RESUMO
BACKGROUND: Experimental evidence suggests that blood cardioplegia (BCP) may be superior to cold crystalloid cardioplegia (CCP) for myocardial protection. However, robust clinical data are lacking. We compared postoperative outcome of patients undergoing aortic valve replacement (AVR) using cold anterograde-retrograde intermittent BCP versus anterograde (CCP). METHODS: Adult consecutive isolated AVR performed between April 2006 and February 2011 at the Royal Infirmary Hospital of Edinburgh were retrospectively analyzed. The use of anterograde CCP was compared with that of intermittent anterograde-retrograde cold BCP. End points were intra-operative mortality, 30-day hospital re-admission, need for RBC or platelet transfusion, mechanical ventilation time and renal failure. RESULTS: Of total 774 cases analyzed, 592 cases of BCP and 182 cases of CCP were identified. Demographics did not differ between groups (mean age: 67±12 years in CCP and 69±12 years in BCP). Groups (BCP vs. CCP) were indistinguishable (P>0.05, not significant) based on: average aortic cross clamp time 77.01±14.47 vs. 75.78±18.78 minutes, cardiopulmonary bypass time 104.07±43.70 vs. 100.34±25.90 minutes, surgery time 190.53±61.80 vs. 204.04±51.09 minutes and postoperative total blood consumption 1.38±2.11 vs. 1.61±2.4 units. The percentage of patients who required platelets' transfusion was similar: 12.8% BCP and 18.7% CCP (Fisher's exact test, P=0.053). Prevalence of respiratory failure was lower in BCP than in CCP: 2.6% vs. 6.3% (P=0.028). Admission time (days) at ICU was 3.63± 21.90 in BCP and 3.07±8.04 in CCP (not significant). Intra-hospital mortality, 30-day hospital re-admission, renal failure, sepsis, wound healing and stroke did not differ between groups. CONCLUSIONS: BCP was strictly not superior to CCP in every aspect. In particular it was definitely not superior in terms of postoperative ventricular function. Our results question the absolute superiority of BCP over CCP in terms of hard outcomes. Likelihood of serious complications should be considered to improve risk profile of patients before choosing a cardioplegic solution.
Assuntos
Valva Aórtica/cirurgia , Soluções Cardioplégicas/uso terapêutico , Parada Cardíaca Induzida/métodos , Implante de Prótese de Valva Cardíaca/métodos , Soluções Isotônicas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Idoso , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Ponte Cardiopulmonar , Soluções Cristaloides , Feminino , Implante de Prótese de Valva Cardíaca/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Patients with end-stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), and exhibit accelerated progression of calcific aortic valve disease (CAVD). We hypothesized that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat valve interstitial cells (VICs) calcification at 4.5 mM (16.4-fold; p < 0.05) whereas Pi treatment alone had no effect. Ca (2.7 mM) and Pi (2.5 mM) synergistically induced calcium deposition (10.8-fold; p < 0.001) in VICs. Ca treatment increased the mRNA of the osteogenic markers Msx2, Runx2, and Alpl (p < 0.01). MVs were harvested by ultracentrifugation from VICs cultured with control or calcification media (containing 2.7 mM Ca and 2.5 mM Pi) for 16 hr. Proteomics analysis revealed the marked enrichment of exosomal proteins, including CD9, CD63, LAMP-1, and LAMP-2 and a concomitant up-regulation of the Annexin family of calcium-binding proteins. Of particular note Annexin VI was shown to be enriched in calcifying VIC-derived MVs (51.9-fold; p < 0.05). Through bioinformatic analysis using Ingenuity Pathway Analysis (IPA), the up-regulation of canonical signaling pathways relevant to cardiovascular function were identified in calcifying VIC-derived MVs, including aldosterone, Rho kinase, and metal binding. Further studies using human calcified valve tissue revealed the co-localization of Annexin VI with areas of MVs in the extracellular matrix by transmission electron microscopy (TEM). Together these findings highlight a critical role for VIC-derived MVs in CAVD. Furthermore, we identify calcium as a key driver of aortic valve calcification, which may directly underpin the increased susceptibility of ESRD patients to accelerated development of CAVD.
Assuntos
Anexina A6/metabolismo , Estenose da Valva Aórtica/metabolismo , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Calcinose/metabolismo , Matriz Extracelular/metabolismo , Vesículas Extracelulares/metabolismo , Hipercalcemia/etiologia , Falência Renal Crônica/complicações , Idoso , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Valva Aórtica/ultraestrutura , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/patologia , Calcinose/etiologia , Calcinose/genética , Calcinose/patologia , Cálcio/metabolismo , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Matriz Extracelular/ultraestrutura , Vesículas Extracelulares/ultraestrutura , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Hipercalcemia/diagnóstico , Falência Renal Crônica/diagnóstico , Masculino , Microscopia Eletrônica de Transmissão , Mapas de Interação de Proteínas , Proteômica/métodos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Vascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of cardiovascular disease, compared to women of a similar age. These gender disparities suggest an influence of sex hormones. Testosterone is the primary and most well-recognised androgen in men. Therefore, we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase (Alpl) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention.