Peri-partum cardiomyopathy (PPCM) is a frequently fatal disease that affects women near delivery, and occurs more frequently in women with pre-eclampsia and/or multiple gestation. The etiology of PPCM, or why it associates with pre-eclampsia, remains unknown. We show here that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble Flt1 (sFlt1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by sub-clinical cardiac dysfunction, the extent of which correlates with circulating levels of sFlt1. Exogenous sFlt1 alone caused diastolic dysfunction in wildtype mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFlt1. These data strongly suggest that PPCM is in large part a vascular disease, caused by excess anti-angiogenic signaling in the peri-partum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.
Carinal resection with primary reconstruction may be accomplished with acceptable mortality rates, but the underlying pathologic process and chance for long-term survival must be carefully considered before the operation is recommended, especially in the case of left carinal pneumonectomy. Anastomotic complications exact a heavy toll on involved patients. Careful patient selection and meticulous anesthetic and surgical technique remain the key to minimizing morbidity and mortality rates.
The presence of perioperative diastolic dysfunction as assessed with Vp is an independent predictor of postoperative CHF and prolonged length of stay after major vascular surgery. Patient age, gender, type of surgery, and renal failure were also predictors of outcome. Perioperative systolic function was not a predictor of postoperative outcome in our patients.
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