Biomedical subjects

S Boesgaard

Publications and source records attributed to S Boesgaard.

At least 19 recordsLinked to original sources

PubMed2005

Diabetes mellitus and cardiogenic shock in acute myocardial infarction.

AIMS: Cardiogenic shock is the leading cause of in-hospital mortality after acute myocardial infarction (MI). This study investigates the importance of age and preexisting diabetes mellitus on the incidence and prognosis of cardiogenic shock in a large group of consecutive patients with MI. METHODS AND RESULTS: Baseline characteristics and in-hospital complications to the infarction were prospectively recorded in 6676 patients with MI. Ten-year mortality was collected. Diabetes was present in 10.8% of the total population. A total of 443 developed cardiogenic shock with an incidence of 6.2% among nondiabetics and 10.6% among diabetics. Age, wall motion index, reinfarction, and the absence of thrombolytic treatment were significant independent predictors of mortality in patients with cardiogenic shock. Intriguingly, diabetes was not a significant predictor for short- and long-term mortality in this population. The 30-day and 5-year mortality rate was equally poor in both diabetic and nondiabetic patients with cardiogenic shock (diabetics: 30-day 63%, 5-year 91%; nondiabetics: 30-day 62%, 5-year 86%; p>0.05). CONCLUSIONS: Cardiogenic shock develops approximately twice as often among diabetics as among nondiabetic patients with acute MI. The prognosis of diabetics with cardiogenic shock is similar to the prognosis of nondiabetic patients with cardiogenic shock.

Aged↗

PubMed2004

N-terminal proBNP and mortality in hospitalised patients with heart failure and preserved vs. reduced systolic function: data from the prospective Copenhagen Hospital Heart Failure Study (CHHF).

UNLABELLED: Preserved systolic function among heart failure patients is a common finding, a fact that has only recently been fully appreciated. The aim of the present study was to examine the value of NT-proBNP to predict mortality in relation to established risk factors among consecutively hospitalised heart failure patients and secondly to characterise patients in relation to preserved and reduced systolic function. MATERIAL: At the time of admission 2230 consecutively hospitalised patients had their cardiac status evaluated through determinations of NT-proBNP, echocardiography, clinical examination and medical history. Follow-up was performed 1 year later in all patients. RESULTS: 161 patients fulfilled strict diagnostic criteria for heart failure (HF). In this subgroup of patients 1-year mortality was approximately 30% and significantly higher as compared to the remaining non-heart failure population (approx. 16%). Using univariate analysis left ventricular ejection fraction (LVEF), New York Heart Association classification (NYHA) and plasma levels of NT-proBNP all predicted mortality independently. However, regardless of systolic function, age and NYHA class, risk-stratification was provided by measurements of NT-proBNP. Having measured plasma levels of NT-proBNP, LVEF did not provide any additional prognostic information on mortality among heart failure patients (multivariate analysis). CONCLUSION: The results show that independent of LVEF, measurements of NT-proBNP add additional prognostic information. It is concluded that NT-proBNP is a strong predictor of 1-year mortality in consecutively hospitalised patients with heart failure with preserved as well as reduced systolic function.

Adult↗

PubMed2003

Cardiogenic shock complicating acute myocardial infarction; prognostic impact of early and late shock development.

AIMS: Cardiogenic shock accounts for the majority of deaths following acute myocardial infarction. The majority of outcome data on this issue are, however, derived from single hospitals, referral centers or selected patients in randomized studies. The purpose of this study was to investigate incidence, outcome and prognostic significance of cardiogenic shock in 6676 consecutive patients with acute myocardial infarction. METHODS AND RESULTS: Demographic and clinical data including the presence of cardiogenic shock were prospectively collected in 6676 non-invasively managed patients with myocardial infarction consecutively admitted to 27 different hospitals during a 2-year period. Six-year mortality data were collected in 99.9% of the population. Cardiogenic shock developed in 444 patients (6.7%). In 59% of these patients cardiogenic shock developed within 48 h, 11% developed shock during days 3 and 4 and 30% later than 4 days after the infarction. Thirty-day and 6-year mortality was 62 and 88% among shock patients compared to 9 and 45% in non-shock patients. Patients with early shock development (days 1-2) had a significantly lower 30-day mortality (45%) than those with intermediate or late shock development (>80%) (P<0.05). In 30-day survivors, survival the following years was lower than in patients without cardiogenic shock but with post-infarction heart failure. CONCLUSIONS: In this nationwide prospectively collected registry, non-invasively managed consecutive myocardial infarct patients with cardiogenic shock had an extremely reduced life expectancy. Every attempt to improve treatment, prevention and identification of patients at risk of shock development should be strongly encouraged.

Aged↗

PubMed2003

Effect of early revascularisation in cardiogenic shock complicating acute myocardial infarction. A single center experience.

BACKGROUND: Five to 10% of patients with acute myocardial infarction develop cardiogenic shock and the majority of these patients are expected to die within the first few weeks. In this study, we review our recent experience in the management of patients with cardiogenic shock complicating MI and examine the effect of early invasive revascularisation on mortality. METHODS: Thirty-six consecutive patients who developed cardiogenic shock less than 48 h after MI were retrospectively evaluated and divided into two treatment groups. One group received early invasive revascularisation (n=24) and the other group had no early invasive revascularisation, but received similar conventional intensive care medical treatment (n=12). RESULTS: Baseline characteristics and hemodynamic variables were similar in both groups. Apart from invasive revascularisation and the use of intra aortic balloon counterpulsation (IABP), treatment strategies did not differ between the two groups. Thirty-day mortality was 21% in the revascularised group of patients and 58% in the non-revascularised group (P<0.05). CONCLUSIONS: Our data support previous observations suggesting that an aggressive treatment strategy including early invasive revascularisation and IABP is associated with improved short and long-term survival in patients with cardiogenic shock. Since early revascularisation appears safe with a considerable treatment benefit, this approach must be considered in patients with short shock duration early after MI.

Abciximab↗

PubMed2003

NT-proBNP: a new diagnostic screening tool to differentiate between patients with normal and reduced left ventricular systolic function.

OBJECTIVE: To evaluate whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be used to differentiate patients with normal and reduced left ventricular ejection fraction (LVEF) in an unselected consecutive group of hospital inpatients. SETTING: City general hospital, Copenhagen, Denmark. PATIENTS AND DESIGN: During a 10 month period 2230 admissions to a city general hospital (80% of targeted patients) had an echocardiographic evaluation of left ventricular function, a comprehensive clinical evaluation, and blood analysis of N-terminal-pro-brain natriuretic peptide (NT-proBNP) within 24 hours of admission. Exclusions resulted from lack of informed consent or failure to obtain the required evaluations before death or discharge from hospital. Echocardiography was unsatisfactory in 37 patients, so the final number studied was 2193. RESULTS: A raised NT-proBNP (>or= 357 pmol/l) identified patients with an LVEF of 40% was more than 97%. This probability rapidly decreased to 70% as the measured NT-proBNP increased to 150% of the predicted value. CONCLUSIONS: A single measurement of NT-proBNP at the time of hospital admission provides important information about LVEF in unselected patients.

Adult↗

PubMed2001

Tetrahydrobiopterin improves endothelium-dependent vasodilation in nitroglycerin-tolerant rats.

Tolerance to nitroglycerin is caused by a nitroglycerin-mediated increase in vascular superoxide anion production. Administration of tetrahydrobiopterin (co-factor for endogenous nitric oxide (NO) formation) may potentially influence nitroglycerin tolerance in at least two different ways. Firstly, tetrahydrobiopterin may act as a scavenger of the nitroglycerin-mediated production of superoxide anions. Secondly, tetrahydrobiopterin may protect endothelial NO synthesis from the deleterious effects of increased oxidative stress. This study investigates whether in vivo nitroglycerin tolerance is affected by tetrahydrobiopterin supplementation and assesses the in vivo role of tetrahydrobiopterin in endogenous NO-mediated vasodilation in normal and nitroglycerin-tolerant rats. The results show that tetrahydrobiopterin does not affect nitroglycerin-derived, NO-mediated vasodilation, but reduces baseline mean arterial blood pressure (by 8 mm Hg, P<0.05) and normalizes endothelium-dependent responses to N(G)-monomethyl-L-arginine (L-NMMA) (from 7+/-1 to 22+/-4 mm Hg, P<0.05) in nitroglycerin-tolerant rats. It is concluded that altered bioavailability of tetrahydrobiopterin is involved in the pathophysiology of endothelial dysfunction seen in nitroglycerin tolerance.

Animals↗

PubMed2001

Endothelium-dependent vasorelaxation in inhibited by in vivo depletion of vascular thiol levels: role of endothelial nitric oxide synthase.

Thiols like glutathione may serve as reducing cofactors in the production of nitric oxide (NO) and protect NO from inactivation by radical oxygen species. Depletion of thiol compounds reduces NO-mediated vascular effects in vitro and in vivo. The mechanisms underlying these actions are not clear, but may involve decreased synthesis of NO and/or increased degradation of NO. This study investigates the effect of glutathione depletion on the response to NO-mediated vasodilation induced by acetylcholine (Ach, 10 micrograms/kg), endothelial NO synthase (eNOS) activity and potential markers of vascular superoxide anion (O2.-) production in conscious chronically catheterized rats. Thiol depletion induced by buthionine sulfoximine (BSO, 1 g i.p. within 24 h) decreased the hypotensive effect of Ach by 30% (MAP reduction before BSO 27 +/- 3 mmHg, 19 +/- 3 mmHg after BSO, (mean +/- SEM), p < .05, n = 8). The impaired effect of Ach was associated with a significant reduction in eNOS activity (control: 7.7 +/- 0.8, BSO: 3.9 +/- 0.4 pmol/min/mg protein (p < .05), n = 6). In contrast, neither NADH/NADPH driven membrane-associated oxidases nor lucigenin reductase activity were significantly (p < .05) affected by BSO (BSO: 4415 +/- 123, control: 4105 +/- 455 counts/mg; n = 6) in rat aorta. It is concluded that in vivo thiol depletion results in endothelial dysfunction and a reduced receptor-mediated vascular relaxation. This effect is caused by reduced endothelial NO formation.

Acetylcholine↗

PubMed2001

Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest.

BACKGROUND AND PURPOSE: Under normal circumstances, autoregulation maintains cerebral blood flow (CBF) constant within a wide range of mean arterial pressure (MAP). It remains unknown whether patients resuscitated from cardiac arrest have preserved CBF autoregulation. In this study, CBF autoregulation was investigated within the first 24 hours after resuscitation from cardiac arrest. METHODS: Eighteen patients and 6 healthy volunteers had relative changes in CBF determined by transcranial Doppler mean flow velocity (V(mean)) in the middle cerebral artery during a stepwise rise in MAP by use of norepinephrine infusion. V(mean) was plotted against MAP, and a lower limit of autoregulation was identified by double regression analysis based on the least-squares method. RESULTS: In patients, V(mean) increased from a median of 33 (range 19 to 73) to 37 (22 to 100) cm/s (P:<0.001) during a norepinephrine-induced rise in MAP from 78 (46 to 118) to 106 (60 to 149) mm Hg. Eight of 18 patients had impaired CBF autoregulation, and in 5 of the 10 patients with preserved CBF autoregulation, the lower limit of autoregulation could be identified. The lower limit of CBF autoregulation was 76 mm Hg (41 to 105 mm Hg) in the volunteers and 114 mm Hg (80 to 120 mm Hg) in the 5 patients with preserved autoregulation (P:<0.01). CONCLUSIONS: We conclude that in a majority of patients in the acute phase after cardiac arrest, cerebral autoregulation is either absent or right-shifted. These results indicate that MAP should be kept at a higher level than commonly accepted to secure cerebral perfusion. We recommend, however, that further randomized clinical trials are performed to determine whether sympathomimetic drugs improve neurological outcome.

Adult↗

PubMed2001

Cerebral blood flow in patients with chronic heart failure before and after heart transplantation.

BACKGROUND AND PURPOSE: Arterial blood pressure and cardiac output are often reduced in patients with chronic heart failure (CHF). Counterregulatory mechanisms with increased neurohormonal activation and changes in the distribution of cardiac output are assumed to secure vital organ perfusion. However, clinical examination of patients with CHF frequently reveals neurological symptoms with dizziness and memory problems, suggesting altered brain perfusion. In this study we determined whether cerebral blood flow (CBF) is reduced in patients with New York Heart Association (NYHA) functional class III and IV (n=12) compared with healthy control subjects (n=12). Furthermore, we examined whether heart transplantation (n=5) could restore CBF. METHODS: CBF was estimated by single-photon emission computed tomography and (133)Xe as tracer, and middle cerebral artery velocity was measured by transcranial Doppler ultrasound. RESULTS: In the CHF patients, CBF was 36+/-1 mL/min per 100 g, corresponding to a 31% reduction compared with the control group (52+/-5 mL/min per 100 g) (P<0.05). After heart transplantation, CBF increased from 35+/-3 mL/min per 100 g before transplantation to 50+/-3 mL/min per 100 g within the first postoperative month (P<0.05). CONCLUSIONS: We conclude that CBF is substantially, but reversibly, reduced in patients with NYHA class III/IV heart failure. This phenomenon suggests that redistribution of cardiac output inadequately secures brain perfusion in patients with severe CHF.

Blood Flow Velocity↗

PubMed2000

[Heart transplantation].

In carefully selected patients with end-stage heart failure heart transplantation has developed from an experimental procedure to standard therapy during the last 30 years. It is currently accepted as a procedure for prolonging life and also for improving quality of life. According to the Registry of the International Society for Heart and Lung Transplantation the overall one-year actuarial survival is 79% and 10-year survival barely 50%. Nine years after the start of the Heart Transplant Program at Rigshospitalet the overall actuarial survival of 157 consecutive patients is 66%. Due to the limited donor access a decline of heart transplant recipients has been recorded during the late nineties. Mechanical replacement of the heart may develop from technological advances and possibly this therapy may gain a complementary status in heart failure, however the human biological replacement is currently the standard.

Contraindications↗

PubMed2000

[Cardiogenic shock in acute myocardial infarction. Time for a more aggressive therapeutic strategy?].

Cardiogenic shock following acute myocardial infarction results in the death of most affected individuals. Longitudinal data suggest that in spite of modern pharmacological inotropic support and thrombolytic regimes, survival from cardiogenic shock has not improved during the last several decades. However, recent observational and limited randomized trial data indicate that some of these high risk patients may derive particular benefit from aggressive percutaneous or surgical revascularisation procedures. This review analyses currently available treatment strategies which appear to hold promise for the future.

Cardiac Surgical Procedures↗

PubMed2000

[Circulatory support with the mechanical heart, "HeartMate"].

Treatment with the mechanical heart, HeartMate, has been introduced in Denmark. Short-term circulatory support can be obtained by intraaortic balloon counterpulsation, an external centrifugal pump and the total artificial heart. Long-term circulatory support can be established by treatment with the HeartMate. The principle of the mechanical heart is simple--a pump is implanted in parallel to the existing heart and connected to external, portable batteries. The patient quickly improves and is brought in an optimal state for transplantation. A few patients have been able to omit the subsequent heart transplantation. The patient's own heart improved during the treatment and the native heart functioned again after the system was explanted. The main complications during treatment are bleeding, infection, thromboembolic events and systemic failure. Permanent, fully implantable mechanical circulatory pumps are under development--which may herald the beginning of a whole new era for treatment of cardiac failure.

Assisted Circulation↗

PubMed1999

[Beta-blockade--a new therapeutic modality in chronic heart insufficiency].

Heart failure due to decreased left ventricular function is a condition with a considerable morbidity and mortality. Until recently beta-blocker treatment has been considered contraindicated in this condition. During the last 20 years a number of investigations have pointed to a possible positive effect of beta-blocker treatment in chronic heart failure and recently several major randomized trials have shown a significantly increased survival during beta-blocker treatment. This review summarizes the background for the use of beta-blocker treatment in chronic heart failure patients.

Adrenergic beta-Antagonists↗

PubMed1999

Nitroglycerin-mediated vasorelaxation is modulated by endothelial calcium-activated potassium channels.

OBJECTIVE: Recent in vitro data suggest, large conductance calcium-activated K+ channels (BKCa) modulate the vascular response to nitric oxide (NO). The in vivo implications and the characteristics of this interaction are not clear. This study firstly investigates whether modulation of BKCa affects the vascular response to nitroglycerin (NTG)-derived NO in vivo and in the isolated heart and secondly examines the influence of endothelial BKCa on NTG-mediated vasodilation in vitro. METHODS: The hypotensive effect of NTG was measured in conscious, chronically catheterized rats during i.v. infusions of iberiotoxin (IbTX, a selective inhibitor of BKCa) or placebo. Similarly, NTG-induced flow-changes in the isolated perfused rat heart were examined before and after IbTX treatment (0.1 microM). Concentration-relaxation curves to NTG in the presence of various K+ channel modulating agents were performed in vitro on porcine coronary arteries with and without intact endothelium. RESULTS: I.v. infusion of IbTX reduced the in vivo hypotensive effect of NTG by 55% (before IbTX: 32.0 +/- 3.0 mmHg, vs. after IbTX: 14.5 +/- 3.2 mmHg, P < 0.05) and nearly abolished NTG-induced increase in coronary flow in the isolated perfused heart (P < 0.05). In vitro, this effect depended on an intact endothelium (endothelium intact segments; NTG: pD2 = 5.8 +/- 0.1, Emax = 97.6 +/- 3.2% vs. NTG + IbTX: pD2 = 4.9 +/- 0.2, Emax = 49.7 +/- 6.2%, P < 0.05; endothelium denuded segments; NTG: pD2 = 6.9 +/- 0.1, Emax = 104.0 +/- 1.4% vs. NTG + IbTX: pD2 = 6.7 +/- 0.1, Emax = 100 +/- 1.2%, P > 0.05). CONCLUSION: The results suggest, that modulation of endothelial BKCa significantly affects NTG-induced vasorelaxation in vitro, in the isolated perfused heart and in vivo.

Animals↗

PubMed1999

Vascular smooth muscle contraction is an independent regulator of endothelial nitric oxide production.

This investigation was conducted to determine whether endothelial nitric oxide (NO) production is regulated by vascular smooth muscle contraction. Unperfused ring segments of rat aorta and mesenteric artery were studied using isometric tension recording (n = 6-8 in all experiments). Following a reference contraction to K+ 80 mM (100%), arteries were left either unstimulated or stimulated by different concentrations of K+ or prostaglandin F2alpha (PGF2alpha) to induce different levels of vascular precontraction. N(G)-nitro-L-arginine methyl ester (L-NAME 0.1-300 microM) or NS 2028 (0.03-3 microM), which is a new specific inhibitor of the NO-sensitive guanylate cyclase, was then added at increasing concentrations to evaluate endothelial NO production. L-NAME and NS 2028 produced a concentration-dependent vasoconstrictor response which was progressively enhanced with increasing levels of precontraction. For L-NAME, this amounted in aorta to (% of reference contraction): 35+/-1% and 105 +/- 4% (precontraction by K(+) 20 and 30 mM) and 22+/-1%, 89+/-1%, 138+/-1% and 146+/-2% (precontraction by PGF2alpha 0.5, 1, 2 and 3 microM). A similar coupling was found in the mesenteric artery. A precontraction as little as 2% was enough to trigger a vasoconstrictor response to L-NAME. In contrast, L-NAME and NS 2028 had no effect in non-contracted arteries, not even when passive mechanical stretch was increased by 100%. The results suggest (i) that endothelial NO formation is progressively increased with increasing vascular tone, and (ii) that vascular isometric contraction per se stimulates endothelial NO formation. It is concluded, that active vascular smooth muscle contraction is an independent regulator of endothelial NO production.

Animals↗

PubMed1998

Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels.

The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed contractions induced by K+ (20 mM) compared with K+ (80 mM). In addition, concentration-relaxation curves for hydralazine (pD2 = 5.38 +/- 0.06; Emax = 85.9 +/- 3.6%) were shifted 10-fold to the right by the BK(Ca) blockers tetraethylammonium (1 mM) and iberiotoxin (0.1 microM). In contrast, nimodipine (a Ca2+-entry blocker), relaxed contractions induced by K+ (20 mM) and K+ (80 mM) equally and nimodipine-induced relaxations were neither antagonized by tetraethylammonium nor by iberiotoxin. In isolated perfused rat hearts, hydralazine (1 microM) increased coronary flow by 28.8 +/- 2.7%. Iberiotoxin (0.1 microM) suppressed this response by 82% (P < 0.05). In conscious, chronically catheterized rats the hypotensive response to hydralazine (0.6 mg kg(-1) min(-1)) was significantly reduced by 41% during infusion of iberiotoxin (0.1 mg kg(-1)). It is concluded, that opening of BK(Ca) takes part in the mechanism whereby hydralazine produces vasodilation.

Animals↗

PubMed1998

Inducible nitric oxide synthase (iNOS) in the human heart: expression and localization in congestive heart failure.

The inducible nitric oxide (NO) synthase (iNOS or NOS2) generates a prolonged release of large amounts of NO which may be cytotoxic and/or inhibit myocyte contractility. It has been suggested that this mechanism specifically contributes to heart failure caused by dilated cardiomyopathy (DCM). To test this hypothesis we compared the myocardial amount and localization of iNOS in myocardial biopsies from patients with heart failure caused by either DCM or ischemic heart disease (IHD). During heart transplantation, myocardial biopsies collected from the diseased heart after explantation were frozen in liquid nitrogen. Twenty-two patients in NYHA class III-IV were included (DCM: n = 8; IHD: n = 14). In each biopsy, iNOS expression was assessed using reverse transcription polymerase chain reaction (RT-PCR), and visualized by immunohistochemistry. iNOS was detected in all biopsies. Intriguingly, the amount of iNOS mRNA (shown as iNOS cDNA normalized to GADPH cDNA) did not differ significantly between the two groups (DCM 30 +/- 7; IHD 20 +/- 6, mean +/- S.E.M., P > 0.05). Similarly, no inter-group differences in the amount of iNOS protein (Western) were observed. iNOS was invariably located to vascular endothelial and smooth muscle cells. In addition, an iNOS reaction in relation to the myocyte membrane was found in 4 of the 22 patients. These four patients (two from each group) had significantly (P < 0.05) higher iNOS/GADPH ratios (54 +/- 20) than patients without myocyte membrane iNOS reaction (17 +/- 15). In conclusion, iNOS is expressed in the myocardium of all patients with heart failure caused by either DCM or IHD. iNOS is located primarily and invariably in the endothelium and vascular smooth muscle cells of the myocardial vasculature and its expression appears to be associated with the condition of heart failure per se rather than related to the heart failure etiology.

Adult↗

PubMed1997

Effect of nitroglycerin in patients with increased pulmonary vascular resistance undergoing cardiac transplantation.

Acute right ventricular failure due to persistent pulmonary hypertension is a risk factor for premature death after cardiac transplantation. The purpose of this study was to follow changes in pulmonary haemodynamics in patients with pulmonary hypertension undergoing heart transplantation, and to examine whether postoperative changes can be predicted from a preoperative nitroglycerin (NTG) challenge. Seventeen consecutive patients with NYHA class IV heart failure and pulmonary hypertension (pulmonal vascular resistance (PVR) > 2.5 Wood units) underwent an NTG infusion before cardiac transplantation and were followed up using measurements of pulmonary haemodynamics before, early (24 h) and late (6 months) after cardiac transplantation. The effect of NTG was measured preoperatively and compared with posttransplantation values. Postoperative (24 h) PVR was reduced in all patients when compared with preoperative findings (PVR from 4.1 +/- 0.2 to 1.9 +/- 0.2 Wood units, Mean +/- SEM, p < 0.05). Mean pulmonary artery pressure (mPAP) was lowered in 16 of out 17 patients (41 +/- 2 to 26 +/- 1 mmHg, p < 0.05). None of the parameters were significantly changed during the subsequent 6 months. Postoperative PVR and mPAP were accurately estimated by preoperative NTG infusion (NTG vs 24 h posttranspl: PVR 2.2 +/- 0.2 vs 1.9 +/- 0.2 Wood units, p > 0.05; mPAP 30 +/- 2 vs 26 +/- 1 mmHg, p > 0.05). Heart transplantation candidates with pulmonary hypertension responsive to NTG can be expected to obtain a postoperative immediate fall in pulmonary pressures and PVR. The magnitude of this circulatory improvement can be predicted from a preoperative NTG infusion and is not different from values measured 6 months after transplantation.

Acute Disease↗