Loss of cardioprotection induced by ischemic preconditioning after an initial ischemic period in isolated rat hearts

BACKGROUND:

The beneficial effect of ischemic preconditioning (PC) has been extensively studied in normal hearts but its effects on diseased hearts remain largely unknown. The effect of PC in the already ischemic myocardium has not been previously studied, although ischemia in varying intervals, which is difficult to assess, is often encountered in clinical practice.

OBJECTIVE:

To investigate whether the cardioprotective effect of PC is preserved when it is applied after a period of ischemia of varying duration.

METHODS:

Male Wistar rats were used for this study. Isolated normal rat hearts were perfused in Langendorff mode. Before 20 min of zero flow global ischemia followed by 45 min of reperfusion, hearts were subjected to an initial 20-min period of ischemia followed by 10 min of reperfusion (group A1); an initial 20-min period of ischemia followed by 10 min of reperfusion and two-cycle PC (3 min of ischemia, 5 min of reperfusion followed by 5 min of ischemia and 5 min of reperfusion) (group A2); and two-cycle PC followed by the initial 20-min period of ischemia and 10 min of reperfusion (group A3).Groups B and C were subjected to an initial ischemia of 15 min and 10 min, respectively, and subgroups 1, 2 and 3 were treated as above. Left ventricular end-diastolic pressure was measured at 45 min of reperfusion (LVEDP45 in mmHg). Postischemic recovery of left ventricular developed pressure was expressed as a percentage of the initial value (LVDP%).

RESULTS:

LVDP% and LVEDP45 were similar between groups A1 and A2, while when ischemic preconditioning preceded the two periods of ischemia (group A3), it resulted in significantly higher LVDP% and significantly lower LVEDP45 compared with groups A1 and A2. Left ventricular functional recovery was not increased in group B2 compared with group B1. LVDP% and LVEDP45 were similar among groups C1, C2 and C3.

CONCLUSION:

Ischemic preconditioning does not improve functional recovery in isolated rat hearts that have been initially subjected to 20 min or 15 min of zero-flow global ischemia, while an initial 10-min ischemic period seems to precondition the heart.     

Immune Modulation in Heart Failure: the Promise of Novel Biologics

Purpose of review

Immune system activation plays a central role in heart failure progression. Large-scale immune modulatory clinical trials targeting tumor necrosis factor-α and broad spectrum immune modulation have been negative. The objective of this review is to highlight past, present, and what is in the horizon for the immunomodulation in heart failure with a focus of biologics.

Recent findings

Strategies targeting interleukin-1 pathway are currently undergoing clinical evaluation and data from pilot studies are promising. The potential of cell therapy for immune modulation is increasingly recognized in clinical trials. Strategies targeting anti-cardiac antibodies such as immunoadsorption and intravenous immunoglobulin have been used in clinical practice with positive outcomes but large pragmatic clinical trials are lacking. The use of an aptamer to block anti-cardiac antibodies is undergoing phase 1 clinical evaluation. Promising targets include inflammasomes, toll-like receptors, chemokines, natural killer cells, and macrophages.

Summary

Large-scale immune modulatory clinical trials have been negative. Nevertheless, the experience gained from them along with increasing understanding of molecular mechanisms of immune pathophysiology in heart failure is leading to rapid recognition of new therapeutic targets and approaches.

     

Invasive techniques in diagnosis and staging of lung cancer

Aim-Background

During the staging process of lung cancer, accurate mediastinal lymph node staging is one of the more important factors to affect patient outcome. Accurate staging of the disease is important not only in determining prognosis but also in deciding the optimal treatment plan. The most significant treatment decision is establishing which patients can benefit from surgical resection and which should receive chemotherapy, radiation, or both. This paper reviews indications and current data regarding minimally invasive approaches for diagnosis and staging of lung cancer. In addition, current advances in diagnostic endoscopy for lung cancer will be reviewed.

Methods

A systematic literature search was performed to identify relevant reports. Studies and articles were identified using online searches of the U.S. National Library of Medicine via www.pubmed.com. We limited our bibliographic search to include only articles from 2008 onward.

Results

The thoracoscopic approach is currently considered the gold standard for the evaluation and treatment of suspected or known pleural effusion and in the diagnosis of indeterminate pulmonary nodules. It also has a complementary role to cervical mediastinoscopy in the invasive staging of mediastinal lymph nodes. Its role continues to evolve with regard to the management of lung cancer.

Conclusions

Mediastinoscopy has remained the ‘gold standard’ in invasive staging tests of the mediastinum. The classic way of invasively assessing the aortopulmonary window is the Chamberlain procedure, also known as an anterior mediastinotomy.     

Heart involvement in systemic sclerosis: a combined echocardiographic and scintigraphic study

The aim of this study is to investigate systemic sclerosis (SSc) patients without clinically evident heart disease for cardiac abnormalities. SSc patients and age- and sex-matched healthy controls from the hospital staff underwent transthoracic echocardiography for the assessment of the left ventricle (LV) morphology and function and estimation of the pulmonary artery systolic pressure (PASP). Patients further underwent stress-rest myocardial perfusion imaging (MPI) scintigraphy by single-photon emission computed tomography (SPECT). Thirty-seven patients were included (33 women, 19 with diffuse, and 18 with limited SSc). LV hypertrophy was more common in SSc patients than controls (24.3 vs 0 %, p?=?0.001). Impaired LV relaxation was found in 45.9 % of patients and 40.5 % controls (p?=?0.639). Excluding patients with arterial hypertension, LV hypertrophy was still found in 23.1 % and LV relaxation impairment in 38.5 %. PASP over 30 mmHg was found in 13 patients (35.1 %), 11 of whom had no history of pulmonary arterial hypertension (PAH). Of 35 patients who underwent SPECT, 21 patients (60 %) exhibited reversible LV perfusion defects. Their mean age was 51.8 years; four patients were younger than 40 years old and eight patients younger than 50 years. In all cases, ischemia was graded as mild or moderate and in a single case, graded as significant. Subclinical heart involvement is common in SSc patients even in the younger age groups. LV hypertrophy and impaired relaxation, raised PASP, and ischemia on MPI with SPECT are found in a significant proportion of SSc patients. Careful screening of SSc patients for potential heart involvement and consultation by a cardiologist may be of value.     

Influence of apneic oxygenation on cardiorespiratory system homeostasis

Purpose

The aim of this study was to elucidate the magnitude of variations in oxygenation indices and the pattern of hemodynamic changes in response to the net effect of tracheal apneic oxygenation (AO) with a view to define the safe time limit of its application.

Methods

After obtaining Animal Research Ethics Committee approval, AO was applied in 12 piglets for 40 min. Arterial (a) and mixed venous (v) blood samples for oxygen (O₂) and carbon dioxide (CO₂) tension (PaO₂/PvO₂, PaCO₂/PvCO₂), O₂ saturation (SaO₂/SvO₂), pHa, base excess (BEa), and bicarbonate (HCO₃a) determination and for alveolar O₂ tension (PAO₂), PaO₂/FiO₂ and PaO₂/PAO₂ ratio, arterial–mixed venous O₂ content (AVDO₂), and O₂ extraction ratio (O₂ER) estimation were collected on anesthesia induction, 10, 20, 30, and 40 min during AO and 10 and 20 min after reconnection to the ventilator. Concomitant hemodynamic data were obtained.

Results

Besides PvO₂ and PAO₂, AO adversely influenced PaO₂ (248–113 mmHg), PaCO₂ (35–145 mmHg), PvCO₂, PaO₂/FiO₂, and PaO₂/PAO₂ in a time-depended fashion, whereas SvO₂, AVDO₂, and O₂ER were minimally affected. P(a ? v)CO₂ was reversed throughout AO. Acid–base status derangement, consisting of HCO₃a elevation, BEa widening, and acidemia (pH 6.9) maximized 40 min after AO. During AO, heart rate, systemic and pulmonary circulation pressures, and cardiac output were progressively elevated, whereas systemic vascular resistance was reduced. All the studied parameters reverted almost to baseline within the 20-min period of ventilator reconnection.

Conclusion

Tracheal AO for 40 min ensures acceptable blood oxygenation, promotes notable hypercapnic acidosis, and consequent transient hemodynamic alterations, which are almost completely reversible after reconnection to the ventilator.     

Are the measurements of water-filled and air-charged catheters the same in urodynamics?

Introduction and hypothesis

The aim of our study was to compare air-charged and water-filled catheters simultaneously in the measurement of the intravesical, abdominal and detrusor pressure during urodynamic investigations.

Methods

Consecutive women with lower urinary tract symptoms, referred for urodynamics were prospectively studied. Readings of intravesical pressure (p_ves), abdominal pressure (p_abd) and detrusor pressure (p_det), recorded by both the air-charged and water-filled catheters, were displayed simultaneously and compared at the end of filling, on standing, on sitting prior to voiding and at the maximum involuntary detrusor contraction. The signals (pressures) recorded by both types of catheter were compared using the Bland–Altman plot and paired samples t test.

Results

Twenty women with a mean age of 49 (range 36–72) were recruited. One patient with normal urodynamics was excluded in view of the poor quality trace. At each of the four comparison points, the air-charged catheters consistently produced higher mean pressures than the water-filled catheters. There were wide variations in the difference between the readings produced by the two types of catheter.

Conclusions

Pressures measured using air-charged catheters are not comparable with water-filled catheters and are therefore not interchangeable. Caution must be used when comparing urodynamic parameters using air-charged and water-filled catheters.