Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.

Evolução a longo prazo e complicaçöes da hipertensão arterial após transplante cardíaco / Long-term follow-up and complications of arterial hypertension after cardiac transplantation

OBJETIVO - Avaliar a evolução da hipertensão arterial (HA), e suas conseqüências, em pacientes submetidos a transplante cardíaco (TC) em uso de ciclosporina (CL). MÉTODOS - Em 65 pacientes submetidos a TC ortotópico, avaliamos a pressão arterial, creatinina sérica e níveis sangüíneos de CL nos períodos pré-operatório (15 dias antes do TC), pós-operatório precoce (15 e 30 dias) tardio (6, 12, 24, 48 e 60 meses); em 20 pacientes analisamos índice cardíaco e resistência vascular no pré, 15 e 30 dias, 6 e 12 meses após TC; em 33 pacientes, estudamos estrutura e função ventricular ao ecocardiograma, 24ñ13 meses após Tc. RESULTADOS - Após 30 dias, a HA estava presente em 58,5 'por cento' dos pacientes (50 'por cento'leve), enquanto na evolução tardia, a incidência da HA aumentou significativamente para 93 'por cento' após um ano (85 'por cento'moderada a grave). A creatinina sérica aumentou progressivamente do pré-TC (1,43ñ0,5mg/dl) até após um ano (1,83ñ0,9mg/dl). Não houve correlação entre a HA, creatinina sérica e níveis de CL. O índice cardíaco aumentou na fase precoce, enquanto a resistência periférica diminuiu no início e aumentou significativamente aos 12 meses. Ao ecocardiograma, 54 'por cento' dos pacientes apresentavam hipertrofia de ventrículo esquerdo com função normal. Dos 31 pacientes que faleceram durante a evolução, dois tiveram a causa mortis diretamente relacionada a HA. CONCLUSÄO - A HA em pacientes submetidos a TC em uso de CL ocorre precocemente, aumenta em prevalência e gravidade com tempo e é mediada por aumento da resistência periférica, não se correlacionando com a nefrotoxicidade e com os níveis sangüíneos da CL, podendo agravar a insuficiência renal ou comprometer a longevidade do transplante, induzindo hipertrofia ventricular.

Beneficial effect of long-term use of a beta-blocker in patients before acute myocardial infarction

The outcome of 38 beta-blocker users (group BB, 28 men and 10 women with a mean age of 56 ñ 4 years) was compared to that of 100 non-users (group NU, 69 men and 31 women with mean age of 57 ñ 8 years) after acute myocardial infarction (AMI). The two groups were compared in terms of electrocardiographic (EKG) location of the AMI (anterior, inferior and lateral), EKG Q and non-Q wave infarction, clincial functional class of Forrester, serum cratine phosphokinase MB fraction (CKMB) peak release and intrahospital mortality.There were no differences between groups concerning sex or severity of coronary artery disease bath arterial hypertension was 3-fold more prevalent group BB. The EKG location of the AMI was similar int he two groups. Non-Q infarction was significantly more prevalent in group BB (37 percent) than in group NU (5 percent). The incidence of clinical functional class IV of Forrester and the serum CKMB peaks were significantly lower in goup BB (2.6 percent vs 16.0 percent and 53 ñ 3 vs 68 ñ 9 UI/1, respectively. Intrahospital mortality was also significantly lower in group BB (2.6 percent) than in group NU (10 percent). These data suggest the beneficial effect of previous long-term use of beta-blockers as indicated by a lower incidence of cardiogenic shock and a significant decrease in intrahospital mortality after AMI