A primary intravascular synovial sarcoma causing deep-vein thrombosis and pulmonary embolism in a 20-year-old woman.

Primary intravascular synovial sarcoma is a rare malignancy with only a few cases documented in the literature. On presentation, this tumour usually resembles a deep venous thrombosis (dvt) or pulmonary embolism (pe). Here, we report the case of a 20-year-old woman complaining of shortness of breath who had a history of dvt 6 weeks before presentation at our institution. Vascular ultrasound detected a suspicious mass in the right groin, which was identified as a monophasic synovial sarcoma by surgical biopsy. The tumour extended from the right superficial femoral vein into the common iliac vein, profound femoral vein, and great saphenous vein. It caused pe with near-total occlusion of the right pulmonary artery. After initial treatment on the cardiac intensive care unit, the patient was referred to the oncology department for neoadjuvant radiochemotherapy with doxorubicin-ifosfamide according to the Interdisziplinäre Arbeitsgemeinschaft Weichteilsarkome [Interdisciplinary AG Sarcomas] protocol and surgical resection of the tumour. No signs of tumour recurrence were found during the subsequent course of the disease, but the patient died from treatment complications approximately 15 months after initial presentation. This case underlines the importance of screening for malignancies even in young patients presenting with dvt or pe. We also recommend whole-leg compression ultrasonography in patients with suspected dvt or pe (as opposed to venography or simple four-point ultrasound examination in the groin and popliteal fossa) to detect possible underlying causes for thrombosis.

[Diagnosis of sleep disordered breathing using portable methods]. / Diagnostik schlafbezogener Atmungsstörungen mittels portabler Verfahren.

Portable monitoring of sleep disordered breathing is the first diagnostic method not only in Germany but today in other countries as well. The conditions under which portable monitoring can be done with reliable results are now well defined. The limitations for the use of portable monitoring are specified as well. The devices used for portable monitoring are classified in four categories according to the number and the kind of signals recorded. New technical developments in the field of portable monitoring (polygraphy) use an indirect assessment of sleep disordered breathing based on signals not directly recording respiration. The recording of ECG and deriving respiration, the analysis of the plethysmographically recorded pulse wave, the recording of jaw movements using magnets, and advanced analysis of respiratory sounds are recent approaches. These new methods are presented with few studies until now. More and larger clinical studies are needed in order to show which of these systems is useful in the diagnosis of sleep disordered breathing and which are the specific strengths and weaknesses.

[Sleep apnoea syndrome in the rehabilitation setting]. / Das Schlafapnoe-Syndrom in der Rehabilitation.

Sleep-related breathing disorders are a common finding in patients undergoing cardiological rehabilitation. Sleep apnoea is recognized as a major risk factor for cardiovascular disorders. The diagnosis of sleep-related breathing disorders begins with taking a thorough sleep medicine-related patient history and answering dedicated questionnaires. The second step involves portable monitoring to assess oxygen saturation, heart rate, respiratory flow and effort. Portable monitoring is able to detect the severity of the breathing disorder and forms the basis on which to refer the patient for further sleep laboratory diagnosis or, in the case of positive results, to initiate appropriate treatment. In order to exclude a sleep-related breathing disorder, to distinguish between obstructive and central sleep apnoea, or to diagnose other sleep disorders a cardiorespiratory polysomnography in a sleep laboratory is required. Polysomnography is also needed if comorbidities are present. Appropriate and prompt treatment of sleep-related breathing disorders can shorten cardiological rehabilitation and improve outcomes in this patient group.

Atomic layer deposition (ALD) as a coating tool for reinforcing fibers.

Layers of alumina were deposited on to bundled carbon fibers in an atomic layer deposition (ALD) process via sequential exposure to vapors of aluminium chloride and water, respectively. Scanning electron microscopic (SEM) images of the coated fibers revealed that each individual fiber within a bundle was coated evenly and separately, fibers are not bridged by the coating. SEM and transmission electron microscopic (TEM) images indicate that the coating was uniform and conformal with good adhesion to the fiber surface. Average deposition rate, measured from SEM images, was 0.06 nm per cycle at 500 °C. SEM also revealed that at deposition temperatures of 500 °C few of the fibers were damaged. At temperatures of 300 °C, no damaged fibers were observed, the average deposition rate decreased down to 0.033 nm per cycle. Oxidation resistance of the alumina-coated fibers was characterized by thermogravimetric analysis (TGA). The alumina coating improved oxidation resistance of the carbon fiber significantly. Oxidation onset temperature was 600 °C for fibers coated with a 45 nm thick alumina. Uncoated fibers, on the other hand, started to oxidize at temperatures as low as 250 °C.

Competitive and seasonal oxidative stress in elite alpine ski racers.

We investigated competitive- and long-term oxidative stress during a competition season in eight top-ranked members of the Austrian Men's Alpine Ski Team. Serum total peroxides, antibody titers against oxidized LDL (oLAb) and lag time of the degradation of the fluorophore 1-palmitoyl-2-((2-(4-(6-phenyl-trans-1,3,5-hexatrienyl)phenyl)ethyl)-carbonyl)-sn-glycero-3-phosphocholine were measured, along with plasma concentrations of ascorbate, alpha- and gamma-tocopherol, beta-carotene, uric acid and the lipid status. Competitive stress was indicated through an increased post-race uric acid level (286 +/- 50 microM pre-race vs 456 +/- 77 microM post-race, P<0.001) in December. Long-term effects were already apparent in November, with the highest concentrations of total peroxides (680 +/- 458 microM H(2)O(2) equivalents vs December 47 +/- 58 microM H(2)O(2) equivalents and January 15 +/- 28 microM H(2)O(2) equivalents, P<0.001) and a concomitant decrease in oLAb titers with an antibody trough in December (439 +/- 150 mU/mL vs baseline 1036 +/- 328 mU/mL; P=0.003). In January, after recovery, they attained nearly pre-season levels of oxidative stress biomarkers. This study indicates midseason oxidative stress in top-level skiers, which was associated with the performance in these athletes.

Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins.

Human GH represents a family of proteins rather than a single hormone. The circulation contains a bewildering array of GH forms, including several monomeric variants, their homo- and heteropolymers, fragments, and complexes with at least two BPs. The net biological activity of this mixture is difficult to predict, as the various molecular forms interact as partial agonists and/or antagonists at the receptor level. The number of GH forms that can be counted in plasma exceeds 100. Table 5 attempts to illustrate what is known and provide estimates for circulating variants. It does not include GH-V and its variants, which have to be added in pregnancy. Of note, what is commonly understood as "plasma GH," i.e. free monomeric 22K, represents only 21% of total immunoreactivity in plasma. In view of this complicated picture, it should be no surprise that different assays of plasma GH yield different results (107, 108, 290). While immunoassays are relatively unaffected by the BPs (291), receptor assays are seriously affected by the high affinity BP (261). Immunoassays, particularly of the monoclonal variety, are vulnerable to differential recognition of molecular variants depending on the unique epitope specificity of the antibody used. Polyclonal assays are more robust in this regard because of "epitope averaging" among the wide spectrum of epitope specificities present in the antibody population. Future work should aim at developing antibodies that are specific for individual GH variants. Such molecular probes will be helpful not only in standardizing immunoassays, but also in delineating the biological role of the various GH forms. The physiological significance of the numerous GH forms (or of the BPs) is still largely unknown. Progress in this area has been hampered, on the one hand, by the unavailability of pure GH variants in quantities sufficient for biological studies, and, on the other, by a certain lack of interest stemming from suspicions about artifacts. The recent resurgence of interest in GH and in its receptor and BPs should also refocus attention on the various molecular forms. Thus far, this interest has been largely confined to monomeric 22K, which is certainly effective for its original intended purpose, namely growth promotion. Whether 22K is sufficient for optimal growth and development, or whether it can fulfill all the functions of the GH family is unknown. It can be argued that evolutionarily conserved GH variants probably have biological importance.(ABSTRACT TRUNCATED AT 400 WORDS)

Insulin-like growth factor I improves aspects of mycophenolate mofetil-impaired anastomotic healing in an experimental model.

BACKGROUND: Patients taking immunosuppressants after transplantation may require intestinal surgery. Mycophenolate mofetil (MMF) has been found to impair the healing of colonic anastomoses in rats. This study examined whether insulin-like growth factor (IGF) I prevents MMF impairment of anastomotic healing. METHODS: Sixty-three rats were divided into three groups (MMF, MMF/IGF and control). Animals underwent a sigmoid colon anastomosis with a 6/0 suture, and were killed on days 2, 4 and 6 after surgery. Investigations included bursting pressure measurement, morphometric analysis, and assessment of mucosal proliferation by 5-bromo-2'-deoxyuridine and Ki67 immunohistochemistry of the anastomoses. RESULTS: The leak rate was three of 21, one of 20 and two of 20 in the MMF, MMF/IGF-I and control groups respectively. Anastomotic bursting pressures were significantly lower in the MMF group than in the control group on days 2 and 4, but there was no significant difference by day 6. Values in the MMF/IGF-I and control groups were similar. Colonic crypt depth was significantly reduced in MMF-treated animals on days 2 and 4, but this impairment was attenuated by IGF-I on day 4. Similarly, IGF-I reduced the negative impact of MMF on mucosal proliferation on days 2 and 6. CONCLUSION: Exogenous IGF-I improves some aspects of MMF-impaired anastomotic healing.

Distribution, blood transport, and degradation of antidiuretic hormone in man.

The distribution, blood transport, and metabolic clearance of physiological concentrations of antidiuretic hormone were studied in 10 hydrated normal subjects with radioiodinated arginine vasopressin (125I-AVP). At 37 degrees C no binding of 125I-AVP to plasma proteins could be demonstrated, but some metabolites were associated with plasma proteins. 125I-AVP was rapidly distributed into a space approximating the extracellular fluid volume. Metabolic breakdown products became demonstrable within minutes after injection. The mean metabolic clearance rate of 125I-AVP was 4.1 ml/min/kg and the mean plasma half-life 24.1 min. Renal clearance had a mean value of 80 ml/min and accounted for 27% of the total metabolic clearance. It is concluded that in man antidiuretic hormone circulates as a free (non-protein bound) peptide, diffuses readily into the extracellular fluid space, and is metabolized within minutes. A plasma half-life of 24 min is consistent with the duration of antidiuresis after hormone administration or release.

Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.

The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein would damp sharp oscillations in GH concentrations otherwise caused by bursts of GH secretion into the blood volume, prolong the apparent half-life of circulating GH, and contribute a reservoir function. To test these implicit considerations, we formulated an explicit mathematical model of pulsatile GH secretion and clearance in the presence of absence of a specific high-affinity GH-BP. Simulation experiments revealed that the pulsatile mode of physiological GH secretion creates a highly dynamic (nonequilibrium) system, in which the half-life of free GH, its instantaneous secretion rate, and the GH-BP affinity and capacity all contribute to defining momentary levels of free, bound, and total GH, the percentage of GH bound to protein, and the percentage occupancy of GH-BP [corrected]. In contrast, the amount of free GH at equilibrium is specified only by the GH distribution volume and secretion rate and the half-life of free hormone. We conclude that the in vivo dynamics of GH secretion, trapping, and clearance from the circulation offer a variety of regulatory loci at which the time structure of free, bound, and total GH delivery to target tissues can be controlled physiologically.

[Echocardiographic evaluation to select patients for cardiac resynchronization therapy]. / Echokardiographische Methoden zur Selektion für die kardiale Resynchronisationstherapie -- Sind Tissue Doppler, Strain- und Strainrate-Imaging und 3D-Echokardiographie die ultimativen Methoden?

Wide QRS complex and asynchronous myocardial contraction in heart failure are associated with poor prognosis. Resynchronization can be achieved by biventricular pacing (BVP), which leads to hemodynamic and clinical improvement and reverse remodeling, and may improve survival. However, there is a substantial subset of patients with wide QRS complexes in the electrocardiogram who does not improve despite BVP, and there are findings which suggest that resynchronization therapy may be also beneficial for heart failure patients with normal QRS duration. QRS width predicts the benefit of BVP only with limitation and only correlates weakly with echocardiographically determined myocardial asynchrony. Determination of asynchrony by tissue Doppler echocardiography seems to be the best predictor for improvement after BVP, although no consensus on the optimal method to assess asynchrony has yet been achieved. To date, most studies evaluating tissue Doppler echo in BVP were performed retrospectively and only one prospective study with patient selection for BVP according to echocardiography and electrocardiography criteria of asynchrony has been published. These new echocardiographic tools will help to prospectively select patients for BVP, help to guide implantation and to optimize device programming.

Spontaneous Minced Cartilage Procedure for Unexpectedly Large Femoral Condyle Surface Defect.

Articular cartilage defects at the knee joint are being identified and treated with increasing frequency. Chondrocytes may have strongest potential to generate high-quality repair tissue within the defective region, in particular when large diameter defects are present. Autologous chondrocyte implantation is not available in every country. We present a case where we spontaneously covered an acute cartilage defect, which was significantly larger than expected and loose during initial arthroscopic inspection after reading preoperative MRI, by mincing the separated fragment and directly implanting the autologous cartilage chips into the defective region.

Assessment of vitamin D status and serum CrossLaps levels in adults with primary lactose malabsorption.

BACKGROUND/OBJECTIVES: Primary adult-type lactose malabsorption (PALM) is a widespread inherited autosomal recessive condition, which is considered to be associated with osteoporosis. This prospective study aimed at assessing the 25-hydroxy-vitamin D (25(OH)D) status and serum CrossLaps levels in individuals with PALM and normal controls. SUBJECTS/METHODS: All participants (n=210) underwent genotyping for the LCT C/T-13910 polymorphism, 25(OH)D and CrossLaps measurements and clinical examinations. In addition, the anthropometric data (that is, height, weight and body mass index) were determined. RESULTS: Fifty-five individuals with PALM (that is, LCT C/C-13910 homozygotes) showed lower 25(OH)D (mean: 24.95±10.04 vs 28.59±9.56 ng/ml, P=0.018) and higher CrossLaps serum levels (mean: 0.46±0.31 vs 0.43±0.49 ng/ml, P=0.251) compared with 155 normal controls (that is, LCT C/T-13910 hetero- or T/T-13910 homozygotes). Anthropometric data were similar between PALM probands and controls. CONCLUSIONS: Individuals with PALM were found to have lower 25(OH)D and higher CrossLaps serum levels compared with normal controls. In order to preserve life-long bone health, routine 25(OH)D and CrossLaps serum measurements should be performed in individuals with PALM.

Pulmonary release and coronary and peripheral consumption of big endothelin and endothelin-1 in severe heart failure: acute effects of vasodilator therapy.

BACKGROUND: We investigated plasma endothelin (ET) levels in patients with congestive heart failure (CHF) during treatment for acute decompensation; we also measured imbalances in ET peptides across the pulmonary, coronary, and peripheral circulation. Methods and Results-In patients with severe CHF (n=21; cardiac index [CI], 1.9+/-0.2 L. min(-1). m(-2); pulmonary capillary wedge pressure [PCWP], 31+/-1 mm Hg), vasodilation was achieved with the nitric oxide donor sodium nitroprusside (n=11) or with the alpha(1)-antagonist urapidil (nitric oxide-independent, n=10). ET concentrations were determined from arterial blood and blood from the pulmonary artery, coronary sinus, and antecubital vein. Depending on sites of measurement, baseline big ET and ET-1 levels were, respectively, 12 to 16 times and 5 to 11 times higher than in controls (n=11), and 4 to 6 times and 2 to 3 times higher than in patients with moderate CHF (n=10; CI, 2.7+/-0.3 L. min(-1). m(-2); PCWP, 14+/-2 mm Hg). Patients with severe CHF demonstrated pulmonary net release and coronary and peripheral net consumption of both peptides (ie, arterial levels [big ET, 7.3+/-1.3 pmol/L; ET-1, 1.8+/-0.1 pmol/L] were higher than levels in the pulmonary artery [6.7+/-1.2 pmol/L; 1. 3+/-0.1 pmol/L], coronary sinus [6.4+/-1.0 pmol/L; 1.4+/-0.1 pmol/L], and antecubital vein [6.6+/-1.1 pmol/L; 1.3+/-0.1 pmol/L]). In these patients, sodium nitroprusside (SNP) and urapidil resulted in comparable hemodynamic improvement after 6 hours (CI: SNP, 63+/-2%; urapidil, 72+/-3%; PCWP: SNP, -50+/-2%; urapidil, -47+/-2%) and a maximum decrease in ET peptides by >50%. After 3 hours, pulmonary net release and coronary and peripheral net consumption were no longer detectable. CONCLUSIONS: In patients with severe CHF, the lungs act as a producer and the heart and the periphery act as consumers of elevated circulating ETs. Short-term vasodilator therapy decreases ETs and restores their pulmonary, coronary, and peripheral balance.

Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution.

BACKGROUND: Immunoadsorption (IA) and subsequent immunoglobulin (Ig) G substitution represent an additional therapeutic approach in dilated cardiomyopathy (DCM). It remains to be elucidated whether this treatment modulates myocardial inflammation, which is possibly a causal factor of ventricular dysfunction. METHODS AND RESULTS: From 25 DCM patients (EF <30%), 12 patients were randomized for IA therapy and subsequent IgG substitution at 1-month intervals until month 3. Before (<7 days) and after IA therapy, right ventricular biopsies were obtained from all patients. Biopsies were also obtained at intervals of 3 months from 13 patients without IA/IgG treatment (controls). IA/IgG treatment induced improvement in left ventricular ejection fraction from 21.3+/-1.7% (+/-SEM) to 27.0+/-1.3% (P<0.01 versus baseline/controls) and reduction of the beta-receptor autoantibody serum levels (P<0.01 versus baseline/controls). The number of CD3 cells decreased from 5.7+/-0.8 to 2.9+/-0.5 cells/mm(2) (P<0.01 versus baseline/controls). This decline was paralleled by a decrease in CD4 (P<0.01 versus baseline/controls) and CD8 (P<0.05 versus baseline/controls) lymphocytes. The number of leukocyte common antigen-positive cells (leukocytes) was reduced from 20.0+/-3.2 to 9.9+/-2.8 cells/mm(2) (P<0.01 versus baseline/P<0.05 versus controls). HLA class II expression decreased from 2.1+/-0.7% to 1.1+/-0.4% (P<0.05 versus controls/baseline). The number of immunopositive cells and the expression of HLA class II in controls remained stable. In both groups, the degree of fibrosis remained unchanged. CONCLUSIONS: IA and subsequent IgG substitution mitigate myocardial inflammation in DCM.

Low plasma growth hormone binding protein in IDDM.

Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth. These derangements in the GH-IGF axis imply a state of GH resistance. The mechanism of GH resistance is unknown; it may involve a defect at the level of the GH receptor, unresponsiveness due to a postreceptor defect in GH action, or both. To investigate a potential receptor involvement, we measured plasma high-affinity GH-binding protein (GHBP), which represents a truncated GH receptor and may reflect GH receptor levels in tissues, in patients with IDDM, patients with non-insulin-dependent diabetes (NIDDM), and nondiabetic control subjects. Patients with IDDM had significantly lower plasma GHBP levels than either patients with NIDDM or nondiabetic control subjects (mean value 18.2 vs. 24.6 and 23.8% GH bound/ml plasma, respectively, P less than 0.001). This difference persisted when only lean patients (less than 115% ideal body wt) were included in the analysis. Basal plasma GH levels were significantly elevated in IDDM compared with either patients with NIDDM or nondiabetic control subjects (mean 6.9 vs. 2.1 and 2.0 micrograms/L, respectively, P less than 0.001), whereas IFG-I levels were not significantly different in IDDM and NIDDM. No correlations were found between levels of GHBP and HbA1, duration of diabetes, or plasma GH. GHBP and IGF-I levels were significantly correlated in NIDDM but not in IDDM. We conclude that IDDM is associated with low GHBP levels and that GH resistance found in this disorder may be mediated, at least in part, by a decrease in GH receptor levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin receptors in embryo and extraembryonic membranes of early somite rat conceptus.

Intact rat conceptuses were cultured from day 9.5 of gestation on. Individual components of the conceptus, including the embryo and the extraembryonic membranes (consisting of yolk sac, amnion, and allantoic placenta), were isolated and examined for insulin receptors at two time points during organogenesis: day 10.4 of gestation (approximately 10-12 somites) when the yolk sac had become vascularized and just before closure of the anterior neuropore and day 11.6 (approximately 27-31 somites) when vascularization of the chorioallantoic placenta had been established and the neural tube was closed completely. The studies were designed to provide inferential insights about the possible role of insulin in embryogenesis during different phases of nutrient delivery. Active insulin degradation occurred with embryo as well as membrane homogenates during incubation at 37 degrees C. Degradation was markedly reduced at 4 degrees C, and binding of 125I-labeled insulin by embryo or membrane homogenates prepared on day 10.4 or 11.6, respectively, of gestation approached equilibrium after a 20-h incubation at this temperature. Values for the specific binding of tracer (0.4 ng/ml) or carrier (10.4 ng/ml) insulin by embryo and membrane homogenates were the same on days 10.4 and 11.6; specific binding was significantly greater with preparations of membranes than embryo at both time points. Full binding curves on day 11.6 showed similar affinities for insulin by embryo and membranes (Ke = 1.2 X 10(8)/M and 4.6 X 10(8)/M, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmogenic effects induced by coronary conversion of pulmonary big endothelin to endothelin: aggravation of this phenomenon in heritable hyperlipidemia.

OBJECTIVES: We investigated whether endogenous pulmonary big endothelin has arrhythmogenic properties under normal conditions and in heritable hyperlipidemia. BACKGROUND: Endothelin (ET), one of the most potent vasoconstrictors, is known to induce ventricular arrhythmias. It is unclear, however, whether its precursor, big endothelin, released from the lung, contributes to arrhythmogenesis. METHODS: In a lung-heart model in which a Langendorff heart is serially perfused with the effluent from the isolated lung of the same animal, we evaluated arrhythmias in control and in Watanabe heritable hyperlipidemic (WHHL) rabbits. RESULTS: In both controls (n=12) and WHHL (n=8), serial perfusion evoked a decrease in coronary flow (controls, -11+/-3%; WHHL, -25+/-6%) and a fourfold increase of ventricular extrasystoles (VES) (controls, 40.7+/-8; WHHL, 40.2+/-5 VES/40 min, p < 0.05). However, WHHL developed more and longer nonsustained ventricular tachycardias (VT) compared with controls (incidence, 1.38+/-1.1 vs. 0.33+/-0.5 VT/40 min, p < 0.05; length, 14.36+/-3.1 vs. 7.25+/-1.5 beats/VT, p < 0.05). Arrhythmias were not ischemia-induced because corresponding mechanical flow reduction had no arrhythmogenic effect (n=6 in controls and WHHL). Although vasoconstriction disappeared entirely, arrhythmias were only partly suppressed by ET(A) antagonists (BQ-123, 2 micromol/liter; A-127722, 20 micromol/liter). The ET-converting enzyme inhibitor phosphoramidon (50 micromol/liter) completely suppressed arrhythmias and vasoconstriction. The ET(B) antagonists (IRL-1038, 4 micromol/liter; IRL-1025, 5 micromol/liter) had no effect (n=6). CONCLUSIONS: Endogenous pulmonary big ET produces arrhythmogenic effects that are aggravated in heritable hyperlipidemia. These effects, requiring coronary conversion of big ET into ET, are partly ET(A)-mediated and ET(B)-independent.

Cardiodepressive mediators are released after ischemia from an isolated heart: role of coronary endothelial cells.

OBJECTIVES: This study was designed to ascertain whether cardiodepressive mediators released after ischemia originate from coronary endothelial cells. BACKGROUND: Endothelial cells modulate myocardial contractility under physiologic conditions. Few data are available describing the role of coronary endothelial cells on myocardial function after ischemia. METHODS: Using a model of sequential perfusion of two isolated rat hearts, the effect of the reoxygenated coronary effluent of heart I was investigated on myocardial contractility of heart II. After 40 min of separate perfusion at constant flow (10 ml/min), the two hearts were perfused sequentially with (group I) or without (control group) preceding ischemia (10 min) of heart I. In groups II and III, the coronary endothelium of heart I was functionally removed by Triton X-100 or hyperkalemic infusion before global ischemia. Endothelial damage was confirmed by functional tests and electron microscopy. RESULTS: Under control conditions no changes were observed in heart II during sequential perfusion. In contrast, after 10 min of ischemia in heart I, a marked reversible decrease in left ventricular pressure, left ventricular dP/dtmax and left ventricular dP/dtmin (-55%, -66% and -70%, respectively) was observed in heart II. Heart rate and coronary perfusion pressure did not change significantly. Selective endothelial damage of heart I before ischemia did not modify the negative inotropic effect observed in heart II. CONCLUSIONS: Cardiodepressive mediators are released after ischemia during reperfusion from an isolated heart and induce a reversible negative inotropic effect in a sequentially perfused heart. It is unlikely that these agents are derived from the coronary endothelium.

Community hospital administration of intravenous tissue plasminogen activator in acute myocardial infarction: improved timing, thrombolytic efficacy and ventricular function.

As an investigational fibrinolytic agent for acute myocardial infarction, intravenous recombinant tissue-type plasminogen activator (rt-PA) has been administered primarily in tertiary care and university centers. To determine the value of early initiation of such therapy, two satellite community hospital emergency rooms were established for use of rt-PA and the experience was compared among 142 consecutive patients who were transferred to a regional center for acute cardiac catheterization after intravenous rt-PA therapy. In Group I (n = 19), patients received rt-PA after interhospital transport to the regional center, but before cardiac catheterization. In Group II (n = 70), rt-PA therapy was initiated by the helicopter physician and nurse team after their arrival at the local community hospital emergency room. Group III patients (n = 53) had rt-PA administered in the local community hospital by the emergency room physician. Group III patients had earlier initiation of therapy (2.1 +/- 0.8 hours in Group III versus 3.8 +/- 1.2 hours in combined Groups I and II, p less than 0.001) and an increased rate of infarct vessel recanalization on the 90 minute coronary angiogram (81 in Group III versus 67% in combined Groups I and II, p = 0.057). The patients in Group III had a higher acute left ventricular ejection fraction (54 +/- 8% versus 50 +/- 9.5% in combined Groups I and II, p less than 0.01) and a trend toward an increased 7 day ejection fraction (55.5 +/- 9% versus 51.7 +/- 9.5%, respectively, p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)