The effects of methanol extract of Galium verum L on cardiac redox state in hypertensive rats

Abstract The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.

Effects of ultrafine particulates on cardiac function in rat isolated heart / 北京大学学报(医学版)

OBJECTIVE@#To evaluate whether ultrafine particulates (UFPs) have direct deleterious effects on cardiac function through activating MAPK signaling.@*METHODS@#Langendorff-perfused Sprague-Dawley rat hearts were randomly divided into 2 groups (n=10/each group). In control group, the rat hearts were perfused with Tyrode's buffer for 40 min; in UFPs-treated group, the hearts were perfused with UFPs at a concentration of 12.5 mg/L. Cardiac function was determined by measuring left ventricular developed pressure (LVDP), left ventricular peak rate of contraction and relaxation (±dp/dtmax) and coronary flow (CF). The levels of malondialdehyde (MDA), superoxide dismutase (SOD), total anti-oxidant capacity (TAOC) were detected in order to evaluate cardiac oxidative stress via the thiobarbituric acid assay, water soluble tetrazolium salt assay and colorimetry, respectively. The expressions of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium were observed using immunohistochemical staining and Western blots.@*RESULTS@#No significant changes in cardiac function were detected before and after the perfusion in control group while UFPs perfused hearts showed a decline in cardiac function in a time-dependent manner (all P < 0.05). In UFPs-treated group, LVDP, +dp/dtmax, -dp/dtmax and CF were statistically reduced from (82.6±2.1) mmHg, (1 624±113) mmHg/s, (1 565±116) mmHg/s, (12.0±0.2) mL/min to (56.8±4.4) mmHg, (1 066±177) mmHg/s, (1 082±134) mmHg/s, (8.7±0.3) mL/min (all P < 0.05), respectively. Furthermore, The comparison between the two groups observed that UFPs perfusion caused a significant decrease in cardiac function at 30 and 40 min compared with the control group (all P < 0.05). At the end of the perfusion, the level of MDA was increased from (0.98±0.14) nmol/L to (1.95±0.18) nmol/L, while SOD and TAOC were reduced from (12.50±1.87) U/mL and (6.83±1.16) U/mL to (6.50 ±1.04) U/mL and (3.67±0.82) U/mL (all P < 0.001) in UFPs group, respectively. In coincidence with these changes, immunohistochemistry and Western blots results showed that the levels of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium significantly increased in UFPs group as compared with control group (all P < 0.05).@*CONCLUSION@#The results of this study demonstrated that the short-term exposure of UFPs to the isolated rat hearts has direct and acute toxic effects on cardiac function, probably related to attenuation of anti-oxidative capacity and activation of MAPK signaling pathways.

Anti-ischemic Effect of Polygala Tenuifolia in Isolated Rat Heart

Polygala tenuifolia (PT) is one of the most well-known traditional herbal medicines in Korea which is commonly used for the treatment of cardiovascular symptoms. The anti-ischemic effects of PT in isolated rat heart was investigated by analyzing changes in blood pressure, aortic flow, coronary flow, and cardiac output. And, its underlying mechanism was examined by quantitating intracellular calcium content in rat neonatal cardiomyocytes. Rats were divided into two groups: an ischemia-induced group without any treatment, and an ischemia-induced group treated with PT. Ischemia of isolated heart was induced by stopping the supply of oxygen and buffer for 10 min. The isolated heart was exposed to PT for the first 5 min of 10 min ischemia. PT treatment significantly prevented the decreases of perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, hemodynamics (except heart rate) of the PT-treated group was significantly recovered 60 min after reperfusion compared to the control group (systolic aortic pressure: 83.3% vs. 64.9%, aortic flow volume: 69.5% vs. 48.7%, coronary flow volume: 77.7% vs. 58.4%, and cardiac output: 71.6% vs. 51.2%, p<0.01). As for the underlying mechanism, PT significantly prevented intracellular calcium increase which was induced by isoproterenol (p<0.01), suggesting that the anti-ischemic effect of PT is mediated by inhibition of intracellular calcium increase.

Comparisons of Myocardial Protective Effects of Sevoflurane at Different Concentrations against Ischemia in Isolated Rat Heart / 대한마취과학회지

BACKGROUND: Sevoflurane, a newly developed halogenated inhalation anesthetic agent shows myocardial protective effects against global ischemia like other inhalation agents. We investigated differences between pharmacologic preconditioning effects at various concentrations of sevoflurane. METHODS: Forty male Sprague-Dawley rats were subdivided into 4 groups (each n = 10). All groups underwent the same procedure (Langendorff preparation, 30 minutes ischemia and 60 minutes reperfusion) except for the concentrations of sevoflurane. The control group received no sevoflurane treatment. The sevo 1.6% group was given 1.6% sevoflurane before ischemia, the sevo 205% group was given 2.05% sevoflurane before ischemia, and the sevo 2.5% group was given 2.5% sevoflurane before ischemia. Hemodynamic parameters of all groups were recorded through a thin, saline-filled latex balloon and a transducer. Coronary flows were also measured. All hearts were stained by triphenyl tetrazolium to measure infarct size. RESULTS: The sevoflurane administered groups showed higher left ventricular end systolic pressures and lower left ventricular end diastolic pressures than the control group after ischemia and reperfusion. The dP/dtMAX of the sevoflurane administration groups showed a more rapid recovery pattern after ischemia than the control. But no differences were found between the sevoflurane administered groups. Infarct sizes in the sevoflurane administered groups were smaller than those in the control group, and there were no significant differences between the sevoflurane administered groups. CONCLUSIONS: Sevoflurane (even below one MAC) administration before myocardial ischemia has a superb cardioprotective effects, i.e., rapid recovery of left ventricular fuctions, less stiffness development, and a reduced infarct size. There were no significant differences between the sevoflurane administered groups.

The Myocardial Protective Effects of Desflurane on Global Ischemia in Isolated Rat Heart via KATP Channel Activation / 대한마취과학회지

BACKGROUND: In experimental models, several volatile anesthetics have been found to beneficially mimic ischemic preconditioning (IPC) during ischemia and reperfusion. These effects of IPC and volatile anesthetics are mediated by KATP channels, the authors examined following hypothesis: Desflurane administration before myocardial ischemia, has pharmacologic preconditioning effects on the myocardium (better functional recovory, and reduced infarct size), and these effects are mediated by KATP channel activation. METHODS: Isolated Sprague-Dawley rat hearts (n = 40) were perfused at a constant pressure with oxygenated modified Kreb's solution. After a stabilization period, they were subdivided into four groups; group 1 to 4. Group 1 underwent 30 minutes of global ischemia and 60 minutes of reperfusion. Group 2 received an ischemic preconditioning period before global ischemia and reperfusion as group 1. In group 3, 6.8 vol% desflurane was added to the perfusion medium for 15 minutes and a 5 minutes wash-out period was introduced before global ischemia and reperfusion. In group 4, during the 6.8 vol% desflurane administration, glibenclamide was injected at a constant rate, before global ischemia and reperfusion. In each group, isovolumetric left ventricular pressure (LVP), heart rate and the maximun rate of change of the ventricular pressure (dP/dtmax) were measured using a thin, saline-filled latex balloon and a transducer. Coronary flow and the LDH level of effluent were measured at 5, 30, 60 minutes after reperfusion. All hearts were stained with triphenyl tetrazolium to determine infarct size. RESULTS: Desflurane administration before global ischemia showed protective effects, like IPC, on functional recovery and infarct reduction. LVP was less depressed in group 3 and group 2. dP/dtmax in group 2 recovered after global ischemia to some degree, but remained slightly depressed in group 3. Decreased heart rate and coronary flow were observed in groups 2, 3 and 4. LDH showed a decreasing pattern in group 2 and 3. Infarct size was smaller in groups 2 and 3 than in groups 1 and 4. These benefical effects of desflurane were blocked by glibenclamide administration. CONCLUSIONS: Desflurane was found to have beneficial effects, and mimicked IPC by preservaing LVP, reducing infarct size, and the degree of cardiac enzyme release. These beneficial effects were abolished by administering the KATP channel blocker, glibenclamide. The protecitve effects of desflurane administration against myocardial ischemia were mediated by KATP channels.

Effects of Ischemic preconditioning on the Post-ischemic Myocardial Dysfunction and Coronary Flow in the Isolated Rat Hearts

BACKGROUND: Brief episodic ischemias prior to subsequent prolonged ischemia limit infarct size and attenuate the reperfusion arrythmia. But the effect of ischemic preconditioning on post-ischemic myocardial dysfunction, coronary flow and nitric oxide (NO) remains unclear. METHODS: To investigate the effect of ischemic preconditioning on myocardial function and coronary flow during reperfusion after 15 minutes of global myocardial ischemia, 30 isolated hearts of Sprague-Dowley rats were perfused under constant pressure. Two episodes of three minutes global ischemia followed by 12 minutes of reflow were employed to precondition the hearts. The hearts were randomized to one of three groups : group I had no preconditioning, group II had preconditioning, group III had preconditioning as well as L-arginine pretreatment. Left ventricular developed pressure (LVDP), LV dp/dt, perfused coronary flow, concentration of NO and heart rate were continuously measured. RESULTS: In preconditioning groups (Group II, Group III), LVDP decreased during reflow and was lower than that of the control group. LV dp/dt decreased after reflow and gradually recovered with time but recovered was less in preconditioning groups. Coronary flow increased in the first few minutes after reflow in all groups, but decreased gradually. The decrease of coronary flow was greater in preconditioning groups. NO increased during the first 10 minutes after reflow and then decreased. In preconditioning groups, NO tends to be lower than that in the non-preconditioning group. CONCLUSION: Ischemic preconditioning was not beneficial to post-ischemic myocardial dysfunction, coronary flow and NO concentration in the flow. Cummulative effect of stunning due to repetitive ischemia for preconditioning may be an explanation for worse post-ischemic myocardial dysfunction and coronary flow in preconditioning groups.

Effects of Ischemic preconditioning on the Post-ischemic Myocardial Dysfunction and Coronary Flow in the Isolated Rat Hearts

BACKGROUND: Brief episodic ischemias prior to subsequent prolonged ischemia limit infarct size and attenuate the reperfusion arrythmia. But the effect of ischemic preconditioning on post-ischemic myocardial dysfunction, coronary flow and nitric oxide (NO) remains unclear. METHODS: To investigate the effect of ischemic preconditioning on myocardial function and coronary flow during reperfusion after 15 minutes of global myocardial ischemia, 30 isolated hearts of Sprague-Dowley rats were perfused under constant pressure. Two episodes of three minutes global ischemia followed by 12 minutes of reflow were employed to precondition the hearts. The hearts were randomized to one of three groups : group I had no preconditioning, group II had preconditioning, group III had preconditioning as well as L-arginine pretreatment. Left ventricular developed pressure (LVDP), LV dp/dt, perfused coronary flow, concentration of NO and heart rate were continuously measured. RESULTS: In preconditioning groups (Group II, Group III), LVDP decreased during reflow and was lower than that of the control group. LV dp/dt decreased after reflow and gradually recovered with time but recovered was less in preconditioning groups. Coronary flow increased in the first few minutes after reflow in all groups, but decreased gradually. The decrease of coronary flow was greater in preconditioning groups. NO increased during the first 10 minutes after reflow and then decreased. In preconditioning groups, NO tends to be lower than that in the non-preconditioning group. CONCLUSION: Ischemic preconditioning was not beneficial to post-ischemic myocardial dysfunction, coronary flow and NO concentration in the flow. Cummulative effect of stunning due to repetitive ischemia for preconditioning may be an explanation for worse post-ischemic myocardial dysfunction and coronary flow in preconditioning groups.

Effects of verapamil in cardioplegic perfusates on the ischemic myocardium in isolated rat heart / 대한흉부외과학회지

Using isolated rat heart preparations, we observed the protective effects of verapamil cardioplegia on ischemic myocardial injury. Isolated rat hearts were subjected to global ischemia at 25degrees C. Twenty four isolated Sprague Dawley rat hearts underwent 30 minutes of the retrograde nonworking perfusion with Krebs-Henseleit buffer solution followed by 25degrees C cardioplegic solution(St. Thomas' Hospital Cardioplegic Solution) for 60 minutes. Before ischemic arrest, rat hearts were treated with cold cardioplegic solution in control group(n=12) and cold cardioplegic solution with verapamil(1mg/L) in experimental group(n=12). After 60 minutes of ischemia, hemodynamic and biochemical parameters such as heart rate, left ventricular pressure(LVP), +dp/dt max, coronary flow and creatine phosphokinase(CPK) were measured before giving cardioplegia and 30 minutes after reperfusion. Verapamil group exhibited greater recovery of heart rate, LVP, +dp/dt max, coronary flow and CPK than control group(p<0.05).

Protective effects of ischemic preconditioning with normothermia or hypothermia on schemia/reperfusion in-jury in isolated rat hearts / 中国介入心脏病学杂志

Using isolated rat hearts perfused on a langendorff apparatus,ischemic preconditioning (IP) was investigated with 5 min normothermic (at 37℃) or hypothermic (at 30 ℃) ischemia, followed by 10 min of reperfusion before the arrest period, as an adjunct to St. Thomas crystalloid cardioplegia during 180 min ischemia. After basline functional data were obtained, IP was induced 1 control hearts underwent no IP. Results showed that IP improved functional recovery from ischemia during 45 min reperfusion in normothermic ischemic preconditioning group (NP) comparing with normothermic control (NC),P

ANTIARRHYTHMIC EFFECT OF TOTAL FLAVONES OF HIPPOPHASE RHAMNOIDES IN THE ISOLATED HEART / 中国药理学通报

In the isolated perfused rat heart, TFH counteracted significantly the arrhythmias caused by perfusing with a solution without oxygen; increased ventricular fibrillation threshold markedly and showed a good dose-effective relation; prolonged the P-R period of electrocardiogram and decreased the heart rate and fell the amplitude of cardiac contraction markedly; and counteracted significantly the decrease of the heart rate and the amplitude of cardiac contraction caused by perfusing with a solution without oxygen. In the isolated guinea pig left atrium, TFH prolonged the function refractory period slightly. In the isolated guinea pig right atrium, TFH increased the accumulated dose of aconitine inducing arrhythmias.