Plasma copeptin levels before and during exogenous arginine vasopressin infusion in patients with advanced vasodilatory shock.

BACKGROUND: Plasma copeptin levels before and during exogenous arginine vasopressin infusion (AVP) were evaluated, and the value of copeptin levels before AVP therapy to predict complications during AVP therapy and outcome in vasodilatory shock patients was determined. METHODS: This prospective, observational study was nested in a randomized, controlled trial investigating the effects of two AVP doses (0.033 vs. 0.067 IU/min) on the hemodynamic response in patients with advanced vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery. Clinical data, plasma copeptin levels and adverse events were recorded before, 24 hours after and 48 hours after randomization. RESULTS: Plasma copeptin levels were elevated before AVP therapy. During AVP, copeptin levels decreased (P<0.001) in both groups (P=0.73). Copeptin levels at randomization predicted the occurrence of ischemic skin lesions (AUC ROC, 0.73; P=0.04), a fall in platelet count (AUC ROC, 0.75; P=0.01) during AVP and intensive care unit mortality (AUC ROC, 0.67; P=0.04). Twenty-five patients (64.1%) exhibited a decrease in copeptin levels. Patients experiencing a decrease in copeptin levels were older (P=0.04), had a higher Sequential Organ Failure Assessment score count before (P=0.03) and during AVP therapy (P=0.04), had a longer intensive care unit stay (P<0.001) and required AVP therapy longer (P=0.008) than patients without a decrease in copeptin levels during AVP. CONCLUSION: Plasma copeptin levels are elevated in patients with advanced vasodilatory shock. During exogenous AVP therapy, copeptin levels decrease, suggesting suppression of the endogenous AVP system.

[Advanced vasodilatory shock. One-year survival after arginine vasopressin therapy]. / Fortgeschrittene vasodilatatorische Schockzustände. Einjahresüberleben nach Argininvasopressintherapie.

BACKGROUND: Arginine vasopressin (AVP) is increasingly being used to treat advanced vasodilatory shock states due to sepsis, systemic inflammatory response syndrome (SIRS) or after cardiac surgery. There are currently no data available on long-term survival. PATIENTS AND METHODS: Demographic and clinical data, length of intensive care unit (ICU) stay, 1-year survival and causes of death after ICU discharge of 201 patients who received AVP because of advanced vasodilatory shock were collected retrospectively. RESULTS: The intensive care unit (ICU) survival rate was 39.8% (80 out of 201 patients). After ICU discharge 13 out of the 80 patients died within 1 year resulting in a 1-year survival rate of 33.3% (67 out of 201 patients). In nine patients, the cause of death was attributed to the same disease that led to ICU admission. One-year survival of patients with shock following cardiac surgery (42.1%) was higher than in patients suffering from SIRS (22.6%, p=0.005) or sepsis (28.3%, p=0.06). CONCLUSIONS: If advanced vasodilatory shock can be reversed with AVP and patients can be discharged alive from the ICU, 1-year survival rates appear to be reasonable despite severe multi-organ dysfunction syndrome (MODS).

Coil embolization of internal mammary artery injured during central vein catheter and cardiac pacemaker lead insertion.

PURPOSE: This study describes several cases of endovascular coil embolization of the proximal internal mammary artery injured by blind approach to the subclavian vein for central venous catheter or pacemaker lead insertion. MATERIALS AND METHODS: We conducted a retrospective analysis of five patients with iatrogenic arterial lesions of the internal mammary artery (IMA). The lesions occurred in three patients from a puncture of the subclavian vein during insertion of a central venous catheter and in two patients from a puncture of the subclavian vein for insertion of a pacemaker lead. Four patients had acute symptoms of bleeding with mediastinal hematoma and hematothorax and one patient was investigated in a chronic stage. A pseudoaneurysm was detected in all five patients. All four acute and hemodynamic unstable patients required hemodynamic support. RESULTS: In all patients, embolization was performed using a coaxial catheter technique, and a long segment of the IMA adjacent distally and proximally to the source of bleeding was occluded with pushable microcoils. In one patient, additional mechanically detachable microcoils were used at the very proximal part of the IMA. Microcoil embolization of the IMA was successful in all patients, and the source of bleeding was eliminated in all patients. CONCLUSION: Transarterial coil embolization is a feasible and efficient method in treating acute bleeding and pseudoaneurysm of the IMA and should be considered if mediastinal hematoma or hemathorax occurs after blind puncture of the subclavian vein.

Molecular imaging of neurovascular cell death in experimental cerebral stroke by PET.

UNLABELLED: Clinical molecular imaging of apoptosis is a highly desirable yet unmet challenge. Here we provide the first report on (18)F-labeled 5-fluoropentyl-2-methyl-malonic acid ((18)F-ML-10), a small-molecule, (18)F-labeled PET tracer for the imaging of apoptosis in vivo; this report includes descriptions of the synthesis, radiolabeling, and biodistribution of this novel apoptosis marker. We also describe the use of (18)F-ML-10 for small-animal PET of neurovascular cell death in experimental cerebral stroke in mice. METHODS: (18)F-ML-10 was synthesized by nucleophilic substitution from the respective mesylate precursor, and its biodistribution was assessed in healthy rats. Permanent occlusion of the middle cerebral artery (MCA) was induced in mice, and small-animal PET was performed 24 h later. RESULTS: Efficient radiolabeling of ML-10 with (18)F was achieved. Biodistribution studies with (18)F-ML-10 revealed rapid clearance from blood (half-life of 23 min), a lack of binding to healthy tissues, and rapid elimination through the kidneys. No significant tracer metabolism in vivo was observed. Clear images of distinct regions of increased uptake, selectively in the ischemic MCA territory, were obtained in the in vivo small-animal PET studies. Uptake measurements ex vivo revealed 2-fold-higher uptake in the affected hemisphere and 6- to 10-fold-higher uptake in the region of interest of the infarct. The cerebral uptake of (18)F-ML-10 was well correlated with histologic evidence of cell death. The tracer was retained in the stroke area but was cleared from blood and from intact brain areas. CONCLUSION: (18)F-ML-10 is useful for noninvasive PET of neurovascular histopathology in ischemic cerebral stroke in vivo. Such an assessment may assist in characterization of the extent of stroke-related cerebral damage and in the monitoring of disease course and effect of treatment.

[Vasopressin as a rescue vasopressor agent. Treatment of selected cardiogenic shock states]. / Vasopressin als Reservevasopressor. Behandlung ausgewählter kardiogener Schockzustände.

Vasodilatory shock is the most common form of shock in the critically ill patient. As a consequence of overwhelming and prolonged mediator production, vasodilatory shock can be the common final pathway of primary non-vasodilatory shock (e.g. cardiogenic or hypovolemic shock). A supplementary infusion of arginine vasopressin (AVP) showed beneficial effects on hemodynamics and potentially on the outcome in patients with vasodilatory shock due to sepsis or after major surgery. In this case series, successful administration of AVP in three surgical patients with primary cardiogenic shock forms is reported. The hemodynamic effects of AVP were comparable to those AVP-induced alterations described in septic shock and seem to be predominantly mediated by potent vasoconstriction and the facilitated reduction of higher, potentially toxic catecholamine doses. Thus, an AVP-induced decrease in heart rate and pulmonary arterial pressures may be particularly beneficial in patients with impaired cardiac function.

Course of vasopressin and copeptin plasma concentrations in a patient with severe septic shock.

In this case report, the course of arginine vasopressin and copeptin, the stable C-terminal part of the arginine vasopressin precursor, is described during the period of critical illness in a septic shock patient. Arginine vasopressin and copeptin concentrations were substantially increased during the initial 36 hours of shock. Subsequently, both hormones continuously decreased, but exhibited another peak in response to stress during extubation. During restoration of cardiovascular stability, endogenous arginine vasopressin levels further decreased and obviously did not contribute to haemodynamic improvement. In contrast, the decrease in arginine vasopressin and copeptin can be at least partly explained by an improvement of cardiovascular function.

A light-activated beta-turn scaffold within a somatostatin analog: NMR structure and biological activity.

Somatostatin owes its biological activity to the presence of a well-defined beta-turn centered around the tetrapeptide Phe-Trp-Lys-Thr. We have developed a light-activated beta-turn scaffold, 1, with the ability to template a beta-turn conformation within the somatostatin tetrapeptide only upon photolysis. The three-dimensional structure of the trans cyclic peptide I obtained by NMR revealed no beta-turn conformation; however, when isomerized to the cis form II with light, the solution structure of the resulting cyclic peptide was found to contain a type II' beta-turn within the Phe-Trp-Lys-Thr sequence. Binding assays with the SRIF receptor demonstrated that the cis peptide displayed enhanced affinity for the receptor over the trans form.

Vasopressin as adjunct vasopressor for vasodilatory shock due to non-occlusive mesenteric ischemia.

We present the case of an 83-year-old patient who underwent cardiac surgery and developed postoperative non-occlusive mesenteric ischemia (NOMI), which was treated with a local intra-arterial papaverine and prostaglandin E1 infusion. After successful mesenteric reperfusion, a multiple organ dysfunction syndrome with severe cardiovascular failure developed. High norepinephrine dosages (1.09 microg/kg body weight/min) and catecholamine-related complications (tachycardiac atrial fibrillation) required initiation of supplementary argininevasopressin (AVP) infusion (4 U/h). AVP stabilized vasodilatory shock, ensured adequate gut perfusion pressure and had no adverse clinical or angiographic effects on restitution of gut integrity. In conclusion, after reperfusion of NOMI in this patient, adjunct AVP therapy combined with local vasodilator infusion was beneficial as a potentially life-saving vasopressor.

The effects of vasopressin on systemic hemodynamics in catecholamine-resistant septic and postcardiotomy shock: a retrospective analysis.

UNLABELLED: We retrospectively investigated the effects of continuous arginine vasopressin (AVP) infusion on systemic hemodynamics, acid/base status, and laboratory variables in patients (mean age [mean +/- SD]= 66.3 +/- 10.1 yr) with catecholamine-resistant septic (n = 35) or postcardiotomy shock (n = 25). Hemodynamic and acid/base data were obtained before; 30 min after; and 1, 4, 12, 24, 48, and 72 h after the start of AVP infusion. Laboratory examinations were recorded before and 24, 48, and 72 h after the start of AVP infusion. For statistical analysis, a mixed-effects model was used. The overall intensive care unit mortality was 66.7%. AVP administration caused a significant increase in mean arterial pressure (+29%) and systemic vascular resistance (+56%), accompanied by a significant decrease in heart rate (-24%) and mean pulmonary arterial pressure (-11%) without any change in stroke volume index. Norepinephrine requirements could be reduced by 72% within 72 h. During AVP infusion, a significant increase in liver enzymes and total bilirubin concentration and a significant decrease in platelet count occurred. Arginine vasopressin was effective in reversing systemic hypotension. However, adverse effects on gastrointestinal perfusion and coagulation cannot be excluded. IMPLICATIONS: In this retrospective analysis, the influence of a continuous infusion of an endogenous hormone (arginine vasopressin) on systemic hemodynamics and laboratory variables was assessed in patients with vasodilatory shock unresponsive to conventional therapy. Arginine vasopressin was effective in reversing systemic hypotension. However, adverse effects on gastrointestinal perfusion and coagulation cannot be excluded.

Risk factors associated with new onset tachyarrhythmias after cardiac surgery--a retrospective analysis.

BACKGROUND: Tachyarrhythmias (TA) represent a frequent and serious problem after cardiac surgery. We retrospectively analyzed 987 cardiac surgery patients admitted to a surgical intensive care unit between 1996 and 1999 to assess incidence and risk factors associated with development of postoperative TA in the intensive care unit. METHODS: TA (n=149) were defined as non-sinus rhythm with a heart rate (HR) > or =100 bpm in patients with preoperative sinus rhythm or as heart rate > or =130 bpm in patients with preoperative atrial fibrillation. A total of 787 patients served as controls (C). Demographic, premorbidity and perioperative data, admission SAPS and MODS-score, presence of clinical syndromes systemic inflammatory response syndrome (SIRS) and sepsis were univariately compared between groups. For prediction of independent risk factors for TA-development two multiple logistic regression models were finally established. RESULTS: Concerning TA, atrial fibrillation and flutter (76%) were observed most frequently, followed by paroxysmal supraventricular tachycardia (15%) and ventricular tachycardia/fibrillation (11%). Age, a history or presence of congestive heart failure, development of SIRS and sepsis, severity of multiple organ dysfunction syndrome and in particular severity of cardiovascular failure proved to be independent risk factors for development of TA. CONCLUSION: In cardiac surgery patients, age, a history or presence of congestive heart failure, postoperative development of a systemic inflammatory response syndrome or sepsis and the severity of multiple organ function syndrome were independent predictors for development of TA in the intensive care unit. The association of severity of cardiovascular dysfunction with TA strongly suggests a causal relationship between catecholamine therapy and TA-development.

[The improvement of polyxenic cultivation of Entamoeba histolytica type HK 9]. / Untersuchungen zur Verbesserung der polyxenischen Kultivation des Entamoeba histolytica-Stammes HK 9.

The serological diagnosis of extraintestinal infections with E. histolytica by indirect immunofluorescence (IFAT) requires a corpuscular antigen. This is produced in our laboratory via polyxenic cultivation of E. histolytica strain HK 9 in a nutrient medium containing a simple salt mixture (Resembling the Ringer-mixture), calf serum and rice starch. It was the aim of the experiments described in this paper to search for a useful medium in which the amebae grow in high density but without substances disturbing the antigen production like debris or rice starch granules. It was shown that the cell culture media of EAGLE MEM and PARKER were easy to handle (contrary to the worldwide used DIAMOND medium TYI-S-33) and brought good results. After a period of 10 subcultures both media were suitable for the cultivation of E. histolytica for making an antigen reasonable for IFAT. As a side effect it was noticed that there was an adaptation phase during which the amebae grew slowly when the medium was changed to another which was completely different (from a cell culture medium to a Ringer-like solution).

On the phospholipase activity in bovine seminal vesicles and its possible role in the regulation of the prostaglandin biosynthesis.

A phospholipid mixture was isolated from bovine vesicle tissue. This phospholipid preparation contained the following prostaglandin precursor fatty acids: 4.7 percent 5,8,11-eicosatrienoic acid, 9.1 percent 5,8,11,14-eicosatetraenoic acid and 0.9% 5,8,11,14,17-eicosapentaenoic acid. With this phospholipid preparation as substrate phospholipase activity could be detected in different fractions of bovine seminal vesicle cells. The highest phospholipase activity was found in the microsomal fraction, less in the mitochondria and essentially no activity in the cytosol. With a microsome preparation (acetone powder) of bovine seminal vesicles the influence of certain effectors on the phospholipase activity was investigated. Prostaglandins E2 and F2alpha (10(-5) M) showed 19 and 41 percent inhibition, DB-c-AMP (2 times 10(-9) M) 54%, c-AMP (10(-9) M) 22%, epinephrine (10(-4) M) 60%, testosterone (10(-5) M) 25% inhibition of the phospholipase activity. Whereas ethanol exhibits also a strong inhibition on the phospholipase activity, it shows a pronounced activation of the prostaglandin synthetase.