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1.
Med Biol Eng Comput ; 62(10): 3013-3023, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38750280

ABSTRACT

We aimed to investigate the electrocardiogram (ECG) features in persons with chronic disorders of consciousness (DOC, ≥ 29 days since injury, DSI) resulted from the most severe brain damages. The ECG data from 30 patients with chronic DOC and 18 healthy controls (HCs) were recorded during resting wakefulness state for about five minutes. The patients were classified into vegetative state (VS) and minimally conscious state (MCS). Eight ECG metrics were extracted for comparisons between the subject subgroups, and regression analysis of the metrics were conducted on the DSI (29-593 days). The DOC patients exhibit a significantly higher heart rate (HR, p = 0.009) and lower values for SDNN (p = 0.001), CVRR (p = 0.009), and T-wave amplitude (p < 0.001) compared to the HCs. However, there're no significant differences in QRS, QT, QTc, or ST amplitude between the two groups (p > 0.05). Three ECG metrics of the DOC patients-HR, SDNN, and CVRR-are significantly correlated with the DSI. The ECG abnormalities persist in chronic DOC patients. The abnormalities are mainly manifested in the rhythm features HR, SDNN and CVRR, but not the waveform features such as QRS width, QT, QTc, ST and T-wave amplitudes.


Subject(s)
Consciousness Disorders , Electrocardiography , Heart Rate , Humans , Electrocardiography/methods , Male , Female , Adult , Consciousness Disorders/physiopathology , Consciousness Disorders/diagnosis , Heart Rate/physiology , Middle Aged , Chronic Disease , Case-Control Studies , Persistent Vegetative State/physiopathology
2.
J Diabetes ; 16(6): e13567, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769875

ABSTRACT

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.


Subject(s)
Hyperglycemia , Independent Living , Nutrition Surveys , Humans , Male , Female , Middle Aged , Independent Living/statistics & numerical data , Hyperglycemia/mortality , Hyperglycemia/blood , Hyperglycemia/epidemiology , Adult , Aged , Cause of Death , Risk Factors , Mortality/trends , Stress, Physiological , United States/epidemiology , Prognosis , Kaplan-Meier Estimate
3.
Open Med (Wars) ; 19(1): 20240935, 2024.
Article in English | MEDLINE | ID: mdl-38584836

ABSTRACT

In up to 30% patients who experience acute myocardial infarction, successful recanalization of the epicardial coronary artery cannot provide adequate microvascular reperfusion. In this study, we sought to determine whether long-pulsed ultrasound (US)-mediated microbubble (MB) cavitation was useful for the treatment of microvascular obstruction, and the therapeutic effects were compared within different long-pulse-length and short-pulsed US. Microvascular obstruction model was established by injecting micro-thrombi into common iliac artery of a rat's hind limb. About 1 MHz US with different long pulse lengths (ranging from 100 to 50,000 cycles) was delivered, compared to short pulse (5 cycles). The control group was given MB only without therapeutic US. Contrast perfusion images were performed at baseline, emboli, and 1, 5, 10 min post-embolization, and peak plateau video intensity (A) was obtained to evaluate the therapeutic effects. Long-tone-burst US showed better thrombolytic effects than short-pulsed US (1,000, 5,000 cycles >500 cycles, >5 cycles, and control) (P < 0.01). 1,000 cycles group showed the optimal thrombolytic effect, but microvascular hemorrhage was observed in 50,000 cycles group. In conclusion, long-tone-burst US-enhanced MB therapy mediated successful thrombolysis and may offer a powerful approach for the treatment for microvascular obstruction within a certain pulse length.

4.
Medicine (Baltimore) ; 102(51): e36333, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38134096

ABSTRACT

RATIONALE: Campylobacter fetus is rare pathogen with high mortality rate in immunosuppressive hosts. This study aimed to summarize clinical and pathological presentation of C fetus induced psoas abscess. PATIENT CONCERNS: A 66-year-old male patient with long medical history of poorly-controlled gouty arthritis and steroid intake complained of a severe low back pain. Physical examination showed tenderness in his psoas. DIAGNOSES: The patient underwent puncture biopsy to the lesion in the psoas under ultrasound guidance. The lesion was indicated as abscess by pathological examination, and its pathogen was indicated as C fetus by the next generation sequencing. INTERVENTIONS: Meropenem 1 g q8.h were administered intravenously for 10 days. Then the antibiotic treatment was switched to amoxicillin/clavulanate potassium 0.375g q.8.h and levofloxacin 0.5g q.d oral administration when discharge. OUTCOMES: The patient's fever and low back pain improved and infectious parameters declined. He was discharged in good general condition with advice for further monitoring and therapy. In the first month follow-up, the patient did not report recurrence or aggravation of his symptoms. LESSONS: C fetus should be noticed in immunosuppressive patient with exposure to livestock who present with rare systematic or local invasive infection. We advocated the meropenem for the first-line treatment against C fetus.


Subject(s)
Arthritis, Gouty , Low Back Pain , Psoas Abscess , Male , Humans , Aged , Campylobacter fetus , Psoas Abscess/diagnosis , Meropenem/therapeutic use , Low Back Pain/complications , Arthritis, Gouty/complications
5.
J Ultrasound Med ; 42(2): 463-475, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36444908

ABSTRACT

OBJECTIVES: This study aims to determine the effect of low-intensity focused ultrasound (LIFU) in ischemic heart failure (IHF) and explore the potential neuroimmune mechanism. METHODS: Sprague-Dawley rats were subjected to ultrasound (US) with specific parameters, and electrocardiograms were recorded to analyze the effect of LIFU and/or vagal denervation on heart rate. Thereafter, myocardial infarction (MI) was induced by left anterior artery ligation, and LIFU was performed three times a day for 25 days after MI. Echocardiography, Masson staining, and ELISA were used to evaluate the effect of LIFU on the structure and function of the heart. Finally, ELISA, flow cytometry, qRT-PCR, and Western blot analysis were performed to determine the effect of LIFU on the inflammation and the expression of the cholinergic anti-inflammatory pathway (CAP)-related mediators. RESULTS: LIFU reduced heart rate in rats (control vs LIFU, P < .01), and vagotomy (VT) eliminated this effect of LIFU on heart rate (VT vs LIFU + VT, P > .01). LIFU-ameliorated IHF in terms of cardiac structure and function (MI vs MI + LIFU, P < .01), but VT abrogated the beneficial effect of LIFU (MI + VT vs MI + LIFU + VT, P > .01). After the treatment of LIFU, decreased levels of inflammatory cytokines, increased proportion of anti-inflammatory macrophages, and increased expression of CAP-related mediators (MI vs MI + LIFU, P < .01). CONCLUSIONS: LIFU ameliorates IHF whereas the CAP plays a promising role. LIFU has the potential to be a novel nonpharmacological and noninvasive therapy for the treatment of coronary artery disease and other cardiovascular diseases.


Subject(s)
Heart Failure , Myocardial Infarction , Rats , Animals , Neuroimmunomodulation , Rats, Sprague-Dawley , Heart , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Heart Failure/diagnostic imaging , Heart Failure/therapy
6.
Quant Imaging Med Surg ; 12(10): 4852-4864, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36185055

ABSTRACT

Background: This study aimed to evaluate the multiple interactions between therapeutic ultrasound (TUS), microbubbles (MB), and recombinant tissue plasminogen activator (r-tPA) by using three-dimensional (3D) ultrasound to examine the impact of thrombolysis with r-tPA on epicardial recanalization and microcirculation in patients with acute ST-segment-elevation myocardial infarction (STEMI). Methods: Acute thrombotic occlusion of the left anterior descending (LAD) artery was induced in 32 Bama pigs, who were fed a high-cholesterol diet and randomized into four groups: (I) a 3D-sono-assisted-thrombolysis (3D/TUS + MB + r-tPA) group; (II) a 3D/TUS + MB group; (III) a full-dose r-tPA group; and (IV) a 3D/TUS alone group. Epicardial angiographic recanalization rate, microcirculation in the at-risk myocardium, ST-segment elevation on electrocardiogram, and changes in the at-risk myocardium and the myocardial infarct area were compared between the groups. Results: After treatment, distal LAD recanalization was observed in 87.5% (7/8) of pigs in the 3D/TUS + MB + r-tPA group, which was significantly higher than the rates observed in the 3D/TUS + MB (37.5%) and the full-dose r-tPA (50.0%) groups (all P<0.05). The average acoustic intensity in the 3D/TUS + MB + r-tPA group (193.78±10.15 dB) was also significantly higher than that in the 3D/TUS + MB (154.29±31.94 dB) and the r-tPA (141.42±28.31 dB) groups (all P<0.05). The decrease in ST-segment elevation in the 3D/TUS + MB + r-tPA group (1.31±1.22 mm) was significantly higher than that in the 3D/TUS + MB (5.38±1.77 mm) and the r-tPA (4.30±2.08 mm) groups (all P<0.05). Furthermore, the ratio of the infarcted myocardial area divided by the at-risk myocardial area was markedly lower in the 3D/TUS + MB + r-tPA group (0.51±0.14) than in the 3D/TUS + MB (0.69±0.28) and r-tPA (0.75±0.23) groups (all P<0.05). Conclusions: Three-dimensional sono-assisted-thrombolysis directly improves infarct-related recanalization rates, enhances microcirculation, reduces r-tPA dosage, and ameliorates the thrombolytic effect of r-tPA in acute STEMI.

7.
Front Cardiovasc Med ; 9: 868634, 2022.
Article in English | MEDLINE | ID: mdl-36312235

ABSTRACT

Background and aims: Standard 12-lead electrocardiogram (ECG) patterns combined with the anatomical cardiac long-axis angle revealed by chest X-ray can prevent the influence of cardiac rotation, physical shape, and lead position, so it may be an ideal means to predict the origin of the outflow tract (OT) ventricular arrhythmias (OTVAs) for ablation procedures. The study explores the value of this strategy in identifying the origin of OTVA. Methods: This study was conducted using a retrospective cohort and a prospective cohort of consecutive patients at two centers. The anatomical cardiac long-axis angle was calculated by measuring the angle between the cardiac long-axis (a line joining the apex to the midpoint of the mitral annulus) and the horizontal plane on a chest X-ray. The V2S angle was calculated as the V2S amplitude times the angle. We ultimately enrolled 147 patients with symptomatic OTVAs who underwent successful radiofrequency catheter ablation (RFCA) (98 women (66.7%); mean age 46.9 ± 14.7 years; 126 right ventricular OT (RVOT) origins, 21 left ventricular OT (LVOT) origins) as a development cohort. The new algorithm was validated in 48 prospective patients (12 men (25.0%); mean age 48.0 ± 15.8 years; 36 RVOT, 12 LVOT origins). Results: Patients with RVOT VAs had greater V2S, long-axis angle, and V2S angle than patients with LVOT VA (all P < 0.001). The cut-off V2S angle obtained by receiver operating characteristic (ROC) curve analysis was 58.28 mV° for the prediction of RVOT origin (sensitivity: 85.7%; specificity: 95.2%; positive predictive value: 99.1%; negative predictive value: 52.6%). The AUC achieved using the V2S angle was 0.888 (P < 0.001), which was the highest among all indexes (V2S/V3R: 0.887 (P < 0.016); TZ index: 0.858 (P < 0.001); V1-2 SRd: 0.876 (P < 0.001); V3 transition: 0.651 (P < 0.001)). In the prospective cohort, the V2S angle had a high overall accuracy of 93.8% and decreased the procedure time (P = 0.002). Conclusion: V2S angle can be a novel measure that can be used to accurately differentiate RVOT from LVOT origins. It could help decrease ablation duration and radiation exposure.

8.
Ultrasound Med Biol ; 47(4): 1014-1023, 2021 04.
Article in English | MEDLINE | ID: mdl-33487472

ABSTRACT

Ultrasound-mediated microbubble cavitation improves perfusion in chronic limb and myocardial ischemia. The purpose of this study was to determine the effects of ultrasound-mediated microbubble cavitation in acute limb ischemia and investigate the mechanism of action. The animal with acute hindlimb ischemia was established using male Sprague-Dawley rats. The rats were randomly divided into three groups: intermittent high-mechanical-index ultrasound pulses combined with microbubbles (ultrasound [US] + MB group), US alone (US group) and MB alone (MB group). Both hindlimbs were treated for 10 min. Contrast ultrasound perfusion imaging of both hindlimbs was performed immediately and 5, 10, 15, 20 and 25 min after treatment. The role of the nitric oxide (NO) pathway in increasing blood flow in acutely ischemic tissue was evaluated by inhibiting endothelial nitric oxide synthase (eNOS) with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). In the US + MB group, microvascular blood volume and microvascular blood flow of the ischemic hindlimb were significantly increased after treatment (both p values <0.05), while the microvascular flux rate (ß) increased, but not significantly (p > 0.05). The increases were observed immediately after treatment, and had dissipated by 25 min. Changes in the US and MB groups were minimal. Inhibitory studies indicated cavitation increased phospho-eNOS concentration in ischemic hindlimb muscle tissue, and the increase was significantly inhibited by L-NAME (p < 0.05). Ultrasound-mediated microbubble cavitation transiently increases local perfusion in acutely ischemic tissue, mainly by improving microcirculatory perfusion. The eNOS/NO signaling pathway appears to be an important mediator of the effect.


Subject(s)
Ischemia/therapy , Microbubbles/therapeutic use , Microcirculation/radiation effects , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide/metabolism , Ultrasonic Therapy , Animals , Enzyme Inhibitors/pharmacology , Hindlimb/blood supply , Ischemia/diagnostic imaging , Ischemia/pathology , Ischemia/physiopathology , Male , Microcirculation/physiology , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/antagonists & inhibitors , Phosphorylation , Random Allocation , Rats , Rats, Sprague-Dawley , Regional Blood Flow , Signal Transduction , Ultrasonography
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(1): 113-118, 2017 Jan 20.
Article in Chinese | MEDLINE | ID: mdl-28109110

ABSTRACT

OBJECTIVE: To evaluate the effects of polyethylene oxide (PEO) on blood perfusion in hind limb skeletal muscles in a rat model of chronic hind limb ischemia. METHDOS: Twelve rat models of chronic hind limb ischemia established by unilateral femoral artery ligation were randomized into PEO and control groups (n=6) and treated with intravenous infusion of PEO and saline through the internal jugular vein every other day for 2 weeks. Contrast-enhanced ultrasonography was performed after the treatments to evaluate the blood flow in the skeletal muscles at different time points and blood flow reserve in the ischemic hind limbs on day 28. RESULTS: Starting from 7 days after femoral artery ligation, blood flow in the ischemic hind limb skeletal muscles was significantly higher in PEO group than in the control group (P<0.05). On day 28, blood flow reserve in the ischemic hind limb was significantly higher (P=0.012), and blood volume was significantly increased in PEO group as compared that in the control group (P=0.024). CONCLUSIONS: PEO can increase blood flow, blood flow reserve and vascular volume in the hind limb skeletal muscles in rats with chronic hind limb ischemia, suggesting that PEO can promote angiogenesis and arterial formation by increasing blood flow shear stress to improve blood supply of ischemic hind limbs.


Subject(s)
Hindlimb/drug effects , Ischemia/drug therapy , Muscle, Skeletal/drug effects , Polyethylene Glycols/pharmacology , Animals , Blood Volume/drug effects , Blood Volume/physiology , Chronic Disease , Disease Models, Animal , Femoral Artery , Hindlimb/blood supply , Ischemia/diagnostic imaging , Ligation , Muscle, Skeletal/blood supply , Neovascularization, Physiologic , Random Allocation , Rats , Regional Blood Flow/drug effects , Regional Blood Flow/physiology
10.
Int J Cardiol ; 228: 886-889, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-27894059

ABSTRACT

BACKGROUND: This study prospectively assessed the left ventricular (LV) diastolic function changes in patients with ST-elevation myocardial infarction (STEMI) and determined if the early revascularization of the infarct-related coronary artery in acute phase achieve a better recovery of diastolic function than late recanalization. METHODS: Forty-five consecutive patients (61.20±11.37years, 8 females) presenting with STEMI and treated with PCI were prospectively enrolled in this study. The important inclusion criteria were first acute coronary syndrome episode and LV ejection fraction exceeded 45%. The patients were divided to two different groups by total ischemia time (TIT): early reperfusion (TIT<6h) and late reperfusion group (TIT≥6h). Transthoracic echocardiography were performed within the first week after PCI, and data were compared between groups. Evaluation of diastolic function was based on integrated assessment of trans-mitral Doppler flow pattern, tissue Doppler, and color M-mode ECT. RESULTS: A normal diastolic filling pattern was seen in only 9 patients, and the other 80% patients had abnormal filling patterns: 16 impaired relaxation, 14 pseudonormal, and 6 restrictive filling patterns. The e'septal velocity was lower in early reperfusion group compared to late reperfusion group (5.52±1.67cm/s vs 7.11±2.14cm/s, P<0.05), but no statistical difference was found in E/e' average (11.99±4.30 vs 9.85±3.47, P>0.05). There was also no statistical difference for left atrial volume index and mitral annulus propagation velocity between groups. CONCLUSIONS: LV diastolic dysfunction was present in most of acute MI patients even after successful PCI. It seemed STEMI patients receiving early myocardial reperfusion had no better diastolic functions compared with late-reperfused patients within the acute phase.


Subject(s)
Myocardial Reperfusion , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/surgery , Ventricular Dysfunction, Left/complications , Aged , Echocardiography , Female , Humans , Male , Middle Aged , Prospective Studies , Recovery of Function , ST Elevation Myocardial Infarction/physiopathology , Time Factors , Treatment Outcome , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology
11.
Int J Nanomedicine ; 11: 6743-6751, 2016.
Article in English | MEDLINE | ID: mdl-28008249

ABSTRACT

Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension.


Subject(s)
Cardiovascular Agents/pharmacology , Hypertrophy, Left Ventricular/drug therapy , Polymers/pharmacology , Animals , Aorta/drug effects , Aorta/pathology , Blood Pressure/drug effects , Body Weight/drug effects , Cardiovascular Agents/administration & dosage , Electrocardiography , Endothelin-1/genetics , Endothelin-1/metabolism , Heart Rate/drug effects , Hypertension/complications , Hypertension/physiopathology , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/physiopathology , Infusions, Intravenous , Male , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Polymers/administration & dosage , Rats, Inbred SHR , Rats, Wistar , Vascular Remodeling
12.
Vascular ; 24(3): 241-5, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26092832

ABSTRACT

OBJECTIVE: Drag-reducing polymers are long-chain, blood soluble macromolecules that can improve microcirculation in vivo. This study aimed to examine the effects of drag-reducing polymers on exercise tolerance in a rat model of hind-limb ischemia. METHODS: After adaptive running training, bilateral femoral artery ligation models were established in 64 Wistar rats. During an exhaustive exercise, polyethylene oxide or normal saline was intravenously injected to each group (n = 32) at 4 mL/h for 10 min. The exhaustive exercise time was recorded, and lactic acid levels in gastrocnemius muscle and serum were measured. Serum levels of nitric oxide, creatine kinase and lactate dehydrogenase were measured as biomarkers of physical fatigue. RESULTS: Compared with saline-treated control group, rats in polyethylene oxide-treated group had longer exhaustive exercise time (774.7 ± 171.5 s vs. 687.6 ± 166.1 s, p = 0.043), and lower lactic acid level in gastrocnemius muscle (p < 0.01) but no significant difference in serum lactic acid level between two groups was observed (p > 0.05). Nitric oxide level was higher in polyethylene oxide group than in controls (p < 0.05), but no significant differences in serum creatine kinase and lactate dehydrogenase levels between two groups were observed (p > 0.05). CONCLUSION: Drag-reducing polymers contribute to the enhancement of exercise endurance and exert anti-fatigue effect.


Subject(s)
Cardiovascular Agents/pharmacology , Exercise Tolerance/drug effects , Ischemia/drug therapy , Microcirculation/drug effects , Muscle, Skeletal/blood supply , Polyethylene Glycols/pharmacology , Animals , Biomarkers/blood , Cardiovascular Agents/administration & dosage , Creatine Kinase/blood , Disease Models, Animal , Hindlimb , Injections, Intravenous , Ischemia/blood , Ischemia/diagnosis , Ischemia/physiopathology , L-Lactate Dehydrogenase/blood , Lactic Acid/blood , Male , Nitric Oxide/blood , Polyethylene Glycols/administration & dosage , Rats, Wistar , Regional Blood Flow/drug effects , Running , Time Factors
13.
J Pharm Pharmacol ; 66(9): 1259-64, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24720776

ABSTRACT

OBJECTIVES: Congenital heart diseases (CHD) are common birth defects in the world. The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most important candidate genes for the development of CHD. This case-control study aimed to evaluate the effect of MTHFR c.382A>G and c.1129C>T genetic polymorphisms as risk factors for the development of CHD. METHODS: A total of 230 CHD patients and 237 non-CHD controls were included in the present study. The genotyping of MTHFR c.382A>G and c.1129C>T genetic polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism and created restriction site-polymerase chain reaction methods, respectively. KEY FINDINGS: The alleles/genotypes distribution from these two genetic polymorphisms were statistically associated with the increased risk of CHD (for c.382A>G, GG versus AA: odds ratio (OR) = 2.39, 95% confidence interval (CI), 1.27 to 4.52, P = 0.006; for c.1129C>T, TT versus CC: OR = 2.73, 95% CI, 1.33 to 5.62, P = 0.005). The allele G and genotype GG of c.382A>G and allele T and genotype TT of c.1129C>T genetic polymorphisms might contribute to CHD susceptibility. CONCLUSION: These preliminary findings indicate that these two MTHFR genetic polymorphisms are related with the risk of CHD in Chinese Han population, and might be potentially utilized as molecular markers.


Subject(s)
Asian People/genetics , Genotype , Heart Diseases/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Single Nucleotide , Alleles , Case-Control Studies , Child, Preschool , Female , Genetic Predisposition to Disease , Humans , Infant , Male , Odds Ratio
14.
Circulation ; 127(6): 710-9, 2013 Feb 12.
Article in English | MEDLINE | ID: mdl-23307829

ABSTRACT

BACKGROUND: Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPCs) promotes recovery of blood flow through the recruitment of proangiogenic monocytes. METHODS AND RESULTS: Hind-limb ischemia was produced in mice by iliac artery ligation, and MAPCs were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPCs indicated that cells survived for 1 week. Contrast-enhanced ultrasound on days 3, 7, and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX(3)CR-1-positive monocytes were significantly higher in MAPC-treated mice than in the control groups at days 3 and 7 after arterial ligation. Muscle immunohistology showed a >10-fold-greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or tumor necrosis factor-α-treated cremaster muscle demonstrated that MAPCs migrate to perimicrovascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14(+) monocytes was 10-fold greater in response to MAPC-conditioned than basal media. CONCLUSIONS: In limb ischemia, MAPCs stimulate the recruitment of proangiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond the MAPC lifespan, suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype.


Subject(s)
Extremities/blood supply , Ischemia/therapy , Molecular Imaging , Neovascularization, Physiologic/physiology , Paracrine Communication/physiology , Stem Cell Transplantation , Adult Stem Cells/diagnostic imaging , Adult Stem Cells/drug effects , Adult Stem Cells/transplantation , Animals , CX3C Chemokine Receptor 1 , Cell Movement/physiology , Extremities/diagnostic imaging , Extremities/pathology , Humans , Iliac Artery/diagnostic imaging , Iliac Artery/drug effects , Iliac Artery/physiopathology , Ischemia/diagnostic imaging , Ischemia/pathology , Lipopolysaccharide Receptors/analysis , Mice , Mice, Inbred C57BL , Microvessels/diagnostic imaging , Microvessels/drug effects , Microvessels/pathology , Microvessels/physiopathology , Monocytes/pathology , Monocytes/physiology , Multipotent Stem Cells/diagnostic imaging , Multipotent Stem Cells/drug effects , Multipotent Stem Cells/transplantation , Muscle, Skeletal/blood supply , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Neovascularization, Physiologic/drug effects , P-Selectin/biosynthesis , Paracrine Communication/drug effects , Receptors, Chemokine/analysis , Transplantation, Heterologous , Tumor Necrosis Factor-alpha/pharmacology , Ultrasonography
15.
Eur Heart J Cardiovasc Imaging ; 13(4): 298-308, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22067143

ABSTRACT

AIMS: Regadenoson is comparable to adenosine in pharmacologic radionuclide stress tests but has not been studied with stress myocardial contrast echocardiography. This study assessed the haemodynamic profile and ability of regadenoson, a novel selective A(2A) receptor agonist, to detect coronary artery stenosis during myocardial contrast echocardiography. METHODS AND RESULTS: Myocardial contrast echocardiography was performed to measure myocardial blood volume, myocardial blood flow velocity, and total regional myocardial blood flow before and after administration of regadenoson (5 µg kg(-1), 10 s bolus) in 10 open-chest dogs with mild-to-moderate coronary stenosis that was not flow limiting at rest. Regadenoson decreased blood pressure but did not change heart rate. It increased coronary blood flow significantly (P < 0.05) for 30 min, which was attenuated in proportion to coronary stenosis severity. Whereas myocardial blood volume maximally increased by 0.5-0.75-fold in the control region, it did not change in the region supplied by the non-flow limiting stenosis. Perfusion defects were visually and quantitatively detectable for as long as 10 min after administration of regadenoson. No arrhythmias were noted with regadenoson either prior to or during myocardial contrast echocardiography. CONCLUSION: Regadenoson can be used as a vasodilator stress agent with myocardial contrast echocardiography to detect the presence of physiologically significant coronary stenosis. The optimum time for image acquisition was 3-10 min after drug administration.


Subject(s)
Adenosine A2 Receptor Antagonists , Coronary Stenosis/diagnosis , Echocardiography/instrumentation , Myocardium/pathology , Purines , Pyrazoles , Analysis of Variance , Aorta/drug effects , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/pathology , Heart Rate/drug effects , Hemodynamics/drug effects , Humans , Myocardial Perfusion Imaging , Stroke Volume , Vasodilator Agents , Ventricular Function, Left
16.
Biorheology ; 48(3-4): 149-59, 2011.
Article in English | MEDLINE | ID: mdl-22156030

ABSTRACT

Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study is to examine the effects of DRPs on microcirculation in rat hind limb during acute femoral artery occlusion. Two groups of 20 male Wistar rats were subjected to either hemodynamic measurement or contrast enhanced ultrasound (CEU) imaging during peripheral ischemia. Both groups were further subdivided into a DRP-treated group or a saline-treated group. Polyethylene oxide (PEO) was chosen as the test DRP, and rats were injected with either 10 ppm PEO solution or saline through the caudal vein at a constant rate of 5 ml/h for 20 min. Abdominal aortic flow, iliac artery pressure, iliac vein pressure, heart rate, carotid artery pressure and central venous pressure (CVP) were monitored, and vascular resistance was calculated by (iliac artery pressure-iliac vein pressure)/abdominal aortic blood flow. Flow perfusion and capillary volume of skeletal muscle were measured by CEU. During PEO infusion, abdominal aortic blood flow increased (p<0.001) and vascular resistance decreased (p<0.001) compared to rats that received saline during peripheral ischemia. There was no significant change in ischemic skeletal capillary volume (A) with DRP treatment (p>0.05), but red blood cell velocity (ß) and capillary blood flow (A×ß) increased significantly (p<0.05) during PEO infusion. In addition, A, ß and A×ß all increased (p<0.05) in the contralateral hind limb muscle. In contrast, PEO had no significant influence on heart rate, mean carotid artery blood pressure or CVP. Intravenous infusion of drag reducing polymers may offer a novel hydrodynamic approach for improving microcirculation during acute peripheral ischemia.


Subject(s)
Extremities/blood supply , Ischemia/drug therapy , Ischemia/physiopathology , Microcirculation/drug effects , Polyethylene Glycols/administration & dosage , Animals , Blood Flow Velocity/drug effects , Disease Models, Animal , Heart Rate/drug effects , Humans , Infusions, Intravenous , Male , Rats , Rats, Wistar
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(8): 1461-3, 2011 Aug.
Article in Chinese | MEDLINE | ID: mdl-21868347

ABSTRACT

OBJECTIVE: To study value of velocity vector imaging (VVI) in assessment of normal left ventricular diastolic function and the corresponding reference values. METHODS: Ninety-seven healthy subjects were selected by combined clinical, ultrasound, and NT-proBNP examinations. Using a Siemens Acuson Sequoia C512 echocardiograph, VVI was adopted to examine the myocardial early diastolic velocity (E) of the septal, lateral, anterior, inferior, anterior septum, and posterior wall of the left ventricle at the level of mitral annulus. The images were analyzed for VVI and the mean diastolic velocity (E(m)) and hence the E/E(m) ratio was calculated based on the offline workstation interface. RESULTS: The reference range of E/E(m) ratio derived from the data of the 97 healthy subjects was (unilateral boundaries with 95% limit) and (1, 22.935), was (1, 22.300) in male subjects and (1, 24.766) in female subjects. The reference E/E(m) range was (0, 22.413) in male subjects under 50 years of age, (1, 24.766) in female subjects under 50 years, (1, 22.300) in male subjects over 50 years, and (1, 24.766) in female subjects over 50 years. CONCLUSION: VVI is a good method for non-invasive evaluation of the left ventricular diastolic function and provides an accurate and reliable means for clinical assessment of the left ventricular diastolic function.


Subject(s)
Diastole/physiology , Echocardiography/methods , Ventricular Function, Left/physiology , Adolescent , Adult , Aged , Blood Flow Velocity/physiology , Female , Humans , Male , Middle Aged , Reference Values , Young Adult
18.
Int J Cardiol ; 147(1): 112-7, 2011 Feb 17.
Article in English | MEDLINE | ID: mdl-21211858

ABSTRACT

BACKGROUND: Recent studies have shown that drag-reducing polymers (DRPs) prolonged survival time in rats with acute myocardial infarction (MI), but their effect on cardiac function post MI remains unknown. This study sought to test the hypothesis that intravenous infusion of DRPs may improve left ventricular (LV) function in rats following surgically induced MI. METHODS: MI was induced by ligation of the left anterior descending coronary artery in 36 Sprague-Dawley rats, and sham operations were performed in 12 animals. DRPs were then administered to 18 of the MI rats. Echocardiograpy was used to evaluate the changes of impaired LV function and global wall motion. Besides, the hydrodynamic effect of DRPs on microcirculation was also assessed. RESULTS: The survival rate at 24h following MI was significantly different among the sham, MI and DRP groups (p = 0.023). DRP-treated animals had marked smaller left ventricular end-systolic diameter and better anterior systolic wall thickness comparison with untreated rats. Significant improvement of fractional shortening and ejection fraction were detected in MI rats with DRP. Wall motion score index and contrast score index were both significantly reduced by DRP treatment. DRPs were shown to have beneficial effects on microvascular variables including red blood cell velocity, diameter, blood flow and calculated wall shear stress in third-order arteriole. CONCLUSIONS: Acute administration of DRPs improved LV function in a rat model of MI possibly by improving microvascular blood flow due to their unique hydrodynamic properties. DRPs may offer a new approach to the treatment of coronary artery ischemic diseases.


Subject(s)
Hydrodynamics , Myocardial Infarction/drug therapy , Polymers/administration & dosage , Ventricular Function, Left/drug effects , Animals , Infusions, Intravenous , Male , Microcirculation/drug effects , Microcirculation/physiology , Myocardial Infarction/physiopathology , Polymers/therapeutic use , Random Allocation , Rats , Rats, Sprague-Dawley , Ventricular Function, Left/physiology
19.
JACC Cardiovasc Imaging ; 3(9): 947-55, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20846630

ABSTRACT

OBJECTIVES: We hypothesized that noninvasive molecular imaging of activated von Willebrand factor (vWF) on the vascular endothelium could be used to detect a high-risk atherosclerotic phenotype. BACKGROUND: Platelet-endothelial interactions have been linked to increased inflammatory activation and prothrombotic state in atherosclerosis. These interactions are mediated, in part, by platelet glycoprotein (GP) Ibα, suggesting that dysregulated endothelial vWF is a marker for high-risk atherosclerotic disease. METHODS: Microbubbles targeted to activated vWF were prepared by surface conjugation of recombinant GPIbα. Flow-chamber studies were used to evaluate attachment of targeted microbubbles to immobile platelet aggregates bearing activated vWF. Contrast-enhanced ultrasound (CEU) molecular imaging of the aorta from mice was performed: 1) ex vivo after focal crush injury and blood perfusion; and 2) in vivo in mice with advanced atherosclerosis produced by deletion of the low-density lipoprotein receptor and ApoBec-1 editing peptide (LDLR(-/-)/ApoBec-1(-/-)). RESULTS: In flow-chamber studies, tracer attachment to vWF was >10-fold greater for microbubbles bearing GPIbα compared with control microbubbles (p < 0.01). In the ex vivo aortic injury model, CEU signal enhancement for vWF-targeted microbubbles occurred primarily at the injury site and was 4-fold greater than at noninjured sites (p < 0.05). In LDLR(-/-)/ApoBec-1(-/-) mice, inflammatory cell infiltrates and dense vWF expression on the intact endothelium were seen in regions of severe plaque formation. Scanning electron microscopy demonstrated widespread platelet-endothelial interaction and only few sites of endothelial erosion. On CEU, signal enhancement for vWF-targeted microbubbles was approximately 4-fold greater (p < 0.05) in LDLR(-/-)/ApoBec-1(-/-) compared with wild-type mice. En face aortic microscopy demonstrated regions where platelet adhesion and microbubble attachment colocalized. CONCLUSIONS: Molecular imaging using GPIbα as a targeting moiety can detect the presence of activated vWF on the vascular endothelium. This strategy may provide a means to noninvasively detect an advanced prothrombotic and inflammatory phenotype in atherosclerotic disease.


Subject(s)
Atherosclerosis/blood , Endothelium, Vascular/physiopathology , Membrane Glycoproteins/physiology , von Willebrand Factor/physiology , Animals , Aorta/diagnostic imaging , Aorta/ultrastructure , Atherosclerosis/diagnostic imaging , Atherosclerosis/physiopathology , Biomarkers , Contrast Media , Disease Models, Animal , Endothelium, Vascular/diagnostic imaging , Humans , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Microbubbles , Microscopy, Electron, Scanning , Molecular Mimicry , Phenotype , Platelet Activation/physiology , Platelet Glycoprotein GPIb-IX Complex , Shear Strength/physiology , Ultrasonography
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(7): 1518-21, 2010 Jul.
Article in Chinese | MEDLINE | ID: mdl-20650755

ABSTRACT

OBJECTIVE: To evaluate the changes of cerebral blood flow (CBF) with real-time contrast-enhanced ultrasound (CEU) in a canine model of acute cerebral ischemia. METHODS: Cerebral perfusion was assessed in 6 dogs subjected to craniotomy with CEU at the time of 0, 30, 60, 90 and 120 min after occlusion of the left common carotid artery (LCCA). The microvascular volume (A) and blood flow velocity (beta) in the brain were measured from the time-versus-acoustic intensity plots, and the value of Axbeta were calculated. 99mTc-ECD brain single photon emission computed tomography (SPECT) was performed on the day before the experiment and at 120 min after LCCA occlusion. The radioactive counts on both sides of the cerebral cortex were calculated. RESULTS: A significant correlation was found between Axbeta from CEU and volume of the blood flow of the CCA from Doppler flowmetry. A, beta and Axbeta values varied significantly between the different time points (P>0.001). The ipsilateral hemisphere showed a low-perfusion state while the contralateral hemisphere showed a high-perfusion state immediately after the occlusion. CONCLUSIONS: The changes of beta is the main regulation mechanism during acute cerebral ischemia in dogs.


Subject(s)
Brain Ischemia/diagnostic imaging , Brain/blood supply , Cerebrovascular Circulation , Animals , Blood Flow Velocity , Dogs , Male , Regional Blood Flow , Ultrasonography
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