RESUMEN
BACKGROUND: Chinese herbal medicine is widely used as a complement or alternative treatment in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in China. We compared the incidence of the major adverse cardiovascular event (MACE) of CAD patients with or without the complement use of Chinese herbal medicine after PCI. METHODS: In this prospective, observational study that was conducted from September 2016 to August 2019 in Fuwai Hospital (China), we followed up consecutive patients who received PCI treatment for two years. MACE was defined as the composite all-cause mortality, revascularization, and myocardial infarction (MI) and was compared between those using (integrative medicine group) or those not using Chinese herbal medicine as an additional treatment to standard Western medicine, with unadjusted (Kaplan-Meier curves) and risk-adjusted (multivariable Cox regression) analyses. RESULTS: A total of 5942 patients after PCI were enrolled in this study, and 5453 patients were included in the final analysis (4189 [76.8%] male; mean age: 61.9 ± 9.9% years). During the follow-ups, 2932 (53.8%) patients used only Western medicine while 2521(46.2%) patients had used Chinese herbal medicine as an additional treatment to standard Western medicine. Patients in the integrative medicine group (IM group) were older than the Western medicine group (WM group), had more females and less previous MI. The incidence of MACE was 15.3% (449/2932) in WM group and 11.54% (291/2521) in IM group. Cox regression analysis showed that cumulative incidence of MACE was 27% lower in patients of the IM group than those in WM group (hazard ratio = 0.73; 95% CI: 0.63-0.85; P < 0.0001). CONCLUSIONS: For CAD patients after PCI treatment, complement use of Chinese herbal medicine is associated with a lower 2-year MACE incidence. Randomized prospective studies are warranted to provide higher levels of benefit evidence in these patients.
RESUMEN
OBJECTIVE: We investigated the effect of ovariectomy (OVX) and 17ß-estradiol (E2) replacement on both mitochondrial and myocardial function in cTnT-Q92 transgenic mice generated by cardiac-restricted expression of a human hypertrophic cardiomyopathy (HCM) mutation. METHODS: The cTnT-Q92 mice were ovariectomized at twenty weeks of age and were treated with either placebo (OVX group) or E2 (OVX+E2 group) for twelve weeks before being sacrificed. Wild-type and cTnT-Q92 female mice receiving sham operation were used as controls. Indices of diastolic function such as mitral early (E) and late (A) inflow as well as isovolumic relaxation time (IVRT) were measured by echocardiography. A Clark-type electrode was used to detect respiratory control, and ATP levels were determined at the mitochondrial level using HPLC. Key components related to mitochondrial energy metabolism, such as peroxisome proliferator-activated receptor α (PPARα), PPARγ coactivator 1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1), were also analyzed using Western blot and RT-PCR. The levels of oxidative stress markers were determined by measuring malondialdehyde (MDA) using the thiobarbituric acid assay. RESULTS: The cTnT-Q92 mice had impaired diastolic function compared with wild-type mice (E/A ratio, 1.39 ± 0.04 vs. 1.21 ± 0.01, p<0.001; IVRT, 19.17 ± 0.85 vs. 22.15 ± 1.43 ms, p=0.028). In response to ovariectomy, cardiac function further decreased compared with that observed in cTnT-Q92 mice that received the sham operation (E/A ratio, 1.15 ± 0.04 vs. 1.21 ± 0.01, p<0.001; IVRT, 28.31 ± 0.39 vs. 22.15 ± 1.43 ms, p=0.002). Myocardial energy metabolism, as determined by ATP levels (3.49 ± 0.31 vs. 5.07 ± 0.47 µmol/g, p<0.001), and the mitochondrial respiratory ratio (2.04 ± 0.10 vs. 2.63 ± 0.11, p=0.01) also decreased significantly. By contrast, myocardial concentrations of MDA increased significantly in the OVX group, and PGC-1α, PPARα and NRF-1decreased significantly. E2 supplementation significantly elevated myocardial ATP levels (4.55 ± 0.21 vs. 3.49 ± 0.31 µmol/g, p=0.003) and mitochondrial respiratory function (3.93 ± 0.05 vs. 2.63 ± 0.11, p=0.001); however, it reduced the MDA level (0.21 ± 0.02 vs. 0.36 ± 0.03 nmol/g, p<0.001), which subsequently improved diastolic function (E/A ratio, 1.35 ± 0.06 vs. 1.15 ± 0.04, p<0.001; IVRT, 18.22 ± 1.16 vs. 28.31 ± 0.39 ms, p=0.007). CONCLUSIONS: Our study has shown that 17ß-estradiol improved myocardial diastolic function, prevented myocardial energy dysregulation, and reduced myocardial oxidative stress in cTnT-Q92 mice.
Asunto(s)
Cardiomiopatía Hipertrófica/tratamiento farmacológico , Cardiomiopatía Hipertrófica/genética , Estradiol/uso terapéutico , Corazón/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Troponina T/genética , Animales , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/fisiopatología , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos/metabolismo , Femenino , Corazón/fisiopatología , Humanos , Ratones , Ratones Transgénicos , Mitocondrias/metabolismo , Mitocondrias/patología , Mitocondrias/ultraestructura , Mutación , Ovariectomía , Estrés Oxidativo/efectos de los fármacos , PPAR alfaRESUMEN
BACKGROUND: No-reflow after emergency percutaneous coronary intervention (PCI) for acute ST segment elevation myocardial infarction (STEMI) is related to the severe prognosis. The aim of this study was to evaluate the efficacy of Tongxinluo, a traditional Chinese medicine, on no-reflow and the infarction area after emergency PCI for STEMI. METHODS: A total of 219 patients (female 31, 14%) undergoing emergency PCI for STEMI from nine clinical centers were consecutively enrolled in this randomized, double-blind, placebo-controlled, multicenter clinical trial from January 2007 to May 2009. All patients were randomly divided into Tongxinluo group (n = 108) and control group (n = 111), given Tongxinluo or placebo in loading dose 2.08 g respectively before emergency PCI with aspirin 300 mg and clopidogrel 300 mg together, then 1.04 g three times daily for six months after PCI. The ST segment elevation was recorded by electrocardiogram at hospitalization and 1, 2, 6, 12, 24 hours after coronary balloon dilation to evaluate the myocardial no-flow; myocardial perfusion scores of 17 segments were evaluated on day 7 and day 180 after STEMI with static single-photon emission computed tomography (SPECT) to determine the infarct area. RESULTS: There was no statistical significance in sex, age, past history, chest pain, onset-to-reperfusion time, Killip classification, TIMI flow grade just before and after PCI, either in the medication treatment during the follow up such as statin, ß-blocker, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between two groups. There was significant ST segment restoration in Tongxinluo group compared to the control group at 6 hours ((-0.22 ± 0.18) mV vs. (-0.18 ± 0.16) mV, P = 0.0394), 12 hours ((-0.24 ± 0.18) mV vs. (-0.18 ± 0.15) mV, P = 0.0158) and 24 hours ((-0.27 ± 0.16) mV vs. (-0.20 ± 0.16) mV, P = 0.0021) reperfusion; and the incidence of myocardial no-reflow was also reduced significantly at 24-hour reperfusion (34.3% vs. 54.1%, P = 0.0031). The myocardial perfusion scores of 17 segments evaluated by static SPECT was improved significantly on day 7 and day 180 after STEMI in Tongxinluo group compared to the control group (0.61 ± 0.40 vs. 0.76 ± 0.42, P = 0.0109 and 0.51 ± 0.42 vs. 0.66 ± 0.43, P = 0.0115, respectively). There was no significant difference in severe adverse events between two groups. CONCLUSION: Tongxinluo as a kind of traditional Chinese medicine could reduce myocardial no-reflow and infarction area significantly after emergency PCI for STEMI with conventional medicine therapy.
Asunto(s)
Circulación Coronaria , Medicamentos Herbarios Chinos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Enfermedad Aguda , Anciano , Método Doble Ciego , Electrocardiografía , Femenino , Humanos , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVE: To evaluate the change of endothelin-1 (ET-1) in the mini-swine model of acute myocardial infarction (AMI) and reperfusion and the effect of Tongxinluo (TXL) on it, and to explore the possible mechanism of no-reflow. METHODS: Forty mini-swines were randomized into 5 groups: the model group, the small,middle and large dose of TXL groups and the sham-operated group, 8 in each group. The AMI reperfusion model was established by coronary ligation for 3 hrs followed with relaxation for 1 hr. Plasma ET-1 content before and after AMI, and after reperfusion was determined respectively by radioimmunoassay. The ET-1 mRNA expression in myocardial tissue of normal, ischemic and no-reflow area were respectively quantified by reverse transcription-polymerase chain reaction. RESULTS: (1) Compared with before AMI, levels of plasma ET-1 at the time points of 5 min and 3 hrs after AMI, 5 min and 1 hrs after reperfusion in the model group were significantly raised, showing an increasing tendency (all P < 0.01). But the increment in the middle and large dose of TXL groups were all lower than that in the model group (P < 0.05). (2) In the model and the TXL groups, levels of ET-1 in myocardial tissue of ischemic and no-reflow area were significantly higher than those in the normal area, and the increment in no-reflow area was higher than that in ischemic area (all P < 0.01). Compared with the model group, significant lowering of ET-1 in ischemic area was only shown in the middle and large dose of TXL groups (P < 0.01). (3) In the model and the TXL groups, ET-1 mRNA expression in ischemic area was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01). CONCLUSION: The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells. was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01). Conclusion The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Endotelina-1/sangre , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Miocardio/metabolismo , Fitoterapia , Animales , Endotelina-1/biosíntesis , Endotelina-1/genética , Femenino , Masculino , Daño por Reperfusión Miocárdica/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Porcinos , Porcinos EnanosRESUMEN
OBJECTIVE: To evaluate the beneficial effects of Tong-xin-luo on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion. METHODS: Forty mini-swine were randomized into 5 equal groups: control group, low-dose group (pretreated with Tong-xin-luo 0.05 g.kg(-1).d(-1) for 3 days), medium-dose group (pretreated with Tong-xin-luo 0.2 g .kg(-1).d(-1) for 3 days), high-dose group (pretreated with Tong-xin-luo 0.5 g.kg(-1).d(-1) for 3 days), and sham-operation group. The swine in the former four groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion. Left ventricle systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP), rate of maximum pressure change in left ventricle (+/- dp/dt(max)), cardiac output (CO), and heart rate (HR) were measured 5 min before AMI in all groups and 180 min after AMI and 60 min after reperfusion in the groups 1-4. Coronary blood volume (CBV) was recorded 5 min before AMI in all groups and immediately and 60 min after reperfusion in the group 1-4. Myocardial contrast echography (MCE) was used before AMI, 3 h after AMI, and 60 min after reperfusion in the group 1-4 so as to calculate the left ventricle wall area (LVWA), ligation area (LS), and %LA. Sixty minutes after reperfusion thioflavin-S was injected into the left ventricle to dye the reperfusion area, then the descending anterior branch was re-ligated at the original site and Evan's blue was injected into the left ventricle to dye the area outside the reperfusion area blue. The heart was taken out immediately to undergo pathological examination and calculation of LVWA, LS, area of no-reflow (SNR), LA, ANR. necrosis area (NS), and NA. RESULTS: (1) In the control group, systolic and diastolic blood pressures (SBP and DBP), LVSP, +/- dp/dt(max), and CO significantly decreased (P < 0.05 or P < 0.01), while LVEDP significantly increased (P < 0.01) 3 hour after AMI, and then LVSP was significantly recovered while +/- dp/dt(max) further significantly decreased (both P < 0.05) 60 minutes after reperfusion. In the 3 Tongxinluo groups, the changes of LVSP, +/- dp/dt(max), CO and LVEDP were the same as those in the control group 3 hours after AMI, and 60 minutes after reperfusion, +/- dp/dt(max), CO and LVEDP were recovered significantly in the high-dose group to degrees better than those in the control group (all P < 0.05). (2) In the control group, the LS values measured by MCE in vivo and by pathological evaluation were similar (P > 0.05), and the SNR was 78.5% by MCE in vivo and was 82.3% by pathological evaluation with the final NS reaching 98.5% of LS. There was no significant difference in LS by both MCE and pathological evaluation between the Tongxinluo groups and control group, though the values of SNR by both methods in the medium and high-dose groups were 41.1% and 42.4% and 24.1% and 25.0% respectively, all significantly lower than those in the control group and low-dose group (P < 0.05 or P < 0.01) with the values in the high-dose group being significantly lower than those in the median-dose group (P < 0.05 and P < 0.01). The final NS of pathological evaluation was also significantly decreased to 90.2%and 81.2% of LS (P < 0.05). In the control group, CBV was significantly decreased to 45.8% and 50.6% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.01). In the high-dose group, CBV was also significantly decreased to 76% and 73.5% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.05), however, both significantly higher than those in the control group (both P < 0.01). CONCLUSION: Tongxinluo is effective in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area during AMI and reperfusion.