Care for the organ transplant recipient on the intensive care unit.

All transplant recipients receive tacrolimus, mycophenolate and glucocorticoids and these drugs have many side-effects and drug-drug interactions. Common complications include surgical complications, infections, rejection and acute kidney injury. Infections as CMV and PJP can be prevented with prophylactic treatment. Given the complexity of organ transplant recipients a multi-disciplinary team of intensivists, surgeons, pharmacists and transplant specialists is essential. After heart transplantation a temporary pacemaker is required until the conduction system recovers. Stiffening of the heart and increased cardiac markers indicate rejection. An endomyocardial biopsy is performed via the right jugular vein, necessitating its preservation. For lung transplant patients, early intervention for aspiration is warranted to prevent chronic rejection. Risk of any infection is high, requiring active surveillance and intensive treatment, mainly of fungal infections. The liver is immunotolerant requiring lower immunosuppression. Transplantation surgery is often accompanied by massive blood loss and coagulopathy. Other complications include portal vein or hepatic artery thrombosis and biliary leakage or stenosis. Kidney transplant recipients have a high risk of cardiovascular disease and posttransplant anemia should be treated liberally. After postmortal transplantation, delayed graft function is common and dialysis is continued. Ureteral anastomosis complications can be diagnosed with ultrasound.

C57BL/6 NK cell gene complex is crucially involved in vascular remodeling.

OBJECTIVE: NK cells are known to be involved in cardiovascular disease processes. One of these processes, vascular remodeling, may strongly differ between individuals and mouse strains such as the C57BL/6 and BALB/c. Moreover, C57BL/6 and BALB/c mice vary in immune responses and in the composition of their Natural Killer gene Complex (NKC). Here we study the role of NK cells, and in particular the C57BL/6 NKC in vascular remodeling and intimal hyperplasia formation. METHODS AND RESULTS: C57BL/6, BALB/c and CMV1(r) mice, a BALB/c strain congenic for the C57BL/6 NKC, were used in an injury induced cuff model and a vein graft model. NK cell depleted C57BL/6 mice demonstrated a 43% reduction in intimal hyperplasia after femoral artery cuff placement compared to control C57BL/6 mice (p<0.05). Cuff placement and vein grafting resulted in profound intimal hyperplasia in C57BL/6 mice, but also in CMV1(r) mice, whereas this was significantly less in BALB/c mice. Significant more leukocyte infiltrations and IFN-γ staining were seen in both C57BL/6 and CMV1(r) vein grafts compared to BALB/c vein grafts. CONCLUSIONS: These data demonstrate an important role for NK cells in intimal hyperplasia and vascular remodeling. Furthermore, the C57BL/6 NKC in CMV1(r) mice stimulates vascular remodeling most likely through the activation of (IFN-γ-secreting) NK-cells that modulate the outcome of vascular remodeling.

Variations in surgical procedures for hind limb ischaemia mouse models result in differences in collateral formation.

OBJECTIVE: To identify the optimal mouse model for hind limb ischaemia, which offers a therapeutic window that is large enough to detect improvements of blood flow recovery, for example, using cell therapies. MATERIALS AND METHODS: Different surgical approaches were performed: single coagulation of femoral and iliac artery, total excision of femoral artery and double coagulation of femoral and iliac artery. Blood flow restoration was analysed with laser Doppler perfusion imaging (LDPI). Immuno-histochemical stainings, angiography and micro-computed tomography (CT) scans were performed for visualisation of collaterals in the mouse. RESULTS: Significant differences in flow restoration were observed depending on the surgical procedure. After single coagulation, blood flow already restored 100% in 7 days, in contrast to a significant delayed flow restoration after double coagulation (54% after 28 days, P<0.001). After total excision, blood flow was 100% recovered within 28 days. Compared with total excision, double coagulation displayed more pronounced corkscrew phenotype of the vessels typical for collateral arteries on angiographs. CONCLUSION: The extent of the arterial injury is associated with different patterns of perfusion restoration. The double coagulation mouse model is, in our hands, the best model for studying new therapeutic approaches as it offers a therapeutic window in which improvements can be monitored efficiently.

Natural killer cells and CD4+ T-cells modulate collateral artery development.

OBJECTIVE: The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. METHODS AND RESULTS: Lymphocytes, detected with markers for NK1.1, CD3, and CD4, invaded the collateral vessel wall. Arteriogenesis was impaired in C57BL/6 mice depleted for Natural Killer (NK)-cells by anti-NK1.1 antibodies and in NK-cell-deficient transgenic mice. Arteriogenesis was, however, unaffected in J alpha281-knockout mice that lack NK1.1+ Natural Killer T (NKT)-cells, indicating that NK-cells, rather than NKT-cells, are involved in arteriogenesis. Furthermore, arteriogenesis was impaired in C57BL/6 mice depleted for CD4+ T-lymphocytes by anti-CD4 antibodies, and in major histocompatibility complex (MHC)-class-II-deficient mice that more selectively lack mature peripheral CD4+ T-lymphocytes. This impairment was even more profound in anti-NK1.1-treated MHC-class-II-deficient mice that lack both NK- and CD4+ T-lymphocytes. Finally, collateral growth was severely reduced in BALB/c as compared with C57BL/6 mice, 2 strains with different bias in immune responsiveness. CONCLUSIONS: These data show that both NK-cells and CD4+ T-cells modulate arteriogenesis. Promoting lymphocyte activation may represent a promising method to treat ischemic disease.

Assessment of ventricular diastolic function in AIDS patients from Congo: a Doppler echocardiographic study.

OBJECTIVE: To investigate the prevalence of left ventricular dysfunction in African patients infected with the human immunodeficiency virus (HIV). The hypothesis was that HIV infected patients with left ventricular dysfunction are asymptomatic. METHODS: M mode, cross sectional, and Doppler echocardiography were performed in 49 consecutive patients (30 HIV positive (HIV+) carriers and 19 AIDS patients). None of the patients or 58 controls had a medical history of cardiovascular abnormalities. RESULTS: Cardiac abnormalities were not suspected on physical, electrocardiographic, and radiological examination. Forty-two of the HIV infected patients had left ventricular diastolic dysfunction; this was more pronounced in AIDS patients than in HIV+ carriers. Systolic function was normal in both stages of HIV infection. Left ventricular isovolumic relaxation time (mean SD)) increased from 87.2 (12.4) ms in the carrier state to 103.9 (19.3) ms in AIDS (p < 0.05, Bonferoni correction), peak early filling velocity declined from 0.54 (0.1) to 0.44 (0.1) m/s (p < 0.05), and late velocity increased from 0.64 (0.1) to 0.69 (0.2) m/s. A restrictive filling pattern was explained by concentric hypertrophy in 23 HIV infected patients, and by systemic amyloidosis with left ventricular dilatation in 12 of 49 HIV infected patients. CONCLUSIONS: Echocardiography is a useful technique for detecting left ventricular diastolic dysfunction in HIV infected patients with clinically unsuspected cardiac lesions. Systolic function was normal despite the presence of such cardiac abnormalities.