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Biomedical subjects

G Cremona

Publications and source records attributed to G Cremona.

At least 37 records · Page 2Linked to original sources
PubMed1995

Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome.

The hypoxaemia of hepatopulmonary syndrome, seen in severe chronic liver dysfunction, occurs as a result of precapillary pulmonary arterial dilatation and arteriovenous communications. These abnormalities contribute to the mismatch between ventilation and perfusion, and the right to left blood flow shunting. Nitric oxide (NO) is a powerful vasodilator concerned with the regulation of pulmonary vascular tone in man. Using a chemiluminescence analyser, we have measured endogenously produced NO in the exhaled air of three patients with the hepatopulmonary syndrome, six normoxaemic cirrhotic patients and six healthy volunteers. The subjects breathed NO-free air throughout the measurements. The molar rate of production of exhaled NO was raised almost threefold in the patients with hepatopulmonary syndrome compared with normal volunteers and with normoxaemic cirrhotic patients. Hypoxia per se, achieved in the normal volunteers by breathing a hypoxic gas mixture, reduced rather than increased the exhaled NO. One hepatopulmonary syndrome patient received an orthotopic liver transplant and achieved normoxaemia after 3 months. The exhaled NO also returned to normal. Increased pulmonary production of NO could contribute to the development of the hepatopulmonary syndrome.

Blood Gas Analysis↗
PubMed1994

Effect of inhibitors of nitric oxide release and action on vascular tone in isolated lungs of pig, sheep, dog and man.

1. The actions of inhibitors of the release or action of nitric oxide (NO) on pulmonary vascular resistance (PVR) were investigated in lungs isolated from pig, sheep, dog and man. 2. In pig, sheep and human lungs perfused with Krebs-dextran solution, both N omega-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) and Methylene Blue (10(-4) M) increased basal PVR. This increase was reversed by sodium nitroprusside (10(-5) M). In pig lungs N omega-monomethyl-L-arginine (10(-4) M) increased PVR by 154%. This increase was partially reversed by L-arginine (10(-3) M). L-NAME had no effect in dog lungs. 3. Pulmonary artery pressure-flow (PPA/Q) relationships were studied over a wide range of flows. In pigs, sheep and human lungs perfused with Krebs-dextran solution, L-NAME increased the PPA/Q slope. This increase was reversed by sodium nitroprusside. In dog lungs L-NAME had no effect. 4. In blood-perfused lungs, the respective responses to L-NAME were similar to those observed with saline. Acute hypoxia in pig and dog lungs increased intercept pressure. Addition of L-NAME during hypoxia increased the PPA/Q slope in both species. 5. In the human, there was no difference in the absolute increase of PVR or PPA/Q slope elicited by L-NAME between hypertensive and control lungs. 6. We conclude that NO is continuously released in the pulmonary vascular bed of pig, sheep and humans under normoxic conditions. In dog lungs inhibition of NO synthesis increases PVR only under hypoxic conditions. In human lungs with pulmonary hypertension, NO is still released under basal conditions.

Adolescent↗
PubMed1994

Mixed expired nitric oxide in primary pulmonary hypertension in relation to lung diffusion capacity.

The mixed expired nitric oxide (NO) production of the lungs of patients with primary pulmonary hypertension (PPH) and normal subjects was measured to determine the relationship between NO production and the diffusion capacity of the lung (KCO). Expired air was collected from eight patients with PPH and 20 healthy volunteers for analysis by a chemiluminescent analyser. Mean pulmonary artery pressure in the PPH patients was 59.5 +/- 6.45 mmHg and their mean cardiac output was 2.95 +/- 0.35 l/min. All patients and subjects underwent measurements of FEV1, VC and KCO. The rate of production of NO in mixed exhaled air was lower in the PPH group compared to the controls (2.85 +/- 0.7 vs. 4.69 +/- 0.35 nM/min; p < 0.05). There was a good correlation of expired NO with the KCO (r = 0.7; n = 30; p < 0.001). When corrected, KCO differences in exhaled NO were not significant (p = 0.09). We conclude that the low exhaled NO observed in PPH patients is a reflection of the reduced blood capillary volume in these patients rather than a decreased basal production of NO.

Adult↗
PubMed1993

Impairment of pulmonary-artery endothelium-dependent relaxation in chronic obstructive lung disease is not due to dysfunction of endothelial cell membrane receptors nor to L-arginine deficiency.

1. Endothelium-dependent relaxation mediated by endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), is impaired in pulmonary arteries (PA) of hypoxic patients with chronic obstructive lung disease (COLD). To determine the mechanisms responsible for this impairment, we compared the response of rings of isolated PA from 12 COLD patients and 8 controls to the endothelium-dependent vasodilators acetylcholine (ACh), adenosine diphosphate (ADP), and the calcium ionophore, A23187. The response of PA rings to the endothelium-independent nitro-vasodilator sodium nitroprusside (SNP) was also studied in both groups. The PA rings had been pre-contracted by the alpha-adrenoceptor agonist phenylephrine (PE). 2. Endothelium-dependent relaxation was significantly reduced in PA rings from COLD patients as compared with controls when tested with ACh (37.8 +/- 8.8% vs 73.4 +/- 7.9%), ADP (38.4 +/- 6.7% vs 80 +/- 5.6%), and the calcium ionophore, A23187 (35.8 +/- 6.1% vs 87 +/- 6.6%). Relaxation with SNP was, however, significantly greater in PA rings from COLD patients (99.4 +/- 0.6% vs 90.3 +/- 3.1%), as was the contractile response to PE (1.91 +/- 0.21 g vs 1.33 +/- 0.15 g). Pretreatment with the specific inhibitor of NO formation, NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) significantly reduced the relaxation to ACh in all PA rings. This inhibition could be reversed by L-arginine (10(-3) M), the substrate for NO synthesis. Pretreatment with L-arginine alone, however, did not restore the impaired endothelium-dependent relaxation of PA rings from COLD patients. 3. We conclude that EDRF (NO) production is impaired in PA rings from COLD patients and that this impairment is neither due to endothelial receptors dysfunction nor a defect of L-arginine availability and/or transport. Our hypothesis is that the abnormality must lie within the biosynthesis pathway of NO from L-arginine, possibly involving the endothelial enzyme cell, NO synthase, the normal function of which might be altered by chronic hypoxia.

Acetylcholine↗
PubMed1993

In vitro pulmonary vasorelaxant effect of the phosphodiesterase inhibitor enoximone.

Enoximone is a phosphodiesterase inhibitor that has both positive inotropic and systemic vasorelaxant activities. The latter are mediated by an increase in vascular smooth muscle concentration of cyclic 3'5' guanosine monophosphate. However, the effect of enoximone on pulmonary vasoreactivity is not established. The authors, therefore, have studied its effect on endothelium-dependent relaxation mediated by the endothelium-derived relaxing factor nitric oxide (NO), as well as endothelium-independent relaxation of isolated porcine pulmonary arteries. Enoximone (10(-7) to 10(-4) M) caused a dose-dependent relaxation in all pulmonary arterial rings. This relaxation neither required the presence of the endothelium nor was affected by the addition of the inhibitor of NO synthase omega-nitro-L-arginine methyl ester (10(-4) M). Also, the vasorelaxant response of the rings to the endothelium-dependent vasodilator adenosine diphosphate (10(-10) to 10(-5) M) was not affected by pretreatment with enoximone. The authors conclude that enoximone is a potent vasodilator that relaxes pulmonary vascular rings through mechanisms independent of the endothelium. This endothelium-independent vasodilatory effect of enoximone makes it a potentially valuable drug for the treatment of pulmonary hypertension. This particularly applies to diseases in man where NO production by the endothelial cells is impaired.

Animals↗
PubMed1993

Acute and chronic hypoxic pulmonary hypertension.

The development of secondary pulmonary hypertension (PH) as a result of pulmonary disease, both in adults and children, considerably worsens prognosis. Chronic hypoxia appears to be the cause, as long-term oxygen therapy (LTOT) reverses or at least impedes the progressive development of PH. There is now clear evidence that acute hypoxia causes smooth muscle contraction in pulmonary arteries through a direct effect on intracellular calcium levels. Subsequent relaxation depends upon activation of ion transport mechanisms which can be modified by circulating hormones such as the naturally occurring ouabain. Sustained hypoxia can cause adaptation of pulmonary endothelium. One change is a reduction in nitric oxide (NO) production, possibly through reduced activity of the formative enzyme nitric oxide synthase. Basal production of NO appears important in many species including man in determining the low pulmonary vascular resistance. Impaired endothelial NO production as a result of sustained hypoxia may well enhance the development of secondary PH. Much attention is now focused on the regulation of nitric oxide synthase, both the constitutive form in endothelium as well as the inducible form of inflammatory cells. It is possible that either gene transcription or translation are modified when endothelial cells are exposed to chronic hypoxia. This allows the opportunity for therapeutic intervention. More needs to be learnt about the cellular and molecular adaptation to hypoxia in man but novel approaches to treatment may soon arrive for patients with chronic obstructive lung disease and secondary pulmonary hypertension.

Amino Acid Oxidoreductases↗
PubMed1993

The role of prostacyclin in the treatment of primary pulmonary hypertension: the Cambridge experience.

Over the last decade new medical and surgical treatments have become available for primary pulmonary hypertension which have influenced the natural history of the disease. Vasodilator therapy is aimed at overcoming pulmonary vasoconstriction with consequent decrease in afterload and improved right ventricular output. The endpoint of vasodilator therapy is therefore to reduce pulmonary vascular resistance, without causing significant systemic hypotension. Prostacyclin, a potent vasodilator and antiaggregating agent, has been successfully used by continuous infusion in the treatment of severe pulmonary hypertension. The marked improvement in quality of life observed with the use of prostacyclin in these patients as well as the increased survival time on the waiting list for transplantation has influenced us to adopt PGI2 infusion as a fundamental element of our therapeutic strategy for the management of this rare but fatal condition.

England↗
PubMed1991

Influence of serum proteins on fructosamine concentration in multiple myeloma.

Serum fructosamine levels in 36 subjects with various types of multiple myeloma and in 64 normal controls were evaluated by means of a Nitroblue tetrazolium colorimetric assay. Only the IgA myeloma group showed significantly raised serum fructosamine values (P less than 0.001). In the IgG myeloma group, which showed a higher mean serum protein concentration, serum fructosamine levels were not significantly different from controls. The study shows that elevated IgA levels do influence serum fructosamine and this effect should be taken into due consideration in order to avoid possible misinterpretations in evaluating this widely used index of glucose metabolism.

Adolescent↗
PubMed1991

Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease.

BACKGROUND: Endothelial cells release endothelium-derived relaxing factor (EDRF) in a variety of vascular beds, including the pulmonary circulation. However, the role of EDRF-mediated pulmonary-artery relaxation in chronic hypoxic lung disease is unknown. METHODS: We studied endothelium-dependent relaxation mediated by EDRF in vitro in pulmonary arteries that had been obtained from 22 patients undergoing heart-lung transplantation for end-stage chronic obstructive lung disease. Control pulmonary arteries were obtained from 15 patients undergoing lobectomy for lung carcinoma who did not have evidence of other chronic lung disease. The responses of all vascular rings (external diameter, 1.2 to 3.4 mm) to the endothelium-dependent vasodilators acetylcholine and adenosine diphosphate were studied immediately after lung excision. RESULTS: Pulmonary arterial rings from the patients with chronic lung disease developed a greater tension (2.19 +/- 0.16 g) in response to phenylephrine (10(-6) M) than the rings from control patients (1.28 +/- 0.18 g, P less than 0.05). Inhibition of EDRF synthesis by treatment with NG-monomethyl-L-arginine (10(-4) M) eliminated this difference, increasing the tension in the rings from the controls (P less than 0.01) but not in those from the patients with chronic lung disease. Rings from control patients relaxed in response to cumulative doses (10(-10) to 10(-5) M) of acetylcholine (maximal relaxation, 81.3 +/- 3.9 percent) and adenosine diphosphate (maximal relaxation, 85.3 +/- 2.6 percent). By contrast, rings from patients with chronic obstructive lung disease achieved only 41.3 +/- 4.8 percent of maximal relaxation in response to acetylcholine (n = 32) and 49.4 +/- 5.5 percent in response to adenosine diphosphate (n = 24) (P less than 0.001, as compared with control rings). Rings from both the controls and the patients with chronic lung disease relaxed similarly in response to the endothelium-independent vasodilator sodium nitroprusside (10(-4) M). There was an inverse correlation between the degree of intimal thickening and the level of maximal relaxation of the rings from the patients with chronic lung disease (r = -0.60, P less than 0.001). Maximal relaxation was also related directly to the partial pressure of arterial oxygen before transplantation (r = 0.68, P less than 0.01) and inversely to the partial pressure of arterial carbon dioxide before transplantation (r = -0.55, P less than 0.01), but not to the forced expiratory volume in one second (r = 0.19, P not significant). CONCLUSIONS: Endothelium-dependent pulmonary-artery relaxation in vitro is impaired in arteries from patients with end-stage chronic obstructive lung disease. Such impairment may contribute to the development of pulmonary hypertension in chronic hypoxic lung disease.

Acetylcholine↗
PubMed1991

Endothelium-derived relaxing factor and the pulmonary circulation.

Endothelium-derived relaxing factor (EDRF) is probably identical to nitric oxide (NO) and is released by the vascular endothelium both in the basal unstimulated state and in response to a wide range of physical and chemical stimuli. Since it was first described 10 years ago, evidence is accumulating that it is an important modulator of vascular smooth muscle tone. EDRF acts on the pulmonary vascular bed as on the systemic circulation. EDRF release to pharmacologic stimuli is impaired in pulmonary arteries from patients with chronic hypoxemia. This impairment is associated with severity of respiratory failure and of structural change of vessel walls. Disturbance of EDRF activity may be important in the pathophysiology of pulmonary vascular disease. This brief review describes the current status of experimental studies concerning the possible role of EDRF on the pulmonary circulation in normal conditions and in the pathogenesis of pulmonary hypertension.

Animals↗
PubMed1991

Transplantation for end-stage lung disease.

The last decade has seen lung and heart-lung transplantation move from experimental procedures to clinical treatments. Innovative surgical techniques combined with the use of ciclosporin as an immunosuppressive agent have enabled successful transplantation in a wide range of end-stage lung diseases. Exclusion criteria for selecting recipients have relaxed, and improved preservation techniques have facilitated distant donor organ procurement and decreased peri-operative mortality. A range of techniques for the physiological monitoring of the graft as well as diagnosis of major complications such as rejection and opportunistic infection have been introduced. Obliterative bronchiolitis remains a major challenge to the immunologist and to the chest physician in terms of etiology, pathogenesis and treatment. As survival rates improve with improved management, lung and heart-lung transplantations are contributing towards effective treatment of end-stage pulmonary disease as well as providing new insight into pulmonary physiology and into mechanisms of lung disease.

Bronchiolitis Obliterans↗
PubMed1991

[Is there a typical radiologic picture of primary pulmonary hypertension? Study of 18 cases].

The conventional chest radiographs were studied of 18 patients with primary pulmonary hypertension, waiting for, or treated with lung transplantation in the Papworth Hospital. The goal of the study was to find out whether there is a pattern characteristic of primary pulmonary hypertension. The following points were considered: a) pulmonary transparency; b) the hila; c) the left hemidiaphragm; d) the pulmonary artery; e) the right ventricle; f) the right atrium; g) the left ventricle. A score was assigned for any degree of abnormality of the points mentioned above. As a result, a radiological pattern was found that can: 1) confirm the presence of pulmonary hypertension; 2) exclude that this hypertension has a detectable cause; 3) measure the severity of the disease, particularly with regard to hypertension degree. The conclusion is that there is a radiological pattern strongly suggestive of primary pulmonary hypertension and that conventional radiology can help in detecting and monitoring this rare disease, which today can only be treated by means of transplantation.

Adult↗
PubMed1991

The alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduce nasal potential difference.

Pretreatment by inhalation with the alpha 1-adrenergic agonist methoxamine and the "loop" diuretic frusemide reduces the bronchial response to certain airway challenges in asthma. To test whether these drugs may act by altering airway epithelial ion and water transport, their effect on nasal potential difference (PD) when applied topically in eight normal volunteers was measured. For comparison, the effect of the Na(+)-channel blocking drug amiloride and the beta 2-adrenergic agonist salbutamol was also tested. Both methoxamine and frusemide significantly reduced PD: at the highest concentration given (10(-3) mol.l-1), there was a mean drop in PD from baseline of 39.5% following methoxamine treatment (p less than 0.05) and a mean drop of 30.2% following frusemide (p less than 0.05). Neither drug was as effective as amiloride, which caused a mean drop in PD of 27.5% from baseline at 10(-6) mol.l-1 and a drop of 71.6% at 10(-3) mol.l-1 (p less than 0.01 for each concentration). Salbutamol had no significant effect on PD (p greater than 0.05). We conclude that methoxamine and frusemide may derive their protective effect on some bronchial challenge, at least in part, from their effect on airway epithelial ion flux.

Adult↗
PubMed1990

Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome.

A comparison has been made between the endothelium-dependent relaxation of pulmonary arteries (PA) obtained at heart-lung transplantation from 4 patients with Eisenmenger's syndrome and secondary pulmonary hypertension, and PA obtained at lobectomy from 4 patients with lung carcinoma, the controls. All vascular rings were studied immediately after lung excision. PA rings from control patients dose-dependently relaxed to cumulative doses of acetylcholine (ACh, 10(-10) to 10(-5) M), achieving a maximal relaxation of 80 +/- 5% (mean +/- s.e. mean) from precontraction with phenylephrine. By contrast, PA rings from Eisenmenger's syndrome patients achieved a maximal relaxation of only 34 +/- 12% (P less than 0.05, unpaired t test), with even paradoxical contraction at high doses of ACh (10(-6) to 10(-5) M). Sodium nitroprusside (10(-4) M) relaxed all PA rings, with and without endothelium (carefully removed before study), obtained from both control and Eisenmenger's syndrome patients. These results provide the first evidence that endothelium-dependent relaxation of PA mediated by endothelium-derived relaxing factors is impaired in Eisenmenger's syndrome patients with secondary pulmonary hypertension.

Acetylcholine↗
PubMed1988

Twenty-four-hour blood pressure monitoring after a single dose of sustained-release verapamil.

The antihypertensive effect of a single dose of 240 mg sustained-release (S-R) verapamil was investigated by ambulatory blood pressure (BP) monitoring in 13 patients with mild to moderate essential hypertension. Following a 2-week washout period, 24-hour BP monitoring was carried out with a Spacelabs ICR 5300 device following random administration of a tablet of S-R verapamil or placebo; BP recording was repeated after crossover 3 to 7 days later. Average whole-day systolic and diastolic BPs were significantly lower after verapamil (130.1 +/- 2.6/87.1 +/- 1.2 mmHg) than after placebo (142.1 +/- 3.3/95.8 +/- 2.1 mmHg) (p less than 0.01). Mean waking BP was 146.4 +/- 3.6/99.1 +/- 2.2 mmHg after placebo and 135.2 +/- 3.3/90.5 +/- 1.7 mmHg after verapamil (p less than 0.01); during sleeping hours BP was 133.8 +/- 3.1/88.7 +/- 2.6 mmHg following placebo and 122.2 +/- 2.3/80.9 +/- 1.8 mmHg following verapamil (p less than 0.01). Blood pressure profile was significantly reduced by verapamil up to 20 hours after tablet administration, while from 21 to 24 hours after drug intake BP values were similar to placebo. Response to verapamil was not correlated to the pretreatment BP values and to the patient's age. In summary, this study suggests that acute administration of 240 mg S-R verapamil in hypertensive patients produces a BP reduction during 24-hour, daytime, and nighttime periods. The hypotensive efficacy is preserved for many hours after tablet intake and seems to be due to individual variation in cardiovascular reactivity to the drug.

Adult↗