Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized ("hyperglycemic memory"). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications.

Oxidative stress and diabetic complications

2-D
: two-dimensional
3-D
: three-dimensional
5-FU
: 5-fluorouracil
ACE
: angiotensin-converting enzyme
ARB
: angiotensin II receptor blocker
ASE
: American Society of Echocardiography
BNP
: B-type natriuretic peptide
CABG
: coronary artery bypass graft
CAD
: coronary artery

/pdf/2016-esc-position-paper-on-cancer-treatments-and-1bzyne0xi3.pdf

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

Background— The recent discovery of circulating endothelial progenitor cells (EPCs) has altered our understanding of new blood vessel growth such as occurs during collateral formation. Because diabetic complications occur in conditions in which EPC contributions have been demonstrated, EPC dysfunction may be important in their pathophysiology. Methods and Results— EPCs were isolated from human type II diabetics (n=20) and age-matched control subjects (n=20). Proliferation of diabetic EPCs relative to control subjects was decreased by 48% (P<0.01) and inversely correlated with patient levels of hemoglobin A1C (P<0.05). Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor-α (TNF-α) (P<0.05). In a Matrigel assay, diabetic EPCs were 2.5 times less likely to participate in tubule formation compared with controls (P<0.05). Conclusions— These findings suggest that type II ...

Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures

No abstract available
Keywords: European Society of Cardiology; arrhythmias; cancer therapy; cardio-oncology; cardiotoxicity; chemotherapy; early detection; ischaemia; myocardial dysfunction; surveillance.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejhf.654

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)

Cardiac dysfunction resulting from exposure to cancer therapeutics
was first recognized in the 1960s, with the widespread introduction
of anthracyclines into the oncologic therapeutic armamentarium.
Heart failure (HF) associated with anthracyclines was then recognized
as an important side effect. As a result, physicians learned to limit their
doses to avoid cardiac dysfunction. Several strategies have been used
over the past decades to detect it. Two of them evolved over time
to be very useful: endomyocardial biopsies and monitoring of left ven-
tricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination
of endomyocardial biopsies proved to be the most sensitive and spe-
cific parameter for the identification of anthracycline-induced LV
dysfunction and became the gold standard in the 1970s. However,
the interest in endomyocardial biopsy has diminished over time
because of the reduction in the cumulative dosages used to treat ma-
lignancies, the invasive nature of the procedure, and the remarkable
progress made in noninvasive cardiac imaging. The noninvasive
evaluation of LVEF has gained importance, and notwithstanding the
limitations of the techniques used for its calculation, has emerged as
the most widely used strategy for monitoring the changes in cardiac
function, both during and after the administration of potentially car-
diotoxic cancer treatment.

Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy: A Report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

Protective Effects of Carvedilol Against Anthracycline-Induced Cardiomyopathy

Background—Although myocardial ischemia is known to be significantly related to the development of coronary collateral vessels (CCVs), there is considerable variation between patients with ischemic heart disease in the presence of collateral development. The nature of this variability is not well known. Likewise, it remains unclear whether diabetes mellitus (DM) has any effect on CCVs. The aim of this study was to evaluate the effect of DM on CCVs. Methods and Results—Of the patients who underwent coronary angiography during the interval between March 1, 1993, and June 20, 1998, in our institution, 306 were diabetic. Those patients in whom coronary angiography is normal or severity of coronary artery stenosis is thought not to be sufficient for the development of CCVs ( 75...

Effect of diabetes mellitus on formation of coronary collateral vessels.

Carbon monoxide (CO) poisoning is an important health problem Cardiac abnormalities may occur in patients with CO poisoning; however, the severity and duration of cardiac abnormalities are not well known In this study, cardiac structures and function in CO poisoning were evaluated prospectively Twenty patients were enrolled in the study Echocardiographic examination was performed in all patients on admission, at 24 hours, and within the first week B-type natriuretic peptide and carboxyhemoglobin levels were measured Patients with increased cardiac markers underwent coronary angiography Cardiac markers were high in 6 patients Patients with high cardiac markers had significantly higher carboxyhemoglobin levels and longer exposure to CO Left ventricular ejection fraction (LVEF) was 55% in 7 patients in group I 24 hours after echocardiography A significant negative correlation was found between B-type natriuretic peptide and LVEF on admission (r = -0586, p <001) The decrease in LVEF was also negatively correlated with carboxyhemoglobin level and CO exposure duration All angiograms showed normal coronary arteries In conclusion, despite normal coronary arteries, myocardial dysfunction may occur in patients with CO poisoning LV systolic function might be normal or mildly to severely impaired However, most of the myocardial dysfunction dissipates at 24 hours in patients with CO poisoning

Cardiovascular Effects of Carbon Monoxide Poisoning

Background—The potential factors that introduce variability into TIMI frame count (TFC) have not been systematically investigated. The goal of this study was to determine if nitrate use, dye injection rate, catheter size, the phase of the cardiac cycle in which dye is injected, or heart rate affect the TFC and to investigate the reproducibility of the TFC. Methods and Results—The dye injection rate was increased 1 mL/s, and angiography was repeated. A coronary angiogram was taken first with an 8F catheter and then with a 6F catheter. After taking angiograms, intracoronary nitrate was given to the patient, and the second angiography was performed. Basal heart rate was increased 20 beats/min, and angiography was repeated. Dye injection was performed at the beginning of systole and diastole. The TFC was not significantly changed by increasing the dye injection rate (P=0.467) or by changing catheter size (P=0.693). Nitrate administration significantly increased the TFC from 26.4±11.9 to 32.8±13.3 frames (P<0....

Effect of Potential Confounding Factors on the Thrombolysis in Myocardial Infarction (TIMI) Trial Frame Count and Its Reproducibility

Doppler tissue imaging (DTI) has been proposed as a tool for the evaluation of diastolic function. Controversy exists regarding whether DTI measurements are influenced by preload. Changes in the circulating volume associated with hemodialysis result in preload reduction. To determine the influence of preload reduction on DTI and standard pulsed-Doppler transmitral diastolic velocities, 30 patients (mean age 41 +/- 14) with chronic renal insufficiency without overt heart disease were studied by DTI and standard pulsed Doppler before and after hemodialysis. From the apical window, DTI sample volume was placed at the lateral and septal mitral annulus and at the midsegment of lateral and septal myocardial wall of the left ventricle. Peak early diastolic annular and myocardial, and peak late diastolic annular and myocardial velocities were measured. Transmitral peak early and late diastolic velocities were also recorded by standard pulsed Doppler. The peak velocity of early diastolic mitral flow decreased from 100 +/- 30 to 85 +/- 34 cm/s (P < 0.001) after hemodialysis. Hemodialysis elicited marked reduction in early diastolic lateral mitral annular and midlateral myocardial velocities (6.9 +/- 3.2 to 6.3 +/- 2.9 cm/s, P < 0.04 and 6.7 +/- 0.3 to 5.5 +/- 2 cm/s, P < 0.001, respectively). Early diastolic, septal mitral annular, and midseptal myocardial velocities were also significantly decreased (5.8 +/- 2.8 to 4.6 +/- 2 cm/s, P < 0.006 and 6.2 +/- 2 to 5.1 +/- 1 cm/s, P < 0.008, respectively). Late diastolic mitral annular and myocardial velocities did not change. It is concluded that early diastolic mitral annular and myocardial velocities are affected by acute preload reduction. It is necessary to consider preload when diastolic function is assessed by DTI.

Namık Kemal Eryol

Papers

Protective Effects of Carvedilol Against Anthracycline-Induced Cardiomyopathy

Effect of diabetes mellitus on formation of coronary collateral vessels.

Cardiovascular Effects of Carbon Monoxide Poisoning

Effect of Potential Confounding Factors on the Thrombolysis in Myocardial Infarction (TIMI) Trial Frame Count and Its Reproducibility

Preload dependence of Doppler tissue imaging derived indexes of left ventricular diastolic function.