Emergent transesophageal echocardiography in hemodynamically unstable obstetric patients.

BACKGROUND: The obstetric population has an increasing incidence of comorbid conditions. These, coupled with the possibility of acute embolic events involving air, amniotic fluid, and thrombus, increase the likelihood of hemodynamic instability. Although the utility of transesophageal echocardiography to guide management in cardiac and high-risk, non-cardiac surgical populations has been well established, the emergent use in critically-ill parturients has not been comprehensively evaluated. METHODS: Using our departmental transesophageal echocardiography database of 28 293 examinations, parturients were identified who underwent emergent transesophageal echocardiography for evaluation of hemodynamic instability, including cardiac arrest, between January 1999 and March 2014. Transesophageal echocardiography findings and their impact on patient management were analyzed. RESULTS: Ten peripartum patients were evaluated. Six patients became unstable during dilation and evacuation procedures; one after a forceps delivery; one during and one after cesarean delivery; and one during a postpartum laparotomy. Six patients proceeded to cardiac arrest; however, all women survived their initial operation and resuscitation. Transesophageal echocardiography was instrumental in determining the etiology and guiding resuscitation in all 10 patients including emergent cardiac surgical intervention with cardiopulmonary bypass (n=2). Seven patients survived to hospital discharge, but three died after experiencing neurologic complications. CONCLUSIONS: Severe hemodynamic instability and cardiac arrest can occur in previously healthy parturients in pregnancy. Our data suggest that emergent transesophageal echocardiography is a valuable tool in determining the etiology and directing therapy of refractory hypotension or cardiac arrest in obstetric patients.

Molecular targets in osteoarthritis: metalloproteinases and their inhibitors.

The debilitating destruction of joint tissues seen in osteoarthritis (OA) is due, in large part, to the degradative activity of metalloproteinase (MP) enzymes that target extracellular matrix (ECM) components within articular cartilage. Although successful in suppressing the pain and inflammation associated with this disease, conventional OA therapeutics do not inhibit the underlying tissue catabolism, allowing the disease to progress into irreversible ECM loss and chronic disability. Therapeutic inhibition of metalloproteinase activity is not a new concept, however, its transfer into clinical use has been frustrating. Disappointing results from clinical trials with small molecule inhibitors of metalloproteinases have highlighted the critical importance of inhibitor specificity, and the need to identify the individual metalloproteinases responsible for joint destruction. We discuss strategies of inhibition using small molecule inhibitors and tissue inhibitors of metalloproteinases (TIMPs) engineered to increase inhibitory specificity, and present new data using of new reagents such as ribozymes and inhibitory RNAs that repress expression of specific enzymes. Recent data has implicated the disease stage-dependent involvement of matrix metalloproteinase-1, -2, -3, -9, -13, ADAM-17/TACE (tumor-necrosis factor-alpha converting enzyme), and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin 1 motifs) as major in vivo mediators of the ECM degradation seen in OA, and as such, they represent promising therapeutic targets. We conclude that the concept of molecular polypharmacy, in which the relevant enzymes are selectively targeted with multiple directed therapies, may offer a new therapeutic strategy that prevents joint destruction and minimizes toxicities.