Streptomycin inhibits electrophysiological changes induced by stretching of chronically infarcted rat hearts.

OBJECTIVE: To investigate stretch-induced electrophysiological changes in chronically infarcted hearts and the effect of streptomycin (SM) on these changes in vivo. METHODS: Sixty Wistar rats were divided randomly into four groups: a control group (n=15), an SM group (n=15), a myocardial infarction (MI) group (n=15), and an MI+SM group (n=15). Chronic MI was obtained by ligating the left anterior descending branch (LAD) of rat hearts for eight weeks. The in vivo blockade of stretch-activated ion channels (SACs) was achieved by intramuscular injection of SM (180 mg/(kg∙d)) for seven days after operation. The hearts were stretched for 5 s by occlusion of the aortic arch. Suction electrodes were placed on the anterior wall of left ventricle to record the monophasic action potential (MAP). The effect of stretching was examined by assessing the 90% monophasic action potential duration (MAPD90), premature ventricular beats (PVBs), and ventricular tachycardia (VT). RESULTS: The MAPD90 decreased during stretching in both the control (from (50.27±5.61) ms to (46.27±4.51) ms, P<0.05) and MI groups (from (65.47±6.38) ms to (57.47±5.76 ms), P<0.01). SM inhibited the decrease in MAPD90 during inflation ((46.27±4.51) ms vs. (49.53±3.52) ms, P<0.05 in normal hearts; (57.47±5.76) ms vs. (61.87±5.33) ms, P<0.05 in MI hearts). The occurrence of PVBs and VT in the MI group increased compared with that in the control group (PVB: 7.93±1.66 vs. 1.80±0.86, P<0.01; VT: 7 vs. 1, P<0.05). SM decreased the occurrence of PVBs in both normal and MI hearts (0.93±0.59 vs. 1.80±0.86 in normal hearts, P<0.05; 5.40±1.18 vs. 7.93±1.66 in MI hearts, P<0.01). CONCLUSIONS: Stretch-induced MAPD90 changes and arrhythmias were observed in chronically infarcted myocardium. The use of SM in vivo decreased the incidence of PVBs but not of VT. This suggests that SACs may be involved in mechanoelectric feedback (MEF), but that there might be other mechanisms involved in causing VT in chronic MI.

Testosterone improves cardiac function and alters angiotensin II receptors in isoproterenol-induced heart failure.

BACKGROUND: The renin-angiotensin-aldosterone system is known to play an important role in the pathophysiology and development of heart failure. Several studies have reported the benefits of testosterone in heart failure. However, the mechanisms of testosterone-induced effects on heart failure require further study. AIMS: To determine the effects of castration and testosterone administration on cardiac function and angiotensin II receptor function in rats with isoproterenol-induced heart failure. METHODS: Wistar rats were divided randomly into control and heart failure groups. The heart failure groups were further divided into the following groups: castration; castration+testosterone replacement; and sham castration. Echocardiography and haemodynamic measurements were used to evaluate cardiac function. Cardiocyte apoptosis and fibrosis were determined using terminal deoxyribonucleotide transferase-mediated dUTP nick-end labelling (TUNEL) staining and Masson's Trichrome staining, respectively. Angiotensin II receptor (AT1 and AT2) messenger ribonucleic acid (mRNA) expression levels were assayed using real-time reverse transcriptase-polymerase chain reactions, while Western immunoblotting was used to estimate Bcl-2 protein expression levels. RESULTS: Castration significantly increased cardiomyocyte apoptosis and fibrosis that was normally induced by isoproterenol (P<0.05). AT2 receptor mRNA expression in the castration group was increased and Bcl-2 protein expression was decreased compared with the castration+testosterone replacement group (P<0.05). CONCLUSION: These data suggest that androgen therapy could play an important role in pathophysiological changes in heart failure and have beneficial effects for its treatment.

Regional differential expression of TREK-1 at left ventricle in myocardial infarction.

BACKGROUND: Altered membrane electrophysiology contributes to arrhythmias after myocardial infarction (MI). TREK-1 channel is essential in various physiological and pathological conditions through its regulation on resting membrane potential and voltage-dependent action potential duration. OBJECTIVES: The aim of this study was to investigate changes in gene expression and electrophysiology of TREK-1 in the left ventricle in a MI model. METHODS: Fifty-five rats were divided into 5 groups: sham-operated group, 6 hours, 24 hours, 3 days, and 7 days post MI group (n=11 per group). TREK-1 messenger RNA (mRNA) expression level in the infarct region (IR) and infarct border region (IBR) were quantified by real-time polymerase chain reaction (PCR), and TREK-1 current density at the IBR was recorded with whole-cell patch-clamp technique. RESULTS: TREK-1 mRNA expression decreased significantly in both endocardial and epicardial cells in the infarct region after MI. Conversely, TREK-1 increased significantly in endocardial and epicardial cells from the IBR (P<0.01). Current density of TREK-1 at IBR increased significantly in both epicardial and endocardial cells after MI (P<0.01). CONCLUSIONS: TREK-1 demonstrates specific changes in expression and electrophysiological function in left ventricle post MI. These results suggest that TREK-1 may participate in pathophysiologic alteration and electrical remodelling of left ventricular myocardium after MI, which may eventually lead to post-MI ventricular arrhythmias.

[Effect of phalloidin on electrophysiological changes induced by stretch of myocardial infarcted hearts in rats].

The present study aimed to explore whether the stretch of ischemic myocardium could modulate the electrophysiological characteristics via mechanoelectric feedback (MEF), as well as the effect of phalloidin on the electrophysiological changes. Thirty-two Wistar rats were randomly divided into 4 groups: control group (n=9), phalloidin group (n=7), myocardial infarction (MI) group (n=9), MI + phalloidin group (n=7). The acute myocardial infarction (AMI) was conducted by ligation of the left anterior descending (LAD) coronary artery for 30 min in isolated rat heart. The volume alternation of a water-filled latex balloon in the left ventricle produced the stretch of myocardium. After perfused on Langendorff, the isolated hearts were stretched for 5 s by an inflation of 0.1, 0.2 and 0.3 mL separately and the effect of stretch was observed for 30 s, including the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dp/dt(max), monophasic action potential duration at 90% repolarization (MAPD90), and occurrence of premature ventricular beats (PVB) and ventricular tachycardia (VT). The stretch caused an increase of MAPD(90) in both control and MI rats (P<0.05, P<0.01). Moreover, MAPD(90) in MI group increased more significantly than that in the control group at the same degree of stretch (P<0.05, P<0.01). Phalloidin (1 µmol/L) had no effect on MAPD(90) in basal state. After stretch, MAPD(90) in phalloidin group slightly increased but was not significantly different from that in the control group. However, phalloidin reduced MAPD(90) in infarcted myocardium, especially when ΔV=0.3 mL (P<0.05). The incidence rates of PVB and VT in MI group were higher than that in the control group (both P<0.01). And there was no significant difference in the incidence rates of PVB and VT between phalloidin group and control group. Phalloidin inhibited the occurrence of PVB and VT in infarcted hearts (both P<0.01). LVSP and +dp/dt(max) in MI group obviously decreased (P<0.01 vs control). With application of phalloidin, LVSP slightly, but not significantly increased in infarcted hearts, while -dp/dt(max) significantly increased (P<0.05). It is suggested that MI facilitates the generation and maintenance of malignant arrhythmias, while phalloidin obviously inhibits the occurrence of arrhythmias.

The effect of streptomycin on stretch-induced electrophysiological changes of isolated acute myocardial infarcted hearts in rats.

AIMS: To explore whether the stretch of ischaemic myocardium could modulate the electrophysiological characteristics, especially repolarization via mechanoelectric feedback (MEF), as well as the effect of streptomycin (SM) on these changes. Methods Thirty-six wistar rats were randomly divided into four groups: control group (n = 9), SM group (n = 9), myocardial infarction (MI) group (n = 9), and MI + SM group (n = 9). After perfused on Langendorff, the isolated hearts were stretched for 5s by a ballon inflation of 0.2mL. After being stretched, the effect of the stretch was observed for 30s, including the 20, 20-70, 70, and 90% monophasic action potential duration (MAPD), i.e. MAPD(20), MAPD(20-70), MAPD(70), and MAPD(90), respectively, premature ventricular beats (PVB), and ventricular tachycardia (VT). Results The stretch caused a decrease in MAPD(20-70) (both P <0.01) and an increase in MAPD(90) (both P <0.01) in both control and MI groups. Moreover, the MAPD(90) in the MI group had increased more significantly than that in the control group (P <0.05). A concentration of 200 micromol/L of SM had no influence on both MAPD(20-70) and MAPD(90) of basic state (P > 0.05, except MAPD(20-70) between the control and SM groups, P < 0.01), whereas it had reduced the length of MAPD(90) (P < 0.05) and inhibited the decrease in MAPD(20-70) induced by the inflation. There was a decrease in the tendency of MAPD(70) after the stretch (P = NS) and SM had reversed the tendency, whereas MAPD(20) had no obvious changes after inflation. The incidence rate of PVB and VT in the MI group was higher than that in the control group after inflation (P < 0.01). The 200 micromol/L SM reduced the incidence rate of PVB, and obviously inhibited the occurrence of VT (P < 0.01). CONCLUSIONS: Stretch could alter the electrophysiological activities of myocardium via MEF, which could enhance in acute myocardial infarction and facilitate the generation and maintenance of malignant arrhythmias. SM could significantly inhibit the occurrence of arrhythmias, which may correlate with the effect on blocking stretch-activated ion channels.