The Effects of Chronic Immunosuppressive Treatment on Morphological Changes in Cardiac Tissue and the Balance between Matrix Metalloproteinases (MMP-2 and MMP-9) and Their Inhibitors in the Rat Heart.

Using different three-drug immunosuppressive treatment regimens in a rat model, we aimed to determine the effects of long-term therapy on metalloproteinase-2 and metalloproteinase-9 activity and the expression of their inhibitors, as well as to assess the morphology of the animals' cardiac tissue. Our results suggest that chronic use of immunosuppressive drugs disrupts the balance between the activity of MMPs and TIMPs. Depending on the type of drug regimen used, this leads to abnormalities in the cardiac structure, collagen fiber accumulation, or cardiomyocyte hypertrophy. The information obtained in the present study allows us to conclude that the chronic treatment of rats with the most common clinical immunosuppressive regimens may contribute to abnormalities in the myocardial structure and function. The results presented in this study may serve as a prelude to more in-depth analyses and additional research into the optimal selection of an immunosuppressive treatment with the lowest possible risk of cardiovascular complications for patients receiving organ transplants.

Immunosuppressive Agents-Effects on the Cardiovascular System and Selected Metabolic Aspects: A Review.

The widespread use of immunosuppressive drugs makes it possible to reduce inflammation in autoimmune diseases, as well as prevent transplant rejection in organ recipients. Despite their key action in blocking the body's immune response, these drugs have many side effects. These actions primarily affect the cardiovascular system, and the incidence of complications in patients using immunosuppressive drugs is significant, being associated with a higher incidence of cardiovascular incidents such as myocardial infarction and stroke. This paper analyzes the mechanisms of action of commonly used immunosuppressive drugs and their impact on the cardiovascular system. The adverse effect of immunosuppressive drugs is associated with toxicity within the cardiovascular system, which may be a problem in the clinical management of patients after transplantation. Immunosuppressants act on the cardiovascular system in a variety of ways, including fibrosis and myocardial remodeling, endothelium disfunction, hypertension, atherosclerosis, dyslipidemia or hyperglycaemia, metabolic syndrome, and hyperuricemia. The use of multidrug protocols makes it possible to develop regimens that can reduce the incidence of cardiovascular events. A better understanding of their mechanism of action and the range of complications could enable physicians to select the appropriate therapy for a given patient, as well as to reduce complications and prolong life.

The Effect of Calcineurin Inhibitors on MMPs Activity in Heart and Their Side Effects-A Review of Literature.

This review focuses on the role of metalloproteinases in the pathogenesis of myocardial injury in various disease entities. It reveals how the expression and serum levels of metalloproteinases and their inhibitors change in many disease states. At the same time, the study offers a review of the impact of immunosuppressive treatment on this relationship. Modern immunosuppressive treatment is based mainly on the use of calcineurin inhibitors, including cyclosporine A and tacrolimus. The use of these drugs may carry a number of side effects, specifically to the cardiovascular system. The scale and degree of long-term influence on the organism remains unclear, but a significant risk of complications for transplant recipients who take immunosuppressive drugs as part of their daily treatment is to be expected. Therefore, the knowledge on this subject should be expanded and the negative effects of post-transplant therapy minimized. Immunosuppressive therapy plays an important role in the expression and activation of tissue metalloproteinases and their specific inhibitors, which leads to many tissue changes. The presented study is a collection of research results on the effects of calcineurin inhibitors on the heart, with particular emphasis placed on the participation of MMP-2 and MMP-9. It is also an analysis of the effects of specific heart diseases on myocardial remodeling through inductive or inhibitory effects on matrix metalloproteinases and their inhibitors.

Questionable Long-Term Results of the Extended Provisional Extension to Induce Complete Attachment (E-PETTICOAT) Technique in the Management of Chronic Type B Aortic Dissection.

BACKGROUND: Published interim results of the extended provisional extension to induce complete attachment (e-PETTICOAT) technique suggested favorable remodeling in chronic type B Aortic Dissection (cTBAD). This report presents long-term results of the e-PETTICOAT technique for the management of cTBAD (without aneurysmal dilatation). METHODS: Patients with cTBAD below the 55 mm aortic size were eligible for the management using the e-PETTICOAT technique. Follow-up was conducted at 1, 2 and 5 years based on the computed tomography angiogram. All the presurgery risk factors (entry >1 cm, inner curve entry, fusiform index >0.65, false lumen > 22 mm, aortic size >40 mm, recurrent pain or hypertension, and Stanford Dissection Risk Calculation) and postsurgery complications were examined in the study. RESULTS: A total of 20 patients underwent the e-PETTICOAT surgery. The survival rate at 1, 2, and 5 years was 75%, 70%, and 64%, respectively, and the percentage of patients without any reinterventions was 100%, 93%, and 18%. Aortic degeneration was recognized in 30%, 55%, and 85% of the patients. Only 3 of the 20 patients were alive and without any reintervention after 5 years. The receiver operating curve analysis does not indicate any factor that would predict the remodeling result in the long-term follow-up. CONCLUSIONS: The use of e-PETTICOAT technique in cTBAD might not have a beneficial influence on the long-term results.

Physician-modified endograft in ruptured aortic arch.

We present the case of a 27-year-old motorcyclist after a multi-organ trauma. He suffered a rupture of the aortic arch located in zone 2 and was disqualified from surgical replacement of the aortic arch due to active bleeding from parenchymal organs. Instead, he was provided with a physician-modified endograft (PMEG) to complete fenestrated thoracic endovascular aortic repair as a damage control procedure. No reports in the world literature are found regarding the use of PMEG technology in truly ruptured post-traumatic pseudo-aneurysm on the border of zone 1 and 2 of the aortic arch in emergency settings. The surgery provided temporary supply of the aorta and allowed all of the other surgical and orthopedic procedures to be completed. Endovascular treatment of aortic arch damage with PMEG is possible and can be effectively used for urgent indications when an open operation is not possible.