Attenuation of tumor necrosis factor-alpha elevation and improved heart function by postconditioning for 60 seconds in patients with acute myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Postconditioning has been shown to reduce infarct size, ischemic/reperfusion injury and myocardial injury in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). This study tested the hypothesis that postconditioning attenuates the elevation of tumor necrosis factor-alpha (TNF-alpha) and improves heart function in patients with AMI after PCI.</p><p><b>METHODS</b>A total of 75 patients were randomly assigned to 1 of 3 groups: the routine group (n = 26), in which no intervention was given at the onset of reperfusion; and the Postcon-30s (n = 25) or Postcon-60 s (n = 24) groups, in which 3 cycles of 30- or 60-second balloon deflation and inflation were repetitively performed. TNF-alpha serum concentration was measured by ELISA. Global and regional left ventricular systolic function was determined by echocardiography at 1 year. Thirty-four normal controls (NC) were enrolled in the study.</p><p><b>RESULTS</b>The TNF-alpha concentration in patients with AMI was significantly elevated at baseline compared to controls (P < 0.01). Concentration levels increased in the routine and Postcon-30s, but not in Postcon-60s group at 7 days (P < 0.05). As for linear associations among the three groups, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were ranked as follows: Postcon-60s > Postcon-30s > routine (P values all < 0.05, 65% vs. 57% vs. 52% and 1.10 vs. 1.27 vs. 1.53) after 1 year. More importantly, there was a significant relevance between the soluble TNF-alpha serum concentration at 7 days and LVEF or WMSI after 1 year (P values all < 0.0001).</p><p><b>CONCLUSIONS</b>Postconditioning, in particular Postcon-60s was associated with long-term cardioprotective effects for inhibition of the inflammatory response and reperfusion injury. The soluble TNF-alpha serum concentration provided powerful prognostic information of global and regional left ventricular systolic function in patients with AMI.</p>

Effects of hydrogen sulfide on the K ATP current in isolated rat ventricular myocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of endogenous and exogenous hydrogen sulfide (H(2)S) on the K(ATP) current in isolated rat ventricular myocytes.</p><p><b>METHODS</b>Ventricular myocytes were isolated from rat heart by modified Langendorff perfusion with collagenase. K(ATP) current of single rat ventricular myocytes was recorded by whole-cell patch-clamp technique.</p><p><b>RESULTS</b>The density of K(ATP) current was significantly reduced by 200 micromol/L DL-propargylglycine (PPG, an irreversible inhibitor of the H(2)S) [(5.3258 +/- 0.7556) pA/pF vs. (3.7856 +/- 0.4312) pA/pF, P < 0.01] in a time-dependent way. The density of K(ATP) current could be significantly increased by NaHS (a H(2)S donor, 9.375, 18.75, 37.5, 75, 150 micromol/L) in a concentration-dependent manner [(6.6310 +/- 0.6092) pA/pF vs. (9.0949 +/- 1.0259) pA/pF at 150 micromol/L, P < 0.01].</p><p><b>CONCLUSION</b>Both endogenous and exogenous H(2)S could open K(ATP) channels and enhance the K(ATP) current in rat ventricular myocytes.</p>

Effects of reperfusion arrhythmia on myocardial apoptosis and left ventricular remodeling in patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe plasma soluble Fas/APO-1 concentration in patients with reperfusion arrhythmia immediately after coronary reperfusion in patients with acute myocardial infarction (AMI) and to investigate the impact of reperfusion arrhythmia on left ventricular (LV) remodeling in AMI patients. To observe the relationship between cardiomyocytes apoptosis with reperfusion arrhythmia in patients with acute myocardial infarction (AMI), and investigate the impact of reperfusion arrhythmia on left ventricular (LV) remodeling in patients with AMI.</p><p><b>METHODS</b>One hundred and fifty-six patients with AMI who received reperfusion therapy were selected as subjects. Fifty-eight patients underwent reperfusion arrhythmia within 24 hour after coronary reperfusion treatment (RA group). Ninety-eight patients did not occurred reperfusion arrhythmia (Non-RA group). Strepavidin-biotin ELISA was used to determine the soluble Fas/APO-1 plasma concentration at baseline, 7 day (d) and 2 - 4 week (W). All patients were followed up with scheduled evaluations of LV function and morphology with left ventriculography for 1 year.</p><p><b>RESULTS</b>1. It was later that the coronary reperfusion occurred in patients of RA group than that of Non-RA group, and the left anterior descending was more frequent infarct related artery (60.3%) than of Non-RA group (36.9%, P < 0.05). 2. The Fas/APO-1 levels in patients of RA group higher than those of Non-RA group at baseline [(13.82 +/- 4.36) microg/L vs (8.19 +/- 3.56) microg/L, P < 0.01]. 3. The highest level of Fas/APO-1 was on 7 d after AMI and the plasma levels of Fas/APO-1 in 2 - 4 W were slightly lower than those in 7 d in the two groups [RA group: (10.91 +/- 3.65) microg/L vs (14.26 +/- 4.98) microg/L, P < 0.05; Non-RA group: (4.69 +/- 1.87) microg/L vs (12.19 +/- 3.25) microg/L, P < 0.01]. However, the Fas/APO-1 level of 2 - 4 W in RA group was slightly higher than the level in Non-RA group [(10.91 +/- 3.65) microg/L vs (4.69 +/- 1.87) microg/L, P < 0.01]. 4. There was on difference between two groups in left ventricular ejection fraction (LVEF) and the left ventricular end-diastolic dimension (LVEDD) one week after AMI [LVEF: (47.7 +/- 9.6)% vs (49.2 +/- 8.9)%, P > 0.05; LVEDD: (59.7 +/- 10.3) mm vs (57.4 +/- 12.4) mm, P > 0.05]. 5. In the Non-RA group, the LVEF significantly increased from 1 W phase to the 1-year phase [from (49.2 +/- 8.9)% to (59.5 +/- 9.2)%, P < 0.05], but unchanged in the 58 patients without reperfusion arrhythmia [from (47.7 +/- 9.6)% to (49.9 +/- 10.1)%, P > 0.05]. The LVEF of Non-RA group was slightly higher than that of RA group at 1 year [(59.5 +/- 9.2)% vs (49.9 +/- 10.1)%, P < 0.05]. The LVEDD had no significant difference between two groups, but there was downtrend in the Non-RA group at 1 year after AMI.</p><p><b>CONCLUSION</b>Reperfusion arrhythmia was related with cardiomyocytes apoptosis in patients with AMI, and might influence left ventricular function and promote LV remodeling.</p>

Serum autoantibodies against the cardiac beta(1)-adrenergic receptor in patients with chronic heart failure: clinical characteristics and response to carvedilol / 中华心血管病杂志

<p><b>OBJECTIVE</b>To detect the serum autoantibodies against the cardiac beta(1)-adrenergic receptor and observe the clinical characteristics and response to carvedilol use in patients with chronic heart failure (CHF).</p><p><b>METHODS</b>Cardiac function was examined by echocardiography and levels of autoantibodies against cardiac beta(1)-adrenergic receptor were detected in 65 patients with CHF by means of enzyme linked immune assay. Carvedilol was added on ACEI, diuretics and digitalis regimen for a target dose of 50 mg/d. All patients were followed up for 6 months.</p><p><b>RESULTS</b>Autoantibodies against cardiac beta(1)-adrenergic receptor were detected in 30 patients (group 1) and not detected in the remaining 35 patients (group 2). The achieved target dose of carvedilol was significantly higher in group 1 than that in group 2 [(36.25 +/- 14.31) mg/d vs. (25.97 +/- 8.83) mg/d, P < 0.01]. Heart rate was significantly higher in group 1 compared to group 2 [(94.19 +/- 14.46) beats/min vs. (86.56 +/- 15.88) beats/min, P < 0.05] before treatment and heart rate and blood pressure of both groups decreased significantly (P < 0.01) and there was no significant difference between two group (P > 0.05) after 6 months treatment. LVEDD and LVESD were significantly larger while LVEF significantly lower in group 1 patients than those in group 2 patients (all P < 0.05) before treatment and LVEDD and LVESD decreased and LVEF increased significantly in both groups (all P < 0.01 vs. before treatment) and there was on significant difference in LVEDD, LVESD and LVEF between two groups (all P > 0.05) post 6 months treatment. Moreover, average titer of autoantibodies against the cardiac beta(1)-adrenergic receptors significantly decreased after 6 months treatment (1:119.35 vs. 1:72.21, P < 0.01).</p><p><b>CONCLUSION</b>The detection of autoantibodies against the cardiac beta(1)-adrenergic receptors is related to severer cardiac dysfunction and autoantibodies title decrease was found with improved cardiac function after standard therapy (ACEI, digitalis, betablocker) in patients with CHF.</p>

Characteristics of the action potentials and the underlying ionic mechanisms in the cardiomyocytes from rabbit pulmonary vein sleeves / 生理学报

To investigate the characteristics of action potentials and their ionic mechanism in cardiomyocytes from rabbit pulmonary vein sleeves (PVC), and to compare them with those in left atrial cardiomyocytes (LAC), the technique of whole-cell patch clamp was applied. We used current-clamp technique to record action potentials, and voltage-clamp technique to record ionic currents. PVC had longer action potential duration (APD) than LAC, and therefore a second plateau response could be induced easily, suggesting a strong tendency of early afterdepolarization (EAD) genesis in PVC. Non-selective cation current (I(NSCC)) was first recorded in both LAC and PVC. This I(NSCC)was permeable to K(+), Na(+) and Cs(+), sensitive to GdCl3 but not sensitive to 4-AP. The current densities of inward rectifier potassium current (I(K1)), transient outward potassium current (I(To)) and I(NSCC) were all significantly less in PVC than those in LAC. These differences in repolarizing ionic currents between PVC and LAC form a basis of the differences in their action potential configurations and might be an important ionic mechanism of the arrhythmogenic characteristics of pulmonary vein muscle sleeves.

Effects of tongxinluo on the myocardial inflammatory reaction and expression of tumor necrosis factor-alpha in rats with myocardial infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effects of Tongxinluo (TXL) on myocardial inflammatory reaction and expression of tumor necrosis factor-alpha (TNF-alpha) in rats with myocardial infarction (MI).</p><p><b>METHODS</b>The rat MI model was established by left anterior descending coronary artery ligation. Experimental rats were randomly divided into 3 groups: the sham operated group, the MI control group and the TXL group (treated by 2.0 g/ kg/day). Conditions of inflammatory cellular infiltration in the infarcted and non-infarcted zone were observed at 1, 2 and 4 weeks after MI with histopathological methods, and the expression of TNF-alpha was detected by semi-quantitative RT-PCR and Western blot.</p><p><b>RESULTS</b>Obvious inflammatory cellular infiltration revealed in both infarcted and non-infarcted zone of model rats at 1-2 weeks after MI, it faded away gradually 4 weeks after MI, while the TNF-alpha expression increased continuously after MI. Compared with the MI control, the infiltration was milder and TNF-alpha expression was lower in the TXL group.</p><p><b>CONCLUSION</b>TXL displays its anti-inflammatory action by way of attenuating the myocardial inflammatory reaction and suppressing the expression of inflammatory cytokine TNF-alpha in MI rats.</p>

Effect of serum autoantibodies against the M2 muscarinic acetylcholine receptors from patients with heart failure on L-Type Ca2+ channel activity in guinea pig cardiac myocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of serum autoantibodies against the human M(2) muscarinic acetylcholine receptors (M(2)-receptors, Abs) from patients with congestive heart failure on L-Type Ca(2+) channel activity in guinea pig cardiac myocytes.</p><p><b>METHOD</b>Using whole cell patch-clamp technique, we quantitatively measured the ionic intensity and density of L-Type Ca(2+) channel (I(Ca-L)).</p><p><b>RESULTS</b>The M(2)-receptors agonist (carbachol) could decrease the I(Ca-L) peak intensity and density stimulated by isoprenaline from (2111.65 +/- 203.13) pA and (18.83 +/- 1.14) pA/pF to (1230.87 +/- 208.14) pA (P < 0.01) and (10.72 +/- 1.06) pA/pF (P < 0.01). The serum Abs could also decrease I(Ca-L) peak intensity and density [from (1995.21 +/- 195.13) pA and (18.13 +/- 1.03) pA/pF to (636.42 +/- 110.07) pA (P < 0.01) and (5.54 +/- 0.81) pA/pF, P < 0.01]. The M(2)-receptors antagonist, atropine was able to block these effects of carbachol and Abs.</p><p><b>CONCLUSIONS</b>The circulating serum autoantibodies against the M(2)-receptors has similar effect as M(2)-receptors agonist on decreasing the isoprenaline stimulated I(Ca-L) in guinea pig cardiac myocytes and possess negative inotropic effect. These results further suggest that serum autoantibodies against the human M(2) muscarinic acetylcholine receptors may participate in the pathophysiological processes in patients with heart failure.</p>

The effect of carvedilol on cardiac function and autoantibodies against the cardiac receptors / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effect of carvedilol on the cardiac function and autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in patients with chronic heart failure (CHF).</p><p><b>METHODS</b>54 patients with CHF were divided randomly into two groups, one was regular treatment group treated with ACE inhibitor, digoxin and diuretic, another was carvedilol treatment group treated with carvedilol on the basis of above regular treatment. All the patients were followed up for six months and measured the changes of cardiac function and three autoantibodies by echocardiography and enzyme-linked immunosorbent assay (ELISA) respectively.</p><p><b>RESULTS</b>(1) After carvedilol treatment, LVEDD and LVESD (57.50 +/- 7.29) mm and (43.17 +/- 8.27) mm were smaller than that in regular treatment group [(64.09 +/- 7.40) mm and (52.93 +/- 8.35) mm], and LVEF [(50.41 +/- 10.91)%] was higher than that [(41.70 +/- 7.45)%] in regular treatment group (P < 0.01). (2) After carvedilol treatment, the positive ratios and average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors all decreased significantly compared with that of pre-treatment (P < 0.05). The positive ratios of autoantibodies against the three receptors in carvedilol treatment group were lower than those in regular treatment group (P < 0.05). The average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in carvedilol treatment group (1:72.44, 1:61.66 and 1:67.30) were lower than those in regular treatment group (1:113.24, 1:110.66 and 1:113.24), P < 0.05.</p><p><b>CONCLUSIONS</b>Carvedilol decreased positive ratio and average titer of autoantibodies against the beta(1), beta(2) and alpha(1) receptors accompanied with the obvious improvement of cardiac function though the blockade of beta(1), beta(2) and alpha(1) receptors. It suggests that the autoantibodies might be involved in the process of pathophysiology and development of CHF. Carvedilol can inhibit this process.</p>

Effect of the positive sera of autoantibodies against the human beta1-adrenoceptor from patients with congestive heart failure on activity of L-type Ca2+ channel in guinea pig cardiac myocytes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effect of the positive sera of autoantibodies against the human beta1-adrenoceptor from patients with congestive heart failure on activity of L-Type Ca2+ channel in guinea pig cardiac myocytes.</p><p><b>METHOD</b>Using whole cell patch-clamp technique, we quantitatively researched the ionic intensity and density of L-type Ca2+ channel (ICa-L).</p><p><b>RESULTS</b>The beta-adrenocepter agonist isoprenaline increased the ICa-L peak intensity and density from (997.09 +/- 227.5) pA and (8.20 +/- 0.86) pA/pF to (2241.01 +/- 348.5) pA and (18.98 +/- 1.18) pA/pF, respectively (P < 0.01). The positive sera of autoantibodies against the beta1-adrenoceptor could also increase ICa-L peak intensity and density from (963.57 +/- 207.56) pA and (8.14 +/- 0.72) pA/pF to (1382.41 +/- 241.36) pA and (11.70 +/- 1.03) pA/pF (P < 0.01). Esmolol, a beta1-adrenoceptor antagonist blocked these effects of isoprenaline and autoantibodies.</p><p><b>CONCLUSIONS</b>Human cardiac positive sera of autoantibodies against the beta1-adrenoceptor has an isoproterenol-like effect on cardiac myocytes receptor. It may participate in the pathophysiologic process of cardiac myocytes.</p>

Study of autoantibodies against the G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors in patients with primary hypertension / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine whether autoantibodies against the cardiac G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors are related to patients with primary hypertension.</p><p><b>METHODS</b>Synthetic peptides corresponding to amino acid sequences of the second extracellular loops of the beta 2- and alpha 1-adrenergic and AT1 receptors were respectively used as antigens to screen sera from patients with hypertensive heart diseases (n = 50) as well as simple hypertension (n = 40) and healthy blood donors (n = 40) using ELISA test.</p><p><b>RESULTS</b>The positive ratio of autoantibodies against beta 2 and alpha 1 and AT1 receptors in patients with hypertensive heart diseases were significantly higher than patients with simple hypertension and healthy donors. The geometric mean titers of autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors had no difference between the patients with hypertensive heart diseases and the patients with simple hypertension, but the geometric mean titers of two groups were higher than healthy donors. In the patients with hypertensive heart diseases, 81.0% of the patients with autoantibodies against beta 2-adrenergic receptor had autoantibodies against alpha 1-adrenergic receptor and 76.2% had autoantibodies against AT1 receptors. The percent of the autoantibodies against three receptors in patients with hypertensive heart diseases were 52.4%.</p><p><b>CONCLUSIONS</b>Autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors play an important role in the pathophysiological changes of primary hypertension, and may participate myocardial and vessel remodeling.</p>