Hongmin Zhu

Magnetic targeting enhances retrograde cell retention in a rat model of myocardial infarction

IntroductionRetrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the establishment of this method as the preferred route for cell delivery. Here, we explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction.MethodsRat mesenchymal stem cells were labeled with superparamagnetic oxide nanoparticles. The magnetic responsiveness of MSCs was observed while cells flowed through a tube that served as a model of blood vessels in a 0.6-Tesla magnetic field. In a Sprague–Dawley rat model of acute myocardial infarction, 1 × 106 magnetic mesenchymal stem cells were transjugularly injected into the left cardiac vein while a 0.6-Tesla magnet was placed above the heart. The cardiac retention of transplanted cells was assessed by using quantitative Y chromosome-specific polymerase chain reaction, cardiac magnetic resonance imaging, and optical imaging. Cardiac function was measured by using echocardiography, and histologic analyses of infarct morphology and angiogenesis were obtained.ResultsThe flowing iron oxide-labeled mesenchymal stem cells were effectively attracted to the area where the magnet was positioned. Twenty-four hours after cellular retrocoronary delivery, magnetic targeting significantly increased the cardiac retention of transplanted cells by 2.73- to 2.87-fold. Histologic analyses showed that more transplanted cells were distributed in the anterior wall of the left ventricle. The enhanced cell engraftment persisted for at least 3 weeks, at which time, left ventricular remodeling was attenuated, and cardiac function benefit was improved.ConclusionsThese results suggest that magnetic targeting offers new perspectives for retrograde coronary venous delivery to enhance cell retention and subsequent functional benefit in heart diseases.

Impact of Coronary Tortuosity on Coronary Blood Supply: A Patient-Specific Study

Background Tortuous coronary arteries are commonly observed in clinical screenings and it may cause a reduction of the coronary pressure. However, whether this reduction leads to significant decreasing in the coronary blood supply is still unknown. The purpose of this study was to investigate the effect of the coronary tortuosity (CT) on the coronary blood supply. Method A computational fluid dynamics (CFD) study was conducted to evaluate the impact of tortuosity on the coronary blood supply. Two patient-specific left anterior descending coronary artery (LAD) models and the corresponding non-tortuous models were reconstructed to perform three-dimensional CFD analysis. The lumped parameter model was coupled to the outlet of the simulated branches to represent the absent downstream vasculatures. The rest and exercise conditions were modeled by specifying proper boundary conditions. Result Under resting condition, the mean flow rate could be maintained by decreasing less than 8% of the downstream vascular beds resistance for tortuous models. While during exercise (maximal dilatation condition), the maximal coronary blood supply would reduce up to 14.9% due to tortuosity. Assuming that the flow rate can be maintained by the auto-regulation effect under the maximal dilatation condition, the distal resistances for CT models still have to reduce more than 23% to maintain blood perfusion. Conclusions Coronary tortuosity has minor influence on coronary blood supply at rest; while during exercise, patients with CT may lack the ability to adjust distal resistance sufficiently to compensate for the extra resistances generated by tortuosity and this may further lead to an ineffective regulation of the blood supply.

Computation of Hemodynamics in Tortuous Left Coronary Artery: A Morphological Parametric Study

Coronary tortuosity (CT) would alter the local wall shear stress (WSS) and may become a risk factor for atherosclerosis. Here we performed a systematic computational study to relate CT morphological parameters to abnormal WSS, which is a predisposing factor to the formation of atherosclerotic lesions. Several idealized left coronary artery (LCA) models were created to conduct a series of morphological parametric studies, in which we concentrate on three specific morphological parameters, the center line radius (CLR), the bend angle (BA), and the length between two adjust bends (LBB). The time averaged WSS (TAWSS), the oscillatory shear index (OSI), and the time averaged WSS gradient (WSSGnd) were explored by using the computational fluid dynamics (CFD) method, in order to determine susceptible sites for the onset of early atherosclerosis. In addition, two realistic LCA models were reconstructed to further validate the findings credibility. The CLR and LBB had great impact on the distributions of WSS-derived parameters, while the BA had minor impact on the hemodynamic of the tortuous arteries. Abnormal regions with low TAWSS (TAWSS < 0.5 Pa), high OSI (OSI > 0.1) and high WSSGnd (WSSGnd > 8) were observed at the inner wall of bend sections in the models with small CLR or small LBB. These findings were also confirmed in the realistic models. Severe CT with small CLR or LBB would lead to the formation of abnormal WSS regions at the bend sections and providing these regions with favorable conditions for the onset and/or progression of atherosclerosis.

Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study

BackgroundAdiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography.ResultsThe results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E′ (correlation coefficient (r) = −0.756 for NT-proBNP, p < 0.001, -0.635 for IL-6, p = 0.002, and −0.626 for E/E′, p = 0.002, respectively) while positively correlated with E/A and E′/A′ (r = 0.683 for E/A, p = 0.001, 0.671 for E′/A′, p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found.ConclusionAdiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.

Association of Renal Biochemical Parameters with Left Ventricular Diastolic Dysfunction in a Community-Based Elderly Population in China: A Cross-Sectional Study

Background Relationship of left ventricular diastolic dysfunction (LVDD) with parameters that could provide more information than hemodynamic renal indexes has not been clarified. We aimed to explore the association of comprehensive renal parameters with LVDD in a community-based elderly population. Methods 1,166 community residents (aged ≥ 65 years, 694 females) participating in the Shanghai Heart Health Study with complete data of renal parameters were investigated. Echocardiography was used to evaluate diastolic function with conventional and tissue Doppler imaging techniques. Serum urea, creatinine, urea-to-creatinine ratio, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were analyzed on their associations with LVDD. Results The prevalence of LVDD increased in proportion to increasing serum urea, urea-to-creatinine ratio and UACR. These three renal parameters were found negatively correlated to peak early (E) to late (A) diastolic velocities ratio (E/A), and positively to left atrial volume index; UACR also positively correlated with E to peak early (E’) diastolic mitral annular velocity ratio (E/E’). Serum urea, urea-to-creatinine ratio and UACR correlated with LVDD in logistic univariate regression analysis, and urea-to-creatinine ratio remained independently correlated to LVDD [Odds ratio (OR) 2.82, 95% confidence interval (CI) 1.34–5.95] after adjustment. Serum urea (OR 1.18, 95%CI 1.03–1.34), creatinine (OR 6.53, 95%CI 1.70–25.02), eGFR (OR 0.22, 95%CI 0.07–0.65) and UACR (OR 2.15, 95%CI 1.42–3.24) were revealed independent correlates of advanced (moderate and severe) LVDD. Conclusions Biochemical parameters of renal function were closely linked with LVDD. This finding described new cardio-renal relationship in the elderly population.

Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.

Objective: To test whether olmesartan ameliorates cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs) through calcineurin pathway. Methods: Twenty-four male SHRs of 6 months were divided into saline- (n = 12) and olmesartan-treated (n = 12) groups. Age-matched WKY (n = 12) rats served as controls. Saline (10 mL·kg·d) or the same volume of olmesartan liquor (2.5 mg·kg·d) was administered by gavage for 3 months. Heart rate, systolic blood pressure, cardiac structure, and function and histological studies were determined. Expression of calcineurin and downstream NFAT3 were also detected. Results: Compared with age-matched Wistar Kyoto rats, SHRs of 6 months exhibited evident cardiac hypertrophy and diastolic dysfunction as demonstrated by elevated systolic blood pressure and E/E′, decreased E/A and E′/A′, while F, left ventricular ejection fraction and fractional shortening remained unimpaired. Treatment with olmesartan significantly decreased systolic blood pressure and ventricular hypertrophy, attenuated fibrosis, and improved diastolic function (all P < 0.05). Meanwhile, both calcineurin and NFAT3 expressions were downregulated in olmesartan group compared with the other 2 groups (both P < 0.05). Conclusions: These data suggest the beneficial effect of olmesartan on cardiac structure and diastolic dysfunction, and it may be mediated through calcineurin pathway. This indicates a new therapeutic target for diastolic dysfunction.

A New Coronary Retroinfusion Technique in theRat Infarct Model: Transjugular Cardiac Vein Catheterization

Cell delivery via the retrograde coronary route boasts less vessel embolism, myocardial injury, and arrhythmogenicity when compared with those via antegrade coronary administration or myocardial injection. However, conventional insertion into the coronary sinus and consequent bleeding complication prevent its application in small animals. To overcome the complication of bleeding, we described a modified coronary retroinfusion technique via the jugular vein route in rats with myocardial infarction (MI). A flexible wire with a bent end was inserted into the left internal jugular vein and advanced slowly along the left superior vena cava. Under direct vision, the wire was run into the left cardiac vein by rotating the wire and changing the position of its tip. A fine tube was then advanced along the wire to the left cardiac vein. This modified technique showed less lethal hemorrhage than the conventional technique. Retroinfusion via transjugular catheter enabled efficient fluid or cell dissemination to the majority areas of the free wall of the left ventricle, covering the infarcted anterior wall. In conclusion, transjugular cardiac vein catheterization may make retrocoronary infusion a more safe and practical route for delivering cell, drug, and gene therapy into the infarcted myocardium of rats.

Observational study of Chinese medicine syndrome distribution in patients with acute myocardial infarction and its impact on prognosis

ObjectiveTo investigate the distribution of Chinese medicine (CM) syndrome in patients with acute myocardial infarction (AMI) on admission and its impact on prognosis.MethodsA total of 525 AMI patients were prospectively recruited and classifified into 4 groups based on their clinical characteristics: excess-heat, excess-cold, deficiency-heat and deficiency-cold syndromes. Major adverse cardiovascular events (MACEs) were followed up.ResultsThe excess syndrome was more common than deficiency syndrome (72.95% vs. 27.05%; P<0.05). Totally 495 (94.29%) of 525 AMI patients were followed up (median 277 days). There were 59 (11.92%) MACEs. After adjusted with confounding factors in Cox regression models, the hazard ratio (95% confifidence interval) of excess-heat, excess-cold, defificiency-heat and defificiency-cold syndrome groups were 1, 1.25 (0.63, 2.49; P<0.05), 2.37 (1.14, 4.94; P<0.05), 3.76 (1.71, 8.28; P<0.05), respectively.ConclusionsExcess syndrome was more common in AMI patients and had better prognosis, while defificiency-cold syndrome had the poorest prognosis. CM syndrome was of value in predicting long-term outcomes in AMI patients.

SHEAR-INDUCED PLATELET ACTIVATION IN TORTUOUS CORONARY ARTERY: A NUMERICAL STUDY

High fluid shear stresses (FSSs) were observed in tortuous coronary arteries, especially during the strenuous exercise condition. Whether these high FSSs would enhance the shear-induced platelet activation is still unknown. A computational fluid dynamics (CFD) study was conducted to evaluate the impact of coronary tortuosity (CT) on the shear-induced platelet activation during various conditions. A patient-specific left anterior descending (LAD) coronary artery model (CT model) and the corresponding non tortuous model (nCT model) were reconstructed to perform three-dimensional CFD analysis. Lagrangian particle analysis was performed to further obtain the platelet activation state (PAS) of the platelet-like particles. No significant difference was observed between CT and nCT models on the PAS values reached by the platelet-like particles at all simulated conditions. PAS values for particles within both CT and nCT models were decreased during exercise conditions, as compared to those during the rest condition. These results confirmed that CT could not enhance the platelet activation even with extreme high FSSs existing at bend sections during the strenuous exercise condition, and the results also implied that high FSSs might not be the critical factor leading to the platelet activation during the strenuous exercise for persons without the coronary obstructive.