Acute Myocardial Ischemia In Rats Research Articles

Responses of neurons in paraventricular nucleus to activation of cardiac afferents and acute myocardial ischaemia in rats

Stimulation of cardiac sympathetic afferents increases sympathetic outflow and blood pressure. Chemicals released during myocardial ischaemia activate cardiac afferents. This study was to determine the responses of neurons in paraventricular nucleus (PVN) to the cardiac afferent activation caused by exogenous chemicals or myocardial ischaemia using an extracellular single-unit recording method. Rats were anaesthetized and underwent bilateral cervical vagal denervation (VD) and carotid and aortic baroreceptor denervation (BD). In 196 spontaneously active neurons in parvicellular PVN, 60 (30.6%), 36 (18.4%) and 91 (46.4%) neurons were respectively sensitive, mildly sensitive and insensitive to capsaicin, while nine (4.6%) neurons showed inhibitory responses to capsaicin. Epicardial application of capsaicin activated capsaicin-sensitive neurons in the PVN and increased mean arterial pressure. These neurons were also sensitive to exogenous bradykinin, adenosine and H(2)O(2). The neuron response is not secondary to a capsaicin-induced increase in mean arterial pressure because a similar degree of pressor response induced by aortic coarctation did not increase the neuron activity. Compared with intact rats, VD or BD or combined VD and BD increased the response of capsaicin-sensitive neurons to epicardial application of capsaicin, while stimulation of vagal afferents inhibited the response. Myocardial ischaemia caused increases in the activity of capsaicin-sensitive neurons and renal sympathetic nerve activity. The results indicate that chemical stimulation of cardiac sympathetic afferents activates capsaicin-sensitive neurons in parvicellular PVN, which is inhibited by the afferent activities of vagi and arterial baroreceptors. Acute myocardial ischaemia activates capsaicin-sensitive neurons in PVN and enhances sympathetic outflow.

Effect of essential oil of Syringa pinnatifolia Hemsl. var. alashanensis on ischemia of myocardium, hypoxia and platelet aggregation

Aim of the study To investigate the cardioprotective potential of Syringa pinnatifolia Hems1. var. alashanensis essential oil (SPEO) against experimental acute myocardial ischemia (AMI), hydrogen peroxide (H 2O 2)-induced myocyte injury and activities against hypoxia and platelet aggregation. Materials and methods Wistar rats, Kunming mice and primary cultured rat neonatal myocytes were used in this study. AMI in rats was induced by ligation of the left anterior descending (LAD) coronary artery, and deviation of ST-segment, as well as changes of myocardial enzyme activities were observed. Hypoxia test in Kunming mice was performed to evaluate the effect of SPEO against hypoxia. The protective effect of SPEO on H 2O 2-induced cell injury was evaluated in terms of cell viability assay. The in vitro effect of SPEO against platelet aggregation was studied using adenosine 5′-diphosphate (ADP) as agonist. Results Administration of SPEO reduced deviation of ST-segment, decreased the levels of lactate dehydrogenase (LDH), creatine kinase (CK) and Troponin T (TnT) while increased the activities of superoxide dismutase (SOD). The protective role of SPEO was further confirmed by histopathological examination. In the hypoxia test, both 8 and 32 mg/kg of SPEO could prolong survival time of mice under hypoxia condition. At the meantime SPEO showed remarkable protective effect on cultured rat myocyte death induced by H 2O 2. SPEO also inhibited ADP-induced rat platelet aggregation by 47.4%, 37.0% and 32.9% at the dose of 5, 2.5 and 1.25 μg/mL, respectively. Conclusions These results suggest that SPEO possessing activities against hypoxia, oxidative stress and platelet aggregation has a significant protective effect against experimental myocardial ischemia.

Impact of CIDAN Mixture on the Hemodynamic Status of Acute Myocardial Ischemia Rats

Abstract The objective of this research is to study the hemodynamics status on the impact of Salvia miltiorrhiza injection and Acanthopanax senticosus injection mixture (CIDAN mixture) against acute myocardial ischemia in rats. Ramus descendens anterior arteriae coronariae sinistrae was ligated, and a plastic angio catheter full of 1% liquemine was inserted into left ventricles from right common carotid artery; the change of left ventricular pressure after 15 min from the ligation was observed. It was found that CIDAN mixture can increase left ventricular systolic pressure (LVSP) (P

Effects of tramadol hydrochloride pretreatment on expression of calcitonin gene-related peptide in myocardium following acute myocardial ischemia in rats

Objective To investigate the effects of tramadol hydrechloride pretreatment on the expression of calcitonin gene-related peptide (CGRP) in ischemic and non-ischemic myocardium following acute myocardial is-chemia in the rats. Method Eighteen adult male SD rats weighing 270 to 300 g were randomly divided into three groups(n = 6, in each): group Ⅰ ,sham operation; group Ⅱ , myocardial isehemia, and group Ⅲ, tramadol hydrochloride pretreatment. The anterior descending branch of left coronary artery was occluded(CAO)for 3 hours in rats of group Ⅱ and Ⅲ. In group Ⅲ, tramadol hydrochloride 12.5 mg·kg~(-1) was injected through caudal vein 15 minutes before CAO. At 3 hours after myocardial ischemia, the hearts were removed for determination of CGRP protein content in ischemic and non-ischemie myocardium by immuno-histochemistry and enzyme immunometric as-say, and the expression of CGRPmRNA by RT-PCR. One-way ANOVA was used for statistical analysis. ResultsOnly β-CGRPmRNA was found in rats myocardium. In the ischemic myocardium, the average light density of CGRP(0.215 ± 0. 100), positive unit (36.95 ± 1.70), concentration (39.06 ± 1.86) and expression of β-CGRP mRNA 0. 946 ± 0. 019) were significantly increased in group Ⅱ compared with those in group Ⅰ (0. 139 ± 0.006), (25.01 ± 1.03), (20.80± 1.24), (0.734±0.025) (P <0.05), and decreased markedly in group Ⅲ(0.158+0.008),(28.53±1.21),(28.58±2.10),(0.872±0.024) (P < 0.05) In the non-ischemic my-ocardium, the average hght density of CGRP(0.156 ± 0.017), positive unit(28.57 ± 2.23), concentration (28.58 ± 1.12) and expression of β-CGRP mRNA(0.810 ± 0.021) were significantly increased in group Ⅱ com-pared with those in group Ⅰ (0.109+0.013, 20.91 ～2.14, 17.35+2.72, 0.701 ～0.018) (P < 0.05), and decreased markedly in group Ⅲ(0.120±0.008), (22.58±1.18), (23.26±2.41), (0.779±0.022) (P < 0.05). Conclusions Tramadol hydrochloride pretreatment can significantly inhibit increase in CGRP expression in myocardium elicited by CAO, which might imply that tramadol hydrochloride might take part in protection of my-ocardium against acute myocardial ischemia by means of pain-relief. Key words: Tramadol Hydrochloride; Pretreatment; Calcitonin gene related pipetide; Myocardial ischemia; Rats

Protective roles of Asperosaponin VI, a triterpene saponin isolated from Dipsacus asper Wall on acute myocardial infarction in rats

Asperosaponin VI is a saponin of the medicinal herb Dipsacus asper (Xuduan), and no pharmacological activity has been reported yet. In this study, we investigated the anti-myocardial ischemia effects of Asperosaponin VI (ASA VI) both in vivo and in vitro. An animal model of myocardial ischemia(MI) injury was induced by coronary occlusion, pretreatment with ASA VI (10 and 20 mg/kg, i.v.) could protect the heart from ischemia injury by decreasing the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (GOT) and cardiac troponin T (cTnT) in serum, increasing the levels of catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels in heart, and decreasing that of malondialdehyde (MDA) level in acute MI rats. ASA VI also raised the activities of mitochondrial enzymes (succinate dehydrogenase (SDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase (MDH) and α-ketoglutarate dehydrogenase (α-KGDH)) and those of adenosine triphosphate (ATP) content, but lowered Ca 2+ level. Electrocardiograph parameters and histopathological observations demonstrated the same protective effects. In vitro experiment, neonatal rat cardiomyocytes were incubated to test the direct cytoprotective effect of ASA VI against H 2O 2 exposure. Pretreatment with ASA VI (30 and 60 µg/ml) prior to H 2O 2 exposure increased cell viability and inhibited H 2O 2-induced reactive oxygen species increase. ASA VI (15, 30 and 60 µg/ml) also increased the activities of LDH in the cultured supernatant and SOD in cardiomyocytes, but decreased the cardiomyocytes MDA level. Our results suggested that ASA VI could provide significant cardioprotective effects against acute MI in rats. The mechanisms might be attributed to scavenging lipid peroxidation products and reactive oxygen species, increasing antioxidant defense enzymes and preventing mitochondrial damage.

Cardio-protective effects of Corocalm on acute myocardial ischemia/reperfusion injury in rats

To investigate the cardio-protective effects of Corocalm on acute myocardial ischemia in rats, and to explore its possible therapeutic mechanisms. The acute ischemic model was prepared by ligating the left anterior descending (LAD) coronary artery in rats. The animals were divided into 6 groups, 8 in each group. The sham operated group underwent heart exposure without ligation and were treated with normal saline 3 ml/kg, while the other 5 groups, the model groups, consisted of acceptable acute ischemic model rats and were also treated with normal saline, with the Guanxin Capsule (GXC) group treated with refined GXC, 600 mg/kg, the low and high dose Corocalm groups treated with 85 mg/kg and 340 mg/kg of Corocalm respectively, and the Diltiazem group, treated with Diltiazem 5 mg/kg, with all the tested drugs prepared with normal saline into equal volume (3 ml/kg) and administrated once via duodenum 10 min before ligation. Myocardial infarction area was determined by the quantitative histological assay with nitroblue tetrazolium (N-BT) stain. And the levels of creatine phosphokinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) content, and the activity of superoxide dismutase (SOD) in serum were measured by biochemical assay and spectrophotometry respectively. Besides, the blood viscosity in another 50 rats was determined, who received for 7 successive days oral administration with different concentration of Corocalm or aspirin. It showed that low and high dose Corocalm could significantly reduce the infarction area, inhibit the increase of serum CK, LDH activity and MDA content, and enhance the SOD activity after ischemia/reperfusion. The whole blood viscosity at different shear rates in rats treated with high dose Corocalm was significantly lower than those treated with normal saline (P < 0.05). Corocalm has favourable protective effects on heart in ischemic condition, the effect of which might be through its actions in inhibiting CK and LDH activity, scavenging oxygen free radicals, and lowering blood viscosity.

Bilateral stellate ganglion block attenuates myocardial ischemia and ventricular arrhythmia

Stellate ganglion block (SGB) is a useful procedure to relieve symptoms of sympathetically maintained pain. However, little is known about its effect on myocardial ischemia. Thus, the aim of this study was to investigate the effects of bilateral stellate ganglion block (SGB) on acute myocardial ischemia and its effect on ventricular arrhythmia in ischemic rats. Under general anesthesia with isoflurane, thirteen Sprague-Dawley rates, weighing 290–400g, were instrumented with arterial and left ventricular catheters and EKG electrodes. Then the rats were divided into 2 groups: Group I (N=6: treatment group), underwent bilateral SGB before a 10 min coronary artery occlusion and followed by a 30 min reperfusion period. Group II (N=7: control group) underwent a similar ischemic insult without SGB. We recorded central and peripheral hemodynamics and arrhythmias. Bilateral SGB was performed according to our newly developed technique using 0.2 ml of bupivacaine 0.25%. Ten minutes after coronary artery occlusion, the ST segment increased from a baseline of 0 to 0.063 ± 0.03 mV in group I animals, and from 0 to 0.5 ± 0.06 MV in group II animals (P<0.001). Furthermore, 5 out of 7 rats in group II had ventricular tachycardia or fibrillation as the result of coronary occlusion and reperfusion injury. On the contrary, only 1 out of 6 rats in group I had ventricular tachycardia from similar myocardial insult. We conclude that bilateral stellate ganglion block attenuated the ST segment changes and arrhythmias associated with acute myocardial ischemia in rats. Further studies are underway to study its underlying mechanisms.

The effects of antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia in rats.

Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.

Effects of compound salviae miltiorrhizae injection on metabolism of phosphoinosititides in myocardial ischemia

Using the model of acute myocardial ischemia in rats formed by ligation of the descending anterior branch of the left coronary artery, this study showed some effects of compound Salviae miltiorrhizae injection (CSMI) on metabolism of phosphoinositide in myocardial ischemia. The results of the experiment showed that after 10 minutes of acute ischemia, the function of myocardial messangers of phosphoinositide increased, and the levels of phosphatidylinositol-4, 5-biphosphate (PIP2) and inositol-1, 4, 5-trisphosphate (IP3) were obviously higher than those of the non-ischemia control groups (P<0.01, n=7). CSMI (2 g/kg body weight) could markedly inhibit myocardial PIP2 and IP3, whose levels became lower than those of the ischemia control groups (P<0.01, n=7).

Effect of endogenous digoxin-like factor and digoxin antibody on myocardial Na+, K+-pump activity and ventricular arrhythmias in acute myocardial ischaemia in rats

The aim was to study whether a circulating sodium pump inhibitor (endogenous digoxin-like factor) contributes to the genesis of early ventricular arrhythmias in acute myocardial ischaemia in rats. Effects of digoxin antibody (260 micrograms.kg-1) on the incidence of ventricular arrhythmias, plasma digoxin-like immunoreactivity (DELFIA immunoassay), Na+, K+, and Mg2+ ions, and activity of the ouabain sensitive Na+, K(+)-pump in different regions of myocardium have been studied in propranolol naive and propranolol pretreated rats exposed to acute coronary artery ligation. Adult male Wistar rats were divided into six experimental groups: (1) saline pretreated controls; (2) saline pretreated coronary artery ligated rats; (3) coronary artery ligated rats pretreated with 260 micrograms.kg-1 digoxin antibody; (4) propranolol pretreated controls; (5) propranolol pretreated rats with acute myocardial ischaemia; (6) rats with acute myocardial ischaemia pretreated with both propranolol and digoxin antibody. Acute myocardial ischaemia in saline pretreated rats was associated with a twofold increase of plasma digoxin-like immunoreactivity and ventricular arrhythmias, but did not lead to changes in myocardial Na+, K(+)-pump activity. Pretreatment of coronary artery ligated rats with digoxin antibody reduced the total duration of ventricular tachycardia and ventricular fibrillation during a 15 minute postligation period from 201 (SEM 34) to 46(18) seconds (p < 0.002) but did not alter activity of the myocardial Na+, K(+)-pump. In rats pretreated with propranolol, acute myocardial ischaemia was associated with a twofold inhibition of the Na+, K(+)-pump in left atrial and left ventricular myocardium, and with a 69% increase in plasma K+ concentration. Administration of digoxin antibody to propranolol pretreated coronary artery ligated rats in parallel with the antiarrhythmic effect prevented the increase in plasma K+ concentration and inhibition of Na+, K(+)-pump in the left atrial, but not the left ventricular myocardium. A circulating digoxin-like factor contributes to the pathogenesis of myocardial ischaemia induced ventricular arrhythmias. As propranolol pretreatment of coronary artery ligated rats inhibited the Na, K(+)-pump in myocardium, the inhibitory effect of endogenous digoxin-like factor on Na+, K(+)-ATPase was probably masked in propranolol naive animals by the stimulatory action of catecholamines on Na+, K(+)-ATPase described previously.

Role of peptido-leukotrienes in the genesis of early ventricular arrhythmias during acute myocardial ischaemia in rats.

Changes in cardiac ventricular concentrations of peptidoleukotrienes (peptido-LTs) following coronary artery ligation and the effects of lipoxygenase inhibition and leukotriene antagonism on the cardiovascular responses to acute myocardial ischaemia were studied in pentobarbitone-anaesthetised rats. It was found that the left ventricular peptido-LT levels significantly increased at 2.5 and 5 min after left coronary artery ligation while the changes in right ventricle were not statistically significant. Pretreatment with nordihydroguaiaretic acid 25, 50 or 100 mg/kg caused marked depletion of ventricular peptido-LT content, but did not significantly prevent the blood pressure or heart rate changes, the occurrence of ventricular tachycardia or fibrillation, or the mortality of the animals following coronary artery ligation. Administration of SK&F 102922, even at doses which caused marked decreases in blood pressure and heart rate, also did not significantly alter the cardiovascular changes and the mortality rate induced by left coronary artery ligation. It is, therefore, suggested that the occurrence of ventricular arrhythmias and haemodynamic changes during the early phase of acute myocardial ischaemia may not be due to the augmented synthesis of peptido-LTs in cardiac tissue.

Gd‐BOPTA/Dimeg: Experimental disease imaging

The novel tissue-specific contrast agent, Gd-BOPTA/Dimeg, was tested in MR imaging of experimental focal liver disease and of acute myocardial ischemia in rats. Directly implanted liver tumors and blood-borne metastases were used as models for focal liver disease and occlusion of the lower anterior descending coronary artery as model for acute ischemia. The studies with implanted tumors, at a dose level of 250 mumol/kg, showed a very high (370%) and persistent (greater than 2 h) increase in the tumor-liver contrast-to-noise ratio (CNR), owing to selective enhancement of normal liver parenchyma signal intensity. While all blood-borne metastases showed a similar late CNR enhancement, some of them experienced early contrast loss due to transient signal intensity enhancement. In myocardial imaging, Gd-BOPTA/Dimeg produced a signal intensity enhancement in normal myocardium and an injured area-normal area CNR enhancement which were both much stronger and more persistent than those produced by Gd-DTPA/Dimeg.

Antiarrhythmic effect of antibodies to digoxin in acute myocardial ischemia in rats

Antiarrhythmic effect of antibodies to digoxin in acute myocardial ischemia in rats

Anaesthetic-Related Occurrence of Early Ventricular Arrhythmias During Acute Myocardial Ischaemia in Rats

The cardiovascular responses of rats anaesthetised with different anaesthetic agents to acute coronary artery ligation were studied. Before thoracotomy, urethane-anaesthetised animals exhibited significantly lower blood pressures. Ligation of the left coronary artery induced a high incidence of ventricular tachycardia or fibrillation in rats anaesthetised with pentobarbitone, urethane, or ether inhalation followed by chloralose. Ketamine-anaesthetised animals had a significantly lower incidence of ventricular arrhythmias. The mortality rate was also lower, though not statistically significant. However, all groups of rats showed essentially similar blood pressure and heart rate changes following coronary artery ligation as well as the time of onset of ventricular tachycardia or fibrillation. The findings demonstrate the influence of anaesthetics on the occurrence of early ventricular arrhythmias following acute coronary artery ligation in rats.

Vitamin E and ventricular fibrillation threshold in myocardial ischemia.

The effect of vitamin E on the ventricular fibrillation threshold was studied in an experimental model of acute myocardial ischemia. An anterior thoracotomy was performed on 23 anesthetized Wistar rats. The ventricular fibrillation threshold was measured. Vitamin E was then administered intravenously to an experimental group (n = 11) and a placebo to a control group (n = 12). The ventricular fibrillation threshold was measured again. Finally, the left anterior descending coronary artery was occluded, producing anteroapical myocardial ischemia. The ventricular fibrillation threshold was measured again. This threshold did not vary significantly when vitamin E or the placebo was administered before occluding the coronary artery but after the occlusion a threshold decrease in the placebo group was observed, whereas no such decrease was manifested in the vitamin E-treated group. The results suggest that vitamin E prevents ventricular fibrillation in acute myocardial ischemia in rats.

Ventricular histamine concentrations and arrhythmias during acute myocardial ischaemia in rats

The relation between ventricular histamine concentrations and the occurrence of early ventricular arrhythmias during acute myocardial ischaemia was investigated in pentobarbitone-anaesthetized rats. There was significant decrease in the left, but not the right, ventricular histamine level at 5 min following acute left coronary artery ligation. Pretreatment with rhodanine caused remarkable reduction in ventricular histamine concentrations as well as significantly lower incidence and slower onset of ventricular tachycardia and fibrillation resulting from acute myocardial ischaemia. On the contrary, aminoguanidine pretreatment did not significantly alter ventricular histamine levels nor did it influence the occurrence of early ventricular arrhythmias induced by coronary artery ligation. The responses of blood pressure and heart rate to acute coronary artery ligation were not noticeably affected by rhodanine or aminoguanidine pretreatment. These findings support the hypothesis that histamine release from cardiac tissues may contribute to the genesis of early ventricular arrhythmias, but not to the changes in blood pressure and heart rate, during acute myocardial ischaemia.

Effects of morphine on cardiovascular responses to acute myocardial ischaemia in rats.

The effects of acute coronary artery ligation on cardiac rhythm and haemodynamics were studied in rats receiving either acute or chronic morphine-treatment. In chronic opiate-treated animals, increasing concentrations of morphine sulphate were administered in drinking water over a 3 week period, and the development of morphine tolerance and dependence was verified by decreased analgesic responses to morphine in the tail-immersion test and the occurrence of naloxone-precipitated withdrawal syndromes, respectively. Acute coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate, and ventricular tachycardia or fibrillation in anaesthetized rats. The changes in blood pressure and heart rate following acute coronary artery ligation were not significantly altered by acute or chronic morphine administration. The incidence and the time of onset of ventricular tachycardia or fibrillation were found to be significantly reduced and prolonged, respectively, in chronically morphine-treated rats, but were not significantly affected by acute morphine administration in naïve animals. These findings suggest that chronic morphine treatment lessens the occurrence of early ventricular arrhythmias caused by acute myocardial ischaemia in rats. The mechanism of this effect is unclear.

Effect of parathyroid extract on the course of experimental acute myocardial ischemia in rats

Effect of parathyroid extract on the course of experimental acute myocardial ischemia in rats