The transmural heterogeneous changes of transient outward potassium currents (Ito) in rabbit hypertrophic cardiaomyocytes and the effects of long-term prophylactic treatment with volsartan were investigated. Rabbits were divided into hypertrophy group (left ventricular hypertrophy induced by partial ligation of abdominal aorta), vol-treated group (volsartan was administrated after the ligation), and control group (sham operated). Myocytes were isolated by a two-step enzymatical method. The sub-endocardial (Endo) and sub-epicardium (Epi) tissues were separated from midmyocardium (Mid) with a razor. Whole-cell patch-clamp technique was used to record potassium currents. The results showed that membrane capacitance was larger in hypertrophic cells than those in control and vol-treated cells (P<0.01 vs control cells, n=30). The densities of Ito in hypertrophic cells were reduced by sub-epicardium (Epi) (27.8 +/- 2.9) %, midmyocardium (Mid) (41.0+/-4.7) %, and sub-endocardium (Endo) (20.3 +/- 3.4) % compared with those in control cells. The decrease of Ito density was more pronounced in Mid than in Epi and Endo (P<0.01 vs Epi or Endo). There were no significant differences in Ito densities between vol-treated group and control group in three layers separately. In conclusion, volsartan can inhibit the transmural heterogeneous changes of Ito in left ventricular hypertrophic cardiomyocytes in rabbit.
Animals ; Antihypertensive Agents ; pharmacology ; Biological Transport, Active ; drug effects ; Female ; Hypertrophy, Left Ventricular ; drug therapy ; pathology ; Male ; Myocytes, Cardiac ; pathology ; Patch-Clamp Techniques ; Potassium Channels ; drug effects ; Rabbits ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives ; pharmacology ; Valsartan

This study evaluated the effects of adenovirus vector mediated human vascular endothelial growth factor-165 (hVEGF165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenoviruses containing hVEGF165 cDNA was directly injected into left side of the injured carotid arteries. On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and immunohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in carotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer. The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF165 gene transfer the VEGF mRNA and antigen expression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima area/media area (I/M), maximal intimal and medial thicknesses (ITmax and MTmax) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of recombinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit thrombokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.
Adenoviridae ; genetics ; metabolism ; Angioplasty, Balloon ; adverse effects ; Animals ; Carotid Artery Injuries ; pathology ; Carotid Stenosis ; physiopathology ; prevention & control ; Cell Division ; drug effects ; Endothelium, Vascular ; injuries ; pathology ; Genetic Therapy ; Hyperplasia ; prevention & control ; Male ; Muscle, Smooth, Vascular ; cytology ; RNA, Messenger ; biosynthesis ; genetics ; Rabbits ; Recombination, Genetic ; Transfection ; methods ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.
Action Potentials ; Animals ; Arrhythmias, Cardiac ; etiology ; Female ; Heart Ventricles ; metabolism ; Male ; Myocardial Infarction ; complications ; metabolism ; pathology ; Myocytes, Cardiac ; cytology ; Patch-Clamp Techniques ; Potassium Channels ; metabolism ; Rabbits

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (MAPs) of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall in 12 open-chest dogs. MAPD90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD90 of Epi, Mid and Endo before autonomic nervous stimulation were 278 +/- 11 ms, 316 +/- 16 ms and 270 +/- 12 ms respectively, the MAPD90 of Mid was significantly longer than that of Epi or Endo (P<0.01). MAPD90 of Epi, Mid and Endo were shortened by 19 +/- 4 ms, 45 +/- 6 ms, 18 +/- 3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44 +/- 4 ms to 15 +/- 3 ms (P<0.01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41%) during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.
Action Potentials ; physiology ; Animals ; Autonomic Nervous System ; physiology ; Dogs ; Electric Stimulation ; Electrocardiography ; Electrodes ; Endocardium ; innervation ; physiology ; Heart Ventricles ; innervation ; Myocardium ; cytology ; Neuromuscular Junction ; Pericardium ; innervation ; physiology ; Ventricular Function

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (MAPs) of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall in 12 open-chest dogs. MAPD90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD90 of Epi, Mid and Endo before autonomic nervous stimulation were 278 +/- 11 ms, 316 +/- 16 ms and 270 +/- 12 ms respectively, the MAPD90 of Mid was significantly longer than that of Epi or Endo (P<0.01). MAPD90 of Epi, Mid and Endo were shortened by 19 +/- 4 ms, 45 +/- 6 ms, 18 +/- 3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44 +/- 4 ms to 15 +/- 3 ms (P<0.01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41%) during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.
Action Potentials/physiology ; Autonomic Nervous System/*physiology ; Electric Stimulation ; Electrocardiography ; Electrodes ; Endocardium/innervation ; Endocardium/physiology ; Heart Ventricles/innervation ; Heart Ventricles/*physiology ; Myocardium/cytology ; Neuromuscular Junction ; Pericardium/innervation ; Pericardium/physiology

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.
Action Potentials ; Arrhythmia/*etiology ; Heart Ventricles/metabolism ; Myocardial Infarction/complications ; Myocardial Infarction/metabolism ; Myocardial Infarction/*pathology ; Myocytes, Cardiac/*cytology ; Patch-Clamp Techniques ; Potassium Channels/*metabolism

OBJECTIVETo investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes.

METHODSRabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg x kg(-1) x d(-1)) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents.

RESULTSMembrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of ICa, L was reduced from 12.8 +/- 0.7 pA/pF in the sham-operated cells, to 7.7 +/- 0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9 +/- 1.0 pA/pF). After IMI treatment, the density of I(Ks,tail) was enhanced from 2.5 +/- 0.1 pA/pF in hypertrophic cells to 4.7 +/- 0.6 pA/pF (n = 7, P < 0.01), which was similar to the sham-operated cells. The densities of Ito and IK1 were significantly increased in IMI-treated cells, from 3.8 +/- 0.4 pA/pF and 3.7 +/- 0.5 pA/pF in the hypertrophic cells to 6.4 +/- 0.8 pA/pF and 6.5 +/- 0.3 pA/pF, respectively, but the IKr densities were not different in the three groups.

CONCLUSIONIMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of ICa, L, IKs, Ito and IK1 in hypertrophic cells.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Calcium Channels ; drug effects ; Female ; Hypertrophy, Left Ventricular ; pathology ; Imidazoles ; pharmacology ; Imidazolidines ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Potassium Channels ; drug effects ; Rabbits ; Random Allocation

In order to assess the diagnostic value of invasive electrophysiologic study (EPS) in the patients with unexplained syncope, the electrophysiologic findings of 268 patients with unexplained syncope despite a complete clinical evaluation were analyzed. Results showed positive EPS finding was 38% in total patients and 50% in the patients aged > 70 years. With increasing age, the diagnostic yield of EPS also increased. No significant differences of complication rate were found among the different age groups. It was concluded that EPS have high diagnostic value in the patients with unexplained syncope. Its complications are few and mild. EPS may be recommended in elderly patients with unexplained syncope.
Adult ; Age Factors ; Aged ; Arrhythmias, Cardiac ; complications ; diagnosis ; Diagnosis, Differential ; Electrocardiography ; Electrophysiology ; Follow-Up Studies ; Humans ; Middle Aged ; Monitoring, Physiologic ; Retrospective Studies ; Syncope ; diagnosis ; etiology ; Tachycardia ; complications ; diagnosis

In order to assess the diagnostic value of invasive electrophysiologic study (EPS) in the patients with unexplained syncope, the electrophysiologic findings of 268 patients with unexplained syncope despite a complete clinical evaluation were analyzed. Results showed positive EPS finding was 38% in total patients and 50% in the patients aged > 70 years. With increasing age, the diagnostic yield of EPS also increased. No significant differences of complication rate were found among the different age groups. It was concluded that EPS have high diagnostic value in the patients with unexplained syncope. Its complications are few and mild. EPS may be recommended in elderly patients with unexplained syncope.
Age Factors ; Arrhythmia/complications ; Arrhythmia/*diagnosis ; Diagnosis, Differential ; *Electrocardiography ; Electrophysiology ; Follow-Up Studies ; Monitoring, Physiologic ; Retrospective Studies ; Syncope/diagnosis ; Syncope/*etiology ; Tachycardia/complications ; Tachycardia/diagnosis

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), mid-myocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs. MAPD90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial ischemia, TDR was increased from 55 +/- 8 ms to 86 +/- 15 ms during sympathetic stimulation (P < 0.01). The TDR (53 +/- 9 ms) during parasympathetic stimulation was not significantly different from that of the control (55 +/- 8 ms) (P > 0.05). The EAD was elicited in the Mid of 2 dogs (16%) 10 min after acute myocardial ischemia, but the EAD were elicited in the Mid of 7 dogs (58%) during sympathetic stimulation (P < 0.01). It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolarization and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which provide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.
Action Potentials ; physiology ; Animals ; Autonomic Nervous System ; physiopathology ; Dogs ; Electric Stimulation ; Female ; Heart Ventricles ; innervation ; Male ; Myocardial Ischemia ; physiopathology ; Neuromuscular Junction ; Ventricular Function