ABSTRACT
BACKGROUND: Cardiovascular disease (CVD), especially ischemic heart disease (IHD) and vascular access occlusion (VAO) is the most common morbidity in dialysis patients. Hyperhomocysteinemia (HHcy) is regarded as an independent risk factor of atherosclerosis in general population, however clinical implication of HHcy in dialysis patients is controversial. Nutritional status of dialysis patients is also known to be closely linked to CVD. METHODS: To investigate the impact of the presence of HHcy and malnutrition on cardiovascular events, especially ischemic heart disease (IHD) and vascular access occlusion (VAO). We measured plasma levels of Hcy and other biochemical parameters with an evaluation of nutritional status using subjective global assessment (SGA) in 44 HD patients and gender-matched control subjects of comparable age. RESULTS: Mean plasma Hcy was 18.6 microM/L (range 5-28), which was significantly higher than normal control (8.6+/-2.0 microM/L, p< 0.05). There was no significant correlation between plasma Hcy and the levels of folate or vit B12. Mean Hcy was significantly higher in patients with normal nutritional status compared to mild-to-moderately malnourished patients (22.0+/-3.2 vs. 15.1+/-4.1 microM/L, p<0.05), and there was a significant positive correlation of Hcy level with serum albumin or nPNA. There was no significant difference in plasma Hcy level according to the presence of IHD or VAO. However, interestingly, in HD patients group with lower serum albumin (<3.9 g/ dL), frequency of VAO was significantly correlated with Hcy (r2=0.68, p<0.001) whereas no significant correlation was observed in patients with higher albumin level. CONCLUSION: The clinical implication of HHcy in HD patients may be different from general healthy population. Nutritional status can be one of the important factors influencing plasma Hcy level. And, high plasma level of Hcy in malnourished HD patients has to be carefully followed up in terms of the development of atherosclerotic CVD and VAO.
Subject(s)
Humans , Atherosclerosis , Cardiovascular Diseases , Dialysis , Folic Acid , Hyperhomocysteinemia , Malnutrition , Myocardial Ischemia , Nutritional Status , Plasma , Renal Dialysis , Risk Factors , Serum AlbuminABSTRACT
To evaluate the clinical efficacy and safety of newly developed recombinant human erythropoietin (Epokine(R)), a phase III clinical trial was performed in patients with end-stage renal disease undergoing maintenance hemodialysis. Epokine(R)was given initially at a dosage of 50unit/kg, intravenously, three times a week after each dialysis session and the dosage was adjusted according to the changes in hemoglobin level. Out of total 79 patients who were enrolled initially, data of 64 patients who have completed 12 weeks study period were analyzed. The results were as following: 1) Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine(R) administration. Hemoglobin increased significantly from 6.8+/-0.8 to 10.4+/-1.3 and hematocrit increased significantly from 20.9+/-2.2 to 31.1+/-5.2 after 12 weeks(P<0.05). Corrected reticulocyte count(%) increased significantly from 0.6+/-0.4 to 1.4+/-0.7 after 2 weeks and to 1.3+/-0.6 after 12 weeks(P<0.05). 2) A significant increase in platelet count was observed from 2 weeks after Epokine(R) administration (P<0.05). 3) Serum ferritin and serum iron decreased significantly and total iron binding capacity increased significantly after 2 weeks(P<0.05). 4) The mean of pre-hemodialysis systolic blood pressure(mmHg) increased significantly from 148+/-21 to 154+/-25 at 12 weeks(P<0.05). Also, post-hemodialysis blood pressure(systolic/diastolic) at 12 weeks increased significantly from baseline levels(146+/-28/ 82+/-15 vs. 153+/-25/87+/-14mmHg, P<0.05). 5) Anti-erythropoietin antibody was not detected in all subjects. 6) Side effects observed in this study were similar to those reported by earlier reports. Headache(9 cases), and flu-like syndrome(7 cases) were the most common side effects. These side effects were not severe and disappeared without discontinuation of Epokine(R) administration in most of the patients. In conclusion, Epokine(R) is safe and effective in treating anemia of hemodialysis patients with end stage renal disease.
Subject(s)
Humans , Anemia , Dialysis , Erythropoietin , Ferritins , Hematocrit , Iron , Kidney Failure, Chronic , Platelet Count , Renal Dialysis , ReticulocytesABSTRACT
BACKGROUND: No-reflow is a specific type of vascular damage occuring when removal of coronary occlusion dose not lead to restoration of coronary flow. There are three major explanations for the no-reflow phenomenon such as endothelial cell edema, microvascular plugging by platelets or thrombi and coronary occlusion by ischemic contracture of the myocardium. But detailed mechanisms of no-reflow phenomenon are not known. The objects of this study are to elucidate the possibility whether elevation of cytosolic Ca2+ concentration during ischemic cardioplegic period is mechanism of no-reflow phenomenon or not. METHODS: Changes in cytosolic Ca2+ concentration were measured under varying experimental condition. Free [Ca2+] in the cytosole [Ca2+]i of single rabbit coronary artery cells was measured with fluorescent Ca2+ indicator, Fura-2. RESULTS: Resting [Ca2+]i was 134.2+/-34 nM (n=43). When single cells were perfused with cardioplegic or ischemic cardioplegic solution, [Ca2+]i was significantly increased and degree of [Ca2+]i elevation was further augmented by ischemic cardioplegic solution. Pretreatment of sarcoplasmic reticulum emptying agent (20mM caffeine) had no effect on cardioplegia-induced [Ca2+]i change, but application of Ca2+ channel blocker (5x10-7M nifedipine) or an antagonist of Na+/Ca2+ exchange (5mM Ni2+ ) partially (nifedipine) or completely (nickel) inhibited the [Ca2+]i elevation. Pretreament of caffeine had no effect on ischemic cardioplegia-induced [Ca2+]i change, but application of nifedipine or nickel partially inhibited the [Ca2+]i elevation. Magnitude of ischemic cardioplegia-induced [Ca2+]i elevation was dependent on the Ca2+ concentration of perfusate from 0 to 2.5mM. When Ni2+ was added to reperfusion solution, recovery of ischemic cardioplegia-induced [Ca2+]i elevation was very rapid compared with control. CONCLUSIONS: From the above results, it may be speculated that ischemic cardioplegia-induced [Ca2+]i elevation may act as one of the mechanism of no-reflow phenomenon in rabbit coronary artery.
Subject(s)
Caffeine , Cardioplegic Solutions , Coronary Occlusion , Coronary Vessels , Cytosol , Edema , Endothelial Cells , Fura-2 , Ischemic Contracture , Muscle, Smooth , Myocardium , Myocytes, Smooth Muscle , Nickel , Nifedipine , No-Reflow Phenomenon , Reperfusion , Sarcoplasmic ReticulumABSTRACT
To elucidate the possibility whether an elevation of intracellular Ca2+ concentration ([Ca2+]i) in rabbit coronary artery myocytes during ischemic cardioplegic period may serve as one of the mechanisms of the "no-reflow' phenomenon or not, the changes in [Ca2+]i were measured under ischemic cardioplegia conditions using a fluorescent Ca2+ indicator, fura 2/AM. When single cells were perfused with cardioplegic or ischemic cardioplegic solutions, [Ca2+]i was significantly increased and the degree of [Ca2+] elevation was further augmented by the ischemic cardioplegic solution. Pretreatment of a sarcoplasmic reticulum emptying agent, 20 mM caffeine, had no effect on ischemic cardioplegia-induced [Ca2+]i changes, but application of a Ca2+ channel blocker, 5 x 10 (-1)M nifedipine, or an antagonist of Na+/Ca2+ exchange, 5 mM Ni2+, significantly inhibited the [Ca2+]i elevation, respectively. The magnitude of ischemic cardioplegia-induced [Ca2+]i elevation was dependent on the Ca2+ concentration of perfusate in the range of 0 and 25 mM. When Ni2+ was added to the reperfusion solution, recovery of ischemic cardioplegia-induced [Ca2+]i elevation was very rapid compared with the controls. It is concluded that ischemic cardioplegia-induced [Ca2+]i elevation may serve as one of the mechanisms of the "no-reflow' phenomenon in rabbit coronary artery smooth muscle cells. We propose that Na+/Ca2+ exchange may serve as a key function in ischemic cardioplegia-induced [Ca2+]i elevation.