Development of perioperative premature ventricular contractions as an indicator of splenic hemangiosarcoma and median survival times.

OBJECTIVE: The objectives of this study are (1) to determine whether there is an association between dogs with splenic hemangiosarcoma (HSA) and the development of premature ventricular contractions (VPCs), (2) to determine if there is a higher likelihood for dogs with ruptured splenic masses to be diagnosed with HSA and to develop VPCs, (3) to determine if the development of VPCs affects median survival times compared to dogs with benign or non-HSA malignant splenic masses. STUDY DESIGN: Retrospective case series. ANIMALS: Forty-five dogs. METHODS: Medical records of dogs undergoing splenectomy were reviewed for signalment, perioperative electrocardiogram (ECG), hematological values, histologic diagnosis, metastasis, and survival times. ECGs were performed preoperatively, intraoperatively, and continuously postoperatively. The presence of VPCs was recorded. The data were evaluated for an association between the development of VPCs and the histologic diagnosis of HSA. RESULTS: Eighteen out of 45 (40%) dogs were diagnosed with HSA with 13/18 (72%) dogs having VPCs postoperatively (P = .02). Ruptured splenic HSA and VPCs were noted in 13 dogs (P = .73). An association between dogs with and without VPCs diagnosed with HSA and median survival times could not be established. CONCLUSION: Postoperative VPCs were more likely with splenic HSA. Splenic masses were more likely to be HSA if ruptured but less likely to develop VPCs. Development of VPCs does not affect median survival times. CLINICAL SIGNIFICANCE: Development of postoperative VPCs may be a potential indicator of HSA, however, this warrants further investigations. Development of VPCs does not have a deleterious effect on survival.

Trypanosoma brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes.

AIMS: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. METHODS AND RESULTS: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca(2+) release (Ca(2+) waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10-15% increase of SERCA activity but reduced SR Ca(2+) content, suggesting a concomitant increased SR-mediated Ca(2+) leak. This conclusion was supported by data demonstrating that TbCatL increased Ca(2+) wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. CONCLUSION: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function.