Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis: is it safe?

To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias (VT, ≥4 successive PVCs) was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control n = 8 vs. BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE.     

High mean platelet volume after myocardial infarction: is it due to consumption of small platelets?

Seventy nine men surviving after sustaining a myocardial infarction in 1982, and who had at that time had raised mean platelet volumes compared with controls, were followed up after 18 months. The shape of each man''s platelet distribution curve was calculated from the mean platelet volume, platelet count, and platelet distribution width. The calculated curves were in close agreement with the curves plotted by the Coulter counter from the raw data. These curves did not differ significantly from those of a current control group, but the curves plotted from the variables measured at the time of myocardial infarction in 1982 showed a deficit of platelets in the volume range 5-12 fl amounting at maximum to 30% (p less than 0.0001); there were no significant differences above 12 fl. The deficit of small platelets became more appreciable during initial admission, was less at one month''s follow up, and had disappeared at one year. The deficit of small platelets is probably an effect rather than a cause of infarction.     

β Blockade after myocardial infarction: systematic review and meta regression analysis

ObjectivesTo assess the effectiveness of β blockers in short term treatment for acute myocardial infarction and in longer term secondary prevention; to examine predictive factors that may influence outcome and therefore choice of drug; and to examine the clinical importance of the results in the light of current treatment.DesignSystematic review of randomised controlled trials.SettingRandomised controlled trials.SubjectsPatients with acute or past myocardial infarction.Interventionβ Blockers compared with control.Mainoutcome measures All cause mortality and non-fatal reinfarction.ResultsOverall, 5477 of 54 234 patients (10.1%) randomised to β blockers or control died. We identified a 23% reduction in the odds of death in long term trials (95% confidence interval 15% to 31%), but only a 4% reduction in the odds of death in short term trials (−8% to 15%). Meta regression in long term trials did not identify a significant reduction in effectiveness in drugs with cardioselectivity but did identify a near significant trend towards decreased benefit in drugs with intrinsic sympathomimetic activity. Most evidence is available for propranolol, timolol, and metoprolol. In long term trials, the number needed to treat for 2 years to avoid a death is 42, which compares favourably with other treatments for patients with acute or past myocardial infarction.Conclusionsβ Blockers are effective in long term secondary prevention after myocardial infarction, but they are underused in such cases and lead to avoidable mortality and morbidity.

Key messages

• The first randomised trials of β blockade in secondary prevention after myocardial infarction were published in the 1960s
• β blockers were once heralded as a major advance, but their use for secondary prevention has declined in recent years
• Firm evidence shows that long term β blockade remains an effective and well tolerated treatment that reduces mortality and morbidity in unselected patients after myocardial infarction
• The benefits from β blockade compare favourably with other drug treatments for this patient group
• Most evidence is for propranolol, timolol, and metoprolol, whereas atenolol, which is commonly used, is inadequately evaluated for long term use

     

The relation between myocardial blush grade and myocardial contrast echocardiography: which one is a better predictor of myocardial damage?

Background. Myocardial blush grade (MBG) and myocardial contrast echocardiography (MCE) are both indices for myocardial perfusion in patients with ST-elevation acute myocardial infarction (STEMI). We aimed to compare MBG with MCE in the infarct-related artery segment for assessing infarct size in patients with STEMI treated with primary percutaneous coronary intervention (PCI).Methods. 43 patients underwent successful (postprocedural TIMI flow 3) primary PCI for STEMI. MBG was assessed at the end of the PCI procedure and MCE was assessed 1.7±1.8 days after PCI. Enzymatic infarct size was estimated by measurementof enzyme activities by using lactate dehydrogenase (LDH) as the referenceenzyme. Cumulative enzyme release (LDHQ₄₈) from at least five serial measurements up to 48 hours after symptom onset was calculated. Also peak creatine kinase, CK-MB and peak LDH were measured.Results. MBG 0/1, 2 and 3 were observed in 14, 12 and 17 patients, respectively, and was compared with tertiles of MCE. We found a parallel correlation between both MBG and MCE and LDHQ₄₈. However, there was no correlation between MCE and MBG. Patients with both normal MCE and a normal MBG had least myocardial damage and those with both impaired MCE and an impaired MBG had most myocardial damage.Conclusion. Both MBG and MCE are good predictors of infarct size in STEMI patients treated with PCI. However, these markers are not mutually related, possibly due to time-related changes in myocardial perfusion. Combining these two markers may yield a more accurate prediction of final myocardial damage. (Neth Heart J 2010;18:25-30.)     

The role of the Golgi apparatus in oxidative stress: is this organelle less significant than mitochondria?

Reactive oxygen species (ROS)/reactive nitrogen species (RNS) and ROS/RNS-mediated oxidative stress have well-established roles in many physiological and pathological processes and are associated with the pathogenesis of many diseases, such as hypertension, ischemia/reperfusion injury, diabetes mellitus, atherosclerosis, stroke, cancer, and neurodegenerative disorders. It is generally accepted that mitochondria play an essential role in oxidative stress because they are responsible for the primary generation of superoxide radicals. Little attention, however, has been paid to the importance of the Golgi apparatus (GA) in this process. The GA is a pivotal organelle in cell metabolism and participates in modifying, sorting, and packaging macromolecules for cell secretion or use within the cell. It is inevitably involved in the process of oxidative stress, which can cause modification and damage of lipids, proteins, DNA, and other structural constituents. Here we discuss the connections between the GA and oxidative stress and highlight the role of the GA in oxidative stress-related Ca(2+)/Mn(2+) homeostasis, cell apoptosis, sphingolipid metabolism, signal transduction, and antioxidation. We also provide a novel perspective on the subcellular significance of oxidative stress and its pathological implications and present "GA stress" as a new concept to explain the GA-specific stress response.     

Smac mimetics and TNFalpha: a dangerous liaison?

Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et al., 2007), now report that Smac mimetics primarily kill cancer cells via a different mechanism, the induction of autoubiquitination and degradation of cIAPs, which culminates in TNFalpha-mediated cell death.     

The economy of inflammation: when is less more?

In ecology, tolerance of parasites refers to host mitigation of the fitness costs of an infection. This concept of parasite tolerance contrasts with resistance, whereby hosts reduce the intensity of an infection. Anti-inflammatory cells and molecules have been implicated as mechanisms of parasite tolerance, suggesting that a major role of tolerance is in minimizing collateral damage associated with inflammation. A framework is proposed here in which the cost-benefit outcome of an inflammatory host-response is hypothesized to be dependent on host life-history, parasite virulence, and the efficacy of a current inflammatory or anti-inflammatory response. Testable predictions, both within and among host species, are presented for this hypothesis.     

Are patients with non-ST elevation myocardial infarction undertreated?

Background

We have previously documented significant differences in orthogonal P wave morphology between patients with and without paroxysmal atrial fibrillation (PAF). However, there exists little data concerning normal P wave morphology. This study was aimed at exploring orthogonal P wave morphology and its variations in healthy subjects.

Methods

120 healthy volunteers were included, evenly distributed in decades from 20–80 years of age; 60 men (age 50+/-17) and 60 women (50+/-16). Six-minute long 12-lead ECG registrations were acquired and transformed into orthogonal leads. Using a previously described P wave triggered P wave signal averaging method we were able to compare similarities and differences in P wave morphologies.

Results

Orthogonal P wave morphology in healthy individuals was predominately positive in Leads X and Y. In Lead Z, one third had negative morphology and two-thirds a biphasic one with a transition from negative to positive. The latter P wave morphology type was significantly more common after the age of 50 (P < 0.01). P wave duration (PWD) increased with age being slightly longer in subjects older than 50 (121+/-13 ms vs. 128+/-12 ms, P < 0.005). Minimal intraindividual variation of P wave morphology was observed.

Conclusion

Changes of signal averaged orthogonal P wave morphology (biphasic signal in Lead Z), earlier reported in PAF patients, are common in healthy subjects and appear predominantly after the age of 50. Subtle age-related prolongation of PWD is unlikely to be sufficient as a sole explanation of this finding that is thought to represent interatrial conduction disturbances. To serve as future reference, P wave morphology parameters of the healthy subjects are provided.     

The Medawar Lecture 1998 is science dangerous?

The idea that science is dangerous is deeply embedded in our culture, particularly in literature, yet science provides the best way of understanding the world. Science is not the same as technology. In contrast to technology, reliable scientific knowledge is value-free and has no moral or ethical value. Scientists are not responsible for the technological applications of science; the very nature of science is that it is not possible to predict what will be discovered or how these discoveries could be applied. The obligation of scientists is to make public both any social implications of their work and its technological applications. A rare case of immoral science was eugenics. The image of Frankenstein has been turned by the media into genetic pornography, but neither cloning nor stem cells or gene therapy raise new ethical issues. There are no areas of research that are so socially sensitive that research into them should be proscribed. We have to rely on the many institutions of a democratic society: parliament, a free and vigorous press, affected groups and the scientists themselves. That is why programmes for the public understanding of science are so important. Alas, we still do not know how best to do this.     

Carbohydrates: is the advice to eat less justified for diabetes and cardiovascular health?

PURPOSE OF REVIEW: Recent randomized controlled trials examining diets of varying carbohydrate composition recommended for people with diabetes and cardiovascular disease and those at risk are summarized. RECENT FINDINGS: Severe carbohydrate restriction results in appreciable initial weight loss and improvement in risk factors. After a year, however, the beneficial effects are equal to or less than those achieved on conventional alternatives. Some people develop elevations of LDL cholesterol. Modest carbohydrate restriction with relatively high intakes of cis-unsaturated fatty acids and protein is acceptable to many people and is more likely to produce sustained benefit in terms of weight loss and cardiovascular risk indicators. SUMMARY: Diets involving moderate carbohydrate restriction are suitable alternatives to high-carbohydrate, high-fibre diets for weight loss and reduction of cardiovascular disease and diabetes risk, as well as to treat individuals with the conditions. As such diets are generally high in protein and unsaturated fatty acids, they are not recommended for those with established or incipient nephropathy. High-carbohydrate, high-fibre diets remain appropriate for use in all those situations, provided carbohydrate is derived principally from minimally processed wholegrain breads and cereals and intact vegetables and fruit. Lower carbohydrate options may be preferable for markedly insulin-resistant individuals.