Christina Petersen

The antioxidant drug dipyridamole spares the vitamin E and thiols in red blood cells after oxidative stress

OBJECTIVE To test the antioxidant effect of therapeutic doses of dipyridamole on cellular membranes, human erythrocytes were chosen as an appropriate model to study oxidative stress induced by cumene hydroperoxide because of their high content in heme-Fe(2+). METHODS The oxidative stress was induced by incubation with 160 micromoll(-1) cumene hydroperoxide and expressed by three main factors: lipid peroxidation by means of kinetics of decrease in fluorescence emission of the probe incorporated in the cell membranes, vitamin E oxidation and intracellular thiol content. The concentrations of dipyridamole tested (2-20 micromoll(-1)) did not exceed pharmacological doses. RESULTS After 7 min of incubation at 25 degrees C with the oxidant and 20 micromoll(-1) dipyridamole thiol content was 50.1%+/-2.6 compared with 31.5%+/-2.4 in the absence of the drug. After 12 min vitamin E content was 88.3%+/-2.3 compared with 64.7%+/-3.4 of untreated cells in the absence of dipyridamole. Dipyridamole added 5 min after the oxidation reaction suppressed the fluorescence decrease for a time proportional to the drug concentration. CONCLUSIONS Thus, at clinically realistic doses dipyridamole shows a concentration-dependent antioxidant effect. It protects membranes from oxidation and spares the antioxidant power of erythrocytes.

Cardiac calcification by transthoracic echocardiography in patients with known or suspected coronary artery disease

OBJECTIVES To estimate the correlation between the total heart calcification score index (CSI), assessed by echocardiography, left ventricle mass index (LVMI), Framingham risk score (FRS), and angiographically assessed coronary artery disease (CAD). BACKGROUND Aortic valve and root sclerosis (AVS, ARS) and mitral annular calcium (MAC) detected by echocardiography have been associated with atherosclerosis. FRS is recommended for estimation of total coronary heart disease risk over the course of 10 years. The anatomic extent of CAD can be assessed with coronary angiography. Total and cardiovascular mortality risk increases with increasing LVMI. METHODS 167 consecutive in-hospital patients (mean age 66.6+/-9.7 yrs, 119 men) underwent: 1) complete transthoracic echocardiography (TTE), with CSI assessment (from 0=normal to 10=diffuse calcification of aortic valve, mitral annulus and aortic root), 2) the FRS evaluation (FRS<or=10=low, FRS>or=11 and <or=20=average risk, and a FRS>or=21=high risk), and 3) coronary angiography (with Duke score evaluation, from 0=normal to 100=severe left main disease). RESULTS The mean CSI of the entire population was 3.94+/-2.1, with a mean of 2.75+/-2 in patients at low risk, with a progressive increase in patients at average risk (4.11+/-2.2), at high risk (4.7+/-1.7), respectively. CSI was associated with the presence of CAD (p=0.003) and the presence of abnormal LVMI (p=0.002). CONCLUSIONS Echocardiographically assessed CSI is correlated to FRS, Duke score and LVMI and can provide a simple, radiation-free index of cardiovascular risk.

Antioxidant effect of oral dipyridamole during cerebral hypoperfusion with human carotid endarterectomy.

We sought to test the hypothesis of an antioxidant effect of dipyridamole in vivo in a model of cerebral hypoperfusion. Twenty-one patients (65+/-10 years, 11 men) undergoing carotid endarterectomy were allocated in two groups (group 1, 10 with dipyridamole, 200 mg p.o., 3-4 h before surgery; group II, 11 with placebo) in a double-blind placebo-controlled randomized design. Blood was sampled from ipsilateral jugular bulb, and plasma vitamin E content was assayed before, after 15 and 30 min of clamp, and 2 and 10 min after declamping. In 12 of them, lipoperoxides were assayed. Vitamin E plasma content decreased significantly in group II (rest, 3.71+/-0.22 mmol/mol of cholesterol, 100%) after clamp (91.5% of rest, p < 0.01) and remained unchanged during declamping (90.9% of rest, p < 0.01), but did not change in group I (rest, 3.5+/-0.44 mmol/mol of cholesterol, 100%) during clamping (99.9% of rest; p = NS) and after declamping (97.6% of rest; p = NS). Lipoperoxide concentration did not change in group I (rest, 302+/-8 a.u.; clamp, 296+/-13 a.u.; p = NS vs. rest; declamp, 304+/-8 a.u.; p = NS vs. rest), and increased significantly in group II (rest, 313+/-5 a.u.; clamp, 352+/-9 a.u.; p < 0.01 vs. rest; declamp, 343+/-6 a.u.; p < 0.05 vs. rest). Cerebral oxidative stress associated with human carotid endarterectomy can be attenuated by pretreatment with oral dipyridamole.

Cardiac reflections and natural vibrations: force-frequency relation recording system in the stress echo lab.

BackgroundThe inherent ability of ventricular myocardium to increase its force of contraction in response to an increase in contraction frequency is known as the cardiac force-frequency relation (FFR). This relation can be easily obtained in the stress echo lab, where the force is computed as the systolic pressure/end-systolic volume index ratio, and measured for increasing heart rates during stress. Ideally, the noninvasive, imaging independent, objective assessment of FFR would greatly enhance its practical appeal.Objectives1 – To evaluate the feasibility of the cardiac force measurement by a precordial cutaneous sensor. 2 – To build the curve of force variation as a function of the heart rate. 3 – To compare the standard stress echo results vs. this sensor operator-independent built FFR.MethodsThe transcutaneous force sensor was positioned in the precordial region in 88 consecutive patients referred for exercise, dipyridamole, or pacing stress. The force was measured as the myocardial vibrations amplitude in the isovolumic contraction period. FFR was computed as the curve of force variation as a function of heart rate. Standard echocardiographic FFR measurements were performed.ResultsA consistent FFR was obtained in all patients. Both the sensor built and the echo built FFR identifiy pts with normal or abnormal contractile reserve. The best cut-off value of the sensor built FFR was 15.5 g * 10-3 (Sensitivity = 0.85, Specificity = 0.77). Sensor built FFR slope and shape mirror pressure/volume relation during stress. This approach is extendable to daily physiological exercise and could be potentially attractive in home monitoring systems.

The impact of carotid plaque presence and morphology on mortality outcome in cardiological patients

BackgroundCarotid plaque severity and morphology can affect cardiovascular prognosis.We evaluate both the importance of echographically assessed carotid artery plaque geometry and morphology as predictors of death in hospitalised cardiological patients.Methods541 hospitalised patients admitted in a cardiological division (age = 66 ± 11 years, 411 men), have been studied through ultrasound Duplex carotid scan and successively followed-up for a median of 34 months. Echo evaluation assessed plaque severity and morphology (presence of heterogeneity and profile).Results361 patients showed carotid stenosis (67% with <50% stenosis, 18% with 50–69% stenosis, 9% with >70% stenosis, 4% with near occlusion and 2% with total occlusion). During the follow-up period, there were 83 all-cause deaths (15% of the total population). Using Coxs proportional hazard model, age (RR 1.06, 95% CI 1.03–1.09, p = 0.000), ejection fraction > 50% (RR = 0.62, 95% CI 0.4–0.96, p = 0.03), treatment with statins (RR = 0.52, 95% CI 0.29–0.95, p = 0.34) and the presence of a heterogeneous plaque (RR 1.6; 95% CI, 1.2 to 2.14, p = 0.002) were independent predictors of death. Kaplan – Meier survival estimates have shown the best outcome in patients without plaque, intermediate in patients with homogeneous plaques and the worst outcome in patients with heterogeneous plaques (90% vs 79% vs 73%, p = 0.0001).ConclusionIn hospitalised cardiological patients, carotid plaque presence and morphology assessed by ultrasound are independent predictors of death.

Dual-Imaging Stress Echocardiography for Prognostic Assessment of High-Risk Asymptomatic Patients with Diabetes Mellitus

Background: In patients with diabetes, the utility of diagnostic screening cardiac tests in subjects without clinical coronary artery disease remains controversial. The aim of this study was to assess the prognostic meaning of dual‐imaging stress echocardiography (conventional wall motion analysis and Doppler‐derived coronary flow velocity reserve [CFVR] of the left anterior descending coronary artery) in high‐risk asymptomatic individuals with diabetes. Methods: This was a prospective analysis of 230 asymptomatic patients with diabetes (128 men; mean age, 66 ± 9 years) with no clinical evidence of coronary artery disease, no Q waves or deep negative waves on the electrocardiogram, and no wall motion abnormalities on resting echocardiography. Of these subjects, 147 (64%) had target organ damage and 83 (36%) had two or more associated cardiovascular risk factors. All patients underwent dipyridamole stress echocardiography with CFVR assessment of the left anterior descending coronary artery by transthoracic Doppler, and test results were entered into a database at the time of testing for a clinical and outcome follow‐up (mean, 4.6 ± 2.7 years). Results: Inducible ischemia and reduced CFVR (≤2) were detected in six and 52 patients, respectively. A total of 54 subjects (23%) had abnormal test results (ischemia or reduced CFVR). During follow‐up, 39 major adverse cardiac events (MACEs) occurred: 22 hard events (18 deaths and four nonfatal myocardial infarctions) and 17 coronary revascularizations. The yearly incidence rates of hard events and MACEs in the entire study population were 2.1% and 3.6%, respectively. Abnormal test results were the only multivariate indicator of both hard events (hazard ratio, 3.69; 95% CI, 1.54–8.80) and MACEs (hazard ratio, 6.12; 95% CI, 3.22–11.62). Conclusions: Abnormal test results were obtained in one of four cases and were a strong and independent predictor of future hard events and MACEs.

Rhabdomyolysis in an HIV-infected patient following coronary angiography: case report and literature review

Rhabdomyolysis is a rare, but possible, complication of combination antiretroviral therapy (cART). We report a unique case of an HIV-positive patient on cART who came to our attention for suspected ischaemic heart disease. Coronary angiography was carried out and complicated in the following days by rhabdomyolysis. We discuss the possible links between rhabdomyolysis, iodinated contrast media and HAART.

Cognitive impairment and polidistrectual atherosclerotic disease in chylomicronemia syndrome: A case report

A case of chylomicronemia syndrome is reported in a 72-year-old male with distinctive features of chronic pancreatic damage, severe hypertriglyceridemia, polidistrectual atherosclerosis and premature cognitive impairment. Although the patient had a positive history for recurrent episodes of pancreatitis the characteristic lesions of the hyperchylomicronemia syndrome, such as eruptive xanthomas and lipemia retinalis, were not present and splenomegaly could not be documented due to a previous post-traumatic splenectomy. Based on clinical phenotype, an apolipoprotein C-II deficiency was excluded by a fresh plasma infusion test, in which clarification of the patient plasma was not obtained. The absence of changes in the lipoprotein electrophoretic plasma after heparin infusion can be secondary to a lipoprotein lipase deficiency, a rare genetic disorder with an incidence of one per million. In relation to the resistance to diet and drugs, plasma exchange therapy was performed. After 3 years of this treatment there was no significant progression of atherosclerosis.