Biomedical subjects
Publications and source records attributed to M Maggiorini.
A case of severe ECG abnormalities occurring during pre-eclampsia is presented. Although these electrocardiographic changes were indicative of severe alterations of coronary flow, neither structural nor functional abnormalities could be documented during subsequent diagnostic workup. The pathogenetic pathways potentially involved in this case including coronary spasms are briefly discussed.
In six dogs and six weight-matched miniature pigs at baseline and after pulmonary embolization, pulmonary arterial compliance was determined using the pulse pressure method (C(PPM)), the three-element windkessel model (C(WK-3)), and the ratio of stroke volume to pulse pressure (SV/PP). C(PPM) was lower in pigs than in dogs at baseline (0.72 +/- 0.23 vs. 1.14 +/- 0.29 ml/mmHg, P < 0.05) and after embolism (0.37 +/- 0.14 vs. 0.54 +/- 0.16 ml/mmHg, P = 0. 07) at matched flow, but not at matched flow and pressure. C(PPM) showed the expected inverse relation with pressure and a direct relation with flow. C(WK-3) was closely correlated with C(PPM), except for all dogs at baseline where C(WK-3) was up to 100% higher than C(PPM). Excluding these data, regression analysis yielded C(WK-3) = -0.01 + 1.30. C(PPM) (r(2) = 0.97). C(WK-3) was found to be unreliable when input impedance first harmonic modulus was close to characteristic impedance, i.e., when reflections were small. SV/PP correlated well with C(PPM) (SV/PP = -0.10 + 1.76. C(PPM), r(2) = 0.89). We conclude that 1) C(PPM) is a consistent estimate of pulmonary arterial compliance in pigs and dogs, 2) C(WK-3) and SV/PP overestimate compliance, and 3) C(WK-3) is unreliable when wave reflections are small.
To evaluate the pathogenetic role of cerebral blood flow (CBF) changes occurring before and during the development of acute mountain sickness (AMS), peak mean middle cerebral artery flow velocities () were assessed by transcranial Doppler sonography in 10 subjects at 490-m altitude, and during three 12-min periods immediately (SA1), 3 (SA2), and 6 (SA3) h after decompression to a simulated altitude of 4,559 m. AMS cerebral scores increased from 0. 16 +/- 0.14 at baseline to 0.44 +/- 0.31 at SA1, 1.11 +/- 0.88 at SA2 (P < 0.05), and 1.43 +/- 1.03 at SA3 (P < 0.01); correspondingly, three, seven, and eight subjects had AMS. Absolute and relative at simulated altitude, expressed as percentages of low-altitude values (%), did not correlate with AMS cerebral scores. Average % remained unchanged, because % increased in three and remained unchanged or decreased in seven subjects at SA2 and SA3. These results suggest that CBF is not important in the pathogenesis of AMS and shows substantial interindividual differences during the first hours at simulated altitude.
Cyclooxygenase (COX) products and nitric oxide (NO) inhibit hypoxic pulmonary vasoconstriction (HPV), and their release could contribute to alterations in gas exchange in lung injury. We tested the hypothesis that combined blockade of COX and NO synthase (NOS) could further increase HPV and better protect gas exchange in lung injury than could blockade of either COX or NOS alone. We determined pulmonary vascular pressure-flow relationships in pentobarbital-anesthetized and ventilated dogs submitted to hypoxic challenges before and after administration of solvent (n = 4), indomethacin alone (2 mg/kg intravenously, n = 8), Nomega-nitro-L-arginine (L-NA) alone (10 mg/kg intravenoulsy, n = 8), indomethacin followed by L-NA (n = 8), and L-NA followed by indomethacin (n = 8). All of the dogs so treated then received oleic acid (0.06 ml/kg intravenously) to induce lung injury. Blood flow was manipulated by establishing a femoral arteriovenous bypass or by inflating an inferior vena caval balloon. Gas exchange was evaluated by measuring arterial PO2 and intrapulmonary shunt (using the inert gas sulfur hexafluoride) at identical cardiac outputs. The magnitude of HPV was not affected by solvent. Indomethacin and L-NA given separately enhanced HPV. L-NA added to indomethacin further enhanced HPV, as did indomethacin added to L-NA. After oleic acid-induced lung injury, gas exchange deteriorated less in dogs pretreated with indomethacin than in dogs pretreated with solvent or with L-NA alone. These results suggest that in pentobarbital-anesthetized dogs: (1) the magnitude of HPV is limited by the corelease of COX metabolites and of NO; and (2) inhibition of COX, but not of NOS, attenuates the deterioration of gas exchange in oleic acid-induced lung injury.
The pig has been reported to present with a stronger hypoxic pulmonary vasoconstriction than many other species, including the dog, but it is not known whether this is associated with a different longitudinal partitioning of pulmonary vascular resistance (PVR). We investigated the relationships between cardiac output (Q) and mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao), and effective pulmonary capillary pressure (Pc') minus Ppao, in seven minipigs and in seven dogs in hyperoxia (FI(O2) 0.4) and hypoxia (FI(O2) 0.1), first without, then with the inhalation of 80 ppm nitric oxide (NO) to inhibit any reversible component of PVR. Pc' was estimated from the Ppa decay curve following pulmonary artery balloon occlusion. In hyperoxia, minipigs compared to dogs had (Ppa - Ppao)/Q and (Pc' - Ppao)/Q plots shifted to higher pressures. Hypoxia at each level of Q increased Ppa - Ppao in minipigs more than in dogs, and Pc' - Ppao in minipigs only. Inhaled NO reversed hypoxia-induced changes in (Ppa - Ppao)/(Q and (Pc' - Ppao)/Q plots. We conclude that the minipig, compared to the dog, presents with higher PVR and reactivity including vessels downstream to the site of Pc' as determined by the arterial occlusion technique.
Pigs have been reported to present with a stronger pulmonary vascular reactivity than many other species, including dogs. We investigated the pulmonary vascular impedance response to autologous blood clot embolic pulmonary hypertension in anesthetized and ventilated minipigs (n = 6) and dogs (n = 6). Before embolization, minipigs, compared with dogs, presented with higher mean pulmonary arterial pressure (Ppa; by an average of 9 mmHg), a steeper slope of Ppa-flow (Q) relationships, and higher 0-Hz impedance (Z0) and first-harmonic impedance (Z1), without significant differences in characteristic impedance (Zc), and a lower ratio of pulsatile hydraulic power to total hydraulic power. Embolic pulmonary hypertension (mean Ppa: 40-55 mmHg) was associated with increased Z0 and Z1 in both species, but the minipigs had a steeper slope of Ppa/Q plots and an increased Zc. At identical Q and Ppa, minipigs still presented with higher Z1 and Zc and a lower ratio of pulsatile hydraulic power to total hydraulic power. The energy transmission ratio, defined as the hydraulic power in the measured waves divided by the hydraulic power in the forward waves, was better preserved after embolism in minipigs. No differences in wave reflection indexes were found before and after embolism. We conclude that minipigs, compared with dogs, present with a higher pulmonary vascular resistance and reactivity and adapt to embolic pulmonary hypertension by an increased Zc without earlier wave reflection. These differences allow for a reduced pulsatile component of hydraulic power and, therefore, a better energy transfer from the right ventricle to the pulmonary circulation.
INTRODUCTION: Purpose of the present study was to evaluate the Lake Louise acute mountain sickness (AMS) score questionnaire at different altitudes and to compare it with the currently used clinical score and the environmental symptoms questionnaire AMS-C score. METHODS: We investigated 490 climbers who stayed over night at 4 huts in the Swiss Alps, located at the altitudes of 2850 m, 3050 m, 3650 m, and 4559 m. AMS was assessed using our previously described clinical score, the Lake Louise consensus AMS score questionnaire and the environmental symptoms questionnaire III. RESULTS: Below 4000 m, the prevalence of AMS, defined by symptoms that force a reduction in activity, was 7%; when assessed with the clinical score (score > or = 3) it was 22%; with the AMS-C score (score > or = 0.7) 4% and with the Lake Louise score (score > 4) 8%. At the altitude of 4559 m, the prevalence of AMS was 30%, 38%, 40%, and 39%, respectively. The standardized regression coefficients from multiple regression analysis (adjusted R2 0.65, p < 0.001) were 0.45 (p < 0.001) for the self-reported Lake Louise score, 0.48 (p < 0.001) for the sum of the points assigned in the clinical section of the Lake Louise questionnaire, and 0.05 (p = 0.27) for the AMS-C score. The sensitivity and specificity of the Lake Louise score > 4 was 78% and 93%, respectively. CONCLUSIONS: The Lake Louise consensus score is adequate and, compared with the AMS-C score, more effective for the assessment of acute altitude illness at different altitudes.
Explore the source record for details and available documents.
Reversible posterior leukoencephalopathy (PLE) is a newly recognized syndrome with characteristic radiologic findings. The clinical picture resembles that of hypertensive encephalopathy. PLE is caused by uncontrolled hypertension as well as other neurotoxic conditions. We report on 3 patients with this syndrome. One patient also had transient hydrocephalus which may have been caused by PLE. Clinicians must be aware of this syndrome as its recognition obviates unnecessary diagnostic procedures. PLE is reversible by lowering elevated blood pressure and treating neurotoxic conditions such as uremia.
We report on a 39-year-old man with Crohn's disease who was admitted with cardiogenic shock after a short history of progressive dyspnea. Echocardiographic examination (transthoracic echocardiography) showed severe aortic regurgitation, mild mitral regurgitation, and enlargement of the sinus of Valsalva and of the ascending aorta at the level of the right pulmonary artery. The left ventricular ejection fraction was 30%. After aortic valve replacement, histologic examination of the ascending aorta showed chronic aortitis resembling syphilitic aortitis (serology for syphilis was negative) and HLA B27 related aortitis. The aortic valve showed deformation and thickening of the cusps by fibrous tissue without evidence of endocarditis. The patient remained well after surgery and echocardiographic examination 6 months later showed normal function of the aortic valve prosthesis. The diameter of the sinus of Valsalva and of the ascending aorta was slightly bigger, possibly indicating ongoing destruction. The left ventricular ejection fraction nearly normalized. It seems possible that this type of aortitis, characterized by its proximity to the valve ring, is another extraintestinal cardiac manifestation of Crohn's disease. The possibility of ongoing destruction of the sinus of Valsalva and of the ascending aorta after valve replacement makes regular echocardiographic control necessary.
Explore the source record for details and available documents.
We investigated the site of pulmonary vasodilation and associated effects on gas exchange in response to inhaled NO in acute microembolic lung injury. Pulmonary arterial (Ppa) and effective capillary (Pc') pressures versus cardiac output (Q) plots were generated in anesthetized dogs before and after, successively, (1) embolization with 100 microns glass beads, (2) administration of either a placebo (n = 5) or 80 ppm inhaled NO followed by cyclooxygenase inhibition by aspirin 1 g given intravenously and again 80 ppm inhaled NO (n = 8). Pc' was estimated from the pressure decay curve after pulmonary artery balloon occlusion. Embolism increased pulmonary vascular resistance, with a slight decrease in its precapillary component, from 77 to 66%. NO decreased Ppa at the highest levels of Q, and aspirin increased Ppa at all levels of Q. Neither NO nor aspirin affected Pc'/Q plots or pulmonary shunt. We conclude that pulmonary vascular resistance in microembolic lung injury increases at the periphery of the pulmonary arterial tree, with partial reversibility by inhaled NO and by endogenous products of the cyclooxygenase pathway upstream from the site of effective capillary resistance. Reduced pulmonary vascular tone does not improve gas exchange in this model of acute lung injury.
Thromboembolism is a well-known complication of the hypercoagulable state associated with antiphospholipid (aPL) antibodies. Acute respiratory failure (ARF) with diffuse pulmonary infiltrates has been reported in only a few patients with aPL antibodies. We describe a 49 year old patient with spiking fever, livedo reticularis, mild haemoptysis and ARF. Chest radiography revealed diffuse bilateral pulmonary infiltrates, and high resolution computed tomography (CT) revealed patchy distribution of areas of ground-glass attenuations. Pulmonary emboli were excluded with angiography. Lung biopsy revealed diffuse microvascular thrombosis, without capillaritis. High serum levels of anticardiolipin (aCL) antibodies were found. The patient's condition improved dramatically after intravenous infection of 1 g methylprednisolone on three consecutive days, followed by 50 mg prednisone orally. The rapid improvement following the administration of glucocorticosteroids suggests that anticardiolipin associated microvascular thrombosis, without inflammatory lesions, may depend on an interference with beta2-glycoprotein I (beta2=GPI) by anticardiolipin.
In cardiac transplant recipients, infection with Toxoplasma gondii may be transmitted with the transplanted organ to immunosuppressed recipients or may be due to reactivation under immunosuppression in cases of pretransplant infection. In the present study the incidence of infection with Toxoplasma gondii and the clinical presentation of the infection in 121 consecutive heart transplant recipients were investigated. Data on IgG and IgM antibodies for Toxoplasma gondii measured by a semiquantitative microparticle immunoassay of donors and recipients were collected prospectively in 121 patients. Infection with Toxoplasma gondii was defined as IgM seroconversion with proven pre-transplant seronegativity (primary infection) or at least a fourfold increase of IgG antibodies (reactivation). Infection with Toxoplasma gondii occurred in 16 of 121 patients (13%) whereas overt clinical disease occurred in 5 of 121 patients (4%). Organ-transmitted infection was more frequent (11/18, 61%) and more often associated with acute disease than reactivation of latent infection (5/69 patients, 7%) (p < 0.01), although one case of Toxoplasma retinochoroiditis occurred in a patient with recrudescence of latent pretransplant infection. Treatment with pyrimethamine and sulfadiazine was efficient in all patients with acute disease and in controlling disease in patients with evidence of acute infection.
Vascular effects of general anesthesia are usually described by changes in vascular resistance, which assumes a linear pressure-flow relationship passing through the zero-flow zero-pressure point, and neglects the pulsatile properties of the circulation. We compared the systemic vascular effects of isoflurane versus propofol anesthesia by measurements of aortic pressure-flow relationships, systemic vascular impedance (SVZ), and pressure transfer function (PTF). Eight mechanically ventilated dogs received isoflurane 1.4% end-tidal and propofol 18 mg.kg-1.h-1 in a random sequence. During both periods, pressure-flow data and SVZ data were obtained at baseline and after stepwise reduction of the cardiac output by inflation of a balloon in the inferior vena cava. Instantaneous pressure and flow were measured at the aortic root using a micromanometer-tipped catheter and an ultrasonic flow probe. Compared to baseline, low flow decreased the aortic pressure and increased the resistance, characteristic impedance, and oscillatory/total work ratio. Compared with isoflurane, propofol resulted in higher aortic pressure, lower characteristic impedance, and lower oscillatory/total work ratio. Low-frequency PTF moduli decreased at low flow and increased with propofol. We conclude that, compared with isoflurane, propofol better preserves aortic pressure and increases aortic compliance, and thus improves the energy transmission from the left ventricle to the arterial system.
An epidemic of primary pulmonary hypertension occurred in Europe in the 1960s, after the introduction of the appetite suppressant aminorex. Recently, a cluster of cases of pulmonary hypertension was observed in France in relation to the intake of the appetite suppressant dexfenfluramine. We previously reported that intravenous dexfenfluramine enhances hypoxic pulmonary vasoconstriction in dogs. We therefore investigated the pulmonary hemodynamic effects of chronic oral intake of this drug. Twenty-four dogs with a strong (n = 12) and a weak hypoxic pulmonary vasoconstriction (n = 12) respectively were randomly allocated in a double blind manner to a twice daily oral intake of either a placebo or dexfenfluramine 1.5 mg/kg for 20 d. A strong hypoxic vasoconstriction was defined as a hypoxia-induced increase in pulmonary artery pressure by more than 3 mm Hg at a standardized cardiac output of 3 L/min/m2. Pulmonary hemodynamics were studied in hyperoxia (fraction of inspired O2 [F(I)O2] 0.4) and in hypoxia (F(I)O2 0.1) before and after treatment. Venous return was manipulated at post-treatment evaluation for isoflow comparisons of pulmonary vascular pressures. Dexfenfluramine had no effect on systemic hemodynamics or blood gases, but increased pulmonary vascular resistance from 155 +/- 17 to 192 +/- 14 dyne x s x cm(-5) in hyperoxia (mean +/- SE, p < 0.05) and from 237 +/- 27 to 293 +/- 47 dyne x s x cm(-5) in hypoxia (p < 0.01). Dexfenfluramine, and not placebo, increased the isoflow pulmonary vascular pressure gradient in hyperoxia and in hypoxia. This effect was unrelated to the magnitude of pretreatment hypoxic vasoconstriction. We conclude that the chronic intake of dexfenfluramine in dogs is associated with a moderate increase in pulmonary vascular resistance which is unrelated to pulmonary vasoreactivity to hypoxia.
We describe two patients treated with a combination of cyclosporin and simvastatin who had to be hospitalized due to rhabdomyolysis. As suggested by reduced cyclosporin clearance, both patients had impaired activity of the hepatic cytochrome P450 enzyme system, which may have contributed to the development of rhabdomyolysis. After cessation of treatment with simvastatin and intensive hydration, both patients recovered within one week. While rhabdomyolysis has been described in several patients receiving the combination lovastatin/cyclosporin, so far only one case has been reported in patients treated with simvastatin/cyclosporin. Our cases therefore suggest that this complication may be more frequent than previously suspected. In patients treated with cyclosporin, HMG-CoA reductase inhibitors should be used cautiously, and concomitant administration of drugs inhibiting the hepatic cytochrome P450 enzyme system should be avoided.
OBJECTIVE: Evaluation and comparison of the therapeutic efficacy of a portable hyperbaric chamber and dexamethasone in the treatment of acute mountain sickness. DESIGN: Randomised trial during the summer mountaineering season. SETTING: High altitude research laboratory in the Capanna Regina Margherita at 4559m above sea level (Alps Valais). SUBJECTS: 31 climbers with symptoms of acute mountain sickness randomly assigned to different treatments. INTERVENTIONS: One hour of treatment in the hyperbaric chamber at a pressure of 193 mbar or oral administration of 8 mg dexamethasone initially, followed by 4 mg after 6 hours. MAIN OUTCOME MEASURES: Symptoms of acute mountain sickness (Lake Louise score, clinical score, and AMS-C score) before one and about 11 hours after beginning the different methods of treatment. Permitted intake of mild analgesics before treatment and in the follow up period. RESULTS: After one hour of treatment compression with 193 mbar caused a significantly greater relief of symptoms of acute mountain sickness than dexamethasone (Lake Louise score: mean (SD) -4.6 (1.9) v -2.5 (1.8); clinical score: -4.0 (1.2) v -1.5 (1.4); AMS-C score: -1.24 (0.51) v -0.54 (0.59)). In contrast after about 11 hours subjects treated with dexamethasone suffered from significantly less severe acute mountain sickness than subjects treated with the hyperbaric chamber (-7.0 (3.6) v -1.6 (3.0); -4.1 (1.9) v -1.0 (1.5); -1.78 (0.73) v -0.75 (0.82) respectively). Intake of analgesics was similar in both groups. CONCLUSION: Both methods were efficient in treatment of acute mountain sickness. One hour of compression with 193 mbar in the hyperbaric chamber, corresponding to a descent of 2250 m, led to short term improvement but had no long term beneficial effect. On the other hand, treatment with dexamethasone in an oral dose of 8 mg initially followed by 4 mg every 6 hours resulted in a longer term clinical improvement. For optimal efficacy the two methods should be combined if descent or evacuation is not possible.