Biomedical subjects
Publications and source records attributed to M Cittadino.
Considering the high frequency of bleeding complications following fibrinolytic treatment, caudal blockade could be used in association with lower doses of tissue plasminogen activator as a possible new therapeutic approach in management of arterial thrombosis in neonates.
Pravastatin is useful in restoring endothelium-dependent relaxation in hypercholesterolemic animals. A single intravenous bolus injection of N(omega)-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthase, causes myocardial necrosis and reduces coronary flow in rats. Since rats do not develop hypercholesterolemia and atherosclerosis, we have tested the hypothesis that pravastatin protects the heart from myocardial lesions induced by L-NAME in the absence of alterations in cholesterol levels and plaque formation. Male Wistar rats fed standard chow were divided into four groups: CONTROL (n=14) - rats that received tap water alone for 18 days; L-NAME (n=14) -- rats that received L-NAME (15 mg/kg, i.v.) on the 14th day of the study; PRAVASTATIN (n=11) -- rats that received pravastatin (6 mg/kg/day) in their drinking water for 18 days; PRAVASTATIN+L-NAME (n=12) -- rats that received pravastatin (6 mg/kg/day) and L-NAME (15 mg/kg, i.v.) as indicated in the preceding groups. At the end of 18 days, the rats were sacrificed and the hearts removed for stereological analysis by light microscopy. Plasma nitrate/nitrite and thromboxane B(2) concentrations were determined immediately before and after L-NAME administration. Pravastatin prevented the ischemic lesions induced by the acute inhibition of NO biosynthesis (the area of myocardial lesions in the L-NAME group was greater than in the Pravastatin+L-NAME group: 101.6 microm(2) vs. 1.2 microm(2), respectively; P<0.0001) and markedly increased the plasma nitrate/nitrate concentrations, even before L-NAME administration. There were no significant changes in the plasma thromboxane B(2) concentrations.
Smoking potentiates the enhanced cardiovascular risk of hypertensive patients. Although nicotine replacement therapy is safe when used by healthy individuals to quit smoking, there is no evidence that nicotine replacement therapy is safe in hypertensive smokers. In this crossover, single-blinded, placebo-controlled study, we compared for 4 h the acute effects of transdermal nicotine on the mean arterial pressure (MAP) and heart rate (HR) of mildly hypertensive smokers treated with hydrochlorothiazide with the responses in normotensive smokers and nonsmokers monitored with Finapres and ambulatory blood pressure systems. The plasma concentrations of thromboxane B2 (TXB2, the stable breakdown product of TXA2) were also measured by ELISA to assess whether transdermal nicotine acutely affects TXA2 production. The use of 21-mg nicotine patches increased the MAP and HR in nonsmokers (from 94+/-4 mm Hg and 69+/-3 beats/min to 117+/-7 mm Hg and 83+/-3 beats/min, respectively; P < .05) as well as the MAP in normotensive smokers (from 83+/-4 to 106+/-7 mm Hg; P < .05). However, MAP and HR remained unaltered in hypertensive smokers after transdermal nicotine. Higher basal TXB2 levels were observed in hypertensive smokers compared with normotensive smokers and nonsmokers (2019+/-402 v 670+/-167 and 556+/-68 pg/mL, respectively; P < .05). Transdermal nicotine increased the TXB2 levels only in nonsmokers (P < .05). These data indicate that the use of transdermal nicotine in mildly hypertensive smokers is probably safe. Further studies involving other classes of hypertensive patients are warranted.
PURPOSE: An impaired generation of cGMP may account for the pulmonary hypertension seen in acute lung injury (ALI). We investigated the hemodynamic changes and the plasma levels of cGMP during air embolism-induced ALI in two different models: venous air infusion (VAI) and massive air embolism (MAE). MATERIALS AND METHODS: After a baseline hemodynamic evaluation, anesthetized dogs received a VAI (0.2 mL/kg/min, n = 10) or a bolus of air (MAE, 2.5 mL/kg, n = 10) intravenously. A group of control dogs (n = 5) received no further treatment. Hemodynamic evaluation was performed 5 to 60 minutes after the VAI was initiated or after the MAE. Blood samples were drawn for plasma cGMP determinations. RESULTS: The VAI increased the pulmonary artery pressure (by 181%, P<.05) after 15 minutes of air infusion without changing the cardiac index. The MAE increased the pulmonary artery pressure (by 252%) and decreased the cardiac index (by 31%) 5 minutes after the air injection (both P<.05). These variables returned to baseline 15 to 30 minutes thereafter. The cGMP concentrations remained unaltered during the VAI. In contrast, cGMP levels increased 26% (P<.05) by 15 minutes after the MAE and returned to basal levels thereafter. CONCLUSION: These findings suggest that a lack of increase in the production of the cGMP may account for the pulmonary hypertension seen in air embolism-induced ALI. Additionally, the small increase in cGMP levels after the MAE may reflect the more severe hemodynamic derangement in this setting.
BACKGROUND: Cigarette smoking is a major risk factor for coronary artery disease and causes endothelial dysfunction, perhaps by decreasing the availability of nitric oxide availability in arteries and veins. Nicotine in cigarette smoke may be responsible for this impaired endothelial response. METHODS: We studied nine healthy nonsmokers and 12 healthy mild to moderate smokers by use of the dorsal hand vein compliance technique. Dose-response curves to bradykinin and sodium nitroprusside were obtained to test the endothelium-dependent and endothelium-independent vasorelaxation before and during the use of a nicotine (21 mg) patch. Mean arterial blood pressure and heart rate were measured beat-to-beat during the 4-hour study and serial blood samples were drawn to assay plasma thromboxane B2 levels. RESULTS: Transdermal nicotine reduced the venous responsiveness to bradykinin in nonsmokers (Emax = 88.0% +/- 17.9% and 54.3% +/- 14.9%, respectively, before and after the nicotine patch; P < .05); the latter response was similar to that in smokers (Emax = 56.3% +/- 16.6%). Sodium nitroprusside-induced venodilation was unaltered. Mean arterial blood pressure increased in both smokers and nonsmokers. Transdermal nicotine increased the plasma thromboxane B2 concentrations only among nonsmokers. CONCLUSION: These findings indicate that nicotine can have a major role in the impaired endothelial function in smokers. The results probably also reflect what occurs in arterial beds because the nicotine patches increased the mean arterial blood pressure in both smokers and nonsmokers.