Early and sustained haemodynamic improvement with levosimendan compared to intraaortic balloon counterpulsation (IABP) in cardiogenic shock complicating acute myocardial infarction

OBJECTIVE: To investigate the haemodynamic effects of levosimendan in patients with cardiogenic shock (CS) complicating acute myocardial infarction in comparison to the effects of intra-aortic balloon counterpulsation (IABP). METHODS: 10 patients with intractable CS under standard therapy (including the use of PCI, inotropes, and vasopressors) received i.v. infusion of levosimendan (bolus 12 microg/kg i.v., followed by continuous infusion 0.1 microg/kg/min for 24 h). Haemodynamic effects were compared to the effects of IABP-placement added to standard care in 12 patients with CS. RESULTS: Within 24 h, both levosimendan and IABP produced a significant increase in cardiac index (CI) and cardiac power index and a decrease in systemic vascular resistance (SVR) (CI [l/min/m2] baseline 1.97+/-0.15, at 24 h 2.82+/-0.22 for levosimendan; baseline 1.98+/-0.17, at 24 h 2.66+/-0.08 for IABP; SVR [dyn*s*cm-5] baseline 1353+/-106, at 24 h 846+/-69 for levosimendan; baseline 1311+/-214, at 24 h 853+/-63 for IABP, respectively). After 3 h of treatment, CI and SVR had significantly improved in patients treated with levosimendan but not in the IABP-group (CI [l/min/m2] at 3 h 2.72+/-0.28 (+38%) for levosimendan versus 2.18+/-0.15 (+10%) for IABP). CONCLUSION: Infusion of levosimendan in acute CS results in early and sustained haemodynamic improvement. Short-term haemodynamic effects compare favourably with those seen after invasive IABP placement.     

Effect of interferon-gamma on allergic airway responses in interferon-gamma-deficient mice

Interferon (IFN)-gamma reduces airway responses after allergen challenge in mice. The mechanisms of this effect are not clear. These studies investigate whether IFN-gamma can reverse prolonged airway responses after allergen challenge in IFN-gamma-deficient (IFN-gammaKO) mice. Sensitized mice (IFN-gammaKO and wild-type [WT]) were challenged with ovalbumin. Airway responsiveness, eosinophils in bronchoalveolar lavage fluid, and lung lymphocyte subsets (CD4(+) and CD8(+)) were measured 24 hours and 8 weeks after challenge. In further experiments, we treated IFN-gammaKO mice with recombinant IFN-gamma starting 4 weeks after the challenge for 1 week or 4 weeks. Airway responsiveness, bronchoalveolar lavage eosinophils, and lung CD4(+) cells were increased 8 weeks after challenge in IFN-gammaKO but not WT mice. IFN-gamma treatment returned lung CD4(+) cell numbers to values obtained in unchallenged mice. One week of IFN-gamma treatment also returned airway responsiveness to baseline levels; however, 4-week treatment with IFN-gamma failed to decrease airway responsiveness below levels observed in untreated animals. This suggests that IFN-gamma plays an essential role in reversing allergen-induced airway inflammation and hyperresponsiveness and that it may have dual actions on the latter. Observations that IFN-gamma reverses airway responses, even when administered after challenge, suggests that IFN-gamma treatment could control allergic disease, including asthma.     

Intravenous epinephrine in life-threatening asthma

STUDY OBJECTIVE: Intravenous epinephrine is a potentially vital therapy for patients with life-threatening asthma but is often avoided because of concerns about its safety. We evaluated the safety of intravenous epinephrine in a series of adults with life-threatening asthma. METHODS: We performed an explicit retrospective chart review on a case series of 27 emergency department patients aged 19 to 58 years (mean 25 years) who were treated with intravenous epinephrine for a life-threatening exacerbation of asthma between 1989 and 1997. Explicit criteria for adverse effects, including cardiac arrhythmia or ischemia, hypotension or hypertension, neurologic injury, and death, were defined before chart review. RESULTS: No patient had an arrhythmia other than sinus tachycardia, and there were no cases of cardiac ischemia, hypotension, neurologic deficit, or death. CONCLUSION: Intravenous epinephrine was safe in this small series of younger adults with acute life-threatening asthma. A prospective trial of its use to better define an efficacy and risk-benefit relationship is justified.     

Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway remodeling in mice

The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling likely play important roles. We have observed sustained airway hyperreactivity and airway remodeling occurring in mice after chronic allergen exposure and persisting beyond resolution of allergen-induced inflammation. The aim of this study was to delineate mechanisms involved in allergen-induced airway hyperreactivity and airway remodeling and to examine evidence for a causal association between airway remodeling and sustained airway hyperreactivity. Wild-type (WT) and interleukin (IL)-4-, IL-5-, and IL-13-deficient (-/-) mice were sensitized and studied 4 weeks after chronic allergen exposure. By measuring airway responsiveness and airway morphometry, we demonstrated that WT mice developed sustained airway hyperreactivity and aspects of airway remodeling after chronic allergen exposure. Both IL-4(-/-) and IL-13(-/-) mice were protected from developing sustained airway hyperreactivity and aspects of airway remodeling. In contrast, IL-5(-/-) mice developed sustained airway hyperreactivity and aspects of airway remodeling similar to that seen in WT mice. Our results confirm that IL-4 and IL-13, but not IL-5, are critical for the development of sustained airway hyperreactivity and airway remodeling after allergen exposure.     

Weight gain and antipsychotics: a drug safety review

Introduction: Second-generation antipsychotics (SGAs) are widely used in several psychiatric disease entities and exert to a different extent a risk for antipsychotic-induced weight gain (AIWG). As AIWG is associated with an increase in metabolic syndrome or cardiovascular events, knowledge of these risks is crucial for further monitoring and the initiation of counteractive measures.

Areas covered: We searched PubMed and Web of Sciences for randomized-controlled trials and naturalistic observational studies published between 2010 and 2014 with sample sizes exceeding 100, including all marketed SGAs apart from zotepine, and providing data on weight increase. We also summarized relevant systematic reviews and meta-analyses of head-to-head comparisons.

Expert opinion: Recently published data still support the hierarchical ranking of SGAs already proposed in previous reviews ranking clozapine and olanzapine as having the highest risk, followed by amisulpride, asenapine, iloperidone, paliperidone, quetiapine, risperidone and sertindole in the middle, and aripiprazole, lurasidone and ziprasidone with the lowest risk. Number needed to harm varied considerably in our meta-analysis. Younger patients and patients with a lower baseline body mass index are most vulnerable. The greatest amount of weight gain occurs within the first weeks of treatment. AIWG occurs in all diagnostic groups and is also common in treatment with first-generation antipsychotics; therefore, awareness of this adverse event is essential for anyone prescribing antipsychotics.     

Qualitative angiographic and quantitative myocardial perfusion assessment using fluorescent cardiac imaging during graded coronary artery bypass stenosis

Intraoperative graft assessment in coronary artery bypass (CAB) grafting is important to avoid early graft failure. This study aimed to evaluate the accuracy of fluorescent cardiac imaging (FCI) for intraoperative qualitative angiographic and quantitative myocardial perfusion assessment during graded CAB stenosis compared to coronary angiography (CA). After CAB grafting to the left anterior descending coronary artery, graded distal bypass stenoses were created in ten pigs by 25, 50, 75, and 100% flow reduction assessed by transit-time flow measurement (TTFM). Visual angiographic assessment was performed by FCI and CA during baseline and graded bypass stenoses. Altered myocardial perfusion was assessed by quantitative intraoperative fluorescence intensity (QIFI) derived from FCI and correlated to TTFM. Patent bypass grafts and graft occlusion were visualized successfully by FCI and CA, while discrimination between various graded bypass stenosis was possible in 73.3%. The degree of CAB stenosis was overestimated in 16.7% and underestimated in 10.0% by FCI compared to CA. Graded CAB stenosis reduced regional myocardial perfusion quantified by decreased QIFI value (p?<?0.001). Mean QIFI value was 76.8 (95% CI 67.2–86.3) during baseline, 55.6 (95% CI 45.3–65.9) during 25% flow-reduction, 30.6 (95% CI 22.3–39.0) during 50% flow-reduction, 20.3 (95% CI 15.4–25.3) during 75% flow-reduction, and 0 during CAB occlusion (p?<?0.001) with a significant correlation to TTFM (r?=?0.955; p?<?0.0001). Solely visual assessment of CAB quality using FCI is limited as compared to CA. Additional QIFI assessment identified graded CAB stenosis and occlusion with a significant correlation to TTFM.     

Early detection of cerebral ischemia during carotid endarterectomy using transcranial Doppler sonography and somatosensory evoked potentials

Cerebral function during carotid endarterectomy can reliably be monitored using somatosensory evoked potentials (SEP). Transcranial Doppler sonography (TCD) is a noninvasive method providing on-line data about cerebral hemodynamics. The combination of both techniques during carotid surgery is helpful in evaluating the hemodynamic ("input") and the functional ("output") consequences of carotid clamping within a short time. In the present report, combined TCD and SEP monitoring early detected left hemispheric ischemia in a 68-year-old woman subjected to left carotid endarterectomy. The impairment of cerebral perfusion occurred before carotid clamping due to an intraoperative thrombosis of the left internal carotid artery as could be revealed after declamping. A temporary shunt was not inserted. Postoperatively, the patient had a new transient neurological deficit. In this case, TCD correctly indicated cerebral ischemia as confirmed by SEP recording. For carotid artery surgery, combined TCD and SEP may be helpful in detecting those patients who will profit from temporary shunting if this is not done routinely.