Publications

BACKGROUND

Ventricular tachycardia (VT) is a common cause of mortality in post-myocardial infarction (MI) patients, even in the current era of coronary revascularization treatment. We report a reproducible VT model in rats with chronic MI induced by ischemia-reperfusion and describe its electrophysiological characteristics using high-resolution optical mapping.

METHODS

An MI was generated by left anterior descending coronary ligation (25 minutes) followed by reperfusion in 20 rats. Electrophysiology study and optical mapping were performed 5 weeks later using a Langendorff-perfused preparation and compared to normal rats.

RESULTS

The conduction velocity of the MI border zone was decreased to 53% of the normal areas remote from the infarct (0.37 +/- 0.16 m/sec vs 0.70 +/- 0.09 m/sec, P < 0.0001). The rate of VT inducibility in MI rats was significantly greater than in normal control rats (70% vs 0%, P = 0.00002). VT circuits involving the infarct area were identified with optical mapping in 83% MI rats. In addition, fixed and functional conduction block were observed in the infarct border zone.

CONCLUSION

This ischemia-reperfusion MI rat model is a reliable VT model, which simulates clinical revascularization treatment. High-resolution optical mapping in this model is useful to study the mechanism of VT and evaluate the effects of therapies.

Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Picornaviridae family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate in vitro, hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike SAFV-3, HTCV-UC6 exhibited slow replication kinetics and demonstrated only a moderate cytopathic effect. Serologic assays revealed that 91% of U.S. adults carry antibodies to the genotype 2 cardioviruses, of which 80% generate neutralizing antibodies, in agreement with previous data showing that cardiovirus infection is widespread in humans. We also demonstrate an acute cardiovirus seroconversion event in a child with diarrhea and vomiting, thus reporting for the first time evidence linking cardiovirus infection to diarrheal disease in humans.

PURPOSE

The purpose of this study was to compare the biomechanical properties of transosseous versus suture anchor repair of the subscapularis tendon. We also performed real-time measurement of contact area and pressure of the repair site under rotational loads.

METHODS

Six paired human cadaveric shoulders were subjected to rotational loading after repair of the subscapularis tendon. Both shoulders were randomized to transosseous or suture anchor repairs. Real-time pressure sensors were placed between the subscapularis tendon and lesser tuberosity. The repair was subjected to cyclical rotational loading and load-to-failure testing.

RESULTS

No significant difference was detected in initial pressurized contact area between transosseous repairs (1.70 +/- 0.99 cm(2), 57.88 +/- 30.02% footprint) and suture anchor repairs (1.08 +/- 0.58 cm(2), 34.26% +/- 17.32% footprint). Under cyclical loading, the conditioning elongation of transosseous repairs (0.64 +/- 0.40 mm) was significantly lower (P < .05) than that of suture anchor repairs (2.38 +/- 1.58 mm). No significant difference was found in mean pressurized contact area between the transosseous repairs (2.72 +/- 1.25 cm(2), 94.2% +/- 37.4% footprint) and suture anchor repairs (2.01 +/- 0.89 cm(2), 65.9% +/- 27.9% footprint). For suture anchor repairs, repair-site contact area was significantly (P < .05) smaller than the area of corresponding native insertional footprints; for transosseous repairs, no significant difference was detected. There were no significant differences in peak pressures between the 2 repairs. In the load-to-failure tensile test, there was no significant difference between transosseous repairs (453.2 +/- 66.1 N) and suture anchor repairs (392.6 +/- 78.0 N).

CONCLUSIONS

Transosseous and suture anchor repairs of the subscapularis tendon have comparable biomechanical properties. Despite increased conditioning elongation in suture anchor repairs, we found no significant differences in mean contact area between the 2 repairs under cyclical loading. The suture anchor repairs do have a smaller contact area than the native insertional area. Real-time pressure and contact area measurements enabled mapping of the repair site throughout cyclical loading.

CLINICAL RELEVANCE

Rotational loading of the subscapularis tendon may provide a more accurate representation of subscapularis tendon injuries. Both techniques showed adequate repair strength; however, neither surgical technique exhibited normal insertional behavior in this time-zero biomechanical study.

HIV "controllers" are persons infected with human immunodeficiency virus, type I (HIV) who maintain long-term control of viremia without antiviral therapy and who usually do not develop the acquired immune deficiency syndrome (AIDS). In this study, we have correlated results from polychromatic flow cytometry and oligonucleotide expression arrays to characterize the mucosal immune responses of these subjects in relation to untreated HIV(+) persons with high viral loads and progressive disease ("noncontrollers"). Paired peripheral blood and rectosigmoid biopsies were analyzed from 9 controllers and 11 noncontrollers. Several cellular immune parameters were found to be concordant between the 2 compartments. Compared with noncontrollers, the mucosal tissues of controllers had similar levels of effector T cells and fewer regulatory T cells (Tregs). Using principal component analysis to correlate immunologic parameters with gene expression profiles, transcripts were identified that accurately distinguished between controllers and noncontrollers. Direct 2-way comparison also revealed genes that are significantly different in their expression between controllers and noncontrollers, all of which had reduced expression in controllers. In addition to providing an approach that integrates flow cytometry datasets with transcriptional profiling analysis, these results underscore the importance of the sustained inflammatory response that attends progressive HIV disease.