ABSTRACT
Speckle tracking echocardiography (STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge (G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group (n=10), mild trans-aortic banding (TAB) group (n=14) and severe TAB group (n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening (FS), left ventricular (LV) mass, and left ventricular end diastolic diameter (LVEDD) (P0.05 for both). STE analysis revealed that longitudinal strain (LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups (P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group (P<0.05). Radial strain (RS) and circumferential strain (CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group (P<0.05 for both) from the postoperative week 1 (P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6 (P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.
ABSTRACT
Speckle tracking echocardiography (STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge (G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group (n=10), mild trans-aortic banding (TAB) group (n=14) and severe TAB group (n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening (FS), left ventricular (LV) mass, and left ventricular end diastolic diameter (LVEDD) (P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures (P>0.05 for both). STE analysis revealed that longitudinal strain (LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups (P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group (P<0.05). Radial strain (RS) and circumferential strain (CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group (P<0.05 for both) from the postoperative week 1 (P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6 (P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.
Subject(s)
Animals , Male , Mice , Cardiomegaly , Disease Models, Animal , Echocardiography , Methods , Heart Failure , Mice, Inbred C57BLABSTRACT
Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 μmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.
ABSTRACT
<p><b>OBJECTIVE</b>Stem cells transplantation is a promising strategy in cardiology. This meta-analysis summarizes the efficacy and safety of stem cells transplantation on top of standard medication on chronic heart failure patients.</p><p><b>METHODS</b>The following databases were searched, including Cochrane Library (Issue 4, 2011), PubMed (1980 to 2011), Embase (1990 to 2011), CBM (1978 to 2011), CNKI (1994 to 2011), VIP (1989 to 2011), and WanFang Data (1998 to 2011). Search criteria:studies were screened and the quality was evaluated according to predefined inclusion and exclusion criteria. Intervention measures: the treatment group using stem cell transplantation therapy on top of standard drug treatment, while the control group using standard drug treatments.</p><p><b>RESULTS</b>A total of 31 studies involving 2375 patients were included. The results show that the improvement of LVEDV in the stem cell treatment group is greater than in the control group [SMD = -11.8% (95%CI: -0.223 - 0.013), P = 0.027] and the relative-risk of cardiac events is lower in stem cell treatment group [RR = 0.77 (95%CI: 0.66 - 0.90), P < 0.01] than in control group.</p><p><b>CONCLUSION</b>Stem cells therapy is effective in improving cardiac remodeling and reducing the relative-risk of cardiac events in patients with chronic heart failure.</p>
Subject(s)
Humans , Chronic Disease , Heart Failure , General Surgery , Stem Cell Transplantation , Ventricular RemodelingABSTRACT
Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 μmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.
Subject(s)
Animals , Rabbits , Action Potentials , Anti-Arrhythmia Agents , Pharmacology , Arrhythmias, Cardiac , Benzylamines , Pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Metabolism , Electrocardiography , Electrophysiologic Techniques, Cardiac , Endocardium , Heart , In Vitro Techniques , Long QT Syndrome , Pericardium , Piperidines , Pharmacology , Protein Kinase Inhibitors , Pharmacology , Pyridines , Pharmacology , Sulfonamides , Pharmacology , Torsades de PointesABSTRACT
BACKGROUND: Calcium calmodulin-dependent kinase Ⅱ (CaMKⅡ) can be more active in patients with left ventricular hypertrophy (LVH), which in turn causes phosphorylation of ryanodine receptors, resulting in inactivation and the instability of intracellular calcium homeostasis. The present study aimed to determine the effect of CaMKⅡ–ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia. METHODS: Forty New Zealand rabbits were randomized into four groups (10 per group): sham group, LVH group, KN-93 group (LVH+KN-93), and ryanodine group (LVH+ryanodine). Rabbits in the LVH, KN-93, and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta, while those in the sham group did not undergo the coarctation. After eight weeks, action potentials (APs) were recorded simultaneously in the endocardium and epicardium, and a transmural electrocardiogram (ECG) was also recorded in the rabbit left ventricular wedge model. Drugs were administered to the animals in the KN-93 and ryanodine groups, and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline (1 mol/L) and high-frequency stimulation. RESULTS: The frequency (animals/group) of triggered APs was 0/10 in the sham group, 10/10 in the LVH group, 4/10 in the KN-93 group, and 1/10 in the ryanodine group. The frequencies of ventricular tachycardia were 0/10, 9/10, 3/10, and 1/10, respectively. The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10, 7/10, 2/10, and 1/10, respectively. The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group (P<0.05). CONCLUSIONS: KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH. The CaMKⅡ–ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.</p><p><b>METHODS</b>Twenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.</p><p><b>RESULTS</b>Compared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.</p><p><b>CONCLUSIONS</b>LPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.</p>
Subject(s)
Animals , Rabbits , Anti-Arrhythmia Agents , Pharmacology , Arrhythmias, Cardiac , Metabolism , Connexin 43 , Metabolism , Lysophospholipids , Oligopeptides , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits.</p><p><b>METHODS</b>Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation (Sham, group A), the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n = 31), amiodarone group (group C, n = 31), AAP10 group (group D, n = 31) and amiodarone plus AAP10 group (group E, n = 31). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg×kg(-1)×d(-1). All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to T-end interval (T(p-e)), and ventricular tachycardia episodes induced by programmed stimulation were recorded. The T(p-e)/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence.</p><p><b>RESULTS</b>The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62.5%, 26.9%, 40.0%, 22.2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The T(p-e)/QT ratio in group B, C, D were greater than in group A. The T(p-e)/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C.</p><p><b>CONCLUSIONS</b>The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the T(p-e)/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10 have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.</p>
Subject(s)
Animals , Male , Rabbits , Amiodarone , Pharmacology , Therapeutic Uses , Anti-Arrhythmia Agents , Pharmacology , Therapeutic Uses , Arrhythmias, Cardiac , Connexin 43 , Metabolism , Myocardial Infarction , Drug Therapy , Metabolism , Oligopeptides , Pharmacology , Therapeutic Uses , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To study the Kv1.3 channel expression changes after CD4(+) and subsets CD28(null)/CD28(+)T cells activation in peripheral blood of patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>CD4(+)T cell in 27 ACS patients and CD4(+)CD28(null)/CD4(+)CD28(+)T cells in 12 out of these 27 ACS patients were isolated from peripheral blood with magnetic cell sorting. The whole-cell Kv1.3 currents for three T cells were recorded with patch-clamp technique before and 72 hours after activation by purified anti-human CD3 Interferon gamma, tumor necrosis factor alpha (TNF-alpha), granzyme B mRNA expression were determined by reverse transcription-PCR before and 72 hours after activation by purified anti-human CD3 in the presence or absence of recombinant Margatoxin (rMgTX, 0.1, 1, 10 nmol/L), a specific Kv1.3 channel blocker.</p><p><b>RESULTS</b>Peak Kv1.3 channel currents of CD4(+), CD4(+)CD28(null), CD4(+)CD28(+)T cells were significantly increased and the mean Kv1.3 channel numbers per cell of these cells were increased by about 90%, 60%, 80% (402 +/- 88 vs. 752 +/- 275, 553 +/- 328 vs. 874 +/- 400, 392 +/- 133 vs. 716 +/- 251, all P < 0.05) after activation compared to baseline values. Baseline CD4(+)CD28(null)T cell numbers were about 40% more than those of CD4(+)CD28(+)T cell (P < 0.05) and were similar after activation (P = 0.102). The mRNA expression of interferon gamma, TNF-alpha and granzyme B were dose-dependently down-regulated by rMgTX.</p><p><b>CONCLUSIONS</b>Kv1.3 channels of peripheral CD4(+)T cell and CD28(null)/CD28(+)T cells from ACS patients significantly increased after activation and Kv1.3-specific channel blocker rMgTX could effectively abolish this effect suggesting a potential role of Kv1.3 channel blocker on plaque stabilization in ACS patients.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Acute Coronary Syndrome , Blood , Metabolism , CD28 Antigens , Metabolism , CD4-Positive T-Lymphocytes , Metabolism , Metabolism , Lymphocyte Activation , Patch-Clamp Techniques , T-Lymphocyte Subsets , MetabolismABSTRACT
<p><b>OBJECTIVE</b>The purpose of our study is to observe the voltage-gated potassium channel Kv1.3 expression on CD4+CD28null T cells from the peripheral blood of ACS patients by the patch clamp technique.</p><p><b>METHODS</b>Kv1.3 potassium channels expression from 17 patients with ACS and 11 healthy age-matched normal controls was detected in single cell (CD4+CD28null T cells and CD4+CD28+ T cells) by fluorescence microscopy and patch clamp.</p><p><b>RESULTS</b>The percent of CD4+CD28nullT cells are higher in the ACS (6.97% +/- 2.05%) than that in the controls (1.38% +/- 0.84%, P < 0.05). The concentration of hsCRP is directly correlated with the number of the CD4+CD28null T cells in the ACS (r = 0.52, P < 0.05). The conductance [(6.89 +/- 1.17) nS vs. (3.36 +/- 0.66) nS], dens [(1.95 +/- 0.80) n/microm2 vs. (1.13 +/- 0.57) n/microm2] and numbers [(574.5 +/- 97.6) n/cell vs. (280.3 +/- 55.3) n/cell] of the Kv1.3 channels on the CD4+CD28null T cells are significantly higher than those on the CD4+CD28+ T cells (all P < 0.01) in ACS patients, but were similar on CD4+CD28+ T cells between ACS patients and controls.</p><p><b>CONCLUSION</b>The CD4+CD28null T cells in the ACS and the numbers of Kv1.3 channels on the CD4+CD28null T cells from the ACS patients are significantly upregulated and might contribute to the pathogenesis of ACS.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome , Blood , Allergy and Immunology , Metabolism , CD28 Antigens , Metabolism , CD4-Positive T-Lymphocytes , Metabolism , Case-Control Studies , Metabolism , Patch-Clamp TechniquesABSTRACT
<p><b>OBJECTIVE</b>To determine current density of voltage-gated potassium channels and Kv1.3 express in T-lymphocyte derived from patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>Peripheral blood mononuclear cells were collected from 12 patients with ACS and 10 control donors. Whole-cell patch clamp technique was used to record the outward K(+) currents (IK) and western blots technique was used to detect the express of Kv1.3 protein in lymphocyte.</p><p><b>RESULTS</b>(1) The current density of voltage-gated potassium channel was significantly higher in ACS patients [(269 +/- 94) pA/pF] than in controls [(191 +/- 64) pA/pF, P < 0.01] while membrane capacitance was similar between the two groups. (2) Kv1.3 protein expression was also significantly increased in ACS patients than in controls (P < 0.01).</p><p><b>CONCLUSION</b>The lymphocyte voltage-gated potassium channel is upregulated in patients with ACS suggesting a role of Kv activation in the pathophysiology of ACS.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome , Metabolism , Metabolism , Patch-Clamp Techniques , T-Lymphocytes , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of KN-93, a calmodulin kinase II inhibitor, on ventricular arrhythmias in rabbits with cardiac hypertrophy.</p><p><b>METHODS</b>Female New Zealand white rabbits were randomly divided into four groups (n = 10 each): Sham; LVH; LVH + KN-92 and LVH + KN-93 group. LVH was induced by partially constricting the abdominal aorta. In Sham group, the abdominal aorta was exposed without constriction. Eight weeks later, the arterially perfused left ventricular wedge preparations were made and transmembrane action potentials (TAP) from epicardium and endocardium and transmural ECG were simultaneously recorded. Incidence of early after depolarization (EAD) and torsade de pointes (Tdp), QT interval, action potential duration (APD) and transmural depolarization dispersion (TDR) at different cycle lengths were observed under slow stimulation (2000 - 4000 ms), hypokalemic (2 mmol/L) and hypomagnesaemic (0.25 mmol/L) Tyrode's solution perfusion.</p><p><b>RESULTS</b>Left ventricular hypertrophy was detected in LVH group by echocardiography and not affected by KN-92 and KN-93. Perfused with hypokalemic, hypomagnesaemic Tyrode's solution and under slow stimulation (2000 - 4000 ms), the incidences of EAD and Tdp in Sham group, LVH group, LVH + KN-92 group (0.5 micromol/L) and LVH + KN-93 group (0.5 micromol/L) were 0/10, 10/10, 9/10, 5/10 and 0/10, 5/10, 4/10, 1/10, respectively. With 1 micromol/L KN-92 and KN-93, the incidences of EAD and Tdp in LVH + KN-92 and LVH + KN-93 group were 9/10, 3/10 and 4/10, 1/10 respectively. The QT interval, APD and TDR were not affected by KN-93.</p><p><b>CONCLUSION</b>The calmodulin kinase II inhibitor KN-93 can effectively suppress ventricular arrhythmias in rabbits with cardiac hypertrophy by decreasing EAD.</p>
Subject(s)
Animals , Male , Rabbits , Arrhythmias, Cardiac , Drug Therapy , Benzylamines , Pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Cardiomegaly , Drug Therapy , Disease Models, Animal , Protein Kinase Inhibitors , Pharmacology , Sulfonamides , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of antiarrhythmic peptide (AAP10) on ventricular arrhythmias in rabbits with healed myocardial infarction (OMI).</p><p><b>METHODS</b>Thirty rabbits were randomly divided into three groups (n = 10 each): Sham group, left thoracotomy was performed without coronary ligation; OMI group and OMI + AAP10 group, the circumflex coronaries were ligated. Three months post operation, the electrophysiological and antiarrhythmic effects of AAP10 were assessed in the arterially perfused rabbit left ventricular wedge preparation. Sham and OMI group were perfused with Tyrode's solution and OMI + AAP10 group was perfused with Tyrode's solution + AAP10 (80 nmol/L). Transmembrane action potentials were recorded simultaneously from endocardium and epicardium together with a transmural ECG by use of 2 separate intracellular floating microelectrodes. The stimulus-response-interval (SRI) of the epicardium and the incidence of ventricular tachycardia (VT) were observed. Whole heart and left ventricular weights, the left ventricular thickness at infarct border zone were measured.</p><p><b>RESULTS</b>Whole heart and left ventricular weights as well as the left ventricular thickness at the infarct border zone significantly increased post infarction. VT was induced in 8 out of 10 rabbits in OMI group and in 2 out of 10 rabbits in OMI + AAP10 group (P < 0.05). SRI was also significantly shortened in OMI + AAP10 group compared to OMI group [SRI-1: (20.59 +/- 0.79) ms vs. (28.71 +/- 0.55) ms; SRI-2: (30.42 +/- 0.74) ms vs. (38.67 +/- 0.49) ms, all P < 0.01]. However, the action potential morphology and duration were similar between OMI and OMI + AAP10 groups.</p><p><b>CONCLUSION</b>The antiarrhythmic peptide (AAP10) can increase gap junctional intercellular conductance without affecting the action potential morphology and duration and decrease the incidence of inducible ventricular tachycardia.</p>
Subject(s)
Animals , Male , Rabbits , Arrhythmias, Cardiac , Myocardial Infarction , Oligopeptides , Pharmacology , Random AllocationABSTRACT
<p><b>AIM</b>To investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models.</p><p><b>METHODS</b>Rabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded.</p><p><b>RESULTS</b>The ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group.</p><p><b>CONCLUSION</b>IMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.</p>
Subject(s)
Animals , Female , Male , Rabbits , Angiotensin-Converting Enzyme Inhibitors , Pharmacology , Calcium Channels , Metabolism , Heart Ventricles , Cell Biology , Imidazolidines , Pharmacology , Myocardial Infarction , Metabolism , Myocytes, Cardiac , Metabolism , Refractory Period, ElectrophysiologicalABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of W-7, a calmodulin inhibitor, on transmural dispersion of repolarization (TDR), early after depolarization (EAD) and torsade de pointes (TdP) induction after administration of d-sotalol in isolated rabbit heart.</p><p><b>METHODS</b>TdP was induced by d-sotalol (30 micromol/L), bradycardia, and hypokalemic (1.5 mmol/L)/hypomagnesaemic (0.35 mmol/L) solution in isolated female rabbit hearts. Thirty six rabbit hearts were divided into 4 groups (n = 9 each): d-sotalol alone, d-sotalol + W-7 (20 micromol/L), d-sotalol + W-7 (50 micromol/L), and d-sotalol + W-7 (100 micromol/L). Monophasic action potentials (MAPs) of the left ventricular epimyocardium (Epi), midmyocardium (M), and endomyocardium (Endo) were recorded simultaneously with ECG. The incidence of EAD and TdP were observed as well.</p><p><b>RESULTS</b>Treatment with d-sotalol alone prolonged ventricular MAP duration and QT interval, increased TDR, and evoked high incidence of EAD (9/9) and spontaneous TdP (7/9) in hypokalemic/hypomagnesaemic solution in female rabbit heart. W-7 concentration-dependently decreased incidence of TdP (4/9 in 20 micromol/L; 2/9 in 50 micromol/L; 1/9 in 100 micromol/L). This effect of W-7 coincided with the decreased incidence of EAD (5/9 in 20 micromol/L; 4/9 in 50 micromol/L; 1/9 in 100 micromol/L). However, the d-sotalol-induced prolongation of QT interval and TDR was not significantly altered by W-7 at the three concentration used.</p><p><b>CONCLUSIONS</b>In isolated female rabbit hearts, calmodulin antagonist W-7 suppresses d-sotalol-induced TdP without altering TDR but does suppress EAD. The effects observed with W-7 also suggest a possible important role for calmodulin-activated enzymes in the induction of TdP.</p>