Clinical implementation of cardiac resynchronization therapy-regional disparities across selected ESC member countries.

BACKGROUND: The present analysis aimed to estimate the penetration of cardiac resynchronization therapy (CRT) on the basis of the prevalence and incidence of eligible patients in selected European countries and in Israel. METHODS AND RESULTS: The following countries were considered: Italy, Slovakia, Greece, Israel, Slovenia, Serbia, the Czech Republic, Poland, Romania, Hungary, Ukraine, and the Russian Federation. CRT penetration was defined as the number of patients treated with CRT (CRT patients) divided by the prevalence of patients eligible for CRT. The number of CRT patients was estimated as the sum of CRT implantations in the last 5 years, the European Heart Rhythm Association (EHRA) White Book being used as the source. The prevalence of CRT indications was derived from the literature by applying three epidemiologic models, a synthesis of which indicates that 10% of heart failure (HF) patients are candidates for CRT. HF prevalence was considered to range from 1% to 2% of the general population, resulting in an estimated range of prevalence of CRT indication between 1000 and 2000 patients per million inhabitants. Similarly, the annual incidence of CRT indication, representing the potential target population once CRT has fully penetrated, was estimated as between 100 and 200 individuals per million. The results showed the best CRT penetration in Italy (47-93%), while in some countries it was less than 5% (Romania, Russian Federation, and Ukraine). CONCLUSION: CRT penetration differs markedly among the countries analyzed. The main barriers are the lack of reimbursement for the procedure and insufficient awareness of guidelines by the referring physicians.

Implantable loop recorders for assessment of syncope: increased diagnostic yield and less adverse outcomes with the latest generation devices.

AIM: Aim of the study was to compare the diagnostic yield of implantable loop recorders (ILR) of two successive generations for the assessment of syncope. METHODS: Data on patients who had undergone ILR implantation for unexplained syncope in four Italian public hospitals were retrospectively acquired from the Medtronic Clinical Service database. After implantation, routine follow-up examinations were performed every 90 days, while urgent examinations were carried out in the event of syncope recurrence. RESULTS: The following findings were regarded as diagnostic: ECG documentation of a syncope recurrence; documentation of any of the arrhythmias listed by the current guidelines as diagnostic findings even if asymptomatic. Between November 2002 and March 2010, 107 patients received an ILR (40 Medtronic Reveal® Plus; 67 Medtronic Reveal® DX/XT) and underwent at least one follow-up examination. Diagnoses were made in 7 (17.5%) and 24 (35.8%) (P=0.043) patients, with a median time of 228 and 65 days, respectively. Three (42.9%) and 21 (87.5%) (P=0.029) diagnoses were based on automatically detected events, while adverse outcomes occurred in 6 and in 1 (P=0.01) patients, respectively. CONCLUSION: Our results show that the new-generation device offer a higher diagnostic yield, mainly as a result of its improved automatic detection function, and is associated with fewer adverse outcomes.

Incidence of paroxysmal atrial tachycardias in patients treated with cardiac resynchronization therapy and continuously monitored by device diagnostics.

AIMS: Little is known about the incidence of paroxysmal atrial tachycardias (PAT) in patients with heart failure (HF). The availability of cardiac resynchronization therapy (CRT) devices with extended diagnostics for AT enables continuous monitoring of PAT episodes. The aim of the study was to assess the incidence over time of PAT in HF patients treated with CRT. METHODS AND RESULTS: Consecutive patients in NYHA functional class III or IV despite optimal drug therapy, QRS duration > or = 130 ms, left ventricular ejection fraction < or = 35%, and left ventricular end-diastolic dimension > or = 55 mm were eligible for enrolment. Patients with permanent or persistent atrial fibrillation (AF) were not included in the study. The first follow-up examination was performed 2 weeks after implantation, to optimize atrial sensing and CRT. Subsequent follow-up examinations were carried out 15 and 28 weeks after implantation, to collect the telemetric data. A total of 173 patients (67 +/- 11 years, M 116) were enrolled. Complete arrhythmia monitoring data were available from 120 patients over a mean follow-up of 183 +/- 23 days. Atrial tachycardia episodes were detected through telemetry in 25 of 120 patients (21%) during at least one follow-up examination. Atrial tachycardia episodes were recorded in 29 and 17% (P = NS) of patients with and without previous history of AF, respectively. CONCLUSION: More than 20% of the overall HF patient population treated with CRT suffer PAT episodes. Paroxysmal atrial tachycardia may interfere with response to CRT. Therefore, telemetric data may be relevant to drive the appropriate therapy in each patient.

A method to calculate tissue impedance through a standard bipolar pacing lead.

UNLABELLED: The transthoracic impedance (T) and its variations may be estimated through the measurement of the electrical impedance between the can and the right ventricular coil of a defibrillation lead. This method may allow the monitoring of fluid overload before a heart failure attack. Aim of this study was to validate in vitro a method to calculate T in case of a standard bipolar pacing lead, by performing 3 measurements: standard unipolar impedance from the tip (Zuni-tip); unipolar impedance from the ring (Zuni-ring); standard bipolar impedance (Zbip). The formula we used is derived from the standard equivalent circuit of a pacing system: [Formula: see text] T represents the tissue impedance between the can and the electrodes of the lead. To validate the method we used a saline solution and 3 different pacing leads manufactured by Vitatron (Vitatron BV, Arnhem, The Netherlands): Impulse II (high impedance lead), Crystalline ActFix (screw-in lead), Brilliant S+ (VDD single-lead). The measured values of the saline solution impedance were compared to the values calculated through the formula. RESULTS: The calculated impedance of the solution, evaluated through the proposed formula, is reliable independently of the electrode used and highly correlated to the corresponding measured values (R>0.9). CONCLUSION: Tissue impedance may be calculated from standard unipolar and bipolar impedance measurements with a standard bipolar pacing lead.

Mitochondrial genome involvement in ischemia/reperfusion-induced adaptive changes in human myocardial cells.

AIM: Following previous studies on the ischemia-induced adaptive changes in human cardiac mitochondria, we examined in the present paper the interaction between nitric oxide-induced (NO) partial inhibition of Cyt. c oxidase (Cyt.OX) and mitochondrial encoded subunit 2 expression. Aim of the study was to investigate specific stages of the biochemical and molecular cascade which takes place in cytoprotective mechanisms of ischemic and reperfused cardiac cell. METHODS: We examined human left ventricle samples obtained from 20 patients undergoing elective valve surgery before aortic cross-clamping, 20+/-2 min (prolonged ischemia), 58+/-5 min after cross-clamping (intermittent ischemia) and 21+/-4 min after reconstitution of coronary blood flow (reperfusion). Cyt.OX activity was determined by spectrophotometric method and adenosine triphosphate (ATP) content using bioluminescent assay. Malondialdehyde (MDA) assumed as reactive oxygen species (ROS) generation marker was determined by high-performance liquid chromatography method. On the same cardiac samples mitochondrial encoded Cyt.OX subunit 2 expression was examined by immunoblot analysis and blu native gel electrophoresis method. Statistical study of obtained data was performed using repeated measures analysis of variance (ANOVA). RESULTS: Prolonged as well intermittent ischemia caused reduction of Cyt.OX activity and ATP, a moderate accumulation of ROS and down-regulation of Cyt.OX subunit 2. When reperfused the cardiomyocytes showed a progressive increase of Cyt.OX activity, ATP pools and Cyt.OX subunit 2 expression. ROS generation was significantly increased by the rapid oxygen re-immission in the cardiac cell. CONCLUSIONS: These data confirm the suggestion that prolonged as well as intermittent ischemia induces activation of cytoprotective mechanisms crucial for cardiac cell survival. Indeed, co-ordinated down-regulation of Cyt.OX activities, ATP pools and mitochondrial encoded Cyt.OX subunit 2 are in favour of an ischemia-activated adaptive mechanism leading to transient and reversible oxidative injury. This observation is confirmed by reduction of apoptosis molecular markers and by complete recovery of mitochondrial oxidative activities in reperfused cardiac tissue.

Mechanisms of cell protection by adaptation to chronic and acute hypoxia: molecular biology and clinical practice.

Several experimental and clinical studies have shown that specific biochemical and molecular pathways are involved in the myocardial and skeletal muscle cell tolerance to acute and/or chronic hypoxic injury. A number of different factors were proposed to play a role in the preservation of tissue viability, but to a few of them a pivotal role in the adaptive mechanisms to hypoxic stimuli could be ascribed. Starting from the observation that mitochondrial electron transport chain (ETC) enzymic complexes are the targets of oxygen reduced availability, most of data are compatible with a mechanism of enzymic adaptation in which the nitric oxide (NO) generation plays the major role. If the partial and reversible NO-induced inhibition of ETC enzymic complexes represents the most rapid and prominent adaptive mechanism in counteracting the damaging effects of hypoxia, the sarcolemmal and mitochondrial K+(ATP) channels activation results to be closely involved in cytoprotection. This process is depending on protein kinase C (PKC) isoform activation triggered by reactive oxygen species (ROS) generation, adenosine triphosphate (ATP) depletion and Ca++ overload. It is well known that all these factors are present in hypoxia-induced oxidative damage and mitochondrial Ca++ altered pools represent powerful stimuli in the damaging processes. The activation of mitochondrial K+(ATP) channels leads to a significant reduction of Ca++ influx and attenuation of mitochondrial Ca++ overload. Closely linked to these adaptive changes signal transduction pathways are involved in the nuclear DNA damage and repair mechanisms. On this context, an essential role is played by the hypoxia-induced factor-1alpha (HIF-1alpha) in terms of key transcription factor involved in oxygen-dependent gene regulation. The knowledge of the biochemical and molecular sequences involved in these adaptive processes call for a re-evaluation of the therapeutic approach to hypoxia-induced pathologies. On this light, some specific aspects of the therapeutic management of critically ill patients are taken into consideration and discussed in relation to the cellular biodynamics.

Deep sedation for magnetic resonance imaging. Personal experience.

AIM: Precision in diagnostic procedure and examination of paediatric patients often requires their absolute immobility. Deep sedation has proven to be an excellent method, allowing optimum technical quality of MRI particularly in younger age groups. The aim of study is to demonstrate the possible application of deep sedation through the use of 2 safe and manageable drugs. METHODS: We carefully evaluated and selected 82 patients (47 males and 35 females; average age 5.4 years): they came from various paediatrics departments. Deep sedation was practiced with: Chloral hydrate (60-80 mg/kg in one oral administration); propofol as intravenous bolus (2-2.5 mg/kg) followed by a maintenance infusion of 75-125 microg/kg/min. This was preceded by midazolam (0.05 mg/kg i.v.) outside the MRI room. Oxygen saturation (SpO2) was monitored in all patients along with heart rate in order to foresee the need for any possible therapeutic intervention. RESULTS: The sedation levels attained permitted the success of MRI assuring the immobilization required. Manually assisted mask ventilation was required for a period of 2-3 min in 5 patients treated with propofol. All other patients breathed autonomously. Complete reawakening occurred within 2 hours of drug administration. Surveillance was prolonged inside their respective units, however, without registering delayed side effects. CONCLUSION: The central point of the success of deep sedation is to define the type and dose of optimum drug for individual patients. This requires a qualified, expert group ready to intervene in the presence of adverse results of drugs administered. Propofol and chloral hydrate are the optimum drugs for diagnostic techniques requiring total immobilization and rapid reawakening.

Computationally inexpensive methods for intra-cardiac atrial bipolar electrogram compression.

AIM: This paper reports studies of mathematical algorithms for intra-cardiac atrial bipolar electrogram compression suitable with implementation on implantable devices. PATIENTS AND METHODS: Bipolar intra-cardiac electrograms (IEGMs) of high right atrium were obtained from 20 patients who underwent electrophysiological studies for arrhythmias. Four thousand seven hundred and eighty-two seconds of IEGM were collected and divided into three rhythm groups: sinus rhythm (SR), atrial fibrillation (AF) and atrial flutter (AFL). Since mathematical algorithms suitable for use with implantable devices demand low computational cost, we employed piecemeal linear approximation methods (ZOP--Zero Order Prediction and SAPA--Scan Along Polygonal Approximation), and beat detection method (Peak) both or which need small numbers of operations to perform electrogram compression. Compression ratio (CR) and percent root mean square difference (PRD) were used to compare the three methods, with statistical analyses performed using paired t-test. RESULTS AND CONCLUSION: The best performance was obtained using the Peak method which reaches an average CR of 10.6 in the case of SR group, 2.8 for AF, and 3.6 for AFL groups, respectively, while PRD lies below 2% for SR and AFL groups and 6% for the AF group. Results show that, for bipolar electrograms, the Peak method reaches statistically significant better performance (P<0.001) in all cases except for Peak vs SAPA applied to AF (P=0.2). The number of operations necessary to compress the data indicate that time consumption can be reduced to be suitable for real time compression in implantable devices. The Peak method, which was assumed to receive the instant of occurrence of each recognized beat, from the hardware of the device, requires fewer operations than ZOP and SAPA. Increasing the length of electrograms recorded in pacemakers will enhance the amount of information provided by the implantable device, allowing more detailed characterization of the intra-cardiac activity and leading to new perspectives in arrhythmia diagnosis and therapy.

[Percutaneous cervical cordotomy in the therapy of incidence pain]. / La cordotomia cervicale percutanea nella terapia del dolore incident.

BACKGROUND: Incident pain does not respond to opioid treatment and it is not easily relieved with other therapeutic strategies (local intrapleural or spinal analgesia, phenol blocks etc.). For this reason cervical percutaneous cordotomy at C(1)-C(2) interspace is the only effective antalgic therapy in patients whose life expectancy is more than three to six months. METHODS: This study is a rectrospective review of 22 patients with cancer and incident pain from brachial, lumbar-sacral plexus injury and gluteal ulcer. RESULTS: Cordotomy provided excellent contralateral side pain relief in 21 patients; pain relief was maintained up to death and to the moment of last observation in living patients. In one deaf patient it was impossible to carry out the procedure due to incomplete co-operation and pain returned after 48 hours. Ventilatory depression caused death in one patient. Other complications recorded included ataxia, headache, motor deficit, dysesthesia and orthostatic hypotension. CONCLUSIONS: The conclusion is drawn that percutaneous cordotomy should, in carefully selected cases, be considered the only technique to relieve incident pain.

Signal transduction mechanisms and nitric oxide in hypoxic and ischemic human cardiac ventricular cell.

BACKGROUND: Nitric oxide (NO) plays a well-known role in regulating endocellular adaptive changes to acute hypoxia and ischemia. The reversible inhibition of complex IV of the mitochondrial respiratory chain fulfils a cytoprotective function, whereas the progressive inhibition of complex I and II reveals the onset of irreversible oxidative damage due to persistent NO production in response to prolonged hypoxia and/or ischemia. In hypoxic or ischemic human myocardial cells, death may be caused by apoptosis or necrosis following the activation of the biomolecular signal transduction mechanisms. The activation of MAPK (mitogen-activated protein kinase) followed by ERK (extracellular regulated kinase) and p21waf is necessary in this respect. The myocardial cell is well known for its postmitotic nature and through their activation these kinases aim to repair DNA damaged by oxidative stress in order to guarantee the survival of the cell itself. A direct correlation has been found between the activation of these kinases and NO production. It was decided to carry out this study in hypoxic and ischemic human heart ventricular tissue in order to confirm this connection. METHODS: In 10 patients undergoing cardiac valvular replacement, ventricular samples were collected before aortic clamping, after 15 min of ischemia and after 60 minutes during which the patients received doses of hematic cardioplegic solution at regular intervals. RESULTS: The results show a rapid increase in NO production in response to ischemia followed by a tendency for levels of this element to fall. MAPK, ERK and p21waf activation was parallel to No production, irrespective of the repeated administration of hematic cardioplegic solution. The heart tissue examined 60 minutes after aortic clamping came from a ventricular area subject to preconditioning mechanisms. In view of this, the data obtained must be seen in terms of the close correlation between the mitochondrial action played by NO and the contemporary and consequent activation of unique signal transduction mechanisms. CONCLUSIONS: This may prove important to our understanding of preconditioning mechanisms involving the myocardial and confirms the role played by the said kinases with regard to the survival of hypoxic and ischemic human heart tissue. Although not final, these deductions may be important in clinical and therapeutic terms for the management of critical patients.

Biomolecular and biochemical response of myocardial cell to ischemia and reperfusion in the course of heart surgery.

BACKGROUND: Previous studies have shown that biomolecular and biochemical adaptive changes antagonize oxidative damage due to hypoxia and ischemia in myocardial cells. The aim of our study was to verify in human ischemic and reperfused cardiac tissue the relationship between mitochondrial enzyme activities and the activation of HSP70 and c-fos syntheses in the context of a cytoprotective mechanism. Nitric oxide (NO) modulating effects on mitochondrial respiratory chain enzyme activities in ischemic and reperfused tissue were investigated (preliminary report). METHODS: During elective coronary artery bypass grafting, in 30 consecutive patients ventricle samples were taken one before aortic clamping the second after 55+/-8 min ischemic period and the third 34+/-5 after final reperfusion. Coronary sinus blood samples were taken in parallel to assess free radical release measured by malonaldehyde (MDA) levels. In a small number of patients (N=5) nitric oxide tissue levels were analyzed. RESULTS: When compared with normoxic tissue, a significant decrease in cytochrome Coxidase (COX) and succinate Cyt-c reductase (SCR) activities in ischemic and reperfused samples were observed. The activation of HSP70-72 and c-fos transcription factor was evident in courses of ischemia and reperfusion. Blood MDA levels underline the concept that oxyradical generation characterize the peroxidative damage in reoxygenated myocardial tissue while adaptive changes which occur in ischemic cells seem to antagonize the oxyradical injury. CONCLUSIONS: In the course of heart surgery the myocardial cell seems to prevent ischemic damage by activating some peculiar biomolecular and biochemical adaptive changes which permit the reversibility of the oxidative injury. In contrast it appears evident that massive and rapid reoxygenation of the cardiac tissue leads to peroxidative damage due to oxyradical generation. Nitric oxide seems to play a crucial role in cellular adaptation to ischemia even if further studies will be needed to elucidate these findings. From the data obtained in this work we cannot draw certain conclusions in terms of human cardiac cell adaptation to ischemia whereas it seems convincible that reoxygenation, as actually employed in clinical practice, compromises the integrity of the cells.

[The nitric oxide metabolism in the hypoxic, ischemic and reperfused human skeletal muscle cell: clinical and therapeutical observations]. / L'ossido nitrico nella cellula muscolare umana ischemica e riperfusa: connessioni cliniche e terapeutiche.

BACKGROUND: The biochemical and metabolic role played by nitric oxide (NO) in course of oxidative stress due to cell hypoxia, ischemia and reperfusion has a determinant relevance in the mitochondrial adaptive changes which antagonize the irreversible morpho-functional damage. In particular conditions, such as in prolonged ischemia and/or exogenous NO supplementation, this element is present in the radical form (NOO*) concurring to peroxidative cell injury. Aim of this study was to investigate these opposite NO aspects in hypoxic, ischemic and reperfused human skeletal muscle tissue. METHODS: Skeletal muscle samples were taken during elective knee orthopedic surgery in 10 consecutive patients. The biopsies were obtained before, after 5+/-1 min and 58+/-2 min from tourniquet application and then after 18+/-3 min following muscle reperfusion. The samples, immediately frozen in liquid nitrogen, were assayed for endocellular free NO following the gas-amperometric method described by Palmerini C. RESULTS: When compared with normoxic tissues, a significant decrease in free NO content was observed in hypoxic samples. After about 60 min of prolonged ischemia the NO levels show an evident increase, while the tissue reperfusion leads to a progressive restoration of physiological content in the cellular free nitric oxide. CONCLUSIONS: The obtained data in hypoxic muscle cell seem to underline the pivotal role played by NO in adapting the cytochrome c oxidase oxidative activity to lower O2 bio-availability. On the other hand the prolonged ischemia leads to a consistent NOO* generation triggered by oxyradical generation and Ca2+ intracellular over load. Even if the tissue reoxygenation restores the normal NO levels it is arguable that the pre-treatment of ischemic cell with antioxidants, Ca-antagonist and Dexamethasone supplementation could represent a crucial and specific therapeutic approach to critically ill patient.

Adaptive changes in response to acute hypoxia, ischemia and reperfusion in human cardiac cell.

BACKGROUND: Previous studies have shown that biomolecular and biochemical adaptive changes antagonize oxidative damage due to hypoxia and ischemia in myocardial cells. The aim of our study was to verify in human ischemic and reperfused cardiac tissue the relationship between mitochondrial enzyme activities and the activation of HSP70 and c-fos synthesis in the context of a cytoprotective mechanism. Nitric oxide (NO) modulating effects on mitochondrial respiratory chain enzyme activities in ischemic and reperfused tissue were investigated (preliminary report). METHODS: During elective coronary artery bypass grafting, in 30 consecutive patients ventricle samples were taken one before aortic clamping the second after 55 +/- 8 min ischemic period and the third 34 +/- 5 after final reperfusion. Coronary sinus blood samples were taken in parallel to assess free radical release measured by malondialdehyde (MDA) levels. In a small number of patients (N = 5) nitric oxide tissue levels were analyzed. RESULTS: When compared with normoxic tissue, a significant decrease in cytochrome oxidase (COX) and succinate Cyt-c reductase (SCR) activities in ischemic and reperfused samples were observed. The activation of HSP70-72 and c-fos transcription factor was evident in courses of ischemia and reperfusion. Blood MDA levels underline the concept that oxyradical generation characterizes peroxidative damage in reoxygenated myocardial tissue while adaptive changes which occur in ischemic cells seem to antagonize the oxyradical injury. CONCLUSIONS: In the course of heart surgery the myocardial cell seems to prevent ischemic damage activating some peculiar biomolecular and biochemical adaptive changes which permit the reversibility of the oxidative injury. In contrast it appears evident that massive and rapid reoxygenation of the cardiac tissue leads to peroxidative damage due to oxyradical generation. Nitric oxide seems to play a crucial role in cellular adaptation to ischemia even if further studies will be needed to elucidate these findings. From the data obtained in this work we cannot draw certain conclusions in terms of human cardiac cell adaptation to ischemia whereas it seems convincing that reoxygenation, as actually employed in clinical practice, compromises the integrity of the cells.

Automatic atrial tachyarrhythmia detection from intracardiac electrograms.

BACKGROUND: Automatic atrial tachyarrhythmia recognition is crucial in order to allow a correct switching-mode function of dual-chamber pacemakers and to avoid inappropriate shocks of ventricular implantable cardioverter-defibrillators. In this paper we considered three algorithms suitable for implantable devices. The first was based on the atrial cycle length; the others analyze different morphologic characteristics of atrial signals. METHODS: Intracardiac bipolar electrogram recordings were obtained from the high right atrium during electrophysiological study. Twenty patients were considered, some of them presenting with different types of cardiac rhythm at different intervals of the study. Cardiac rhythms were divided into three groups: sinus rhythm consisting of 2,196 s obtained from 12 subjects, atrial fibrillation consisting of 771 s obtained from 7 subjects, and atrial flutter consisting of 1,793 s obtained from 7 subjects. The automatic detection was performed on each electrogram segment lasting 1 or 4 s. Atrial segments were separated into two subgroups: the first for the training of the algorithm and the second for testing and validation of results. We considered two types of statistical analysis: comparison between pairs of rhythm (paired classification), and classification among the three different groups (direct classification). RESULTS: The combination of the cycle length algorithm with a morphological method achieved the best performance for both statistical analyses. Paired classification resulted in the following: atrial fibrillation vs sinus rhythm was detected with no error; atrial flutter vs sinus rhythm with a total accuracy of 99.3% (sensitivity 99.4%, specificity 99.2%); atrial fibrillation vs atrial flutter with a total accuracy of 99.1% (sensitivity 98.5%, specificity 99.4%). The total accuracy achieved for the direct classification was 98.6% (average sensitivity 98.5%, specificity 98.8%). CONCLUSIONS: Our results support the association of algorithms for future enhancement of atrial tachyarrhythmia detection in dual-chamber devices, thanks to the limited computational effort.

[Biochemical and metabolic aspects of oxyradical pathology in the hypoxic-ischemic reperfused human skeletal muscle tissue. Clinical markers and therapeutic approach]. / Aspetti biochimici e metabolici della patologia ossiradicalica nel muscolo scheletrico umano ipossico-ischemico-riperfuso. Parametri valutativi nella clinica e nella terapia del paziente critico.

BACKGROUND: Following our previous studies on the biomolecular and biochemical aspects of the human tissue oxidative damage due to hypoxia, ischemia and reperfusion, aim of the present work is to evaluate the role played by oxyradical generation in the morphofunctional cellular injury. We evaluated the tissue levels of some metabolic markers (MDA, Catalase, Uric Acid) to obtain a pathogenic picture and then a therapeutic approach closely related to the cellular biodynamics. METHODS: A skeletal muscle samples were taken during elective knee orthopedic surgery in 20 consecutive patients. The biopsies were taken in normoxic conditions and after 5 +/- 1 and 62 +/- 3 min form tourniquet application and finally 21 +/- 2 min following muscle reperfusion. The samples were assayed for tissue Malondialdeyade (MDA), uric acid and catalase (CAT) contents with HPLC and fluorimetric procedures. All data were evaluated in terms of computerized statistical analysis. RESULTS: When compared to normoxic tissue (1.24 +/- 0.26 nmoli.mg-1 protein), the MDA levels show a moderate increase in hypoxic (1.66 +/- 0.12) and ischemic tissue (1.78 +/- 0.13), while highly significant is the rise in reperfused muscle MDA content (5.94 +/- 0.15). The uric acid as far as CAT shows no appreciable alterations in hypoxia and ischemia. Following reoxygenation an increase in uric acid contents with a concomitant CAT tissue consumption appear evident. CONCLUSIONS: The obtained data seem to underline the cytoprotective role played by adaptive changes in the hypoxic and ischemic human cells. On the contrary, the rapid reoxygenation of the ischemic tissue appears to start oxyradical neo-generation. In clinical and therapeutic terms these observations underline a peculiar and different approach to the critically ill patient.

Detecting incipient vasovagal syncope: intraventricular acceleration.

The peak endocardial acceleration (PEA) caused by ventricular isometric contraction can be measured with an implantable microaccelerometer located inside the tip of a normal unipolar pacing lead. It has been shown that PEA correlates with myocardial contractility and the maximum rate of rise of ventricular pressure (peak dP/dt) of the left ventricle. A PEA measuring system was temporarily inserted into the apex of the right ventricle in seven patients affected by syncope of uncertain origin. Each patient subsequently underwent 60 degrees tilt testing with three different protocols: without pharmacological challenge (baseline); potentiated with sublingual trinitroglycerin (at a dose of 0.3 mg); and with isoproterenol infusion (at a dose of 3 micrograms/min). Each phase lasted 20 minutes. Syncope was induced in 1 patient during the baseline phase, in 3 patients during the trinitrin phase, and in 4 patients during the isoproterenol phase. Six patients had a negative response during the baseline phase and served as a control group. From the beginning of upright posture to the time of maximum heart rate, PEA increased by about the same amount in both positive and negative patients, but absolute values were from two- to three fold higher with isoproterenol (from 1.2 +/- 0.5 G to 1.6 +/- 0.8 G, from 0.8 +/- 0.2 G to 1.2 +/- 0.4 G, and from 2.8 +/- 1.8 G to 3.6 +/- 1.8 G, respectively, for negative, positive baseline or trinitrin, and positive isoproterenol tests). At the time of syncope, PEA values fell to baseline values. PEA changes were inversely correlated with blood pressure changes and directly correlated with heart rate changes. Thus, tilt induced syncope occurred both at low and high levels of left ventricular contractility. Whether spontaneous syncopes occur at low or high PEA behavior remains to be established. Since heart rate correlates well with changes in PEA and is far easier to measure, it is unlikely that a PEA measurement system or, in general, a contractility-based system, might become an ideal sensing parameter for the introduction of devices to combat vasovagal syncope.