Influence of the 21-aminosteroid U74389F on ischemia-reperfusion injury in the rat.

We examined the effects of the administration of 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9( 11)-triene-3,20-dione, monomethansulfonate (U74389F), a 21-aminosteroid and so-called lazaroid, that is characterized by an inhibitory activity against iron-dependent lipid peroxidation, on ischemia-reperfusion renal injury in a rat model. After either 60 or 90 min of ischemia, plus 2 or 24 h of reperfusion, kidneys were assayed for glutathione, adenine nucleotides and lipid peroxidation products. 60 min of ischemia produced too little oxidative stress and/or too much spontaneous recovery to allow visualization of the protective effect of the drug. 90 min of ischemia followed by reperfusion induced significant glutathione oxidation, the free oxidized glutathione to total glutathione redox ratio (%) being enhanced from 4.6 +/- 0.7% before kidney clamping to 11 +/- 1 and 8.6 +/- 1.4% at 2 and 24 h reperfusion, respectively. Treatment with the lazaroid provided significant protection against this oxidation (4.9 +/- 1.05% at 24 h reperfusion). Results of lipid peroxidation confirmed the antioxidant effect of the lazaroid. In conclusion this study provides evidence for a protective role of the tested lazaroid against ischemia-reperfusion renal injury in the rat.

Abdominal aortic aneurysms surgery in over 75 years old patients. Experience in 142 cases treated between 1980-1989.

The paper describes the Authors' experience of abdominal aortic aneurysm surgery in over 75-year-old patients. One hundred and forty-two cases were operated over a 10-year period (1980-89). Seventy-two patients were treated electively and 70 underwent emergency surgery following rupture of the aneurysm. Operative mortality during elective surgery was comparable to that in younger patients, whereas the mortality rate during emergency surgery was notably higher than that in under 75-year-old patients. Follow-up confirmed that the life expectancy of operated patients is significantly better than that of patients with untreated abdominal aortic aneurysms.

[Surgery of thoraco-abdominal aneurysms. Personal experience in 35 cases]. / La chirurgia degli aneurismi toraco-addominali. Esperienza personale su 35 casi.

The paper describes the authors personal experience of the surgical treatment of thoracoabdominal aneurysms. Thirty-five patients underwent surgery during the period from 1972 to the present. Operative mortality is compared according to the different surgical approaches used. Special attention is paid to the techniques of protecting the spinal cord, and in particular to liquor drainage.

[Wall stress in the assessment of left ventricular function in surgery of abdominal aortic aneurysm. Validity and importance of transesophageal echocardiography (TEE) in intraoperative monitoring]. / Lo stress parietale nella valutazione della funzione del ventricolo sinistro nella chirurgia degli aneurismi dell'aorta addominale. Validità ed importanza dell'ecocardiografia transesofagea (TEE), nel monitoraggio intraoperatorio.

OBJECTIVE: To verify the applicability and the clinical significance of left ventricular wall stress determinations by intraoperative transesophageal echocardiography (TEE) during resections of abdominal aortic aneurysms. DESIGNS: Prospective comparison of changes in left ventricular wall stress between two groups of patients with and without coronary artery disease. SETTING: Operatory room of Universitary Institute. PATIENTS: Twenty-three patients with abdominal aortic aneurysms; 8 had clinically evident coronary artery disease (CAD+); 15 patients did not have clinical or electrocardiographic evidence of coronary artery disease (CAD-). INTERVENTIONS: Resection of the aortic aneurysm and insertion of a synthetic prosthesis. MEASUREMENTS AND MAIN RESULTS: During operation transesophageal monitoring of left ventricular volumes and wall stress was performed during induction of anesthesia (T1), for two minutes after aortic clamping (T2), at the end of the proximal anastomosis (T3), for two minutes after aortic declamping (T4) and at the end of the procedure (T5). Circumpherential stress at end systole (sES) and end diastole (sED) was more sensitive than hemodynamic and volumetric parameters in detecting changes i function of the ischemic myocardium. In detail we observed: a significant increase of sES in CAD+versus CAD- at T2: 98 (sd 18) vs 83 (sd 14) 10(3) dyne/cm2. a significant increase of sED in CAD + versus CAD- at T2: 28.5 (sd 6) vs 22 (sd 4.5) 10(3) dyne/cm3. a similar trend of sES and sED at T4: 73 (sd 20.5) vs 46 (sd 15) 10(3) dyne/cm2 and 31 (sd 12) vs 16 (sd 7.7) 10(3) dyne/cm2 respectively. a significant increase of sED in CAD + at T5 (about 20' after T4): 26.5 (sd 9.5) vs 16 (sd 5.2) 10(3) dyne/cm2 which is expression of a persistent reduction of ventricular compliance in the ischemic patients. CONCLUSIONS: Wall stress modifies MVO2 and subsequently is sensitive in detecting changes in myocardial performance. TEE could valuably integrate routine hemodynamic monitoring of patients with coronary heart disease who undergo surgical resection of abdominal aortic aneurysms.

Protection from renal ischemia-reperfusion injury by the 2-methylaminochroman U83836E.

BACKGROUND: In a prior study the 21-aminosteroid (lazaroid) U74389F provided in vivo protection from oxidative stress when used as a preventive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current study the very lipophilic 2-methylaminochroman U83836E, a recently developed lazaroid, was administered to rats at 3 mg/kg before renal ischemia-reperfusion. In addition to the biochemical parameters, the renal function and the histological appearance were carefully evaluated. METHODS: Glutathione, adenine nucleotides and lipid peroxidation products were determined in kidneys reperfused for 2 and 24 hours after 90 minutes of ischemia. Renal function was assessed by plasma creatinine, and renal injury by histological examination. RESULTS: Reperfusion-induced glutathione oxidation, expressed as an oxidized-to-total glutathione ratio, was significantly attenuated both after 2 and 24 hours of reperfusion by treatment with U83836E. Adenosine triphosphate (ATP) was still significantly depleted after 24 hours in the control group, while at the same time treated animals had already recovered to baseline values. Lipid peroxidation products were significantly lower in lazaroid-groups both after 2 and 24 hours of reperfusion. Renal function after 24 hours of reperfusion was notably better in the treated rats. Histological examination confirmed the protective action of the drug. After 24 hours the control group showed large areas of parenchymal hemorrhage and necrosis with dilated tubules and blood vessel thrombosis, while treated animals showed small necrotic areas with a background of mild interstitial inflammatory cells. CONCLUSIONS: Our results suggest that there is a protective effect of U83836E in ischemia-reperfusion injury, in that tissue damage due to oxidative stress is reduced, thus ameliorating renal function impairment.