[Characteristics of electrophysiology and effects of ouabain on transient outward potassium current and L-type calcium current of left atrium posterior wall in rabbits].

OBJECTIVE: To investigate the properties of electrophysiology and effects of ouabain upon transient outward potassium current (I(to)) and L-type calcium current (I(Ca-L)) of left atrium posterior wall (LAPW) and left atrium appendage tissue (LAA)in rabbit so as to provide the scientific explanations that LAPW and ouabain can enhance atrial fibrillation (AF) vulnerability through increasing electrophysiological heterogeneity and electrical remodeling of different regions of left atrium in rabbits. METHODS: Atrial myocytes from LAPWs and LAAs of rabbits on an in vitro heart perfusion system were obtained by enzymatic dissociation. The whole-cell patch-clamp technique was used to assess the effects of ouabain upon I(to) and I(Ca-L). The current-voltage (I-V) curves of I(to) and I(Ca-L) in LAPW and LAA myocytes were fitted before and after ouabain administration. RESULTS: (1) With holding potential +50 mV and commanding potential +50 mV, the current densities of LAPW I(to) decreased slightly less than that of LAA I(to) in control groups (P > 0.05). After ouabain administration, the current densities of LAPW I(to) were significantly larger than that of LAA I(to) [(10.97 +/- 0.58) pA/pF vs (9.39 +/- 0.83) pA/pF, P < 0.05]. The I-V curve of LAPW I(to) was slightly lowered to I-V curve of LAA I(to) in control groups. But with perfusion of ouabain, the I-V curve of LAPW I(to) opposed to I-V curve of LAA I(to) significantly changed from the bottom to the top with the same upward direction. (2) With the voltage clamp protocol of I(Ca-L), the current densities of LAPW I(Ca-L) markedly decreased compared with that of LAA I(Ca-L) in control groups (P < 0.05). With the addition of ouabain, the peak of amplitude of LAPW I(Ca-L) at +20 mV obviously increased to that of LAA I(Ca-L) [(-11.13 +/- 0.99) pA/pF vs (-8.86 +/- 0.51) pA/pF, P < 0.01]. In the control groups, the I-V curve of LAPW I(Ca-L) was shifted to the bottom of all I-V curves of I(Ca-L). Through the effects of ouabain, the I-V curve of LAPW I(Ca-L) was completely upgraded to the top of other I-V curves of I(Ca-L). However, all shapes and directions of current peak of I-V curves of I(Ca-L) remained unchanged in both groups. CONCLUSION: The distribution properties of I(Ca-L) have significant difference in LAPW. Ouabain can accentuate the electrophysiological heterogeneity and electrical remodeling of I(to) and I(Ca-L) in LAPW of rabbits. It may become the triggering factor and persisting basis of AF vulnerability.

[Effects of BmKIM on sodium current of isolated cardiomyocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits].

OBJECTIVE: To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (I(Na)) of isolated ventricular myocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits. METHODS: Ventricular myocytes were enzymatically dissociated from adult rabbits. Whole-cell patch-clamp technique was used to record voltage-dependent I(Na). Standard transmembrane action potentials in rabbit hearts in vivo were recorded by using floating glass microelectrodes. Incidence of arrhythmias, the early after depolarization (EAD) and/or delay after depolarization (DAD) were measured in vivo in rabbits post aconitine (100 microg/kg, iv) in the absence or presence of BmKIM (50 microg/kg iv). RESULTS: (1) BmKIM significantly inhibited I(Na) in a voltage-dependent manner and significantly shifted the I-V curves of I(Na) upward. BmKIM left shifted the inactivation curve of I(Na) and voltages at 50% inactivation of I(Na) were changed from (-70.8 +/- 2.6) mV to (-84.8 +/- 3.5) mV (P < 0.05). BmKIM prolonged the recovery of inactivation of I(Na). In the presence of BmKIM, the time constants of recovery (both tau(f) and tau(s)) of I(Na) were significantly prolonged from (28.9 +/- 6.1) ms and (107 +/- 21.6) ms in control group to (54.2 +/- 7.9) ms (P < 0.05) and (211.1 +/- 34.6) ms (P < 0.01), respectively. (2) BmKIM significantly shortened 50% and 90% of action potential duration (APD(50) and APD(90)), and reduced action potential amplitude (APA), declined maximum up stroke velocity of action potential (V(max)) in vivo. The Q-T duration was shortened and heart rate significantly increased post BmKIM injection. (3) Incidence of aconitine induced ventricular arrhythmias (77.8%) was significantly reduced by BmKIM (22.2%, P < 0.01). CONCLUSIONS: BmKIM significantly blocked I(Na) through affecting the inactivated state of I(Na) in rabbit ventricular myocytes. BmKIM could attenuate the influx of I(Na), therefore shorten action potential duration and reduce action potential amplitude and reduce the incidence of aconitine induced arrhythmias.

Decreased infiltration of macrophages and inhibited activation of nuclear factor-kappa B in blood vessels: a possible mechanism for the anti-atherogenic effects of losartan.

UNLABELLED: Short-term administration of losartan reduced the aortic surface lesion area and mean intimal thickness. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased macrophage proliferation and accumulation in the arterial wall, decreased activation of nuclear factor-kappa B and expression of its target gene ICAM-I. OBJECTIVE: Recent studies suggest that angiotensin II (Ang II) may contribute to the vascular inflammatory response and atherosclerosis. Losartan is a specific AT1 receptor antagonist which can effectively inhibit the effects of Ang II. However, the effects of losartan on atherogenesis have been rarely demonstrated. We designed this study to investigate the effects of short-term administration of losartan on atherosclerotic lesions in the aorta from rabbits fed a cholesterol-enriched diet and the possible mechanisms of its anti-atherogenic effects. METHODS AND RESULTS: The rabbits were randomly divided into three groups: (a) cholesterol group; (b) losartan-treated group; (c) normal control group. We observed that mean serum lipid levels in the cholesterol group were significantly higher than those in normal control rabbits, while blood pressure between two groups did not change significantly. Treatment with losartan did not affect serum lipid levels or systolic blood pressure but did reduce the aortic surface lesion area and mean intimal thickness. The number of macrophages markedly decreased after administration of losartan. Losartan also attenuated the activation of nuclear factor-kappa B and the expression of its target gene ICAM-I. CONCLUSIONS: In summary, losartan inhibited atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased activation of nuclear factor-kappa B.

[Study on linkage between polymorphism of interleukin 6 gene -572C/G and susceptibility to myocardial infarction].

OBJECTIVE: To observe the polymorphism and gene frequency of interleukin 6 (IL6) gene -572C/G in Chinese Han nationality population, that associating with susceptibility to myocardial infarction(MI) and impacting on the extent of coronary artery lesions; to analyze the function of IL6 gene -572C/G polymorphism. METHODS: With PCR-RFLP method, IL6 gene -572C/G polymorphism was genotyped to 232 MI patients and 260 healthy adults. The effect of IL6 gene -572C/G polymorphism was observed to the extent of coronary artery lesions and the ability of IL6 production from peripheral blood mononuclear cells (PBMC). RESULTS: There was IL6 gene -572C/G polymorphism in Chinese Hans. -572CG+GG genotype and G allele were more frequent in patients than in controls (P< 0.01). The relative risk for G allele carrier to suffer from MI was 1.68 times of CC genotype individual (95%CI 1.17-2.41, P< 0.01). However, the distribution of IL6 gene -572C/G polymorphism was no significant difference among patients with single-vessel, two-vessel and three-vessel lesions (P> 0.05). After PBMC cultured for 24 hours, the IL6 concentration in supernatant was significantly higher in subjects with CG genotype than those with CC genotype (P< 0.05). CONCLUSION: IL6 gene -572G allele may be a genetic susceptibility factor to MI attack of Chinese Hans population, and related to the high expression of IL6.

[Interleukin-6-597G/A and -572C/G polymorphisms and risk of coronary heart disease].

OBJECTIVE: To explore the relationship between interleukin-6 (IL-6) gene polymorphisms and the risk of coronary heart disease (CHD). METHODS: IL-6/-597G/A and -572C/G polymorphisms were genotyped in 245 CHD patients and 260 healthy adults by PCR-RFLP. Serum IL-6 level was examined by ELISA. Logistic regression was performed to observe the relationship between IL-6/-572C/G polymorphism and other risk factors of CHD. RESULTS: IL-6/-597G/A genotype was similar between the two groups. The frequencies of IL-6/-572C/G genotype and G allele were more frequent in patients with CHD than that in controls (P < 0.01). Compared with CC genotype, the relative risk for CHD in people with CG and GG genotypes was 1.46 (95% CI: 1.01 - 2.10, P < 0.05) and 5.19 (95% CI: 1.69 - 15.89, P < 0.01), respectively. The serum levels of IL-6 were similar between carriers of the IL-6/-572G allele and patients with CC genotype (P > 0.05). IL-6/-572 C/G is related to total cholesterol (OR 1.76, 95% CI: 1.05 - 3.16, P < 0.05) and triglyceride (OR = 2.51, 95% CI: 1.04 - 6.45, P < 0.05), respectively. CONCLUSION: IL-6/-597G/A polymorphism was not associated with susceptibility to CHD, but IL-6-572C/G polymorphism may be a possible genetic susceptibility factor for CHD in Chinese Hans population.

Enhanced inflammatory response of blood monocytes to C-reactive protein in patients with unstable angina.

BACKGROUND: Previous studies showed that monocytes from patients with unstable coronary disease exhibit a greatly enhanced production of interleukin-6 (IL-6) in response to lipopolysaccharide and artery injury. Moreover, accumulating evidence suggest that C-reactive protein (CRP) may have direct proinflammatory effects on the cells of vascular wall. Whether this enhanced inflammatory response also exists, however, in cultured monocytes from patients with unstable angina, in response to CRP, has not been investigated. METHODS: Monocytes were isolated from blood of 15 healthy volunteers (normal control), 15 patients with stable angina, and 15 patients with unstable angina by Ficoll density gradient and were stimulated by 20 microg/ml of CRP for 24 h. Measurements of IL-6 and tumor necrosis factor-a (tnf-alpha) were performed from supernatants of cultured medium in duplicate, using a commercial assay kit. RESULTS: the data showed that IL-6 and tnf-alpha concentrations of spontaneous secretion (baseline) were higher in patients with unstable angina than in patients with stable angina and normal control (IL-6: 179+/-19 vs. 87+/-6 and 89+/-8 pg/ml, p<0.05, respectively; tnf-alpha: 69+/-13 vs. 30+/-4 and 27+/-3 pg/ml, p<0.05, respectively). CRP induced the enhanced release of IL-6 and tnf-alpha by 17-fold and 23-fold increase, respectively, in patients with unstable angina, while it did about 11-fold and 19-fold increase in patients with stable angina and normal group (IL-6: 3129+/-333 vs. 991+/-134 and 987+/-102 pg/ml, p<0.01, respectively; tnf-alpha: 1554+/-784 vs. 560+/-135 and 558+/-152 pg/ml, p<0.01, respectively). CONCLUSIONS: Increased baseline concentrations of IL-6 and tnf-alpha can be a marker of the hyperresponsiveness of the inflammatory system in patients with unstable coronary disease. CRP could enhance even further this response, suggesting that a persisted and enhanced inflammatory responsiveness to CRP may be involved in the pathogenesis of unstable coronary disease.

[Change of glucose transporter 4 and its influence on glucose and fatty-acid metabolism in type 2 diabetic myocardium].

OBJECTIVE: To investigate the relationship between sarcolemmal content of glucose transporter 4 (GLUT4) and the myocardial glucose and fatty acid utilization in type 2 diabetes. METHODS: Twenty-four Sprague-Dawley rats were randomized into four groups: control, HFD/STZ, control/RSG and HFD/STZ/RSG. Sprague-Dawley rats were fed with high-fat diet (40% of the calories was supplied by fat) for 4 weeks, intraperitoneally injected with 35 mg/kg streptozotocin to establish type 2 diabetes model, and 24 diabetic rats were randomized into four groups: HFD/STZ/RSG group [fed with high fat food and given rosiglitazone (3 mg.kg(-1).d(-1)) for 2 weeks], HFD/STZ group (fed with high fat food and given normal saline), control/RSG [fed with normal food and given rosiglitazone (3 mg.kg(-1).d(-1)) for 2 weeks], and control group (fed with normal food and given normal saline). Then the rats were killed and their hearts were taken out to be mounted onto a Langendorff perfusion apparatus to be perfused with Krebs-Henseleit buffer in the presence of 5 mmol/L glucose and 0.4 mmol/L (3)H labeling palmitate. Glucose uptake and (3)H2O collection were used to evaluate the rate of carbohydrate and fatty acid oxidation. The sarcolemmal content of GLUT4 protein was detected by Western blotting method. RESULTS: Compared with the control group, the diabetic rats had a significantly depression of glucose uptake of the heart [(55 +/- 6) micromol/g dry weight vs (69 +/- 6) micromol/g dry weight, P < 0.01], the oxidation rate of glucose decreased from 25% to 18% and the oxidation rate of palmitate increased from 75% to 82%, and the sarcolemmal GLUT4 content was decreased by 53% after 30 minutes' perfusion. In the HFD/STZ/RSG group the glucose uptake level was (64 +/- 6) micromol/g dry weight, significantly higher than that of the HFD/STZ group (P < 0.05), the proportions of glucose oxidation and fatty acid oxidation were 24% and 76% respectively, and the GLUT4 expression was 92% that of the normal rats, significantly higher than that of the HFD/STZ group (47%, P < 0.01). CONCLUSION: The sarcolemmal GLUT4 content in the type 2 diabetic myocardium is obviously decreased, which may be associated with the decrease of glucose uptake and increase of fatty acid oxygen. Rosiglitazone treatment may exert beneficial effects on the energy substrate utilization by increasing the expression of GLUT4.

[Changes in content of plasma brain natriuretic peptide in dilated cardiomyopathy in rabbits].

OBJECTIVE: To determine the changes in plasma brain natriuretic peptide (BNP) in adriamycin-induced dilated cardiomyopathy (DCM) in rabbit, and to evaluated the significance. METHODS: Twenty-two rabbits were randomly divided into control group (n=10) and model group(n=12). The DCM model was reproduced by injecting adriamycin via ear vein for 8 weeks. Echocardiogram was performed and plasma BNP were measured before administration, and at 8 th and 11 th week after the challenge. Indexes of hemodynamics and pathological changes were observed. RESULTS: Indexes of echocardiogram and hemodynamics of model group were consistent with pathologic changes of DCM. Plasma levels of BNP of the model group were increased significantly after administration of the drug(all P<0.01), though the values before the drug administration were approximately the same as in the control group. Plasma BNP levels were significantly higher in DCM group at the 11 th week than at the 8 th week (P<0.05). Plasma levels of BNP were positively correlated with and left ventricular end-diastolic volume(LVEDV), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic pressure(LVEDP) and negatively correlated with left ventricular systolic pressure(LVSP), and left ventricular ejection fraction (LVEF). CONCLUSION: Administration of intravenous adriamycin to rabbits results in DCM which in suitable for the conduction of research of neuroendocrine abnormality of heart. Overload of the left ventricle and increasing tension of left ventricular wall are key factors for regulating BNP excretion. Plasma BNP level is a good marker for evaluating degree of severity of cardiac function in DCM.

[The role of isoprenaline-induced, calcium-activated transient outward chloride current in atrial electrical remodeling of rabbit].

OBJECTIVE: To investigate the relationship between the changes of the L-type calcium current (I(Ca, L)) and the calcium-activated transient outward chloride current (I(Cl, Ca)), and the repolarization characteristic of action potential in phase 1 under isoprenaline (ISO) stimulation in atrium myocytes of rabbit. METHODS: Atrium myocytes were obtained by enzymatic dissociation from a section of atrial free wall. The membrane currents and action potential were recorded by the whole-cell patch-clamp technique. RESULTS: After recording I(Ca, L), atrium myocytes were perfused with ISO (1 micromol/L) immediately. Five minutes later, a transient outward current (I(to)) was significantly induced, and the peak of I(to) was gradually increased while I(Ca, L) gradually decreased with increasing in clamp voltage. The I(to) was resistant to 4-AP (3 mmol/L) but sensitive to DIDS (150 micromol/L, Cl(-) channel blocker). This current was blocked by CdCl(2) (200 micromol/L, Ca(2+) channel blocker). The elicited rate of I(to) was 91.67% (P < 0.05). (2) The shape of AP was like an inverse triangle with no plateau in Phase 2 after ISO (1 micromol/L) perfusion. Moreover, compared to the parameters of control group, APD(50) and APD(90) were significantly shortened from (65.4 +/- 4.2) ms and (95.8 +/- 3.8) ms to (12.8 +/- 3.8) ms and (27.0 +/- 4.7) ms, and reduced to 80.46% and 71.87%, respectively (P < 0.01, n = 12). 4-AP (3 mmol/L) had on obvious effect on the shape of AP, however, the plateau of AP in phase 2 was recovered by DIDS (150 micromol/L) perfusion, APD(50) and APD(90) were (41.1 +/- 4.5) ms and (79.6 +/- 3.4) ms respectively. Compared to the parameters of control group, there were no significant differences (P > 0.05, n = 12). These results indicated that ionic transport were changed by ISO perfusion in atrium myocytes and I(to) played an important role in the phase 1 repolarization of AP. CONCLUSIONS: Before ISO administration, we could only observe I(Ca, L) in atrium myocytes of rabbit. After isoproterenol intervention, certain intracellular ionic consistency and membrane ionic channels were changed. Calcium activated chloride channel and I(to2) revealed obvious predominance which shorten APD significantly. Action potential showed a triangle with no plateau, suggesting an electrical remodeling in atrium myocytes. The remodeling of ionic channel is related possibly with the opening of Ca(2+)-activated Cl(-) current, which maybe the electrophysiological base of reentrant atrial tachycardia.

Ischemic preconditioning detected by treadmill exercise tests in patients with stable angina.

The aim of this study was to explore the ischemic preconditioning (IP) phenomenon in patients with chronic stable angina (SA) by using treadmill exercise tests (TETs). Twenty-nine patients with SA were divided into 2 groups: group A (n = 15) and group B (n = 14). There was no difference between the 2 groups in both clinical characteristics and extent of coronary stenosis. Group A was subjected to 2 TETs at a 10-minute interval, but group B had a 60-minute interval according to Bruce protocol. The occurrence and time of chest pain, maximal value, duration of ST segment depression, and arrhythmias that occurred during TETs were analyzed for differences in the 2 tests in the 2 groups. In group A, 9 patients (60.0%) complained of chest pain in the first test, whereas only 4 (26.7%) did in the second test (p < 0.01); The time of occurrence of chest pain during exercise was 1.88 +/- 0.2 min in the first test, 2.3 +/- 0.4 min in the second test (p < 0.05); The maximal value of ST segment depression decreased from 0.21 +/- 0.09 mV in the first test to 0.14 +/- 0.05 mV in the second (p < 0.01); the duration of ST segment depression decreased from 7.12 +/- 0.9 min in the first test to 4.42 +/- 0.3 min in the second (p < 0.01). The incidence of arrhythmia decreased from 40.0% in the first test to 13.3% in the second (p < 0.05). However, no significant difference was observed in the multiple parameters, mentioned above, in group B. In conclusion, the first ischemic event could induce the IP phenomenon and protect the heart from more serious damage at a 10-minute interval. However, this effect disappeared when the second test was done at a 60-minute interval.

Increased C-reactive protein level after renal stent implantation in patients with atherosclerotic renal stenosis.

Elevated C-reactive protein (CRP) level has been demonstrated in patients with coronary artery disease after coronary stent implantation, but no data are available in patients with atherosclerotic renal artery stenosis concerning whether such changes of CRP also exist after renal artery stent implantation. The authors hypothesize that elevated CRP level may also be present in patients with atherosclerotic renal artery stenosis after stent implantation owing to mechanical disruption of atherosclerotic plaque. In total, 24 patients were enrolled in this study. Of these, 14 patients with atherosclerotic renal artery stenosis received renal angioplasty plus stent implantation (group A, mean age 51 +/- 8 years), and 14 age- and gender-matched patients underwent renal angiography for diagnostic purpose as a control group (group B, mean age 50 +/- 8 years). Peripheral blood samples were taken before the procedure and at 6 and 24 hours after the procedure in both groups. Plasma CRP concentration was measured by using immunoturbidimetry. The results showed that there was no difference in clinical characteristics or in baseline CRP levels between the 2 groups. However, median CRP level was found to increase significantly at 6 hours from 0.13 to 0.17 mg/dL (p < 0.05), and peaked at 24 hours (0.21 mg/dL) after renal artery stent implantation (p < 0.001). Mean CRP rose from 0.30 +/- 0.09 to 0.37 +/- 0.15 mg/dL at 6 hours (p < 0.05) and peaked at 24 hours (0.43 +/- 0.18 mg/dL) after renal artery stent implantation (p < 0.01), while no such changes were observed after renal angiography in group B (p > 0.05, respectively, at different time points). The results of the present study indicate, from evidence of increased plasma CRP concentrations, that renal artery stent implantation could trigger an inflammatory response due to mechanical disruption of atherosclerotic plaque of the renal artery, which is a pattern very similar to that of coronary stent implantation.

Circadian variation in ischemic threshold in patients with stable angina: relation to plasma endothelin-1.

To investigate circadian variation in ischemic threshold in chronic coronary heart disease (CHD) and its relation to plasma endothelin-1 (ET-1), 21 patients with stable angina underwent treadmill exercise tests twice within a day, performed at 8-9 AM for the first test and at 3-4 PM for the second one. Ischemic threshold was defined as the heart rate at the onset of 1 mm ST segment depression during exercise tests. Blood samples were taken at 5 minutes before each exercise test, and plasma ET-1 was measured for determining the possible relation to ischemic threshold in patients with CHD. The results showed that the heart rate-ischemic threshold in individual patients varied by 10 +/- 1% (range, 2-15%) in the morning and 9 +/- 1% (range, 2-14%) in the afternoon, while there was a mean (11.2%) reduction in the ischemic threshold between 2 time points, with the ischemic threshold being significantly lower in the morning compared with that in the afternoon (115 +/- 22 bpm vs 128 +/- 31 bpm p<0.04). ET-1 values were 6.20 +/- 2.44 ng/L in the morning hours and 4.02 +/- 1.61 ng/L in the afternoon hours, with a statistical significant difference (p<0.01). In conclusion, the present study indicated that circadian variation of plasma levels of ET-1 was likely to be one of the most likely mechanisms involved in reduction in the ischemic threshold in the morning hours.

Elevated level of plasma C-reactive protein in patients with unstable angina: its relations with coronary stenosis and lipid profile.

C-reactive protein (CRP) is a sensitive marker of inflammation, and elevated levels have been associated with future risk of cardiovascular events. To explore the role and relationship of CRP and coronary stenosis in the development of unstable angina (UA), plasma levels of CRP were determined on admission in 45 patients with UA, and in 42 patients with stable angina (SA) using high-sensitivity ELISA. Coronary angiography was performed in all patients with coronary heart disease (CHD), and severity of coronary stenosis was evaluated by a quantitative analysis. Lipid measurement was performed using automatic biochemical analyzer. Data available from patients with CHD were compared with those of 41 control subjects. The results showed that plasma levels of CRP are significantly higher in patients with UA than those in patients with SA and control subjects (5.1 +/- 1.4 mg/L vs 1.7 +/- 0.4 mg/L and 1.3 +/- 0.2 mg/L, p<0.01, respectively) with no difference between the latter two groups (p>0.05); the total incidence of clinical events during in-hospital follow-up was higher in the group A (p<0.01); the scores of coronary stenosis are significantly higher in patients with SA than those in patients with UA (4.9 +/- 2.1 vs 3.4 +/- 1.4, p<0.05); there is no correlation between plasma levels of CRP and serum total cholesterol (TC) as well as high-density lipoprotein cholesterol (HDL-C) in both groups (p>0.05 respectively); there was no correlation between plasma levels of CRP and severity of coronary stenosis was found in patients with UA (p>0.05) but a significant positive association in patients with SA (p<0.001); and the patients with persistent, severe, treatment-unresponsive UA had significantly higher CRP levels as well as incidence of clinical events than patients with treatment-responsive UA (7.4 +/- 1.8 mg/L vs 2.6 +/- 1.3 mg/L, p<0.01; 0 vs 22.2%, p<0.05). The present data suggested that inflammation may play an important role in the pathogenesis of UA, and the plasma levels of CRP might have a higher prognostic value than the severity of coronary stenosis correlated with the clinical outcome of instability despite of lipid profile status.

Acetylcholine-regulated K+ current remodelling in the atrium after myocardial infarction and valsartan administration.

BACKGROUND: Atrial fibrillation (AF) is a common complication of myocardial infarction (MI). Angiotensin II receptor antagonists prevent the promotion and propagation of AF. However, the activation of the acetylcholine-regulated K(+) current (I(K,ACh)) in the atrium after MI and the effect of valsartan on I(K,ACh) are less understood. METHODS: Twenty-four adult rabbits were randomly divided into three groups: sham-operated, MI and MI plus valsartan administration (MI+valsartan). The sham-operated group received a median sternotomy without left ventricular coronary artery ligation. Both the MI group and the MI+valsartan group received a median sternotomy followed by ligation of the midpoint of the left ventricular coronary artery. The MI+valsartan group was administered oral valsartan for 12 weeks. After 12 weeks, the initiation of AF was measured by vagal stimulation followed by quick excision of the heart. I(K,ACh) in the left atrial myocardium was measured by the patch clamp technique. RESULTS: AF was induced in four animals in the MI group, two in the sham-operated and two in the MI+valsartan groups, with the total AF duration expectedly longer in the MI group than in the sham-operated and MI+valsartan groups (38 s versus 9 s and 9 s, respectively). Furthermore, the mean (+/- SEM) density of I(K,ACh) increased significantly more in the left atrial myocardia of the MI group than in the sham-operated and the MI+valsartan groups (-13+/-0.42 pA/pF versus -9+/-0.38 pA/pF and -10+/-0.37 pA/pF, respectively at -100 mV; and 4.1+/-0.28 pA/pF versus 3.1+/-0.27 pA/pF and 3.3+/-0.27 pA/pF, respectively at 20 mV; P<0.05). However, there was no statistically significant difference in I(K,ACh) between the sham-operated group and the MI+valsartan group. CONCLUSIONS: AF is associated with increased I(K,ACh) after MI. Inhibition of increased IK,ACh may be the mechanism by which valsartan prevents AF following MI.

Effect of vagal stimulation and differential densities of M2 receptor and IK,ACh in canine atria.

OBJECTIVE: We investigated the electrophysiological effect of vagal stimulation (VS) on atrial myocardium in vivo and differential densities of M(2) receptor and acetylcholine-induced inward rectifier K(+) current (I(K,ACh)) to discuss the mechanisms of atrial fibrillation (AF). METHODS: With the monophasic action potential (MAP) recording technique, data from twenty-four sites, i.e. right atrial appendage (RAA), left atrial appendage (LAA), right atrium (RA) and left atrium (LA) were recorded by electrode probes, which were applied to the epicardial atrial surface of each dog. After cervical vagosympathetic cut, VS(1) (20 Hz, 0.2 ms pulse duration and at a voltage 10 V), VS(2) (20 Hz, 0.2 ms pulse duration and at a voltage 30 V) and sinus node (SN) damage were administrated respectively. MAP, dispersion of action potential duration (dAPD) and AF was recorded. Then, RAA, LAA, RA and LA were dissected. Finally, distribution of M(2) receptors and I(K,ACh) in atrial myocardium were measured by western blot and patch clamp respectively. RESULTS: During VS(1) and VS(2), AF could be induced at first in right atrial appendage (RAA) and right atrium (RA) without left atrial appendage (LAA) and left atrium (LA). Compared to the parameters in control group and VS(2) group, dAPD was increased significantly by VS(1) and SN damage, but there was no significant difference between control group and VS(2) group. However, AF was not evoked after SN damage. Densities of M(2) receptor and I(K,ACh) were higher in RAA, LAA than those in LA and RA (M(2) receptor: 1 and 1.01 over 0.83 and 0.51, P<0.05; I(K,ACh): 20+/-0.89, 19+/-0.82, 14+/-0.64, 9+/-0.45 pA/pF, P<0.05). Furthermore, densities of M(2) receptor and I(K,ACh) were higher in LA than those in RA (P<0.05). CONCLUSIONS: Decreased APD is the base in initiation of cholinergic AF by VS and increased dAPD alone can not induce AF. A greater abundance of M(2) receptor and I(KACh) in RAA and LAA imply atrial appendage plays an important role in initiation of cholinergic AF.

The research of molecular and ionic mechanisms in vagally mediated atrial fibrillation in canine.

BACKGROUND: The reentrant mechanism of vagally mediated AF is not clearly elucidated. METHODS AND RESULTS: After vagal stimulation, thirty dogs were divided AF group (AF could be induced) and control group (AF could not be induced). Western blot and patch clamp were used to determine M(2) receptor and I(K,ACh) in left atrial appendage (LAA), right atrial appendage (RAA), left atrium (LA), right atrium (RA), pulmonary veins (PVs) and superior vena cava (SVC). In control group, the densities of M(2) receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PVs and SVC. However, there was no significant difference in LAA, RAA and LA. In AF group, the densities of M(2) receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PVs and SVC. Furthermore, the densities of the M(2) and I(K,ACh) in LAA and RAA were higher than that in LA. CONCLUSIONS: Atrial appendage perhaps play an important role in initiation of cholinergic AF. However, PVs and SVC less often play an important role in vagotonic paroxysmal AF.

Differential densities of muscarinic acetylcholine receptor and I(K,ACh) in canine supraventricular tissues and the effect of amiodarone on cholinergic atrial fibrillation and I(K,ACh).

BACKGROUND: Vagal nerve plays an important role in the induction and maintenance of atrial fibrillation (AF). This study investigated the differential densities of M2 receptor and acetylcholine-induced inward rectifier K+ current (I(K,ACh)) in atrial appendage, atrium, pulmonary vein (PV) and super vena cava (SVC) to discuss the role of atrial appendage and PV in cholinergic AF. METHODS AND RESULTS: In 10 dogs, action potential duration was determined at 24 sites during bilateral cervical vagal stimulation and amiodarone administration. AF could be induced at first in right atrial appendage (RAA) and right atrium (RA) without left atrial appendage (LAA) and left atrium (LA). Amiodarone decreased the initiation of AF in vivo. Western blot and patch clamp were used to determine M2 receptor and I(K,ACh) in RAA, LAA, RA, LA, PV and SVC. The densities of M2 receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PV and SVC (21.34 +/- 0.92 vs. 8.24 +/- 0.45 pA/pF, p < 0.05). Furthermore, the densities of the M2 receptor and I(K,ACh) in LAA and RAA were higher than that in LA (21.34 +/- 0.92 vs. 14.17 +/- 0.65 pA/pF, p < 0.05). After amiodarone administration, densities of I(K,ACh) in LA and RA were not different, but densities of I(K,ACh )were also less in atrium than in atrial appendage. CONCLUSIONS: Densities of the M2 receptor and I(K,ACh) are higher in atrial appendage than other sites. Atrial appendage perhaps plays an important role in initiation of cholinergic AF. However, PV and SVC less often play an important role in vagotonic paroxysmal AF. Reduced dispersion of I(K,ACh) is the mechanism for amiodarone to therapy AF.

[The distribution of gene polymorphisms in the intron 2 and exon 2 of interleukin-1 receptor antagonist and their correlation with the serum lipoprotein level].

OBJECTIVE: To study the distribution of variable numbers of tandem repeat (VNTR) polymorphism in the intron 2 and the single nucleotide polymorphism (SNP) at position +8006 in the exon 2 of IL-1RN in healthy Chinese Han Population of Wuhan province and to analyze their correlation with the serum lipoprotein level. METHODS: IL-1RN (VNTR) and IL-1RN (+8006) polymorphisms were detected by PCR and PCR-RFLP methods in 251 healthy Chinese Han Population of Wuhan, and the levels of serum lipoprotein, IL-1 and IL-1Ra were inspected simultaneously. RESULTS: In IL-1RN (VNTR), allele I appeared most common, then allele II, and allele IV was rare. At the position of IL-1RN (+8006), allele T was most commonly seen followed by allele C. Allele II of IL-1RN (VNTR) always existed with allele C of IL-1RN (+8006). The levels of serum lipoprotein, IL-1 and IL-1Ra were not different among the different genotypes of the two polymorphisms. CONCLUSION: There were two gene polymorphisms in the intron 2 and exon 2 of IL-1RN, which were not correlated with the levels of serum lipoprotein, IL-1 and IL-1Ra. However, there seemed to be a linkage disequilibrium between IL-1RN (VNTR) and IL-1RN (+8006).

Autologous transplantation of bone marrow mononuclear cells improved heart function after myocardial infarction.

AIM: To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function. METHODS: Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of culture. After being labeled with bromodeoxyuridine (BrdU), the cells were auto-transplanted into bordering zone of the infarcted area at 2 weeks after injury. The animals were killed at 3 days, 2 weeks, 1 month, and 2 months after transplantation, respectively. The left ventricular functions, capillary density, and cardiac nerve density were measured and the differentiation of the engrafted cells was determined by immunostaining. RESULTS: BrdU-labeled MNCs were well aligned with the host cardiomyocytes. Parts of them were incorporated into capillary and arteriolar vessel walls. In addition to inducing angiogenic ligands (basic fibroblast growth factor, vascular endothelial growth factor) and inflammation cytokines (interleukin 1-beta) during the early period of MNCs implantation, MNCs induced 2.0-fold increase in capillary density as well. Moreover, GAP43-positive and TH-positive nerve density were markedly higher in the MNCs-treated groups than that in the non-treated hearts. Left ventricular ejection fraction, LV+dp/dt(max), and LV-dp/dt(max) were 47%, 67%, and 55% in MNCs-treated heart respectively, which was higher than that of the control heart, whereas left ventricular end-diastolic volume, left ventricular end-diastolic diameter, and left ventricular end-diastolic pressure were 45%, 22%, and 50% respectively in MNCs-treated heart, which was lower than that of the control heart at 2 months after cell transplantation. CONCLUSION: Autologous transplantation of MNCs induced angiogenesis and nerve sprouting and improved left ventricular diastolic function.