Markus Lins

Detection of Diverse Bacterial Signatures in Atherosclerotic Lesions of Patients With Coronary Heart Disease

Background— Bacterial infection has been discussed as a potential etiologic factor in the pathophysiology of coronary heart disease (CHD). This study analyzes molecular phylogenies to systematically explore the presence, frequency, and diversity of bacteria in atherosclerotic lesions in patients with CHD. Methods and Results— We investigated 16S rDNA signatures in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD, control material from postmortem patients (n=15), and heart-beating organ donors (n=11) using clone libraries, denaturating gradient gel analysis, and fluorescence in situ hybridization. Bacterial DNA was found in all CHD patients by conserved PCR but not in control material or in any of the normal/unaffected coronary arteries. Presence of bacteria in atherosclerotic lesions was confirmed by fluorescence in situ hybridization. A high overall bacterial diversity of >50 different species, among them Staphylococcus species, Proteus vulgaris, Klebsiella pneumoniae, and Streptococcus species, was demonstrated in >1500 clones from a combined library and confirmed by denaturating gradient gel analysis. Mean bacterial diversity in atheromas was high, with a score of 12.33±3.81 (range, 5 to 22). A specific PCR detected Chlamydia species in 51.5% of CHD patients. Conclusions— Detection of a broad variety of molecular signatures in all CHD specimens suggests that diverse bacterial colonization may be more important than a single pathogen. Our observation does not allow us to conclude that bacteria are the causative agent in the etiopathogenesis of CHD. However, bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.

Randomized Comparison of a Titanium-Nitride-Oxide–Coated Stent With a Stainless Steel Stent for Coronary Revascularization The TiNOX Trial

Background—Stent coating with titanium-nitride-oxide has been shown to reduce neointimal hyperplasia in the porcine restenosis model. We designed a prospective, randomized, clinical study to investigate the safety and efficacy of titanium-nitride-oxide–coated stents compared with stainless steel stents. Methods and Results—Ninety-two patients with de novo lesions were randomly assigned to treatment with titanium-nitride-oxide–coated stents (n=45) or stainless steel stents of otherwise identical design (n=47; control). Baseline characteristics were similar in both groups. At 30 days, no stent thromboses or other adverse events had occurred in either group. Quantitative coronary angiography at 6 months revealed lower late loss (0.55±0.63 versus 0.90±0.76 mm, P=0.03) and percent diameter stenosis (26±17% versus 36±24%, P=0.04) in lesions treated with titanium-nitride oxide–coated than in control stents. Binary restenosis was reduced from 33% in the control group to 15% in the titanium-nitride oxide–coated stent group (P=0.07). Intravascular ultrasound studies at 6 months showed smaller neointimal volume in titanium-nitride-oxide–coated stents than in control stents (18±21 versus 48±28 mm3, P<0.0001). Major adverse cardiac events at 6 months were less frequent in titanium-nitride-oxide–coated stents than in control stent–treated patients (7% versus 27%, P=0.02), largely driven by a reduced need for target-lesion revascularization (7% versus 23%, P=0.07). Conclusions—Revascularization with titanium-nitride-oxide–coated stents is safe and effective in patients with de novo native coronary artery lesions. Titanium-nitride-oxide–coated stents reduce restenosis and major adverse cardiac events compared with stainless steel stents of otherwise identical design.

Pericardiocentesis: differential aspects of a common procedure.

Objective: To evaluate the risk and effectiveness of pericardiocentesis in primary and repeat cardiac tamponade Design: Retrospective analysis. Setting: Intensive care unit in a medical university hospital. Patients: Sixty-three consecutively admitted patients with cardiac tamponade. Interventions: In all patients pericardiocentesis was performed via the subxiphoid pathway after echocardiographic detection of the pericardial effusion. Measurements and results: There was no adverse event in patients undergoing primary pericardiocentesis, which was sufficient to resolve pericardial effusion in 51 of 63 patients (81 %). However, repeat pericardiocentesis necessitated by the recurrence of symptomatic pericardial effusion yielded suboptimal results in 10 of 12 patients (83 %). Conclusion: Pericardiocentesis is the treatment of choice for primary symptomatic pericardial effusion. In recurrent pericardial effusion surgical approaches appear to be preferable.

Hypoxic Renal Tissue Damage by Endothelin-Mediated Arterial Vasoconstriction during Radioangiography in Man

In vivo, a high rate of renal blood flow provides a more than sufficient rate of oxygen supply to the kidney. Limitations in tissue oxygenation may occur under systemic circulatory alterations (i.e. cardiovascular failure, arterioscelorosis), respiratory insuffiency (i.e. lung diseases, hypoxia, extreme anemia, acclimation to high altitude), or during perfusion of isolated organs with blood substitutes (Klause, N., and Gronow, G., 1990; Klause, N., et al., 1990). Hypoxic limitation of renal function at a maintained systemic respiration and circulation is less well understood. One example is tissue hypoxia in the kidney due to a vasoconstrictory side effect of radiocontrast media (RCM). Recent animal experiments support evidence that in the pathophysiology of RCM-induced renal vasoconstriction the balance between production of endothelium derived nitric oxide (NO) and endothelin (ET) is disturbed, whereby NO does not seem to play an important role (Bagnis et al., 1997, Morcos et al., 1997).

COAGULATION ACTIVATION IN PATIENTS UNDERGOING DIRECTIONAL CORONARY ATHERECTOMY

Restenosis is a major problem of percutaneous transluminal coronary angioplasty (PTCA) and related procedures. To better understand the underlying pathophysiologic mechanisms, coagulation and fibrinolytic variables were analysed prospectively in 35 patients after directional coronary atherectomy (DCA) and in 20 control patients undergoing diagnostic heart catheterisation and coronary angiography. Blood samples were taken before and 1 h, 24 h and 48 h after the procedure. No subacute thrombosis or unstable angina were documented in any patient. In 8 out of these 35 patients late restenosis was diagnosed during follow-up angiography 3-6 months after DCA. In these 8 patients prothrombin fragments (F1 + 2) rose from 0.7 to 0.9 nmol/l (P < 0.01) and thrombin-antithrombin III complexes (TAT) from 2.9 to 6.0 micrograms/l (P < 0.01), but not significantly in 27 patients without restenosis and in the control patients. In patients with late restenosis plasminogen activator inhibitor (PAI-1) also increased from 2.4 to 4.9 U/ml (P < 0.05) 24 h after DCA while there were no significant changes in patients without restenosis and in control patients. D-Dimer/TAT ratio reflecting the balance between clotting activation and fibrinolysis was significantly lower after 24 h in restenosis patients. The findings suggest that coagulation activation and hypofibrinolysis during 48 h after DCA might be associated with the development of late restenosis.

First-In-Man Experience With a New 7F Vascular Closure Device (EXOSEAL™): The 7F ECLIPSE Study

OBJECTIVE This feasibility study examined safety and effectiveness of the new EXOSEAL™ Vascular Closure Device (VCD) designed to promote hemostasis and early ambulation after percutaneous procedures. BACKGROUND Most VCDs currently approved by the United States FDA have been associated with significantly shorter time-to-hemostasis (TTH) and time-to-ambulation (TTA) compared to standard manual or mechanical compression, but their ease of use, patient comfort during deployment, and safety profiles are variable. METHODS Patients underwent diagnostic or interventional procedures using 7F introducer sheaths. Primary safety endpoint was the 30-day combined rate of access-related complications and primary effectiveness endpoints were TTH and TTA. RESULTS Sixty patients were enrolled prospectively (mean age 63.3 ± 11.3 year, 17% diabetics). Device and procedural success was achieved in 92% and 93%, respectively. Mean TTH and TTA was 3.2 ± 3.0 minutes and 3.0 ± 6.2 hours, respectively. No deaths or serious access-related adverse events occurred. A ≥6 cm access-site hematoma was the only adverse event, observed in 3 patients. CONCLUSIONS Use of the 7F EXOSEAL™ VCD was associated with short TTH and TTA, as well as low rates of procedural and 30-day access-related complications.

Relationship between therapeutic time intervals and intermediate term left ventricular systolic function in patients treated with facilitated percutaneous coronary intervention for acute myocardial infarction

SummaryBackgroundThe concept of initiating fibrinolytic therapy in patients who cannot undergo immediate percutaneous coronary intervention (PCI) in the setting of acute ST-segmentelevation myocardial infarction (STEMI) has been proposed as a strategy to improve outcomes. However, evidence supporting the use of this strategy is not conclusive, and the results of recent randomized controlled trials are apparently contradictory. Probably, the time points of administration of the adjunctive thrombolytics and antiplatelet agents and the time loss until coronary intervention have a major influence on the discrepancy of outcomes in different trials. Therefore, the relationship between therapeutic time intervals and outcome in patients treated with facilitated PCI has been analyzed.MethodsIn this single center retrospective study, 131 patients with STEMI were treated with a combined pharmaco-mechanical reperfusion strategy using half-dose r-tPA combined with a glycoprotein (GP) IIb/IIIa antagonist prior to PCI. Specific time points were recorded for each patient, including the time of symptom onset, the time of first medical contact, the start of intravenous thrombolysis, the time of administration of the GP IIb/IIIa antagonist and the start of coronary intervention. We then examined the relationship between the time delay from symptom onset to the initiation of various steps of treatment and the residual myocardial damage as expressed by the severity of both global and regional myocardial dysfunction calculated from a left ventriculography study performed 3 months later.ResultsThe median time from symptom onset to the first medical contact, with 25th and 75th percentiles in parentheses, was 1.25 h (0.75, 3), from symptom onset to initiation of thrombolytic therapy 2.25 h (1.25, 3), to initiation of GP IIb/ IIIa inhibitor therapy 3.5 h (2, 5.69), and to the start of coronary intervention 4.81 h (2.85, 7.91). The time between symptom onset and initiation of both thrombolytic therapy and coronary intervention was significantly related to the global ejection fraction and to the extent of regional hypokinesia at the 3-month follow-up (p<0.05). The time to the initiation of GP IIb/IIIa inhibitors was only significantly related to the global ejection fraction (p<0.05), while the time to the first medical contact did not show a similar relationship (p>0.05). Furthermore, we observed a significant relationship between the infarct-related artery (IRA) patency at the initial angiogram and the residual regional myocardial damage at follow-up; normokinesia at follow- up was found in 61.3% of patients with an initially patent IRA and in 41.2% of patients with an initially occluded IRA, whereas severe hypokinesia was found in 13.8% and 37.3%, respectively (p<0.05).ConclusionIn patients with STEMI treated with a facili tated PCI strategy using half dose r-tPA in combination with a glycoprotein IIb/IIIa receptor blocker, the 3-month global and regional residual myocardial dysfunction is significantly related to the time elapsed between the onset of symptoms and the start of both fibrinolytic therapy and coronary intervention.

Chylous cardiac tamponade in acute pancreatitis

SummaryA 47-year-old woman with acute necrotizing pancreatitis developed sudden cardiorespiratory arrest and needed resuscitation. A pericardial effusion was found, and 350 ml of a white nontransparent milky fluid was aspirated that contained 1020 mg triglycerides/100 ml. The diagnosis of chylous cardiac tamponade was made. Absence of amylase in the chylous effusion militates against the popular hypothesis that lymphatic transport of exocrine digestive enzymes from the inflamed pancreas produces the frequent intrathoracic serosal effusions in acute pancreatitis. The data of our patient rather suggest that these effusions result from the leakage of pancreatic inflammatory exudates through the diaphragm which, apparently, may even result in the loss of pericardial and adjacent thoracic lymph vessel integrity. Although pericardial tamponade is a rare complication, it should be considered if otherwise unexplained circulatory deterioration occurs in a patient with acute pancreatitis.

Swimming and hemostasis during rehabilitation in patients with coronary heart disease

Coronary heart disease and acute myocardial infarction are frequent causes of death in Western industrial countries. Therefore, prevention of myocardial infarction and rehabilitation after myocardial infarction are of significant medical interest. In epidemiologic studies, physical inactivity was detected as a coronary risk factor and, on the other hand, a meta analysis of 22 randomized studies showed that continuous physical exercise induces a reduction of cardiac mortality by 20% [25,26]. However, the risk of hypercoagulability induced by exercise exists especially among patients with heart and vessel diseases [11]. The influence of physical exercise by running and bicycle ergometer on the human haemostatic system has been well investigated [6,11,14,33]. However, for swimming there are nearly no data available, although swimming is included in the training program of many of the so-called coronary sport groups. As an endurance sport with training effect swimming is suited as rehabilitation. This is only true for patients with normal physical workload, since everybody has an increased energy turnover equal to an ergometer workload of 75 W in water at 25–29 jC even without physical activity [22]. Thus, knowledge about the activation of clotting and the fibrinolytic system is important. It has been demonstrated that patients after physical exercise by running and cycling have an activation of clotting factors with the potential risk for thrombosis [6,11,14,33]. Comparable investigations for swimming are lacking. Therefore, in the present study parameters for the assessment of clotting and fibrinolytic system in patients before and after swimming were investigated.

Immunoglobulin A and secretory immunoglobulin A in the bronchoalveolar lavage from patients after lung transplantation.

Secretory immunoglobulin A (sIgA) is the most important Ig on mucosal surfaces. In bronchoalveolar lavage (BAL) fluid, sIgA is mainly produced by bronchus‐associated lymphoid tissue (BALT). The presence of pre‐formed antibodies against donor tissue in kidney transplantation is associated with hyperacute rejection, indicating a humoral (antibody‐mediated) reaction. In heart and liver transplantation, humoral rejection has also been documented. The goal of this study was to evaluate the role of IgA in patients after lung transplantation. An enzyme‐linked immunosorbent assay was established to determine the levels of sIgA, IgA, and total protein in the lavage. IgA and sIgA were both detectable in BAL from transplanted lungs. IgA and sIgA levels were both higher during episodes of infection than during episodes of rejection or during the control episodes. The level of IgA during episodes of rejection equaled the level of IgA during the control episodes. The level of sIgA was significantly decreased during episodes of acute rejection (1.8±1.0 μg/mL) when compared with the control (7.2±1.0 μg/mL; p=0.013). This study demonstrates that BALT retains the ability to produce Ig even after lung transplantation. The levels of IgA and sIgA and their ratio do not contribute to the differentiation between rejection and infection in lung‐transplanted patients.