High Pulmonary Vascular Resistance Research Articles

Maternal Hypoxemia Suppresses Muscarinic Acetylcholine Receptor Dependent Contraction of Pulmonary Arteries from Fetal Sheep

Muscarinic acetylcholine (ACh) receptor (mAChR) activation relaxes arteries through endothelium‐dependent signaling pathways, yet ACh can contract pulmonary arteries (PA). The impact of development and chronic hypoxia (CH) on PA contraction and intimacy between endothelium and myocyte function led to the hypothesis that chronic hypoxia (CH) reduces mAChR‐dependent PA contractility. This was tested by performing wire‐myography on endothelium‐denuded PA rings from term‐fetal or adult sheep that lived at low altitude or 3,200 meters for <100 days. The roles for the three mAChR isoforms were assessed using the mAChR agonist carbachol and various antagonists, including non‐selective (atropine), or M1 (Pirenzepine), M2 (AFDX‐116), and M3 (Dau5884, 4‐DAMP) selective blockers. Carbachol responses as a function of arterial diameter were also examined. Carbachol contracted very few vessels from fetal CH sheep. However, in fetal normoxic and adult CH sheep, smaller arteries contracted more than larger ones, and in adult normoxic medium arteries contracted the most. The M2 receptor predominated in fetal normoxic while M3 was most important in adult normoxic and CH arteries. These results suggest M2 mAChR reactivity contributes to high pulmonary vascular resistance in the fetus and loss of contractility in the CH fetus may influence pulmonary vascular disease of the newborn. NIH P01HD031226, R01HD003807 (LDL).

Hemodynamic Characteristics and Predictors of Pulmonary Hypertension in Patients With Sickle Cell Disease

Pulmonary hypertension is a common co-morbidity of sickle cell disease with an associated increased mortality risk, but its etiology is not well-understood. To evaluate the hemodynamic characteristics, clinical predictors, and cardiovascular manifestations of elevated pulmonary arterial pressure in this population, we performed noninvasive hemodynamic assessments of 135 patients with sickle cell disease using Doppler echocardiography. A diagnosis of pulmonary hypertension was determined by gender-, age-, and body mass index-specific normal reference ranges for tricuspid regurgitation jet velocities (TRVs). A high TRV was noted in 34 patients (25%). Pulmonary vascular resistance was elevated in only 2 (6%) of the 34 patients with suspected pulmonary hypertension but was significantly greater than in those with normal TRV. On univariate regression, the TRV correlated with age, body mass index, left atrial pressure, and right ventricular stroke volume and was negatively associated with hemoglobin and glomerular filtration rate. The left atrial pressure, right ventricular stroke volume, and hemoglobin remained independent predictors of TRV in a multivariate model. A greater TRV was also associated with larger right ventricular and right atrial chamber sizes and greater N-terminal probrain natriuretic peptide levels. In conclusion, our results suggest that the mild elevation in TRV often observed in patients with sickle cell disease is rarely associated with a high pulmonary vascular resistance and that multiple factors-including the compensatory high output state associated with anemia, pulmonary venous hypertension, and pulmonary vasculopathy-can contribute to an elevated pulmonary arterial pressure in these patients.

Pulmonary Hypertension in Elderly Patients with Diastolic Dysfunction and Preserved Ejection Fraction

Purpose:Patients with diastolic dysfunction may have a disproportionate degree of elevation in pulmonary pressure, particularly in the elderly. Higher pulmonary vascular resistance in the elderly patients with heart failure but preserved ejection fraction suggests that beyond the post-capillary contribution of pulmonary venous congestion, a pre-capillary component of pulmonary arterial hypertension occurs. We aim to identify if pulmonary vascular resistance in elderly patients with diastolic dysfunction is disproportionately higher than patients with systolic dysfunction independent of filling pressures.Methods:389 patients identified retrospectively between 2003- 2010; elderly with preserved ejection fraction, elderly with depressed ejection fraction, and primary arterial hypertension who underwent right-heart catheterization at Rush University.Results:No significant difference in pulmonary vascular resistance between systolic and diastolic dysfunction. The mean difference in pulmonary vascular resistance was not statistically significant at 0.40 mmHg·min/l (95% CI -3.03 to 3.83) with similar left ventricular filling pressures with mean difference of 3.38 mmHg (95% CI, -1.27 to 8.02). When adjusted for filling pressures, there remained no difference in pulmonary vascular resistance for systolic and diastolic dysfunction. The mean pulmonary vascular resistance is more elevated in systolic heart failure compared to diastolic heart failure with means 3.13 mmHg·min/l and 3.52 mmHg·min/l, respectively.Conclusion:There was no other association identified for secondary pulmonary hypertension other than diastolic dysfunction and chronic venous pulmonary hypertension. Our results argue against any significant arterial remodeling that would lead to disproportionate pre-capillary hypertension, and implies that treatment should focus on lowering filling pressure rather than treating the pulmonary vascular tree.

Inhaled Nitric Oxide for Elevated Cavopulmonary Pressure and Hypoxemia After Cavopulmonary Operations

Background. Elevated cavopulmonary pressure early after surgical creation of cavopulmonary connections is an important hemodynamic problem with grave prognostic significance. We examined the effect of administration of inhaled nitric oxide (iNO) to patients with elevated cavopulmonary pressure in the early postoperative period. Methods. We retrospectively reviewed data pertaining to all 14 patients with superior (n = 6) and total (n = 8) cavopulmonary connections who were treated with iNO in the early postoperative period during an interval of six years. Changes in the cavopulmonary pressure, the transpulmonary gradient, and the oxygen saturation after the institution of iNO were evaluated. The preoperative characteristics of the patients were compared to those of a control group of patients with cavopulmonary operations not treated with iNO postoperatively. Results. Twelve hours after the initiation of iNO therapy, significant reduction in the cavopulmonary pressure (16.6 ± 3.5 mm Hg vs 18.1 ± 2.3 mm Hg, P = .006), reduction in the cavopulmonary gradient (7.0 ± 3.5 mm Hg vs 9.8 ± 3.7 mm Hg, P = .009), and elevation of the arterial oxygen saturation (84.5% ± 6.0% vs 78.7% ± 5.9%, P = .001) were observed. Linear correlation analysis confirmed tendencies for reduction in the cavopulmonary pressure (P = .13), reduction in the cavopulmonary gradient (P = .02), and elevation of the oxygen saturation (P = .10). Compared to the control group, the treated patients tended to have higher preoperative pulmonary arterial pressures (PAPs) 17 (11-30) mm Hg versus 12 (10-25) mm Hg, P = .10; higher pulmonary vascular resistance (PVR) 2.04 (0.27-6.94) Wood units versus 1.02 (0.49-5.20) Wood units, P = .37; and longer bypass times 154 (41-218) versus 91 (15-276) minutes, P = .13. Conclusions. Administration of iNO was associated with diminuition of cavopulmonary pressure and transpulmonary gradient and increasing oxygen saturation in our small group of patients. In our experience selected patients with preoperatively elevated PAP above 17 mm and PVR above 2 Wood units can undergo cavopulmonary operations with iNO treatment early postoperatively.

Anesthetic considerations during heart-lung transplantation in a patient with an unresectable pulmonary artery sarcoma

Anesthetic considerations during heart-lung transplantation in a patient with an unresectable pulmonary artery sarcoma

"Treat-to-target" in pulmonary arterial hypertension and the use of extracorporeal membrane oxygenation as a bridge to transplantation

To the Editor: A 30-yr-old female was referred to the Hanover Medical School (Hanover, Germany) in July 2007 following a diagnosis of idiopathic pulmonary arterial hypertension (PAH). She had no other comorbidities. At the time of diagnosis she was in World Health Organization functional class (WHO FC) III with a 6-min walk distance (6MWD) of 402 m. Cardiopulmonary exercise testing (CPET) showed that her peak oxygen uptake ( V ′O2) was markedly impaired (11.6 mL·min−1·kg−1; target range >15 mL·min−1·kg−1) [1]. Echocardiography revealed a tricuspid annular systolic plane excursion (TAPSE) of 1.6 cm (normal value >2 cm) indicating serious impairment of right ventricular function. The results of right heart catheterisation (RHC) are shown in table 1. Haemodynamics were compatible with diagnosis; a low cardiac output and high pulmonary vascular resistance. In accordance with guideline recommendations [1], treatment was initiated with sildenafil 20 mg three times daily. This was well tolerated and 3 months later her functional status had improved to WHO FC II and her 6MWD had increased to 465 m. Although her TAPSE had improved to 1.8 cm, it was still below normal, suggesting her right ventricular (RV) function remained impaired. To further investigate this CPET was repeated, which revealed that her peak V ′O2 had only slightly improved from baseline (12.5 mL·min−1·kg−1) and that her oxygen pulse ( V ′O2/heart rate), an indirect measure of stroke volume, was only approximately half of that predicted. Taken together these data indicated the patient's response to sildenafil was suboptimal, particularly with respect to RV function. The decision was then made to initiate treatment with bosentan in addition to her existing sildenafil regimen. Combination therapy was well tolerated, and there was no …

Abstract 8951: Assessment of Pressure Reflection in the Pulmonary Circulation Using Echocardiography Identifies Patients with Normal as Well as Increased Pulmonary Vascular Resistance

Background and aim. Pulmonary hypertension (PH) is a frequent finding in patients with cardiopulmonary disorders. It is important to recognize PH due to increased pulmonary vascular resistance (PVR). In a recent study we describe a new echocardiography method to identify patients with increased PVR (>3 WU) based on detection of pressure reflection (PR) in the pulmonary artery (PA). The patient population was biased towards high PVR and therefore, in the present study we evaluate the method in a more representative population undergoing right heart catheterization. Methods and results. Echocardiography and catheterization were performed within one week in 108 patients. We selected 3 variables related to PR: the interval from valve opening to peak velocity in the PA (AcT, ms), the interval between PA peak velocity and peak tricuspid velocity (tPV-PP, ms), and the right ventricular pressure increase after peak velocity in the PA (augmented pressure, AP, mm Hg). Cut-of values indicating increased PVR for Act/tPV-PP/AP were 89 ms/>8 mmHg. Forty-six percent had left heart disease, 21% were heart transplant patients and 18% had pulmonary arterial hypertension. The proportion with increased PAMP (>25 mmHg) was 54%, increased pulmonary capillary wedge pressure (PCWP>12 mHg) 40%, increased PVR (>3 WU) 36% or both increased PVR and PCWP 15%. The table shows how the number of PR variables affected the diagnostic performance. The positive predictive value was 94% with equal to or > 2 PR variables and the negative predictive value was 92% with no PR variables present. Conclusions. Assessment of PR in the pulmonary circulation identifies patients with normal as well as increased PVR.

Abstract 16642: Clinical Outcomes and Improved Survival in Patients With Protein Losing Enteropathy After the Fontan Operation

Background: Patients (pts) with protein losing enteropathy (PLE) following the Fontan operation (op) have a reported 50% mortality at 5 years (yrs) post diagnosis. We review our clinical outcomes in this pt population. Methods: From 1997 to 2010, 42 pts (55% M) with PLE following the Fontan op were identified from clinical databases. Data were collected by retrospective chart review. Results: Mean age at PLE diagnosis was 18.9 yrs + 11 (4.7-57.9 yrs) and initial Fontan op was 10.1 yrs + 10.8 (1.8-37.6 yrs). Mean time from Fontan op to PLE diagnosis was 8.4 yrs + 14.2 (30 days-27yrs). Types of Fontan op included: atriopulmonary connection (28, 67%), lateral tunnel or intraatrial conduit (6, 14%), or extracardiac conduit (8, 19%). Mean time from diagnosis to last follow-up was 8 yrs + 6 (1-22yrs). Survival was 88% at 5 yrs. There were 11 deaths, mean age 32 yrs + 7.7 (22-47 yrs). Mean time interval from diagnosis to death was 7.5 yrs + 5.4 (1-18yrs). Causes of death include: sepsis (7), complications after Fontan conversion (1), and unknown (3). Decreased survival was seen in pts with high Fontan pressure (mean >15mmHg, p=0.04), decreased ventricular function (EF < 55%, p=0.03), and NYHA class >2 at diagnosis (p=0.04). Pts who died had higher pulmonary vascular resistance (3.8 + 1.6 WU vs 2.1 + 1.1 WU, p=0.017), lower cardiac index (1.6 L/min/m 2 + 0.4 vs 2.7 L/min/m 2 + 0.7, p<0.0001), and lower mixed venous saturation (53% versus 66%, p=0.01) compared to survivors. All factors were obtained at initial PLE diagnosis. Pts treated with medical therapy only (n=15) resulted in symptomatic improvement in 7 pts (47%), no improvement in 5 (33%), and death in 3 (20%). Pts treated with medical + surgical/interventional catheterization procedures (n=27) resulted in symptomatic improvement in 10 pts (37%), no improvement in 9 (33%), and death in 8 (30%). Treatments used more in survivors included spironolactone (21, 68%), octreotide (7, 21%), sildenafil (6, 19%), fenestration creation (15, 48%), and relief of Fontan obstruction (7, 23%). Of the 31 survivors, 17 pts remain well-controlled. Conclusions: PLE remains difficult to treat, but in the current era, survival has improved with advances in treatment. Further study is needed to understand the mechanism of disease and ideal treatment strategy.

A Cell-Based Adhesion Molecule Bioassay Detects Unexpected Properties of Plasma From Patients with Sickle Cell Disease with Documented Pulmonary Hypertension

Abstract 2120Pulmonary hypertension (PH) is a common complication in adults with sickle cell disease (SCD) associated with early mortality. Several mechanistic pathways appear to be involved in PH in SCD, one of them being activation of pulmonary endothelium and increased adherence of circulation blood cells. In the past, levels of soluble adhesion molecules in the plasma of patients with SCD have been found to correlate with severity of pulmonary hypertension and risk of mortality.We investigated the association between endothelial-cell based adhesion molecules and markers of PH. We developed a new cell-based ELISA assay and evaluated the induction of cell surface expression of adhesion molecules on cultured microvascular endothelium cells by plasma from subjects with SCD who had undergone right heart catheterization. We found no difference in baseline Intercellular Cell Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1) and P-selectin induction by SCD plasma compared to healthy controls. Surprisingly, we found an inverse relationship of cell surface VCAM-1 induction with diagnosis and severity of PH, as indicated by mean pulmonary artery pressure (mPAP) on right heart catheterization. Patients who fell into the upper quartile of VCAM-1 induction had mPAP of 27.6 ± 3.2 mmHg, compared to the middle two quartiles 32 ± 2.3 mmHg, and lower quartile 38.2 ± 4.0 mmHg, (p=0.034). The prevalence of abnormally high pulmonary vascular resistance (>2 standard deviations above the mean) in the high, medium or low VCAM-1 induction groups was 20%, 35% and 80%, respectively (p=0.0066). We also found statistically significant correlations of cell surface VCAM-1 to cardiac output, transpulmonary gradient, pulse pressure, Doppler echocardiography tricuspid regurgitation velocity (TRV) and a marker of systemic iron overload, serum ferritin. Induced cell surface VCAM-1 expression did not correlate significantly in the same subjects with the plasma level of soluble VCAM-1, a previously documented marker associated with high TRV. We found very similar patterns of induction of cell surface expression of P-selectin. These results indicate that the ability of plasma to induce cell surface expression of cell adhesion molecules is a new marker predictive of the diagnosis of catheterization-proven PH in SCD, but it is independent of the levels of the soluble ectodomains of these cell adhesion molecules. These results are consistent with recent publications in the cell adhesion molecule field indicating that independent inflammation-mediated mechanisms regulate adhesion molecule expression and its ectodomain shedding via sheddases.Our findings lead us to speculate that increased sheddase activity may contribute to the high levels of soluble adhesion molecules found in PH, simultaneously reducing the level of cell surface adhesion molecules. Future studies of sheddase activity in SCD PH would help to elucidate this interesting observation. Disclosures:No relevant conflicts of interest to declare.

Noninvasive Assessment of the Early Transitional Circulation in Healthy Term Infants

Background: The early neonatal circulatory transition usually occurs smoothly but occasionally it is incomplete or reverts to the fetal state of high pulmonary vascular resistance, resulting in significant neonatal morbidity. Objective: To define the normal values for echocardiographic parameters during the early transitional circulation in term infants. Methods: Two-dimensional, M-mode, pulsed and color flow Doppler echocardiography was used to assess healthy term infants in the first 4 h of life. Left and right ventricular outputs (LVO and RVO) and myocardial performance indices (MPI), left ventricular fractional shortening, end-systolic diameter and end-diastolic diameter, ductal size, shunt and peak velocities, tricuspid regurgitation and left pulmonary artery diastolic velocities were documented. Results: A total of 21 normal term infants were assessed with median gestation of 39 weeks, birth weight of 3,470 g and postnatal age of 3 h and 22 min. The median echocardiographic values were LVO 193 ml/kg/min, RVO 216 ml/kg/min, left MPI 0.41, right MPI 0.63, and fractional shortening 29%. The ductus was patent in all 21 infants with a median size of 2.3 mm; ductal flow was bidirectional in 86% with median peak left-to-right velocity of 1.07 m/s. The median left pulmonary artery diastolic velocity was 0.31 m/s and physiological tricuspid regurgitation was present in all infants. Conclusion: This study defines normal values for echocardiographic measurements in healthy term infants during the first 4 h after birth. These normative data may be useful in early identification of infants with abnormal circulatory transition, allowing more rapid determination of cardiovascular dysfunction.

Long-term outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

Pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. Although several reports demonstrated excellent medium-term survival after pulmonary endarterectomy, long-term outcomes remain unclear. We reviewed long-term outcomes and determined risk factors for early and late adverse events. Seventy-seven patients were studied. Mean pulmonary arterial pressure was 47±10 mm Hg and pulmonary vascular resistance was 868±319 dyne·s·cm(-5). Disease was classified as chronic thromboembolic pulmonary hypertension type 1 (n=61), type 2 (n=12), or type 3 (n=4). Median and maximum follow-up periods were 5.6 and 20 years, respectively. There were 11 in-hospital deaths. Nonsurvivors had significantly higher mean pulmonary arterial pressure and pulmonary vascular resistance than did survivors (54±10 vs 46±10 mm Hg; P=.02; 1124±303 vs 824±303 dyne·s·cm(-5); P<.01). In multivariate analysis, preoperative pulmonary vascular resistance was associated with in-hospital death (odds ratio, 1.003; 95% confidence interval, 1.001-1.005; P<.01). During follow-up, there were 10 all-cause deaths, including 5 related to chronic thromboembolic pulmonary hypertension. Freedom from adverse events, including disease-specific death or New York Heart Association functional class III, was 70% at 10 years. In the Cox proportional hazard model, postoperative mean pulmonary arterial pressure was associated with adverse events (hazard ratio, 1.12; 95% confidence interval, 1.03-1.21; P<.01). Receiver operating characteristic curve analysis showed mean pulmonary arterial pressure of 34 mm Hg as cutoff for adverse events. Pulmonary endarterectomy had sustained favorable effects on long-term survival. High pulmonary vascular resistance was associated with in-hospital death, and postoperative mean pulmonary arterial pressure was an independent predictor of adverse events.

Pulmonary vascular effects of serotonin and selective serotonin reuptake inhibitors in the late-gestation ovine fetus.

Maternal use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) is associated with an increased risk for persistent pulmonary hypertension of the newborn (PPHN), but little is known about 5-HT signaling in the developing lung. We hypothesize that 5-HT plays a key role in maintaining high pulmonary vascular resistance (PVR) in the fetus and that fetal exposure to SSRIs increases 5-HT activity and causes pulmonary hypertension. We studied the hemodynamic effects of 5-HT, 5-HT receptor antagonists, and SSRIs in chronically prepared fetal sheep. Brief infusions of 5-HT (3-20 μg) increased PVR in a dose-related fashion. Ketanserin, a 5-HT 2A receptor antagonist, caused pulmonary vasodilation and inhibited 5-HT-induced pulmonary vasoconstriction. In contrast, intrapulmonary infusions of GR127945 and SB206553, 5-HT 1B and 5-HT 2B receptor antagonists, respectively, had no effect on basal PVR or 5-HT-induced vasoconstriction. Pretreatment with fasudil, a Rho kinase inhibitor, blunted the effects of 5-HT infusion. Brief infusions of the SSRIs, sertraline and fluoxetine, caused potent and sustained elevations of PVR, which was sustained for over 60 min after the infusion. SSRI-induced pulmonary vasoconstriction was reversed by infusion of ketanserin and did not affect the acute vasodilator effects of acetylcholine. We conclude that 5-HT causes pulmonary vasoconstriction, contributes to maintenance of high PVR in the normal fetus through stimulation of 5-HT 2A receptors and Rho kinase activation, and mediates the hypertensive effects of SSRIs. We speculate that prolonged exposure to SSRIs can induce PPHN through direct effects on the fetal pulmonary circulation.

Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative stress and causes pulmonary vasodilation in neonatal pulmonary hypertension.

Although inhaled NO (iNO) therapy is often effective in treating infants with persistent pulmonary hypertension of the newborn (PPHN), up to 40% of patients fail to respond, which may be partly due to abnormal expression and function of soluble guanylate cyclase (sGC). To determine whether altered sGC expression or activity due to oxidized sGC contributes to high pulmonary vascular resistance (PVR) and poor NO responsiveness, we studied the effects of cinaciguat (BAY 58-2667), an sGC activator, on pulmonary artery smooth muscle cells (PASMC) from normal fetal sheep and sheep exposed to chronic intrauterine pulmonary hypertension (i.e., PPHN). We found increased sGC α(1)- and β(1)-subunit protein expression but lower basal cGMP levels in PPHN PASMC compared with normal PASMC. To determine the effects of cinaciguat and NO after sGC oxidation in vitro, we measured cGMP production by normal and PPHN PASMC treated with cinaciguat and the NO donor, sodium nitroprusside (SNP), before and after exposure to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an sGC oxidizer), hyperoxia (fraction of inspired oxygen 0.50), or hydrogen peroxide (H(2)O(2)). After treatment with ODQ, SNP-induced cGMP generation was markedly reduced but the effects of cinaciguat were increased by 14- and 64-fold in PPHN fetal PASMC, respectively (P < 0.01 vs. controls). Hyperoxia or H(2)O(2) enhanced cGMP production by cinaciguat but not SNP in PASMC. To determine the hemodynamic effects of cinaciguat in vivo, we compared serial responses to cinaciguat and ACh in fetal lambs after ductus arteriosus ligation. In contrast with the impaired vasodilator response to ACh, cinaciguat-induced pulmonary vasodilation was significantly increased. After birth, cinaciguat caused a significantly greater fall in PVR than either 100% oxygen, iNO, or ACh. We conclude that cinaciguat causes more potent pulmonary vasodilation than iNO in experimental PPHN. We speculate that increased NO-insensitive sGC may contribute to the pathogenesis of PPHN, and cinaciguat may provide a novel treatment of severe pulmonary hypertension.

Pharmacological Treatment of Hypoxemia during One-lung Ventilation

Pharmacological Treatment of Hypoxemia during One-lung Ventilation

Noninvasive assessment of pulmonary vascular resistance and pressure in patients with congenital heart disease: a new method using M-mode echocardiography.

The accurate evaluation of pulmonary vascular resistance (PVR) and mean pulmonary artery pressure is important to determine the optimal management and therapeutic strategy for patients with congenital heart disease (CHD). We evaluated the PVR and mean pulmonary artery pressure in 46 patients with several CHD types using the interventricular septum (IVS) motion determined by M-mode echocardiography. We divided the patients into 2 groups according to the different IVS motions. We measured the maximum anterior displacement from the baseline during early systole (a) and the maximum posterior displacement from the baseline during early diastole (b). We defined type A to be a/b greater than or equal to 1.0, and type B to be a/b less than 1.0. The PVR and mean pulmonary artery pressure in type A patients were significantly higher than those in type B patients (p<0.05). Type A IVS motion predicted patients with high PVR (>2.5unit/m(2)) and high mean pulmonary artery pressure (>25mmHg) (sensitivity 89%, specificity 89% and sensitivity 70%, specificity 91%, respectively). Our method can noninvasively separate high and low PVR among patients with CHD. This noninvasive method is therefore considered to be useful in the management of patients with CHD in a clinical setting.

Vaikų plautinė hipertenzija

Straipsnyje supažindinama su vaikų plautinės hipertenzijos klasifikacija, diagnostika, simptomais, gydymo galimybėmis.

Heart Transplantation in Biventricular Congenital Heart Disease: Indications, Techniques, and Outcomes

Heart transplantation is an accepted therapeutic modality for end-stage congenital heart disease for both biventricular and univentricular anomalies. Many transplant centers have pushed the limits of transplantation to include patients with high pulmonary vascular resistance, high panel reactive antibodies, positive cross-matches, and ABO-incompatibility. Excellent results have been possible, particularly with the development of improved diagnostic and therapeutic algorithms to prevent and treat rejection, infection, and post-transplant lymphoproliferative disease. Late graft failure and chronic rejection remain vexing problems. The vast majority of patients with biventricular congenital heart disease have undergone prior cardiac surgical procedures. Indications for transplantation in this subgroup are primarily progressive refractory heart failure following prior cardiac surgical reconstructive procedures. Contraindications to transplantation mimic those for other forms of end-stage heart disease. A determination of pulmonary vascular resistance is important in listing patients with biventricular congenital heart disease for heart transplantation. Modifications in the implant technique are necessary and vary depending on underlying recipient anatomy. Risk factors for perioperative outcomes in patients with biventricular congenital heart disease include the need for reoperation, the degree of anatomic reconstruction necessary during the implant procedure, and the degree of antibody sensitization, in addition to a number of other recipient and donor factors. Postoperative outcomes and survival are very good but remain inferior to those with cardiomyopathy in most series. In conclusion, patients with end-stage biventricular congenital heart disease represent a complex group of patients for heart transplantation, and require careful evaluation and management to ensure optimal outcomes.

Rationale and design of a trial on the role of bosentan in Fontan patients: Improvement of exercise capacity?

Background The Fontan circulation is a palliative procedure performed in patients with complex congenital heart disease (CHD), making transpulmonary blood flow dependent on the systemic venous pressure. In a Fontan circulation a low pulmonary vascular resistance (PVR) is crucial, as is epitomized by the observation that a high PVR is a strong predictor of mortality. Long-term follow-up has shown that PVR may rise many years after the Fontan procedure has been performed, possibly due to micro-emboli from a dilated right atrium or from the venous system. Other mechanisms of increased PVR might be aging, obstructed airways caused by lymphatic dysfunction, lack of pulsatile pulmonary flow causing a release of endothelium-derived vasoactive molecules, and prolonged overexpression of vasoconstrictors such as endothelin-1. Mean plasma level of endothelin-1 has been shown to be significantly higher in Fontan patients compared to healthy controls. In patients with pulmonary arterial hypertension (PAH), therapy with bosentan, an endothelin-1 receptor antagonist, has demonstrated to improve exercise capacity and to reduce the elevated PVR. In addition, reduction of PVR is shown early and late after the Fontan procedure on treatment with exogenous NO, another advanced PAH therapy. However, the long term effect of reducing the PVR by bosentan treatment on exercise capacity in Fontan patients is still unknown. Methods We designed a prospective, multicenter, randomized open label trial to study the effect of bosentan in Fontan patients. The primary endpoint will be the change in maximum exercise capacity (peak V'O2). Conclusion We hypothesize that treatment with bosentan, an endothelin-1 receptor antagonist, improves maximum exercise capacity and functional capacity in adult Fontan patients.

The role of milrinone in children with cardiovascular compromise: review of the literature

Cardiovascular instability is a common complication in children after cardiac surgery and in various forms of shock. Systematic literature review. Four randomized controlled trials (RCTs) were included in this systematic literature review. In children after corrective surgery for congenital heart disease milrinone significantly reduced the risk of development of LCOS compared with placebo. In another study in children with high pulmonary vascular resistance and impaired oxygenation after Fontan operation, inhalation of NO with milrinone led to the most significant reduction of pulmonary vascular resistance and improvement of oxygenation. When only milrinone was given these changes were less pronounced. In non-hyperdynamic septic shock, CI, SVI, and DO₂ significantly increased while SVRI significantly decreased after milrinone when compared to placebo. There are a limited number of RCTs in children that suggest a beneficial effect of milrinone in the optimization of cardiovascular function after cardiac surgery and in septic shock.

Vascular abnormalities in human newborns with pulmonary hypertension

Pulmonary vascular disease embodies all congenital or acquired pathologies that affect the pulmonary vasculature. One of them is pulmonary hypertension of the newborn (PHN), which is clinically characterized by a persistent high pulmonary vascular resistance postnatally and an abnormal vascular response. Morphologically, the vascular walls of the small pulmonary arteries become thickened, leading to increased resistance of these vessels and thus a worsening of gas exchange. PHN occurs as a primary disease or in association with abnormal lung development, for example as in congenital diaphragmatic hernia, and is a critical determinant of morbidity and mortality. Here we review the current knowledge about vascular abnormalities in PHN and discuss the vascular abnormalities in different conditions associated with pulmonary hypertension in human newborns in relation to recent findings from molecular biology.