Effects of High-Dose Rocuronium on the QTc Interval During Anaesthesia Induction in Patients Undergoing Coronary Artery Bypass Graft Surgery.

OBJECTIVE: Existing myocardial damage in coronary artery disease patients causes prolonged QT syndrome. The primary objective of this trial is to explore the effects of different doses of the muscle relaxant agent rocuronium (0.6 mg kg(-1) and 1.2 mg kg(-1)) on QTc following anaesthetic induction. The second objective is to determine the incidence and kinds of arrhythmias. METHODS: In this prospective and randomized trial, patients undergoing elective coronary artery revascularization surgery were included in one of two groups. Both groups took the same anaesthetic induction agents: midazolam and fentanyl. Rocuronium was administered in Group 1 (n=20) with dose of 0.6 mg kg(-1) and in Group 2 (n=20) with a dose of 1.2 mg kg(-1) for muscle relaxation. Heart rate, average arterial pressure and QTc were recorded before induction (T0), after induction (T1), after muscle relaxant (T2), and 2 minutes (T3) and 5 minutes after intubation (T4). RESULTS: QTc was significantly longer 2 minutes after intubation (in Group 1 and Group 2, respectively, 447.9±28.3 and 466.1±37.8 ms) than at the beginning (respectively, 426.9±25.7, 432.0±35.5 ms) (p<0.01). In the intergroup comparison, average QTc values were similar in all trial periods (p>0.05). The prevalence of arrhythmias in between Group 1 (35%, n=7) and Group 2 (15%, n=3) was similar (p=0.06). Arrhythmias were recorded 2 minutes after intubation in both groups (n=10, 25%). CONCLUSION: In patients undergoing coronary artery revascularization surgery, rocuronium doses of 0.6 mg kg(-1) and 1.2 mg kg(-1) prolong the QTc interval after intubation. Cardiac arrhythmias related to long QTc arising after intubation should be taken into consideration.

[Beyond lowering LDL cholesterol]. / LDL kolesterolü düsürmenin ötesi.

Compelling evidence from randomized controlled studies demonstrated the crucial role of lowering low-density lipoprotein cholesterol (LDL-C) in the prevention of vascular events. However, not all patients with low LDL-C levels show similar reduction in event rates. The residual risk factors associated with ongoing vascular events despite achieving low LDL-C levels remain to be elucidated. New data suggest that beyond statin therapy, inflammatory mediators, high non-HDL (high-density lipoprotein) cholesterol or apolipoprotein B, small dense LDL-C, type 2 diabetes mellitus, and lifestyle features may have impact on residual vascular risk. In this review, we discussed the significance of identifying these residual risk factors and developing new treatment strategies to further decrease vascular events. The importance of imaging arterial wall to evaluate the effect of various medical therapies has also stated.

Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease.

Single point mutations in the genes coding for hemostatic factors were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of non-diabetic coronary artery disease [nDCAD] remains controversial. Angiographically demonstrated nDCAD patients (n = 86) and healthy controls (n = 90) were included in the study. Genotype analysis of hemostatic gene polymorphisms were assessed by using CVD strip assay, based on allele specific oligonucleotide probes. The carrier frequency of factor V (FV) H1299R, prothrombin G20210A, glycoprotein (Gp) IIIa L33P, plasminogen activator inhibitor-I (PAI-1) 4G/5G, 4G/4G, 5G/5G, methylenetetrahydrofolate reductase (MTHFR) A1298C and beta-fibrinogen -455 G > A were similar between patients and controls. In contrast, frequency of FV Leiden was significantly higher among patients (12.5%) than controls (5%, OR: 7.94; 95%CI: 1.9-49.6) and FXIII V34L was significantly lower among patients (23.7%) than controls (40%, OR: 0.24; 95%CI: 0.1-0.89). In addition, the frequency of the MTHFR C677T polymorphism was 32.5% among patients compared with 42.5% in controls, of which the T/T genotype was significantly lower among patients (5%) than controls (17.5%, OR: 0.06; 95%CI: 0.01-0.58). No difference was observed in prevalence of prothrombin G20210A, FV H1299R, Gp IIIa L33P, PAI-1 4G5G, MTHFR A1298C, beta fibrinogen 455 G > A mutations between patients and controls. However, lower frequency of FXIII Val34Leu and MTHFR C677T polymorphisms may decrease, while FV Leiden polymorphism may increase development of nDCAD.

Effect of losartan on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation.

OBJECTIVES: The aim of this study was to assess the effects of losartan treatment on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation (MR) secondary to mitral valve prolapse or rheumatic heart disease. METHODS: Twenty-seven patients (14 males, 13 females, mean age 51+/-11, range 21-76) with moderate MR due to mitral valve prolapse or rheumatic heart disease were examined by means of Doppler echocardiography. The subjects were submitted to treadmill exercise tests using the modified Bruce protocol at baseline, after six hours and after the six-week treatment period to be evaluated based on their exercise tolerance. Mitral Regurgitant Volume (MRV), effective regurgitant orifice diameter, left atrial volume, left ventricle (LV) end-diastolic volume index, LV end-systolic volume index, LV ejection fraction (LVEF), left ventricle mass index were calculated at baseline and after six weeks of treatment with single dose of losartan (50 mg/day). RESULTS: Total treadmill exercise time increased from 477.7+/-147.9 to 535.7+/-149.0 seconds after six hours (p<0.01) and to 559.6+/-142.8 seconds after six weeks of treatment. Also, metabolic equivalent values increased following six hours of first dose and six weeks of losartan treatment (from 10.9+/-2.9 to 11.8+/-3.1, p=0.006 and 12.4+/-3.1, p=0.002; respectively). However, peak exercise systolic blood pressure (BP) was reduced after six hours and six weeks of treatment, and resting diastolic BP did not change after six hours but reduced at the end of the treatment period. MR volume decreased significantly from 29.3+/-14.1 ml to 25.1+/-14.8 ml, (p=0.025) without significant change in regurgitant orifice diameter (0.72+/-0.37 cm vs. 0.66+/-0.37 cm, p=NS), left atrium diameter and area while LVEF increased from 51.70+/-13.37 to 54.11-11.75 (p=0.015) with losartan. CONCLUSION: We conclude that the angiotensin II receptor antagonist losartan improves exercise tolerance and echocardiographic parameters in patients with moderate MR.

Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis.

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and statins (hydroxy-methyl-glutaryl-CoA reductase inhibitors) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis (RA). METHODS: A total of 45 patients with longterm RA were randomized into 3 groups to receive 8 weeks of treatment with placebo (n = 15), simvastatin (20 mg/day, n = 15), or quinapril (10 mg/day, n = 15) as an adjunct to existing antirheumatic drug treatment. Factors with a role in the development of endothelial dysfunction, such as C-reactive protein (CRP), fibrinogen, nitric oxide (NO), and serum cytokine concentrations including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and in the posttreatment period. Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions. RESULTS: Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups. Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [from 5.3 +/- 1.1% to 8.9 +/- 1.4% (p = 0.025)], while there was no difference in endothelium-independent vasodilatation [9.0 +/- 1.8% to 11.2 +/- 2.5% (p = 0.17)]. The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [from 6.1 +/- 0.8% to 7.8 +/- 0.7% (p = 0.06)]. Treatment with the 2 drugs had no significant effects on resting arterial diameter. CONCLUSION: We show that simvastatin 20 mg daily improves endothelial function in patients with RA. Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response.

Endothelial dysfunction in patients with primary Sjögren's syndrome.

The aim of this study was to determine the endothelial function in patients with primary Sjögren's syndrome (SS). We also aimed to determine whether endothelial (dys)function correlates with extraglandular manifestations, specific autoantibodies and the severity of salivary gland involvement of SS. Endothelium-dependent vasodilation and endothelium-independent vasodilation of the brachial artery were assessed by a high-resolution ultrasound on 25 patients with primary SS and on 29 healthy controls. Patients with primary SS had significantly less mean endothelium-dependent vasodilation than did controls (3.0 +/- 0.4% vs 4.2 +/- 0.3%; p = 0.012). Endothelium-independent vasodilation induced by sublingual glycerol trinitrate was not different between the two groups (12.9 +/- 1.4% vs 14.1 +/- 1.2%; p = 0.86). We concluded that endothelium-dependent vasodilation was impaired in primary SS patients, in particular those presenting with Raynaud's phenomenon, when compared with the healthy controls and this impairment was not associated with the presence of RF, ANA, anti-Ro/SS-A, anti-La/SS-B and with the other extraglandular manifestations of the disease.

Selective COX-2 inhibition with different doses of rofecoxib does not impair endothelial function in patients with coronary artery disease.

In this study, we investigated the effects of both 25 and 50 mg daily doses of rofecoxib on the endothelial functions of patients with coronary artery disease (CAD). For this purpose, 34 patients with documented severe CAD and who were under aspirin treatment (300 mg/day) were randomized to receive 4 weeks of treatment with a placebo (n = 10, group I), rofecoxib 25 mg/day (n = 12, group II), and rofecoxib 50 mg/day (n = 12, group III). Brachial artery vasodilator responses were measured in order to evaluate endothelial function. The percentage of change in endothelial-dependent vasodilation in groups I, II, and III were similar at the baseline level and showed no significant change after treatment (6.2+/-3.9% vs. 5.9+/-3.1% and 5.8+/-3.3% vs. 5.6+/-3.8% and 6.1+/-4.5% vs. 5.8+/-4.1%, respectively; P > 0.05). Compared with the baseline, endothelium-independent vasodilatation, as assessed by nitroglycerine (NTG), remained unchanged after the treatment period (11.2+/-6.9% vs. 10.3+/-7.1% and 11.2+/-6.3% vs. 9.9+/-5.1% and 9.5+/-4.9% and 8.8+/-4.6%, respectively; P> 0.05). Treatment with both doses also showed no significant effects on high-sensitivity C-reactive protein (hs-CRP) levels and resting arterial diameters (P > 0.05). In conclusion, 4 weeks of treatment with standard and high doses of rofecoxib showed no significant effects on either endothelial-dependent or independent vasodilator response or plasma hs-CRP levels in patients with severe CAD taking concomitant aspirin.

[Evaluation of diastolic function by transmitral color M-mode flow propagation velocity in hypertensive patients]. / Hipertansif olgularda transmitral renkli M-mod akim yayilma hizi ile diyastolik fonksiyonlarin degerlendirilmesi.

OBJECTIVE: Diastolic dysfunction is considered as the most important cause of heart failure and morbidity in hypertensives. This study was designed to evaluate the relationship between the transmitral diastolic color M-mode flow propagation velocity (FPV) and left ventricular relaxation by using Doppler echocardiography. METHODS: In the present study, thirty-nine patients (21 male, 58.3%, age mean 52.7+/-5.9 years) with hypertension stage-I and over, were included. Transmitral diastolic E and A velocities, E-deceleration time (DT) and isovolumic relaxation time (IVRT) were measured by pulse Doppler method. We performed color M-mode technique for measurement of FPV of transmitral diastolic flow in the apical four-chamber view. We measured slope of aliasing velocity (blue aliasing) determined by color M-mode images. RESULTS: Flow propagation velocity values were not statistically related with age and gender, whereas differentiation of age groups were estimated as poor parabolic relationship, specially in patients over fifty years, FPV is estimated to be decreasing. Color M-mode FPV is correlated with DT, (r=-0.715, p<0.01), IVRT (r=-0.736, p<0.01) and interventricular septum thickness (r=-0.498, p<0.01), but not correlated with E/A ratio. CONCLUSION: Color M-mode FPV is correlated with DT and IVRT, which are important parameters for evaluation of diastolic function in hypertensive patients. This parameter is related with left ventricular relaxation and should be considered as a routine echocardiographic evaluation, because it is not affected by minimal changes in left ventricular filling pressure.

Endometrial thickness and the Doppler sonographic parameters of the uterine arteries as discriminators of endometrial status in postmenopausal women receiving anti-hypertensive treatment.

AIM: The aim of the present study was to establish the Doppler sonographic parameters of the uterine arteries in postmenopausal patients with or without hypertension and to determine the value of their measurement in the prediction of endometrial pathology. METHODS: Healthy postmenopausal women (n = 23) and the ones receiving anti-hypertensive medication (n = 34) examined for both endometrial thickness and Doppler velocimetry of the uterine arteries by transvaginal sonography. RESULTS: There was no significant difference between endometrial thickness and uterine artery Doppler sonographic parameters in hypertensive postmenopausal women compared to normotensive controls. CONCLUSION: The role of Doppler examination in the differential diagnosis of endometrial pathology in patients with or without hypertension seemed not to be effective.

[Serum level of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in acute coronary syndromes and relationship with prognosis]. / Akut Koroner Sendromlarda Insülin Benzeri Büyüme Faktörü-I ve Insülin Benzeri Büyüme Faktörü Baglayici Protein-3 Düzeyleri ve Prognozla Iliskisi.

OBJECTIVE: The aim of the present study was to examine the levels of insulin-like growth factor (IGF-I) and binding protein-3 (IGFBP-3) in acute coronary syndrome (ACS) and their relationship with prognosis. METHODS: Thirty patients with ACS (22 male, 8 female) were included in our study. Patient's population included 20 patients with ST elevation myocardial infarction (STEMI) and 10 with non-ST-elevation ACS. Death, re-infarction, revascularization and malignant arrhythmia were monitored during 3 months. Study group was compared with 20 healthy subjects (Controls). Blood samples were collected in the first 24 hours and at the end of third month. Serum IGF-I and IGFBP-3 levels were determined by radioimmunoassay method. RESULTS: We found decreased level of IGF-I only in the STEMI group (105+/-84 ng/ml vs. 715+/-150 ng/ml, p<0.0001). There were no significant differences in IGFBP-3 levels between two groups. Serum IGF-I levels were significantly increased after 3rd month in the STEMI group (356+/-72 ng/ml vs. 105+/-84 ng/ml, p=0.025). There was no relationship between IGF-I, IGFBP-3 levels and cardiovascular events occurred during 90 days of follow-up. CONCLUSION: These data allows to suggest that significantly decreased level of IGF-I in STEMI group of ACSs can be used as a marker of myocardial necrosis. There was no relationship between IGF-I level and cardiovascular events occurred in 90 days, so this parameter can not be used as a negative prognostic factor.

[The effects of clarithromycin treatment on cardiac events in acute coronary syndrome patients]. / Akut Koroner Sendromlu Hastalarda Klaritromisin Tedavisinin Kardiyak Olaylar Uzerine Etkisi.

OBJECTIVE: The assessment of short duration early clarithromycin treatment on major cardiac events in acute coronary syndrome patients. METHODS: One hundred and thirteen patients with acute coronary syndrome had been enrolled in the study in a prospective manner. Fifty-seven of 113 patients received peroral clarithromycin 1g/day for 14 days in addition to standard therapy. The remaining 56 patients were considered as control group. The treatment and control groups had similar major cardiac risk factors such as diabetes, hypertension, dyslipidemia and smoking habits. The occurrence of unstable angina pectoris, non-ST elevation myocardial infarction and ST elevation myocardial infarction was comparable in both groups. The use of thrombolytic therapy and glycoprotein IIb/IIIa receptor blockers administration was also similar in both groups. The patients were followed for major cardiac events for 6 months. RESULTS: During the follow-up, no difference was observed between groups in the occurrence of unstable angina pectoris, myocardial infarction, the need for revascularization with percutaneous coronary intervention or cardiac surgery and cardiac death. We observed a reduction of myocardial infarction and cardiac death occurrence and an increase in the necessity of percutaneous interventions in the treatment group even though this difference did not reach statistical significance. CONCLUSION: No benefit of short duration early clarithromycin therapy was observed in the occurrence of major cardiac events in acute coronary syndromes. Studies with longer treatment and follow-up period using different antibiotics are necessary to elucidate the possible effect of antibiotics on major cardiac events in patients with acute coronary syndrome.

[Doppler index of myocardial performance and its relationship with mitral E wave deceleration time in acute Q-wave myocardial infarction]. / Akut Q-Dalgali Miyokard Infarktüsünde Miyokardiyal Performans Indeksi ve Mitral E Dalga Deselerasyon Zamani Arasindaki Iliski.

OBJECTIVE: The objectives of the study were to assess myocardial systolic and diastolic functions by myocardial performance index (MPI) and its relationship with E - wave deceleration time (DT) in early phase of acute Q-wave myocardial infarction (MI). METHODS: We performed nongeometric Doppler-derived echocardiography to assess combined systolic and diastolic functions using myocardial performance index in 50 patients with acute Q-wave MI at early phase of events, (25 pts with anterior MI and 25 pts with inferior MI). The index is defined as the sum of the isovolumic contraction and isovolumic relaxation times divided by ventricular ejection time and was obtained by Doppler measurement from the diastolic mitral inflow and left ventricular outflow velocity-time intervals. RESULTS: As a result, the index was 0.54+/-0.1 in all patients with MI. We also estimated the higher MPI and DT values in anterior than in inferior MI (MPI: 0.61+/-0.07 vs. 0.46+/-0.06, p<0.001; DT: 244+/-64 msec vs. 204+/-31.2 msec, p=0.005, respectively). Myocardial performance index was positively correlated with DT in inferior MI (r=0.42, p<0.035) and negatively correlated with anterior MI; (r=- 0.72, p=0.0001). CONCLUSION: These data suggest that Doppler-derived MPI reflects severity of global left ventricular dysfunction in early phase of acute MI and may be a useful parameter in these patients.

The effect of tirofiban on ST segment resolution in patients with non-ST elevated myocardial infarction.

ST segment resolution in ST elevated myocardial infarction has independent predictive value for congestive heart failure and death at 30 days. ST segment depression in unstable angina pectoris (UAP) and non-ST elevated myocardial infarction (NSTEMI) predicts high risk of MI and death and may discriminate patients likely to have greater benefit from aggressive antithrombotic and interventional therapy. This study assessed the effect of tirofiban added to conventional treatment on ST segment resolution in NSTEMI patients. Sixty-four patients were randomized to one of the two groups: 32 patients received conventional treatment while tirofiban was added in the second group of 32 patients. In the first group, 6 patients refused to participate further after giving initial informed consent while 1 patient in the tirofiban group dropped out. We had 26 patients (mean age, 59 years) in the conventional treatment group and 31 patients (mean age, 59 years) received also tirofiban. Tirofiban was administered by intravenous infusion over a 72 hour period. More than 50% regression of depression was considered to be ST segment resolution. The characteristics of the two groups were comparable (Table I). The ST segment resolution evolution did not differ at the 4th and 24th hours between the two groups. Significant differences occurred in the 72nd hour ECG (Table III). ST resolution was present in 67.9% of the tirofiban patients and in 32.1% of the conventional treatment group (P < 0.05). Tirofiban treatment was not associated with an increase in major bleeding even though there was a trend toward an increase in minor bleeding cases and did not influence the occurrence of refractory angina pectoris.