Hemodynamics during inhaled nitric oxide in lung transplant candidates.
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Administration, Inhalation↗
Biomedical subjects
F Pugliese
Publications and source records attributed to F Pugliese.
Occupational asthma and rhinitis caused by 1,2-benzisothiazolin-3-one in a chemical worker.
We report a case of occupational asthma and rhinitis caused by inhalation of 1,2-benzisothiazolin-3-one, an additive used as a microbicidal in detergent production, in a 26-year-old man employed in a chemical factory producing detergents. The subject's task consisted of pouring raw materials into the recipient of a machine which mixed the substances. Two months after the beginning of this job the patient complained of rhinitis and asthma at the workplace. The specific challenge test with 1,2-benzisothiazolin-3-one, one of the raw materials to which the subject was exposed, provoked an immediate prolonged asthmatic response and nasal symptoms, whereas exposure to other agents (e.g., alpha-amylase, alcalase or bezalkonium chloride) to which the patient was also exposed at work did not. To our knowledge this is the first case of occupational asthma and rhinitis caused by this compound.
Adult↗
Nonsteroidal anti-inflammatory drugs (NSAIDs) and the kidney.
In patients with PG-dependent renal function, NSAID administration constantly reduces GFR and RBF in a dose-dependent fashion. In this situation, the risk of overt acute renal failure is high and should be taken into proper account. In contrast, the incidence of NSAID-related renal structural alterations appears to be very low, yet the absolute number of patients may be significant considering the wide use of such drugs. Concerning the antiproteinuric effect of NSAIDs, the unfavourable ratio risk/benefit does not seem to support their indication in proteinuric nephropathies. The development of PGHS-2 selective inhibitors is promising, and may open new therapeutical strategies in the treatment of the progression of renal disease.
Animals↗
High glucose level unmasks a genetic predisposition to enhanced extracellular matrix production in mesangial cells from the Milan normotensive strain.
A growing body of evidence indicates that the individual genetic background plays a role in the pathogenesis of diabetic glomerular disease by either favoring or protecting against injury produced by hyperglycemia. Two genetically related rat strains, the Milan normotensive strain (MNS) and the Milan hypertensive strain (MHS) display different susceptibilities to develop glomerulosclerosis with age. Glomerular sclerosing lesions occur in the MNS rats, which remain normotensive throughout their entire life-span, but not in the MHS rats, despite the presence of arterial hypertension. Previous studies have reported that extracellular matrix production and cell proliferation increased with donor-aging in mesangial cells isolated from MNS rats, but not in those from MHS rats, thus suggesting the existence of an inherited defect in the regulation of cell and matrix turnover, which translates into an abnormal response to growth-promoting stimuli favoring the development of glomerulosclerosis. In the study presented here, it was hypothesized that, in addition to donor-aging, other independent risk factors for the development of glomerular disease, such as metabolic injury by hyperglycemia, would be able to trigger and/or precipitate the occurrence of these changes in mesangial cells from the susceptible normotensive strain, but not in those from the protected hypertensive strain. To test this hypothesis, mesangial cells obtained from these rat strains (before the onset of either glomerulosclerosis or hypertension) were used to assess the effects of prolonged (4 wk) exposure to high (30 mmol/L) versus normal (5.5 mmol/L) glucose concentrations on extracellular matrix and cytokine production and cell proliferation. The accumulation and/or gene expression of the matrix components fibronectin, laminin, and collagen IV, and of the cytokines insulin-like growth factor-I (IGF-I) and transforming growth factor-beta (TGF-beta) did not change under normal glucose and increased progressively in response to high glucose in both MNS and MHS cells. These increases, with the exception of the increment in TGF-beta gene expression, were significantly more pronounced in MNS cells than in MHS cells. In contrast, the proliferative response to serum was not affected by high glucose, but increased in MNS cells, and decreased, although not significantly, in MHS cells during the 4-wk period, thus mimicking the changes previously observed in these rat strains as a function of age. These results indicate that high glucose unmasks a genetic tendency to produce increasing amounts of extracellular matrix, not yet evident under normal glucose conditions, and suggest that a genetically determined propensity of mesangial cells to hyperrespond to chronic hyperglycemia may be implicated in the pathogenesis of diabetic glomerular disease.
Animals↗
Upregulation of mesangial growth factor and extracellular matrix synthesis by advanced glycation end products via a receptor-mediated mechanism.
Enhanced advanced glycosylation end product (AGE) formation has been shown to participate in the pathogenesis of diabetes-induced glomerular injury by mediating the increased extracellular matrix (ECM) deposition and altered cell growth and turnover leading to mesangial expansion. These effects could be exerted via an AGE-receptor-mediated upregulation of growth factors, such as the IGFs and transforming growth factor-beta (TGF-beta). We tested this hypothesis in human and rat mesangial cells grown on nonglycated or native bovine serum albumin (BSA), glycated BSA with AGE formation (BSA-AGE), or glycated BSA in which AGE formation was prevented by the use of aminoguanidine (BSA-AM), in the presence or absence of an antibody, alpha-p60, directed against the p60/OST protein named AGE-receptor 1 (AGE-R1), or normal control (pre-immune) serum. The mRNA and/or protein levels of IGF-I, IGF-II, IGF receptors, IGF binding proteins (IGFBPs), TGF-beta1 and the ECM components fibronectin, laminin, and collagen IV were measured, together with cell proliferation. Both human and rat mesangial cells grown on BSA-AGE showed increased IGF-I and total and bioactive TGF-beta medium levels and enhanced IGF-I, IGF-II, and TGF-beta1 gene expression, compared with cells grown on BSA, whereas total IGFBP and IGFBP-3 medium content, IGF receptor density and affinity, and IGF-I receptor transcripts were unchanged. Moreover, cells grown on BSA-AGE showed increased ECM protein and mRNA levels versus cells cultured on BSA, whereas cell proliferation was unchanged in human mesangial cells and slightly reduced in rat mesangial cells. Growing cells on BSA-AM did not affect any of the measured parameters. Co-incubation of BSA-AGE with anti-AGE-R1, but not with pre-immune serum, prevented AGE-induced increases in IGF-I, TGF-beta1, and ECM production or gene expression; anti-AGE-R1 also reduced growth factor and matrix synthesis in cells grown on BSA. These results demonstrate that mesangial IGF and TGF-beta1 synthesis is upregulated by AGE-modified proteins through an AGE-receptor-mediated mechanism. The parallelism with increased ECM production raises the speculation that the enhanced synthesis of these growth factors resulting from advanced nonenzymatic glycation participates in the pathogenesis of hyperglycemia-induced mesangial expansion.
Animals↗
[A case of duodenal duplication causing invagination in a patient with intestinal malformation: non-invasive imaging].
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Adult↗
Hemodynamic and metabolic effects of transjugular intrahepatic portosystemic shunt (TIPS) during anesthesia for orthotopic liver transplantation.
Recently, the transjugular intrahepatic portosystemic shunt (TIPS) has been advocated as a safe bridge to orthotopic liver transplantation (OLT). We retrospectively studied 53 consecutive cirrhotic patients who underwent OLT: 27 patients with TIPS were compared to 26 controls. Hemodynamic and oxyphoretic data (Fick method) were collected during six phases of OLT. There were no significant differences in demographic data and Child-Pugh class, nor in surgical time and blood product requirements before the anhepatic phase between TIPS patients and controls. In the TIPS group, we observed a marked hyperdynamic profile with a lower systemic vascular resistance index, higher cardiac index, and depressed oxygen consumption before native liver removal. During the same period, the TIPS group developed a greater acidosis and was treated with a larger amount of NaHCO3. Following the anhepatic phase, no differences between the two groups were detected. All transplantations were successful, and no complications related to TIPS were observed. These results seem to be the consequence of a reduced liver function reserve with a direct hemodynamic effect due to the TIPS.
Acidosis↗
Regulatory role of eicosanoids in extracellular matrix overproduction induced by long-term exposure to high glucose in cultured rat mesangial cells.
Accumulation of extracellular matrix in the mesangium and altered renal eicosanoid synthesis are two prominent features of diabetic glomerular disease. We investigated the relationship between eicosanoid and extracellular matrix production in rat mesangial cells cultured under high glucose vs normal glucose conditions. Long-term exposure of rat mesangial cells to high glucose, but not to iso-osmolar mannitol, significantly increased extracellular matrix accumulation and gene expression and transforming growth factor-beta (TGF-beta) mRNA levels, and decreased prostaglandin (PG) E2 synthesis without affecting production of either thromboxane (TX) B2 or PGF2 alpha, with respect to cells incubated in normal glucose. Addition of exogenous PGE2 resulted in a dose-dependent reduction of matrix protein and mRNA levels and TGF-beta gene expression in cells cultured in either normal or high glucose conditions, whereas exposure to exogenous PGF2 alpha produced a significant increment in matrix production and matrix and TGF-beta gene expression in cells grown in normal glucose, but only a slight increase in those cultured in high glucose. Stimulation of endogenous endoperoxide metabolism towards PGE2 and PGF2 alpha synthesis with FCE-22,178, a drug originally developed as TXA2 synthase inhibitor, resulted in a dose-dependent decrease in matrix accumulation and matrix and TGF-beta gene expression which was suppressed by coincubation with the cyclo-oxygenase inhibitor fenoprofen blocking the FCE-22,178-enhanced PG production. In both cell lines, the rate of synthesis of TXA2 was very low and the selective blockade of its synthesis (by two other TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor antagonist BM-13,177) did not alter matrix production or TGF-beta mRNA levels. These results suggest that the cyclo-oxygenase pathway is involved in the regulation of matrix changes induced by high glucose in rat mesangial cells; the reduced production of PGE2 may enhance the synthesis or potentiate the effect of stimulators of ECM formation such as TGF-beta, whereas TXA2 does not appear to be involved. These data also indicate that glucose-enhanced mesangial matrix accumulation may be prevented by exogenous PGE2 or by drugs capable of increasing endogenous PGE2 synthesis.
Animals↗
Adhesion of U-937 monocytes induces cytotoxic damage and subsequent proliferation of cultured human mesangial cells.
In an in vitro model of monocyte adhesion to glomerular cells, U-937 myelomonocytic leukemia cells irreversibly bind to human mesangial cell monolayers. Adhesion is enhanced in mesangial cells proliferating in response to fetal bovine serum, and in the presence of several cytokines and vasoactive agents. In the present study, co-culture with U-937 followed by removal of non-adherent cells time-dependently decreased viability of mesangial cells, measured either by fluorometry after dual labeling with calcein acetoxymethylester and ethidium homodimer, or by the release of lactate dehydrogenase. The cytotoxic effects of co-culture with U-937 cells were significantly reduced by a combination of free radical scavengers, indicating involvement of reactive oxygen species. U-937 cells also stimulated subsequent proliferation of mesangial cells, assessed by [3H]-TdR incorporation and direct cell counts 24 hours later (from 1,034 +/- 83 to 14,611 +/- 959 and from 2,931 +/- 201 to 19,400 +/- 2,124 cpm/well, quiescent/cycling mesangial cells, respectively, P < 0.01). Controls to rule out TdR incorporation by adherent U-937 cells included selective [3H]-TdR labeling and demecolcine pretreatment. Cell counts at 24 hours confirmed U-937-induced proliferation of quiescent HMC, from 50,575 +/- 3,596 to 143,012 +/- 10,039 cells/cm2 (P < 0.01). Agents that promote U-937 cell adhesion, such as the TxA2 mimetic, U-46619, or angiotensin II, enhanced cytotoxicity while inhibiting the proliferation of both quiescent and cycling mesangial cells, when added during co-culture and the subsequent 24 hours (+1 microM U-46619, 1,875 +/- 131 and 2,546 +/- 125 cpm/well, respectively, 79,793 +/- 5,744 cells/cm2, P < 0.01 vs. U-937 only; +1 microM Ang II, 5066 +/- 560 and 5,784 +/- 306 cpm/well, respectively, 81,068 +/- 4,671 cells/cm2, P < 0.05). Blocking antibodies against the adhesion molecule ICAM-1 and leukocyte counterreceptors (LFA-1, VLA-4) prevented the proliferative response, which could not be duplicated with the conditioned media of U-937 alone or co-cultured with mesangial cells. These findings may reflect the interactions occurring in vivo between infiltrating leukocytes and resident cells during glomerular inflammation.
Animals↗
Brain penetration of intrathecal iomeprol in dogs.
PURPOSE: Iomeprol, a new nonionic iodinated compound for intravascular use, is being evaluated as a myelographic contrast agent because of its low neurotoxicity. This study aimed to assess the degree of brain penetration of iomeprol after intrathecal administration. MATERIAL AND METHODS: Brain penetration in dogs was investigated by CT and compared with that of iopamidol, iohexol, and ioversol, currently used as myelographic contrast media (CM). Nervous tissue density was determined in different brain structures by recording Hounsfield values. RESULTS: The experiments revealed that CM diffused from the cisternae into the parenchyma, reaching a maximum at 5-24 h after injection. The density of the examined brain regions was still higher than the preinjection levels 24 h later. No differences in brain penetration were observed among the CM investigated. CONCLUSION: The study has shown that iomeprol penetrates into the brain to the same extent as the most widely used myelographic CM.
Animals↗
Insulin-like growth factors I and II stimulate extracellular matrix production in human glomerular mesangial cells. Comparison with transforming growth factor-beta.
An enhanced paracrine/autocrine activity of the insulin-like growth factor (IGF) system within the glomerulus has been implicated together with up-regulation of transforming growth factor-beta (TGFbeta) in the pathogenesis of diabetic glomerular disease. This would imply their ability to modulate extracellular matrix (ECM) and cell turnover at the mesangial level, but the direct effects of IGFs on ECM production have not been demonstrated to date. These experiments in cultured human mesangial cells were aimed at assessing the effects of IGF-I and IGF-II, compared with those of TGFbeta, on 1) ECM medium accumulation and gene expression, and 2) total protein synthesis and cell proliferation. Human mesangial cells were grown to subconfluence, growth arrested for 48 h, and then exposed for 4-24 h to serum-free medium containing IGF-I (10(-7) - 10(-11) M), IGF-II (10(-7) - 10(-11) M), TGFbeta (10(-9) - 10(-11) M), or various combinations of two of these growth factors (10(-9)M). All three growth factors dose dependently increased ECM protein and messenger RNA levels. The combination of either IGF-I or IGF-II with TGFbeta, but not the two IGFs together, produced additive effects on matrix production. Total protein synthesis was also increased by IGF-I, IGF-II, and TGFbeta, although to a lesser extent than ECM production, whereas cell proliferation was enhanced by IGFs but not by TGFbeta. These results demonstrate that IGF-I and IGF-II are effective, although less potent than TGFbeta, in stimulating the production of the ECM components that accumulate in the mesangial region during the course of diabetic glomerular disease.
Cell Division↗
Regulation of capacitative calcium influx in cultured human mesangial cells: roles of protein kinase C and calmodulin.
Sustained Ca2+ influx follows discharge of intracellularly stored Ca2+ in a variety of cell types previously equilibrated in Ca(2+)-free media, including cultured human mesangial cells. This Ca2+ influx pathway has been referred to as capacitative Ca2+ entry or Ca2+ release-activated Ca2+ influx (iCRAC). This study investigated two cellular mechanisms potentially controlling iCRAC in human mesangial cells, protein kinase C (PKC), a key signalling kinase activated by vasoconstrictors that release Ca2+ from internal stores, and calmodulin, a Ca(2+)-binding protein that may couple Ca2+ release to the putative channel(s). The PKC activator phorbol myristate acetate (PMA) dose-dependently inhibited both Ca2+ influx in resting cells and iCRAC, assessed by microfluorometry in fura-2-loaded monolayers, when added before or after 1 uM angiotensin II (AngII) (Ca2+ influx at 1 mM (Ca2+)e +278 +/- 56%/+80 +/- 8%, at 10 mM + 473 +/- 59%/+250 +/- 24% (Ca2+)e, -/+ PMA, respectively, P < 0.05). PMA did not affect 5 uM ionomycin-induced iCRAC, possibly because it downregulated Ca2+ release by AngII but not by ionomycin, suggesting a key role of released Ca2+ in triggering subsequent Ca2+ influx. This was confirmed by buffering the (Ca2+)i elevation induced by AngII with intracellularly trapped 1,2-bis-(0-Aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA), which abolished any subsequent iCRAC. Moreover, the calmodulin inhibitors calmidazolium (10 uM), trifluoperazine (0.1 mM), or W-7 (0.1 mM) significantly inhibited AngII- or ionomycin-activated iCRAC (+106 +/- 38/229 +/- 53, +58 +/- 9/195 +/- 29, +161 +/- 38/180 +/- 40% at 1/10 mM (Ca2+)e, all P < 0.05), but did not affect basal Ca2+ entry, consistent with a direct role of cytoplasmic Ca2+ in the regulation of ion gating. These results indicate that iCRAC is under the control of both PKC and calmodulin, and that the site of regulation is distal to the emptying of Ca2+ stores. iCRAC may represent a key mechanism for the control of Ca(2+)-regulated mesangial functions.
Angiotensin II↗
Evaluation of antihypertensive effects of once-a-day isradipine and fosinopril: a double-blind crossover study by means of ambulatory blood pressure monitoring.
We compared the efficacy and tolerability of isradipine (ISR) and fosinopril (FOS) once-a-day administration in 17 outpatients, 9 men and 8 women, aged 35-65 years (mean +/- SD = 58 +/- 10 years), affected by mild to moderate primary systemic hypertension. The patients were given single-blind placebo for 2 weeks and thereafter, in double-blind, randomized, crossover sequence, ISR (5 mg) and FOS (20 mg), both for 4 weeks. At the end of each period, patients underwent 24-h noninvasive blood pressure (BP) monitoring by means of an A&D TM 2420 Monitor Model 7, with readings taken very 10 min during the day (from 7 A.M. to 11 P.M.), and every 20 min during the night (from 11 P.M. to 7 A.M.) Similarly, BP load (BPL) as percentage of systolic and diastolic BP reading > 140 and > 90 mmHg was investigated. Both ISR and FOS induced a highly significant (p < 0.0001) decrease in BP from 158/96 +/- 7/6 mmHg to 133/86 +/- 6/6 and to 132/83 +/- 10/7 mmHg, respectively. Mean BP decreased from 117 +/- 6 mmHg to 102 +/- 6 mmHg (ISR) (p < 0.0001) and to 99 +/- 8 mmHg (FOS) (p < 0.0001). Both ISR and FOS significantly (p < 0.0001) reduced systolic BPL from 78 +/- 16% to 44 +/- 13% and 28 +/- 12%, respectively, and diastolic BPL from 70 +/- 15% to 40 +/- 13% (p < 0.0001) and 35 +/- 13% (p < 0.0001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Growth abnormalities in cultured mesangial cells from rats with spontaneous glomerulosclerosis.
Age-related glomerulosclerosis (GS) occurs in normotensive rats of the Milan strain (MNS), but not in genetically-matched hypertensive animals (MHS). Altered mesangial cell (MC) proliferation and matrix expansion are common features of the glomerular scarring process. We evaluated proliferation and matrix protein synthesis of cultured MC from MNS and MHS animals aged 1 and 8 months, that is, before and after the occurrence of GS. [3H]-thymidine (TdR) incorporation into DNA of MC from MNS rats stimulated by 10% FBS serum increased with donor aging from 115 +/- 6.0 to 176 +/- 15, P < 0.01 (% cpm/well over quiescent controls +/- SEM). Under the same experimental conditions, cell counts changed from 101 +/- 4.0 to 146 +/- 5.0, P < 0.01 (% cells/well over quiescent controls). Additionally, cytosolic Ca2+ concentration ([Ca2+]i) rised from 115 +/- 19 to 220 +/- 32 nM and from 112 +/- 24 to 734 +/- 136 nM when fura-2-loaded cells from young and old MNS rats, respectively, were stimulated with 1% FBS. The rate of collagen production also increased with donor age, as well as collagen IV and laminin B1 mRNA expression. In contrast, in MC from MHS rats both DNA synthesis and cell replication rate declined as function of donor age. No differences in the [Ca2+]i responses to FBS were observed, nor collagen production changed with MHS rat senescence. We conclude that the age-associated decline of proliferative activity in MC from MHS animals could actually reflect a normal process of cell aging, possibly protecting from the occurrence of GS.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Long-term thromboxane-synthase inhibition prolongs survival in murine lupus nephritis.
Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by nephritis, in which mortality is largely influenced by the severity of renal involvement. As there are evidences that thromboxane (TX)A2 plays an important role in the pathogenesis of lupus nephritis, we decided to assess the effects of long-term suppression of TXA2 synthesis on the progression of the disease, by designing a study of TXA2-synthase inhibition having adequate size to detect an effect on mortality as the primary end-point. Thus, we randomized 362 NZBxNZW mice (11-week-old at entry) to one of the following treatments: a TXA2 synthase inhibitor, FCE 22178 (300 mg/kg daily), saline or cyclophosphamide (5 mg/mouse weekly x 4 weeks) used as reference treatment. The TXA2 synthase inhibitor suppressed TXA2 biosynthesis, as reflected by urinary TXB2 and 2,3-dinor-TXB2 excretion (by 78% and 90%, respectively) and significantly reduced mortality (death rate: 34% vs. 61% in controls, at 37 weeks, P < 0.01). A significant reduction in proteinuria (9 +/- 1.6 vs. 17.3 +/- 2.4 mg/24 hr in FCE 22178 vs. saline, P < 0.01) and glomerular lesions was observed up to 30 weeks but not at 37 weeks. In contrast, cyclophosphamide prevented the development of proteinuria and histologic lesions, and reduced mortality to 8% at 37 weeks. Renal plasma flow and glomerular filtration rate were lower (by 29% and 52%, respectively) in 37-week-old as compared to young NZBxNZW mice. These parameters were further depressed by cyclophosphamide (by 48% and 45% vs. age-matched controls, respectively, P < 0.01) but were not altered significantly by FCE 22178.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regulation of U-937 monocyte adhesion to cultured human mesangial cells by cytokines and vasoactive agents.
Leukocyte adhesion to kidney cells is an early event in renal inflammation, such as glomerulonephritis. We developed an experimental model of monocyte adhesion to cultured human mesangial cells. U-937 myelomonocytic leukaemia cells, similar to peripheral blood human monocytes, irreversibly bound to mesangial cell monolayers upon 30-180 min coincubations (to a max. of 13,600 +/- 1100/cm2 monolayer), as assessed by cell counting, U-937 labelling with 3H-thymidine, and colorimetry of nuclear staining with crystal violet. Adhesion was enhanced in mesangial cells proliferating in response to 17% fetal bovine serum, indicating expression of a proinflammatory phenotype. E. coli lipopolysaccharide (LPS), tumour necrosis factor-alpha (TNF-alpha) and protein kinase C activation with phorbol myristate acetate (PMA) potentiated monocyte binding during either coincubation or 24-h pretreatment (0.1 microM PMA, +200 +/- 21%). Binding was also promoted by pretreatment with vasoconstrictors, such as the thromboxane A2 mimetic, U-46619 (10 nM-1 microM, max. +35 +/- 3%), or 1 microM angiotensin II (+64 +/- 4%). To elucidate the mechanisms of monocyte adhesion, we analysed the adhesion molecules expressed by human mesangial cells, employing reverse transcription/polymerase chain reaction to detect ICAM-1, VCAM-1 and E-selectin gene expression. Proliferating cells express VCAM-1 and ICAM-1, confirmed by immunocytochemical staining and 79 +/- 3% inhibition of stimulated adhesion by pretreatment of mesangial cells with an anti-ICAM-1 monoclonal Ab. E-selectin transcription was not detectable.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
[Anesthesia in experimental single-lung transplantation: hemodynamic and respiratory changes during prostaglandin E1 and nitroglycerin infusion].
INTRODUCTION: The haemodynamic and oxyforetic modifications induced by continuous infusion (c.i.) of Prostaglandin E1 (PGE1) and Nitroglycerin (NG) during experimental lung transplantation have been studied. METHODS: Twenty lung transplants have been performed on pigs (Landrace). Haemodynamic monitoring consisted of ECG, femoral cannulation for arterial pressure and Swan Ganz catheter. Continuous infusion of drugs started during pneumonectomy. Data have been collected in phase 1: after the induction of anaesthesia; in phase 2: 30 min after the start of pulmonary vasodilation in one lung ventilation with left pulmonary artery clamped; in phase 3: 30 min after lung revascularization; in phase 4: at the end of the surgery. The animals have been divided in two groups. Group A consisted of 10 cases treated with 50 ng/kg/min in phase 2 and 25 ng/kg/min in phase 3 and 4 of PGE1; group B consisted of 10 cases treated with 1 ncg/kg/min in phase 2 and 0.5 ncg/kg/min in phase 3 and 4 of NG. RESULTS: In phase 2 and 4 PA, RVSWI, PRVI increased in group B more than in group A (p < 0.05); in phase 3 PA, PAWP increased in group B more than in group A (p < 0.05). DISCUSSION: In our experience PGE1 has shown to be a stronger pulmonary vasodilator than NG. PGE1 can be considered the drug of choice for pulmonary vasodilation in experimental single lung transplantation, even if more investigations are needed for reaching the real goal of this procedure.
Alprostadil↗
The effects of nonsteroidal anti-inflammatory drugs on human hypertensive vascular disease.
The co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive agents often, but not always, results in blunting of the effect of antihypertensive therapy. Although NSAIDs have no detectable pressor effects in normal subjects or untreated hypertensive people, they seem to antagonize the action of the majority of antihypertensive agents, making it necessary to increase their dosage, and often preventing proper control of blood pressure, particularly in black and elderly patients. The mechanism of this pharmacodynamic interaction is not completely understood, but may involve inhibition of vascular and renal prostaglandin (PG) synthesis, with resulting vasoconstriction and impaired renal excretion of Na+ and water. Also, suppression of a possible intermediary action of PG in the antihypertensive action of agents such as angiotensin converting enzyme inhibitors has been proposed. Certain antihypertensive drugs, such as Ca(2+)-channel blockers, centrally acting alpha agonists, and diuretics seem less sensitive to antagonism by NSAIDs. Aspirin and sulindac seem to be devoid of pressor effects, and thus provide a safe alternative in patients at risk for this interaction. These compounds may, in selected circumstances, even potentiate the effects of antihypertensive medications. Studies are underway to evaluate the hemodynamic effects of more selective blockers of arachidonate metabolism, such as thromboxane synthase inhibitors and selective inhibitors of PGH synthase-2.
Anti-Inflammatory Agents, Non-Steroidal↗