7 research outputs found

    Right ventricular myocardial energetic model for evaluating right heart function in pulmonary arterial hypertension

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    Background: Pulmonary arterial hypertension (PAH) increases right ventricular (RV) workload and decreases myocardial oxygen reserve, eventually leading to poor cardiac output. This study created and assessed a novel model of RV work output based on RV hemodynamics and oxygen supply, allowing new insight into causal mechanisms of RV dysfunction. Methods: The RV function model was built upon an earlier, left ventricular model and further adjusted for more accurate clinical use. The model assumes that RV total power output (1) is the sum of isovolumic and stroke power and (2) is linearly related to its right coronary artery oxygen supply. Thus, when right coronary artery flow is limited or isovolumic power is elevated, less energy is available for producing cardiac output. The original and adjusted models were validated via data from patients with idiopathic PAH (n = 14) and large animals (n = 6) that underwent acute pulmonary banding with or without hypoxia. Results: Both models demonstrated strong, significant correlations between RV oxygen consumption rate and RV total power output for PAH patients (original model, R 2 = 0.66; adjusted model, R 2 = 0.78) and sheep (original, R 2 = 0.85; adjusted, R 2 = 0.86). Furthermore, the models demonstrate a significant inverse relationship between required oxygen consumption and RV efficiency (stroke power/total power) (p < 0.001). Lastly, higher NYHA class was indicative of lower RV efficiency and higher oxygen consumption (p = 0.013). Conclusion: Right ventricular total power output can be accurately estimated directly from pulmonary hemodynamics and right coronary perfusion during PAH. This model highlights the increased vulnerability of PAH patients with compromised right coronary flow coupled with high afterload

    Nicotinic Acetylcholine Receptor-Mediated Protection of the Rat Heart Exposed to Ischemia Reperfusion

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    Abstract Reperfusion injury following acute myocardial infarction is associated with significant morbidity. Activation of neuronal or non-neuronal cholinergic pathways in the heart has been shown to reduce ischemic injury, and this effect has been attributed primarily to muscarinic acetylcholine receptors. In contrast, the role of nicotinic receptors, specifically α-7 subtype (α7nAChR), in the myocardium remains unknown, which offers an opportunity to potentially repurpose several agonists/modulators that are currently under development for neurologic indications. Treatment of ex vivo and in vivo rat models of cardiac ischemia/reperfusion (I/R) with a selective α7nAChR agonist (GTS21) showed significant increases in left ventricular developing pressure and rates of pressure development, without effects on heart rate. These positive functional effects were blocked by co-administration with methyllycaconitine (MLA), a selective antagonist of α7nAChRs. In vivo, delivery of GTS21 at the initiation of reperfusion reduced infarct size by 42% (p < 0.01) and decreased tissue reactive oxygen species (ROS) by 62% (p < 0.01). Flow cytometry of MitoTracker Red-stained mitochondria showed that mitochondrial membrane potential was normalized in mitochondria isolated from GTS21-treated compared with untreated I/R hearts. Intracellular adenosine triphosphate (ATP) concentration in cultured cardiomyocytes exposed to hypoxia/reoxygenation was reduced (p < 0.001), but significantly increased to normoxic levels with GTS21 treatment, which was abrogated by MLA pretreatment. Activation of stress-activated kinases JNK and p38MAPK was significantly reduced by GTS21 in I/R. We conclude that targeting myocardial α7nAChRs in I/R may provide therapeutic benefit by improving cardiac contractile function through a mechanism that preserves mitochondrial membrane potential, maintains intracellular ATP and reduces ROS generation, thus limiting infarct size

    Surgical Infection Society: Chest Wall Injury Society Recommendations for Antibiotic Use during Surgical Stabilization of Traumatic Rib or Sternal Fractures to Reduce Risk of Implant Infection

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    Surgical stabilization of rib fractures is recommended in patients with flail chest or multiple displaced rib fractures with physiologic compromise. Surgical stabilization of rib fractures (SSRF) and surgical stabilization of sternal fractures (SSSF) involve open reduction and internal fixation of fractures with a plate construct to restore anatomic alignment. Most plate constructs are composed of titanium and presence of this foreign, non-absorbable material presents opportunity for implant infection. Although implant infection rates after SSRF and SSSF are low, they present a challenging clinical entity often requiring prolonged antibiotic therapy, debridement, and potentially implant removal. The Surgical Infection Society\u27s Therapeutics and Guidelines Committee and Chest Wall Injury Society\u27s Publication Committee convened to develop recommendations for antibiotic use during and after surgical stabilization of traumatic rib and sternal fractures. Clinical scenarios included patients with concomitant infectious processes (sepsis, pneumonia, empyema, cellulitis) or sources of contamination (open chest, gross contamination) incurred as a result of their trauma and present at the time of their surgical stabilization. PubMed, Embase, and Cochrane databases were searched for pertinent studies. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation. For patients undergoing SSRF or SSSF in the absence of pre-existing infectious process, there is insufficient evidence to suggest existing peri-operative guidelines or recommendations are inadequate. For patients undergoing SSRF or SSSF in the presence of sepsis, pneumonia, or an empyema, there is insufficient evidence to provide recommendations on duration and choice of antibiotic. This decision may be informed by existing guidelines for the concomitant infection. For patients undergoing SSRF or SSSF with an open or contaminated chest there is insufficient evidence to provide specific antibiotic recommendations. This guideline document summarizes the current Surgical Infection Society and Chest Wall Injury Society recommendations regarding antibiotic use during and after surgical stabilization of traumatic rib or sternal fractures. Limited evidence exists in the chest wall surgical stabilization literature and further studies should be performed to delineate risk of implant infection among patients undergoing SSSRF or SSSF with concomitant infectious processes
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