Search

Background LIVE (Less Invasive Ventricular Enhancement) with Revivent TC™ is an innovative therapy for symptomatic ischemic Heart Failure (HF). It is designed to reconstruct a negatively remodeled left ventricle (LV) after an anterior myocardial infarction (MI) by plication of the scar tissue. Its indications are specific and, as with any other structural heart intervention, the success of the procedure starts with appropriate patient selection. We aim to present the indications of the technique, crucial aspects in patient selection and individual case planning approach. Methods and Results After clinical evaluation, transthoracic echocardiography is the first imaging modality to be performed in a potential candidate for the therapy. However, definitive indication and detailed case planning rely on late gadolinium-enhanced cardiac magnetic resonance imaging or multiphasic contrast-enhanced cardiac computed tomography. These imaging modalities also assist with relative or absolute contra-indications for the procedure. Individual assessment is done to tailor the procedure to the specifics of the LV anatomy and location of the myocardial scar. Conclusion LIVE procedure is a unique intervention to treat symptomatic heart failure and ischemic cardiomyopathy after anterior MI. It is a highly customizable intervention that allows a patient-tailored approach, based on multimodality imaging assessment and planification.

Key message We mutated all seven Physcomitrium (Physcomitrella) patens phytochrome genes using highly-efficient CRISPR-Cas9 procedures. We thereby identified phy5a as the phytochrome primarily responsible for inhibiting gravitropism, proving the utility of the mutant library. Abstract The CRISPR-Cas9 system is a powerful tool for genome editing. Here we report highly-efficient multiplex CRISPR-Cas9 editing of the seven-member phytochrome gene family in the model bryophyte Physcomitrium (Physcomitrella) patens. Based on the co-delivery of an improved Cas9 plasmid with multiple sgRNA plasmids and an efficient screening procedure to identify high-order multiple mutants prior to sequencing, we demonstrate successful targeting of all seven PHY genes in a single transfection. We investigated further aspects of the CRISPR methodology in Physcomitrella, including the significance of spacing between paired sgRNA targets and the efficacy of NHEJ and HDR in repairing the chromosome when excising a complete locus. As proof-of-principle, we show that the septuple phy− mutant remains gravitropic in light, in line with expectations, and on the basis of data from lower order multiplex knockouts conclude that phy5a is the principal phytochrome responsible for inhibiting gravitropism in light. We expect, therefore, that this mutant collection will be valuable for further studies of phytochrome function and that the methods we describe will allow similar approaches to revealing specific functions in other gene families.

Objectives: Ischemic cardiomyopathy is the principal cause of heart failure. In patients with left ventricular (LV) dilatation,low ejection fraction (EF), and transmural scar in anteroseptal distribution, surgical ventricular reconstruction (SVR) can beconsidered, although it is an invasive surgical procedure. Less Invasive Ventricular Enhancement (LIVE) technique emergedas a unique intervention to exclude scarred myocardium, improving symptoms and quality of life. We aim to present LIVEcontemporary short and mid-term outcomes. Methods: LIVE procedure has evolved from open sternotomy to a hybrid procedure done with right internal jugular veinaccess and a left minithoracotomy. LV shape and size are restored without extracorporeal circulation by plication of thescarred myocardium. This is achieved by implantation of a series of internal and external microanchors brought togetherover a poly-ether-ether-ketone (PEEK) tether to make a longitudinal approximation between the LV free wall and theanterior septum. Internal anchors are deployed by a transcatheter technique, through the right internal jugular vein, on theright side of the ventricular septum. Result: Between July 2018 and August 2020, a total of 71 patients (84.5% men;mean age 61 ± 12.3 years) weresubmitted to the LIVE procedure in 18 institutions in Europe, North America, and Asia. Procedural success was 100%. Amean of 2.4 anchor pairs (median 3) was used to reshape the LV. Echocardiographic data showed an increase in LV EF from31.0 ± 9.2 to 38.9 ± 12.6% (change +29.8%, p < 0.001) and LV end-systolic volume index (LVESVI) reduction from 68.0 ± 28.8 mL/m2 to 42.3 ± 20.7 mL/m2 (change: -37.9%, p < 0.001) after the procedure. No sternotomy conversion was needed.New onset tricuspid valve regurgitation was observed in one patient. There was no case of ventricular septal defect.Observed mortality was 2.8% (2 patients): one due to severe contrast dye induced anaphylactic shock and another one dueto COVID-19. In the follow-up, NYHA class improved a median of 1 grade and there was no late mortality. Conclusion: Hybrid LV reshaping and volume reduction has proven to be a useful solution for patients with symptomaticheart failure after left anterior descending territory myocardial infarction. These results from the latest iteration of thetechnique show that this approach is safe, reproducible, and has a significant short and mid-term impact on improving EFand reducing LV size.

In mosses such as Physcomitrella patens phytochrome photoreceptors steer directional/vectorial responses to unilateral/polarized light. In this chapter, we describe procedures to assay phototropism and polarotropism quantitatively in wild type and mutant lines. Protonemata are placed on agar-based medium in square Petri dishes in darkness for 1 week, allowing caulonemata to develop and grow negatively gravitropically. For phototropism, the dishes are placed vertically in black boxes and unilaterally irradiated with continuous red light. For polarotropism, Petri dishes are placed horizontally and irradiated with linearly polarized red light from above. After irradiation, the filaments are photographed using a macroscope with CCD camera and the bending angles measured using image processing software. The data are transfered to a spreadsheet program, placed into 10° bending angle classes and illustrated using a circular histogram.

Here we describe procedures for gene disruption and excision in Physcomitrella using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR-associated 9) methods, exemplarily targeting phytochrome (PHY) gene loci. Thereby double-strand breaks (DSBs) are induced using a single guide RNA (sgRNA) with the Cas9 nuclease, leading to insertions or deletions (indels) due to incorrect repair by the nonhomologous-end joining (NHEJ) mechanism. We also include protocols for excision of smaller genomic fragments or whole genes either with or without homologous recombination-assisted repair. The protocol can be adapted to target several loci simultaneously, thereby allowing the physiological analysis of phenotypes that would be masked by functional redundancy. In our particular case, multiple PHY gene knockouts would likely be valuable in understanding phytochrome functions in mosses and, perhaps, higher plants too. Target sites for site-directed induction of DSBs are predicted with the CRISPOR online-tool and are inserted in silico into sequence matrices for the design of sgRNA expression cassettes. The resulting DNAs are cloned into Gateway DONOR vectors and the respective expression plasmids used for moss cotransformation with a Cas9 expression plasmid and a selectable marker (either on a separate plasmid or on one of the other plasmids). After the selection process, genomic DNA is extracted and transformants are analyzed by PCR fingerprinting.

International audience; Here we describe procedures for gene disruption and excision in Physcomitrella using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR-associated 9) methods, exemplarily targeting phytochrome (PHY) gene loci. Thereby double-strand breaks (DSBs) are induced using a single guide RNA (sgRNA) with the Cas9 nuclease, leading to insertions or deletions (indels) due to incorrect repair by the nonhomologous-end joining (NHEJ) mechanism. We also include protocols for excision of smaller genomic fragments or whole genes either with or without homologous recombination-assisted repair. The protocol can be adapted to target several loci simultaneously, thereby allowing the physiological analysis of phenotypes that would be masked by functional redundancy. In our particular case, multiple PHY gene knockouts would likely be valuable in understanding phytochrome functions in mosses and, perhaps, higher plants too. Target sites for site-directed induction of DSBs are predicted with the CRISPOR online-tool and are inserted in silico into sequence matrices for the design of sgRNA expression cassettes. The resulting DNAs are cloned into Gateway DONOR vectors and the respective expression plasmids used for moss cotransformation with a Cas9 expression plasmid and a selectable marker (either on a separate plasmid or on one of the other plasmids). After the selection process, genomic DNA is extracted and transformants are analyzed by PCR fingerprinting.

In mosses such as Physcomitrella patens phytochrome photoreceptors steer directional/vectorial responses to unilateral/polarized light. In this chapter, we describe procedures to assay phototropism and polarotropism quantitatively in wild type and mutant lines. Protonemata are placed on agar-based medium in square Petri dishes in darkness for 1 week, allowing caulonemata to develop and grow negatively gravitropically. For phototropism, the dishes are placed vertically in black boxes and unilaterally irradiated with continuous red light. For polarotropism, Petri dishes are placed horizontally and irradiated with linearly polarized red light from above. After irradiation, the filaments are photographed using a macroscope with CCD camera and the bending angles measured using image processing software. The data are transfered to a spreadsheet program, placed into 10° bending angle classes and illustrated using a circular histogram.

During this study, new Ni-base alloys precipitating cubic γ′ were developed which shall be used for the production of polycrystalline nanoporous membranes. The polycrystalline nanoporous membranes are produced through a combination of cold rolling and heat treatment in order to get directional coarsening of the γ′-phase which is selectively dissolved afterwards. Conventional Ni-based superalloys have a γ/γ′ -microstructure with cubic γ′-precipitates and show the needed etching behaviour but their high strength and limited ductility at room temperature do not allow to produce the polycrystalline nanoporous membranes by means of the before mentioned method. Thus, the new alloys with simpler composition were developed which have a γ/γ′ microstructure. The alloy Ni–13Fe–8Al–4Ti (composition in atomic percent) which was produced by Schmitz (Cullivier, ISBN 978-3-86955-523-2, 16) served as basis and showed the promising characteristics. To obtain cubic γ′-precipitates, the misfit was estimated to values of at least |0.2| % by a method presented by Mishima (Acta Metall 33:1161–1169, 23). Further, the phase compositions as well as phase volume fractions of γ-matrix and γ′-phase were calculated by means of Thermocalc® simulations (database: TTNi7). The etching behaviour of the new alloys was adjusted by adding chromium and molybdenum which passivate the γ-matrix so that the γ′-precipitates dissolve during the leaching process. The well-aligned cubic γ′-precipitates were obtained by partially replacing titanium by niobium. Furthermore, the hardness could be significantly lowered compared to conventional superalloys by reduction of alloying elements. Hence, the promising alloys were found to get directional coarsening of the γ′-precipitates in a combined process of cold rolling and heat treatment.

Interventions in aorto-coronary venous bypass grafts (CABG) can cause acute procedural complications due to distal embolization of debris. In the FIRST (First European Investigation Regarding the Systematic use of the TriActiv device) multicenter trial the distal endovascular protection system TriActiv (Kensey Nash) was evaluated during intervention of CABG. 195 patients in 17 centers in Germany with significant disease of a vein graft were enrolled. Inclusion and exclusion criteria were comparable to the SAFER trial. Acute procedural success was achieved in 98% of cases. Aspirated debris was found in 96.5% of patients. Primary endpoints (MACE at 30 days) occurred in 8.7% of all pts. (ITT). No patient died and 7.2% of patients suffered from MI. The rate of early revascularization was 1.5%. Secondary endpoints (MACCE at 30 days) were found in 9.2% and at hospital discharge in 8.7% of patients. The TriActiv system is safe and effective. Normal post procedural flow can be preserved and the MACE rate is with 8.7% considerably low. The FIRST trial supports the growing belief that PCI of CABG should be performed with protection systems.

Background— Catheters are typically stiff and incorporate a pull-wire mechanism to allow tip deflection. While standing at the patient’s side, the operator manually navigates the catheter in the heart using fluoroscopic guidance. Methods and Results— A total of 42 patients (32 female; mean age, 55±15 years) underwent ablation of common-type (slow/fast) or uncommon-type (slow/slow) atrioventricular nodal reentrant tachycardia (AVNRT) with the use of the magnetic navigation system Niobe (Stereotaxis, Inc). It consists of 2 computer-controlled permanent magnets located on opposite sides of the patient, which create a steerable external magnetic field (0.08 T). A small magnet embedded in the catheter tip causes the catheter to align and to be steered by the external magnetic field. A motor drive advances or retracts the catheter, enabling complete remote navigation. Radiofrequency current was applied with the use of a remote-controlled 4-mm, solid-tip, magnetic navigation–enabled catheter (55°C, maximum 40 W, 60 seconds) in all patients. The investigators, who were situated in the control room, performed the ablation using a mean of 7.2±4.7 radiofrequency current applications (mean fluoroscopy time, 8.9±6.2 minutes; procedure duration, 145±43 minutes). Slow pathway ablation was achieved in 15 patients, whereas slow pathway modulation was the end point in the remaining patients. There were no complications. Conclusions— The Niobe magnetic navigation system is a new platform technology allowing remote-controlled navigation of an ablation catheter. In conjunction with a motor drive unit, this system was used successfully to perform completely remote-controlled mapping and ablation in patients with AVNRT.

In patients with myocardial infarction, left ventricular sympathetic denervation exceeds the size of the scar tissue. However, little is known about the regional innervation in patients with coronary artery disease (CAD) but no myocardial infarction. Using positron emission tomography (PET) with N-ammonia and C-hydroxyephedrine (HED), resting perfusion and presynaptic sympathetic innervation were studied in eight patients (seven males, one female; 58+/-9 years) with multi-vessel CAD and no history of myocardial infarction. Using polar map analysis of the PET data, the results were regionally compared with normal databases. The mean HED retention was 8.0%+/-2.0% x min(-1). Myocardial resting perfusion was normal in 23 of 24 vascular territories. Despite normal resting perfusion, significantly reduced HED retention, indicating dysinnervation, was found in 14 of 23 (61%) vascular territories (six of eight patients). Of the dysinnervated territories, 11 (79%) showed angiographically severe stenosis (or=90% of native vessel/coronary artery bypass graft), eight (57%) showed ischaemia (myocardial perfusion scintigraphy/stress-electrocardiogram) and 12 (86%) had been revascularized. Of the nine segments with normal innervation, two (22%) revealed severe stenosis, two (22%) showed ischaemia and seven (78%) had been revascularized. It can be concluded that, in patients with advanced CAD and normal left ventricular function, dysinnervation can occur in the absence of myocardial infarction. This is consistent with the hypothesis that sympathetic neurones are more susceptible than myocytes to ischaemic damage.

In patients with severe angina pectoris due to coronary artery disease, who are not candidates for either percutaneous coronary angioplasty or coronary artery bypass surgery, transmyocardial laser revascularization (TMR) often leads to improvement of clinical symptoms and increased exercise capacity. One drawback of TMR is the need for surgical thoracotomy in order to gain access to the epicardial surface of the heart. Therefore, a catheter-based system has been developed, which allows creation of laser channels into the myocardium from the left ventricular cavity.Between January 1997 and November 1999, this "percutaneous myocardial laser-revascularization" (PMR) was performed in 85 patients at the Herzzentrum Leipzig. In 43 patients, only one region of the heart (anterior, lateral, inferior or septal) was treated with PMR; in 42 patients two or three regions were treated in one session. 12.3±4.3 (range 4-22) channels/region were created into the myocardium.Six months after PMR, the majority of patients reported significant improvement of clinical symptoms (CCS class at baseline: 3.3±0.4; after 6 months: 1.6±0.9) (p < 0.001) and an increased exercise capacity (baseline: 349±138 s; after 6 months: 470±193 s) (p < 0.05); however, thallium scintigraphy failed to show increased perfusion in the PMR treated regions.PMR seems to be a safe and feasible new therapeutic option for patients with refractory angina pectoris due to end-stage coronary artery disease. The first results indicate improvement of clinical symptoms and increased exercise capacity; evidence of increased perfusion in the laser-treated regions is still lacking.

Bei Patienten mit schwerer Angina pectoris aufgrund einer koronaren Herzerkrankung, bei denen aufgrund der Koronarmorphologie oder vorausgegangener Interventionen keine Moglichkeit einer Ballondilatation oder einer Bypassoperation mehr besteht, konnen die klinische Symptomatik und die korperliche Belastbarkeit haufig durch eine transmyokardiale Laserrevaskularisation (TMR) gebessert werden. Ein Nachteil der TMR ist die Notwendigkeit eines chirurgischen Zugangs zum Herzen, um die Kannale vom Epikard aus in das Myokard einzubringen. Daher wurde ein Kathetersystem entwickelt, mit dem die Laserkanale vom linksventrikularen Kavum aus in das Myokard eingebracht werden konnen. Bisher wurden am Herzzentrum Leipzig 101 Patienten mit therapierefraktarer Angina pectoris mit dieser “perkutanen myokardialen Laserrevaskularisation” (PMR) behandelt. Bei 63 Patienten wurde nur eine Region des Herzens (anterior, lateral, inferior oder septal) behandelt, bei 38 Patienten wurden wahrend einer Intervention zwei oder drei Regionen des Herzens behandelt. Hierbei wurden 12,3 ± 4,5 (Bereich 4 bis 22) Laserkanale je Myokardregion eingebracht. Bereits drei Monate nach PMR waren bei der uberwiegenden Zahl der Patienten eine deutliche Verbesserung der klinischen Symptomatik (CCS-Klasse vor PMR: 3,3 ± 0,4, nach sechs Monaten: 1,6 ± 0,8) (p

Das Still-Syndrom des Erwachsenen ist gekennzeichnet durch Fieber, Arthralgien, Exantheme und Leukozytose mit Linksverschiebung als Hauptsymptome sowie Rachenentzundung, Lymphadenopathie und/oder Splenomegalie, Leberdysfunktion sowie negativem Rheumafaktor und negativen antinuklearen Antikorpern als untergeordnete Symptome. Wir beschreiben einen Fall, der sich klinisch zunachst als Racheninfektion prasentierte, im weiteren Verlauf muste auf Grund entsprechender EKG-Veranderungen differentialdiagnostisch eine Perimyokarditis berucksichtigt werden, die auch durch eine Herzmuskelbiopsie nicht ausgeschlossen werden konnte. Wegen hoher Temperaturen und Leukozytose mit Linksverschiebung wurde initial unter dem Verdacht auf einen schweren bakteriellen Infekt mit verschiedenen Antibiotikaregimen letztlich erfolglos behandelt. Erst im weiteren klinischen Verlauf kamen Symptome wie Leberenzymerhohungen und Arthralgien hinzu, die die Diagnose eines Still-Syndroms wahrscheinlich machten. Nach Beginn einer hochdosierten Kortikoidtherapie kam es zu einer dramatischen Besserung des klinischen Bildes und zu einer Normalisierung der Temperaturen. Der Patient ist unter einer Kortikoid-Erhaltungstherapie nun seit mehreren Monaten anhaltend beschwerdefrei.

OBJECTIVESThis study evaluates the feasibility and safety of a catheter-based laser system for percutaneous myocardial revascularization and analyses the first clinical acute and long-term results in patients with end-stage coronary artery disease (CAD) and severe angina pectoris.BACKGROUNDIn patients with CAD and intractable angina who are not candidates for either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), transmyocardial laser revascularization (TMR) has been developed as a new treatment that results in reduced angina pectoris and increased exercise capacity. However, surgical thoracotomy is required for TMR with considerable morbidity and mortality.METHODSA catheter-based system has been developed that allows creation of laser channels in the myocardium from within the left ventricular cavity. Laser energy generated by a Holmium: YAG (Cardiogenesis Corporation, Sunnyvale, California) laser was transmitted to the myocardium via a flexible optical fiber capped by an optic lens. The optical fiber was maneuvered to the target area under biplane fluoroscopy through a coaxial catheter system permitting movement in three dimensions.RESULTSThirty-four patients with severe CAD not amenable to either CABG or PTCA and refractory angina pectoris (Canadian Cardiologic Society [CCS] Angina Scale Class III–IV) were included in the study. Ischemic regions were identified by coronary angiography and confirmed by thallium scintigraphy. The percutaneous myocardial revascularization (PMR) procedure was successfully completed in all patients. In 29 patients, one vascular territory of the left ventricle and in 5 patients, two vascular territories were treated. Eight to fifteen channels were created in each ischemic region. Major periprocedural complications were limited to an episode of arterial bleeding requiring surgical repair. There was one death early after PMR, due to a myocardial infarction (MI) in a nontreated region. Clinical follow-up at 6 months (17 patients) demonstrated significant improvement of angina pectoris (CCS class before PMR: 3.0 ± 0.0, six months after PMR: 1.3 ± 0.8, p < 0.0001) and increased exercise capacity (exercise time on standard bicycle ergometry before PMR: 384 ± 141 s, six months after PMR: 514 ± 158 s, p < 0.05), but thallium scintigraphy failed to show improved perfusion of the laser treated regions.CONCLUSIONSPercutaneous myocardial revascularization is a new safe and feasible therapeutic option in patients with CAD and severe angina pectoris not amenable to either CABG or PTCA. Initial results show immediate and significant improvement of symptoms and exercise capacity but evidence of improved myocardial perfusion is still lacking.

The purpose of this study was to investigate the influence of different injury levels in persons with spinal cord injury (SCI) on epinephrine (Epi) and norepinephrine (NE) at rest and during graded wheelchair exercise and the related changes in heart rate and O2 uptake (V˙o 2). Twenty tetraplegics (Tetra), 10 high-lesion paraplegics (HLPara), 20 paraplegics with SCI below T5 (MLPara), and 18 able-bodied, nonhandicapped persons (AB) were examined. Because of the higher level of interruption of the sympathetic pathways, Tetra persons showed lower Epi and NE at rest and only slight increases during exercise compared with all other groups; the Tetra subjects’ impaired cardiac sympathetic innervation caused restricted cardioacceleration and strongly reduced maximalV˙o 2. When compared with AB persons, HLPara had comparable NE but lower Epi levels as a result of partial innervation of the noradrenergic system and denervation of the adrenal medulla. MLPara subjects showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity compared with AB subjects. The increase in heart rate in relation toV˙o 2 was higher in HLPara because of a smaller stroke volume as a result of venous blood pooling. The different exercise response in persons with SCI is a result of the interruption of pathways in the spinal cord to the peripheral sympathetic nervous system in addition to the motor paralysis.

In interventional cardiology an increasing demand to treat complex coronary lesions (i.e. distal lesions, tortuous vessels, chronic occlusions) has developed within the last years. New devices to fulfill this demand are therefore needed.The magnetic navigation system (Niobe System; Stereotaxis Inc.) represents a novel system which allows 3-dimensional control of the guide wire tip using magnetic fields. Two computer controlled permanent magnets on each side of the patient create a uniform magnetic field which can freely be directed. A small magnet at the guide wire tip will align according to the vector of the magnetic field. Advancing and retracting of the wire is to be done manually. The remaining steps of angioplasty (i.e. balloon angioplasty and stent implantation) are performed conventionally, after magnetically guided crossing of the target lesion.The study was performed to proof the feasibility of the technique in the treatment of coronary lesions. Seventy seven patients with 82 coronary lesions underwent magnetic guided coronary interventions. Sixty three lesions (77%) could be crossed successfully using magnetic guidance, 13 more by switching to conventional guide wires. Successful angioplasty (with or without stent implantation) was achieved in 74 lesions (90%). Mean fluoroscopy time was 13,9+/-8 min.The use of magnetic guidance in coronary interventions is a promising tool to treat complex coronary lesions. With more experience and improved devices (i.e. coated wires, steerable microcatheters) the safety and efficacy of the procedures should be improved.

UNLABELLED The anomalous origin of the left coronary artery from the main pulmonary trunk (also known as Bland-White-Garland syndrome) is a rare congenital malformation that occurs in 0.4% of patients with cardiac anomalies. We present an adult case (a 58-year-old woman) of atypical Bland-White-Garland syndrome. The patient displayed a stenosis at the ostium of the anomalous origin of the left coronary artery and an aortopulmonary fistula. Using conventional angiography, it was not possible to differentiate between an anomalous origin of the pulmonary coronary artery and total stenosis of the left main coronary artery in combination with a pulmonary fistula. However, transesophageal echocardiography (TEE) succeeded in making this differential diagnosis. CONCLUSION If there is subtotal or total occlusion, TEE can be used for detection of coronary vessel morphology, particularly in cases of coronary anomalies.

This study investigated the effect of percutaneous laser revascularisation (PMR) on regional myocardial blood flow. PMR is a new therapeutic modality for patients suffering from angina pectoris due to coronary artery disease (CAD) that is not amenable to revascularisation. Initial clinical studies discovered reduced angina pectoris and increased exercise capacity after PMR. There are no previous clinical studies reporting the impact of PMR on perfusion. Thirty-six patients with end-stage CAD underwent thallium-201 single-photon emission tomography studies on four different occasions: immediately before PMR and 3, 6 and 12 months following PMR. Each study consisted of pharmacological stress and rest scintigraphy. Semiquantitative evaluation was performed by use of 14 standardised wall segments which were classified (a) according to the localisation of the PMR target region into treated segments, segments adjacent to the treated area and non-treated segments and (b) according to the pre-therapeutic local perfusion into four groups: no (0), slight (I), moderate (II) or severe (III) perfusion deficit. At stress in treated segments of groups II and III local scintigraphic count densities increased from 60.1% and 34.7% at baseline to 65.3% and 48.3% after 12 months (P

Spinal cord lesion leads to an interruption of pathways from brain to the peripheral sympathetic nervous system, which results in pathological changes in sympathetic innervation. Free epinephrine (E), norepinephrine (NE) and dopamine (DA) were measured in 30 tetraplegics (TETRA), 15 high-lesion paraplegics (T1 and T4, HPARA), 15 paraplegics with injuries between T5 and T10 (MPARA), 15 low-lesion paraplegics (below T10, LPARA) and 16 non-handicapped control persons (C) at rest, at 60 and 100% of maximal oxygen consumption during graded wheelchair ergometry (WCE). The TETRA showed significant lower E and NE levels at rest and only slight increases during physical exercise. The E and NE concentrations of the paraplegics with a lesion below T5 were significantly higher than those of the high-lesion paraplegics, as well as those of the control persons at every point in the study. All paraplegics and the control persons showed, at submaximal and maximal exercise, a significant increase in NE. Only a slight increase in E in HAPRA was shown. No differences were found at rest and during exercise in E and NE levels in the MPARA and LPARA. No significant differences were found in the dopamine concentration at rest or during exercise for any of the groups. In summary, different levels of lesion and the resulting interruption to sympathetic pathways in the spinal cord are decisive factors in the degree of impairment of sympathetic innervation in SCI persons. Tetraplegics show less preganglionic resting activity because of interruption of impulses from central centers and no considerable stimulation of the sympathetic nervous system during maximal exercise. Individuals with high paraplegia have a partial impairment of catecholamine release, especially of epinephrine, at rest and during exercise. Paraplegics with a lesion level below T5 showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity in comparison to control persons.