Aged

Acoustic analysis of the closing sounds of bileaflet prosthetic valves in a sheep model.

Previous investigations of mechanical valve sounds have shown that (1) frequency spectra of sounds produced by abnormal valves differ from those of properly functioning valves and (2) leaflets of normally functioning bileaflet valves do not close synchronously. This investigation studied effects of mechanical valve size, environment, and hemodynamic state on closing sounds. A single 25 mm bileaflet mitral mechanical valve was implanted in six sheep and a single 27 mm valve in four sheep. With digital signal processing, asynchronous leaflet closure and frequency spectra were assessed after alterations in animal position, respiratory phase, heart rate, afterload, contractility, and preload. Both asynchronous leaflet closure and frequency spectra varied among animals, and, except for a decrease in asynchrony with increasing contractility, were largely independent of valve size and hemodynamics. Baseline asynchrony ranged from 0.5 to 4.2 msec. Frequency spectra were characterized by the first three resonant peaks. Lowest resonant peaks ranged from 2.5 to 3.4 kHz, middle from 4.7 to 6.8 kHz, and highest from 7.2 to 9.6 kHz. These results indicate that accurate assessment of mechanical valve function with acoustic analysis requires baseline studies in all patients by means of a system with a frequency response of more than 10 kHz.

Animals

One heart, two bodies: insight from the transplanted heart and its new electrocardiogram.

Cardiac transplantation provides a unique opportunity to record the electric field generated by a human heart in a new somatic environment. By examining pre- and posttransplantation electrocardiograms (ECGs), it is possible to address questions on the effect of rotation of the heart on its long axis on the surface ECG, the effect of thoracic anatomy on ECG voltage and predisposing factors for conduction defects observed after transplant surgery. To examine these questions, we reviewed a series of 35 matched donor and recipient ECGs. There were no differences in the mean height of the donors and recipients, but age, weight and body surface area were higher in the recipients (p less than 0.025). We found no significant differences in the mean heart rate or precordial voltage but the PR and QT intervals were shorter (p less than 0.025), and the precordial transitional zone was more to the left after transplantation (p less than 0.0005). New evidence of right bundle branch delay was found in 11 recipients and this was not related to pretransplantation hemodynamic factors or the period of ischemic arrest. Thus, there is indeed an anatomic basis for the ECG determination of clockwise rotation of the heart when the precordial transition zone is to the left. Age and body habitus, per se, do not appear to affect precordial voltage and evidence of right bundle delay in the transplant recipient appears to be related to the altered position of the heart and not to injury or changes in right ventricular hemodynamics.

Adolescent

Successful coronary artery bypass grafting for high-risk left main coronary artery atherosclerosis after cardiac transplantation.

Severe stenosis of the left main coronary artery developed in a 58-year-old woman 9 years after orthotopic heart transplantation. Because of serious reversible myocardial ischemia and the high-risk nature of the coronary disease, coronary artery bypass grafting was performed, with no complications. Possible risk factors for the development of coronary arterial disease and its management in the transplant population are discussed.

Coronary Artery Bypass

Bromocriptine as an adjuvant to cyclosporine immunosuppression after heart transplantation.

Prolactin, a pituitary hormone, has been shown to have an active role in the regulation of the immune system. Prolactin receptors have been described on the membrane of lymphocyte cells, and competitive binding to these receptors by cyclosporine and circulating prolactin has been demonstrated. Experimental evidence suggests a synergistic effect of cyclosporine and bromocriptine, an inhibitor of pituitary release of prolactin, on immunosuppression. Between July 1986 and January 1988, 54 patients were randomly assigned to two groups of immunosuppression treatment. Thirty patients (group 1) were administered cyclosporine, azathioprine, and prednisone and 24 patients (group 2), a modified protocol aimed at decreasing the level of circulating prolactin by adding bromocriptine to the immunosuppression regimen. The two groups were similar in regard to age, preoperative diagnosis, and duration of follow-up. Minimal side effects related to bromocriptine were observed. The overall incidences of rejection and infection were similar, although actuarial analysis showed that freedom from these complications among patients treated with bromocriptine was significantly higher throughout the first 2 months after heart transplantation compared with that of patients in the control group. Other variables such as serum cyclosporine levels and lymphocyte counts were similar in both groups. In conclusion, suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine, at least during the early postoperative period when the risk of rejection and infection is higher, and could be a promising avenue to successful hormonal manipulations of the immune process after organ transplantation.

Actuarial Analysis

Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grafting. Department of Veterans Affairs Cooperative Study on Antiplatelet Therapy.

The perioperative consequences of preoperative aspirin administration were assessed in a large prospective cooperative study of 772 patients undergoing coronary artery bypass grafting. The 772 patients were randomized to receive either aspirin (325 mg once a day), aspirin (325 mg three times a day), aspirin plus dipyridamole (325 and 75 mg together three times a day) (aspirin group), sulfinpyrazone (267 mg three times a day) or placebo (nonaspirin group). The therapy, except in the aspirin group, was started 48 h before the operation. In all aspirin subgroups, one 325 mg aspirin dose was given 12 h before surgery and maintained thereafter according to the assigned regimen. Patients in the aspirin group had significantly more postoperative bleeding and received more packed blood cells and blood products than did patients in the nonaspirin group. Although total operative duration and cardiopulmonary bypass duration were not different, the interval between completion of cardiopulmonary bypass and wound closure was significantly longer (p = 0.035) in the aspirin group. Thirty-one (6.6%) of 471 patients in the aspirin group and 5 (1.7%) of 301 patients in the nonaspirin group also required reoperation for control of postoperative bleeding (p = 0.002). The site of bleeding found at reoperation was not different between the two groups. There was no difference in operative mortality rates, incidence of other bleeding complications or occurrence of other post-operative complications between the two groups. Thus, antiplatelet regimens involving preoperative initiation of aspirin therapy, which has been shown to improve graft patency, increase the risk of abnormal postoperative bleeding and the need for reoperation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin

Use of the pericardial fat pad in pulmonary transplantation.

Historically, the healing of tracheal or bronchial anastomoses has been the Achilles heel in pulmonary transplantation. In the past, steps taken to enhance healing of these structures and have allowed single-lung, double-lung, and heart-lung transplantation to be accomplished safely. This report presents a simplified technique for protection of the tracheal anastomosis in heart-lung and double-lung transplantation. This technique, wherein the pericardial fat pad from the right side is utilized to wrap the tracheal anastomosis, not only allows for excellent healing of the anastomosis but separates the aorta from the trachea. In 19 patients having heart-lung (N = 13) or double-lung (N = 6) transplantation there were no tracheal healing problems, dehiscence or stenosis found.

Adipose Tissue

Hemodialysis clearance of intravenously administered ribavirin.

A patient with an implanted artificial heart, acute, anuric renal failure, and disseminated influenza virus type A infection received intravenous ribavirin. Drug elimination by hemodialysis was measured. Plasma dialysis clearance averaged 93.9 +/- 8.6 ml/min. The maximum amount of ribavirin removed from the body during one period of hemodialysis was 79.1 mg. Ribavirin is not removed in important quantities by hemodialysis.

Adult

Heart transplantation: current status.

Two hundred ninety-three patients transplanted between March 1979 and October 1990 are reviewed. A comparison of survival curves suggests that our current triple therapy results in a half-life (15 years) which is twice that anticipated with either conventional or CsA and P therapy. Rejection occurs primarily in the first 1-3 months after transplantation and with our current therapy, is rarely seen thereafter. Infection, however, continues to be a threat with an incidence of approximately 10% per year. The major threats to long-term survival appear to be graft arteriosclerosis, infection, and malignancy.

Drug Therapy, Combination