Blood lead level in Chinese adults with and without coronary artery disease.

BACKGROUND: The Trial to Assess Chelation Therapy study found that edetate disodium (disodium ethylenediaminetetraacetic acid) chelation therapy significantly reduced the incidence of cardiac events in stable post-myocardial infarction patients, and a body of epidemiological data has shown that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. However, limited studies have focused on the relationship between angiographically diagnosed coronary artery disease (CAD) and lead exposure. This study compared blood lead level (BLL) in Chinese patients with and without CAD. METHODS: In this prospective, observational study, 450 consecutive patients admitted to Beijing Anzhen Hospital with suspected CAD from November 1, 2018, to January 30, 2019, were enrolled. All patients underwent coronary angiography, and an experienced heart team calculated the SYNTAX scores (SXscore) for all available coronary angiograms. BLLs were determined with atomic absorption spectrophotometry and compared between patients with angiographically diagnosed CAD and those without CAD. RESULTS: In total, 343 (76%) patients had CAD, of whom 42% had low (0-22), 22% had intermediate (23-32), and 36% had high (≥ 33) SXscore. BLLs were 36.8 ± 16.95 µg/L in patients with CAD and 31.2 ± 15.75 µg/L in those without CAD (P = 0.003). When BLLs were categorized into three groups (low, middle, high), CAD prevalence increased with increasing BLLs (P < 0.05). In the multivariate regression model, BLLs were associated with CAD (odds ratio (OR): 1.023, 95% confidence interval (CI): 1.008-1.039; P = 0.0017). OR in the high versus low BLL group was 2.36 (95% CI: 1.29-4.42,P = 0.003). Furthermore, BLLs were independently associated with intermediate and high SXscore (adjusted OR: 1.050, 95% CI: 1.036-1.066; P < 0.0001). CONCLUSION: BLLs were significantly associated with angiographically diagnosed CAD. Furthermore, BLLs showed excellent predictive value for SXscore, especially for complex coronary artery lesions.

Protein kinase A-mediated cardioprotection of Tongxinluo relates to the inhibition of myocardial inflammation, apoptosis, and edema in reperfused swine hearts.

BACKGROUND: Our previous studies have demonstrated that Tongxinluo (TXL), a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A (PKA)-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. METHODS: In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL (0.05 g/kg, gavaged one hour prior to ischemia), and TXL + H-89 (a PKA inhibitor, intravenously and continuously infused at 1.0 µg/kg per minute) groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein (p-CREB) (Ser(133)), tumor necrosis factor α (TNF-α), P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. RESULTS: TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% (P < 0.05). TXL pretreatment increased the PKA activity and the expression of Ser(133) p-CREB in the reflow and no-reflow myocardium (P < 0.05). TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-α and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. CONCLUSION: PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.

Tongxinluo reduces myocardial no-reflow and ischemia-reperfusion injury by stimulating the phosphorylation of eNOS via the PKA pathway.

The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 µg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.

[Effect of tongxinluo on mini-swine cytokines and myocardial no-reflow in early reperfusion of acute myocardial infarction].

OBJECTIVE: To assess the effect of Tongxinluo on cytokines and myocardial no-reflow in early reperfusion of acute myocardial infarction (AMI). METHODS: Forty mini-swine were divided into five groups randomly, sham group, control group, low dose (0.1 g/kg), medium dose (0.2 g/kg) and high dose (0. 4 g/kg) group of Tongxinluo (which were administered 2 h before reperfusion), eight swine in each group. Animals except those in the sham group were subjected to 1.5 h of coronary occlusion followed by 3 h of reperfusion. Serum contents of P-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), interleukin 6 (IL-6) and interleukin 10 (IL-10), as well as myocardial contrast echocardiography (MCE) were evaluated at baseline, and after 1.5 h of AMI and 3 h of reperfusion. RESULTS: (1) Compared with that of the control group, high dose of Tongxinluo could reduce serum contents of P-selectin and ICAM-1 at 1.5 h of AMI (all P<0.05), and P-selectin, ICAM-1, VCAM-1, and IL-6 at 3 h of reperfusion significantly (all P< 0.05), accompanied by significantly elevated IL-10 (P<0.05). (2) Compared with that of control group, high dose of Tongxinluo could reduce no-reflow area at 3 h of reperfusion significantly [(6.59 +/- 1.73) cm2 vs (4.68 +/- 1.53) cm2, P<0.05]. CONCLUSION: High dose of Tongxinluo could effectively reduce serum contents of adhesion and pro-inflammatory cytokines, regulate anti-inflammatory factor levels, and attenuate no-reflow area in the early reperfusion of AMI. It thus provided experimental basis for its clinical application.

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism.

BACKGROUND: The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. METHODS: Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively. RESULTS: Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. CONCLUSIONS: Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.

[Effects of tongxinluo on mini-swine vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction].

OBJECTIVE: To assess the effects of tongxinluo on vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction. METHODS: Forty mini-swines were divided into five groups randomly, sham group, control group, low dose (0.1 g/kg), medium dose (0.2 g/kg) and high dose (0.4 g/kg) groups of Tongxinluo. It was administered at 2 hours pre-reperfusion. Animals except in sham group were subjected to 1.5 hour of coronary occlusion followed by 3 hours of reperfusion. Content of VE-cadherin, beta-catenin, matrix metalloproteinase (MMP)-2 and 9 in myocardium were evaluated; no-reflow area was examined with myocardial contrast echocardiography (MCE) at 1.5 hour of AMI and 3 hours of reperfusion. RESULTS: (1) Compared with that of normal myocardium, content of VE-cadherin and beta-catenin decreased in reperfusion and no-reflow myocardium while MMP-2 and 9 increased significantly (all P < 0.05); (2) Compared with that of control group, a high dose of Tongxinluo could increase significantly the content of VE-cadherin in both reperfusion and no-reflow myocardium, (22.2 +/- 3.2)% vs (32.0 +/- 3.9)% and (14.5 +/- 2.8)% vs (28.3 +/- 2.2)% respectively, beta-catenin, (20.5 +/- 3.5)% vs (27.3 +/- 2.9)% and (13.3 +/- 2.1)% vs (20.6 +/- 2.4)%, while reduce MMP-2, (48.3 +/- 4.1)% vs (29.4 +/- 3.5)% and (57.3 +/- 4.3)% vs (38.2 +/- 4.0)% respectively, MMP-9, (55.6 +/- 4.0)% vs (34.3 +/- 3.5)% and (62.4 +/- 4.8)% vs (44.4 +/- 4.1)%, all P < 0.05; (3) Compared with that of control group, a high dose of Tongxinluo could reduce significantly both no-reflow area, (6.6 +/- 1.7) cm2 vs (4.7 +/- 1.5) cm2, P < 0.05, and percentage (90.8 +/- 3.8)% vs (71.4 +/- 4.1)%, P < 0.05, at 3 hours of reperfusion. CONCLUSION: A high dose of tongxinluo could effectively maintain the integrity of vascular endothelium and attenuate no-reflow area in early reperfusion of acute myocardial infarction.