Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension

BACKGROUND: Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS: Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS: Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS: This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.     

High-resolution CT of the chest in four patients with pulmonary capillary hemangiomatosis or pulmonary venoocclusive disease

OBJECTIVE: Clinical differentiation of isolated pulmonary hypertensive arteriopathy from pulmonary capillary hemangiomatosis or pulmonary venoocclusive disease can be difficult on a clinical basis alone. Differentiation is important because misdiagnosis of pulmonary capillary hemangiomatosis or pulmonary venoocclusive disease may lead to severe vasodilator-induced pulmonary edema. The objective of our study was to determine whether high-resolution CT of the chest could distinguish pulmonary capillary hemangiomatosis or pulmonary venoocclusive disease from isolated pulmonary hypertensive arteriopathy. CONCLUSION: Pulmonary hypertension in patients who also have pulmonary capillary hemangiomatosis or pulmonary venoocclusive disease shows characteristics on high-resolution CT that are not seen in patients with isolated pulmonary hypertensive arteriopathy.     

Intravascular ultrasonic characteristics and vasoreactivity of the pulmonary vasculature in children with pulmonary hypertension

We sought to describe the morphologic characteristics of pulmonary arteries by intravascular ultrasound (IVUS) in children with and without pulmonary hypertension to compare these anatomic findings with those of pulmonary wedge angiography, and to determine the relation between these structural findings and functional reactivity to pulmonary vasodilators. Direct evaluation of pulmonary vascular structure in children with pulmonary hypertension with current imaging techniques has been limited and little is known about the relation between structural and functional characteristics of the pulmonary vasculature. In 23 children undergoing cardiac catheterization (15 with pulmonary hypertension and 8 controls) we performed IVUS and pulmonary wedge angiography of the distal pulmonary arteries in the same lobe. IVUS was performed in 44 pulmonary arteries measuring 2.5 to 5.0 mm internal diameter with a 3.5Fr 30-MHz IVUS catheter. We assessed vasoreactivity to inhaled nitric oxide (NO) and oxygen in 13 of 15 children with pulmonary hypertension. Baseline pulmonary vascular resistance (PVR) was greater in the 15 children with pulmonary hypertension than in the 8 controls (9.5+/-1.9 vs 1.5+/-0.3 U x m2, p <0.05). NO lowered PVR in patients with pulmonary hypertension (p <0.05). IVUS studies in patients with pulmonary hypertension showed a thicker middle layer, wall thickness ratio, and diminished pulsatility than did those in controls (p <0.05). The inner layer was not visualized by IVUS in any control patient, but was seen in 9 of 15 patients with pulmonary hypertension. Pulmonary artery wedge angiography correlated with baseline mean pulmonary artery pressure and PVR as well as with IVUS findings of wall thickness ratio and inner layer thickness. The inner layer was not visualized by IVUS in any patient with grade 1 wedge angiograms or in 86% of patients with grade 2 wedge angiograms. All patients with grade 4 and 80% of patients with grade 3 wedge angiograms had a visible inner layer. Vasoreactivity to NO and oxygen did not correlate with structural assessment of the pulmonary vasculature by IVUS. Structural changes in the pulmonary arteries in children with pulmonary hypertension can be directly visualized by IVUS, but are not predictive of NO-induced pulmonary vasodilation. IVUS examination of pulmonary arteries may complement current techniques utilized in the evaluation of children with pulmonary hypertension.     

Paradoxic pulmonary vasoconstriction in response to acetylcholine in patients with primary pulmonary hypertension

Pulmonary vascular reactivity was assessed during diagnostic heart catheterization in two patients with pulmonary hypertension unexplained by pulmonary or cardiac disease and in five patients with atypical chest pain and normal coronary arteriograms. Acetylcholine, an endothelium-dependent vasodilator that also has a direct contracting effect on vascular smooth muscle cells, was infused in the right atrium in a step-wise increasing dose in order to obtain final blood concentrations in the pulmonary circulation ranging from 10(-6) mol/L to 10(-4) mol/L. In the five control patients, acetylcholine induced a dose-related decrease of pulmonary vascular resistance (-52 percent +/- 9 percent). In the patients with primary pulmonary arterial hypertension, however, acetylcholine caused a paradoxic increase of pulmonary arterial pressure and of pulmonary vascular resistance. Thus, it appears that endothelium-dependent vasodilation is impaired in the pulmonary circulation of patients with primary pulmonary arterial hypertension. Endothelial dysfunction in the pulmonary circulation may play a role in the pathophysiology of this disease.     

Salicylate-induced pulmonary edema

A case of pulmonary edema secondary to salicylate intoxication is described. The pulmonary wedge pressure was normal, excluding cardiogenic pulmonary edema. Thus salicylate intoxication should be considered as a rare cause in the differential diagnosis of pulmonary edema with a normal heart size. The pulmonary edema resolved gradually over 8 days. Literature relative to salicylate-induced pulmonary edema is reviewed.     

Effects of ginkgolide B on isobaric hypoxic pulmonary hypertension in rats

We examined the effects of ginkgolide B (BN52021), a specific platelet activating factor (PAF) antagonist, on hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Chronic hypoxia can cause pulmonary hypertension and pulmonary vascular remodeling in rats. Treated with BN52021, the rat's pulmonary hypertension, pulmonary vascular remodeling and right ventricular hypertrophy at 3 weeks of hypoxic exposure (FiO2 = 0,10) could be reduced. The results suggest that PAF contributes to the development of chronic hypoxic pulmonary hypertension and pulmonary vascular remodeling, and PAF antagonist may be an useful agent for preventing hypoxic pulmonary hypertension.     

A patch technique for reconstruction of stenotic pulmonary bifurcation in a Rastelli-type operation after palliations for cyanotic congenital heart disease. A report of two cases

A Rastelli-type operation was successfully performed on two patients with cyanotic congenital heart disease with pulmonary artesia (PA) and severe stenosis or obstruction of the pulmonary bifurcation, following the improvement of a pulmonary artery index (PA index) after palliative systemic pulmonary shunts. It is a point that stenotic or obstructive pulmonary bifurcation was reconstructed by a patch technique. An extracardiac conduit was used a combination of a bicuspid valved pericardial roll and a prosthetic vessel graft. In a 5-year-old male with an extreme type of tetralogy of Fallot associated with PA and patent ductus arteriosus (PDA), the enlargement of stenotic pulmonary bifurcation was attempted using a brimshaped equine pericardial patch in order to get sufficient suture margin and be safely anastomosed with a conduit. In a 6-year-old female with complete transposition of the great arteries, PA, PDA and right aortic arch (RAA), an obstructive pulmonary bifurcation behind the RAA was enlarged using a brimshaped equine pericardial patch. The attachment of the conduit was shifted to the left pulmonary artery to avoid compression of an extracardiac conduit and pulmonary artery behind RAA. Reconstruction of the pulmonary bifurcation using an equine pericardial patch is useful to anastomose an extracardiac conduit and the stenotic or obstructive pulmonary bifurcation.     

Plasma levels of adrenomedullin in primary and secondary pulmonary hypertension in patients <20 years of age

To elucidate the pathophysiologic significance of adrenomedullin in pulmonary hypertension, we measured plasma adrenomedullin-like immunoreactivity (AM-LI) concentrations in blood samples obtained from various sites during cardiac catheterization by using radioimmunoassay in patients with pulmonary hypertension in comparison with patients without pulmonary hypertension. In patients with pulmonary hypertension, plasma AM-LI concentrations were significantly elevated and there was a significant uptake of AM-LI in pulmonary circulation, indicating the involvement of adrenomedullin in the cardiovascular regulation of pulmonary circulation in pulmonary hypertension.     

Neonates with congenital heart disease, Part II: Congenital cardiac defects with increased pulmonary blood flow

Generally, cardiac lesions with increased pulmonary blood flow demonstrate cardiomegaly, increased pulmonary vascular markings, and pulmonary congestion on the chest x-ray. These findings occur as a result of the following: 1. A left-to-right shunt or mixing lesion in which excess volume of blood flow causes dilation of cardiac chambers, resulting in the appearance of cardiomegaly, and in which increased pulmonary artery blood flow causes increased pulmonary vascular markings 2. Obstruction of blood flow that produces pulmonary venous hypertension and resultant pulmonary edema The next article in this series will address cardiac lesions with decreased pulmonary blood flow.     

Bilateral pulmonary artery aneurysms in a patient with Behcet syndrome: evaluation with radionuclide angiography and V/Q lung scanning

The case of a 14-year-old girl with Behcet syndrome is described. Besides painful and recurrent oral ulcerations, the patient had a cough and intermittent hemoptysis. The initial chest roentgenogram revealed bilateral parahilar opacities. CT and MRI scans of the thorax showed bilateral thrombosing aneurysms of the pulmonary arteries. Pulmonary blood flow imaging was performed after technegas ventilation lung scanning and Tc-99m MAA injection using a first-pass radionuclide angiography procedure. Altered blood flow in the left pulmonary artery was shown. Bilateral and well-defined ventilation/perfusion mismatched areas suggested a high probability of pulmonary embolism. Little additional information was obtained on subsequent contrast pulmonary angiography. The high incidence of pulmonary artery hypertension and associated vascular injury risk makes pulmonary angiography an unsafe procedure in patients with pulmonary Behcet syndrome. The need for pulmonary angiography could be obviated in such cases with the use of high-precision MRI and ventilation/perfusion lung scanning, including radionuclide pulmonary angiography.     

Pulmonary arterial reconstruction with autologous pulmonary arterial tissue for pulmonary artery sling

One-year and two-month-old boy with pulmonary artery sling underwent pulmonary artery reconstruction with autologous pulmonary arterial tissue. Surgical repair consisted of the transection of the left pulmonary artery at its origin with trimming a button hole and the creation of an oval hole with the same size to the left pulmonary button. An autologous pulmonary patch and the left pulmonary button were exchanged and sutured to the former partner's place. He recovered uneventfully in post-operative course. Postoperative CT revealed a well developed left pulmonary artery from 5 mm to 10 mm in diameter without any distortion or stenosis. This exchange method could allow the natural growth of the anastomotic places without narrowing or distortion.     

Commissioning for health

Whether or not the pericytes exist in the intra-acinar pulmonary arteries and their normal structure and morphological changes during development of the structural remodeling of pulmonary vessels were observed using a pulmonary hypertension model in rats induced by monocrotaline injection. The results showed that the pericytes in the peripheral pulmonary vessels proliferated and transformed into smooth muscle cells during development of pulmonary hypertension, and at the same time, the pericytes could synthesize and secrete extracellular matrix including collagen, suggesting that the pericytes play an important role in the development of pulmonary hypertension and structural remodeling of the pulmonary vessels.     

Effect of pulmonary microembolism on arteriovenous shunt flow

The effects of acute pulmonary hypertension on the fraction of cardiac output shunted through pulmonary arteriovenous communications have been studied in dogs as a possible cause of hypoxia following pulmonary embolization. Pulmonary artery pressure was increased twofold and then fourfold above control values by embolization of the pulmonary vascular bed with polystyrene microspheres. Quantitative measurements of arteriovenous shunt were determined from the fraction of 50 mu radioactively labeled microspheres injected into the inferior vena cava which passed through the pulmonary circulation into systemic vascular beds. There was no increase in the fraction of pulmonary blood flow passing through pulmonary arteriovenous connections, 50 mu in diameter or greater, with pulmonary microembolism when FIo2 was 1. There was a small increase in arteriovenous shunt fraction when pulmonary artery pressure was increased with an FIo2 of 0.21. Physiological shunt measured by the oxygen technique did not increase with pulmonary embolism, but total venous admixture rose significantly. Postmortem gravimetric measurements of lung water indicated pulmonary edema. We conclude that anatomic arteriovenous shunt channels have little physiological significance after pulmonary microembolism in the dog lung. The major cause of hypoxia immediately after pulmonary microembolism is ventilation/perfusion imbalance, probably caused by pulmonary edema.     

A rare case of severe pulmonary artery hypertension. Thrombosing pulmonary microangiopathy due to tumor

We report a case of acute respiratory insufficiency with acute cor pulmonale and a fatal outcome. Right cardiac catheterisation enabled a diagnosis of precapillary pulmonary arterial hypertension to be made with a mean pulmonary arterial pressure of 61 mmHg and a pulmonary capillary pressure of 12 mHg. An autopsy was carried out and this revealed a microscopic pulmonary tumour emboli with lymphangitis carcinomatosis. In particular, it showed an association of fibrocellular proliferation at the level of the intima in the small calibre pulmonary arteries and arterioles permitting the unusual diagnosis of thrombosing pulmonary microangiomathy due to tumour. The physiopathological mechanism of this particular form of pulmonary tumour emboli is discussed; it would be secondary to an activation of the coagulation systems by the embolic tumour cells. Once activated, it is the lesions in the intima and not the carcinoma cells which generate the pulmonary arterial hypertension by vascular obstruction.     

Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow

BACKGROUND: Children with increased pulmonary blood flow may experience morbidity as the result of increased pulmonary vascular resistance after operations in which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. OBJECTIVES: In a lamb model of increased pulmonary blood flow after in utero placement of an aortopulmonary shunt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothelin-1 and endothelin-A receptor activation in postbypass pulmonary hypertension. METHODS: In eleven 1-month-old lambs, the shunt was closed, and vascular pressures and blood flows were monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic variables were monitored, and plasma endothelin-1 concentrations were determined before, during, and for 6 hours after cardiopulmonary bypass. RESULTS: After 90 minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmonary vascular resistance increased significantly in saline-treated lambs during the 6-hour study period (P <.05). In lambs pretreated with PD 156707, pulmonary arterial pressure and pulmonary vascular resistance decreased (P <. 05). After bypass, plasma endothelin-1 concentrations increased in all lambs; there was a positive correlation between postbypass pulmonary vascular resistance and plasma endothelin-1 concentrations (P <.05). CONCLUSIONS: This study suggests that endothelin-A receptor-induced pulmonary vasoconstriction mediates, in part, the rise in pulmonary vascular resistance after cardiopulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation.     

Clinical implications and possible association of malposition of the branch pulmonary arteries with DiGeorge syndrome and microdeletion of chromosomal region 22q11

We describe a series of 10 patients with malposition of the branch pulmonary arteries (4 patients with crossing [crossed pulmonary arteries] and 6 patients without crossing), 2 of whom had a short main pulmonary artery segment that resulted in iatrogenic right pulmonary artery stenosis after pulmonary artery band placement. DiGeorge syndrome was seen in 5 patients and 4 had microscopic deletion of chromosomal region 22q11.     

Chronic thromboembolic pulmonary hypertension

Acute pulmonary hypertension has a high mortality at the onset. Patients surviving the first phase will usually recanalize the pulmonary arteries through intrinsic thrombolytic mechanisms and medical treatment. However, in some cases there is insufficient resolution of the emboli with subsequent thrombotic and fibrotic reorganization, leading to a worsening of the pulmonary obstruction. In the open pulmonary arteries the disease may lead to hypertrophy of the media and intimal proliferation, thus leading to a further increase in the pulmonary vascular resistance. This again leads to hypertrophy of the right ventricle and ultimately to right-sided heart failure. Untreated, chronic thromboembolic pulmonary hypertension has a five-year mortality approaching 100%, but extensive pulmonary thrombendarterectomy using extracorporeal circulation and deep hypothermia has been shown to lower the pulmonary vascular resistance and thereby improve the prognosis significantly. Operative treatment can now be offered in Denmark, and the purpose of this review is to draw attention to the disease, its symptoms, diagnosis and the surgical treatment.     

Aberrant left pulmonary artery presenting as a right paratracheal mass in an adult

Aberrant left pulmonary artery, or pulmonary sling, is a rare variation of the pulmonary vasculature, with only one previous report of the condition being recognized in an adult. In this report a second case recognized de novo in an adult is presented. Both of these adults were evaluated because of right paratracheal masses which required differentiation from pulmonary malignancies. The barium swallow shows a characteristic indentation of the anterior esophageal wall and the lateral tomogram demonstrates absence of the left pulmonary artery from its normal position in the left hilum. The pulmonary arteriogram is diagnostic and allows avoidance of more invasive diagnostic measures.     

The role of thrombosis in severe pulmonary hypertension

Considering the important surface in pulmonary circulation where blood can interact with the endothelium, the maintenance of blood fluidity through the lung, by antithrombotic pathways and products of the endothelium, is essential. This function appears to be ineffective in primary pulmonary hypertension and in severe secondary pulmonary hypertension. Thrombotic lesions are frequently found in pulmonary arteries in these diseases. Thrombin activity appears to be increased in severe pulmonary hypertension. Antithrombotic pathway disorders may account for this abnormality, particularly in chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. Injured endothelium, a constant feature in severe pulmonary hypertension, either primary or secondary, enhances thrombus formation in pulmonary vessels. This is probably related to thrombomodulin and tissue factor imbalance, impairment of prostacyclin and nitric oxide release, as well as inefficiency of fibrinolysis. Moreover, platelets appear to be activated in the pulmonary circulation of these patients. They release several mediators acting on vascular tone and as mitogenic agents, and may also contribute to thrombin and clot generation. Long-term oral anticoagulant and continuous infusion of prostacyclin, treatments which impede thrombosis, are known to improve the survival rate in patients with primary pulmonary hypertension. These are the strongest arguments, so far, in favour of the role of thrombosis in severe pulmonary hypertension. However, we do not know whether these abnormalities result from a previous vascular injury or represent the primary disturbance.     

Brain natriuretic peptide is stable in whole blood and can be measured using a simple rapid assay: implications for clinical practice

Patients with moderate and severe pulmonary hypertension have a very high mortality rate when undergoing orthotopic liver transplantation. Because nitric oxide has been successful in reducing pulmonary artery pressures in certain patients with pulmonary hypertension, the efficacy of NO inhalation (40 and 80 ppm) in 4 patients with pulmonary hypertension associated with liver disease was determined. No clinically significant changes in pulmonary artery pressures or other hemodynamic parameters were observed using either concentration of NO. In conclusion, no pulmonary vasodilatory response from inhalation of NO in 4 patients with severe liver disease and pulmonary hypertension was found.