A pragmatic approach for mortality prediction after surgery in infective endocarditis: optimizing and refining EuroSCORE.

OBJECTIVE: To simplify and optimize the ability of EuroSCORE I and II to predict early mortality after surgery for infective endocarditis (IE). METHODS: Multicentre retrospective study (n = 775). Simplified scores, eliminating irrelevant variables, and new specific scores, adding specific IE variables, were created. The performance of the original, recalibrated and specific EuroSCOREs was assessed by Brier score, C-statistic and calibration plot in bootstrap samples. The Net Reclassification Index was quantified. RESULTS: Recalibrated scores including age, previous cardiac surgery, critical preoperative state, New York Heart Association >I, and emergent surgery (EuroSCORE I and II); renal failure and pulmonary hypertension (EuroSCORE I); and urgent surgery (EuroSCORE II) performed better than the original EuroSCOREs (Brier original and recalibrated: EuroSCORE I: 0.1770 and 0.1667; EuroSCORE II: 0.2307 and 0.1680). Performance improved with the addition of fistula, staphylococci and mitral location (EuroSCORE I and II) (Brier specific: EuroSCORE I 0.1587, EuroSCORE II 0.1592). Discrimination improved in specific models (C-statistic original, recalibrated and specific: EuroSCORE I: 0.7340, 0.7471 and 0.7728; EuroSCORE II: 0.7442, 0.7423 and 0.7700). Calibration improved in both EuroSCORE I models (intercept 0.295, slope 0.829 (original); intercept -0.094, slope 0.888 (recalibrated); intercept -0.059, slope 0.925 (specific)) but only in specific EuroSCORE II model (intercept 2.554, slope 1.114 (original); intercept -0.260, slope 0.703 (recalibrated); intercept -0.053, slope 0.930 (specific)). Net Reclassification Index was 5.1% and 20.3% for the specific EuroSCORE I and II. CONCLUSIONS: The use of simplified EuroSCORE I and EuroSCORE II models in IE with the addition of specific variables may lead to simpler and more accurate models.

Cardiac complications during pregnancy are better predicted with the modified WHO risk score.

BACKGROUND/OBJECTIVE: Several risk scores (RSs) have been used to stratify risk of cardiac complications (CCs) in pregnant patients with heart disease. We aimed to compare and contrast the accuracy of several RSs for predicting CC in this population. METHODS: Prospective inclusion of all consecutive pregnant patients with heart disease, and follow-up until 6 months postpartum. CCs were defined as primary if admission was required due to heart failure, arrhythmia or thromboembolic events, and secondary if the decline in NYHA class compared with baseline was >2 or urgent invasive cardiac procedures were needed. The discriminatory power of each RS was assessed by the area-under-the receiver-operating characteristic (ROC) curve (AUC). RESULTS: 179 patients, mean age: 32 years, accounted for 13.4% of CC (primary 11.7%, secondary 1.7%); the main diagnosis was congenital heart disease (CHD) in 68% followed by valvulopathies in 16%, arrhythmia in 7% and myocardiopathies in 5%. 22% (n=40) were classified as mWHO=1, 59% (n=105) mWHO=2 including subgroup 2-3, 14% (n=26) mWHO=3 and 4%(n=7) mWHO=4; 1 patient was unclassifiable. mWHO showed a better AUC (0.763) than CARPREG (0.67). For the CHD population, ZAHARA RS showed an AUC of 0.74, and Khairy an AUC of 0.632. CONCLUSIONS: mWHO was better at predicting CC than CARPREG; mWHO was also better at predicting CC than the specific CHD RS in the CHD subgroup. PRACTICE: There are an increasing number of pregnant women with HD. IMPLICATIONS: Improved prediction of CC risk during pregnancy can provide better preconception assessment in women with HD.

[SPECT, coronary angio-CT, invasive coronary angiography and fusion images in stable coronary disease]. / SPECT, angio-TC coronaria, coronariografía invasiva e imágenes de fusión en la cardiopatía isquémica estable.

OBJECTIVES: To evaluate the usefulness of the information obtained with SPECT, coronary angio-CT and fusion images, in patients with stable ischemic disease who need invasive coronary angiography (IA). MATERIAL AND METHODS: Forty-six patients (65.98±8.3 years) with coronary disease were prospectively included. The fusion images generated after undergoing IA were used to evaluate the performance of these techniques in the diagnosis of multi-vessel coronary disease, the detection of the culprit vessel and the therapeutic management of these patients. RESULTS: In the IA, 29 of the 46 patients (63%) had multi-vessel disease. SPECT could detect it in 48.2% and coronary angio-CT could detect it in 89.6%. Concordance between coronary angio-CT and IA in the diagnosis of the culprit vessel was 77% (kappa 0.6), and between SPECT and IA it was 73% (kappa 0.56). Although fusion images could have been obtained prior to IA, they would not have changed the therapeutic approach derived from SPECT and IA. CONCLUSIONS: Coronary angio-CT has a high ability for the diagnosis of multi-vessel disease and the culprit lesion, and SPECT is a good functional complement of the IA in the detection of the most ischemic territory. However, the performance of fusion images in patients with stable ischemic disease, who have undergone a SPECT as the first non-invasive study and need IA, does not seem indicated because they would not have changed the therapeutic management derived from SPECT and IA information.

[Obtaining a formula that improves maximum oxygen consumption estimation in cycle ergometer exercise tests]. / Obtención de una fórmula que mejora la estimación del consumo máximo de oxígeno en las pruebas de esfuerzo con bicicleta ergométrica.

OBJECTIVES: To evaluate if the estimation of the maximal oxygen consumption (MO2C) in METs (metabolic equivalents) by means of the table proposed in the guidelines of the Spanish Society of Cardiology is a sufficiently reliable method when applied to the bicycle exercise test. MATERIAL AND METHODS: The MO2C in METs was obtained by gas-exchange analysis on bicycle ergometer tests in 97 healthy subjects (group i). It was compared with the estimate of METs using the table in which only watts and patient's weight were included. A better-adjusted formula was validated in 289 subjects with normal exercise myocardial perfusion gated-SPECT (group ii) using the introduction of clinical and ergometric variables. RESULTS: In group i individuals a good correlation between METs estimated with the table and those obtained through gas-exchange analysis (CCI: 0.93) was observed. However, the best adjusted formula to estimate METs in group ii subjects included watts, body mass index (BMI), age and gender (METS=11.820-0.054×age-0.189×BMI+1.031×gender+0.020×watts) (women: 0, men: 1). This formula allowed the reclassification of 46.9% of group ii subjects into the category <5METs versus the estimation by table. CONCLUSIONS: Estimating the METs with the conventional table is reliable. However, the best adjustment in subjects with normal bicycle exercise SPECT was obtained when, in addition to watts and BMI, age and gender were also considered.

Defective sarcoplasmic reticulum-mitochondria calcium exchange in aged mouse myocardium.

Mitochondrial alterations are critically involved in increased vulnerability to disease during aging. We investigated the contribution of mitochondria-sarcoplasmic reticulum (SR) communication in cardiomyocyte functional alterations during aging. Heart function (echocardiography) and ATP/phosphocreatine (NMR spectroscopy) were preserved in hearts from old mice (>20 months) with respect to young mice (5-6 months). Mitochondrial membrane potential and resting O2 consumption were similar in mitochondria from young and old hearts. However, maximal ADP-stimulated O2 consumption was specifically reduced in interfibrillar mitochondria from aged hearts. Second generation proteomics disclosed an increased mitochondrial protein oxidation in advanced age. Because energy production and oxidative status are regulated by mitochondrial Ca2+, we investigated the effect of age on mitochondrial Ca2+ uptake. Although no age-dependent differences were found in Ca2+ uptake kinetics in isolated mitochondria, mitochondrial Ca2+ uptake secondary to SR Ca2+ release was significantly reduced in cardiomyocytes from old hearts, and this effect was associated with decreased NAD(P)H regeneration and increased mitochondrial ROS upon increased contractile activity. Immunofluorescence and proximity ligation assay identified the defective communication between mitochondrial voltage-dependent anion channel and SR ryanodine receptor (RyR) in cardiomyocytes from aged hearts associated with altered Ca2+ handling. Age-dependent alterations in SR Ca2+ transfer to mitochondria and in Ca2+ handling could be reproduced in cardiomyoctes from young hearts after interorganelle disruption with colchicine, at concentrations that had no effect in aged cardiomyocytes or isolated mitochondria. Thus, defective SR-mitochondria communication underlies inefficient interorganelle Ca2+ exchange that contributes to energy demand/supply mistmach and oxidative stress in the aged heart.

RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-α in cardiac ischaemia/reperfusion injury.

Despite optimal therapy, the morbidity and mortality of patients presenting with an acute myocardial infarction (MI) remain significant, and the initial mechanistic trigger of myocardial "ischaemia/reperfusion (I/R) injury" remains greatly unexplained. Here we show that factors released from the damaged cardiac tissue itself, in particular extracellular RNA (eRNA) and tumour-necrosis-factor α (TNF-α), may dictate I/R injury. In an experimental in vivo mouse model of myocardial I/R as well as in the isolated I/R Langendorff-perfused rat heart, cardiomyocyte death was induced by eRNA and TNF-α. Moreover, TNF-α promoted further eRNA release especially under hypoxia, feeding a vicious cell damaging cycle during I/R with the massive production of oxygen radicals, mitochondrial obstruction, decrease in antioxidant enzymes and decline of cardiomyocyte functions. The administration of RNase1 significantly decreased myocardial infarction in both experimental models. This regimen allowed the reduction in cytokine release, normalisation of antioxidant enzymes as well as preservation of cardiac tissue. Thus, RNase1 administration provides a novel therapeutic regimen to interfere with the adverse eRNA-TNF-α interplay and significantly reduces or prevents the pathological outcome of ischaemic heart disease.

[Variables that influence the indication of a second myocardial perfusion gated-SPECT after a normal stress-rest gated SPECT]. / Variables que influyen en la indicación de una segunda gated-SPECT de perfusión miocárdica después una gated-SPECTde estrés-reposo normal.

OBJECTIVE: The objective of this study was to investigate predictor variables at the moment of normal stress-rest myocardial perfusion gated SPECT for indication of a second gated SPECT. MATERIAL AND METHODS: A prospective, single center cohort study was conducted. We evaluated 2326 consecutive patients (age 63.6 ± 13 years, 57.3% females) without perfusion defects and with normal left ventricular ejection fraction on a myocardial perfusion gated SPECT. Clinical and stress test variables were studied to predict indication of a second gated SPECT and presence of reversible perfusion defects in the second gated SPECT. RESULTS: During a mean follow-up of 3.6 ± 2 years a second gated SPECT was performed in 286 patients (12.3%). Independent predictor variables of a second gated SPECT were presence of three or more cardiovascular risk factors (χ(2): 5.510; HR: 1.4; p=0.019), previous acute myocardial infarction (χ(2): 3.867; HR: 1.4; p=0.049), previous coronary revascularization (χ(2): 41.081; HR: 2.5; p<0.001), and a positive stress test (χ(2): 8.713; HR: 1.5; p=0.003). Observation of perfusion defects in the 280 patients in whom a second stress-rest gated SPECT was performed was more likely in male patients (χ(2): 4.322; HR: 1.9; p=0.038) who had a first pure pharmacological gated-SPECT (χ(2): 7.182; HR: 2.6; p=0.007). CONCLUSIONS: In patients with a first normal myocardial perfusion gated SPECT, various clinical factors and variables derived from the stress test affect the indication of a second gated SPECT and the presence of ischemia in the latter.

[Analysis of the diastolic function by myocardial perfusion gated SPECT after coronary revascularization in acute myocardial infarction]. / Análisis de la función diastólica mediante gated-SPECT de perfusión miocárdica tras revascularización coronaria en el infarto agudo de miocardio.

OBJECTIVE: To evaluate the evolutive changes in diastolic function after percutaneous coronary revascularization (PCR) in acute myocardial infarction (AMI), using myocardial perfusion gated SPECT. METHODS: Thirty-two patients (mean 61.9±9.7 years, 7 women) were studied by two at rest gated SPECT: the first gated-SPECT-1 was performed with an injection of a dose of (99m)Tc-tetrofosmin prior to PCR and the second gated-SPECT-2 between the fourth and fifth weeks after AMI. Changes of peak filling rate (PFR) and the time to peak filling rate (TTPF) were assessed between both studies, and were related to the extent of salvaged myocardium (SM), end-diastolic (EDV) and end-systolic (ESV) volumes, and left ventricular ejection fraction (LVEF) changes. RESULTS: An improvement was observed in diastolic function parameters Gated-SPECT-2: PFR increased significantly (P=0.011) while the TTPF decreased without reaching statistical significance (P=0.288). In multivariate analysis, adjusted by clinical and coronary variables, improvement of PFR was significantly associated with percentage of SM (P=0.030), increase in LVEF (P=0.004) and with ESV volume reduction (P=0.005). Improvement of TTPF was only related significantly to the percentage of SM (P=0.046). PFR increased 0.01 EDV/sec. and TTPF decreased 1.14ms for each cm(2) increase of the area of SM. CONCLUSIONS: After PCR in AMI, the myocardial perfusion gated SPECT makes it possible to assess the significant improvement in diastolic function mainly related to the amount of MS.

[Impact of myocardial perfusion gated-SPECT on the decision to perform coronary angiography in patients with left ventricular dysfunction of ischemic origin]. / Impacto de la gated-SPECT de perfusión miocárdica en la indicación de una coronariografía en pacientes con disfunción ventricular izquierda de origen isquémico.

OBJECTIVES: The aim of this study was to analyze how the myocardial perfusion gated-SPECT (Single Photon Emission Computed Tomography) influences the practice of a coronary angiography in patients with ischemic cardiomyopathy (IM). PATIENTS AND METHODS: A total of 120 consecutive patients (mean age: 64.9±11.5 years, 25 female) with IM (left ventricular ejection fraction ≤40%) and without previous coronary angiography were evaluated by myocardial perfusion gated-SPECT (96 stress-rest and 24 only at rest). The ventricular ejection fraction (EF) was obtained at rest by gated-SPECT in all patients. The ischemic origin of the systolic dysfunction was established by means of coronary angiography in 64 patients and by previous myocardial infarction in the rest. Gated-SPECT results of these 64 patients were compared with those of 56 patients in whom coronary angiography had not been indicated. RESULT: Scintigraphic myocardial ischemia (HR: 5.2; CI 95%: 2.68 to 10.35) in patients who were able to perform the stress-rest test) and who had severely impaired EF (<30%) (HR: 0.9; CI 95%: 0.89 to 0.99) were the best independent predictors of coronary angiography. On the contrary, scintigraphic criteria of viability were not a determinant, from the statistical point of view, of coronary angiography in this series. CONCLUSIONS: In patients with IM, demonstration of ischemia and severe reduction of the EF, but not detection of viable myocardium, prompted the performance of coronary angiography.

[Short exercise-rest versus long myocardial perfusion gated SPECT protocols in patients with ischemic cardiomyopathy]. / Protocolo corto esfuerzo reposo frente a protocolo largo en la gated-SPECT de perfusión miocárdica de pacientes con miocardiopatía isquémica.

OBJECTIVE: The purpose of this study was to analyze left systolic ventricular function and myocardial perfusion characteristics between short one day exercise-rest and long two days gated SPECT (Single Photon Emission Computed Tomography) protocols in patients with ischemic cardiomyopathy (ICM). METHODS: A prospective study of 40 patients (59.6±8.9 years, 3 women) with IHD (left ventricular ejection fraction (EF) ≤40%) was performed with myocardial perfusion gated SPECT. From 5 to 10 days after a one-day exercise-rest study (gated SPECT-1), patients were called back for a second rest study (gated SPECT-2) in order to compare EF and differences in perfusion summed rest score (ΔSRS=SRS1-SRS2) and summed difference score (ΔSDS=SDS1-SDS2) between both protocols. RESULTS: Between rest-gated SPECT-1 (short protocol) and rest-gated SPECT-2 (long protocol) EF increased (34% vs 37%, P= 0.008) in 26 patients (65%), and in 11 patients (27.5%) the increase was ≥5%. There were no significant differences in clinical and coronary angiography variables between patients with and without increase of the EF ≥5%. In the multivariate analysis, ΔSRS (95% CI: -1.1 to -29.2) and ΔSDS (0.179-1.236) were predictors for this EF increase between both studies. CONCLUSIONS: Exercise-rest short protocol can underestimate EF in patients with CM. Stunning but also contamination of rest images by previous exercise images in a short protocol could explain these results.

Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study.

OBJECTIVES: To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk. DESIGN: A prospective multicentre registry. SETTING: In hospital, after discharge and follow-up by telephone call. PATIENTS AND METHODS: 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included. RESULTS: Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk. CONCLUSIONS: In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

Platelet deposition in remote cardiac regions after coronary occlusion.

BACKGROUND: Activated platelets might contribute to endothelial dysfunction in non-ischaemic territories during acute myocardial infarction. We assessed platelet deposition, coronary flow reserve and contractile function in remote cardiac regions after transient coronary occlusion and their association with systemic platelet activation. MATERIALS AND METHODS: In 10 pigs (series A) subjected to 48-min occlusion of the left anterior descending coronary artery (LAD), 99mTc-platelet content in the right coronary artery (RCA) and its dependent myocardium was counted after reflow. In 10 pigs (series B) receiving the same occlusion of the RCA, the hyperaemic response at the LAD and systolic shortening in LAD-dependent myocardium were monitored after reperfusion. P-selectin expression on circulating platelets was assessed in both series by flow cytometry. RESULTS: In series A, platelet counts in the RCA and non-ischaemic myocardium were correlated with platelet content, polymorphonuclear leukocyte infiltration and infarct size in the reperfused zone, as well as with the percentage of P-selectin-positive platelets after reflow. In series B, a transient reduction in peak hyperaemic response in the LAD and sustained contractile dysfunction in non-ischemic myocardium were observed after releasing the RCA occlusion, these changes being also correlated with platelet activation status. CONCLUSIONS: Ischaemic injury triggers macro- and microvascular platelet deposition and causes an impairment in coronary flow reserve and contractile function in distant regions of the heart, which are related to activation of circulating platelets.

Role of the reverse mode of the Na+/Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury.

OBJECTIVE: We have recently shown that spontaneous Ca2+ oscillations elicit irreversible hypercontracture of cardiomyocytes during reoxygenation. The aim of this study was to investigate whether influx of exterior Ca2+ through the reverse mode of the Na+/Ca2+ exchanger (NCE) contributes to the development of these oscillations and, therefore, to reoxygenation-induced hypercontracture. METHODS: Isolated cardiomyocytes and hearts from rats were used as models. Cardiomyocytes were exposed to 60 min simulated ischemia (pH(o) 6.4) and 10 min reoxygenation (pH(o) 7.4). During reoxygenation cardiomyocytes were superfused with medium containing 1 mmol/l Ca2+ (control), with nominally Ca2+-free medium or with medium containing 10 micromol/l KB-R 7943 (KB), a selective inhibitor of the reverse mode of the NCE. RESULTS: In reoxygenated cardiomyocytes rapid Ca2+ oscillations occurred which were reduced under Ca2+-free conditions or in presence of KB. Hypercontracture was also significantly reduced under Ca2+-free conditions or in presence of KB. After 30 min of normoxic perfusion isolated rat hearts were subjected to 60 min global ischemia and reperfusion. KB (10 micromol/l) was present during the first 10 min of reperfusion. LVEDP, LVdevP and lactate dehydrogenase (LDH) release were measured. Presence of KB reduced post-ischemic LVEDP and improved left ventricular function (LVdevP). In KB treated hearts the reperfusion induced release of LDH was markedly reduced from 81.1 +/- 9.9 (control) to 49.3 +/- 8.8 U/60 min/g dry weight. CONCLUSION: Our study shows that inhibition of the reverse mode of the NCE, during reperfusion only, protects cardiomyocytes and whole hearts against reperfusion injury.

Intravenous administration of the natriuretic peptide urodilatin at low doses during coronary reperfusion limits infarct size in anesthetized pigs.

OBJECTIVE: It has been shown that cGMP content is reduced in post-ischemic myocardium, and that stimulation of cGMP synthesis prevents cardiomyocyte hypercontracture and cell death in vitro. This study was aimed at determining whether administration of the natriuretic peptide urodilatin (URO) at the time of reperfusion could limit myocardial cell death secondary to transient coronary occlusion. METHODS: The relation between cGMP content in reperfused myocardium and the extent of cell death was investigated in isolated rat hearts (n=62) receiving different URO concentrations during initial reperfusion. The dose of intravenous URO necessary to obtain the targeted increase in cGMP in reperfused myocardium was investigated in ten pigs submitted to transient coronary occlusion (CO), and the effect of two selected doses of URO on infarct size was investigated in 22 pigs. RESULTS: cGMP was severely reduced in post-ischemic rat hearts. Addition of 0.01 microM URO during the first 15 min of reperfusion had no effect on myocardial cGMP content, functional recovery or LDH release in hearts submitted to 40 or 60 min of ischemia. At 0.05 microM, URO increased myocardial cGMP to 111% of values in normoxic hearts, improved functional recovery (P=0.01) and reduced peak LDH released by 40% (P=0.02). The beneficial effect of urodilatin was abolished by ANP receptor inhibition. At 1 microM, URO increased cGMP in reperfused myocardium to 363% of normoxic controls and had no beneficial effect. In pigs allocated to 47 min of CO and 5 min of reperfusion, cGMP was markedly reduced in reperfused myocardium. Intravenous URO at 10 ng/kg per min during the first 25 min of reperfusion normalized myocardial cGMP after 5 min of reflow (95% of control myocardium), and reduced infarct size by 40% (P=0.04). At 50 ng/kg per min, urodilatin increased myocardial cGMP in reperfused myocardium to 335% of control myocardium and failed to significantly reduce infarct size (46 vs. 66%, P=0.125). None of these doses had detectable hemodynamic effects. CONCLUSIONS: Intravenous low-dose URO at the time of reperfusion normalizes myocardial cGMP and limits necrosis. Large doses of URO increasing myocardial cGMP well over normal values may lack this beneficial effect.

Persistence of gap junction communication during myocardial ischemia.

During myocardial ischemia, severe ATP depletion induces rigor contracture followed by intracellular Ca2+ concentration ([Ca2+]i) rise and progressive impairment of gap junction (GJ)-mediated electrical coupling. Our objective was to investigate whether chemical coupling through GJ allows propagation of rigor in cardiomyocytes and whether it persists after rigor development. In end-to-end connected adult rat cardiomyocytes submitted to simulated ischemia the interval between rigor onset was 3.7 +/- 0.7 s, and subsequent [Ca2+]i rise was virtually identical in both cells, whereas in nonconnected cell pairs the interval was 71 +/- 12 s and the rate of [Ca2+]i rise was highly variable. The GJ blocker 18alpha-glycyrrhetinic acid increased the interval between rigor onset and the differences in [Ca(2+)]i between connected cells. Transfer of Lucifer yellow demonstrated GJ permeability 10 min after rigor onset in connected cell pairs, and 30 min after rigor onset in isolated rat hearts submitted to nonflow ischemia but was abolished after 2 h of ischemia. GJ-mediated communication allows propagation of rigor in ischemic myocytes and persists after rigor development despite acidosis and increased [Ca2+]i.

Dynamic intracoronary thrombosis does not cause significant downstream platelet embolization.

OBJECTIVE: A mural intracoronary thrombus is a potential source of platelet emboli that may obstruct downstream microvessels, but this phenomenon has not been characterized. The present study aimed to assess the magnitude of myocardial platelet accumulation downstream of a mural intracoronary thrombus and its modification by a concomitant transient coronary occlusion (OC) or by treatment with aspirin. METHODS: The myocardial content of 99mTc-labelled platelets was analyzed in 26 pigs submitted to intimal injury of the left anterior descending coronary artery (LAD) followed by no intervention (n=6), 25-min OC (n=6), or 48-min OC preceded (n=8) or not (n=6) by intravenous administration of 250 mg aspirin. RESULTS: After 2 h, 24 animals had had 12+/-1 cyclic flow reductions (CFRs) reflecting dynamic LAD thrombosis. Myocardial platelet content in the inferior region was similar among groups. Platelet content in the LAD region was not significantly different to that in the inferior region (129+/-19%, P=NS) in the no intervention group, but was increased following OC (172+/-20 and 312+/-71% after 25- and 48-min OC, respectively, P<0.05). Pre-treatment with aspirin lessened the number of CFRs but did not reduce platelet accumulation in LAD myocardium (483+/-148%). Myocardial platelet accumulation was not associated with the magnitude of platelet deposition in the LAD nor with the number of CFRs, but was correlated with myeloperoxidase activity (r=0.91, P<0.001) and with infarct size (r=0.52, P=0.05). Histological analysis frequently showed sparse platelets or small platelet or leukoplatelet aggregates in small vessels, but arteriolar emboli were rare. In none of seven additional experiments coronary angiography showed obstructions of arterial branches during CFRs. CONCLUSION: The magnitude of platelet embolization from a mural intracoronary thrombus into downstream myocardium is small despite the presence of repetitive CFRs.

L-Arginine administration prevents reperfusion-induced cardiomyocyte hypercontracture and reduces infarct size in the pig.

OBJECTIVE: Stimulation of cGMP synthesis protects cardiomyocytes against reoxygenation-induced hypercontracture. The purpose of this study was to determine whether L-arginine supplementation has a protective effect against reperfusion-induced hypercontracture and necrosis in the intact animal. METHODS: Twenty-four Large-White pigs were randomized to receive either 100 mg/kg of L-arginine i.v. or vehicle 10 min before 48 min of coronary occlusion and 2 h of reperfusion. Hemodynamic variables, coronary blood flow and myocardial segment length changes (piezoelectric crystals) were monitored. Postmortem studies included quantification of myocardium at risk (in vivo fluorescein), infarct size (triphenyltetrazolium reaction), myocardial myeloperoxidase activity and histological analysis. Systemic, coronary vein, and myocardial cGMP concentration were measured in additional animals. RESULTS: Administration of L-arginine had no significant effect in hemodynamics or coronary blood flow. During reperfusion, myocardial cGMP content was reduced in the LAD as compared to control myocardium (P=0.02). L-Arginine increased myocardial cGMP content and caused a transient increase in plasma cGMP concentration during the initial minutes of reperfusion (P=0.02). The reduction in end-diastolic segment length induced by reperfusion, reflecting hypercontracture, was less pronounced in the L-arginine group (P=0.02). Infarct size was smaller in pigs receiving L-arginine (47.9+/-7.2% of the area at risk) than in controls (62.9+/-4.9%, P=0.047). There were no differences between groups in leukocyte accumulation in reperfused myocardium (P=0.80). CONCLUSION: L-Arginine supplementation reduces myocardial necrosis secondary to in situ ischemia-reperfusion by a direct protective effect against myocyte hypercontracture.