First clinical experiences with an endovascular clamping system for neuroprotection during carotid stenting.

OBJECTIVES: This report evaluates the feasibility and efficacy of an endovascular blood flow blockage technique to prevent intracerebral embolization of plaque debris during carotid artery stenting. METHODS: Forty-two patients were enrolled in five clinical sites in Germany and Italy with either an asymptomatic internal carotid artery stenosis > or =75% (mean 87%) or a symptomatic stenosis > or =60% (mean 85%). Cerebral protection during the stenting procedure was achieved using an endovascular clamping technique, obtained by occlusion of the external and common carotid artery via two independently inflatable balloons integrated in the Mo.Ma system. Blood with particulate plaque debris was aspirated before flow was restored. The patient's clinical and the neurological status were assessed during intervention, at discharge, and at 3 months follow-up. RESULTS: Stenting was performed in all but one patient. The mean flow occlusion time was 10.6+/-6.5 min. Transient clamping intolerance was observed in five patients (12%). In two patients, neurological deficits persisted for 2 and 12 h, respectively. Two minor strokes (4,7%) occurred at 5 and 72 h after the procedure. No major strokes or deaths were observed at 3 months follow-up. CONCLUSIONS: This first clinical experience with the Mo.Ma device substantiates the feasibility of endovascular clamping in preventing cerebral embolization during carotid artery stenting.

Experimental treatment of the acute cardiovascular toxicity of caffeine.

STUDY DESIGN: The intravenous infusion of caffeine-sodium salicylate (15 mg/kg/min) into artificially ventilated and anesthetized rats caused a progressive fall in arterial blood pressure which was mainly due to a decrease in peripheral resistance. Cardiac output increased initially by 15% but then declined after 30 minutes. The electroencephalogram showed sinus tachycardia and ectopic beats mainly in the form of monomorphic ventricular bigeminy which began after 22.8 minutes. Fatal ventricular fibrillation occurred in all animals by 66.9 +/- 3.1 minutes. Treatment of cardiac arrhythmia by repeated intravenous injections of propranolol (1 mg/kg) or verapamil (1 mg/kg) was effective and prolonged survival time to 91.7 +/- 4.4 or 84.3 +/- 2.9 minutes, respectively (p < 0.05). Propranolol also prolonged survival time when administered in a single dose of 20 mg/kg i.v. 10 minutes before the initiation of caffeine infusions. Repeated administrations of quinidine sulfate (5 mg/kg), phenytoin (5 mg/kg), or lidocaine (1-5 mg/kg), on the other hand, exerted very short antiarrhythmic activity and did not prolong survival time at all. Fluid therapy with polygeline plasma expander (0.5 mL/kg/min) did not influence caffeine-induced cardiovascular failure in any way. CONCLUSIONS: Ventricular ectopia leading to fibrillation accounts for the lethal outcome of caffeine poisoning in anesthetized rats and can be antagonized by treatment with propranolol or verapamil.

Electrophysiological characteristics of bipolar membrane carbon leads with and without steroid elution compared with a conventional carbon and a steroid-eluting platinum lead.

In a controlled study, the following four bipolar leads with passive fixation were implanted in 46 patients with the Siemens-Multilog-VVI or Sensolog-VVIR-pacemakers: membrane covered activated porous carbon with steroid elution (Siemens 1402 T, 11 patients) and without (Siemens 1403 T, 15 patients); activated carbon (Siemens 1010 T, 10 patients); and platinum with steroid elution (Medtronic Cap-Sure 5026, 10 patients). Stimulation threshold (STH) (assessed by a vario-test), impedance (IMP), and the intracardial R wave potential (IRW) (both gauged by a telemetric method) were measured 1, 5, and 10 days as well as 3 and 6 months after implantation during unipolar and bipolar stimulation, chronaxie rheobase product (CRP) and energy consumption (EC) were systematically determined. Differing insignificantly at the first day after implantation, STH is significantly lower for the 1402 T and CapSure 5026 leads at the tenth day. However, the 1402 T lead shows a significant increase of STH in the follow-up, in contrast to the other leads. The lowest chronic STH was found in the CapSure 5026 lead (CRP is significantly lower in all other leads, too). IMP is significantly lower in the CapSure 5026 lead compared to 1010 T lead. EC does not differ significantly during chronic stimulation in spite of the best possible programming of pulse amplitude and duration. No significant changes of IRW were observed. Unipolar versus bipolar stimulation shows significantly lower STH, CRP, and IMP, differences of EC and IRW were insignificant. In conclusion, the addition of steroid in membrane covered carbon leads protracts the increase of STH, but does not prevent it. The CapSure 5026 lead shows advantageous stimulation characteristics, but energy consumption is not significantly reduced because of low impedance and impossibility of programming an appropriate low output in Multilog pacemakers.

[Detection of stress-induced myocardial ischemia in isolated coronary ectasia and aneurysm (dilatative coronaropathy)]. / Untersuchungen zum Nachweis einer belastungsinduzierten Myokardischämie bei isolierten Koronarektasien und -aneurysmen ("dilatative Koronaropathie").

Forty eight patients with bilateral isolated non-stenotic coronary artery ectasia or aneurysm without associated cardiac defects ("dilated coronaropathy") were identified in consecutive diagnostic cardiac catheterizations between 1986-6/1994 (angiographic incidence 0.44%). Ectasia was defined as a luminal dilatation of the 1.5-2-fold, aneurysm of more than double the normal limits. In 16 patients a myocardial infarction (5 non-q-infarctions/11 q-wave-infarctions) was the indication for coronary angiography, a thrombotic occlusion of the infarct vessel was documented in 8/16 patients. In patients without myocardial infarction (study group) an evaluation of exercise-induced myocardial ischemia was performed by means of a coronary sinus lactate study, treadmill ergometry and Thallium-201-scintigraphy. A corresponding coronary insufficiency was objective in all tests in the study group. An exercise-induced myocardial ischemia was found in 21/31 in the coronary sinus study, 19/29 in the treadmill ergometry and 13/26 patients in the scintigraphy; significant differences were found in comparison to the results of a control group of patients without heart disease (n = 29, p < 0.001). After administration of 0.8 mg nitroglycerin (NTG) a further significant deterioration of myocardial ischemia was measured in the 21 patients with pathologic lactate metabolism developing a frank cardiac lactate production (p < 0.03). The extent of myocardial ischemia in the coronary sinus study was significantly correlated to the coronary diameters of the proximal and middle segments of the Ramus interventricularis anterior and the middle segment of the Ramus circumflexus (r = 0.87, p < 0.02). A differentiation between ectasia and aneurysm therefore seems to be of functional relevance. Angiographic stigmata of an impaired coronary blood flow such as a segmental to and from movement and a local deposition of dye were found significantly more often with increasing coronary diameters (p < 0.04). "Dilated coronaropathy" is an entity of non-stenotic, ischemic coronary artery disease. NTG was of no therapeutic benefit or led to an aggravation of the exercise-induced myocardial ischemia. Because of this potential adverse effect the administration of NTG should be avoided in "dilated coronaropathy".

[Transient pacemaker dysfunction and spontaneous arrhythmias in symptomatic and asymptomatic patients with ventricular demand pacemakers]. / Transitorische Schrittmacherfehlfunktionen und spontane Arrhythmien bei symptomatischen und asymptomatischen Patienten mit Kammerbedarfsschrittmachern.

This prospective cross-sectional study include 100 consecutive patients (56 males, 44 females, 29 to 86 (mean = 67.5 +/- 12.2) years) with ventricular inhibited demand pacemakers 0.1 to 94.7 (mean 23.3 +/- 25.4) months after pacemaker implantation. Fifty-two patients were free of symptoms, whereas 48 patients were still complaining of syncope, dizziness, or palpitations. After history, physical examination, and 12-lead standard ECG all patients underwent 24-h Holter monitoring. A computer-aided analysis of spontaneous arrhythmias was done first. In a second run computed-aided analysis of transient pacemaker dysfunctions was performed with a specially designed pacemaker module. There were no significant differences between asymptomatic and symptomatic patients with regard to the incidence of transient pacemaker dysfunctions, with regard to defined types of pacemaker dysfunctions, spontaneous ventricular arrhythmias, and with regard to supraventricular tachycardias. A significant difference between asymptomatic and symptomatic patients was found, however, regarding the Lown classification of ventricular arrhythmias, because asymptomatic patients showed class 0 and I/II arrhythmias more frequently (p < 0.025). In the 100 patients a total of 6609 pacemaker dysfunctions were observed, 5104 failures to sense and 1505 inappropriate inhibitions. Most patients showed up to 240 pacemaker dysfunctions per 24 h. There were no failures to capture. Different types of pacemaker dysfunctions were found with different clinical implications. Due to the Holter findings in nine patients pacemakers were reprogrammed or replaced. After pacemaker implantation the number of patients with severe symptoms significantly decreased compared to the number of patients before pacemaker implantation. Nonetheless, there was a number of patients still complaining of symptoms after pacemaker implantation. In only a few patients did pacemaker implantation worsen symptoms . Our data show that with use of long-term ECG transient pacemaker dysfunctions and spontaneous arrhythmias are more frequent than patients' history and common standard techniques in the pacemaker clinic may suggest Holter monitoring, therefore, is a useful diagnostic tool, not only in symptomatic, but also in asymptomatic pacemaker patients. It allows to obtain a reliable survey of the real amount of transient pacemaker dysfunctions in the individual patient, which is the base for further therapeutic decisions.

Detection of a hypercoagulable state in nonvalvular atrial fibrillation and the effect of anticoagulant therapy.

The purpose of the study was to evaluate alterations of the hemostatic system and the effect of anticoagulant therapy in nonvalvular atrial fibrillation. A set of molecular hematologic markers was measured prospectively in 69 patients with atrial fibrillation and 28 age-matched patients in sinus rhythm. Significantly elevated levels of thrombin-antithrombin III complex (8.5 +/- 1.6 vs. 2.5 +/- 0.3 micrograms/l; p < 0.001), fibrin monomers (27.1 +/- 3.2 vs. 13.4 +/- 3.7 nM; p < 0.001), D-dimers (788 +/- 76 vs. 405 +/- 46 micrograms/l; p < 0.005), and tissue-type plasminogen activator (9.6 +/- 0.5 vs. 7.2 +/- 0.5 micrograms/l; p < 0.05) were observed in patients with atrial fibrillation compared to those in sinus rhythm. In a subgroup of patients in whom anticoagulant therapy with oral coumadin or standard intravenous heparin was established after the initial study, hemostatic activation decreased significantly. In conclusion, molecular hematologic markers indicate a hypercoagulable state in atrial fibrillation which may characterized a group of patients at elevated risk of thromboembolic disease.

[Noninvasive diagnosis of coronary heart disease with cardiokymography: use of signal averaging technique]. / Nichtinvasive Diagnostik der koronaren Herzerkrankung mit Kardiokymographie: Einsatz der Signalmittelungstechnik.

Regional wall motion abnormality is the best indicator for coronary ischemia. Myocardial wall motion is registrated by cardiokymography (CKG), a mechanocardiographic method. Because of the high incidence of artefacts, echocardiography and nuclear imaging technique have been preferred. Computer-assisted signal averaging CKG improves practicability and allows measurements during exercise testing. Exercise testing was performed in 54 patients with suspected ischemic heart disease without mitral or aortic valve dysfunction, myocardial infarction or prior cardiac surgery. The results of simultaneously recorded ECG and CKG were compared with coronary angiographic results. CKG sensitivity and specificity were higher than that of ECG (76 and 80% vs 71 and 52%). If diagnosis was based on pathological or nonpathological results of both CKG and ECG, sensitivity and negative predictive value increased to 87 and 83%, respectively. Sensitivity reached 93% when only one pathological result was required. CKG combined with signal-averaging techniques has advanced to become a specific and sensitive tool in the non-invasive diagnostic approach to ischemic heart disease.

[The reliability of computer-assisted long-term ECG analysis of pacemaker malfunction in patients with ventricular demand pacemakers]. / Zuverlässigkeit computergestützter Langzeit-EKG-Analyse von Schrittmacherfehlfunktionen bei Patienten mit Kammerbedarfsschrittmachern.

The importance of the pacemaker follow-up clinic has markedly increased in the face of the currently available multiprogrammable pacemakers. In contrast to the common standard techniques in assessing pacemaker dysfunctions, Holter monitoring allows the detection of transient pace-maker dysfunctions during a long period of time. Especially computer-aided analysis provides a considerable progress, because different pacemaker dysfunctions can be detected during prolonged time periods, and--in contrast to visual analysis--a reliable survey of the real extent of transient pacemaker dysfunctions in the individual patient is assessed. The reliability of computer-aided analysis by a specially designed module was prospectively investigated in 100 consecutive patients with permanent ventricular inhibited demand pacemakers. It could be demonstrated that the positive predictive accuracy of this analysis was limited to 60.2% in detecting failures to sense and 63.2% in detecting inappropriate inhibitions, respectively. All detected failures to capture were false positive events. The positive predictive accuracy, therefore, was not calculated for this category of event. The overall positive predictive accuracy was 59.9%. In contrast, the sensitivity of computer-aided analysis was remarkably high. Possible causes of false positive and false negative findings are described. The reliability of pacemaker pulse detection was also investigated. Out of 100 analyzed Holter recordings five showed a temporary total loss of pacemaker pulses. Loss of single pacemaker pulses was found in 30 patients. False positive pacemaker pulses were seen in three patients. These results show that visual control and validation by an experienced physician are mandatory.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary angiosarcoma of the heart. Report of a case and review of the literature.

We report on a 44-year-old male with primary cardiac angiosarcoma who died 11 months after onset of nonspecific symptoms (thoracic pain and general fatigue) of intracerebral metastases. A right atrial tumor mass and a pericardial effusion could be demonstrated by transthoracic and transesophageal echocardiography. Cardiac angiography showed a right atrial hemangioma, fed by the right coronary artery. In a review of 108 cases of primary cardiac angiosarcoma we summarize clinical features, diagnostic means, therapeutic approaches and life expectancy of this rare disease.

[Pacemaker syndrome with AV-synchronized stimulation of the heart]. / Schrittmachersyndrom bei AV-synchronisierter Stimulation des Herzens.

Characteristic signs of the pacemaker syndrome occurred in a 69-year-old woman with intermittent 3 degrees atrioventricular (AV) block after implantation of a dual-chamber AV-synchronized pacemaker. Cannon beats due to inappropriate atrial timing were the main haemodynamic finding. Their development and size depended on the programmed AV interval and AV-synchronized mode of stimulation. Very long AV intervals in the DDD mode at a heart rate of 100/min caused very unpleasant palpitations and pulsations in the upper thorax. The symptoms due to the cannon beats were avoided by changing to a short AV interval. The clinical and haemodynamic events were thus the consequence of preserved sinus node function with subsequent atrial triggering.

Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction.

In a previous study on the diagnostic efficiency of troponin T measurements in patients with suspected acute myocardial infarction (AMI), the authors found a high variability of troponin T serum concentration changes on day 1 in patients with AMI who underwent thrombolytic treatment. Therefore, the aims of the present study were to investigate the intracellular compartmentation of troponin T and to analyze the effects of AMI reperfusion on the appearance kinetics of cardiac troponin T in serum. Cardiac troponin T was measured with a newly developed bideterminant sandwich assay using cardiospecific, affinity-purified polyclonal antibodies and peroxidase-labeled monoclonal antibody. An unbound cytosolic troponin T pool was found in ultracentrifuged homogenates of myocardial tissue of different species ranging from 0.013 to 0.036 mg/g wet weight. The soluble troponin T molecule had electrophoretic properties identical to troponin T compartmented in the myofibrils. The clinical study group comprised 57 patients with AMI undergoing thrombolytic treatment. Blood flow to the infarct zone and point of time of reperfusion were tested by immediate and late angiography. The appearance of troponin T in serum on day 1 after the onset of AMI depended strongly on reperfusion and on duration of ischemia before reperfusion. Thus, in patients with early reperfused AMI, a marked peak in troponin T serum concentrations was found at 14 hours after the onset of pain. This early troponin T peak was absent in patients with AMI reperfusion occurring greater than 5.5 hours after the onset of pain and in patients with nonreperfused AMI. By contrast, the kinetics of troponin T release after the first day after AMI were unaffected by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive assessment of perioperative myocardial cell damage by circulating cardiac troponin T.

Troponin T is a unique cardiac antigen which is continuously released from infarcting myocardium. Its cardiospecificity as a marker protein might be particularly useful in assessing myocardial cell damage in patients undergoing cardiac surgery. Therefore, circulating troponin T was measured in serial blood samples from 56 patients undergoing cardiac surgery and in two control groups--22 patients undergoing minor orthopaedic surgery and 12 patients undergoing lung surgery by median sternotomy. In both control groups no troponin T could be detected, whereas activities of creatine kinase were raised in all 12 lung surgery controls and activities of the MB isoenzyme were raised in five of the 12 patients in the lung surgery group and in four of the 22 patients in the orthopaedic surgery group, respectively. All the patients undergoing coronary artery bypass grafting (n = 47) and cardiac surgery for other reasons (n = 9) had detectable concentrations of troponin T. Five patients had perioperative myocardial infarction detected as new Q waves and R wave reductions. In these five patients troponin T release persisted and serum concentrations (5.5-23 micrograms/l) reached a peak on the fourth postoperative day. In the 51 patients without perioperative myocardial infarction serum concentrations and the release kinetics of troponin T depended on the duration of cardiac arrest. In patients in whom aortic cross clamping was short troponin T increased slightly on the first postoperative days; in patients with longer periods of aortic cross clamping troponin T concentrations were higher and remained so beyond the fifth postoperative day. In patients with non-specific changes on the electrocardiogram troponin T concentrations were significantly higher on days 1 and 4 after operation than in patients with normal postoperative electrocardiograms(11.2 (5) and 4.5 (2.6) v 8.2 (3.4) and 2.9 (1.6) 1microg/l). Serum concentrations of troponin T showed some myocardial cell damage in every patient undergoing cardiac surgery. The persistent increases that were more common in patients with longer periods of cardiac arrest must have been caused by damage to the contractile apparatus. These results suggest that perioperative myocardial cell necrosis may be more common than indicated by changes of the QRS complex on the electrocardiogram.

Diagnostic efficiency of troponin T measurements in acute myocardial infarction.

BACKGROUND: The present study was designed to evaluate the efficiency of a newly developed troponin T enzyme immunoassay for the detection of acute myocardial infarction. METHODS AND RESULTS: The study comprised 388 patients admitted with chest pain and suspected myocardial infarction and 101 patients with skeletal muscle damage and additional suspected myocardial cell damage. Troponin T was elevated to more than twice the analytical sensitivity of the assay (0.5 microgram/l) in all patients with non-Q wave (range, 1.2-5 micrograms/l) and Q wave infarction (range, 3-220 micrograms/l). Troponin T appeared in serum as early as 3 hours after onset of pain in 50% of the patients and remained elevated in all patients for more than 130 hours, revealing release kinetics of both free cytosolic and structurally bound molecules. The diagnostic efficiency of troponin T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98% until 5.5 days after admission, if patients with unstable angina were excluded from analysis. In the 79 patients with unstable angina, troponin T was elevated (range, 0.55-3.1 micrograms/l) in at least one blood sample from each of 37 patients (56%). Circulating troponin T was correlated to the presence of reversible ST segment or T wave changes on the electrocardiogram (p less than 0.005) and to the frequency of in-hospital complications. In the 101 patients with skeletal muscle damage and suspected additional cardiac muscle damage, troponin T was the most useful test; its efficiency was 89% or 94% (depending on the discriminator value used) as compared with 63% for creatine kinase-MB. CONCLUSIONS: Thus, the data of the study indicate that the newly developed troponin T test improves the efficiency of serodiagnostic tools for the detection of myocardial cell necrosis as compared with conventionally used cardiac enzymes.

The complete sequence of the human beta-myosin heavy chain gene and a comparative analysis of its product.

We have isolated and sequenced the gene and the cDNA coding for the human cardiac beta-myosin heavy chain (designated MYH7). The gene is 22,883 bp long. The 1935 amino acids of this protein (Mr223,111) are encoded by 38 exons. The 5' untranslated region (86 bp) is split by two introns. The 3' untranslated region is 114 bp long. Three Alu repeats were identified within the gene and a fourth one in the 3' flanking intergenic region. The molecular organization of this gene reflects the conservative pattern with respect to size, coding ratio, and number or position of introns characteristic of vertebrate sarcomeric myosin heavy chain genes. The protein sequence of the human beta-heavy chain was compared with corresponding (homologous) sequences of rabbit, rat, and hamster as well as with the (heterologous) embryonic heavy chain sequences of rat, chicken, and man. The results show that protein subregions responsible for basic functions of myosin heavy chains (nucleotide binding and actin binding) are very similar in homologous and heterologous heavy chains. Regions that differ in their primary sequences in heterologous heavy chains appear to be highly conserved within mammalian beta-myosin heavy chains. Constant and variable subregions of heavy chains are discussed in terms of functional significance and evolutionary relatedness.

Expression of human beta-myosin heavy chain fragments in Escherichia coli; localization of actin interfaces on cardiac myosin.

A cDNA clone coding for an internal fragment of slow-cardiac beta-myosin heavy chain was isolated from a lambda gt10 human skeletal muscle library. Six overlapping cDNA subclones, which span myosin heavy chain subregions and presumably interact with actin, were derived from this clone, fused to a beta-galactosidase vector and expressed in Escherichia coli. Three of the subclones were obtained by PCR (polymerase chain reaction) which enables gene or cDNA fragments to be amplified independently of preexisting restriction sites. Initially, various experiments were carried out using a long MHC (myosin heavy chain) fusion protein containing the 50 kDa-20 kDa connecting region, the whole 20 kDa region and the short subfragment 2 region. This MHC fusion protein was chemically or proteolytically cleaved in the same conditions as the native myosin molecule. Whole and truncated forms of the MHC fusion protein were separated on polyacrylamide gels, electroblotted on nitrocellulose sheets and renatured. They were then assayed in overlay experiments with F-actin and/or myosin light chains in solution. Specific antibodies were used to detect interactions between heavy chain fragments and F-actin or light chains. We thus observed that one long heavy chain fragment synthesized by E. coli behaved like proteolytic or chemical MHC preparations made from native myosin molecules. Two chymotryptic fragments of the MHC fusion protein, which are soluble at low ionic strength, cosedimented with F-actin in solution. Our results demonstrate that, in actin overlay experiments with whole fusion proteins, interactions seem to be due to the heavy chain fragment, not to the bacterial component. All interactions were non ATP-sensitive. We further investigated the possible participation of the six recombinant MHC fragments in contributing to the actomyosin interfaces on the 50 kDa-20 kDa regions of the human cardiac beta-MHC. The present procedure, which enables the synthesis of any MHC fragment independent of any protease site, is a powerful new tool for studying structure-function relationships within the myosin molecule family.

Studies of antidote therapy for nisoldipine intoxication in experimental animals.

In anesthetized rats under artificial respiration, intravenous infusion of nisoldipine (0.1 mg/kg x min) caused significant decreases in blood pressure, heart rate, cardiac output and peripheral resistance. The animals died 54.7 +/- 11.1 min after initiation of the infusion. The electrocardiogram showed sinus bradycardia, increasing AV blockade and displacement of the pacemaker into the AV node or the bundle of His. Survival time under nisoldipine infusion increased more than two-fold with simultaneous infusion of calcium gluconate, isoprenaline (isoproterenol) or dopamine. Norepinephrine (noradrenaline) had no significant effect on survival time; the latter decreased to 19.4 +/- 1.6 min by plasma volume expansion with polygeline. All antidotes prolonging survival time also normalized the cardiac output diminished after nisoldipine. Electrocardiographic changes were antagonized only by isoprenaline. Suitable antidotes for intoxication or over-dosage of nisoldipine are calcium salts as well as beta-sympathomimetic drugs; sheer volume substitution and peripheral vascular constriction should not be resorted to.