ObjectiveTo investigate the effect of isoflurane preconditioning on calcitonin gene-related peptide (CGRP) and NF-kappa B following local cerebral ischemia/reperfusion (I/R) in rabbits.MethodsFiftyfour adult New Zealand white rabbits of both sexes weighing 2.0-2.5 kg were randomly divided into three groups (n ＝ 18 each):sham operation group (group S),group I/R and isoflurane preconditioning group(group I).After anesthesia induction with intramuscular injection of ketamine 70 mg/kg and scopolamine 0.006 mg/kg and maintenance of anesthesia with intravenous injection of midazolam 0.1 mg/kg,fentanyl 0.01 mg/kg and vecuronium 0.1 mg/kg,endotracheal intubation was performed and mechanical ventilation was employed.In groups I/R and S,midazolam at 0.1 mg·kg-1·h-1 was infused through the left ear vein.After the rabbits in group I inhaling 1.4％ isoflurane for 30 minutes,which was then eluted for 10 minutes,local cerebral ischemia was made in groups I/Rand I with thread ligation method and reperfusion was made 2 hours later,simultaneously midasolam at 0.1 mg·kg- 1 · h - 1 was injected.All the rabbits in three groups were infused with fentanyl at 0.05 mg· kg- 1 · h- 1 and vecurenium at 0.10 mg· kg-1 · h-1.After blood samples were collected from the central artery of the ear for determination of plasma CGRP before anesthesia,immediately before reperfusion,and 1,2,3,4,and 5 h of reperfusion,all the animals were sacrificed at the corresponding time points and brain tissues were obtained for determination of NF-κB activity and its expression with Western blotting and immunohistochemistry staining.ResultsThe plasma concentration of CGRP,the activity and expression of NF-κB were higher in group I/R than in group S ( P <0.05).The plasma concentration of CGRP was higher and the activity and expression of NF-κB were lower in group I than in group I/R ( P < 0.05 ).ConclusionIsoflurane preconditioning can reduce local cerebral I/R injury in rabbits through promoting CGRP release and inhibiting NF-κB function.

AIM: To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), and to investigate the changes of action potential duration (APD),transient outward potassium current (I to ), delayed rectifier potassium current (I K) and inward rectifier potassium current (I K1 ) of left ventricular myocytes in noninfarcted zone of HMI. METHODS: 12 rabbits were randomly assigned in two groups: HMI group (thoracotomy and ligation of the circumflex coronary); sham-operated group (thoracotomy but no conorary ligation). 3 months after operation, whole cell patch clamp technique was used to record APD, I to , I K and I K1 of ventricular myocytes in non-infarcted zone. RESULTS: Membrane capacitance was larger in HMI group than that in sham-operated group. Action potential duration was lengthened significantly in HMI group and early after depolarization (EAD) appeared in HMI group. The densities of I to , I K,tail and I K1 were reduced significantly in HMI group (P

Objective To explore the changes of expression of platelet PECAM-1,P-selectin in patients with acute cerebral infarction.Methods The platelet expression levels of PECAM-1,P-selectin in 35 patients with acute cerebral infarction were serially measured with whole blood flow cytometry 24,48 hours and 5,7,14 days after the onset,and were compared with those of 30 normal controls.Results The platelet expression levels of PECAM-1 and P-selectin in patients with cerebral infarction 24 hours after the onset(78.35?10.48,7.75?3.04 respectively)were higher than those of controls(48.89?10.84,2.18?0.83 respectively,all P

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 ; Autonomic Nervous System/*physiopathology ; Electric Stimulation ; Heart Ventricles/innervation ; Heart Ventricles/*physiology ; Myocardial Ischemia/*physiopathology ; Neuromuscular Junction

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

To evaluate the protective effect of puerarin on ischemic myocardium in dogs with acute myocardial infarction (AMI) and to reveal its possible mechanism, 10 dogs were randomly divided into puerarin group (group G) and control group (group C). AMI model was established in all dogs. Puerarin or saline was administered over a period of 21 days. Coronary angiography was performed before and after ligation of coronary artery. Eight hemorheological parameters were examined before and 22 days after the operation. The infarct area and vessel density of myocardium were assessed. The infarct area in group G was smaller than that in group C. Angiography 2 h and 22 d after ligation of coronary artery revealed significant augmentation of collateral vessels in group G as compared with control group. The platelet aggregation and the blood viscosity were increased during AMI when compared with control phase, and the increased indexes during AMI would be inhibited when puerarin were given. Capillaries and distribution vessel density in ischemic zone on day 22 showed statistically significant augmentation in group G as compared with control group. Puerarin might improve the opening and formation of coronary collateral circulation, and might inhibit the increase of platelet aggregation and the blood viscosity during AMI,and thereby improve microcirculation and restrict myocardial infarct area.

To evaluate the protective effect of puerarin on ischemic myocardium in dogs with acute myocardial infarction (AMI) and to reveal its possible mechanism, 10 dogs were randomly divided into puerarin group (group G) and control group (group C). AMI model was established in all dogs. Puerarin or saline was administered over a period of 21 days. Coronary angiography was performed before and after ligation of coronary artery. Eight hemorheological parameters were examined before and 22 days after the operation. The infarct area and vessel density of myocardium were assessed. The infarct area in group G was smaller than that in group C. Angiography 2 h and 22 d after ligation of coronary artery revealed significant augmentation of collateral vessels in group G as compared with control group. The platelet aggregation and the blood viscosity were increased during AMI when compared with control phase, and the increased indexes during AMI would be inhibited when puerarin were given. Capillaries and distribution vessel density in ischemic zone on day 22 showed statistically significant augmentation in group G as compared with control group. Puerarin might improve the opening and formation of coronary collateral circulation, and might inhibit the increase of platelet aggregation and the blood viscosity during AMI,and thereby improve microcirculation and restrict myocardial infarct area.

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

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