Infective Endocarditis Surgery. Insights from 328 Patients Operated in a University Tertiary Hospital. / Cirurgia de Endocardite Infecciosa. Análise de 328 Pacientes Operados em um Hospital Universitário Terciário.

BACKGROUND: Infectious endocarditis (IE) refers to infection of the endocardial surface of the heart and usually occurs in native or prosthetic valves. OBJECTIVE: This study aimed to raise IE data reflecting the surgical therapy in a University Hospital in the interior of the State of Sao Paulo-Brazil. METHOD: Retrospective and observational approach of 328 patients with IE who underwent surgery between 1982 and 2020. RESULTS: The main data (n=121/37%), congestive heart failure (n=114/35%), valve disease (n=92/28%), diabetes mellitus (n=85/26%), chronic kidney disease (n=59/18%), and rheumatic fever (49/15%). Renal failure is one of the main and most relevant pre-surgical risk factors for a poor prognosis. CONCLUSION: For a better clinical and surgical outcome, an early syndromic and etiological diagnosis of IE is necessary, especially in patients with multiple comorbidities.

FUNDAMENTO: A endocardite infecciosa (EI) refere-se à infecção da superfície endocárdica do coração e geralmente ocorre em valvas nativas ou protéticas. OBJETIVO: Este estudo teve como objetivo levantar dados de EI refletindo a terapêutica cirúrgica, em um Hospital Universitário do interior do estado de São Paulo ­ Brasil. MÉTODO: Abordagem retrospectiva e observacional de 328 pacientes com EI operados entre 1982 e 2020. RESULTADOS: Os principais dados (n=121/37%), insuficiência cardíaca congestiva (n=114/35%), valvopatia (n=92/28%), diabetes mellitus (n=85/26%), doença renal crônica (n=59/18%) e febre reumática (49/15%). A insuficiência renal é um dos principais e mais relevantes fatores de risco pré-cirúrgicos para um mau prognóstico. CONCLUSÃO: Para um melhor resultado clínico e cirúrgico é necessário o diagnóstico sindrômico e etiológico precoce da EI, principalmente em pacientes com múltiplas comorbidades.

Cirurgia de Endocardite Infecciosa. Análise de 328 Pacientes Operados em um Hospital Universitário Terciário / Infective Endocarditis Surgery. Insights from 328 Patients Operated in a University Tertiary Hospital

Resumo Fundamento A endocardite infecciosa (EI) refere-se à infecção da superfície endocárdica do coração e geralmente ocorre em valvas nativas ou protéticas. Objetivo Este estudo teve como objetivo levantar dados de EI refletindo a terapêutica cirúrgica, em um Hospital Universitário do interior do estado de São Paulo - Brasil. Método Abordagem retrospectiva e observacional de 328 pacientes com EI operados entre 1982 e 2020 Resultados Os principais dados (n=121/37%), insuficiência cardíaca congestiva (n=114/35%), valvopatia (n=92/28%), diabetes mellitus (n=85/26%), doença renal crônica (n=59/18%) e febre reumática (49/15%). A insuficiência renal é um dos principais e mais relevantes fatores de risco pré-cirúrgicos para um mau prognóstico. Conclusão Para um melhor resultado clínico e cirúrgico é necessário o diagnóstico sindrômico e etiológico precoce da EI, principalmente em pacientes com múltiplas comorbidades.

Abstract Background Infectious endocarditis (IE) refers to infection of the endocardial surface of the heart and usually occurs in native or prosthetic valves. Objective This study aimed to raise IE data reflecting the surgical therapy in a University Hospital in the interior of the State of Sao Paulo-Brazil. Method Retrospective and observational approach of 328 patients with IE who underwent surgery between 1982 and 2020 Results The main data (n=121/37%), congestive heart failure (n=114/35%), valve disease (n=92/28%), diabetes mellitus (n=85/26%), chronic kidney disease (n=59/18%), and rheumatic fever (49/15%). Renal failure is one of the main and most relevant pre-surgical risk factors for a poor prognosis. Conclusion For a better clinical and surgical outcome, an early syndromic and etiological diagnosis of IE is necessary, especially in patients with multiple comorbidities.

Methylene Blue to Treat Protamine-induced Anaphylaxis Reactions. An Experimental Study in Pigs.

Objective: To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects. Methods: The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA). Malondialdehyde plasma levels were estimated using the thiobarbiturate technique. Results: 1) Groups Sham and MB presented unchanged parameters; 2) Group P - a) Intravenous protamine infusion caused mean arterial pressure decrease and recovery trend after 25-30 minutes, b) Cardiac output decreased and remained stable until the end of protamine injection, and c) Sustained systemic vascular resistance increased until the end of protamine injection; 3) Methylene blue infusion after protamine (Group P/MB) - a) Marked mean arterial pressure decreased after protamine, but recovery after methylene blue injection, b) Cardiac output decreased after protamine infusion, recovering after methylene blue infusion, and c) Sustained systemic vascular resistance increased after protamine infusion and methylene blue injections; 4) Methylene blue infusion before protamine (Group MB/P) - a) Mean arterial pressure decrease was less severe with rapid recovery, b) After methylene blue, there was a progressive cardiac output increase up to protamine injection, when cardiac output decreased, and c) Sustained systemic vascular resistance decreased after protamine, followed by immediate Sustained systemic vascular resistance increase; 5) Plasma nitrite/nitrate and malondialdehyde values did not differ among the experimental groups. Conclusion: Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view.

Methylene blue to treat protamine-induced anaphylaxis reactions. An experimental study in pigs

ABSTRACT Objective: To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects. Methods: The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA). Malondialdehyde plasma levels were estimated using the thiobarbiturate technique. Results: 1) Groups Sham and MB presented unchanged parameters; 2) Group P - a) Intravenous protamine infusion caused mean arterial pressure decrease and recovery trend after 25-30 minutes, b) Cardiac output decreased and remained stable until the end of protamine injection, and c) Sustained systemic vascular resistance increased until the end of protamine injection; 3) Methylene blue infusion after protamine (Group P/MB) - a) Marked mean arterial pressure decreased after protamine, but recovery after methylene blue injection, b) Cardiac output decreased after protamine infusion, recovering after methylene blue infusion, and c) Sustained systemic vascular resistance increased after protamine infusion and methylene blue injections; 4) Methylene blue infusion before protamine (Group MB/P) - a) Mean arterial pressure decrease was less severe with rapid recovery, b) After methylene blue, there was a progressive cardiac output increase up to protamine injection, when cardiac output decreased, and c) Sustained systemic vascular resistance decreased after protamine, followed by immediate Sustained systemic vascular resistance increase; 5) Plasma nitrite/nitrate and malondialdehyde values did not differ among the experimental groups. Conclusion: Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view.

Remarkable 23-year survival after bilateral thoracic melanoma metastasectomy.

The prognosis of patients with metastatic melanoma is poor, with an annual risk of death of approximately 20% during the first 3 years. The survival average is only 6 to 8 months, and the 5-year survival rate is around 5%. This report describes a remarkable clinical outcome of complete resection of pulmonary metastatic melanoma. The 72-year-old woman is still alive without relapse 27 years after the initial diagnosis and 23 years after the last tumor excision. This remarkable outcome would indicate that the tumor cell population was composed of a particular metastatic phenotype.

Exhaled and plasma nitrite: a comparative study among healthy, cirrhotic and liver transplant patients.

CONTEXT: There is a relative lack of studies about exhaled nitrite (NO2-) concentrations in cirrhotic and transplanted patients. OBJECTIVE: Verify possible differences and correlations between the levels of NO2-, measured in plasma and exhaled breath condensate collected from patients with cirrhosis and liver transplant. METHOD: Sixty adult male patients, aged between 27 and 67 years, were subdivided into three groups: a control group comprised of 15 healthy volunteers, a cirrhosis group composed of 15 volunteers, and a transplant group comprised of 30 volunteers. The NO2- concentrations were measured by chemiluminescence. RESULTS: 1) The analysis of plasma NO2- held among the three groups showed no statistical significance. 2) The comparison between cirrhotic and control groups, control and transplanted and cirrhotic and transplanted was not statistically significant. 3) The measurements performed on of NO2- exhaled breath condensate among the three groups showed no statistical difference. 4) When comparing the control group samples and cirrhotic, control and transplanted and cirrhotic and transplanted, there was no significant changes in the concentrations of NO2-. CONCLUSION: No correlations were found between plasma and exhaled NO2-, suggesting that the exhaled NO2- is more reflective of local respiratory NO release than the systemic circulation.

EXHALED AND PLASMA NITRITE: a comparative study among healthy, cirrhotic and liver transplant patients / Nitrito exalado e plasmático: um estudo comparativo entre pacientes transplantados saudáveis, cirrose e fígado

Context There is a relative lack of studies about exhaled nitrite (NO2-) concentrations in cirrhotic and transplanted patients. Objective Verify possible differences and correlations between the levels of NO2-, measured in plasma and exhaled breath condensate collected from patients with cirrhosis and liver transplant. Method Sixty adult male patients, aged between 27 and 67 years, were subdivided into three groups: a control group comprised of 15 healthy volunteers, a cirrhosis group composed of 15 volunteers, and a transplant group comprised of 30 volunteers. The NO2- concentrations were measured by chemiluminescence. Results 1) The analysis of plasma NO2- held among the three groups showed no statistical significance. 2) The comparison between cirrhotic and control groups, control and transplanted and cirrhotic and transplanted was not statistically significant. 3) The measurements performed on of NO2- exhaled breath condensate among the three groups showed no statistical difference. 4) When comparing the control group samples and cirrhotic, control and transplanted and cirrhotic and transplanted, there was no significant changes in the concentrations of NO2-. Conclusion No correlations were found between plasma and exhaled NO2-, suggesting that the exhaled NO2- is more reflective of local respiratory NO release than the systemic circulation. .

Contexto Observa-se relativa falta de estudos sobre nitrito (NO2-) exalado como biomarcador de lesão, após transplante de fígado. Objetivo Verificar possíveis diferenças e correlações entre os níveis de nitrito (NO2-), medido no plasma e condensado do exalado pulmonar de pacientes com cirrose e transplante de fígado. Método Sessenta pacientes adultos, masculinos, idades entre 27 e 67 anos, foram divididos em três grupos: grupo controle composto por 15 voluntários saudáveis, grupo cirrose, composto por 15 voluntários e, grupo de transplante, composto por 30 voluntários. As dosagens plasmáticas e do condensado do exalado pulmonar foram realizadas por quimioluminescência. Resultados A análise os valores de NO2- plasmático não mostrou diferença entre os grupos. As comparações entre grupos cirrose e controle, controle e transplantados e cirrose e transplante não foram significativas. As medidas em amostras de condensado do exalado pulmonar entre os três grupos não evidenciaram diferenças estatísticas. Ao comparar as amostras dos grupos controle e cirrótico, controle e transplantado e cirróticos e transplantados, não houve alterações significativas nas concentrações de NO2-. Conclusão Não foram encontradas correlações entre plasma e condensado do exalado pulmonar, sugerindo que o NO exalado reflete mais as condições respiratórias locais de liberação de NO do que a circulação sistêmica. .

Curbing inflammation in the ischemic heart disease.

A modern concept considers acute coronary syndrome as an autoinflammatory disorder. From the onset to the healing stage, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Inflammatory response following acute myocardial infarction has been well documented since the 1940s and 1950s, including increased erythrocyte sedimentation rate, the C-reactive protein analysis, and the determination of serum complement. It is surprising to note, based on a wide literature overview including the following 30 years (decades of 1960, 1970, and 1980), that the inflammatory acute myocardium infarction lost its focus, virtually disappearing from the literature reports. The reversal of this historical process occurs in the 1990s with the explosion of studies involving cytokines. Considering the importance of inflammation in the pathophysiology of ischemic heart disease, the aim of this paper is to present a conceptual overview in order to explore the possibility of curbing this inflammatory process.

Effects of elevated perfusion pressure and pulsatile flow on human saphenous veins isolated from diabetic and non-diabetic patients.

OBJECTIVE: This study was carried out to determine high pressure and pulsatile flow perfusion effects on human saphenous vein (HSV) segments obtained from diabetic and non-diabetic patients. METHODS: The veins were perfused with oxygenated Krebs solution for 3 h, with a pulsatile flow rate of 100 mL/min and pressures of 250 × 200 or 300 × 250 mmHg. After perfusion, veins were studied by light microscopy; nitric oxide synthase (NOS) isoforms, CD34 and nitrotyrosine immunohistochemistry and tissue nitrite/nitrate (NO(x)) and malondialdehyde (MDA) quantification. RESULTS: Light microscopy revealed endothelial denuding areas in all HSV segments subjected to 300 × 250 mmHg perfusion pressure, but the luminal area was similar. The percentage of luminal perimeter covered by endothelium decreased as perfusion pressures increased, and significant differences were observed between groups. The endothelial nitric oxide synthase (eNOS) isoform immunostaining decreased significantly in diabetic patients' veins independent of the perfusion pressure levels. The inducible NOS (iNOS), neuronal NOS (nNOS) and nitrotyrosine immunostaining were similar. Significant CD34 differences were observed between the diabetic 300 × 250 mmHg perfusion pressure group and the non-diabetic control group. Tissue nitrite/nitrate and MDA were not different among groups. CONCLUSIONS: Pulsatile flow and elevated pressures for 3 h caused morphological changes and decreased the eNOS expression in the diabetic patients' veins.

Cardiovascular therapeutics targets on the NO-sGC-cGMP signaling pathway: a critical overview.

In a brief overview, in NO-sGC-cGMP signaling in a blood vessel, l-arginine is converted in the endothelium monolayer by the endothelial nitric oxide synthase (eNOS) to NO which diffuses into both the vessel lumen and the vessel wall, thereby activating soluble guanylate cyclase (sGC). Heme-dependent sGC stimulators and hem-independent sGC activators increase the cellular cGMP concentration via the direct activation of sGC, which results in both vasorelaxation and inhibition of platelet aggregation. Studies of the 90's definitively established the role of endothelium in all cardiovascular diseases, which were associated with endothelial dysfunction by impaired release of endothelium-derived relaxing factors with consequent risk of spasm and thrombosis. The rationale of this review is based on the fact that the discovery of NO changed the concepts of cardiovascular disease mechanisms. However, considering the jargon "from the bench to clinical practice" we concluded that a potential therapeutic revolution did not follow the pathophysiological revolution. The review is focused on general aspects without regard for advanced research aspects, and designed in two main groups: the NO/cGMP positive stimulators and blockers as "future and encouraging" new therapeutic drugs. The potential vasodilators include 1) NOS uncoupling; 2) NOS enhancers (AVE compounds); 3) NO donors (nitrovasodilators); 4) NO-independent activators (BAY compounds), and; 5) PDE5 inhibitors. The potential vasoconstrictors include 1) NOS-blockers (L-NAME, L-NMMA); 2) sGC-blockers (methylene blue), and; 3) PDEs. Few texts, selected by excellence and relevance, were crucial and considerably facilitated the elaboration of this text, in addition to our own experimental and clinical experience working on vasoplegic endothelium dysfunction.

Diabetes and vascular disease: basic concepts of nitric oxide physiology, endothelial dysfunction, oxidative stress and therapeutic possibilities.

The vascular manifestations associated with diabetes mellitus (DM) result from the dysfunction of several vascular physiology components mainly involving the endothelium, vascular smooth muscle and platelets. It is also known that hyperglycemia-induced oxidative stress plays a role in the development of this dysfunction. This review considers the basic physiology of the endothelium, especially related to the synthesis and function of nitric oxide. We also discuss the pathophysiology of vascular disease associated with DM. This includes the role of hyperglycemia in the induction of oxidative stress and the role of advanced glycation end-products. We also consider therapeutic strategies.

Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate.

Segments of the canine internal mammary artery (35 mm in length) were suspended in vitro in an organ chamber containing physiological salt solution (95% O2/5% CO2, pH = 7.4, 37 degrees C). Segments were individually cannulated and perfused at 5 ml/minute using a roller pump. Vasorelaxant activity of the effluent from the perfused internal mammary arteries was bioassayed by measuring the decrease in tension induced by the effluent of the coronary artery endothelium-free ring which had been contracted with prostaglandin F2alpha (2 x 10(-6) M). Intraluminal perfusion of adenosine diphosphate (10(-5) M) induced significant increase in relaxant activity in the effluent from the perfused blood vessel. However, when adenosine diphosphate (10(-5) M) was added extraluminally to the internal mammary artery, no change in relaxant activity in the effluent was noted. In contrast, acetylcholine produced significant increase in the relaxant activity on the effluent of the perfused internal mammary artery with both intraluminal and extraluminal perfusion. The intraluminal and extraluminal release of endothelium-derived relaxing factor (EDRF) by acetylcholine (10(-5) M) can be inhibited by site-specific administration of atropine (10(-5) M). These experiments indicate that certain agonists can induce the release of EDRF only by binding to intravascular receptors while other agonists can induce endothelium-dependent vasodilatation by acting on neural side receptors.

Blood cardioplegia with N-acetylcysteine may reduce coronary endothelial activation and myocardial oxidative stress.

OBJECTIVES: The aim of this prospective study was to compare the efficacy of intermittent antegrade blood cardioplegia with or without n-acetylcysteine (NAC) in reducing myocardial oxidative stress and coronary endothelial activation. METHODS: Twenty patients undergoing elective isolated coronary artery bypass graft surgery were randomly assigned to receive intermittent antegrade blood cardioplegia (32 degrees C-34 degrees C) with (NAC group) or without (control group) 300 mg of NAC. For these 2 groups we compared clinical outcome, hemodynamic evolution, systemic plasmatic levels of troponin I, and plasma concentrations of malondialdehyde (MDA) and soluble vascular adhesion molecule 1 (sVCAM-1) from coronary sinus blood samples. RESULTS: Patient demographic characteristics and operative and postoperative data findings in both groups were similar. There was no hospital mortality. Comparing the plasma levels of MDA 10 min after the aortic cross-clamping and of sVCAM-1 30 min after the aortic cross-clamping period with the levels obtained before the aortic clamping period, we observed increases of both markers, but the increase was significant only in the control group (P= .039 and P= .064 for MDA; P= .004 and P= .064 for sVCAM-1). In both groups there was a significant increase of the systemic serum levels of troponin I compared with the levels observed before cardiopulmonary bypass (P< .001), but the differences between the groups were not significant (P= .570). CONCLUSIONS: Our investigation showed that NAC as an additive to blood cardioplegia in patients undergoing on-pump coronary artery bypass graft surgery may reduce oxidative stress and the resultant coronary endothelial activation.

Efficacy and safety of aprotinin use for reoperative valvular surgery.

BACKGROUND: Preservation of the hemostatic system during cardiac surgery is a main concern, primarily after repeated cardiac operations. METHODS: We compared the outcomes of adult patients undergoing isolated reoperative valvular surgery receiving full-dose of aprotinin (redo group, n = 70) with patients experiencing primary isolated valvular surgery not receiving aprotinin (primary group, n = 135). RESULTS: The mean age was lower in the redo group (45 +/- 14 years vs 50 +/- 17 years, p = 0.036). The redo group had more female patients (73% vs 51%, p = 0.003), patients in functional class IV (15% vs 4% p = 0.009), and patients with chronic atrial fibrillation (48% vs 24%, p = 0.001). The cardiopulmonary bypass duration was longer in the redo group (119 +/- 50 minutes vs 103 +/- 41 minutes, p = 0.014). However, the blood loss was significantly lower (300 +/- 279 mL vs 776 +/- 584 mL, p = 0.001) and fewer patients needed transfusions (3.0% vs 13%, p = 0.023) in the redo group. The postoperative morbidity was similar in both groups. The postoperative in-hospital mortality was 7% in the primary group and 10% in the redo group (p = 0.419). Factors associated with postoperative in-hospital mortality were the following: age greater than 60 years (p = 0.040, odds ratio [OR] 3.0), New York Heart Association class IV (p = 0.022, OR 5.0), preoperative critical state (p < 0.001, OR 12), emergent operation (p = 0.012, OR 7.0), endocarditis (p = 0.004, OR 10.0), and reoperation due to mechanical mitral prosthesis dysfunction (p = 0.009, OR 7). CONCLUSIONS: The mortality and morbidity in redo valve surgery with aprotinin administration was comparable with primary valve surgery without aprotinin. Bleeding and transfusion requirements were significantly lower in redo patients receiving aprotinin.