Search PubMed⌕ Search

Biomedical subjects

M Guazzi

Publications and source records attributed to M Guazzi.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Intra- and extravascular volumes in congestive heart failure and their redistribution following extracorporeal ultrafiltration].

In advanced congestive heart failure with fluid retention, extracorporeal ultrafiltration (UF) causes persistent relief of edema or anasarca through hemodynamic and humoral changes that interrupt refractoriness to diuretics. The intra and extravascular fluid partition in congestive heart failure, as well as changes occurring in the two compartments following fluid withdrawal with UF, are unknown. In 8 congestive heart failure patients with severe fluid retention undergoing UF, we measured total (TBV), intrathoracic (ITBV) and pulmonary blood volumes (PBV), and extravascular lung water (EVLW). The intra and extravascular volumes were evaluated by a fiberoptic thermal dye dilution monitoring system, before, at the end of UF (3697 +/- 699 ml) and 24 hours later. Baseline data were compared with those of 10 subjects without heart failure undergoing coronary bypass surgery. In congestive heart failure patients, as compared with controls, TBV was normal, the intrathoracic blood content (ITBV, PBV and PBV/TBV ratio) was increased and EVLW was normal. UF did not induce significant changes in TBV and in EVLW, and reduced ITBV, PBV and PBV/TBV ratio, suggesting that a shift of fluid from the intra to the extrathoracic intravascular compartment occurred. Because both TBV and EVLW were not affected by the procedure, the largest proportion of fluid removed by UF derived from the systemic extravascular space. Both pulmonary wedge and right atrial pressures significantly decreased after UF, and cardiac output increased. In conclusion, congestive heart failure is associated with normal TBV and EVLW content and with intravascular intrathoracic hypervolemia and extrathoracic hypovolemia. UF induces hemodynamic improvement through a selective fluid removal from the extravascular systemic space without changes in both TBV and EVLW.

Aged↗
PubMed1998

Brief periods of occlusion and reperfusion increase skeletal muscle force output in humans.

Prolonged periods of ischemia/reperfusion are known to deleteriously affect skeletal muscle performance. However, in animal models, brief bouts of both skeletal and cardiac muscle ischemia/reperfusion have been shown to decrease skeletal muscle injury and increase skeletal muscle force output, a phenomenon termed "preconditioning". Because there are transient periods of ischemia/reperfusion during isometric and concentric muscle contractions, the purpose of this study was to examine how short duration forearm occlusion/reperfusion prior to exercise, influenced isometric skeletal muscle force output in humans. Eleven subjects (6 men and 5 women, mean age 25 +/- 1 years) participated in this study. Using a Biodex multijoint ergometer, a protocol of isolated, isometric forearm wrist flexions was utilized to measure muscle force output in two separate trials. In the first trial, 15 isometric maximal voluntary contractions (MVCs) of the wrist flexors were performed in 20 intervals interspersed with 10 s of rest. In the second trial, forearm occlusion was induced (2 min at 200 mmHg by blood pressure cuff occlusion, with 10 s of hyperemia) prior to exercise. Following cuff occlusion, an identical exercise protocol was followed, i.e. 15 isometric wrist flexor MVCs performed in 20 intervals interspersed with 10 s of rest. The total force output over 15 MVCs was greater following intermittent cuff occlusion (no occlusion 2619 +/- 320 ft.lbs vs cuff occlusion 2986 +/- 195 ft.lbs; p < 0.05). The mean force output per MVC also increased during exercise following intermittent cuff occlusion (no occlusion 174 +/- 21 ft.lbs vs cuff occlusion 199 +/- 13 ft.lbs; p < 0.05). In a second set of experiments, we found a 3 to 4 fold hyperemic blood flow following cuff occlusion. These data suggest that brief periods of cuff occlusion/reperfusion may increase repetitive MVC force output by skeletal muscle. Although further study is needed to fully understand the effects of occlusion/reperfusion on skeletal muscle force output, we hypothesize that, in part, this putative effects is secondary to the hyperemic blood flow which follows cuff occlusion.

Adult↗
PubMed1997

Comparison of changes in respiratory function and exercise oxygen uptake with losartan versus enalapril in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

In congestive heart failure (CHF), some of the effects of angiotensin-converting enzyme (ACE) inhibitors, such as an increase in exercise oxygen uptake (VO2), are mediated through prostaglandins. Angiotensin (AT1) receptor blockers apparently do not share potentiation of this biosystem. We tested whether losartan improves exercise VO2 in CHF and if the effect is the same as for enalapril. Sixteen men with CHF and 8 volunteers, all nonsmokers and not taking ACE, AT1 receptor, or cyclooxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plus aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatments. Pulmonary function and VO2 were assessed at the end of each treatment. In CHF, losartan and enalapril caused a similar improvement of VO2 and exercise tolerance, which was absent in controls and was counteracted by aspirin (prostaglandin inhibition) when obtained with enalapril and not with losartan. While on enalapril, we also detected an increase in the diffusing lung capacity for carbon monoxide, which correlated with changes in VO2 and was antagonized by aspirin, suggesting the possibility that a prostaglandin-mediated functional improvement of the alveolar capillary membrane contributes to the rise in VO2. Thus, losartan is as effective as enalapril for exercise VO2 and exercise tolerance, but the mechanism seems to be dissociated from a prostaglandin biosystem activation. Losartan may represent an advancement in CHF because its efficacy on VO2 is similar to that of enalapril, but is not antagonized by aspirin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Evidence of multifocal activity of coronary disease in patients with acute myocardial infarction.

BACKGROUND: Destabilization of the fibrous cap facilitates plaque rupture, thrombus formation, and myocardial infarction. Because systemic stimuli, such as lipoproteins, infectious agents, and autoantigens, may incite this reaction, one may wonder whether disruption mechanisms are only local or systemic and infarction is caused by an arbitrary plaque event or by a systemic, acute activity of the coronary disease. METHODS AND RESULTS: Early (3 to 5 days) and late (1 month) peri-infarction coronary angiographic data in 23 patients with first infarction were compared with that in 23 similar patients, with angiography performed because of stable angina and repeated after 1 month before angioplasty. Nonculprit lesion changes at the narrowest point defined progression or regression when exceeding 0.27 mm. In patients with recent infarction we found that 16 had progression, 4 had regression, 1 had both, 2 were steady (values in patients with stable angina being 2 [P<.0011, 1 [NS], 0 [NS], and 20 [P<.001]); 27 lesions were infarct related; 17 of the 45 nonculprit lesions progressed and 5 regressed (values in stable angina being 2 [P<.001] and 1 [P<.05] out of 78); minimal diameter reduction of progressing stenoses averaged 0.39 mm; lumen increase of regressing lesions averaged 0.30 mm; 3 patients developed interim rest angina associated with progression of a nonculprit lesion. CONCLUSIONS: A greater proportion of subjects and lesions with progression or regression (in infarction versus stable angina) supports the hypothesis that infarction is a hallmark of systemic coronary disease activity. Changes might vary according to the "maturation" stage of an atheroma, and maximal expression would be at the level of the offending plaque. Shrinkage, thrombolysis, or vascular remodeling would determine the residual plaque morphology.

Analysis of Variance↗
PubMed1997

Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin.

BACKGROUND: KII ACE, the enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the lungs; its blockade reduces exposure to angiotensin II and enhances exposure to prostaglandins generated by local kinin hyperconcentration. Our hypothesis is that ACE inhibitors improve pulmonary function in chronic heart failure (CHF) by readjusting lung vessel tone and permeability or alveolar-capillary membrane diffusion. METHODS AND RESULTS: In 16 CHF patients and 16 normal volunteers or mild untreated hypertensives, pulmonary function and exercise tests with respiratory gas analysis were assessed on placebo, enalapril (10 mg BID), enalapril plus aspirin (325 mg/d), or aspirin, in random order and double blind, for 15 days each. In CHF, enalapril increased pulmonary carbon monoxide diffusion (DLCO), oxygen consumption (VO2), and exercise tolerance and reduced the ratio of dead space to tidal volume (VD/VT) and the ventilatory equivalent for carbon dioxide production (VE/VCO2). On enalapril, VO2 (r = .80, P < .0001) and VD/VT (r = -.69, P = .003) changes from placebo correlated with those in DLCO. These effects were inhibited by aspirin and were absent in control subjects. In 8 additional patients, hydralazine-isosorbide dinitrate, as an alternative treatment for reducing pulmonary capillary wedge pressure (PCWP) and increasing exercise capacity, were more effective than enalapril for the PCWP but did not affect DLCO and VE/VCO2; amelioration in VO2 and VD/VT was unrelated to DLCO and was not modified by aspirin. CONCLUSIONS: ACE inhibition improved pulmonary diffusion in CHF. Hydralazine-isosorbide dinitrate failed to provide this result. Counteraction by aspirin, a prostaglandin inhibitor, bespeaks prostaglandin participation while on enalapril that might readjust capillary permeability or alveolar-capillary membrane diffusion.

Aged↗
PubMed1997

Changes in pulmonary venous return during head-up tilting in man.

1. In a supine position, the heart fills to close to the limits of pericardial constraint and the pericardium may act to redistribute central blood volume from the left side of the heart back to the more compliant lung. 2. We probed whether, and through which mechanisms, a redistribution of blood from the lungs to the left heart occurs during vertical displacement and compensates for reduced venous return. 3. We investigated 16 normal volunteers with Doppler-echocardiography during 20 degrees, 40 degrees and 60 degrees head-up tilting. Tilting was stopped at 10 min in 10 subjects (group 1) and at 45 min in 6 subjects (group 2). 4. At 10 min we observed a reduction in right ventricular diastolic dimension and left ventricular end-diastolic pressure, as estimated by the difference between the duration of the pulmonary venous flow during atrial contraction (Z wave) and that of the mitral A wave. We also recorded a decrease during systole (X wave) and an increase during diastole (Y wave) of the pulmonary venous forward flow velocity. These variations were evident at 20 degrees and became progressively greater with increasing degrees of tilting. In group 2, changes at 10 min and at 45 min for any degree of displacement were similar. 5. A decrease in right ventricular dimensions (ventricular interdependence) and underfilling of the lung compartment due to volume redistribution to the periphery (diminished lung contribution to pericardial constraint) augment compliance within the pericardial space, reduce downstream pressure for pulmonary venous return and move the pulmonary venous flow predominantly to ventricular diastole, allowing diastolic filling. 6. During head-up tilting a favourable interaction between heart and lungs increases compliance within the pericardial space and facilitates redistribution of blood from the lungs, resulting in a sustained compensation for the reduced venous return.

Adult↗
PubMed1997

[Biventricular-pulmonary interaction as the prime mechanism in the adaptation of the human heart to orthostatic posture].

The purpose was to identify the basic circulatory adjustments to the erect position in man and what the role may be of the heart-lung coupling. Requirements for this study are that: subjects be normal, changes in posture be gradual; pulmonary venous flow, ventricular filling and output be assessed; the methods be noninvasive. In 10 normal men (mean age 34 +/- 8 years) the flow pattern in the right upper pulmonary vein and through the atrioventricular mitral valve, and the right and left ventricular (RV and LV) end-diastolic dimensions were assessed with Doppler echocardiography, in the supine position, after 20, 40 and 60 degrees tilting for 10 min. At 20 degrees displacement: blood pressure, heart rate, stroke volume and LV dimension did not change: RV dimension reduced: pulmonary venous forward flow velocity diminished during systole (X wave) and rose in diastole (Y wave); E wave velocity of the mitral flow and the E/A ratio reduced (consistent with a lower atrioventricular pressure gradient); difference between duration of the pulmonary venous flow reversal during atrial contraction (Z wave) and duration of the mitral A wave (the difference is an index of LV end-diastolic pressure) also diminished, suggesting an improvement of LV compliance. Tilting at 40 and 60 degrees were associated with increase in heart rate and diastolic blood pressure; decrease in systolic blood pressure and stroke volume; reduction of diastolic dimension of both ventricles; some enhancement of the flow changes already described. X was related to stroke volume while supine (r = 0.75; p < 0.01) and not during tilting; at any level of tilting, X/Y ratio was inversely related to the E/A ratio and directly related to the difference in duration between Z and A. During vertical displacement, blood shifts from lungs to systemic circulation resulting in: contribution to replenishment of the arterial side of the circuit; enhancement in LV compliance, due to reduction of RV diastolic volume (interdependence) and pericardial constraint; facilitation and predominance of blood drainage for the lungs during ventricular diastole. Thus, the basic adaptation to erect positioning in man seems to be a mechanical one, mainly consisting of an interplay between heart and lungs. Increase in heart rate and vasoconstriction appear to be supportive mechanisms at more vertical postures.

Adaptation, Physiological↗
PubMed1997

[Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure].

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.

Aged↗
PubMed1997

[The antagonistic effect of aspirin on the expression of prostaglandin participation in the antihypertensive activity of ACE inhibitors].

ACE-inhibitors antagonize both angiotensin production and bradykinin breakdown, resulting in enhancement of vasodilating prostaglandin release. This provides an explanation for the experimental observation that cycloxygenase blockers (such as aspirin or indomethacin) may counteract the antihypertensive efficacy of the ACE-inhibitors; it may be also possible that hypertensive patients taking aspirin as an antiplatelet agent may fail to benefit from ACE-inhibition. This study was aimed at: evaluating the magnitude and incidence of the inhibitory phenomenon; defining the minimal aspirin dosage that produces an antagonistic effect, as well as the possible reasons for a different individual susceptibility. We have studied untreated patients with mild (10 cases, Group 1), moderate (16 cases, Group 2) or severe (26 cases, Group 3) hypertension. The ACE-inhibitor enalapril was used at doses of 10 mg bid (groups 1 and 2) or 20 mg bid (Group 3). Active drug treatment periods had a 5-day duration. A daily dose of aspirin of 100 mg had no effect on the antihypertensive efficacy of enalapril. On the contrary, when a dose of 300 mg was used, 60, 57 and 50% of patients in Group 1, 2 and 3, respectively, showed a > 20% restraint of the mean arterial pressure fall with enalapril (20% was the lower arbitrary limit for defining antagonism). Inhibition was independent of the sequence of drug administration. In these patients counteraction averaged 60, 70 and 90%, respectively. In them, and not in the remaining patients in each group, aspirin substantially attenuated the renin rise elicited by ACE-inhibition. These data suggest that: a dosage of 100 mg aspirin is devoid of any inhibitory effect; more that 50% of ACE inhibited patients are, at least in the short term, susceptible to the action of 300 mg aspirin, regardless of the severity of hypertension; counteraction is seemingly mediated through a prostaglandin inhibition and depends on the individual predominance of prostaglandin activation (also as a renin secretory stimulus) or angiotensin inhibition by the ACE-inhibitor.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

[Peri-infarct angiographic behavior of "non-culprit" coronary infarct lesions].

Because systemic factors, such as lipoproteins, autoantigens, infectious agents, may facilitate plaque rupture, thrombus formation and coronary occlusion, the question may arise of whether thrombosis be only a local plaque event or the consequence of an acute activity of the entire coronary tree. Taking changes at the narrowest point of non culprit lesions as reflecting progression or regression of the disease when > 0.27 mm, early (within a few days) and late (within 1 month) coronarographic findings in 23 patients with first infarction were compared with those of patients with stable angina, in whom coronary angiography was performed for diagnostic purposes and was repeated 1 month later, before angioplasty. Sixteen infarction patients had progression, 4 had regression, 1 had both, and 2 had steadiness; corresponding values in stable angina group were 2 (p < 0.001), 1 (NS), 0 (NS) and 20 (p < 0.001). In the infarction group, 17 out of the 45 non culprit lesions progressed and 5 regressed; corresponding figures in stable angina group were 2 (p < 0.001) and 1 (p < 0.05). Three of the infarction patients developed interim angina at rest that was associated with progression of a culprit lesion in each of them. These results support the hypothesis that in a number of cases infarction may not reflect an arbitrary plaque event but rather a systemic coronary disease activity with maximal expression at the level of the offending plaque.

Angina Pectoris↗
PubMed1997

[The influence of ACE inhibitors on urinary electrolyte secretion and the response to transitory hypovolemia in chronic heart failure].

Renin-angiotensin system promotes sodium and chloride retention, participates in the defense response to hypovolemia and, in congestive heart failure, contributes to edema formation and progression of the disease. We investigated whether ACE-inhibitors interfere with the action of the renin-angiotensin system on the nephron, and therefore with water and urinary electrolytes excretion. The interaction among renin-angiotensin system, diuretic treatment and urinary electrolytes was evaluated both during chronic treatment and in response to acute renin-angiotensin system activation as that observed after extracorporeal ultrafiltration-induced transient hypovolemia. Plasma renin activity and aldosterone, body fluid balance and urinary sodium, chloride and potassium concentrations were evaluated in 30 patients with congestive heart failure in NYHA II-III functional class, grouped according to whether long-term therapy did not include (Group I, n = 15) or included (Group II, n = 18) ACE-inhibitors. All parameters were evaluated at baseline and after a single session of extracorporeal ultrafiltration. At baseline, urinary output and urinary sodium and chloride concentrations were similar in the two groups, while urinary potassium concentration was lower in patients assuming ACE-inhibitors (Group II). Plasma renin activity was higher and aldosterone was lower in Group II than in Group I. After removal of similar amounts of plasma water by extracorporeal ultrafiltration, body weight decreased in both groups but the decrease was maintained in the following days only in Group II patients. A transient reduction (48 hours) of both plasma volume and urinary output was observed after ultrafiltration in both groups. Despite plasma renin activity and aldosterone increase, urinary electrolytes response to ultrafiltration was different in the two groups: sodium and chloride were reduced, and potassium did not change in Group 1 while, in Group II, sodium and chloride did not change and potassium excretion was significantly increased. In conclusion, chronic treatment with ACE-inhibitors does not enhance the excretion of sodium in congestive heart failure but just mitigates potassium loss. The role of these drugs becomes particularly relevant during acute renin-angiotensin system activation due to hypovolemia; in this setting ACE-inhibitors counteract sodium and chloride retention resulting in a potential hazard due to interference with the defence mechanisms toward hypovolemia, and an amplification of extracorporeal ultrafiltration efficacy by preventing edema recovery after its mechanical removal.

Aged↗
PubMed1996

Contribution of PO2, P50, and Hb to changes in arteriovenous O2 content during exercise in heart failure.

Arteriovenous O2 content (a-vCO2) differences increase during exercise in normal subjects through several mechanisms including PO2, O2 pressure at which hemoglobin (Hb) is half saturated with O2 (P50), and Hb concentration changes. The present study was undertaken to evaluate how much these biochemical changes are relevant to a-vCO2 difference through exercise in patients with heart failure. Twenty-seven patients with congestive heart failure [10 patients in functional class A (peak exercise O2 uptake >20 ml x kg-1 x min-1), 9 in class B (20-15 ml x kg-1 x min-1), and 8 in class C (15-10 ml x kg-1 x min-1)] underwent a cardiopulmonary exercise test with once-per-minute simultaneous blood sampling from the pulmonary and systemic arteries for determination of Hb, PO2, PCO2, pH, O2 content (CO2), Hb saturation and lactic acid (pulmonary artery only), and calculation of P50. Analysis of data was done at six exercise stages: the first at rest, the last at peak exercise, and the second to the fifth at one-, two-, three-, and four-fifths of O2 consumption increase. a-vCO2 difference at peak exercise was 14.3 +/- 2.1, 16.9 +/- 2.4, and 14.7 +/- 2.1 (SD) ml/dl in class A, B, and C patients, respectively. The contribution of Hb, P50, and PO2 changes to the increments of a-vCO2 difference during exercise was 21, 17, and 63%, respectively; the only interclass difference observed was for P50, which plays a greater role in a-vCO2 difference in class A. Hb changes act mainly at the arterial site, whereas P50 and PO2 act at the venous site. Hb increase was constant through the test, venous P50 increase was greater above anaerobic threshold, and venous PO2 reduction was most remarkable at the onset of exercise; in class C patients, no venous PO2 change was recorded in the second half of exercise. Thus a-vCO2 difference increase during exercise is notable in patients with heart failure but unrelated to the severity of the syndrome. Hb, P50, and, to the greatest degree, PO2 changes participate in the increment of a-vCO2 difference. In class C patients, the lack of PO2 reduction in the second half of exercise suggests the achievement of a "whole body critical venous PO2."

Anaerobic Threshold↗
PubMed1996

Influence of ACE Inhibition on Fluid Metabolism in Chronic Heart Failure and Its Pathophysiologic Relevance.

BACKGROUND: In congestive heart failure with water retention, subtraction of body fluid by ultrafiltration causes greater diuresis and clinical improvement in patients who are angiotensin-converting enzyme (ACE)-inhibited, suggesting an influence of ACE inhibitors on fluid metabolism. METHODS AND RESULTS: Patients with moderate congestive heart failure were subjected to ultrafiltration (around 2000 mL) and followed up for 3 months. Usual outpatient therapy, consisting of digoxin, furosemide, and ACE inhibitors (18 patients, group A) and of digoxin and furosemide only (18 patients, group B), was continued throughout the trial. Hemodynamics, renal function, body fluid and electrolytes, plasma norepinephrine, renin activity, aldosterone, and plasma volume were monitored. At 30 and 90 days after ultrafiltration, hormones, renal function, functional capacity (based on cardiopulmonary tests), and extravascular lung water (chest radiograph score) were determined. Soon after ultrafiltration, body weight, plasma volume, and diuresis were reduced (hypovolemia) and hormones were raised (reaction to hypovolemia). In the next 4 days, all these variables reverted to the pre-ultrafiltration values in group B; in group A diuresis and plasma volume recovered, body weight was still reduced, and hormones became lower than baseline. These changes persisted in the next 3 months. An early reduction of extravascular lung water continued long term in group A only, associated with increase of exercise tolerance time and oxygen uptake and decrease of the dead space/tidal volume ratio. CONCLUSIONS: In congestive heart failure, ACE inhibition persistently prevented fluid accumulation once the excess of body fluid had been withdrawn with a nonpharmacologic method, resulting in sustained improvement in functional capacity. Reduction in circulating norepinephrine, aldosterone, and renin did not seem to be the cause but the consequence of this action, whose mechanisms remain undefined.

Journal Article↗
PubMed1996

[Acetylsalicylic acid antagonism vs ACE inhibitor in congestive heart failure as shown by a diminished respiratory and exercise capacity].

Our hypothesis is that regulation of the lung vessel tone and microvascular permeability may be disrupted in chronic heart failure (CHF) and angiotensin converting enzyme (ACE) inhibition may contribute to their readjustment. This hypothesis is based on the fact that KII-ACE, the same enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the luminal surface of the lung vessels and its blockade in CHF may reduce their exposure to an excess of angiotensin II and augment the action of prostaglandins and nitric oxide (NO) deriving from local kinin hyperconcentration. We probed whether ACE-inhibitors influence the pulmonary function; this is peculiar of CHF; they act as KII- or ACE-blockers. Aspirin was utilized as a prostaglandin synthesis inhibitor. We investigated 16 CHF patients and 16 age- and sex-matched normal volunteers or mild untreated hypertensives. All were non-smokers, not taking ACE-inhibitors, aspirin or other cyclooxygenase inhibitors. Pulmonary function tests, exercise testing with respiratory gases and echocardiography were performed in the run-in and repeated at the end of placebo, enalapril (10 mg t.i.d.), enalapril plus aspirin (325 mg/day) and aspirin given in random order and double-blind fashion for 15 days each. Enalapril, as compared to placebo, caused an increase in mean voluntary ventilation (MVV) and alveolar-capillary diffusing capacity for carbon monoxide (DLCO) in CHF, that were counteracted by the addition of aspirin. Aspirin alone was not effective. Enalapril and aspirin were ineffective on the pulmonary function of controls. As to the functional capacity, enalapril increased exercise tolerance time, oxygen consumption (VO2p), minute ventilation (VEp) tidal volume (VTp) and reduced the ratio of volume of dead space gas (VDp) to VTp (VD/VTp), at peak exercise in CHF patients. These effects all were inhibited by the combination of aspirin and were not observed in controls. In CHF VO2p changes from placebo correlated with those in DLCO (r = 0.80, p < 0.0001) and not with those in ejection fraction. This correlation was abolished by aspirin and was not seen in controls. Variations in VD/VTp in CHF patients while on enalapril were related to those in DLCO (r = -0.69, p = 0.003). In CHF the ventilatory equivalent for carbon dioxide production per minute at 1 liter was diminished with enalapril and not in combination with aspirin. Derangements related to CHF are the substrate for benefits of ACE-inhibition on pulmonary function and exercise capacity. Pulmonary diffusion limitation is an important mediator of exercise impairment and its improvement with enalapril goes in parallel with VD/VT, MVV, VT, VE to VCO2 relationship and not with ejection fraction. These patterns reflect changes occurring within the lung that are not related to left ventricular function. The counteracting influence of aspirin on these affects bespeaks a substantial participation of prostaglandins that might readjust capillary permeability and lung interstitial fluid content or alveolar capillary membrane diffusing capacity.

Aged↗