In utero exposure to chemotherapy: effect on cardiac and neurologic outcome.
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Antineoplastic Agents↗
Biomedical subjects
Javier Ganame
Publications and source records attributed to Javier Ganame.
Peroxisome proliferator-activated receptor-alpha,gamma-agonist improves insulin sensitivity and prevents loss of left ventricular function in obese dyslipidemic mice.
OBJECTIVE: We investigated the effect of a dual peroxisome proliferator-activated receptor (PPAR)alpha,gamma-agonist on atherosclerosis and cardiac function in mice with combined leptin and low-density lipoprotein receptor deficiency (DKO). In these mice, obesity, diabetes, and hyperlipidemia are associated with accelerated atherosclerosis and loss of cardiac function. METHODS AND RESULTS: We treated 12-week-old DKO mice with the PPARalpha,gamma-agonist (S)-3-(4-(2-carbazol-9-yl-ethoxy) phenyl-2-ethoxy-propionic-acid) for 12 weeks. The agonist lowered free fatty acids with 42% and increased insulin sensitivity with 76%. It had no effect on plasma cholesterol and triglycerides. RT-PCR analysis showed that the agonist increased the expression of fatty acid transport protein-4, fatty acid binding protein-4, glucose transporter-4, hormone-sensitive lipase, and adiponectin in white adipose tissue that was associated with the increase in insulin sensitivity. At 24 weeks, the shortening fraction (SF) of placebo DKO mice was 30% lower than that of C57BL6 mice. The PPAR agonist increased PPARgamma but not PPARalpha expression in the heart and prevented loss of left ventricular function. Adiponectin correlated positively with PPARgamma in the heart and with SF. The agonist had no effect on atherosclerosis in the aortic arch of DKO mice. CONCLUSIONS: The dual PPARalpha,gamma-agonist improved insulin sensitivity without affecting cholesterol and triglycerides. This was associated with induction of PPARgamma in the heart and prevention of loss of left ventricle function.
Animals↗
Rapid ventricular remodeling with left ventricular unloading postventricular assist device placement: new insights with strain imaging.
We report the case of a 6-year old girl who presented with severe dilated cardiomyopathy. Cross-sectional echocardiography demonstrated a severely dilated hypokinetic left ventricle with an ejection fraction less than 10%. She developed intractable ventricular tachyarrhythmias and subsequently had a left ventricular assist device implanted. Within 1 week of mechanical support, echocardiography demonstrated dramatic reverse remodeling of the left ventricle with marked improvement in myocardial deformation using strain rate imaging. This report further highlights the potential for rapid remodeling after mechanical support of the failing myocardium.
Cardiomyopathy, Dilated↗
Ultrasonic strain rate and strain imaging of the right ventricle in children before and after percutaneous closure of an atrial septal defect.
This study examined the influence of preload alterations on systolic right ventricular (RV) velocities and deformation indices in patients with atrial septal defect (ASD). A total of 21 patients with ASD underwent 2-dimensional echocardiography and color Doppler myocardial imaging scan before and 24 hours after transcatheter ASD closure. The data were compared with those obtained from 30 healthy age-matched children. Longitudinal peak systolic velocities, peak systolic strain rate (SR), and end-systolic strain (epsilon) were calculated in the midsegment of the RV free wall and the septum. In patients with ASD, higher RV peak systolic velocities were recorded, which returned to normal values after closure of the defect. In contrast, RV deformation indices in the patients with ASD were not different from normal values. These RV indices did not change significantly after ASD closure. We found a significantly decreased septal function after percutaneous ASD closure. This may be attributed to the device within the atrial septum, affecting deformation of the interventricular septum. In conclusion, RV longitudinal systolic deformation indices were not significantly influenced by chronic ventricular volume overload and sudden abolishment of this volume overload. These findings suggest that SR/epsilon are relatively load-stable measures of contractile function in the clinical setting. In contrast, myocardial velocities are clearly load dependent.
Adolescent↗
Different deformation patterns in intracardiac tumors.
We report on the ultrasound characteristics of two different intracardiac tumors in newborns. The first infant presented with multiple rhabdomyomas in the context of tuberous sclerosis. Ultrasound-based strain and strain rate analysis showed that the tumors deformed in the opposite direction from the surrounding myocardial segments. The second child presented with a large cardiac fibroma as confirmed by pathological examination. In this case strain and strain rate analysis showed the absence of deformation in the tumor. These findings suggest that this new technique could be used to differentiate between different types of myocardial tumors.
Diagnosis, Differential↗
Importance of measurements at or after the J-point for evaluation of ST-segment deviation and resolution during treatment for acute myocardial infarction.
BACKGROUND: Determination of ST-segment deviation (STdev) and its resolution (STR) by reperfusion strategies have become important tools in the assessment of patients with acute myocardial infarction (AMI). STdev has been measured at different time-points, i.e. at 20-80 ms after the J-point. There are no data comparing STR at different time-points. METHODS AND RESULTS: STdev was measured using a new computer-assisted workflow. The intraclass correlation coefficients (ICC) for validity and agreement vs. classical manual measurements (n=1020) were both 0.996 (p<0.0001). The reliability indices were 0.991 (95% CI 0.990-0.992) for the manual vs. 0.995 (95% CI 0.995-0.996) for the computer-assisted method, indicating superiority of the latter. 12-lead STdev were determined on ECGs before (baseline) and 180 min after start of thrombolytic therapy, measured both at the J-point (STdev(J)) and 20 ms after the J-point (STdev(J20); n=2400). STdev(J20) was on average 0.01+/-0.03 mV higher than STdev(J) (p<0.0001) with a tendency towards larger differences for higher ST-elevations (p<0.001). Although the average STR calculated from STdev(J20) and STdev(J) was not statistically different in any infarct location group, in 26% of the patients the difference was >10%, and 11% of the patients were classified into another ST-resolution group. Analysing STdev only in the single lead with the highest ST-elevation at baseline (a simplified measurement which may eliminate the confounding effect of ST-depressions) showed an even higher classification discordance (14% of the patients). CONCLUSIONS: The time-point of STdev measurement is an important variable to be accounted for when evaluating ST resolution data. Uncontrolled extrapolation of classification schemes based on STdev(J20) to other time-points cannot be justified.
Electrocardiography↗
Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice.
BACKGROUND: Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown. METHODS AND RESULTS: We studied the effect of diet restriction-induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia, and insulin resistance are associated with hypertension, impaired left ventricular function, and accelerated atherosclerosis in those mice. Compared with lean mice, peroxisome proliferator-activated receptors (PPAR)-alpha and PPAR-gamma expression was downregulated in obese double-knockout mice. Diet restriction caused a 45% weight loss, an upregulation of PPAR-alpha and PPAR-gamma, and a change in the expression of genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress, and inflammation, most of which are under the transcriptional control of these PPARs. Changes in gene expression were associated with increased insulin sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. PPAR-alpha and PPAR-gamma expression was inversely related to plaque volume and to oxidized LDL content in the plaques. CONCLUSIONS: Induction of PPAR-alpha and PPAR-gamma in adipose tissue, heart, and aortic arch is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight loss. Improved lipid metabolism and insulin signaling is associated with decreased tissue deposition of oxidized LDL that increases cardiovascular risk in persons with the metabolic syndrome.
Adipose Tissue↗