American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 978-982, (2002)
© 2002 American Thoracic Society
Diabetes Worsens Pulmonary Diffusion in Heart Failure, and Insulin Counteracts This Effect
Marco Guazzi,
Roberto Brambilla,
Stefano De Vita and
Maurizio D. Guazzi
Istituto di Cardiologia dell'Università degli Studi, Milan, Italy
Correspondence and requests for reprints should be addressed to Maurizio D. Guazzi, M.D., Ph.D., Istituto di Cardiologia dell'Università degli Studi, Via C. Parea, 4, 20138 Milano, Italy. E-mail: maurizio.guazzi{at}unimi.it
 |
ABSTRACT
|
|---|
Chronic heart failure (CHF) (hydrostatic stress) and diabetes (basal laminae thickening) share the potentiality of damaging the alveolar-capillary membrane. We investigated 15 control subjects and 3 groups of 15 patients each having type 2 diabetes (Group 1), CHF (Group 2), and diabetes and CHF (Group 3), to probe whether addition of diabetes worsens lung diffusion in CHF and whether insulin counteracts this effect. Compared with control subjects, carbon monoxide diffusing capacity (DLCO) and diffusing capacity of the alveolar-capillary membrane at rest were increasingly depressed from Group 1 through Group 3. DLCO was lower than predicted in 11 patients each in Groups 1 and 2 and in all patients in Group 3. Regular insulin (10 IU) was ineffective in CHF alone, whereas it improved DLCO and diffusing capacity of the alveolar-capillary membrane in diabetes; changes, however, were significantly greater in the patients with both diabetes and CHF (+17.6%, +27.3%) than in those with diabetes alone (+9.2%, +13.1%). Insulin did not affect lung spirometry, volumes, and hemodynamics. Thus, gas transfer is depressed in a number of patients with diabetes or CHF; comorbidity increases the frequency and extent of this disorder. Insulin facilitates diffusion in diabetes, through an influence on alveolar-capillary conductance, and its efficacy is greater in comorbidity; diabetes is more disturbing in patients with CHF and produces a synergistic rather than a simple additive effect.
Key Words: diabetes mellitus • heart failure • insulin • pulmonary gas exchange
|
INTRODUCTION
|
|---|
It is known that when the left ventricle is dysfunctioning, as in chronic heart failure (CHF), increased pulmonary venous pressure becomes the leading cause for damage of the alveolar–capillary interface that impairs the pulmonary gas transfer and enhances the patient's physical limitation (1–3). Diabetes mellitus may also be associated with mild and silent impairment in gas exchanging function (4, 5), possibly as a consequence of a microangiopathic process and nonenzymatic glycosylation of tissue proteins (6) that alter the alveolar and pulmonary capillary laminae (7).
Because patients with diabetes have a four- to fivefold increased risk of CHF (8), the probability of developing respiratory impairment might be similarly augmented. This raises the question whether, in case of comorbidity, diabetes mellitus aggravates the lung dysfunction that frequently accompanies CHF. The issue appears even more important if it is considered that deterioration in gas conductance through the alveolar–capillary interface is a powerful independent predictor of worse prognosis in stable CHF (9). In subjects having type 1 diabetes without heart failure, chronic infusion of insulin is associated with lower impedance to pulmonary gas transfer (10). This observation has suggested to us that insulin may be particularly worthy of trial in patients suffering from the two diseases.
The present study was undertaken to clarify whether coexistence of type 2 diabetes enhances the deterioration of pulmonary gas exchange in CHF, whether this is an additive or a synergistic effect, and whether insulin counteracts the alveolar-capillary membrane consequences of comorbidity.
|
METHODS
|
|---|
Patients
We recruited 15 control subjects, 15 patients with type 2 diabetes (Group 1), and 30 patients with CHF. Of the 30 patients with CHF, 15 were normoglycemic (Group 2) and 15 had diabetes (Group 3). Informed consent was obtained, and the institutional review board approved the protocols. Control subjects had atypical chest pain, with normal coronary angiography. Five patients with diabetes alone and seven with comorbidity, in addition to sulfanylurea (n = 17) or metformin (n = 13), required insulin (18.7 ± 1.9 IU) for glycemic control. They were classified as having type 2 diabetes (11) because hyperglycemia had previously been controlled with oral agents in them and all had never had ketoacidosis. Glycosylated hemoglobin averaged 6.1 ± 0.3% in patients with diabetes and 6.3 ± 0.2% in those with comorbidity. Patients with CHF alone and those with diabetes in addition to CHF were in stable clinical condition (New York Heart Association Class II to III), and CHF was due to previous myocardial infarction or idiopathic cardiomyopathy, with an ejection fraction of 40% or less and a FEV1/vital capacity (VC) ratio of more than 70%. All had a pack-years index of smoking of less than 10 and had abstained from tobacco products over the last 8 months (12). None had a history of pulmonary disease, carboxyhemoglobin of more than 2%, distal neuropathy, autonomic insufficiency, and renal impairment. Antifailure treatment included digoxin and furosemide (in all), ACE-inhibitors (15 patients), and aspirin (15 patients). Mitral regurgitation did not exceed Grade 2 (subjective scale from 0 to 5).
Pulmonary Function and Hemodynamics
VC, FEV1, and carbon monoxide diffusing capacity (DLCO) (measured with Sensormedics 2200 Pulmonary Function Test System; Sensormedics, Yorba Linda, CA) were expressed in absolute values and as percent normal predicted values. Reference equations (13, 14) were used in these analyses when values were expressed as percent predicted. DLCO was determined twice with washout intervals of at least 4 minutes (the average was taken as the final result), with a standard single breath technique. The maneuver was performed using a test gas with 0.28% carbon monoxide, 0.3% acetylene, 0.3% methane, 21% oxygen (O2), and the balance made up of nitrogen, and was then repeated using test gases with 40 and with 60% O2 concentrations. The diffusing capacity of the alveolar-capillary membrane (DM) and pulmonary capillary blood volume available for gas exchange (VC) were determined using the classic method described by Roughton and Forster (15). This method partitions pulmonary diffusing capacity into its component resistances, the diffusive resistance of the alveolar-capillary membrane (1/DM) and the reactive resistance due to pulmonary capillary blood (1/ VC, where = the rate of reaction of carbon monoxide with hemoglobin), according to the following equation: 1/DLCO = 1/DM + 1/VC. The 1/ value was determined using the following equation, which assumes that the red cell membrane has a negligible resistance to gas exchange:
 |
where Hb is the subject's hemoglobin concentration (g/dl), and PAO2 is the alveolar O2 partial pressure. A plot of 1/DLCO against 1/, drawn using DLCO measured at different PAO2 values, will yield a straight line with a y-intercept of 1/DM and a gradient of 1/VC.
Under similar protocols (16), we have not found carbon monoxide back-tension effects on serial DLCO, DM, and VC measurements. Alveolar volume (VA) was derived by methane dilution. Mitral regurgitation and ejection fraction were assessed by Doppler echocardiography (17). Pulmonary hemodynamics were measured with a 5 F double-lumen thermodilution catheter.
Study Protocol
Patients were maintained on their current treatment and were fed a diet containing 160 g of carbohydrate per day. Hypoglycemic drugs and insulin were withdrawn 24 hours before studies, which were performed after an overnight fast. Baseline measurements were performed after catheter positioning and 30 minutes' rest. Then, 50 ml of saline either containing or not containing 10 IU of regular insulin were infused (1.0 ml/minute). Measurements were performed again 10 minutes after the end of infusion. On the following morning, these procedures were repeated while patients were switched to insulin or inactive solution, according to a random block design. Blood glucose was kept steady during the experiments by infusing 20% dextrose solution (15–100 ml), according to the degree of glycemia. Control subjects were not made to undergo insulin infusion; in them, hemodynamics were measured immediately before coronary angiography, and pulmonary function was assessed the day after by the same methods used in patients.
Statistical Analysis
Data are presented as mean ± SD; descriptive parameters were compared by  2 analysis. Data were analyzed by two-way repeated measures analysis of variance, Newman-Keuls multiple comparison procedure, and a linear regression. A p value of less than 0.05 was considered significant.
|
RESULTS
|
|---|
Baseline Evaluation
Control subjects and patients in the three groups were similar in sex, age, body characteristics, and blood pressure. Wedge pulmonary pressure, left ventricular ejection fraction, cardiac index, and systemic and pulmonary vascular resistance were similarly altered in patients with CHF and in those with comorbidity compared with those with diabetes alone and control subjects. Patients with CHF and those with coexisting diseases received similar doses of digoxin and furosemide and showed a comparable degree of mitral regurgitation; cases in these groups that were prescribed other cardiovascular drugs in addition to digitalis and diuretics were fairly well balanced. Fasting blood sugar, cholesterol, triglyceride, and glucohemoglobin were mildly or moderately higher in patients with diabetes than in patients without diabetes and control subjects (Table 1)
.
Compared with healthy subjects, percent normal predicted (Table 1) and absolute values (Table 2)
of DLCO and DLCO/VA at rest were increasingly depressed from patients with diabetes to patients with CHF to patients with comorbidity, the baseline alveolar interface conductance (DM) and transfer coefficient (DM/VA) were diminished, and the proportion of total pulmonary resistance ascribable to alveolar-capillary membrane (DLCO/DM) was raised (Table 2). Pulmonary capillary volume available for gas exchange, expressed either in absolute values (Figure 1)
or per unit alveolar gas volume (VC/VA) (Table 2), was not significantly different between the three patient groups. The percent normal predicted DLCO was reduced in 11 patients with diabetes, in 11 subjects with CHF, and in all 15 patients with comorbid diseases; values in patients whose current treatment included insulin for glycemic control showed a trend to cluster in the higher range (Figure 2)
.
View this table:
[in this window]
[in a new window]
|
TABLE 2. Plasma glucose concentration and hemodynamic and respiratory values in control subjects and patients at baseline and in patients, 60 minutes after saline or regular insulin (10 iu) infusions (mean ± sd)
|
|
View larger version (34K):
[in this window]
[in a new window]
|
Figure 1. Individual responses of the pulmonary gas exchange capacity to the infusion of insulin in Groups 1, 2, and 3. Full circles represent mean ± SD values.  p < 0.01 versus corresponding value in Group 1; * p < 0.01 versus pre; open triangle, p < 0.01 versus corresponding value in Group 2. Pre, before insulin; post, after insulin.
|
|
View larger version (23K):
[in this window]
[in a new window]
|
Figure 2. Individual percentages of predicted normal values of DLCO before and after insulin infusion in Groups 1, 2, and 3. Full circles represent the mean ± SD values. Arrowheads indicate patients whose current therapy included insulin for adequate glycemic control. p < 0.01 versus corresponding value in Group 1; *p < 0.01 versus pre; open triangles, p < 0.01 versus corresponding value in Group 2. Pre, before insulin; post, after insulin.
|
|
Responses to Insulin
The individual responses of the gas exchange capacity to the intravenous infusion of insulin, expressed in absolute values, are depicted in Figure 1. Among patients with diabetes, 10 patients showed amelioration of DLCO that resulted in an average increase by 9.2% from baseline, with DM increasing by 13.1%. Improvement in DLCO and DM with insulin was significantly greater in patients with comorbidity (+17.6 and + 27.3%, respectively) and involved all cases but one. In this group, the transfer coefficient (DM/VA) rose by 20.4%, and the proportion of total lung diffusing resistance attributable to the alveolar–capillary interface (DLCO/DM) fell from 73 ± 8.8 to 64.4 ± 9.9%. In the group with diabetes, DM/VA augmented by 12.3%, and DLCO/DM diminished from 63.2 ± 7.9 to 60.5 ± 6.2%. In one patient with diabetes and in four patients with diabetes and CHF, DLCO attained or exceeded 100% of normal predicted. All these changes were not present 24 hours later at measurements before the infusion of saline alone in subjects who had received insulin the day before. In patients having CHF without diabetes, differences in DLCO and DM between pre- and postinsulin were not significant (Figures 1 and 2); some improvement was seen only in three of them. We did not find a correlation between age and DLCO in all groups and between DLCO and time from diabetes diagnosis. The infusion of saline alone did not produce any effect on the pulmonary gas exchanging capacity in all groups (Table 2).
Hemodynamics, Lung Spirometry, and Volumes
As shown in Table 2, ejection fraction, wedge pulmonary pressure, pulmonary arteriolar resistance, VC, FEV1, and alveolar gas volume were not significantly affected by the hormone in any group. Systemic vascular resistance only showed a trend to reduce with insulin.
|
DISCUSSION
|
|---|
Sustained elevation of the pulmonary venous pressure, as induced by chronic left ventricular dysfunction, can injure the alveolar–capillary interface (18, 19) and cause a persistent depression of the gas exchanging function (2, 3, 20, 21). A current opinion is that in diabetes there is a random pattern of pulmonary tissue involvement, which explains the presence of lung dysfunction in some patients (22). Accordingly, in this study, DLCO was less than normal predicted in 73% of patients with diabetes and patients with CHF, and values were less depressed in the former (87% predicted) than in the latter (78% predicted) group.
Comorbidity has not been investigated before. Our findings clearly show that in this category of patients, gas transfer is significantly more depressed compared with the patients with single diseases, and the majority of cases present with DLCO reduced to levels lower than those reported in the literature for CHF alone (2). This raises a basic question concerning the mechanisms of the interaction between cardiac dysfunction and diabetes. Both in patients with CHF alone and in those having diabetes in addition to CHF, VC was similar to that in control subjects, DM was reduced, and the proportion of total lung diffusion resistance ascribable to alveolar–capillary interface (DLCO/DM) was raised. In addition, the transfer coefficient (DM/VA) varied from one group to another according to the membrane conductance and not according to the alveolar gas volume. Thus, depression in alveolar-capillary membrane conductance was a common background for pulmonary dysfunction in these patients, and differences in lung physiology could not be explained by differences in the underlying mechanisms. Yet, etiology and severity of cardiac dysfunction probably did not make the difference because cases of ischemic heart disease and dilated cardiomyopathy were well distributed and left ventricular ejection fraction, cardiac index, wedge pulmonary pressure, degree of mitral regurgitation, and drug treatment were similar in the two groups. A more convincing interpretation is that in case of comorbidity, the diabetes-mediated disturbances added to or interacted with those produced by CHF, so that frequency and extent of impairment in gas transfer were increased. Although smoking may represent a potential confounding factor, it is remarkable that all patients were ex-smokers, and with smoking cessation, DLCO ameliorates to within-normal levels in subjects with lesser cigarette consumption (12).
Considering that diabetes in our patients was fairly well controlled with the background therapy, it seems unlikely that hypoglycemic agents or metabolic control per se is capable of preventing patients with type 2 diabetes from developing impedance to gas transfer. On the contrary, insulin seems to possess such an ability. In fact, patients who currently received insulin for adequate glycemia control showed a better membrane conductance; more consistently, an acute infusion of the hormone in patients with diabetes, either alone or combined with CHF, was associated with a considerable increase of DM and DM/VA, and a reduction of DLCO/DM, documenting an improved efficiency of gas exchange. Cardiac output, ejection fraction, pulmonary wedge pressure and arteriolar resistance, VC, FEV1, and VA were not significantly affected by insulin; the glucose rate required to maintain plasma glucose constant during infusion was low and was not significantly different among the groups, suggesting that these variables did not have a major part in the response. These results altogether are in favor of a specific influence of insulin, in type 2 diabetes, on the conductance of the alveolar-capillary membrane, which is seemingly dissociated from changes in glycemia (blood glucose, in fact, was kept at baseline levels for the duration of the experiments). It is noteworthy that insulin was not significantly beneficial in the group with CHF alone, whereas it was clearly such in the comorbidity group, and that the responses of DLCO and DM were greater in these patients than in those with diabetes alone. This may suggest that the diabetes-mediated injury of the alveolar–capillary interface is enhanced in the presence of CHF so that diabetes produces a synergistic rather than a simple additive effect in case of comorbidity.
A reasonable explanation for an acute improvement of DM is a shortening of the diffusion path for gas exchange. An example may be an acute decrease of fluid filtration from the capillary to the interstitial alveolar space, as may result from ventricular unloading and acute reduction of the hydrostatic forces. Even though insulin possesses vasodilating and ventricular unloading properties (23), this mechanism does not fit findings in the study because the hormone was effective in patients having diabetes with CHF and was not effective in patients having CHF without diabetes; paradoxically, decrease in systemic vascular resistance with insulin was significant in the patients with CHF and was not significant in those with comorbidity; more consistently, there were no changes in pulmonary hemodynamics in any group following insulin documenting hydrostatic variations. Another possibility for an acute shortening of the diffusion path may be that of an increased alveolar epithelial fluid clearance by enhancement of the transcellular movement of sodium coupled to specific substrates such as D-glucose (24, 25). It is presumable, however, that if this were the basic mechanism, patients having CHF without diabetes would also benefit from the administration of insulin; our data show that this was not the case. A third possibility, which is in agreement with findings in this study, is that insulin in diabetes activates the defective release of substances such as endothelium-derived nitric oxide (26, 27) and vasodilating prostaglandins (28), which are deeply involved in the modulation of the pulmonary vascular tone and permeability and possess the ability of reducing the tissue component of resistance to the transfer of O2 from the alveolus to its uptake by hemoglobin.
In conclusion, this study shows that both type 2 diabetes mellitus and CHF may depress the efficiency of gas exchange in some patients; comorbidity increases frequency and extent of the lung injury, and diabetes probably exerts a synergistic activity with CHF rather than a simple additive effect; and insulin counteracts these influences of diabetes. Whether the hormone may have a therapeutic indication in patients having type 2 diabetes in addition to CHF is a question of potential clinical relevance (9) that deserves investigation.
|
FOOTNOTES
|
|---|
This study was supported in part by a grant from the Ministry of Health, Rome, and by the Luigi Berlusconi Foundation, Milan, Italy.
Received in original form April 23, 2002;
accepted in final form July 2, 2002
|
REFERENCES
|
|---|
- Kraemer MD, Kubo SH, Rector TS, Brunsvold N, Bank AJ. Pulmonary and peripheral vascular factors are important determinants of peak exercise oxygen uptake in patients with heart failure. J Am Coll Cardiol 1993;21:641–648.[Abstract]
- Puri S, Oakley CM, Hughes JMB, Cleland JGF. Increased alveolar-capillary gas resistance to gas transfer in patients with chronic heart failure. Br Heart J 1994;72:140–144.[Abstract/Free Full Text]
- Guazzi M, Marenzi G, Alimento M, Contini M, Agostoni P. Improvement in alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin. Circulation 1997;95:1930–1936.[Abstract/Free Full Text]
- Cooper BG, Taylor R, Alberti KGMM, Gibson GJ. Lung function in patients with diabetes mellitus. Respir Med 1990;84:235–239.[Medline]
- Sandler M, Bunn AE, Stewart RI. Pulmonary function in young insulin-dependent diabetic subjects. Chest 1986;90:670–675.[Abstract/Free Full Text]
- Berkam CJ, Rifkin H. Newer aspects of diabetic microangiopathy. Annu Rev Med 1966;17:83–112.[CrossRef][Medline]
- Vracko R. A comparison of the microvascular lesions in diabetes mellitus with those of normal aging. J Am Geriatr Soc 1982;30:201–205.[Medline]
- Savage MP, Krolewski AS, Kenien GG, Lebeis MP, Christlies AR, Lewis SM. Acute myocardial infarction in diabetes mellitus and significance of congestive heart failure as a prognostic factor. Am J Cardiol 1988;62:665–669.[CrossRef][Medline]
- Guazzi M, Pontone G, Brambilla R, Agostoni P, Reina G. Alveolar-capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure. Eur Heart J 2002;23:467–476.[Abstract/Free Full Text]
- Niranjan V, McBrayer DG, Ramirez LC, Raskin P, Hsia CCW. Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus. Am J Med 1997;103:504–513.[CrossRef][Medline]
- Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183–1197.[Medline]
- Knudson RJ, Kaltenborn WT, Burrows B. The effects of cigarette smoking and smoking cessation on the carbon monoxide diffusing capacity of the lung in asymptomatic subjects. Am Rev Respir Dis 1989;140:645–651.[Medline]
- Knudson RJ, Kaltenborn WT, Knudson DE, Burrows B. The single breath carbon monoxide diffusing capacity: reference equations derived from a healthy nonsmoking population and effects of hematocrit. Am Rev Respir Dis 1987;135:805–811.[Medline]
- Cotes JE. Lung function: assessment and application in medicine, 4th ed. Oxford, England: Blackwell Scientific Publications; 1979. p. 230–250.
- Roughton FJW, Forster FE. Relative importance of diffusion and chemical reaction rate of exchange of gases in human lung, with special reference to true diffusing capacity of blood in the lung capillaries. J Appl Physiol 1957;11:290–302.[Abstract/Free Full Text]
- Guazzi M, Agostoni P, Bussotti M, Guazzi MD. Impeded alveolar-capillary gas transfer with saline infusion in heart failure. Hypertension 1999;34:1202–1207.[Abstract/Free Full Text]
- Henry WL, De Maria A, Gramiak R, King DL, Kisslo JA, Popp RL, Sahn DJ, Schiller NB, Tajik A, Teichholz LE, et al. Report of the American Society of Echocardiography Committee on nomenclature and standard in two-dimensional echocardiography. Circulation 1980;62:212–217.[Free Full Text]
- Chang SC, Chang HI, Liu SY, Shiao GM, Perng RP. Effects of body position and age on membrane diffusing capacity and pulmonary capillary volume. Chest 1992;102:139–142.[Abstract/Free Full Text]
- West JB, Mathieu-Costello O. Structure, strength, failure and remodeling of the pulmonary blood gas barrier. Annu Rev Physiol 1999;61:543–572.[CrossRef][Medline]
- Kuebler WM, Ying X, Singh B, Issekutz AC, Bhattacharya J. Pressure is proinflammatory in lung venular capillaries. J Clin Invest 1999;104:495–502.[Medline]
- Guazzi M. Alveolar-capillary membrane dysfunction in chronic heart failure: pathophysiology and therapeutic implications. Clin Sci 2000;98:633–641.[Medline]
- Sandler M. Is the lung a "target organ" in diabetes mellitus? Arch Intern Med 1990;150:1385–1388.[Abstract]
- Baron AD. Hemodynamic actions of insulin. Am J Physiol 1994;267:E187–E202.[Abstract/Free Full Text]
- Matthay MA, Folkesson HG, Verkman AS. Salt and water transport across alveolar and distal airway epithelia in the adult lung. Am J Physiol 1996;270:L487–L503.[Abstract/Free Full Text]
- Bland RD. Lung epithelial ion transport and fluid movement during the perinatal period. Am J Physiol 1990;259:L30–L37.[Abstract/Free Full Text]
- McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, Grath LT, Henry WR, Andrews JW, Hayes JR. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1992;35:771–776.[Medline]
- Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction: implications for the syndrome of insulin resistance. J Clin Invest 1996;97:2601–2610.[Medline]
- Williams SB, Cusco JA, Roddy MA, Johnstone MT, Craeger MA. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 1996;27:567–574.[Abstract]
This article has been cited by other articles:
|
|
|
|
 
S. G. Brown, M. Gallacher, R. E. Olver, and S. M. Wilson
The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells
Am J Physiol Lung Cell Mol Physiol,
May 1, 2008;
294(5):
L942 - L954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi, R. Arena, and M. D. Guazzi
Evolving changes in lung interstitial fluid content after acute myocardial infarction: mechanisms and pathophysiological correlates
Am J Physiol Heart Circ Physiol,
March 1, 2008;
294(3):
H1357 - H1364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Edgerton, D. W. Neal, M. Scott, L. Bowen, W. Wilson, C. H. Hobbs, C. Leach, S. Sivakumaran, T. R. Strack, and A. D. Cherrington
Inhalation of Insulin (Exubera) Is Associated With Augmented Disposal of Portally Infused Glucose in Dogs
Diabetes,
April 1, 2005;
54(4):
1164 - 1170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi, G. Tumminello, F. Di Marco, C. Fiorentini, and M. D. Guazzi
The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure
J. Am. Coll. Cardiol.,
December 21, 2004;
44(12):
2339 - 2348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi, G. Reina, G. Tumminello, and M. D. Guazzi
Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure
J Appl Physiol,
November 1, 2004;
97(5):
1866 - 1873.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch
Management of Diabetes and Hyperglycemia in Hospitals
Diabetes Care,
February 1, 2004;
27(2):
553 - 591.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi, G. Tumminello, M. Matturri, and M. D. Guazzi
Insulin ameliorates exercise ventilatory efficiency and oxygen uptake in patients with heart failure-type 2 diabetes comorbidity
J. Am. Coll. Cardiol.,
September 17, 2003;
42(6):
1044 - 1050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guazzi
Alveolar-Capillary Membrane Dysfunction in Heart Failure: Evidence of a Pathophysiologic Role
Chest,
September 1, 2003;
124(3):
1090 - 1102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Boulbou, K. Gourgoulianis, P. A. Molyvdas, M. Guazzi, R. Brambilla, S. De Vita, and M. D. Guazzi
Insulin Effect on Lung Diffusion: NO Pathway
Am. J. Respir. Crit. Care Med.,
August 1, 2003;
168(3):
398 - 399.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Laghi and M. J. Tobin
Disorders of the Respiratory Muscles
Am. J. Respir. Crit. Care Med.,
July 1, 2003;
168(1):
10 - 48.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Sleep-Disordered Breathing, Control of Breathing, Respiratory Muscles, and Pulmonary Function Testing in AJRCCM 2002
Am. J. Respir. Crit. Care Med.,
February 1, 2003;
167(3):
306 - 318.
[Full Text]
[PDF]
|
|
|
Copyright © 2002 American Thoracic Society
|
TOP
ABSTRACT
INTRODUCTION