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.)     

Sphingolipid therapy in myocardial ischemia–reperfusion injury

Sphingolipids are known to play a significant physiological role in cell growth, cell differentiation, and critical signal transduction pathways. Recent studies have demonstrated a significant role of sphingolipids and their metabolites in the pathogenesis of myocardial ischemia–reperfusion injury. Our laboratory has investigated the cytoprotective effects of N,N,N-trimethylsphingosine chloride (TMS), a stable N-methylated synthetic sphingolipid analogue on myocardial and hepatic ischemia–reperfusion injury in clinically relevant in vivo murine models of ischemia–reperfusion injury. TMS administered intravenously at the onset of ischemia reduced myocardial infarct size in the wild-type and obese (ob/ob) mice. Following myocardial I/R, there was an improvement in cardiac function in the wild-type mice. Additionally, TMS also decreased serum liver enzymes following hepatic I/R in wild-type mice. The cytoprotective effects did not extend to the ob/ob mice following hepatic I/R or to the db/db mice following both myocardial and hepatic I/R. Our data suggest that although TMS is cytoprotective following I/R in normal animals, the cytoprotective actions of TMS are largely attenuated in obese and diabetic animals which may be due to altered signaling mechanisms in these animal models. Here we review the therapeutic role of TMS and other sphingolipids in the pathogenesis of myocardial ischemia–reperfusion injury and their possible mechanisms of cardioprotection.     

Should patients with an incidental finding of focal myocardial 18FDG uptake be screened by myocardial perfusion scintigraphy?

PurposeFocal F-18-fluoro-deoxy-glucose uptake in the myocardium can be a sign of resting myocardial ischemia. The purpose of our study was to assess the relevance of performing myocardial perfusion scintigraphy to screen for myocardial ischemia in patients with an incidental finding of focal myocardial F-18-fluoro-deoxy-glucose uptake on a routine F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography.MethodsIn our retrospective multicentric study, patients were included if they had had an incidental finding of myocardial focal F-18-fluoro-deoxy-glucose uptake on a routine F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography and had also undergone myocardial perfusion scintigraphy within 3 months before or after the F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography. Patients with a pattern of ischemia or scar on the myocardial perfusion scintigraphy in the same territory as the focal F-18-fluoro-deoxy-glucose uptake were considered positive.ResultsSeven of the 34 included patients were positive, with an abnormality on the MPS data in the same territory as the focal myocardial F-18-fluoro-deoxy-glucose uptake. 2 of the 6 patients with focal F-18-fluoro-deoxy-glucose uptake in the left anterior descending vascular supply territory and 2 of the 4 patients with focal F-18-fluoro-deoxy-glucose uptake in the standard right coronary artery territory had an abnormal myocardial perfusion scintigraphy. All 12 patients with focal F-18-fluoro-deoxy-glucose uptake restricted to the basal anterolateral and basal inferolateral segments were negative.ConclusionPatients with an incidental finding of focal F-18-fluoro-deoxy-glucose uptake on a routine F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography may be considered as being at risk for coronary artery disease, when this uptake is multisegmentary in the same typical coronary territory and not restricted to the basal anterolateral and basal inferolateral segments.     

Is there an effect of ischemic conditioning on myocardial contractile function following acute myocardial ischemia/reperfusion injury?

Ischemic conditioning induces cardioprotection; the final infarct size following a myocardial ischemic event is reduced. However, whether ischemic conditioning has long-term beneficial effects on myocardial contractile function following such an ischemic event needs further elucidation. To date, ex vivo studies have shown that ischemic conditioning improves the contractile recovery of isolated ventricular papillary muscle or atrial trabeculae following simulated ischemia. However, in vivo animal studies and studies in patients undergoing elective cardiac surgery show conflicting results. At the subcellular level, it is known that ischemic conditioning improved energy metabolism, preserved mitochondrial respiration, ATP production, and Ca²⁺ homeostasis in isolated mitochondria from the myocardium. Ischemic conditioning also presents with post-translational modifications of proteins in the contractile machinery of the myocardium. The beneficial effects on myocardial contractile function need further elucidation. This article is part of a Special Issue entitled: The power of metabolism: Linking energy supply and demand to contractile function edited by Torsten Doenst, Michael Schwarzer and Christine Des Rosiers.     

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.     

Interferon-γ ablation exacerbates myocardial hypertrophy in diastolic heart failure

Diastolic heart failure (HF) accounts for up to 50% of all HF admissions, with hypertension being the major cause of diastolic HF. Hypertension is characterized by left ventricular (LV) hypertrophy (LVH). Proinflammatory cytokines are increased in LVH and hypertension, but it is unknown if they mediate the progression of hypertension-induced diastolic HF. We sought to determine if interferon-γ (IFNγ) plays a role in mediating the transition from hypertension-induced LVH to diastolic HF. Twelve-week old BALB/c (WT) and IFNγ-deficient (IFNγKO) mice underwent either saline (n = 12) or aldosterone (n = 16) infusion, uninephrectomy, and fed 1% salt water for 4 wk. Tail-cuff blood pressure, echocardiography, and gene/protein analyses were performed. Isolated adult rat ventricular myocytes were treated with IFNγ (250 U/ml) and/or aldosterone (1 μM). Hypertension was less marked in IFNγKO-aldosterone mice than in WT-aldosterone mice (127 ± 5 vs. 136 ± 4 mmHg; P < 0.01), despite more LVH (LV/body wt ratio: 4.9 ± 0.1 vs. 4.3 ± 0.1 mg/g) and worse diastolic dysfunction (peak early-to-late mitral inflow velocity ratio: 3.1 ± 0.1 vs. 2.8 ± 0.1). LV ejection fraction was no different between IFNγKO-aldosterone vs. WT-aldosterone mice. LV end systolic dimensions were decreased significantly in IFNγKO-aldosterone vs. WT-aldosterone hearts (1.12 ± 0.1 vs. 2.1 ± 0.3 mm). Myocardial fibrosis and collagen expression were increased in both IFNγKO-aldosterone and WT-aldosterone hearts. Myocardial autophagy was greater in IFNγKO-aldosterone than WT-aldosterone mice. Conversely, tumor necrosis factor-α and interleukin-10 expressions were increased only in WT-aldosterone hearts. Recombinant IFNγ attenuated cardiac hypertrophy in vivo and modulated aldosterone-induced hypertrophy and autophagy in cultured cardiomyocytes. Thus IFNγ is a regulator of cardiac hypertrophy in diastolic HF and modulates cardiomyocyte size possibly by regulating autophagy. These findings suggest that IFNγ may mediate adaptive downstream responses and challenge the concept that inflammatory cytokines mediate only adverse effects.     

Are there ventricle-specific postnatal maturational differences in myocardial beta-adrenoceptors?

Newborn hearts have restricted functional reserve and variable responsiveness to inotropes that could be partly due to differences in myocardial beta-adrenoceptors (beta-AR). To clarify this issue, this study documented ventricle-specific changes in myocardial beta-AR density and affinity during postnatal maturation. In vivo left and right ventricle (LV and RV, respectively) biopsies were obtained from newborn (3-day-old, n = 11), immature (14-day-old, n = 7), and adult (n = 6) pigs. Total beta-AR density (B(max), fmol/g) and dissociation constant (K(d), pmol/L) were determined by radioligand binding with I125 iodocyanopindolol. Overall, beta-AR B(max) in the LV significantly decreased with maturation. Interestingly, newborn animal hearts (LV and RV) subdivided into 2 groups: an adult-like low K(d) group with low B(max) and a fetal-like high K(d) group with high B(max), which were significantly different from one another. The high K(d) newborn group also had significantly higher K(d) and B(max) than both immature and adult hearts. Newborns had similar Bmax but higher Kd in the LV than the RV, whereas immature and adult hearts did not have ventricular differences. During maturation, beta-AR density decreased, whereas LV beta-AR binding affinity increased. Variable beta-AR maturity was also identified immediately post partum, which could potentially explain the newborn heart's variable responsiveness to inotropes. The subset of newborn hearts with lower binding affinity (reduced responsiveness) could also contribute to the newborn heart's overall reduction in functional reserve.     

Healing the diabetic heart: does myocardial preconditioning work?

Diabetes mellitus-associated ischemic heart disease is a major public burden in industrialized countries. Reperfusion to a previously ischemic myocardium is obligatory to reinstate its function prior to irreversible damage. However, reperfusion is considered ‘a double-edged sword’ as reperfusion per se could augment myocardial ischemic damage, known as myocardial ischemia-reperfusion (I/R) injury. The brief and repeated cycles of I/R given before a sustained ischemia and reperfusion are represented as ischemic preconditioning, which protects the heart from lethal I/R injury. Few studies have demonstrated preconditioning-mediated cardioprotection in the diabetic heart. In contrast, considerable number of studies suggests that myocardial defensive effects of preconditioning are abolished in the presence of chronic diabetes mellitus that raised questions over preconditioning effects in the diabetic heart. It is evidenced that chronic diabetes mellitus-associated deficit in survival pathways, impaired function of mito-K_ATP channels, MPTP opening and high oxidative stress play key roles in paradoxically suppressed cardioprotective effects of preconditioning in the diabetic heart. These controversial results open up a new area of research to identify potential mechanisms influencing disparities on preconditioning effects in diabetic hearts. In this review, we discussed first the discrepancies on the modulatory role of diabetes mellitus in I/R-induced myocardial injury. Following this, we addressed whether preconditioning could protect the diabetic heart against I/R-induced myocardial injury. Moreover, potential mechanisms pertaining to the attenuated cardioprotective effects of preconditioning in the diabetic heart have been delineated. These are important to be understood for better exploitation of preconditioning strategies in limiting I/R-induced myocardial injury in the diabetic heart.     

Erectile dysfunction after myocardial infarction--myth or a real problem?

Erectile dysfunction is a common problem whose relation to cardiovascular diseases has scientifically been proved, but it has not been studied sufficiently in patients recovering from myocardial infarction. The objective of this study was to establish the frequency of erectile dysfunction in patients recovering from myocardial infarction. We examined 89 patients (aged 30 to 75 years) included in the program of cardiac rehabilitation after myocardial infarction. The results were compared with 91 healthy examinees of the same age. Even 82% of the patients who recovered from myocardial infarction have problems with erectile dysfunction, compared to 42.9% of healthy examinees. The prevalence of erectile dysfunction increases with the age in both groups. In the group of patients recovering from myocardial infarction aged 30 do 39 years, the erectile dysfunction decreased after 6 months, while in other age subgroups and between controls, there were no significant changes in erectile dysfunction prevalence during the analysed time period. We concluded that erectile dysfunction is a significant problem in patients recovering from myocardial infarction. It should be recognized on time in order to provide a better life quality for the patient with a multidisciplinary approach.     

Singlet oxygen: a potential culprit in myocardial injury?

The purpose of this study was to explore the role of singlet oxygen in cardiovascular injury. To accomplish this objective, we investigated the effect of singlet oxygen [generated from photoactivation of rose-bengal] on the calcium transport and Ca²⁺-ATPase activity of cardiac sarcoplasmic reticulum and compared these results with those obtained by superoxide radical, hydrogen peroxide and hydroxyl radical. Isolated cardiac SR exposed to rose bengal (10 nM) irradiated at (560 nm) produced a significant inhibition of Ca ²⁺ uptake; from 2.27 ± 0.05 to 0.62 ± 0.05 µmol Ca⁺/mg.min (mean ± SE) (P < 0.01) and Ca²⁺-ATPase activity from 2.08 ± 0.05 µmol Pi/min. mg to 0.28 ± 0.04 µmol Pi/min. mg (mean ± SE) (P < 0.01). The inhibition of calcium uptake and Ca²⁺-ATPase activity by rose bengal derived activatedoxygen (singlet oxygen) was dependent on the duration of exposure and intensity of light. The singlet oxygen scavengers ascorbic acid and histidine significantly protected SR Ca²⁺-ATPase against rose bengal derived activated oxygen species but superoxide dismutase and catalase did not attenuate the inhibition. SDS-polyacrylamide gel electrophoresis of SR exposed to photoactivated rose bengal up to 14 min, demonstrated complete loss of Ca²⁺-ATPase monomer band which was significantly protected by histidine. Irradiation of rose bengal also caused an 18% loss of total sulfhydryl groups of SR. On the other hand, superoxide (generated from xanthine oxidase action on xanthine) and hydroxyl radical (0.5 mM H₂O₂ + Fe²⁺ -EDTA) as well as H₂O₂ (12 mM) were without any effect on the 97,000 dalton Ca²⁺-ATPase band ofsarcoplasmic reticulum. The results suggest that oxidative damage of cardiac sarcoplasmic reticulum may be mediated by singlet oxygen. This may represent an important mechanism by which the oxidative injury to the myocardium induces both a loss of tension development and arrhythmogenesis.     

Optimal pharmacological therapy in ST-elevation myocardial infarction—a review

Antithrombotic therapy is an essential component in the optimisation of clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. There are currently several intravenous anticoagulant drugs available for primary percutaneous coronary intervention. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. However, these effective treatment strategies may be associated with bleeding complications. Compared with clopidogrel, prasugrel and ticagrelor are more potent and predictable, which translates into better clinical outcomes. Therefore, these agents are the first-line treatment in primary percutaneous coronary intervention. However, patients can still experience adverse ischaemic events, which might be in part attributed to alternative pathways triggering thrombosis. In this review, we provide a critical and updated review of currently available antithrombotic therapies used in patients with STEMI undergoing primary PCI. Finding a balance that minimises both thrombotic and bleeding risk is difficult, but crucial. Further randomised trials for this optimal balance are needed.     

Ablation of cereblon attenuates myocardial ischemia–reperfusion injury

Cereblon (CRBN) was originally identified as a target protein for a mild type of mental retardation in humans. However, recent studies showed that CRBN acts as a negative regulator of AMP-activated protein kinase (AMPK) by binding directly to the AMPK catalytic subunit. Because AMPK is implicated in myocardial ischemia–reperfusion (I–R) injury, we reasoned that CRBN might play a role in the pathology of myocardial I–R through regulation of AMPK activity. To test this hypothesis, wild-type (WT) and crbn knockout (KO) mice were subjected to I–R (complete ligation of the coronary artery for 30 min followed by 24 h of reperfusion). We found significantly smaller infarct sizes and less fibrosis in the hearts of KO mice than in those of WT mice. Apoptosis was also significantly reduced in the KO mice compared with that in WT mice, as shown by the reduced numbers of TUNEL-positive cells. In parallel, AMPK activity remained at normal levels in KO mice undergoing I–R, whereas it was significantly reduced in WT mice under the same conditions. In rat neonatal cardiomyocytes, overexpression of CRBN significantly reduced AMPK activity, as demonstrated by reductions in both phosphorylation levels of AMPK and the expression of its downstream target genes. Collectively, these data demonstrate that CRBN plays an important role in myocardial I–R injury through modulation of AMPK activity.     

&quot;Mushroom cloud&quot;: a giant left ventricular pseudoaneurysm after a myocardial infarction due to myocardial bridging – a case report

Left ventricular pseudoaneurysm is an uncommon complication after transmural myocardial infarction, occurring when a free wall rupture is contained by adhesions of the overlying pericardium preventing acute tamponade. In this report, an unusual case of a 61 year-old male with a giant apical left ventricular pseudoaneurysm after an unnoticed myocardial infarction is presented. On coronary angiogram myocardial bridging of the distal left anterior descending artery was judged to be the infarct related lesion. The echocardiographic diagnosis allowed for a timely surgical intervention which resulted in the patient's full recovery.     

PIAS1 protects against myocardial ischemia-reperfusion injury by stimulating PPARγ SUMOylation

Background

Myocardial ischemia-reperfusion injury (IRI) has become one of the most serious complications after reperfusion therapy in patients with acute myocardial infarction. Small ubiquitin-like modification (SUMOylation) is a reversible process, including SUMO E1-, E2-, and E3-mediated SUMOylation and SUMO-specific protease-mediated deSUMOylation, with the latter having been shown to play a vital role in myocardial IRI previously. However, little is known about the function and regulation of SUMO E3 ligases in myocardial IRI.

Results

In this study, we found dramatically decreased expression of PIAS1 after ischemia/reperfusion (I/R) in mouse myocardium and H9C2 cells. PIAS1 deficiency aggravated apoptosis and inflammation of cardiomyocytes via activating the NF-κB pathway after I/R. Mechanistically, we identified PIAS1 as a specific E3 ligase for PPARγ SUMOylation. Moreover, H9C2 cells treated with hypoxia/reoxygenation (H/R) displayed reduced PPARγ SUMOylation as a result of down-regulated PIAS1, and act an anti-apoptotic and anti-inflammatory function through repressing NF-κB activity. Finally, overexpression of PIAS1 in H9C2 cells could remarkably ameliorate I/R injury.

Conclusions

Collectively, our findings demonstrate the crucial role of PIAS1-mediated PPARγ SUMOylation in protecting against myocardial IRI.