Remifentanil does not impair left ventricular systolic and diastolic function in young healthy patients.

BACKGROUND: Experimental studies and investigations in patients with cardiac diseases suggest that opioids at clinical concentrations have no important direct effect on myocardial relaxation and contractility. In vivo data on the effect of remifentanil on myocardial function in humans are scarce. This study aimed to investigate the effects of remifentanil on left ventricular (LV) function in young healthy humans by transthoracic echocardiography (TTE). We hypothesized that remifentanil does not impair systolic, diastolic LV function, or both. METHODS: Twelve individuals (aged 18-48 yr) without any history or signs of cardiovascular disease and undergoing minor surgical procedures under general anaesthesia were studied. Echocardiographic examinations were performed in the spontaneously breathing subjects before (baseline) and during administration of remifentanil at a target effect-site concentration of 2 ng ml(-1) by target-controlled infusion. Analysis of systolic function focused on fractional area change (FAC). Analysis of diastolic function focused on peak early diastolic velocity of the mitral annulus (e') and on transmitral peak flow velocity (E). RESULTS: Remifentanil infusion at a target concentration of 2 ng ml(-1) did not affect heart rate or arterial pressure. There was no evidence of systolic or diastolic dysfunction during remifentanil infusion, as the echocardiographic measure of systolic function (FAC) was similar to baseline, and measures of diastolic function remained unchanged (e') or improved slightly (E). CONCLUSION: Continuous infusion of remifentanil in a clinically relevant concentration did not affect systolic and diastolic LV function in young healthy subjects during spontaneous breathing as indicated by TTE.

Diffusion-weighted imaging findings differ between stroke attributable to spontaneous cervical artery dissection and patent foramen ovale.

BACKGROUND AND PURPOSE: Spontaneous cervical arterial dissection and patent foramen ovale (PFO) are important causes of stroke in younger patients. We tested whether characteristics of cerebral ischaemia visible on diffusion-weighted imaging (DWI) aid in differentiating between these two aetiologies. METHODS: Diffusion-weighted imaging was performed after a median of 2 days [interquartile range (IQR) 1-3 days] in 94 consecutive patients with an acute ischaemic stroke caused either by carotid or vertebral artery dissection (n = 33) or PFO (n = 61). We compared number, size, location and predefined patterns of DWI lesions between both aetiologies. RESULTS: Ninety-three out of 94 patients had acute DWI lesions and were included in the analysis. Multiple DWI lesions occurred more frequently in patients with dissection (23/33, 70%) than in those with PFO (26/60, 43%, P = 0.02). Lesions were larger in the dissection group [median diameter of largest lesion, 50 mm (IQR 19-68 mm)] than in the PFO group [23 (9-48) mm; P = 0.02]. The distribution of lesion patterns differed between the two aetiologies (P < 0.001): single, non-territorial infarcts were more frequent in PFO (25/60, 42%) than in dissection (2/33, 6%); large territorial infarcts with or without additional smaller lesions in the same territory occurred in 20/33 (61%) patients with dissection and in 16/60 (27%) patients with PFO. CONCLUSIONS: Diffusion-weighted imaging characteristics differ between PFO and dissection, suggesting differences in the pathogenesis of brain infarction between these aetiologies. A single non-territorial infarct seems to favour PFO as stroke aetiology. Whether this or other features are distinctive enough to diagnose PFO or dissection in individual patients requires further testing.

Different effects of sevoflurane, desflurane, and isoflurane on early and late left ventricular diastolic function in young healthy adults.

BACKGROUND: Knowledge on the effects of volatile anaesthetics on left ventricular (LV) diastolic function in humans in vivo is limited. We tested the hypothesis that sevoflurane, desflurane, and isoflurane do not impair LV diastolic function in young healthy humans. METHODS: Sixty otherwise healthy subjects (aged 18-48 yr) undergoing minor procedures under general anaesthesia were studied. After randomization for the anaesthetic, transthoracic echocardiographic examinations were performed at baseline and under anaesthesia with 1 minimum alveolar concentration (MAC) of the volatile anaesthetics during spontaneous breathing and intermittent positive pressure ventilation (IPPV). Peak early (E') and late (A') diastolic velocities of the mitral annulus were studied as the main echocardiographic indicators of diastolic function. RESULTS: During anaesthesia with 1 MAC under spontaneous breathing, E' increased with desflurane (P<0.001), was not significantly different with isoflurane (P=0.030), and decreased with sevoflurane (P=0.006). During IPPV, E' was similar to baseline with desflurane (P=0.550), insignificantly decreased with isoflurane (P=0.029), and decreased with the sevoflurane group (P<0.001). In contrast, A' was similarly reduced in all groups during spontaneous breathing without further changes during IPPV. Haemodynamic changes were comparable in all study groups. CONCLUSIONS: The findings of this in vivo study indicate that desflurane and isoflurane, and most likely sevoflurane, have no relevant direct negative effect on early diastolic relaxation in young healthy humans. In contrast, all three volatile anaesthetics appear to impair late diastolic LV filling during atrial contraction.

Optimization of imaging before pulmonary vein isolation by radiofrequency ablation: breath-held ungated versus ECG/breath-gated MRA.

Isolation of the pulmonary veins has emerged as a new therapy for atrial fibrillation. Pre-procedural magnetic resonance (MR) imaging enhances safety and efficacy; moreover, it reduces radiation exposure of the patients and interventional team. The purpose of this study was to optimize the MR protocol with respect to image quality and acquisition time. In 31 patients (23-73 years), the anatomy of the pulmonary veins, left atrium and oesophagus was assessed on a 1.5-Tesla scanner with four different sequences: (1) ungated two-dimensional true fast imaging with steady precession (2D-TrueFISP), (2) ECG/breath-gated 3D-TrueFISP, (3) ungated breath-held contrast-enhanced three-dimensional turbo fast low-angle shot (CE-3D-tFLASH), and (4) ECG/breath-gated CE-3D-TrueFISP. Image quality was scored from 1 (structure not visible) to 5 (excellent visibility), and the acquisition time was monitored. The pulmonary veins and left atrium were best visualized with CE-3D-tFLASH (scores 4.50 +/- 0.52 and 4.59 +/- 0.43) and ECG/breath-gated CE-3D-TrueFISP (4.47 +/- 0.49 and 4.63 +/- 0.39). Conspicuity of the oesophagus was optimal with CE-3D-TrueFISP and 2D-TrueFISP (4.59 +/- 0.35 and 4.19 +/- 0.46) but poor with CE-3D-tFLASH (1.03 +/- 0.13) (p < 0.05). Acquisition times were shorter for 2D-TrueFISP (44 +/- 1 s) and CE-3D-tFLASH (345 +/- 113 s) compared with ECG/breath-gated 3D-TrueFISP (634 +/- 197 s) and ECG/breath-gated CE-3D-TrueFISP (636 +/- 230 s) (p < 0.05). In conclusion, an MR imaging protocol comprising CE-3D-tFLASH and 2D-TrueFISP allows assessment of the pulmonary veins, left atrium and oesophagus in less than 7 min and can be recommended for pre-procedural imaging before electric isolation of pulmonary veins.

Intra-operative myocardial ischaemia cannot be detected by analysis of transmitral inflow patterns in patients undergoing off-pump coronary surgery.

BACKGROUND AND OBJECTIVE: Transmitral inflow patterns have been used for detection of myocardial ischaemia. However, its diagnostic value has not been tested in anaesthetized and mechanically ventilated patients undergoing coronary artery bypass graft surgery. METHODS: Transmitral inflow patterns were studied by transoesophageal Doppler echocardiography in 43 patients undergoing coronary artery bypass graft surgery without cardiopulmonary bypass after opening of the sternum (baseline) and during grafting of the left anterior descending artery. Peak early (E) and peak late (A) transmitral velocities and their ratio (E/A) were recorded. Myocardial ischaemia was defined by standard criteria using two-dimensional echocardiography and seven-lead electrocardiogram. RESULTS: Thirty-one patients (64 +/- 8 yr, 9 women) fulfilled the predefined inclusion criteria for analysis. During distal revascularization, 16 patients showed myocardial ischaemia and 15 did not. The use of vasoactive drugs, haemodynamic findings and transmitral inflow patterns were similar in both groups at baseline and during grafting. In the ischaemic group, E was 67.1 +/- 13.9 cm s-1 at baseline and 69.5 +/- 23.2 cm s-1 during grafting, and the E/A ratios were 1.3 +/- 0.3 and 1.4 +/- 0.9, respectively. In the non-ischaemic group, E was 64.0 +/- 17.1 cm s-1 at baseline and 60.9 +/- 14.8 cm s-1 during grafting, and the E/A ratios were 1.4 +/- 0.7 and 1.2 +/- 0.3, respectively. CONCLUSIONS: Analysis of Doppler findings of transmitral inflow patterns did not allow for detection of myocardial ischaemia during surgical revascularization of the myocardium.

[28-year old patient with successfully treated dilatative cardiomyopathy]. / 28-jähriger Patient mit erfolgreich behandelter dilatativer Kardiomyopathie.

A 28-year was admitted with heart failure. His medical history included treatment for hypogonadotropic hypogonadism. Echocardiography showed dilatation of all chambers. Elevated serum ferritin levels and liver biopsy indicated hereditary hemochromatosis. Cardiac iron overload was seen on magnetic resonance imaging. Genetic testing revealed homozygosis for G320 V mutation, confirming the diagnosis of juvenile hemochromatosis. Phlebotomy on a biweekly regimen was started and after twelve months of therapy the patient had normal ferritin values as well as normal ejection fraction on echocardiography.

Selection bias of elderly patients with chronic angina referred for catheterization.

BACKGROUND: Registry patients are generally older and more sick than patients enrolled in trials questioning the generalizability of trial results. We assessed whether such a selection bias also exists in elderly patients with chronic angina referred for catheterization. METHODS AND RESULTS: All 119 patients age>or=75 years with Trial of Invasive versus Medical Therapy in the Elderly (TIME) inclusion but no major exclusion criteria referred for catheterization during the TIME trial inclusion period in four TIME centers were registered and followed-up for one year. Registry patients differed from the 188 trial patients in the same hospitals in that they were younger, somewhat more frequently male, with less antianginal drugs and studied more often after acute chest pain at rest but with more comorbidities than study patients. Left ventricular ejection fraction and vessel disease were similar. One year mortality was 11.4% in registry and 9.6% in invasive TIME patients but differences disappeared after adjustment for baseline differences. Symptomatic status after one year was similar too. CONCLUSIONS: In elderly patients with chronic angina, a bias in the selection for invasive management exists which seems different from that reported in younger patient settings. After adjustment for these selection factors, however, one-year outcome was remarkably similar in registry and trial patients.

Expression of translation initiation factor 4A from yeast and mouse in Saccharomyces cerevisiae.

The eukaryotic translation initiation factor 4A (eIF-4A) plays an important role in regulating initiation. To analyze its function in yeast, we carried out a mutational analysis of the TIF1 and TIF2 genes, which encode eIF-4A. Expression of these two yeast genes has also been investigated at the transcriptional level and it has been found that both are expressed in wild-type yeast cells. Analysis of the expression of eIF-4A-beta-galactosidase fusion proteins reveals that the TIF2 gene is more highly expressed than the TIF1 gene. Interestingly, the yeast eIF-4A protein shows a high degree of amino acid sequence similarity to the mouse homologue. However, we find that the mammalian factor does not support protein synthesis in yeast either in vivo or in vitro.

Noninvasive evaluation of global left ventricular function with use of cine nuclear magnetic resonance.

Previous reports have validated the accuracy of nuclear magnetic resonance (NMR) imaging for quantitating ventricular volumes and myocardial mass. In this study, a new rapid NMR imaging method, cine NMR imaging, was used to compare left ventricular volumes determined from the transverse plane and short-axis plane in healthy volunteers and patients with dilated cardiomyopathy. With use of the short-axis plane, left ventricular mass at end-systole and end-diastole were determined and left ventricular systolic wall thickening at three different levels was assessed. For validation in the current study, cine NMR imaging and two-dimensional echocardiographic measurements of left ventricular volumes were correlated. Left ventricular volumes of the normal volunteers (end-systolic volume = 34 +/- 3.8 ml, end-diastolic volume = 90.4 +/- 7.2 ml) and patients with cardiomyopathy (end-systolic volume = 173 +/- 28.3 ml, end-diastolic volume = 219.5 +/- 29.6 ml) obtained in the transverse plane were nearly identical to those obtained in the short-axis plane (normal volunteers, end-systolic volume = 30.3 +/- 3.5 ml, end-diastolic volume = 84.7 +/- 7.0 ml and patients with cardiomyopathy, end-systolic volume = 179.1 +/- 27.8 ml, end-diastolic volume = 227 +/- 30.9 ml) and correlated highly (r = 0.91) with volumes obtained by two-dimensional echocardiography. Assessment of left ventricular mass over a broad range using cine NMR imaging in a short-axis plane was identical at end-systole (normal volunteers, 117 +/- 10 g; patients with cardiomyopathy, 202 +/- 20 g) and end-diastole (normal volunteers, 115 +/- 10 g; patients with cardiomyopathy, 194 +/- 21 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Time dependence of left ventricular recovery after delayed recanalization of an occluded infarct-related coronary artery: findings of a pilot study.

OBJECTIVES: We sought to test the hypothesis that late recanalization of infarct-related coronary arteries (IRAs) improves long-term left ventricular (LV) function. BACKGROUND: Reperfusion within 24 h of an acute myocardial infarction (MI) has been shown to improve myocardial healing and to reduce infarct expansion. Uncontrolled data suggest that there may be a time window of several weeks for such an effect. METHODS: Sixteen asymptomatic patients 10 +/- 4 days after a first Q wave anterior wall MI with persistent left anterior descending coronary artery occlusion and infarct-zone akinesia were randomized to immediate (2 weeks) or delayed (3 months) angioplasty. Repeat catheterization and cardiac magnetic resonance imaging (MRI) were performed after 3 and 12 months. RESULTS: Angiography 3 months after MI revealed that LV ejection fraction (LVEF) had increased ([mean +/- SD] 54.4 +/- 4.3% vs. 63.9 +/- 7.4%, p < 0.01) as a result of improved regional function (p < 0.01) and LV end-systolic volume had decreased (p < 0.002), whereas LV end-diastolic volume remained unchanged. With delayed angioplasty, LVEF, infarct zone wall motion and LV volumes did not improve. Cardiac MRI at baseline and at 3 and 12 months confirmed these findings and extended them up to 1 year, indicating that delayed angioplasty could no longer improve LV function because of marked LV dilation (p < 0.01). Immediate angioplasty had a high success rate, but restenosis (50%) was accompanied by new severe angina as a clinical indicator of salvaged myocardium, which did not occur after delayed angioplasty. CONCLUSIONS: This pilot study in selected patients supports the hypothesis that myocardial viability persists ("hibernation") for 2 to 3 weeks but not for 3 months after MI, during which time it may be worthwhile to restore blood flow to a large myocardial territory, even in asymptomatic patients, to improve long-term LV function.

Effect of high intensity exercise training on central hemodynamic responses to exercise in men with reduced left ventricular function.

OBJECTIVES: The aim of this study was to evaluate the effects of high intensity exercise training on left ventricular function and hemodynamic responses to exercise in patients with reduced ventricular function. BACKGROUND: Results of studies on central hemodynamic adaptations to exercise training in patients with chronic heart failure have been contradictory, and some research has suggested that training causes further myocardial damage in these patients after a myocardial infarction. METHODS: Twenty-five men with left ventricular dysfunction after a myocardial infarction or coronary artery bypass graft surgery were randomized to an exercise training group (mean age +/- SD 56 +/- 5 years, mean ejection fraction [EF] 32 +/- 7%, n = 12) or a control group (mean age 55 +/- 7 years, mean EF 33 +/- 6%, n = 13). Patients in the exercise group performed 2 h of walking daily and four weekly sessions of high intensity monitored stationary cycling (40 min at 70% to 80% peak capacity) at a residential rehabilitation center for a period of 2 months. Ventilatory gas exchange and upright hemodynamic measurements (rest and peak exercise cardiac output; pulmonary artery, wedge and mean arterial pressures; and systemic vascular resistance) were performed before and after the study period. RESULTS: Maximal oxygen uptake (VO2max) increased by 23% after 1 month of training, and by an additional 6% after month 2. The increase in VO2max in the trained group paralleled an increase in maximal cardiac output (12.0 +/- 1.8 liters/min before training vs. 13.7 +/- 2.5 liters/min after training, p < 0.05), but maximal cardiac output did not change in the control group. Neither stroke volume nor hemodynamic pressures at rest or during exercise differed within or between groups. Rest left ventricular mass, volumes and EF determined by magnetic resonance imaging were unchanged in both groups. CONCLUSIONS: High intensity exercise training in patients with reduced left ventricular function results in substantial increases in VO2max by way of an increase in maximal cardiac output combined with a widening of maximal arteriovenous oxygen difference, but not changes in contractility. Training did not worsen hemodynamic status or cause further myocardial damage.

Calcium inhibition of glycolysis contributes to ischaemic injury.

STUDY OBJECTIVE: The purpose of the study was to confirm that [Ca2+]i and .[H+]i increase during ischaemia in hypertensive hearts but not in thyrotoxic hearts, and that the rise in [Ca2+]i and [H+]i inhibits glycolysis, causing a rise in phosphomonoester sugars and thereby influencing postischaemic recovery. DESIGN: Rats were made hypertensive by aortic banding and thyrotoxic by injection of L-thyroxine. [Ca2+]i was studied in isolated hearts by surface fluorometry assessing calcium dependent changes in the fluorescent dye INDO-1, while [pH]i and phosphomonoester sugars were studied by 31P nuclear magnetic resonance (NMR). Global ischaemia was carried out by turning off all flow to the heart for 30 min. Hearts were then reperfused for 30 min. SUBJECTS: 72 Sprague-Dawley rats, weight 500-600 g, were used. Left ventricular hypertrophy was generated by aortic banding in 36, half of which were treated with verapamil. Eighteen were injected with L-thyroxine and there were 18 controls. MEASUREMENTS AND RESULTS: With all groups, developed pressure immediately declined after the onset of global ischaemia. During ischaemia the phosphomonoester sugars rose less in the hearts of thyrotoxic rats and the verapamil treated aortic constricted rats than in those of untreated aortic constricted and normal rats. During ischaemia there was no significant difference in [pH]i among the four groups. During ischaemia intracellular calcium rose least in thyrotoxic and verapamil treated aortic constricted rats, and most in untreated aortic constricted and normal rats. Intracellular calcium rose 10-15 min after the onset of ischaemia in verapamil treated pressure overload and control hearts; calcium rose immediately after the onset of ischaemia in the untreated aortic constricted hearts, but negligibly in hearts from thyroxine treated animals. Verapamil treatment of the aortic constricted hearts prevented the rise in intracellular calcium, and attenuated phosphomonoester sugar accumulation. Postischaemic recovery was complete in hearts in thyroxine treated and verapamil treated aortic constricted rats, but not in hearts from untreated aortic constricted and normal rats. Postischaemic recovery was inversely related to ischaemic diastolic [Ca2+]i and phosphomonoester sugar levels, but was not related to ischaemic values for [pH]i. CONCLUSIONS: Postischaemic recovery may depend on the ability of the cell to maintain mitochondrial activity as evidenced by oxygen consumption, thereby controlling the voltage of the cell, and influencing the ability of the myocardium to maintain its calcium homeostasis.

Bradykinin improves postischaemic recovery in the rat heart: role of high energy phosphates, nitric oxide, and prostacyclin.

OBJECTIVE: The aim was to define: (1) whether bradykinin administration during reperfusion improves postischaemic myocardial recovery; (2) whether high energy phosphate compounds are involved in the protective effects of bradykinin; and (3) whether bradykinin-induced release of prostacyclin and nitric oxide mediate the protective effects of bradykinin. METHODS: In the Langendorff rat heart preparation, coronary flow, left ventricular developed pressure, and, using 31P magnetic resonance spectroscopy, the high energy phosphate compounds phosphocreatine and beta-ATP were assessed during 15 min of global ischaemia and 30 min of reperfusion. Administration of 10(-7) M bradykinin was started before ischaemia and maintained throughout the experiment (BK-pre). This was compared to 10(-7) M bradykinin given exclusively with reperfusion (BK-post). Then 10(-7) M bradykinin was given simultaneously with 10(-4) M N omega-nitro-L-arginine-methyl ester (BK-LNAME) or 10(-5) M indomethacin (BK-indo). RESULTS: In comparison to control hearts, BK-pre exerted a significant protective effect on the postischaemic recovery of coronary flow [71(5)% v 43(4)%, P < 0.05], left ventricular pressure [81(8)% v 42(5)%, P < 0.05], phosphocreatine [105(4)% v 67(8)%, P < 0.05], and beta-ATP [78(9)% v 48(7)%, P < 0.05]. With BK-post, recovery of coronary flow [71(4)% v 43(4)%, P < 0.05] and left ventricular pressure [78(4)% v 42(5)%, P < 0.05] significantly improved; however the recovery of phosphocreatine [70(4)% v 67(8)%, NS] and beta-ATP [58(2)% v 48(7)%, NS] was not different from control. When bradykinin and L-NAME or indomethacin was given the beneficial effects of bradykinin on ischaemic hearts were abolished. CONCLUSIONS: (1) Bradykinin improved postischaemic myocardial recovery when given before ischaemia or starting exclusively with reperfusion; (2) this was only partially related to a protective action on the high energy phosphate compounds during ischaemia; (3) the beneficial effects of bradykinin on ischaemic hearts are dependent from an unrestrained action of prostacyclin and nitric oxide.

Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists.

OBJECTIVES: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. METHODS: [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. RESULTS: Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. CONCLUSIONS: The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulum.

Relationship between posterior thalamic nucleus unit activity and parietal cortical rhythms (beta) in the waking cat.

Cat behavioural states of attentive fixation on a target are associated with episodes of electrocortical rhythms at 40 Hz ("beta rhythms") in the parietal cortex. Previous field potential studies indicate that the nucleus posterior pars medialis of the thalamus displays this particular rhythmic activity. We investigated single units of the nucleus posterior pars medialis and its surrounding nuclei to assess their participation in the cortical beta rhythms. Only a small proportion of thalamic cells underwent changes in their firing pattern during beta episodes. "Beta-related cells" were localized in the nucleus posterior pars medialis or its immediate vicinity; no such beta-related cells were found in other regions of the lateral thalamus. Some beta-related cells showed a one-spike to one-wave relationship ("homorhythmicity"), while others displayed a prolonged decrease or a suppression of their firing throughout each beta episode ("pause cells"). For comparison, neurons in the same thalamic area were also recorded during sleep episodes with slow waves and spindles: there was no correlation between spindles and cell firing. Thus, the nucleus posterior pars medialis thalamic nucleus contains cells whose firing is correlated with the beta rhythms. No such correlation was found with sleep spindles.

Oral anticoagulation in the prevention of one-year vein graft occlusion after aortocoronary bypass surgery: optimal therapeutic range and practical limitations. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.

To assess the optimal level of oral anticoagulation to prevent occlusion of vein coronary bypass grafts, 318 patients from a graft patency trial were analysed retrospectively. Oral anticoagulant therapy was started one day before surgery and continued for one year, after which graft occlusion was assessed by angiography. The aimed level of anticoagulation was 2.8-4.8 International Normalized Ratio (INR). Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis and major bleeding. The observed anticoagulation level was 2.8-4.8 INR for 54%, and 1.8-3.8 INR for 75% of time per patient. Occlusion rates in patients who spent < 35, 35-70, and > or = 70% of time within INR range 2.8-4.8 were 10.5%, 10.8% and 11.8%, respectively (differences not statistically significant). Patients who spent > or = 70% of time within INR range 1.8-3.8 versus 2.8-4.8 showed comparable occlusion rates. The risk of graft occlusion was not related to quality of anticoagulation early (0-3 months) or late (3-12 months) after surgery. Myocardial infarction, thrombosis and major bleeding occurred in 1.3%, 2.0% and 2.9% of patients. To maintain vein graft patency in the first postoperative year by oral anticoagulation, a level within INR range 1.8-3.8 for > or = 70% of time seems to be sufficient.

The inverse Nehb J lead increases the sensitivity of Holter electrocardiographic monitoring for detecting myocardial ischemia.

A major reason for the relatively low sensitivity of Holter electrocardiography (ECG) for detecting ischemia is that the sensitivity of bipolar leads used for Holter ischemia monitoring has not been systematically evaluated, making lead selection difficult. Therefore, this study evaluated the sensitivity of 6 bipolar Holter leads for detecting ischemia during percutaneous transluminal coronary angioplasty. Seventy-five patients, each of whom had > 1 mm ST-segment elevation on an intracoronary electrocardiogram from the myocardium distal to the stenosis during balloon occlusion, were studied for the occurrence of > or = 1 mm ST-segment elevation or depression on the simultaneously recorded Holter leads II, III, aVF, CM5, CR4, and inverse Nehb J. The study found that the inverse lead Nehb J provided a significantly higher overall sensitivity for detecting myocardial ischemia than Holter leads II, III, aVF, CM5, and CR4. Also, the use of inverse lead Nehb J significantly increased the sensitivity of 2- and 3-lead Holter ischemia monitoring. These findings were based on a significantly higher sensitivity of inverse lead Nehb J for detecting ischemia induced by transient occlusion of the left anterior descending coronary artery and a slightly higher sensitivity for detecting ischemia induced by occlusion of the left circumflex coronary artery. None of the bipolar leads studied provided a very high sensitivity for detecting ischemia induced by occlusion of the right coronary artery. These findings show that adequate lead selection can increase the sensitivity of Holter ischemia monitoring. Furthermore, the lack of a highly sensitive lead for detection of inferior ischemia indicates that further evaluation of bipolar leads is warranted.

Improved myocardial ischemia detection by combined physical and mental stress testing.

The hypothesis that addition of mental stress to physical exercise would modify the circulation response to stress and improve noninvasive detection of myocardial ischemia was tested in a randomized, crossover radionuclide angiocardiographic study. Compared with physical exercise or mental stress alone, combined stress led to higher heart rates and rate-pressure products in early stress stages, to more pronounced symptoms, and to a better discrimination of subjects with and without coronary artery disease by radionuclide angiography.

Combined blockade of endothelin-1 and thromboxane A(2) receptors against postischaemic contractile dysfunction in rat hearts.

1. Endothelin-1 (ET-1) may play a role in myocardial ischaemia/reperfusion injury because both the release and vasoconstrictor effect of ET-1 are increased after ischaemia. Since the increased vasoconstrictor effect of ET-1 can be mediated by ET-1-induced release of thromboxane A(2) (TXA(2)), the aim of this study was to test whether combined blockade of ET and TXA(2) receptors protects the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion. 2. Bosentan (antagonist for ET(A) and ET(B) receptors, 1 microM based on concentration-response curves of ET-1), SQ 30,741 (antagonist of TXA(2) receptors, 0.1 microM), or the combination thereof was administered to isolated perfused rat hearts undergoing 15 min of global ischaemia and 60 min of reperfusion. 3. Neither bosentan or SQ 30,741 alone, nor the combination thereof, improved the incomplete postischaemic recovery of coronary flow, left ventricular developed pressure, phosphocreatine, or ATP. However, they attenuated ischaemia-induced acidosis but this did not translate into a measurable effect on haemodynamic or metabolic variables. 4. Thus, combined blockade of ET and TXA(2) receptors does not protect the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion in isolated perfused rat hearts. This finding suggests that neither ET-1 nor ET-1-induced release of TXA(2) play a major role in the postischaemic recovery of the cardiac contractile function and energy metabolism.

Cardiac rehabilitation in Switzerland. Efficacy of the residential approach following bypass surgery.

BACKGROUND: The traditional central European approach to cardiac rehabilitation involves sending patients to an idyllic setting, where they reside for a specified period following a cardiac event. Favorable results have been demonstrated using this approach in Germany, but to our knowledge no data have been reported from Switzerland, where these programs tend to be short (4 weeks) and exercise training is concentrated (2 h daily, 6 days per week). METHODS AND RESULTS: Seventeen patients (aged 58 +/- 6 years) who resided in a rehabilitation center for 4 weeks were compared with 11 patients (aged 54 +/- 7 years) given usual community care beginning approximately 6 weeks after coronary artery bypass surgery (CABS). Exercise training consisted of 1 h of group walking twice daily, with the intensity stratified into 4 levels based on clinical status and initial exercise capacity. All patients underwent pulmonary function testing and maximal ramp exercise testing on a cycle ergometer with continuous ventilatory gas exchange and lactate analysis before and after the study period. Patients receiving beta-blockers and those with cardiomyopathy or valvular heart disease were excluded. Medication status was not changed during the study period. Although maximal oxygen uptake increased by approximately 12 percent within both groups, the change was not significant between groups. Analysis of variance demonstrated that mean lactate levels were reduced throughout exercise within both groups (p < 0.001); however, there were no differences between groups. Oxygen uptake at the lactate threshold was not different in either group after the study period. CONCLUSIONS: Similar changes occur in the functional status of post-CABS patients regardless of their participation in the short but concentrated rehabilitation programs common in Switzerland, suggesting that these programs either begin too soon after CABS or are too short to achieve training benefits.