Pulmonary arterial hypertension due to congenital somatopulmonary shunts belongs to the first category, namely arterial pulmonary hypertension. The annual incidence of congenital disease-associated PAH is 3 per 1 million people, respectively, and a registry study in the Netherlands showed a 4.2% incidence of PAH in adult precocious patients.
Globally, 1.5 million children with congenital heart disease are born each year, 96,000 of whom are born in China, and 50% of patients with a defect >1.5 cm in diameter with a ventricular septal defect develop pulmonary hypertension. Without effective diagnosis and treatment of PAH, the prognosis is extremely poor, comparable to that of malignancy. Approximately 10,000 patients die each year in the United States because of PAH.
The reversibility of PAH depends on the degree of pulmonary vascular disease, and lung biopsy can generally determine the degree and extent of pulmonary vascular disease, which in turn provides a basis for the selection of surgical indications and surgical efficacy. However, lung biopsy is an invasive test with certain risks and should not be used as a routine. Therefore, cardiac catheterization is a common clinical technique to evaluate pulmonary vascular lesions, and to understand the degree of pulmonary vascular lesions by evaluating the pulmonary vascular resistance.
Normal pulmonary vascular resistance is less than 3woods. When the pulmonary resistance rises to 6-8woods, the risk of surgery increases significantly, when 8-10woods, the risk of surgery is high, and when it is greater than 10woods units, surgery is generally not considered. After the pulmonary vascular resistance increases to a certain degree, it is mostly irreversible pathological changes, and even after surgery, the pulmonary vascular resistance cannot be reduced to normal, and there is still a risk of sudden death due to pulmonary hypertension crisis.
As for pulmonary hypertension due to transposition of the great arteries, some authors believe that it is reversible, and there are many reports on it. However, due to the hemodynamic peculiarities of patients with transposition of the great arteries, the accuracy of the evaluation of their pulmonary resistance is strongly questioned. There are also reports of good follow-up results with palliative transposition, but the period results still need to be supported by more evidence.
The management of secondary pulmonary hypertension due to precordial disease is significantly preventive, i.e., aggressive treatment of the primary disease and early surgery. Oxygen administration reduces pulmonary vasospasm and decreases pulmonary vascular resistance, while having little effect on the body circulation. Generally speaking, the longer the oxygen is administered, the better, but inhaling high concentrations of oxygen for a long time can lead to lung injury. Therefore, oxygen inhalation is generally used to treat acute pulmonary hypertension and hypoxemia.
Mechanical ventilation in clinical practice, acidosis can lead to strong pulmonary vasoconstriction and aggravate pulmonary hypertension. Excessive mechanical ventilation can correct acidosis and reduce pulmonary vascular resistance and pulmonary artery pressure. However, mechanical ventilation is only used in the short term for the treatment of acute pulmonary hypertension and can lead to pneumatic injuries and oxygen toxicity if used improperly.
In addition, drug therapy has been the main means of treating pulmonary hypertension, but the effect is not satisfactory. The main drugs currently used to treat pulmonary hypertension are vasodilators. Since the discovery in the 1940s that intravenous use of toltrazurine could simultaneously reduce the pressure of the body and pulmonary circulation, vasodilators have been widely used. From calcium channel blockers and prostacyclin in the 1980s to selective pulmonary vasodilators represented by NO in the 1990s, research has opened up new avenues for the treatment of pulmonary hypertension.
The following classes of drugs are commonly used to treat pulmonary hypertension.
1.Adrenergic receptor blocking agents
Toltrazurin, as a non-selective a-adrenergic receptor blocker, can dilate the pulmonary vasculature and thus reduce pulmonary artery pressure. However, it reduces the pulmonary artery pressure and at the same time makes the blood pressure of body circulation drop significantly, and when the blood volume is insufficient, it can make the ventricular filling pressure drop and the cardiac output decrease, and the action time of tolarsuline is short, and it needs to maintain the static point for a long time.
2.Calcium channel blockers
Studies have shown that different calcium channel blockers have different strength and selectivity of action on the heart and blood vessels. Nifedipine (cardiac pain) is a calcium channel blocker mainly acting on vascular smooth muscle, which has strong dilating effect on peripheral blood vessels and pulmonary blood vessels, and can reduce pulmonary vascular resistance and pulmonary artery pressure in patients with congenital heart disease.
In addition, in vitro experiments have shown that calcium channel blockers can inhibit the pro-proliferative effect of various growth factors (such as basic fibroblast growth factor and PDGF) on vascular smooth muscle cells, suggesting that calcium channel blockers may have an indirect inhibitory effect on pulmonary vascular structural reconstruction, but there are no reports of long-term application of calcium channel blockers to relieve pulmonary vascular reconstruction. Calcium channel blockers have negative inotropic effects, which most children with congenital heart disease cannot tolerate for a long time, which limits their clinical application.
3.Phosphodiesterase (PDE) inhibitors
Sildenafil is a specific inhibitor of PDE-5, which increases the content of cAMP in vascular smooth muscle cells by blocking the degradation of cAMP, thus reducing the release of calcium ions from the sarcoplasmic reticulum and causing vascular smooth muscle diastole. Sildenafil was found to have a selective pulmonary vasodilating effect, an effect that depends on the patient’s pulmonary artery pressure and the magnitude of pulmonary vascular resistance.
In patients with left-to-right shunt congenital heart disease combined with pulmonary hypertension, sildenafil has a significant selective dilating effect on the pulmonary vasculature. In addition, sildenafil can dilate blood vessels and inhibit smooth muscle cell proliferation by increasing cytoplasmic cGMP levels. At present, this drug has been used in clinical practice, and has achieved good results.
4.ETA receptor antagonist
Bosentan is the first non-selective ETA receptor antagonist applied to pulmonary arterial hypertension, which can alleviate the reconstruction of pulmonary vascular structure and the formation of pulmonary hypertension in rats. Bosentan can reduce pulmonary artery pressure and improve pulmonary hemodynamic index. The drug has been widely used in clinical practice, and its effects have been confirmed in large sample studies.
5.ACEI and AT receptor antagonists
ACEI can reduce the production of AT-II by inhibiting angiotensin-converting enzyme, which has a diastolic effect and inhibits the proliferation of vascular smooth muscle cells, and AT receptor antagonists have similar effects to ACEI by inhibiting the effect of AT-II. and has been widely used in clinical practice. However, the effect of ACEI varies from patient to patient and can be aggravated if not properly applied.
The combined results of the study by Webster et al.
(1) ACEI is most appropriate in the early stage of left-to-right shunt congenital heart disease, when there is no significant increase in pulmonary vascular resistance and heart failure is present. Because the diastolic effect of ACEI on the pulmonary vasculature is much less than that of the body circulation, the use of ACEI at this time can reduce the abnormally increased resistance of the body circulation without changing the resistance of the pulmonary circulation, thus reducing the left-to-right shunt flow and slowing the formation of pulmonary hypertension.
When there is only pulmonary hypertension without heart failure, ACEI should not be used; at this time, the resistance of pulmonary circulation is high, but the resistance of body circulation is not high, ACEI not only cannot reduce the left-to-right shunt flow and improve hemodynamics, but also may make the condition worse.
When left-to-right shunt congenital heart disease develops to the stage of obstructive pulmonary hypertension, ACEI is even more inappropriate. at this time, ACEI will lead to an increase in right-to-left shunt, reduce oxygen saturation and aggravate hypoxia.
6.Prostaglandin-based drugs
Clinical data show that PGE1 can significantly improve the preoperative hemodynamic index of patients with congenital heart disease combined with pulmonary hypertension, and reduce the patient’s pulmonary artery pressure before and after surgery. However, PGE1 is a non-selective vasodilator, which reduces pulmonary artery pressure while causing a significant decrease in body circulation pressure, which greatly limits its clinical application.
In conclusion, prevention of pulmonary hypertension due to preconditioning is important, and the primary preconditioning should be corrected as early as possible. Once irreversible changes in the secondary pulmonary vasculature occur, the prognosis is poor, and pharmacological treatment is not satisfactory at present, perhaps lung transplantation can only be the last option.