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The saphenous nerve is the longest branch of the femoral nerve, which runs down the lower leg inward from the medial thigh

Cardiac deaths and events tend to cluster within the early-phase after starting dialysis. Our goal is to clarify the influence of severity of coronary atherosclerosis on early-phase death after starting hemodialysis (HD) therapy.Eighty-three consecutive patients [mean age 62 years; male/female 64/19; diabetic nephropathy in 50 (54%)] with end-stage renal disease who admitted to our hospital to initiate regular HD treatment, and then received coronary angiography within 3 months after first dialysis therapy, were eligible for this study. Angiographical severity of coronary atherosclerosis was scored by numerically using Gensini scoring system. The patients who died within one year from starting HD were compared with those who survived as control by means of logistic regression analysis.Of 83 patients, 12 (14%) died less than one year after starting dialysis therapy. Of these 12 patients, nine died for cardiac causes. Confirmed predictors of death from cardiac cause were older age (70 years), lower mean blood pressure (100 mmHg), presence of ischemic heart disease (IHD), myocardial infarction (MI), angina pectoris (AP), chronic heart failure (CHF), poor cardiac function, abnormal wall motion of left ventricule (LV) and angiographical severity of coronary atherosclerosis by univariate model. Adjusting for confounding variables by multivariate model, only severity of coronary atherosclerosis (Gensini score40 points) had a powerful influence, increasing risk for cardiac cause of early-phase death by about 17 times.Severity of coronary atherosclerosis predicts death in the first year of HD. These findings suggest that the strategy for prevention of coronary atherosclerosis should be instituted during the early phase of chronic renal failure.

Background/Aims: Identification of end-stage renal disease (ESRD) patients at high risk for cardiac events is important for clinical dialysis management. The present study determined whether the combination of cardiac function and coronary atherosclerosis could predict future cardiac events after starting renal replacement therapy (RRT). Methods: We prospectively assessed left ventricle ejection fraction (EF) and Gensini score (GS) using angiographic severity of coronary atherosclerosis in 88 consecutive ESRD patients [mean age 62 years; 69 males (78%); 55 patients (64%) with diabetic nephropathy] at the initiation of RRT. EF was analyzed by echocardiogram, and GS was scored by coronary angiography within 3 months after starting RRT. The study end point was cardiac death. For analysis of the association between cardiac death and EF and GS measures, the univariate and multivariate Cox proportional hazards model was used. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value, and accuracy of event-free prediction were evaluated. Results: Twenty-four patients (27%) had low cardiac function (EF 15; high GS). During a follow-up period of 3 years, cardiac death occurred in 21 patients (24%). The PPV of low EF and high GS was 42 and 39%, respectively; the highest PPV (53%) was obtained when low EF and high GS were combined. The cumulative survival rate at 5 years in patients with both low EF and high GS was significantly lower than those with high EF and low GS (91 vs. 22%, p < 0.0005). Conclusion: The combined assessment of cardiac function and coronary atherosclerosis at the initiation of RRT strongly predicts future cardiac events.

1. The association between the stimulation of the angiotensin subtype 2 receptor (AT2-R) and the change in tissue levels of cyclic nucleotide was assessed on neointima formation in rat aorta following aortic balloon injury. 2. Tissue levels of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate levels (cAMP) in the injured and uninjured aorta was determined by enzyme immunoassay at baseline and again 30 s after administration of 10(-7) M angiotension II. 3. Injured and uninjured aorta showed no difference in basal levels of cGMP. Angiotension II reduced the basal level of cGMP in the injured aorta only. 4. This decrease was blocked by a selective AT2-R antagonist (PD123319) and by a nonselective angiotensin II antagonist (angiotensin II antipeptide), but not by a selective angiotensin subtype 1 antagonist (CV-11974). 5. Stimulation with a selective AT2-R caused no change in the level of cAMP in the injured or uninjured aorta. 6. Results suggest that stimulation of AT2-R in proliferative neointima leads to a decreased tissue level of cGMP.

We investigated the effects of angiotensin converting enzyme inhibitors on acetylcholine-induced endothelium-dependent vasodilation in the presence of nitroglycerin tolerance in rings of rabbit thoracic aorta mounted in tissue baths and precontracted with 10(-6) M norepinephrine. The vasorelaxant effects of acetylcholine were measured before and after 1 h treatment with 5 x 10(-4) M nitroglycerin. The acetylcholine dose-response curve shifted to the right after the induction of nitroglycerin tolerance. Pretreatment with captopril (a sulfhydryl angiotensin converting enzyme inhibitor), but not with M-1 (a metabolite of delapril and a nonsulfhydryl angiotensin converting enzyme inhibitor) restored acetylcholine-induced relaxation. Pretreatment with N-acetylcysteine also restored reduced acetylcholine-induced relaxation. These results suggest that the sulfhydryl group plays a major role in restoration of reduced acetylcholine-induced vasodilation in the presence of nitroglycerin tolerance.

The effects of angiotensin-converting enzyme (ACE) inhibitors on vascular reactivity were investigated using isolated canine femoral arteries with and without endothelium. N-N-(S)-1-carboxy-3-phenylpropyl-L-alanyl-N-(indan-2-yl)glycine (M-1; an active metabolite of delapril, a nonsulfhydryl ACE inhibitor) and captopril (a sulfhydryl ACE inhibitor, 10(-8) to 10(-5) M) relaxed in a dose-dependent manner canine femoral arterial rings precontracted with prostaglandin F2 alpha in the presence of endothelium only. The endothelium-dependent relaxations by M-1 and captopril were completely blocked by methylene blue, an inhibitor of soluble guanylate cyclase; NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis; and oxyhemoglobin, an inactivator of nitric oxide; they were partially blocked by aspirin, an inhibitor of cyclooxygenase and were enhanced by superoxide dismutase, a radical scavenger. The inhibitory effect of L-NMMA on the relaxations by M-1 and captopril were reversed by a high dose of L-arginine. Moreover, a bradykinin antagonist partially inhibited these relaxations. These results suggest that endothelium-dependent relaxations by M-1 and captopril in canine femoral arteries are mediated through the release of both prostanoids and endothelium-derived nitric oxide via endogenous bradykinin.

1. 1. Rings of porcine pulmonary arteries were mounted in tissue organ baths and incubated in physiological solution. The rings were allowed to equilibrate for > 1 hr under a resting tension of 1.0 g. The presence of endothelium was confirmed by 10−6 M acetylcholine (ACh)-induced relaxation (60–80%) of 10−6 M norepinephrine (NE) contraction. 2. 2. Relaxation response generated by nitroglycerin (NTG) (10−9–10−5 M), ACh (10−9–10−5 M), bradykinin (BK) (10−13–10−6 M) and nitric oxide (NO) after NE (10−6 M) contraction was compared before and after 1 hr treatment of NTG (5 × 10−4 M). Then tissues were pretreated with N G -monomethyl- l -arginine (LNMMA) (10−4 M) each before and after NTG treatment respectively, and ACh-induced relaxation was compared. 3. 3. After 1 hr treatment with 5 × 10−4 M NTG, the relaxation response of NTG at concentrations > 10−7 M was attenuated significantly. This indicates that 1 hr treatment with 5 × 10−4 M NTG induces NTG tolerance in isolated porcine pulmonary arterial rings. 4. 4. The relaxation response of ACh at concentrations > 10−7 M was attenuated significantly after NTG tolerance induction. 5. 5. Relaxation response of BK at concentrations > 10−10 M was attenuated significantly after NTG tolerance induction. 6. 6. NTG tolerance had no effect on NO-induced vascular smooth muscle relaxation. 7. 7. The relaxation response of ACh pretreated with LNMMA at concentrations higher than 10−7 M was attenuated after NTG tolerance. 8. 8. These results demonstrate that ACh releases an endothelium-derived relaxing factor (EDRF) or several EDRFs other than NO which is (are) affected by NTG tolerance.

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The aim of this study was to assess the effects of hydrophilic pravastatin and lipophilic atorvastatin on glucose metabolism and lipid metabolism in non-diabetic patients with hypercholesterolemia.Fasting plasma glucose (FPG), hemoglobin A(1c) (HbA(1c)), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) levels were determined before and after statin treatment.A total of 44 nondiabetic patients (FPGor =125 mg/mL; HbA(1c)5.8%) undergoing treatment with either pravastatin (n=21) or atorvastatin (n=23) for hypercholesterolemia were investigated.FPG level in the pravastatin but not atorvastatin group was significantly lowered after vs before treatment. Accordingly, the HbA(1c) level in the atorvastatin but not in the pravastatin group was significantly increased. As expected, both TC and LDL-C levels were significantly lowered in both groups. In particular, the TC level in the atorvastatin group was more remarkably and significantly improved than in the pravastatin group. On the other hand, the HDL-C level in the pravastatin group but not in the atorvastatin group was significantly increased after the administration period. The TG level was unaffected in both groups.Pravastatin was suggested to act favorably, while atorvastatin adversely, regarding it's effects on glucose metabolism in nondiabetic hypercholesterolemic patients, although atorvastatin exerted more potent cholesterol-lowering effects compared with pravastatin.

We evaluated the effect of endothelin-1 (ET) on the angiotensin converting enzyme (ACE) activity in rat aortic smooth muscle cells (VSMCs). ACE activity was determined by radioimmunoassay of the amount of angiotensin II generated after the addition of angiotensin I (500 pg/ml) to cultured VSMCs. The antibody used had less than 0.1% cross-reactivity with angiotensin I. ACE activity increased 1.9-fold 5 hr after the addition of 10(-6) M ET under serum-free conditions. This stimulatory effect of ET on ACE activity in VSMCs was completely inhibited by 10(-7) M captopril. Results suggested that the ACE present in SMCs is stimulated by ET.

There is epidemiologic evidence that the prognosis of patients with nonischemic heart failure is better than that for patients with ischemic heart failure. In addition, studies have revealed that patients with ischemic heart failure show a poorer response to medical therapy. However, the pathophysiologic difference between ischemic and nonischemic heart disease is unclear. To clarify this point, we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in plasma and pericardial fluid in patients with ischemic or nonischemic heart disease undergoing cardiac surgery. The pericardial ET-1 concentration in patients with ischemic heart disease was statistically greater than that in patients with nonischemic heart disease (about 1.5-fold), although no difference was found in the plasma ET-1 concentration. These findings suggest that the production and secretion of ET-1 from the myocardium in patients with ischemic heart disease are augmented to a greater extent than in patients with nonischemic heart disease. This result may lead to a greater understanding of the pathophysiology of ischemic heart disease.

We investigated the mechanism of vascular relaxation produced by dobutamine, a positive inotropic agent with beta 1-adrenergic action. Dobutamine concentration-dependently (10 nM-10 microM) relaxed ring segments of rabbit aorta partially precontracted with 1 microM phenylephrine (PE) but did not relax those precontracted with 40 mM K+ or 5 microM prostaglandin F2 alpha (PGF2 alpha). The relaxation was not completely inhibited by pretreatment with 10 microM propranolol. Dobutamine did not significantly increase tissue cyclic AMP levels concomitantly with relaxation as does isoproterenol (ISO) in rabbit aorta. Dobutamine produced a parallel rightward shift in concentration-response curves to PE. The Schild plot analysis resulted in a linear regression of a slope of 1.077 +/- 0.077, which was not significantly different from unity. The pA2 value of dobutamine as compared with PE in rabbit aorta was 6.81 +/- 0.03. Dobutamine causes arterial dilatation mediated not only through a beta-adrenergic action but also through an alpha-adrenergic blocking action in rabbit aorta.