The coronary microcirculation plays a key role in modulating blood supply to the myocardium. Several factors like myocardial oxygen demands, endothelial and neurogenic conditions determine its function. Although there is available evidence supporting microvascular dysfunction as an important cause of myocardial ischaemia, with both prognostic and symptomatic implications, its diagnosis and management in clinical practice is still relegated to a second plane. Both diagnostic and therapeutic approaches are hampered by the broadness of the concept of microvascular dysfunction, which fails addressing the plurality of mechanisms leading to dysfunction. Normal microcirculatory function requires both structural integrity of the microcirculatory vascular network and preserved signalling pathways ensuring adequate and brisk arteriolar resistance shifts in response to myocardial oxygen demands. Pathological mechanisms affecting these requirements include structural remodelling of microvessels, intraluminal plugging, extravascular compression or vasomotor dysregulation. Importantly, not every diagnostic technique provides evidence on which of these pathophysiological mechanisms is present or predominates in the microcirculation. In this paper we discuss the mechanisms of coronary microvascular dysfunction and the intracoronary tools currently available to detect it, as well as the potential role of each one to unmask the main underlying mechanism.

Targeting the dominant mechanism of coronary microvascular dysfunction with intracoronary physiology tests

Garlic oil has been reported to protect the cardiovascular system; however, the effects and mechanisms behind the cardioprotection of garlic oil on diabetes-induced cardiaomyopathy are unclear. In this study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether garlic oil could protect the heart from diabetes-induced cardiomyopathy. Wistar STZ-induced diabetic rats received garlic oil (0, 10, 50 or 100 mg kg−1 body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction and cardiac pathologic hypertrophy responses were observed in diabetic rat hearts. Cardiac function was examined using echocardiography. In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Garlic oil treatment significantly inhibited the up-regulation in MAPK (e.g., p38, JNK and ERK1/2) and IL-6/MEK5/ERK5 signaling pathways in the diabetic rat hearts, reducing the levels of cardiac pathologic hypertrophy markers such as ANP and BNP, and improving the cardiac contractile function. Collectively, data from these studies demonstrate that garlic oil shows the potential cardioprotective effects for protecting heart from diabetic cardiomyopathy.

/pdf/garlic-oil-alleviates-mapks-and-il-6-mediated-diabetes-2q11705j9l.pdf

Garlic Oil Alleviates MAPKs- and IL-6-mediated Diabetes-related Cardiac Hypertrophy in STZ-induced DM Rats.

The aim of the present study was to evaluate the protective effect and mechanism of Astragaloside IV (ASIV) on myocardial injury induced by type 2 diabetes, with a focus on energy metabolism. Blood glucose, the hemodynamic index, left ventricular weight/heart weight (LVW/HW), the left ventricular systolic pressure (LVSP), the left ventricular end diastolic pressure (LVEDP) and cell survival rate were measured in streptozotocin‑induced diabetes model rats. Western blot analysis, PCR, hematoxylin‑eosin and TUNEL staining, flow cytometry and ELISA were used to detect: i) Cardiomyocyte damage indicators such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cytochrome c (Cyt C), caspase‑3, cleaved caspase‑3 and the apoptotic rate; ii) energy metabolism indicators such as ATP/AMP and ADP/AMP; and iii) energy metabolism associated pathway proteins such as peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC‑1α) and nuclear respiratory factor 1 (NRF1). The present demonstrated increased blood glucose, LVW/HW, LVSP, LVEDP and the cardiomyocyte damage indicators (ANP, BNP, Cyt C and caspase‑3), in the diabetic and high glucose‑treated groups, which were decreased by ASIV. The expression of NRF‑1 and PGC‑1α significantly changed in the model group and was markedly improved following ASIV treatment. Furthermore, the abnormal energy metabolism in the model group was reversed by ASIV. According to the results, ASIV can regulate energy metabolism by regulating the release of PGC‑1α and NRF1 to rescue the abnormal energy metabolism caused by diabetes mellitus, thus decreasing the myocardial damage caused by diabetic cardiomyopathy.

/pdf/astragaloside-iv-alleviates-myocardial-damage-induced-by-2wpcllc0gl.pdf

Astragaloside IV alleviates myocardial damage induced by type 2 diabetes via improving energy metabolism

Background

This study aims to evaluate the relationship between IMR (Index of Microcirculatory Resistance) and the echocardiographic evolution of left ventricular (LV) systolic and diastolic performance after ST-elevation acute myocardial infarction (STEMI), undergoing primary angioplasty (P-PCI).



Methods

IMR was evaluated immediately after P-PCI. Echocardiograms were performed within the first 24 hours (Echo1) and at 3 months (Echo2): LV volumes, ejection fraction (LVEF), wall motion score index (WMSI), E/e ratio, global longitudinal strain (GLS), and left atrial volume were measured.



Results

Forty STEMI patients were divided in 2 groups according to median IMR: Group 1 (IMR   = 26), with more microvascular dysfunction. In Echo1 GLS was significantly better in Group 1 (−14.9 vs. −12.9 in Group 2, P = 0.005). However, there were no significant differences between the two groups in LV systolic volume, LVEF and WMS. Between Echo1 and Echo2, there were significant improvements in LVEF (0.48 ± 0.06 vs. 0.55 ± 0.06, P < 0.0001), GLS (−14.9 ± 1.3 vs. −17.3 ± 7.6, P = 0.001), and E/e ratio (9.3 ± 3.4 vs. 8.2 ± 2.0, P = 0.037) in Group 1, but not in Group 2: LVEF (0.49 ± 0.06 vs. 0.50 ± 0.05, P = 0.47), GLS (−12.9 ± 2.4 vs. −14.4 ± 3.2, P = 0.052), and E/e ratio (8.8 ± 2.4 vs. 10.0 ± 4.7, P = 0.18). WMSI improved significantly more in Group 1 (reduction of −17.1% vs. −6.8% in Group 2, P = 0.015).



Conclusion

Lower IMR was associated with better myocardial GLS acutely after STEMI, and with a significantly higher recovery of the LVEF, WMSI, E/E' ratio and GLS, suggesting that IMR is an early marker of cardiac recovery, after acute myocardial infarction.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/joic.12278

The Index of Microcirculatory Resistance as a Predictor of Echocardiographic Left Ventricular Performance Recovery in Patients With ST-Elevation Acute Myocardial Infarction Undergoing Successful Primary Angioplasty.

Diabetic cardiovascular dysfunction is a representative complication of diabetes. Inflammation associated with the onset and exacerbation of type 2 diabetes mellitus (T2DM) is an essential factor in the pathogenesis of diabetic cardiovascular complications. Diabetes-induced myocardial dysfunction is characterized by myocardial fibrosis, which includes structural heart changes, myocardial cell death, and extracellular matrix protein accumulation. The mice groups in this study were divided as follows: Cont, control (db/m mice); T2DM, type 2 diabetes mellitus mice (db/db mice); Vil.G, db/db + vildagliptin 50 mg/kg/day, positive control, dipeptidyl peptidase-4 (DPP-4) inhibitor; Bla.C, db/db + blackcurrant 200 mg/kg/day. In this study, Bla.C treatment significantly improved the homeostatic model evaluation of glucose, insulin, and insulin resistance (HOMA-IR) indices and diabetic blood markers such as HbA1c in T2DM mice. In addition, Bla.C improved cardiac function markers and cardiac thickening through echocardiography. Bla.C reduced the expression of fibrosis biomarkers, elastin and type IV collagen, in the left ventricle of a diabetic cardiopathy model. Bla.C also inhibited TD2M-induced elevated levels of inflammatory cytokines in cardiac tissue (IL-6, IL-1β, TNF-α, and TGF-β). Thus, Bla.C significantly improved cardiac inflammation and cardiovascular fibrosis and dysfunction by blocking inflammatory cytokine activation signals. This showed that Bla.C treatment could ameliorate diabetes-induced cardiovascular complications in T2DM mice. These results provide evidence that Bla.C extract has a significant effect on the prevention of cardiovascular fibrosis, inflammation, and consequent diabetes-induced cardiovascular complications, directly or indirectly, by improving blood glucose profile.

Blackcurrant Improves Diabetic Cardiovascular Dysfunction by Reducing Inflammatory Cytokines in Type 2 Diabetes Mellitus Mice.

Introduction and objectives. Diabetes mellitus (DM) is associated with the development of both impaired left ventricular diastolic function (LVDF) and pathological changes in the coronary macro- and microcirculation. The aim of this study was to investigate the relationship between these manifestations of diabetic heart disease. Methods. The severity of atherosclerosis in the left anterior descending coronary artery (LAD) was quantified using intravascular ultrasound (IVUS) in 13 patients with DM and ischemic heart disease. The coronary flow velocity reserve (CFVR), instantaneous hyperemic diastolic velocity pressure slope index (IHDVPS) zero-flow pressure were derived from digital intracoronary pressure and flow velocity measurements. The relationships between indices of LVDF (ie, E/A and E/e’ ratios) and intracoronary measurements were assessed. Results. The left ventricular ejection fraction was 66% (7%), and the LVDF indices were: E/A=0.92 (0.38) and E/e’=9.90 (2.80). There was a direct proportional relationship (r=0.62; P=.02) between E/e’ and coronary resistance (1.93 [0.74] mm Hg/s) and an inverse proportional relationship (r=–0.64; P=.02) between E/e’ and IHDVPS (1.56 [0.50] cm/s/mm Hg). However, no significant relationship was found between either LVDF index and CFVR (2.43 [0.56]) or coronary zero-flow pressure (40.41 [10.66] mm Hg). The volume of atheroma in the proximal 20 mm of the LAD (179.34 [57.48] µL, with an average plaque area of 8.39 [2.20] mm 2 ) was not related to either LVDF index. Conclusions. In patients with DM and coronary atherosclerosis, there appeared to be a relationship between LVDF impairment (assessed by the E/e’ ratio) and structural changes in the microcirculation.

Diastolic dysfunction in diabetic patients assessed with Doppler echocardiography: relationship with coronary atherosclerotic burden and microcirculatory impairment.

Introduccion y objetivos La diabetes mellitus (DM) se asocia al desarrollo tanto de alteraciones de la funcion diastolica ventricular izquierda (FDVI) como al de patologia macrovascular y microvascular coronaria. El objetivo del estudio fue estudiar la posible relacion entre ambas manifestaciones de la cardiopatia diabetica. Metodos En 13 pacientes con DM y cardiopatia isquemica se cuantifico la carga aterosclerotica (CA) mediante ecografia intracoronaria (IVUS) en la rama DA. A partir del registro digital de presion y velocidad de flujo intracoronarias, se calculo la reserva de velocidad de flujo coronario (RVFC), la conductancia coronaria, la presion de flujo cero (Pf0) y la resistencia coronaria. Se estudio la relacion entre parametros de FDVI (relaciones E/A y E/e’) y las mediciones intracoronarias. Resultados Se documento una FEVI del 66% ± 7%, y una FDVI con E/A = 0,92 ± 0,38 y E/e’ = 9,9 ± 2,8. Se documento una relacion directamente proporcional (r = 0,62; p = 0,02) entre E/e’ y la resistencia coronaria (1,93 ± 0,74 mmHg/cm/s) y una relacion inversamente proporcional (r = −0,64; p = 0,02) entre E/e’ y la conductancia coronaria (1,56 ± 0,5 cm/s/mmHg). No se encontro relacion significativa entre los parametros de FDVI y la RVFC (2,43 ± 0,56) o la Pf0 (40,41 ± 10,66 mmHg). El volumen de ateroma en los 20 mm proximales de la DA (179,34 ± 57,48 μl; area media de placa, 8,39 ± 2,2 mm2) no se relaciono con la FDVI. Conclusiones En los pacientes con DM y aterosclerosis coronaria parece darse una relacion entre la disfuncion de la FDVI (estimada con el indice E/e’) y la afeccion estructural de la microcirculacion.

Disfunción diastólica del paciente diabético estimada con ecocardiografía Doppler: relación con la ateromatosis y la disfunción microcirculatoria coronarias

Marcos Gutiérrez

Papers

Diastolic dysfunction in diabetic patients assessed with Doppler echocardiography: relationship with coronary atherosclerotic burden and microcirculatory impairment.

Disfunción diastólica del paciente diabético estimada con ecocardiografía Doppler: relación con la ateromatosis y la disfunción microcirculatoria coronarias