Circulating immunoreactive cardiac troponin forms determined by gel filtration chromatography after acute myocardial infarction.

BACKGROUND: Cardiac troponin I (cTnI) and cTnT measurements are used in the diagnosis of acute myocardial infarction (AMI). Together with troponin C (TnC), the cTnI and cTnT forms make up the ternary cTnT-cTnI-TnC (TIC) complex found within myocardium. Whether cTn occurs in the circulation after AMI as ternary TIC, binary cTnI-TnC (IC) complexes, or free troponin forms has not been thoroughly investigated. METHODS: Blood samples from 10 AMI patients were collected at hospital admission and then at 12, 24, and 48 h after onset of chest pain. Serum was subjected to gel filtration chromatography and cTnT (Roche cTnT) and cTnI (Siemens Centaur UltraTnI and Beckman Access AccuTnI) concentrations were measured in the gel filtration chromatography fractions. RESULTS: cTnT was present predominantly as free cTnT and cTnI as binary IC complex. These 2 forms were present at every time point. Lesser quantities of TIC complex (6%-32% of total cTnT and <50% of total cTnI) were detected in 4 patients at varying times. Minor quantities of a high molecular mass form of cTnI were detected occasionally. No free cTnI was found. Both cTnI assays identified a similar pattern of cTnI forms. CONCLUSIONS: After AMI, cTnI is present in serum as TIC and IC complexes. cTnT may be present as a combination of TIC and free cTnT or exclusively as free cTnT.

Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: This study's aim was to examine whether treatment with pioglitazone, added to conventional lipid-lowering therapy, would improve myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL). BACKGROUND: Thiazolidinediones were found to improve insulin sensitivity and MGU in type 2 diabetes and MBF in Mexican Americans with insulin resistance. Familial combined hyperlipidemia is a complex genetic disorder conferring a high risk of premature coronary artery disease, characterized by high serum cholesterol and/or triglyceride, low high-density lipoprotein (HDL) cholesterol, and insulin resistance. METHODS: We undertook a randomized, double-blind, placebo-controlled study in 26 patients with FCHL, treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, followed by 45 mg daily for 12 weeks. Positron emission tomography was used to measure MBF at rest and during adenosine-induced hyperemia and MGU during euglycemic hyperinsulinemic clamp at baseline and after treatment. RESULTS: Whereas no change was observed in the placebo group after treatment, patients receiving pioglitazone showed a significant increase in whole body glucose disposal (3.93 +/- 1.59 mg/kg/min to 5.24 +/- 1.65 mg/kg/min; p = 0.004) and MGU (0.62 +/- 0.26 micromol/g/min to 0.81 +/- 0.14 micromol/g/min; p = 0.0007), accompanied by a significant improvement in resting MBF (1.11 +/- 0.20 ml/min/g to 1.25 +/- 0.21 ml/min/g; p = 0.008). Furthermore, in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (-35%; p = 0.017) was reduced. CONCLUSIONS: In patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGU and MBF, with a favorable effect on blood lipid and metabolic parameters. (A study to investigate the effect of pioglitazone on whole body and myocardial glucose uptake and myocardial blood flow/coronary vasodilator reserve in patients with familial combined hyperlipidaemia; http://www.controlled-trials.com/mrct/trial/230761/ISRCTN78563659; ISRCTN78563659).

Effect of left ventricular assist device combination therapy on myocardial blood flow in patients with end-stage dilated cardiomyopathy.

BACKGROUND: Changes in myocardial blood flow (MBF) and coronary flow reserve (CFR) are independent prognostic risk factors in idiopathic dilated cardiomyopathy (DCM). The aim of this study was to assess the impact of left ventricular unloading using left ventricular assist device (LVAD) combination therapy on resting MBF and CFR in patients with end-stage heart disease. METHODS: We studied 11 patients with deteriorating end-stage DCM (New York Heart Association Class 4) treated with LVAD support combined with pharmacologic therapy in a recovery program. Absolute MBF was measured using oxygen-15-labeled water (H(2)(15)O) positron emission tomography (PET) at rest during LVAD support and 15 minutes after the LVAD was switched off. Data were corrected for rate pressure product (RPP) when appropriate. Hyperemic MBF (intravenous adenosine, 140 mug/kg . min) was also measured in 6 patients with the LVAD switched off. CFR was calculated as the ratio MBF adenosine/MBF LVAD off (corrected). Data are expressed as mean +/- SD. RESULTS: At 317 +/- 193 days after device implantation, resting MBF was 0.95 +/- 0.29 (LVAD on) and 1.46 +/- 0.62 (LVAD off, corrected) ml/min . g (p = 0.01). MBF (LVAD on) was comparable with that of 11 age- and gender-matched normal controls (1.09 +/- 0.22 ml/min . g). CFR in the LVAD group was 1.49 +/- 0.99 compared with 3.56 +/- 1.42 in normal controls (p < 0.01). CONCLUSIONS: During LVAD support, resting MBF (LVAD on) was comparable to MBF in normal controls and increased when the LVAD was switched off. However, CFR was significantly impaired, even though all patients studied showed varying degrees of myocardial recovery. The implications of these findings, particularly in the long term, require further study.