Evaluation of profilin 1 as a biomarker in myocardial infarction.

OBJECTIVE: Profilin 1 (Pfn1) is likely to be involved in atherogenesis and myocardial infarction (MI). Clinical data on this subject are very limited. The aim of this study was to search for associations between serum Pfn1 and a number of parameters in MI patients: symptom onset to PCI time (OPT), myocardial necrosis markers, thrombolysis in myocardial infarction (TIMI) flow, antiplatelet drugs, heparin administration and typical atherosclerosis risk factors. PATIENTS AND METHODS: We included patients with type 1 MI (according to the Third Universal Definition of Myocardial Infarction) who were able to precisely determine the time of symptom onset. Exclusion criteria involved conditions potentially altering platelet function. We screened 114 patients and included 65. We assessed serum Pfn1 in three time points: on admission (Pfn1_0), 24 hours post PCI (Pfn1_24) and 48 hours post PCI (Pfn1_48) and correlated it with OPT, cardiac necrosis markers (troponin T, CK, CKMB), TIMI flow in the infarct-related artery, pre-hospital P2Y12-antagonist and heparin administration and known atherosclerosis risk factors. RESULTS: Patients with a shorter OPT had higher Pfn1_0 (838.5 vs. 687.1 pg/ml, p=0.007). Patients with impaired coronary flow post PCI had lower Pfn1_24 (748.2 vs. 925.2 pg/ml, p=0.017) and Pfn1_48 (744.5 vs. 879.8, p=0.031. Pfn1_24 and Pfn1_48 were lower in patients who received a P2Y12 antagonist prior to hospital admission. Diabetic patients presented with lower Pfn1_0 concentrations. CONCLUSIONS: This is the first study assessing Pfn1 in type 1 MI patients in relation to the chosen parameters. Pfn1 may be a biochemical tool to objectify information on OPT in MI patients. We found an association between Pfn1 and post-PCI TIMI flow, antiplatelet drug administration and diabetes mellitus.

The role of chemokine CCL5/RANTES and metalloproteinase-9 as inflammatory modulators in symptomatic internal carotid artery stenosis.

Up to 80% of all ischemic strokes (IS) attributed to internal carotid athero-occlusive artery stenosis (ICAS) are related to a thromboembolic mechanism. One athero-occlusive ischemic event increases the risk for ischemia in another vascular territory, resulting from inflammation within the atherosclerotic plaque induced by cytokines. Thus, ultrasonographic characteristics of vulnerable plaques in ICAS, including plaque echolucency and ulceration might correspond to cytokine activity. The present study aimed to investigate the associations between serum cytokines and atherosclerotic plaque characteristics and the 3-year risk of a major adverse coronary and carotid ischemic event (MACCE) in symptomatic patients treated for ICAS. Plaque characteristics on ultrasonography, serum levels of C-C motif chemokine ligand 5 (CCL5)/regulated on activation, normal T-cell expressed and secreted (RANTES), metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), transforming growth factor beta (TGF-ß), C-X-C motif chemokine ligand 16 (CXCL16), FAS ligand (FASL) and high sensivity C-reactive protein (hs-CRP) were analyzed in 103 symptomatic patients with ICAS prior to carotid revascularization. The incidence of MACCE: cardiovascular death (CVD), myocardial infarction (MI) and recurrent ischemic stroke (IS) were recorded prospectively for up to 5 years (median 37; IQR 21 - 40 months). Echolucent plaques, in comparison to echogenic plaques, displayed lower median levels of RANTES (P = 0.042) but higher median levels of IL-6 (P = 0.039). There was no relationship between plaque characteristics and median levels of MMP-9, TGF ß, CXCL16, FASL, or hs-CRP (P = NS). During follow-up, MACCE occurred in 15 (14.6%) patients. Univariate Cox proportional hazard analysis indicated median RANTES levels < 45.5ng/mL (hazard ratio (HR) = 3.95; 95%CI = 1.10 - 14.2; P = 0.035), MMP-9 > 0.6 µg/mL (HR 4.5; 95%CI = 1.4 - 13.9; P = 0.009), renal impairment (HR 3.48; 95%CI = 1.29 - 9.34; P = 0.013) as potential MACCE risk factors. On multivariate Cox proportional hazard analysis, MMP-9 > 0.6 µg/mL and RANTES < 45.5 ng/ml were associated with a 4.72-fold (95%CI = 1.3 - 17.0; P = 0.017) and a 3.8-fold risk increase (95%CI = 1.07 - 13.89; P = 0.038) of MACCE. Kaplan-Meier analysis showed significant differences in MACCE-free survival rates depending on RANTES and MMP-9 median levels. We conclude that serum RANTES, IL-6, and MMP-9 were associated with plaque vulnerability and predicted adverse MACCE in patients treated for ICAS.

Polymorphism in the chemokine receptor 7 gene (CCR7) is associated with previous myocardial infarction in patients undergoing elective coronary angiography.

Coronary artery disease (CAD) remains a major cause of death in developed countries. Both environmental and, less known, genetic factors contribute to progression of CAD to myocardial infarction (MI). Immune system is activated in patients with CAD through dendritic cells (DCs), which present plaque antigens to T lymphocytes. Production of proinflammatory cytokines by activated T cells contributes to plaque rupture in MI. Chemokine receptor 7 (CCR7) on DCs is required for their chemotaxis from plaque to lymph nodes. This makes possible an interaction of DCs with T lymphocytes and initiation of specific immune response. We hypothesized that single nucleotide polymorphisms (SNPs) in CCR7 gene locus are associated with previous MI in patients with CAD. To test this hypothesis, we genotyped six SNPs from the CCR7 gene locus in 300 consecutive patients, admitted for elective coronary angiography. We performed univariate-, multivariate- (including potential confounders) and haplotype-based tests of association of SNPs with previous MI and results of angiography. Allele A of rs17708087 SNP was associated with previous MI. This association remained significant after adjustment for age, sex, smoking, hypercholesterolaemia and drugs used by patients (odds ratio 2.13, 95% confidence interval: 1.13-3.86). Therefore, we conclude that CCR7 gene locus harbours a polymorphism that modifies risk of MI in patients with CAD. Replication of this association could be sought in a prospective cohort of initially healthy individuals.

Chemokine RANTES is increased at early stages of coronary artery disease.

Cardiovascular diseases, and in particular coronary artery disease (CAD), are the leading causes of death in Europe and represent around 50% of overall mortality. Numerous cardiovascular markers have been proposed in relation to cardiovascular risk prediction, in relation to cardiac and vascular and cerebral events. Chemokines which regulate immune cell vascular chemotaxis, including CCL5/RANTES are points of great interest. We hypothesized that chemokine RANTES level measured in peripheral blood may be associated with severity of atherosclerosis in patients with stable angina undergoing coronary angiography. RANTES and interleukin 18 (IL-18) levels were measured by ELISA. Classical and novel cardiovascular risk factors like brachial flow mediated dilation and intima-media thickness were analyzed in the context of chemokine levels and severity of atherosclerosis. Study included 62 consecutive patients with coronary atherosclerosis demonstrated by coronary angiography, (mean age 59.3 years (S.D. = 7.4)), divided into two groups: group I with lower severity of atherosclerosis, (n = 45) and group 2 with severe CAD (n = 17) based on coronary angiography. Groups were well balanced for classic risk factors for atherosclerosis. Mean RANTES level were significantly higher in patients in group I (67.9 ng/ml, S.E.M. = 3.97) than in group II (50.5 ng/ml, S.E.M. = 7.49; P = 0.03). In contrast, IL-18 levels were similar in both groups (255 pg/ml in group I and 315 pg/ml, S.E.M. = 40.91 in group I, P = 0.12), as well as hsCRP concentration (3.45 S.E.M. = 2.66 ng/ml and 4.69 ng/ml S.E.M.= 1.64 ng/ml respectively; P = 0.47). Flow-mediated dilatation (FMD) values have been significantly lower in group II than in group I (6.31; S.E.M. = 0.61; vs 4.41; S.E.M. = 0,56, respectively, P = 0.026), while nitroglycerine-mediated dilatation (NMD) did not differ, indicating more pronounced endothelial dysfunction. No significant correlations between chemokine RANTES levels and intima-media thickness (IMT), FMD measurements have been found in the total population studied. Chemokine RANTES level could become a useful marker of severity of coronary artery disease. Its lower levels were observed in patients with more diffuse disease. Elevated level of chemokine RANTES in patients with stable angina pectoris may evaluate patients to high risk group in plaque formation at early stages of atherosclerosis.

Thrombin generation in acute coronary syndrome and stable coronary artery disease: dependence on plasma factor composition.

BACKGROUND: Acute coronary syndrome (ACS) is associated with thrombin formation, triggered by ruptured or eroded coronary atheroma. We investigated whether thrombin generation based on circulating coagulation protein levels, could distinguish between acute and stable coronary artery disease (CAD). METHODS AND RESULTS: Plasma coagulation factor (F) compositions from 28 patients with ACS were obtained after onset of chest pain. Similar data were obtained from 25 age- and sex-matched patients with stable CAD. All individuals took aspirin. Patients on anticoagulant therapy were excluded. The groups were similar in demographic characteristics, comorbidities and concomitant treatment. Using each individual's coagulation protein composition, tissue factor (TF) initiated thrombin generation was assessed both computationally and empirically. TF pathway inhibitor (TFPI), antithrombin (AT), factor II (FII) and FVIII differed significantly (P < 0.01) between the groups, with levels of FII, FVIII and TFPI higher and AT lower in ACS patients. When thrombin generation profiles from individuals in each group were compared, simulated maximum thrombin levels (P < 0.01) and rates (P < 0.01) were 50% higher with ACS while the initiation phases of thrombin generation were shorter. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. The differences between the thrombin generation profiles for each population were primarily dependent upon the collective contribution of AT, FII and FVIII. CONCLUSION: Simulations of thrombin formation based on plasma composition can discriminate between acute and stable CAD.

[Risk of hypertension after heart transplantation in the follow-up period]. / Ryzyko nadcisnienia tetniczego po przeszczepieniu serca w obserwacji odleglej.

From October 1988 to March 2000, 58 patients underwent orthotopic heart transplantation (HTX). Data of 220 heart recipients with the follow up > or = 3 months after HTX were analyzed using the average values of blood pressure measured with the sphigmo-manometer. 65% of patients were diagnosed with the hypertension (HA). 39.9% of those patients (NTA group) had the systolic blood pressure < or = 140 mmHg and diastolic blood pressure < or = 90 mmHg during pharmacotherapy. 60.1% of hypertensive patients (NTB group) had the systolic pressure > 140 mmHg and/or diastolic pressure > 90 mmHg despite pharmacotherapy. 35% of all patients had normal blood pressure after HTX (HNA group). Patients with hypertension were older and the end stage ischemic cardiomyopathy was more frequently indication for HTX. Significantly more females were in NTA group. We observed no influence of the daily dose of cyclosporine or other immunosuppressive drugs on HA. The average blood concentration of cyclosporine A and mycophenolate mofetil was similar in all groups. The calcium channel blockers and inhibitors of angiotensin converting enzyme were main tool of pharmacotherapy used. In NTA group calcium channels blockers were used more frequently. In NTB group there was a statistically significant higher blood level of creatinine. After HTX there is a high risk of HA, which: increases with age, with the ischemic cardiomyopathy as indication to HTX, is significantly higher in males, there is no correlation between HA and the dosage and blood level of cyclosporine, increases with kidney insufficiency. In monotherapy calcium channel blockers seem to be especially effective.

[Clinical outcome in patients after single vessel PTCA with multiple stent implantation]. / Ocena chorych leczonych angioplastyka wiencowa i implantacja dwóch i wiecej stentów do jednej tetnicy.

Multiple stenting in a coronary artery may improve the angiographic result of unsatisfactory percutaneous coronary angioplasty (PTCA) but little is known about its clinical outcome. We evaluated 42 patients who underwent multiple contiguous stent implantation (2-4 stents) within a single coronary artery in order to achieve optimal vessel reconstruction. Procedural success rate was 95%. In-hospital events included myocardial infarction in 2 patients (5%) and acute stent thrombosis in 2 patients (5%). Acute stent thrombosis was successfully treated with repeated PTCA and abciximab infusion. The mean stented segment length was 33.5 +/- 9.9 mm. In 23 patients (54.8%) stents were implanted due to abrupt or threatened artery closure (bailout), in 9 (21.4%) following total chronic artery occlusion and in 10 (23.8%) due to a suboptimal result of angioplasty (i.e. provisional stenting). The bailout stent implantation was most frequent in the left anterior descending artery (15 out of 23 patients, i.e. 65.2%). Long-segment multiple stenting was performed mainly in the right coronary artery to maintain recanalization after the chronic artery occlusion (6 out of 9 patients, i.e. 66.7%). Mean data for all studied patients revealed a significant improvement in the exercise stress test parameters after the procedure (exercise time: 8.5 +/- 3.9 vs. 11.4 +/- 3.5 min, maximal load: 5.4 + 3.0 vs. 7.6 +/- 2.9 METS, percent of the maximal predicted effort 75.5 +/- 10.3 vs. 83.2 +/- 9.2%, p < 0.01 for all). Although the sub-group analysis showed a significant increase in exercise test parameters in patients treated with stent implantation due to the bailout (p < 0.05), the increase did not reach statistical significance in the group of patients who underwent multiple stent implantation to maintain recanalization after chronic artery occlusion or to improve the result of angioplasty. At 14.9 +/- 8.3 months follow-up restenosis was found in 14 (33%) patients. It was successfully treated either with re-PTCA (10 patients, i.e. 23%) or with bypass surgery (4 patients, i.e. 10%). Interestingly, the length of the stented segment was not significantly higher in those patients who developed restenosis. No patient died sustained myocardial infarction or subacute stent thrombosis. We conclude that multiple stent implantation is a safe procedure, with an insignificant complication rate. Best outcome is seen when multiple stent implantation is performed for the left anterior descending artery bailout. Reconstruction of the right coronary artery due to chronic total occlusion usually requires multiple stent implantation. When multiple contiguous stent implantation is performed due to the suboptimal PTCA result, it does not seem to improve the clinical outcome as evaluated by exercise stress test. Although the risk of restenosis is increased, subacute stent thrombosis seems rare with multiple one-vessel stenting.

Ischemic and reperfusive release of the endogenous purines and its influence on the myocardial viability during beta-adrenergic blockade.

The aim of this study was to estimate ischemic and reperfusive release of myocardial adenosine degradation products (MADP) during beta-adrenergic blockade and its relation to infarct size (IS) and viable myocardium size (VM). In a group of 24 shepherd-mongrel dogs, randomly assigned to a metoprolol (M-) and placebo-group (P-group), occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion with recombinant tissue plasminogen activator was performed. Regional myocardial blood flow (MBF) was measured by the radiolabelled microsphere technique. Blood samples from aorta and great cardiac vein were collected to evaluate the concentrations of MADP. The triphenyltetrazolium chloride perfusion and fixation technique was used for infarct size measurement. MBF in the area at risk decreased in both groups during ischemia, but it was significantly higher (p = 0.013) in M-group. Recanalization of LAD was associated with an increase in flow in postischemic vascular bed. MBF was significantly higher (p = 0.024) in P-group during late reperfusion. In M-group IS was smaller (p = 0.007) and VM was bigger (p = 0.007). The correlation between arterial adenosine concentration during early reperfusion and IS (p = 0.044, r = -0.588) or VM (p = 0.036, r = 0.607) in M-group was noted. Values of net MADP balances significantly increased during early reperfusion. The correlation between reperfusive net MADP balance and IS (p = 0.00005, r = 0.906) or VM (p = 0.016, r = -0.675) in M-group was observed. The amount of MADP released during reperfusion correlates with the IS and is inversely proportional to the area of VM. The endogenously released adenosine may have additional cardioprotective effect during beta-adrenergic blockade.

[Percutaneous renal artery angioplasty--review of current indicators]. / Angioplastyka tetnic nerkowych--aktualne wskazania.

The most frequent cause of secondary arterial hypertension is renal artery stenosis. The aetiology of renal artery stenosis is mainly atherosclerotic (75-80%), in the remaining cases fibromuscular dysplasia is the causative factor. Renovascular hypertension has a poorer prognosis than spontaneous because it is more resistant to antihypertensive treatment, signifies an increased risk for the development and progression of malignant hypertension and may lead to irreversible renal dysfunction due to ischaemia. Renal revascularisation has been proved an effective treatment modality in patients with arterial hypertension or renal failure due to renal artery stenosis. However, surgical treatment is associated with the mortality rate of 6-9% due to the concomitant presence of ischaemic heart disease, cerebral and peripheral arteriosclerosis. Percutaneous transluminal renal angioplasty is equally effective in the treatment of arterial hypertension as surgical operation, leading to the improvement or stabilisation of renal function. The advent of renal stenting has markedly changed the efficacy and safety of procedures with PTRA becoming an alternative to surgery. The high efficacy of PTRA is associated with low mortality and relatively few complications as compared with surgical treatment. However, there is continuous discussion concerning the efficacy of percutaneous and surgical renal revascularisation in arterial hypertension. PTRA is currently increasingly frequently recommended in patients with renovascular hypertension not only to control blood pressure but also to protect renal function.

[Personality and restenosis after percutaneous transluminal coronary angioplasty]. / Osobowosc a restenoza po zabiegu przezskórnej angioplastyki wiencowej.

The paper is an attempt to find out which personality traits predispose to increased risk of restenosis in patients after first percutaneous transluminal coronary angioplasty (PTCA). The Eysenck Personality Questionnaire-Revised (EPQ-R) was used in 87 consecutive men (31 persons with university education, 26 secondary, and 20 occupational education; mean age 50 years, range from 32 to 72) on the second day after PTCA. Raw data were used in statistical analysis of EPQ-R. Restenosis was identified in coronary angiography within several weeks to 6 months after PTCA. Restenosis was detected in 25 patients. Groups with and without restenosis were compared with respect to EPQ-R parameters referring to neurotism (14.8 +/- 3.26 vs. 12.4 +/- 5.63; p < 0.01), extroversion (13.7 +/- 3.82 vs. 13.7 +/- 3.95; NS) and psychotism (5.7 +/- 3.20 vs. 7.2 +/- 4.8; p = 0.08). There was positive correlation between the level of neurotism and the frequency of restenosis (logistic regression coefficient = 0.225; OR = 1.252; p = 0.03), but not with age and the level of education. In contrast, psychotism did not correlate significantly with frequency of restenosis. In conclusion, neurotism appears to affect the frequency of restenosis, which means that emotional imbalance through reducing immunity to stress and skills of effective coping with it increases the risk of restenosis. Psychological intervention directed at developing the skills of coping with stress should be a part of the therapy in patients after PTCA.

A randomized comparison of elective high-pressure stenting with balloon angioplasty: six-month angiographic and two-year clinical follow-up. On behalf of AS (Angioplasty or Stent) trial investigators.

BACKGROUND: Previous randomized trials have shown beneficial effects of coronary stenting on restenosis and event-free survival rates. However, it has not yet been fully established if routine high-pressure stenting with an antiplatelet regimen can show similar results. METHODS: We compared the 6-month angiographic restenosis rate and 2-year event-free survival rate in 400 patients randomly assigned to stent or angioplasty. Aspirin and ticlopidine were prescribed in both groups. RESULTS: The procedural success rate did not significantly differ between the stent and angioplasty groups (97.92% vs 97.45%, P = not significant). No stent thrombosis was found. The 6-month restenosis rate was lower in the stent group (18. 18% vs 24.87%, P =.055). At 2 years target lesion revascularization rate was 17.19% in the stent group and 25.51% in the angioplasty group (P =.02, 33% reduction). No significant differences with regard to death and myocardial infarction were observed. Event-free survival rate at 6, 12, and 24 months was 86.77% vs 78.84%, 84.13% vs 76.70%, and 83.07% vs 73.54% for stent and angioplasty groups, respectively (P =.0172). CONCLUSIONS: The 6-month angiographic and 2-year clinical outcomes were better in patients who received stent than in those after balloon angioplasty. The difference in 2-year event-free survival rate was explained by a reduction in target lesion revascularization rate in the stent group.

Balloon positioning difficulties during nonsurgical septal reduction therapy in a patient with hypertrophic obstructive cardiomyopathy.

Dual chamber (DDD) pacing and catheter-based nonsurgical septal reduction therapy (NSRT) with ethanol are evaluated for treatment of patients with hypertrophic cardiomyopathy. This report describes a patient with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction who had failed to respond to DDD pacing but showed benefit from subsequent NSRT. Procedural difficulties during NSRT due to massive septal hypertrophy are presented.

Influence of an early adrenergic blockade on thrombotic infarct size and myocardial metabolism.

To evaluate the extent to which the protective effect of metoprolol was accompanied by changes in myocardial oxygen consumption and metabolism, thrombotic occlusion of coronary artery followed by infusion of metoprolol or placebo was performed in twenty four German Shepherds. To restore a coronary blood flow rt-PA was administered. Plasma levels of oxygen, glucose, lactic acid, non esterified fatty acids, triacylglyceride and adenosine breakdown products were measured before and at the end of the occlusion and in the early and late reperfusion periods. Regional myocardial blood flow was measured by means of radioactive tracer microspheres. Infarct size was estimated after perfusion and staining of excised hearts with Evans blue. Plasma levels of metoprolol were determinated before the end of occlusion and during reperfusion and therapeutic concentrations were confirmed. The infarct size was smaller in dogs receiving metoprolol (21.6 +/- 20.7 vs 43.0 +/- 17.3% p. < 0.02). Coronary collateral blood flow was greater in metoprolol than in placebo dogs (18.68 +/- 7.58 vs 11.05 +/- 6.10 ml/min/100g, p. < 0.01). As a consequence of myocardial ischemia a shift toward carbohydrate utilization, the myocardial lactate release and the accompanying symptoms of diminished myocardial lipid uptake were observed. A washout of adenosine degradation products during early reperfusion was also noticed. In beta 1 blocked animals the reduction of myocardial oxygen consumption and preserved myocardial uptake of lactate and non esterified fatty acids were documented.

[Stents for treatment of transluminal percutaneous coronary angioplasty (PTCA) complications]. / Stenty w leczeniu powiklanej angioplastyki wiencowej (PTCA).

UNLABELLED: This study describes initial results of stent implantation in bailout situations in 38 patients with obstructive dissection after percutaneous transluminal coronary angioplasty (PTCA). Before stent introduction 1.8% of all patients after PTCA required emergency bypass grafting (CABG) because of postprocedural complications. In 1997 the rate of such emergency operations decreased to only 0.5% (p < 0.05). The success rate of stent deployment in patients included in the study was 95%. Mean final inflation pressure used for stent deployment was 12.0 +/- 2.3 atm. After stent implantation average residual stenosis was -0.81 +/- 5.75%. Of the 38 patients, 15 (40%) were treated before stent implantation with prolonged inflations with perfusion catheter. Bailout stenting was performed in 10 (25%) patients undergoing PTCA for restenotic lesions. The stents were placed in the left anterior descending coronary artery in 26 patients (69%), left circumflex coronary artery in 3 patients (8%), and in the right coronary artery in 9 patients (23%). Before bailout stenting 28 patients (75%) presented with type C and D dissection. One patient (2.5%) developed acute stent thrombosis. No episodes of subacute stent thrombosis were noted. During six-months clinical follow up no death and no Q-MI were observed. Angiographic follow up restenosis rate was 13/30 (43%), predominantly in patients treated with prolonged perfusion balloon inflations before stent implantation. The incidence of repeated PTCA and elective CABG due to restenosis was 12/30 (40%) and 1/30 (3%), respectively. There were no vascular complication at the puncture site. IN CONCLUSION: the introduction of coronary stenting has provided an excellent non-surgical modality for treatment of imminent or acute vascular closure complicating coronary angioplasty.

[Coronary bypass grafting after failed percutaneous angioplasty (PTCA)]. / Pilne pomostowanie tetnic wiencowych po powiklanych angioplastykach wiencowych (PTCA).

Between January 1991 and September 1997, in the Cardiovascular Surgery Department of the Institute of Cardiology of Jagiellonian University Medical School, 23 patients underwent emergency CABG due to acute myocardial ischaemia in result of failed PTCA. Over the same period of time invasive cardiologists performed 1883 PTCAs out of which 23 (1.2%) were emergency cardiosurgical procedures, and in 38 patients, stents were implanted in the damaged coronary arteries. The patients' age ranged from 37 to 67 years (median 52.2). In all patients good left ventricular function was preserved, median ejection fraction being 64%. Two patients required IABP to support left ventricular function. 1-4 bypass grafts were implanted (median 1.9 per patient). In one patient, internal mammary artery was collected and then implanted into anterior interventricular branch. The most common complication was myocardial infarction which occurred in 12 patients (52%). In ten patients low output was observed postoperatively. One operated patient (a female died (4.3%). The mean time of hospitalization was 11 days. Emergency myocardial revascularisation procedures performed after failed PTCA, bring higher risk of mortality and dangerous postoperative complications.

Simvastatin-induced myopathy in a patient treated for hypercholesterolemia. Morphological aspects.

Functional and histological changes in skeletal muscle developing during hypolipemic therapy, especially with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are rare. This paper reports a case of simvastatin-induced myopathy confirmed histopathologically and ultrastructurally.

Determinants of depressed left ventricular ejection fraction in pure mitral stenosis with preserved sinus rhythm.

BACKGROUND AND AIM OF THE STUDY: Although depressed left ventricular ejection fraction is present in a considerable proportion of subjects with pure mitral stenosis (MS), its mechanisms are not clearly identified. The purpose of this study was to identify determinants of depressed ejection fraction in young patients with isolated mitral stenosis in sinus rhythm. METHODS: We retrospectively analyzed 320 records of patients with MS (mitral valve area < or = 2.0 cm2) who underwent invasive diagnostic procedure in our center. Of these 39 subjects aged 20-40 years with isolated MS in sinus rhythm were selected for the final analysis. RESULTS: An ejection fraction not exceeding 50% was found in 12 patients (group A). When comparing group A to the remainder (group B), group A patients had lower left ventricular end-diastolic volume indices (60.5 +/- 21.6 ml/m2 vs. 76.1 +/- 16.1 ml/m2, p = 0.02) and stroke volume indices (28.0 +/- 10.4 vs. 47.9 +/- 12.0, p < 0.001). No significant differences between the groups in patients' age, end-systolic volume index, mitral valve area, mean transmitral gradient, left-sided cardiac pressures, pulmonary wedge pressure, systemic vascular resistance, and cardiac output were found. Indices of left ventricular isovolumic contraction and relaxation as well as end-systolic indices of left ventricular function were also comparable. Group A had significantly higher pulmonary vascular resistance, pulmonary artery pressures, and higher heart rate. An approximate index of left ventricular compliance was significantly lower in group A with similar left ventricular minimal and end-diastolic pressures. CONCLUSIONS: Depressed ejection fraction in pure mitral stenosis with preserved sinus rhythm seems attributable to left ventricular underfilling that appears to be precipitated by other factors in addition to a narrowed mitral orifice, e.g. decreased passive left ventricular compliance and/or altered interventricular interactions.

Intravenous metoprolol preceding thrombolysis in acute thrombotic myocardial infarction in the dog; effects on infarct size, myocardial blood flow, and left ventricular function.

Intravenous (i.v.) metoprolol preceding thrombolysis in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery helps limit infarct size (IS). We wished to determine whether these effects are caused at least in part by enhancement of collateral blood flow to the area at risk (AAR). Thrombotic occlusion was provoked by a copper-coil technique. We measured intracardiac pressures and their derivatives by catheter-tip micromanometers, cardiac output (CO) by thermodilution method, regional myocardial blood flow (RMBF) by radioactive microspheres technique, global and regional left ventricular (LV) function by ventriculography, and IS with triphenyltetrazolium at the end of the experiment. Measurements were performed before and after 60-min occlusion and after 30- and 90-min reperfusion. Received fifteen minutes after occlusion, 12 dogs metoprolol 0.3 mg/kg i.v. followed by 0.3 mg/kg/h; 12 received saline. Thrombolysis was performed in all dogs after 60-min occlusion with recombinant tissue-type plasminogen activator (rt-PA) 10 micrograms/kg/min for 30 min. Hemodynamic findings were similar in both groups. During occlusion, collateral flow to total AAR (18.6 +/- 7.5 vs. 11.0 +/- 6.1 ml/min/100 g), to its subepicardial (22.1 +/- 8.1 vs. 12.2 +/- 7.2 ml/min/100 g), midmyocardial (16.0 +/- 8.9 vs. 8.0 +/- 5.5 ml/min/100 g), and endocardial (14.1 +/- 8.1 vs. 7.3 +/- 6.0 ml/min/100 g) layers was higher (p < or = 0.03) in metoprolol than in placebo-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oral pretreatment with metoprolol on left ventricular wall motion, infarct size, hemodynamics, and regional myocardial blood flow in anesthetized dogs during thrombotic coronary artery occlusion and reperfusion.

OBJECTIVES: To study the effects of oral pretreatment with metoprolol over 3 days on hemodynamics, left ventricular function, regional myocardial blood flow, and infarct size in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery treated with thrombolysis. METHODS: Ten dogs received 200 mg metoprolol (Selozok) orally and 8 dogs received placebo for 3 days twice daily and 1 hour before the experiment. Under general anesthesia, thrombotic occlusion was provoked by the copper-coil technique. Intracardiac pressures and their derivatives, cardiac output (thermodilution method), regional coronary blood flow (microspheres), global and regional left ventricular function (ventriculography), and infarct size (triphenyltetrazolium staining) were measured. Measurements were performed during control, after 60 minutes of occlusion, and after 30 and 90 minutes of reperfusion. Thrombolysis was performed in all dogs 60 minutes after occlusion by intravenous infusion of 10 micrograms/kg/min of rt-PA for 30 minutes. RESULTS: During control cardiac output was lower, total peripheral resistance higher, and Tau and the left ventricular isovolumic relaxation time greater in the metoprolol group. During occlusion and after reperfusion, there were no significant hemodynamic differences between both groups. Blood flow to the area at risk and circumflex territory during occlusion were, respectively, 12.8 +/- 5.80 ml/100 g/min versus 9.65 +/- 8.35 ml/100 g/min (p > 0.05) and 42.58 +/- 7.86 ml/100 g/min versus 61.52 +/- 20.43 ml/100 g/min (p = 0.01) in the metoprolol- and placebo-treated dogs. The ratios of flow area at risk/circumflex territories in the epicardial, midmyocardial, and endocardial layers were, respectively, 0.44 +/- 0.20, 0.19 +/- 0.09, and 0.20 +/- 0.13 in the metoprolol- versus 0.24 +/- 0.16, 0.08 +/- 0.06, and 0.06 +/- 0.07 (p > or = 0.04) in the placebo-treated dogs. The ratio of flow endocardium/epicardium was higher (p > or = 0.02) in the active treatment group during the control period, both in the area at risk and circumflex territory; this was also the case in the circumflex territory at the end of the experiment (p = 0.003). Thirty minutes after occlusion, blood flow to the three layers of the area at risk rose to 2-3 times control values in both groups; a significant increase above control values also occurred in the circumflex territory. After 90 minutes reperfusion, blood flow to both territories was similar in both groups but was comparable to the control; however, in necrotic tissue of the subendocardial layer of both groups, flow fell below control values (p < 0.05). End-systolic volume rose from 21.2 +/- 7.4 ml to 36.1 +/- 11.5 ml (p < 0.05), end-diastolic volume remained constant (46.0 +/- 13.8 vs. 47.9 +/- 12.1 ml; p > 0.05), and ejection fraction fell from 53.9 +/- 8.3% to 25.8 +/- 10.2% (p < 0.05) at the end of the experiment in the metoprolol group. Respective figures for the placebo group were 19.4 +/- 7.9 versus 27.9 +/- 10.9 (p < 0.05), 38.5 +/- 13.0 versus 42.1 +/- 11.0 (p > 0.05), and 50.6 +/- 5.7 versus 35.5 +/- 11.7 (p < 0.05). Fractional shortening of the chords analyzed was similar in both groups during the control period; it fell significantly at the end of the experiment in three chords of the metoprolol group and in five chords of the placebo group. The apical chord in the placebo, but not in the metoprolol, dogs was dyskinetic: fractional shortening was -0.86 +/- 9.7 versus 7.5 +/- 13.5% (p > 0.05). The area at risk was 41.6 +/- 10.6 cm2 in metoprolol- and 40.5 +/- 7.2 cm2 in placebo-treated dogs (p > 0.05); the infarct size, expressed as a percentage of the area at risk, was 29.0 +/- 22.5% and 45.3 +/- 23.6% (p = 0.02), respectively. CONCLUSIONS: Oral pretreatment with metoprolol limited infarct size and improved regional left ventricular function, probably due to its negative chronotropic and inotropic effects, and also due to an enhancement of collateral flow fr