Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consist...Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries(50-20 μm), arterioles(20-10 μm), and capillaries(< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcircula-tory resistance during maximal hyperemia, which is calculated by dividing pressure by flow(distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.展开更多
Background: Cardiac Allograft Vasculopathy (CAV) is characterized by vascular inflammation and intimal proliferation which results in luminal stenosis and myocardial infarction. During vascular inflammation elaboratio...Background: Cardiac Allograft Vasculopathy (CAV) is characterized by vascular inflammation and intimal proliferation which results in luminal stenosis and myocardial infarction. During vascular inflammation elaboration of several cytokines and differential expression of growth factors have been noted. CAV remains the major threat to long-term graft survival. CD4 and CD8 T-cell subsets play a significant role in the development of transplant rejection. Chronic transplant rejection often leads to development of CAV. A new CD4 effector cell subset that produces IL-17 (Th17) has been shown to be up-regulated in the murine system in the setting of CAV. This study assesses the level of IL-17 in cardiac transplant patients with and without CAV as compared to nontransplanted controls. Methods: Levels of IL-17, IL-6, MCP-1 were measured by ELISA in plasma of four nontransplanted controls, nine cardiac allograft recipients with CAV (HT-GVD) and eight post transplant subjects without a diagnosis of CAV (HT-No GVD). All post transplant patients were immune suppressed with cyclosporine. HT-GVD patients were 1-15 years post transplant while HT-No GVD subjects were 1 - 10 years post transplant. Results: IL-17, MCP-1 and IL-6 were significantly down regulated in HT-GVD subjects compared to the HT-No GVD subjects (p 0.001) but not significant between controls and HT-No GVD (p = ns). Conclusions: A decrease in IL-17 in HT-GVD subjects as compared to HT-No GVD in the presence of cyclosporine treatment could be a consequence of down regulation of IL-6. It is likely that cyclosporine differentially regulates pro inflammatory molecules in the setting of graft vascular disease.展开更多
For heart transplant patients, there are a number of non-immunosuppressant medications that are routinely prescribed to mitigate the side-effects of immunosuppression, treat the related complications, and improve long...For heart transplant patients, there are a number of non-immunosuppressant medications that are routinely prescribed to mitigate the side-effects of immunosuppression, treat the related complications, and improve long-term survival. This review focuses on the medications used to prevent and manage cardiac allograft vasculopathy (CAV), hypertension, dyslipidemia and osteoporosis. The rationale and evidence supporting their use are summarized and the immunosuppressant drugs are only discussed briefly, as they relate to each of these medical issues. Pharmacy practitioners are likely to encounter patients post-cardiac transplant in a variety of clinical settings;therefore, a concise appreciation of the principles for the long-term medical management of these patients is important when providing collaborative care.展开更多
While life expectancy is greatly improved after a heart transplant, survival is still limited, and compared to the general population, the exercise capacity and healthrelated quality of life of heart transplant recipi...While life expectancy is greatly improved after a heart transplant, survival is still limited, and compared to the general population, the exercise capacity and healthrelated quality of life of heart transplant recipients are reduced. Increased exercise capacity is associated with a better prognosis. However, although several studies have documented positive effects of exercise after heart transplantation(HTx), little is known about the type, frequency and intensity of exercise that provides the greatest health benefits. Moreover, the long-term effects of exercise on co-morbidities and survival are also unclear. Exercise restrictions apply to patients with a denervated heart, and for decades, it was believed that the transplanted heart remained denervated. This has since been largely disproved, but despite the new knowledge, the exercise restrictions have largely remained, and up-to-date guidelines on exercise prescription after HTx do not exist. High-intensity, interval based aerobic exercise has repeatedly been documented to have superior positive effects and health benefits compared to moderate exercise. This applies to both healthy subjects as well as in several patient groups, such as patients with metabolic syndrome, coronary artery disease or heart failure. However, whether the effects of this type of exercise are also applicable to heart transplant populations has not yet been full yestablished. The purpose of this article is to give an overview of the current knowledge about the exercise capacity and effect of exercise among heart transplant recipients and to discuss future exercise strategies.展开更多
Cardiac Allograft Vasculopathy, an accelerated form of arterial occlusive disease, is the major cause of death in the long-term after heart transplantation. Multiple factors influence the initiation and progression of...Cardiac Allograft Vasculopathy, an accelerated form of arterial occlusive disease, is the major cause of death in the long-term after heart transplantation. Multiple factors influence the initiation and progression of CAV. These include ischemia-reperfusion, dyslipidemia, insulin resistance, and hypertension due to the use of immunosuppressive agents, the direct effects of immunosuppressive agents on endothelial function, and viruses (CMV). Impaired endothelial function reflects abnormalities in the production or activity of several vasoactive substances. Disruption of the nitric oxide synthase (NOS) pathway leads to changes in vascular reactivity, structure, and interaction with circulating blood components. Since endothelium-derived nitric oxide (NO) suppresses vascular cell proliferation and vascular inflammation, a deficit in vascular NO facilitates development of CAV. The link between oxidative stress and CAV largely exists in the balance between free radical superoxide generation and NO production. This review focuses on identifying the oxidative stress factors affecting CAV.展开更多
Objective Develop the model of post-transplant cardiac allograft vasculopathy (CAV) and prevent or treat CAV through Expression of iNOSmRNA.Methods Rat model of heterotopic heart transplantation was developed and thre...Objective Develop the model of post-transplant cardiac allograft vasculopathy (CAV) and prevent or treat CAV through Expression of iNOSmRNA.Methods Rat model of heterotopic heart transplantation was developed and three groups were divided as following: Comparison group, CsA group, iNSOmRNA group. Hearts were harvested at post-operative two weeks and four weeks and CAV was detected by immunohitochemical technique and in situ hybridization technique.Results iNOSmRNA group had no CAV develpment and synthetizing vast NO.Conclusion Expression of iNOSmRNA can prevent CAV development.展开更多
Objective To study the mechanism of glucose transporting by the way of in different blood state myocardium.Methods The expression of GLUT4、 GLUT1 was dectected with Western blotting analysis.Results GLUT4、GLUT1 was ...Objective To study the mechanism of glucose transporting by the way of in different blood state myocardium.Methods The expression of GLUT4、 GLUT1 was dectected with Western blotting analysis.Results GLUT4、GLUT1 was increased when phenylephrine was used before ischemia. During ischemia,GLUT4、GLUT1 was increased. Phenylephrine given during repefusin increased GLUT4、GLUT1.Prazosin given during ischemia,GLUT4、GLUT1 was reduced. During reperfusion,GLUT4、GLUT1 was decreased.Conclusion Changing the expression of GLUT4、 GLUT1,adjustting transporting of glucose,controlling glucose transport in different states of cardiac muscle cell by α1-adrenoceptors.展开更多
文摘Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries(50-20 μm), arterioles(20-10 μm), and capillaries(< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcircula-tory resistance during maximal hyperemia, which is calculated by dividing pressure by flow(distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.
文摘Background: Cardiac Allograft Vasculopathy (CAV) is characterized by vascular inflammation and intimal proliferation which results in luminal stenosis and myocardial infarction. During vascular inflammation elaboration of several cytokines and differential expression of growth factors have been noted. CAV remains the major threat to long-term graft survival. CD4 and CD8 T-cell subsets play a significant role in the development of transplant rejection. Chronic transplant rejection often leads to development of CAV. A new CD4 effector cell subset that produces IL-17 (Th17) has been shown to be up-regulated in the murine system in the setting of CAV. This study assesses the level of IL-17 in cardiac transplant patients with and without CAV as compared to nontransplanted controls. Methods: Levels of IL-17, IL-6, MCP-1 were measured by ELISA in plasma of four nontransplanted controls, nine cardiac allograft recipients with CAV (HT-GVD) and eight post transplant subjects without a diagnosis of CAV (HT-No GVD). All post transplant patients were immune suppressed with cyclosporine. HT-GVD patients were 1-15 years post transplant while HT-No GVD subjects were 1 - 10 years post transplant. Results: IL-17, MCP-1 and IL-6 were significantly down regulated in HT-GVD subjects compared to the HT-No GVD subjects (p 0.001) but not significant between controls and HT-No GVD (p = ns). Conclusions: A decrease in IL-17 in HT-GVD subjects as compared to HT-No GVD in the presence of cyclosporine treatment could be a consequence of down regulation of IL-6. It is likely that cyclosporine differentially regulates pro inflammatory molecules in the setting of graft vascular disease.
文摘For heart transplant patients, there are a number of non-immunosuppressant medications that are routinely prescribed to mitigate the side-effects of immunosuppression, treat the related complications, and improve long-term survival. This review focuses on the medications used to prevent and manage cardiac allograft vasculopathy (CAV), hypertension, dyslipidemia and osteoporosis. The rationale and evidence supporting their use are summarized and the immunosuppressant drugs are only discussed briefly, as they relate to each of these medical issues. Pharmacy practitioners are likely to encounter patients post-cardiac transplant in a variety of clinical settings;therefore, a concise appreciation of the principles for the long-term medical management of these patients is important when providing collaborative care.
文摘While life expectancy is greatly improved after a heart transplant, survival is still limited, and compared to the general population, the exercise capacity and healthrelated quality of life of heart transplant recipients are reduced. Increased exercise capacity is associated with a better prognosis. However, although several studies have documented positive effects of exercise after heart transplantation(HTx), little is known about the type, frequency and intensity of exercise that provides the greatest health benefits. Moreover, the long-term effects of exercise on co-morbidities and survival are also unclear. Exercise restrictions apply to patients with a denervated heart, and for decades, it was believed that the transplanted heart remained denervated. This has since been largely disproved, but despite the new knowledge, the exercise restrictions have largely remained, and up-to-date guidelines on exercise prescription after HTx do not exist. High-intensity, interval based aerobic exercise has repeatedly been documented to have superior positive effects and health benefits compared to moderate exercise. This applies to both healthy subjects as well as in several patient groups, such as patients with metabolic syndrome, coronary artery disease or heart failure. However, whether the effects of this type of exercise are also applicable to heart transplant populations has not yet been full yestablished. The purpose of this article is to give an overview of the current knowledge about the exercise capacity and effect of exercise among heart transplant recipients and to discuss future exercise strategies.
文摘Cardiac Allograft Vasculopathy, an accelerated form of arterial occlusive disease, is the major cause of death in the long-term after heart transplantation. Multiple factors influence the initiation and progression of CAV. These include ischemia-reperfusion, dyslipidemia, insulin resistance, and hypertension due to the use of immunosuppressive agents, the direct effects of immunosuppressive agents on endothelial function, and viruses (CMV). Impaired endothelial function reflects abnormalities in the production or activity of several vasoactive substances. Disruption of the nitric oxide synthase (NOS) pathway leads to changes in vascular reactivity, structure, and interaction with circulating blood components. Since endothelium-derived nitric oxide (NO) suppresses vascular cell proliferation and vascular inflammation, a deficit in vascular NO facilitates development of CAV. The link between oxidative stress and CAV largely exists in the balance between free radical superoxide generation and NO production. This review focuses on identifying the oxidative stress factors affecting CAV.
文摘Objective Develop the model of post-transplant cardiac allograft vasculopathy (CAV) and prevent or treat CAV through Expression of iNOSmRNA.Methods Rat model of heterotopic heart transplantation was developed and three groups were divided as following: Comparison group, CsA group, iNSOmRNA group. Hearts were harvested at post-operative two weeks and four weeks and CAV was detected by immunohitochemical technique and in situ hybridization technique.Results iNOSmRNA group had no CAV develpment and synthetizing vast NO.Conclusion Expression of iNOSmRNA can prevent CAV development.
文摘Objective To study the mechanism of glucose transporting by the way of in different blood state myocardium.Methods The expression of GLUT4、 GLUT1 was dectected with Western blotting analysis.Results GLUT4、GLUT1 was increased when phenylephrine was used before ischemia. During ischemia,GLUT4、GLUT1 was increased. Phenylephrine given during repefusin increased GLUT4、GLUT1.Prazosin given during ischemia,GLUT4、GLUT1 was reduced. During reperfusion,GLUT4、GLUT1 was decreased.Conclusion Changing the expression of GLUT4、 GLUT1,adjustting transporting of glucose,controlling glucose transport in different states of cardiac muscle cell by α1-adrenoceptors.
