Acute myocardial uptake of digoxin in humans: Correlation with hemodynamic and electrocardiographic effects

Acute myocardial uptake of digoxin was measured at a constant paced heart rate (75 beats/min) for 30 min after an intravenous bolus injection of 500 µg of digoxin in 14 patients with ischemic heart disease. Myocardial digoxin content, determined by serial measurement of aortocoronary sinus digoxin concentration gradients and coronary sinus blood flow, was expressed relative to coronary sinus blood flow at rest and correlated with simultaneous hemodynamic and electrocardiographic changes.Myocardial digoxin uptake was extensive (4.1 ± 0.7% of total injected dose at 30 min) and prolonged, with rapid initial uptake (75.3 ± 6.6% of maximum at 3 min), followed by a variable phase of slower accumulation. Peak left ventricular positive first derivative of left ventricular pressure (dP/dt) increased progressively (p < 0.01), with a similar time course to that of myocardial digoxin accumu- lation; maximal change was 18.5 ± 4.7% at 27 min. The ratio of inotropic effect to myocardial digoxin content did not vary significantly over the period of the experiment. However, peak inotropic effects in individual patients were not significantly related to peak myocardial digoxin content. The spontaneous PR interval increased transiently, with a peak increase of 5.9 ± 1.8% (p < 0.05) 12 min after digoxin administration.It is concluded that after intravenous bolus administration, 1) peak effects of digoxin on atrioventricular (AV) conduction occur early, whereas positive inotropic effects increase progressively for ≥27 min; and 2) digoxin accumulation in the human myocardium is prolonged and is a determinant of inotropic effects, but not of prolongation of AV node conduction

The second Euro Heart Survey on acute coronary syndromes: characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004

Aims Our study aimed to examine the management of acute coronary syndromes (ACS) in Europe and the Mediterranean basin, and to compare adherence to guidelines with that reported in the first Euro Heart Survey on ACS (EHS-ACS-I), 4 years earlier. Methods and results In a prospective survey conducted in 2004 (EHS-ACS-II), data describing the characteristics, treatment, and outcome of 6385 patients diagnosed with ACS in 190 medical centres in 32 countries were collected. ACS with ST-elevation was the initial diagnosis in 47% of patients, no ST-elevation in 48%, and undetermined electrocardiographic pattern in 5% of patients. Comparison of data collected in 2000 and 2004 showed similar baseline characteristics, but greater use of recommended medications and coronary interventions in EHS-ACS-II. Among patients with ST-elevation, the use of primary reperfusion increased slightly (from 56 to 64%), with a significant shift from fibrinolytic therapy to primary percutaneous coronary intervention (PPCI). The use of PPCI rose from 37 to 59% among those undergoing primary reperfusion therapy. Analysis of data in 34 centres that participated in both surveys showed even greater improvement with respect to the use of recommended medical therapy, interventions, and outcome. Conclusion Data from EHS-ACS-II suggest an increase in adherence to guidelines for treatment of ACS in comparison with EHS-ACS-I

Heat Acclimatization Protects the Left Ventricle from Increased Diastolic Chamber Stiffness Immediately after Coronary Artery Bypass Surgery: A Lesson from 30 Years of Studies on Heat Acclimation Mediated Cross Tolerance

During the period of 1986–1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rat's heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17–33°C) vs. patients in colder weather (spring in non-desert areas, 6–19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing “heat acclimatization combined with exercise training” were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance

Targeted anti-inflammatory systemic therapy for restenosis: The Biorest Liposomal Alendronate with Stenting sTudy (BLAST)—a double blind, randomized clinical trial

Background Activation of systemic innate immunity is critical in the chain of events leading to restenosis. LABR-312 is a novel compound that transiently modulates circulating monocytes, reducing accumulation of these cells at vascular injury sites and around stent struts. The purpose of the study was to examine the safety and efficacy of a single intravenous bolus of LABR-312 in reducing restenosis in patients treated for coronary narrowing. Patient response was examined in light of differential inflammatory states as evidenced by baseline circulating monocyte levels, diabetes mellitus, and acute coronary syndrome. Methods BLAST is a Phase II prospective, randomized, multicenter, double-blind, placebo-controlled trial that assessed the safety and efficacy of LABR-312. Patients were randomized to receive LABR-312 at 2 dose levels or placebo as an intravenous infusion during percutaneous coronary intervention and bare metal stent implantation. The primary end point was mean angiographic in-stent late loss at 6 months. Results Patients (N = 225) were enrolled at 12 centers. There were no safety concerns associated with the study drug. For the overall cohort, there were no differences between the groups in the primary efficacy end point (in-stent late loss of 0.86 ± 0.60 mm, 0.83 ± 0.57 mm, and 0.81 ± 0.68 mm for the placebo, low-dose, and high-dose group, respectively; P = not significant for all comparisons). In the prespecified subgroups of patients with a baseline proinflammatory state, patients with diabetes mellitus, and patients with high baseline monocyte count, there was a significant treatment effect. Conclusions Intravenous administration of LABR-312 to patients undergoing percutaneous coronary intervention is safe and effectively modulates monocyte behavior. The average late loss did not differ between the treatment and placebo groups. However, in the inflammatory patient group with baseline monocyte count higher than the median value, there was a significant reduction in late loss with LABR-312.BIOrest Ltd

ESC Committe for Practice Guideline (CPG). Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology.

The combination of the aging of the population in many countries, and improved survival after acute myocardial infarction has created a rapid growth in the number of patients currently living with chronic heart failure, with a concomitant increase in the number of hospitalizations for decompensated heart failure and of the episodes of acute heart failure. These guidelines were the first to describe the rationale behind the diagnosis and treatment of acute heart failure in the adult populatio