Protective effects of baicalin on experimental myocardial infarction in rats

Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.

The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

Protective effect of dexmedetomidine against myocardial ischemia-reperfusion injury in rabbits

Abstract Purpose: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits. Methods: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated. Results: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05). Conclusion: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

Role of endothelial cell dysfunction in essential hypertension.

BACKGROUND: Hypertension is associated with functional and morphological alterations of the endothelium, which disturbs delicate balance of endothelium-derived factors resulting in endothelial dysfunction. The endothelial dysfunction could then facilitate the maintenance of elevated peripheral resistance, which would favor the occurrence of atherosclerosis. AIMS AND OBJECTIVES: The aim of the present study was to determine the circulating levels of vasodilators [nitric oxide (NO) and prostacyclin (PGI2)] and vasoconstrictors [endothelin I (ET-I) and thromboxane (TX)A2)], which reflect endothelial cell dysfunction. METHOD: Nitric oxide as nitrites and nitrates (NOx) were measured spectrophotometrically; ET-I, TXA2 (as TXB2) and PGI2 (as 6 keto PGFIalpha) were measured using enzyme immunoassay methods in 54 male subjects having predominantly untreated, mild hypertension and compared with age-matched 75 healthy controls. RESULTS: Significantly higher levels of ET-I (p<0.001) and TXB2 (p<0.001) were found in essential hypertension subjects (EHT) as compared to controls. No significant difference was observed in NOx and 6 keto PGFIalpha between the two groups. There was significant increase (p = 0.005) in the ratio of TXB2/6 keto PGFIalpha in EHT subjects as compared to controls. CONCLUSIONS: Elevated levels of vasoconstrictors in untreated essential hypertension subjects as compared to controls confirmed the presence of endothelial dysfunction, even in mild cases of hypertension. Early detection of endothelial dysfunction may be a useful measure to guide therapy before the damaging effects of hypertension manifests.

The role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in pathogenesis of dengue hemorrhagic fever (DHF).

In previous studies it has been demonstrated that the levels of plasma 6 keto-prostaglandin F1 alpha (6-K-PGF1), the stable metabolite of PGI2 were elevated in DHF patients during shock. In this study it is hypothesized that excessive PGI2 production plays a very important role in developing serious clinical manifestations of dengue shock syndrome (DSS) patients. In addition, an attempt was made to determine whether TXA2 has any significant role in such patients. Plasma 6-K-PGF1 and thromboxane B2 (TXB2), the stable metabolites of TXA2 were determined in 43 normal healthy children (NC) and 54 DHF patients without shock (DHF-N) and 33 DHF patients with shock (DHF-S). Subjects aged between 2 and 14 years. Plasma 6-K-PGF1 and TXB2 were measured by radioimmunoassay and the ratio of TXB2/6-K-PGF1 were also calculated. In 43 NC the values of plasma TXB2, 6-K-PGF1 and TXB2/6-K-PGF1 ratio were (mean +/- SE) 372.3 +/- 17.1, 150.1 +/- 2.4 and 2.52 +/- 0.12 pg/ml, respectively. In 54 DHF-N patients the corresponding values were 409.1 +/- 16.0, 278.4 +/- 11.6 and 1.54 +/- 0.06 pg/ml; whereas those in 33 DHF-S patients were 254.3 +/- 26.2, 349.1 +/- 20.5 and 0.757 +/- 0.073 pg/ml, respectively. Plasma 6-K-PGF1 levels of DHF-N and DHF-S patients were significantly greater than those in normal children (p < 0.001, p < 0.01 respectively). The plasma 6-K-PGF1 levels seem to be greater in DHF-S patients than in the DHF-N patients, however the difference in values were not statistically significant (p > 0.05). These findings indicate that plasma PGI2 level is significantly increased in DHF particularly during shock. Plasma TXB2 levels of DHF-N had no significant statistical difference from those of NC (p > 0.05); however, those in DHF-S patients were significantly lowered (p < 0.001) than those of NC and DHF-N patients. The findings suggest the important role of TXA2 to compensate for excessive PGI2 secretion in DHF patients. The failure or inadequate TXA2 production may eventually lead to shock. The ratios were significantly reduced in both DHF-N and DHF-S patients when compared to those of NC (p < 0.001 both). The ratio in DHF-S patients was also significantly lowered than that in DHF-N patients (p < 0.001). It is suggested that the imbalance between TXA2 and PGI2 production exists during DHF infection. The more reduction of plasma TXA2/PGI2 ratio leads to more overt and serious clinical manifestations of the disease.

A study of platelet aggregation, thromboxane A2 and prostacyclin in central aortic and coronary sinus blood in ischemic heart disease.

Aortic and coronary sinus platelet aggregation, thromboxane A2 (TXA2) and prostacyclin (PG12) levels were studied in fourteen patients of stable angina (SA), six of vasopastic angina (VA) and six control subjects (C). Patients of SA were studied at rest and during incremental atrial pacing and patients with VA were studied at rest and during various stages of vasospasm. Platelet aggregation was studied with different working concentrations of ADP, epinephrine and collagen. TX A2 and PGI2 concentrations were estimated by measuring levels of their stable metabolites viz. thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) respectively. Platelet aggregation was increased in SA and VA patients (p < 0.01) and further increase was seen during vasospasm (p < 0.001). However, it failed to increase on incremental atrial pacing. Similarly, TXB2 and PGF1 alpha levels were raised in SA and VA patients. While TXB2 further increased during vasospasm but not during atrial pacing. PGF1 infinity failed to rise with either. Thus platelets are in an activated state in SA and VA. This activated state is a cause and not an effect in SA and VA. An imbalance in the levels of TXA2 and PG12 could account for the vasospasm.

Lipid peroxidation and plasma thromboxane A2 / prostacyclin RAT10 in type 2 diabetics

This study was carried out with the aim to investigate the relationship between plasma level of lipid peroxides and the degree of diabetic control in type 2 diabetics, and if such relation have any correlation to thromboxane A2/prostacyclin, which reflecting the platelet coagulability status, and if all these changes can be related to the accelerated atherosclerosis in type 2 diabetics. In conclusion, it was suggested that the changes in the oxidative status and the accelerated atherosclerosis in type 2 diabetes are related to the increase in plasma lipid peroxides and the hyperaggregability status in uncontrolled diabetics. Furthermore, the correlation with the degree of metabolic imbalance suggested a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes. They also support the clinical recommendation of tight diabetes control in retarding the macroangiopathic complications and support the consideration of natural antioxidants [like vitamin C and E] as additive therapeutic tools in the global management of the diabetic state in type 2 [NIDDM] patients, and that the usage of sulfonylurea that improves oxidative status and platelet aggregation is a better choice in managing those patients