Transplantation in end-stage heart failure

The benefits and limitations of cardiac transplantation as a treatment option are presented. Also discussed are the phases of the transplant process and pertinent nursing interventions. Advances in immunosuppressive drugs and patient management are highlighted, and long-term considerations and possible advances for the future are presented.     

Chronic end-stage kidney failure in Mexico

It has been previously reported that in 2 C57BL mouse sublines a dark pigmentation of the cranial part of the spleen occurs in up to 30% of the animals within the populations. It was not clear whether this discoloration is caused by melanosis, lipofuscinosis or haemosiderosis. With the use of light and electron microscopy of stained spleen sections, we identified the pigment in 14 out of 60 C57BL mice aged 8-10 wks. In the mice with pigmented spleens there was accumulation of melanin, predominantly in melanophores. Literature data indicate that apart from melanin, lipofuscin and haemosiderin can be observed in splenic macrophages provided that the mice are older than those studied by us. We conclude that melanin is the principal pigment causing spleen discoloration in young C57BL mice. Splenic melanosis displays inter-individual variation, but its relevance from a pathophysiological point of view remains obscure.     

Cardiac surgery in patients with end-stage renal failure

End-stage renal failure is commonly considered a significant factor for an increased risk after coronary artery bypass grafting. This holds true for patients who have received a kidney transplant (NTX group) as well as for patients who require chronic hemodialysis (HD group). To assess the risk in our population we performed a retrospective analysis of 22 patients with end-stage renal failure (HD group: 17, NTX group: 5) who underwent cardiac surgery. The perioperative course was compared to a normal population. In addition to standard data we assessed the following factors: renal failure etiology, risk factors, concurrent diseases, duration of renal failure, function of renal graft, ECG (paying special attention to signs of previous myocardial infarctions and rhythm disorders), results of cardiac catheterization and coronary angiography, NYHA class and urgency of operative intervention. Complications and mortality were the main measures of the perioperative course. We analyzed the hospital charts retrospectively and requested the patients' physicians to complete a questionnaire about the patient's present condition. All HD group patients were dialyzed on the day before surgery. The first postoperative HD was performed for hyperkalemia or signs of volume overload (pulmonary capillary wedge pressure > 20 mmHg) when signs of pulmonary function deterioration were seen. HD was successful in treating these conditions. 3 of the 17 patients on HD expired postoperatively, 4 died within 3 years, all of unrelated diseases. Mortality and morbidity was 0% in the NTX group. In one NTX patient who required intermittent HD preoperatively because of poor renal graft function, renal function improved postoperatively, presumably secondary to better renal perfusion, and he did not require HD after his cardiac surgery. By surgical intervention the NYHA class of all patients improved (by 1.6 on the average) as well as their quality of life. Because of these good short- and long-term results and relatively low operative risk we support an approach of prompt work-up and surgical intervention when necessary in HD and NTX patients.     

Amiodarone in cardiac failure

Several epidemiological studies suggest that exposure to ultraviolet radiation and immunological responsiveness of the host contribute to the etiology of melanoma. In addition, a growing experimental evidence indicates a stimulant effect of ultraviolet radiation and a high immunogenicity of melanocytic tumors. These findings lead to the hypothesis of an ultraviolet-induced alteration of the immune response that decreases the host-resistance to melanoma antigens.     

Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans

OBJECTIVES: The present investigation was designed to evaluate the growth reserve capacity of the aged and senescent myocardium. BACKGROUND: Aging affects the ability of the heart to sustain alterations in ventricular loading, and this phenomenon may be coupled with attenuation of the hypertrophic reaction of the myocardium. However, because myocyte cellular hyperplasia has been documented experimentally in the old heart, a similar adaptation may also occur in humans and play a role in this process. METHODS: The changes in number and size of ventricular myocytes were measured quantitatively in pathologic hearts of elderly subjects. Morphometric methodologies were applied to the analysis of 13 hypertrophic hearts obtained at autopsy from patients 80 +/- 4 (mean +/- SD) years old. An identical number of nonhypertrophic hearts collected from subjects 76 +/- 7 years old were used as control hearts. RESULTS: A 71% increase in left ventricular weight was associated with a 33% increase in average myocyte cell volume per nucleus and a 36% augmentation in the total number of myocyte nuclei in the ventricular myocardium. However, a 55% increase in right ventricular weight was the result of a 59% increase in the aggregate number of myocyte nuclei, with no change in myocyte cell volume. These cellular processes were associated with a 95% and 83% enlargement of the myocardial interstitium in the left and right ventricle, respectively. CONCLUSIONS: Myocyte nuclear and possibly cellular hyperplasia appear to be the prevailing growth mechanism of the overloaded aging myocardium. Proliferation of myocyte nuclei and connective tissue accumulation are the major determinants of ventricular remodeling in the hypertrophic senescent heart.     

Treatment of end-stage renal failure after heart transplantation

BACKGROUND: Five to 10% of heart-transplant recipients develop end-stage renal failure (ESRF). Little is known about the outcome of these patients under renal replacement therapy. METHODS: We conducted a retrospective study in 16 men (mean age 52.8+/-7.4 years at heart transplantation) who developed ESRF 5.3+/-2.1 years later. Results. Haemodialysis (HD) was the first-line treatment (mean Kt/V 1.35+/-0.4). Vascular access was unsuccessful in six patients (37.5%) due to peripheral arteriopathy and they were treated with tunnelled catheters for an average 15 months without bacterial infection. Mean weight was 68.4+/-10 kg at onset of HD and 61.7+/-9 kg one month later. Despite this reduction in extracellular overload, one antihypertensive drug was required in 75% of patients and two drugs in 12.5%. One patient tolerated automated peritoneal dialysis (PD) for 16 months (weekly Kt/V 2.1) despite persistent anuria. Renal transplantation (RT) was contraindicated in eight patients because of aortoiliac arteriopathy (n=5), poor general status (n=2), or ischaemic heart disease (n=1). RT was performed in eight patients with no acute episode of heart or renal graft rejection. There were no serious infectious complications. Three months after RT, mean serum creatinine was 115 micromol/l. One patient developed post-transplant lymphoproliferative disorder 3.5 months after RT and was successfully treated with transplant nephrectomy. Sudden death occurred in two patients 18 and 33 months after RT. Overall patient survival was 100, 78, and 59%, 1, 2 and 3 years after HD onset respectively. Using a time-dependent variable, the Cox model analysis demonstrated that heart-transplant recipients with ESRF have a relative risk of death 3.2 times higher than those without ESRF (95% CI = 1.3-7.8). CONCLUSIONS: HD, PD, and RT can be useful for the treatment of ESRF after heart transplantation. After initiating HD, patient survival is nearly the same as that reported in patients in Europe undergoing HD for other causes. But ESRF seems to reduce life expectancy in heart-transplant recipients.     

Advantages of epidural anesthesia in patients with end-stage chronic renal failure

The authors analyze the experience gained in anesthesiological management of 667 surgeries in patients with the end-stage chronic renal failure. 206 patients were operated on under epidural anesthesia and 461 under general anesthesia. The technique of anesthesia, preparation of patients, and the management during and after surgery are described. 63 hemodialysis procedures were performed for 4 h before and 154 for 12 h after surgery. The complications occurring during and after anesthesia by both methods are analyzed. Epidural anesthesia was found to be more safe for patients with the end-stage chronic renal failure. General anesthesia more often led to hemodynamic, respiratory, metabolic disorders, and other hemostasis disturbances.     

Cytokine profile in chronic cardiac failure

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.     

Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure

Long-term administration of prostacyclin (PGI2) improves the hemodynamic state, symptoms, and survival in patients with primary pulmonary hypertension, but it increases mortality in patients with heart failure despite obvious hemodynamic benefits when it is given acutely. We evaluated the mechanisms of action of PGI2 in patients with heart failure and secondary pulmonary hypertension. Nineteen patients with end-stage heart failure and pulmonary hypertension, all candidates for heart transplantation, underwent right- and left sided cardiac catheterization with micromanometer-tipped catheters and were tested for PGI2 at incremental doses. PGI2 infusion significantly improved pulmonary hemodynamics with a 47% reduction in pulmonary vascular resistance (p=0.0003) and a doubling of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary vascular tone. The dose of PGI2 necessary to reach this hemodynamic effect correlated significantly to the baseline severity of pulmonary artery compliance (r=0.54, p=0.01). Furthermore, PGI2 produced a significant positive inotropic effect (contractile element maximum velocity increased from 1.10+/-0.09 to 1.33+/-0.13 circ/s, p <0.009). The hemodynamic effects of PGI2 infusion were independent of the plasma and urinary levels of endogen prostaglandins. Thus, PGI2 at therapeutic doses exerts a positive inotropic effect in patients with heart failure, which may explain the increased mortality rate observed with the long-term use of PGI2 in this type of patient. The spectacular acute benefits on right ventricular afterload, however, may be useful in unstable patients with heart failure and secondary pulmonary hypertension or in transplanted patients with acute right ventricular failure of the donor heart.     

Mechanisms of cardiac failure]

Heart failure is defined as the inability of the heart to deliver a cardiac output sufficient for the needs of the periphery. The mechanisms responsible for ventricular failure always correspond for changes in ventricular filling that may have 2 origins: decrease in ventricular systolic function, leading the ventricle to operate on the vertical part of its pressure volume relationship; primary decrease in ventricular distensibility. An increase neurohormonal stimulation participates in sodium retention and in the preservation of blood pressure. The mechanisms leading to the progressive alteration of the haemodynamic status are not perfectly known, but a progressive increase in wall stress and myocyte loss are likely to occur.     

Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure

OBJECTIVES: The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF). BACKGROUND: Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance. METHODS: Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170+/-37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract. RESULTS: The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7+/-0.7 vs. 2+/-0.5 and 2.4+/-0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22+/-8 vs. 27+/-9 mm Hg; p < 0.001). CONCLUSIONS: This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.     

Myocyte cell death in the diseased heart

We examined the antipruritic effects of various oleanolic acid glycosides from natural medicines such as Kochiae Fructus (the fruit of Kochia scoparia SCHRAD.) and Momordicae Radix (the roots of Momordica cochinchinensis SPRENG.) using a compound 48/80-induced pruritic model in mice. Oleanolic acid 3-O-monodesmosides showed an antipruritic effect, while oleanolic acid 3,28-O-bisdesmosides and their common sapogenol oleanolic acid lacked the activity. This evidence indicated that the 3-O-glycoside moiety and the 28-carboxyl group in oleanolic acid glycosides were essential for exhibiting the antipruritic effect. Furthermore, it was found that the 3-O-glucuronides showed more potent activity than the corresponding 3-O-glucosides.     

Recovery of cardiac function by long-term left ventricular support in patients with end-stage cardiomyopathy

Effects of long-term left ventricular (LV) support on end-stage cardiomyopathy patients is unclear. We applied our LV assist system (LVAS) to six heart transplant candidates, aged 17 to 49, with dilated cardiomyopathy, including one dilated phase hypertrophied cardiomyopathy. LVAS was installed between the left atrium and the ascending aorta, and the pump was positioned parecorporeally. In all patients, their general condition improved, and their pump flows were kept at 4 to 5 L/min. Exercise was started after stabilization of their general condition under constant pump flow. Natural heart size and function were examined by echocardiography. In the beginning of assist, all patients showed impaired cardiac function and LV dilation. During LV assist, systolic function measured by ejection time improved in all patients. Left ventricular end-diastolic dimension (LVDd), showed a remarkable decrease in two patients, who were weaned from LVAS after 3 months of support. They are doing well more than 1 year and 3 years after removal; peak VO2 levels (ml/min/kg) were 30 at 1.2 years and 27 at 2.7 years after removal. In the other four patients, however, LVDd had no remarkable changes, and three could not be weaned from LVAS. The last was discontinued from LVAS after 5 months of support because of infection and died 2 months after removal. From this experience, long-term LVAS may provide the chance for recovery of the natural heart in patients with end-stage cardiomyopathy. The patients whose hearts showed remodeling were able to be weaned from LVAS, and their heart function maintained in good condition for several years.     

Methodological findings and considerations in measuring colorectal epithelial cell proliferation in humans

The methodological issues for measuring colorectal epithelial cell proliferation, an intermediate end point for studies of colon neoplasia, in epidemiological studies are deceptively numerous and complex, with few methodological data available. Accordingly, during our experience with measuring colorectal epithelial cell proliferation from nearly 500 participants attending over 1300 study visits over a 6-year period, we recorded data on a variety of measurement variations. Methods investigated included rectal biopsy technique, general histological and labeling procedures [including the tritiated thymidine, 5-bromodeoxyuridine (BrdUrd), and the proliferating cell nuclear antigen (PCNA) immunohistochemical techniques used to label S-phase cells in colonic crypts in rectal biopsy specimens], biopsy scoring procedures, and summary scoring methods. Findings include that the PCNA technique was the simplest, most economical, and least time-consuming. The BrdUrd labeling failure rate was 15% versus < 1% for PCNA. The percentage of labeled cells (labeling index) was highest using PCNA in biopsies processed without prior incubation, intermediate using PCNA in biopsies processed with prior incubation as for BrdUrd, and lowest using BrdUrd. The percentage of labeled cells that were in the upper 40% of the crypt (phi h) was higher using BrdUrd than PCNA; visit-to-visit correlations were higher using PCNA (r = 0.51 versus 0.35), and visit-to-visit variability was lower and between-person variability was higher using PCNA. Intra- and inter-rater reliabilities for the techniques were comparable (PCNA intra-rater r = 0.93, inter-rater r = 0.92). The PCNA technique, compared to the BrdUrd technique, is more feasible and reliable, provides a more accurate estimate of the labeling index, and cell proliferation measures determined with PCNA have statistical properties that are generally more favorable for detecting differences in clinical trials. Thus, the PCNA technique may be preferable to techniques requiring incubation of biopsies. Other methodological findings lead us to recommend that, for larger studies measuring colorectal epithelial cell proliferation on outpatient rectal biopsies, biopsies should be taken 10 cm above the anus using a flexible, preferably jumbo cup, endoscopic forceps through a rigid sigmoidoscope, and histological sections should be 3 microns thick taken 50 microns apart.