Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure

In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT(7) receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively. 5-HT(7) immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT(7) immunoreactivity. The selective 5-HT(7) receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently. Our in vitro experiments suggest an involvement of the 5-HT(7) receptor subtype in contractility of equine intestine. While the 5-HT(7) receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT(7) receptor ligand SB-269970, suggesting it exerting inverse agonist properties.

Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry

BACKGROUND Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. METHODS AND RESULTS This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. CONCLUSIONS In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

Complex pelvic traumas: Data linkage of the German Pelvic Injury Register and the TraumaRegister DGU®

BACKGROUND Complex pelvic traumas, i.e., pelvic fractures accompanied by pelvic soft tissue injuries, still have an unacceptably high mortality rate of about 18 %. PATIENTS AND METHODS We retrospectively evaluated an intersection set of data from the TraumaRegister DGU® and the German Pelvic Injury Register from 2004-2009. Patients with complex and noncomplex pelvic traumas were compared regarding their vital parameters, emergency management, stay in the ICU, and outcome. RESULTS From a total of 344 patients with pelvic injuries, 21 % of patients had a complex and 79 % a noncomplex trauma. Complex traumas were significantly less likely to survive (16.7 % vs. 5.9 %). Whereas vital parameters and emergency treatment in the preclinical setting did not differ substantially, patients with complex traumas were more often in shock and showed acute traumatic coagulopathy on hospital arrival, which resulted in more fluid volumes and transfusions when compared to patients with noncomplex traumas. Furthermore, patients with complex traumas had more complications and longer ICU stays. CONCLUSION Prevention of exsanguination and complications like multiple organ dysfunction syndrome still pose a major challenge in the management of complex pelvic traumas.

[Ventricular assist device – Possibilities of long-term mechanical circulatory support]

In Switzerland 200’000 people suffer from congestive heart failure. Approximately 10’000 patients find themselves in an advanced state of the disease. When conservative treatment options are no longer available heart transplantation is the therapy of choice. Should this not be an option due to long waiting lists or medical issues assist device therapy becomes an option. Assist device therapy is separated in short-term and long-term support. Long-term support is nowadays performed with ventricular assist devices (VADs). The native heart is still in place and supported in parallel to the remaining function of the heart. The majority of patients are treated with a left ventricular assist device (LVAD). The right ventrical alone (RVAD) as well as bi-ventricular support (BiVAD) is rarely needed. The modern VADs are implantable and create a non-pulsative bloodflow. A percutaneous driveline enables energy supply and pump-control. Indication strategies for VAD implantations include bridge to transplant (short term support), bridge to candidacy and bridge to transplant. VADs become more and more a definite therapeutic option (destination therapy). VAD therapy might be a realistic alternative to organ transplantation in the near future.