Genetic polymorphisms in post-mortem alcoholics

We investigated the hypothesis that alcoholism risk may be mediated by genes for neurotransmitters (dopamine, serotonin, opioid, GABAA and glutamate) associated with the dopamine reward system, and with genes involved in ethanol metabolism and fibrogenesis (ADH2, ADH3, ALDH2, CYP2E1, COL1A2, and ApoE). DNA was extracted from brain tissue collected at autopsy from pathologically characterised alcoholics and controls. PCR-based studies showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) Taq1 B (p 0.005) and the GABAA 2 subunit C1412T (p 0.007) genes but not with the glutamate receptor subunit gene NR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the Mu opioid receptor gene MOR1 (A118G and C1031G), the dopamine D2 receptor gene DRD2 Taq1 A or the GABAA 1(A15G), 6(T1519C) and 2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (p 0.024). The genotype for the most active alcohol dehydrogenase ADH3 was associated with a lower risk of alcoholism (p 0.027) and was less prevalent in alcoholics with DRD2 Taq1 A2/A2 (p 0.007), Taq1 B2/B2 (p 0.038) and GABAA-2 1412C/C (p 0.005) and EAAT2 603G/A (p 0.020) genotypes. Combined genotypes of DRD2 Taq1 A and B, GABAA-2, and EAAT2 G603A polymorphisms suggested a concerted influence of dopamine, GABAA and glutamatergic neurotransmitters in the predisposition to alcoholism.

Comparison between myocardial integrated backscatter and strain rate imaging in the quantitative assessment of subepicardial function post-myocardial infarction

Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.

Local geometric changes in left ventricular remodeling post-infarction can lead to apparent reduction in scar thickness

Serial reduction in scar thickness has been shown in animal models. We sought whether this reduction in scar thickness may be a result of dilatation of the left ventricle (LV) with stretching and thinning of the wall. Contrast enhanced magnetic resonance imaging (CMRI) was performed to delineate radial scar thickness in 25 patients (age 63±10, 21 men) after myocardial infarction. The LV was divided into 16 segts and the absolute radial scar thickness (ST) and percentage scar to total wall thickness (%ST) were measured. Regional end diastolic (EDV) and end systolic volumes (ESV) of corresponding segments were measured on CMRI. All patients underwent revascularization and serial changes in ST, %ST, and regional volumes were assessed with a mean follow up of 15±5 months. CMRI identified a total of 93 scar segments. An increase in EDV or ESV was associated with a serial reduction inST(versusEDV, r =−0.3, p = 0.01; versusESV, r =−0.3, p = 0.005) and%ST(versusEDV, r =−0.2, p = 0.04; versus ESV, r =−0.3, p = 0.001). For segts associated with a positive increase in EDV (group I) or ESV (group II) there was a significant decrease in ST and %ST, but in those segts with stable EDV (group III) or ESV (group IV) there were no significant changes in ST and %ST (Table).

Reduction in scar thickness post myocardial infarction is secondary to increase in regional left ventricular volumes

We sought to determine the relative impact of myocardial scar and viability on post-infarct left ventricular (LV) remodeling in medically-treated patients with LV dysfunction. Forty patients with chronic ischemic heart disease (age 64±9, EF 40±11%) underwent rest-redistribution Tl201 SPECT (scar = 50% transmural extent), A global index of scarring for each patient (CMR scar score) was calculated as the sum of transmural extent scores in all segts. LV end diastolic volumes (LVEDV) and LV end systolic volumes (LVESV) were measured by real-time threedimensional echo at baseline and median of 12 months follow-up. There was a significant positive correlation between change in LVEDV with number of scar segts by all three imaging techniques (LVEDV: SPECT scar, r = 0.62, p < 0.001; DbE scar, r = 0.57, p < 0.001; CMR scar, r = 0.52, p < 0.001) but change in LV volumes did not the correlate with number of viable segments. ROC curve analysis showed that remodeling (LVEDV> 15%) was predicted bySPECTscars(AUC= 0.79),DbEscars(AUC= 0.76),CMR scars (AUC= 0.70), and CMR scar score (AUC 0.72). There were no significant differences between any of the ROC curves (Z score