Hemodynamic changes associated with manual and automated lateral rotation in mechanically ventilated intensive care patients

Objective: To investigate hemodynamic responses to lateral rotation. ^ Design: Time-series within a randomized controlled trial pilot study. ^ Setting: A medical intensive care unit (ICU) and a medical-surgical ICU in two tertiary care hospitals. ^ Patients: Adult patients receiving mechanical ventilation. ^ Interventions: Two-hourly manual or continuous automated lateral rotation. ^ Measurements and Main Results: Heart rate (HR) and arterial pressure were sampled every 6 seconds for > 24 hours, and pulse pressure (PP) was computed. Turn data were obtained from a turning flow sheet (manual turn) or with an angle sensor (automated turn). Within-subject ensemble averages were computed for HR, mean arterial pressure (MAP), and PP across turns. Sixteen patients were randomized to either the manual (n = 8) or automated (n = 8) turn. Three patients did not complete the study due to hemodynamic instability, bed malfunction or extubation, leaving 13 patients (n = 6 manual turn and n = 7 automated turn) for analysis. Seven patients (54%) had an arterial line. Changes in hemodynamic variables were statistically significant increases ( p < .05), but few changes were clinically important, defined as ≥ 10 bpm (HR) or ≥ 10 mmHg (MAP and PP), and were observed only in the manual-turn group. All manual-turn patients had prolonged recovery to baseline in HR, MAP and PP of up to 45 minutes (p ≤ .05). No significant turning-related periodicities were found for HR, MAP, or PP. Cross-correlations between variables showed variable lead-lag relations in both groups. A statistically, but not clinically, significant increase in HR of 3 bpm was found for the manual-turn group in the back compared with the right lateral position ( F = 14.37, df = 1, 11, p = .003). ^ Conclusions: Mechanically ventilated critically ill patients experience modest hemodynamic changes with manual lateral rotation. A clinically inconsequential increase in HR, MAP, and PP may persist for up to 45 minutes. Automated lateral rotation has negligible hemodynamic effects. ^

Dynamic Remodeling of the Stressed Heart: Role of Protein Degradation Pathways

The heart is a remarkable organ. In order to maintain its function, it remodels in response to a variety of environmental stresses, including pressure overload, volume overload, mechanical or pharmacological unloading and hormonal or metabolic disturbances. All these responses are linked to the inherent capacity of the heart to rebuild itself. Particularly, cardiac pressure overload activates signaling pathways of both protein synthesis and degradation. While much is known about regulators of protein synthesis, little is known about regulators of protein degradation in hypertrophy. The ubiquitin-proteasome system (UPS) selectively degrades unused and abnormal intracellular proteins. I speculated that the UPS may play an important role in both qualitative and quantitative changes in the composition of heart muscle during hypertrophic remodeling. My study hypothesized that cardiac remodeling in response to hypertrophic stimuli is a dynamic process that requires activation of highly regulated mechanisms of protein degradation as much as it requires protein synthesis. My first aim was to adopt a model of left ventricular hypertrophy and determine its gene expression and structural changes. Male Sprague-Dawley rats were submitted to ascending aortic banding and sacrificed at 7 and 14 days after surgery. Sham operated animals served as controls. Effective aortic banding was confirmed by hemodynamic assessment by Doppler flow measurements in vivo. Banded rats showed a four-fold increase in peak stenotic jet velocities. Histomorphometric analysis revealed a significant increase in myocyte size as well as fibrosis in the banded animals. Transcript analysis showed that banded animals had reverted to the fetal gene program. My second aim was to assess if the UPS is increased and transcriptionally regulated in hypertrophic left ventricular remodeling. Protein extracts from the left ventricles of the banded and control animals were used to perform an in vitro peptidase assay to assess the overall catalytic activity of the UPS. The results showed no difference between hypertrophied and control animals. Transcript analysis revealed decreases in transcript levels of candidate UPS genes in the hypertrophied hearts at 7 days post-banding but not at 14 days. However, protein expression analysis showed no difference at either time point compared to controls. These findings indicate that elements of the UPS are downregulated in the early phase of hypertrophic remodeling and normalizes in a later phase. The results provide evidence in support of a dynamic transcriptional regulation of a major pathway of intracellular protein degradation in the heart. The discrepancy between transcript levels on the one hand and protein levels on the other hand supports post-transcriptional regulation of the UPS pathway in the hypertrophied heart. The exact mechanisms and the functional consequences remain to be elucidated.

Progressive regression of left ventricular hypertrophy two years after bariatric surgery.

BACKGROUND: Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass. METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic metabolism, together with body mass index (BMI), waist and hip circumferences, body composition (fat mass and lean mass), and resting energy expenditure were measured at 0, 3, 9, 12, and 24 months. RESULTS: Left ventricular mass continued to decrease linearly over the entire period of observation, while rates of weight loss, loss of lean mass, loss of fat mass, and resting energy expenditure all plateaued at 9 [corrected] months (P <.001 for all). Parameters of systemic metabolism normalized by 9 months, and showed no further change at 24 months after surgery. CONCLUSIONS: Even though parameters of obesity, including BMI and body composition, plateau, the benefits of bariatric surgery on systemic metabolism and left ventricular mass are sustained. We propose that the progressive decrease of left ventricular mass after weight loss surgery is regulated by neurohumoral factors, and may contribute to improved long-term survival.

Role of adenosine signaling in penile erection and erectile disorders.

INTRODUCTION: Penile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection. AIM: To summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders. MAIN OUTCOME MEASURES: Evidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism. METHODS: The article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism. RESULTS: Adenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A(2B) receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism. CONCLUSION: Overall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism.

Outcomes of truncal vascular injuries in children.

BACKGROUND: Pediatric truncal vascular injuries occur infrequently and have a reported mortality rate of 30% to 50%. This report examines the demographics, mechanisms of injury, associated trauma, and outcome of patients presenting for the past 10 years at a single institution with truncal vascular injuries. METHODS: A retrospective review (1997-2006) of a pediatric trauma registry at a single institution was undertaken. RESULTS: Seventy-five truncal vascular injuries occurred in 57 patients (age, 12 +/- 3 years); the injury mechanisms were penetrating in 37%. Concomitant injuries occurred with 76%, 62%, and 43% of abdominal, thoracic, and neck vascular injuries, respectively. Nonvascular complications occurred more frequently in patients with abdominal vascular injuries who were hemodynamically unstable on presentation. All patients with thoracic vascular injuries presenting with hemodynamic instability died. In patients with neck vascular injuries, 1 of 2 patients who were hemodynamically unstable died, compared to 1 of 12 patients who died in those who presented hemodynamically stable. Overall survival was 75%. CONCLUSIONS: Survival and complications of pediatric truncal vascular injury are related to hemodynamic status at the time of presentation. Associated injuries are higher with trauma involving the abdomen.