Pulmonary Arteriolar Resistance Research Articles

RIGHT VENTRICULAR DYSFUNCTION AND TRICUSPID VALVE SURGICAL CORRECTION: ROOM FOR STRESS ECHOCARDIOGRAPHY?

Abstract We report the case of a 50–years–old young woman with multi–operated rheumatic valvular heart disease; aortic, mitral, and tricuspid commissurotomy (1994); aortic valve replacement with bioprosthesis for endocarditis (1998); mitro–aortic replacement with mechanical prosthesis and tricuspid valve plastic repair (1999); mitral valve replacement and re–do of tricuspid plastic repair (2003). Concomitant conduction pathway disease (BAV II type 1 and RBB). The patient was admitted in June 2023 for wet & warm NYHA IV right heart failure with severe peripheral congestion and ascites. On echocardiography: LV with systo–diastolic compression, EF 51%; normo–functioning aortic prosthesis; dilated (TDA 24 cm2), hypokinetic (TAPSE 9mm,S‘ 4 cm/s,FAC 25%) right ventricole (RV), with poor load adaptation (load adaptation index 16, RVCPI 108 mm*mmHg, ePAPI 1.1); torrential IT, caval plethora with systolization of hepatic venous flow. Medical therapy was initiated with intravenous bolus diuretics, nitroglycerin and inotropic support (dobutamine 2.5 y). In order to define the best therapeutic strategy in the persistence of torrential IT and RV dysfunction we performed: trans–oesophageal echocardiography, showed massive IT from ring dilatation and wide flail of the septal flap not suitable for edge–to–edge correction, total–body angioTC, with no relevant findings, right cardiac catheterization, which documented pulmonary pressure and arteriolar resistances within limits (wedge 12 mmHg,PAP25/15/18 mmHg,RAP 11 mmHg,PAPI 0. 9,RVSWI 4.8) with reduced cardiac index (2.14 l/min/cm2) and stress–echocardiography with dobutamine that showed presence of RV contractile reserve (FAC 28%>39%). In consideration of the functional properties of the tricuspid valve, absence of pulmonary hypertension and given the presence of RV contractile reserve, patient underwent tricuspid valve replacement surgery with a bioprosthesis (SJ Epic 27 mm) in mini–thoracotomy with smooth postoperative course. At 3 months follow–up showed functional recovery (NYHA II), with good prosthetic function and partial reverse remodeling of the RV (TDA 14 cm2, FAC of 30%). In conclusion, by documenting right ventricular contractile reserve, stress echocardiography proved to be an important aid in predicting absence of RV failure in the immediate post–surgical period, presenting attractive prospects in the assessment of RV functional reserve in patients undergoing to corrective tricuspidal surgery.

The Effects of Vasopressin and Oxytocin on the Fetoplacental Distal Stem Arteriolar Vascular Resistance of the Dual-Perfused, Single, Isolated, Human Placental Cotyledon.

Vasoactive agents administered to counter maternal hypotension at cesarean delivery may theoretically intensify the hypoxemic fetoplacental vasoconstrictor response and, hence, negatively impact transplacental oxygen delivery to the fetus. Yet, this aspect of their pharmacodynamic profiles is seldom mentioned, let alone investigated. We hypothesized that vasopressin, a potent systemic vasoconstrictor, and oxytocin, a uterotonic agent administered routinely at cesarean delivery, which, in contrast to vasopressin, possesses significant systemic vasodilator properties, would not influence distal stem villous arteriolar resistance. The dual-perfused, single, isolated cotyledon, human placental perfusion model was used to examine the resistance response of the fetoplacental circulation to oxytocin and vasopressin in placentae harvested from healthy women. Twelve of a total of 17 individual experiments were conducted successfully during which either oxytocin (n = 6) or vasopressin (n = 6) was introduced into the fetal reservoir in concentration increments of 10 M. Fetoplacental distal stem villous arteriolar perfusion pressure (FAP) was measured continuously. The fetal circuit concentration of either oxytocin or vasopressin was raised in a stepwise fashion from 10 to 10 M or 10 to 10 M, respectively. Both reservoirs were then purged of drug, after which 1-mL 1.0 mM 5-hydroxytryptamine (2.5 µM), an agent well known to manifestly increase fetoplacental distal stem villous arteriolar resistance, was introduced into the fetal circuit. A significant increase in FAP from baseline in response to exposure to 5-hydroxytryptamine confirmed that the fetoplacental vasoconstrictor response remained reactive. The primary outcome of this study was changes in FAP after incremental dosing of vasopressin and oxytocin. No changes in FAP were observed with either oxytocin or vasopressin regardless of the drug concentration tested. For each drug and concentration, a mean pressure change greater than ±10 mm Hg was excluded with 95% confidence. In contrast, 5-hydroxytryptamine significantly increased perfusion pressure in all 12 successful experiments. Oxytocin and vasopressin do not influence human fetoplacental distal stem villous arteriolar resistance. The neutral impact of vasopressin noted here is thus analogous to the reported negligible influence of the drug on human pulmonary arteriolar resistance. Neither drug seems likely to adversely influence the compensatory hypoxemic fetoplacental vasoconstrictor response.

Ginsenoside Rg1 attenuates hypoxia and hypercapnia-induced vasoconstriction in isolated rat pulmonary arterial rings by reducing the expression of p38.

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary arteriolar resistance. Pulmonary vasoconstriction has been proved to play a significant role in PAH. We previously reported that Panax notoginseng saponins (PNS) might attenuate hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV). In the present study, our specific objective was to investigate the role of ginsenoside Rg1, a major component of PNS, in this process and the possible underlying mechanism. The second order pulmonary rings isolated from the Sprague-Dawley rats were treated with different dosage of ginsenoside Rg1 at 8, 40, or 100 mg/L respectively, both before and during the conditions of hypoxia and hypercapnia. Contractile force changes of the rings were detected. Furthermore, SB203580, the selective inhibitor for p38 activation was applied to the rings. Pulmonary arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic conditions, and ginsenoside Rg1 was administered to detect the changes induced by p38. Under the hypoxic and hypercapnic conditions, we observed a biphasic pulmonary artery contractile response to the second pulmonary artery rings. It is hypothesized that the observed attenuation of vasoconstriction and the production of vasodilation could have been induced by ginsenoside Rg1. This effect was significantly reinforced by SB203580 (P<0.05 or P<0.01). The expression of p38 in the PASMCs under hypoxic and hypercapnic conditions was significantly activated (P<0.05 or P<0.01) and the observed activation was attenuated by ginsenoside Rg1 (P<0.05 or P<0.01). Our findings strongly support the significant role of ginsenoside Rg1 in the inhibition of hypoxia and hypercapnia-induced vasoconstriction by the p38 pathway.

Hemodynamics in the Cardiac Catheterization Laboratory of the 21st Century

There has been a striking evolution in the role of the cardiac catheterization laboratory over the past decades.1 In the 1950s and 1960s, hemodynamic assessment in the cardiac catheterization laboratory was essential for understanding the physiology and pathophysiology of patients with cardiovascular diseases. With the development of surgical interventions to treat patients with valvular and congenital heart disease, it became necessary for the cardiac catheterization laboratory to provide an accurate hemodynamic assessment, laying out a therapeutic road map. Nearly all patients who had open heart surgery underwent a complete hemodynamic catheterization before surgery. In the 1980s and 1990s, the evolution of 2-dimensional echocardiography and Doppler echocardiography provided an alternative noninvasive approach for the assessment of both cardiac anatomy and hemodynamics in patients with structural heart disease.2 By measuring blood flow velocities noninvasively, Doppler echocardiography was able to provide information on volumetric flow, intracardiac pressures, pressure gradients, and valve areas, as well as diastolic filling of the heart. Furthermore, noninvasive studies could be repeated easily, allowing the practitioner to follow the progress of his/her patient's condition longitudinally. At the same time, there was growing emphasis on coronary angiography for defining epicardial coronary disease with the subsequent development of interventional approaches for coronary disease with catheter-based therapies. As the major focus in the catheterization laboratory shifted to the diagnosis and treatment of the patient with acute and chronic coronary artery disease, the hemodynamic assessment of patients with structural heart disease was left to the noninvasive echocardiographic laboratory. As a consequence, many cardiac catheterization laboratories provided neither the training nor the expertise to assess hemodynamics properly. However, the advent of procedures such as balloon valvotomy, percutaneous valve implantation, and septal ablation has revived interest in structural heart disease and provided the invasive cardiologist with an armamentarium to treat patients who previously …

The Impact of Pulmonary Venous Hypertension on the Pulmonary Circulation in the Young

Pulmonary venous hypertension is a well-characterized cause of pulmonary hypertension in adults, but little is known regarding the relationship between left atrial pressure and pulmonary arteriolar resistance in the young. Also, in adults relief of pulmonary venous hypertension results in a marked fall in pulmonary arteriolar resistance, but this could be different in children because vascular changes are more severe in young patients than adults with mitral stenosis. We inspected records of children at Children's Hospital Boston having mitral balloon valvuloplasty, and patients ≤5 years old having mitral valve replacement, to determine (1) the relationship between left atrial pressure and pulmonary arterial pressure and resistance (n = 94 children, median age 17.8 months) and (2) how pulmonary arteriolar resistance changes after mitral valve replacement. The average indexed pulmonary arteriolar resistance was 7.8 ± 5.9 units and was unrelated to age but was positively related to left atrial pressure. There was great variability in pulmonary arteriolar resistance for any given left atrial pressure. Pulmonary arterial pressure (n = 16) and pulmonary arterial resistance (n = 9) were measured before and after mitral valve replacement (median = 29.4 months old). Despite preoperative indexed pulmonary arterial resistance of ≥5 units in 11 of 15 patients, postoperative pulmonary arterial pressure was substantially lower in all save three, and two patients with high pulmonary arterial pressure still had high left atrial pressure postoperatively (25 mmHg). We conclude that in young children, as in adults, pulmonary arterial resistance generally falls greatly with reduction in left atrial pressure.

Mitral stenosis acute pulmonary edema and rheumatic fever pneumonitis: A hypothesis to an old enigma

Mitral stenosis, although a heart defect extensively studied over the years, still presents many facts that are controversial, including some physiopathological details. Among these details, a persistent enigma is the occurrence of acute pulmonary edema, even as the first manifestation in patients without accentuated mitral stenosis. We conducted some studies in the eighties, involving 20 patients with isolated rheumatic mitral stenosis, in order to contribute to better understanding the pathophysiology of mitral stenosis. A significant correlation between the mitral valve area and the functional class according to the New York Heart Association (NYHA), the cardiac index, the mitral valve flow rate, the systemic vascular resistance, the total pulmonary resistance, and the resistance at the level of the stenotic valve was observed. No significant correlation was obtained between the mitral area and the pulmonary wedge pressure, the ventricular work the gradient through the mitral valve, and the pulmonary arteriolar resistance [1]. The work capacity measured in the cycloergometer was consistently low in all patients, no significant effect from the use of digitalis and the previous occupational activities was detected, and, there was no significant correlation between these data and the hemodynamic findings and the actual mitral valve area [2]. Pulmonary function tests were carried out in the preoperative period of cardiac surgery for the correction of mitral stenosis, and the mitral valve area values did not show any statistical correlation with the pulmonary functional parameters [3]. Before presenting the hypothesis it is interesting to emphasize three important aspects:

The relationship between pulmonary hemodynamics and chest X-ray findings in patients with sequelae of pulmonary tuberculosis

For better understanding of pathophysiological aspects of tuberculosis sequelae, we investigated the relationship between pulmonary hemodynamics and chest X-ray findings. One hundred and seven patients with sequelae of pulmonary tuberculosis were examined by the right cardiac catheterization, and pulmonary hemodynamic values were measured and calculated. Chest X-ray findings were defined and classified into the following five items. The items were emphysematous change; fibrosis, bronchiectasis and/or cavity (hereafter abbreviated as "fibrosis"); pulmonary resection and/or atelectasis; pleural thickening; and thoracoplasty. The extent of each finding was defined. We tried to describe chest X-ray findings by applying and categorizing these classifications and the extent to each case. First, we tried to estimate the grade of pulmonary hypertension by categorized X-ray findings. Further, we analyzed what kinds of findings were most influential on the increase of pulmonary artery mean pressure (PPA) and pulmonary arteriolar resistance (PAR). Secondly, we investigated whether PPA, cardiac index (CI) and PAR changed before and after oxygen administration. Thirdly, we analyzed what kind of X-ray findings most affected pulmonary hemodynamics under 100% oxygen administration for 10 minutes. The results were as follows: (1) Out of 107 cases, it was possible to predict PPA by categorized chest X-ray findings in 75 cases by Hayashi's first method of quantification, one of multivariative analyses. "Pleural thickening" was the most influential finding on the increase of PPA. "Fibrosis" was the most influential on the increase of PAR. (2) The values of PPA, CI and PAR decreased more after 100% oxygen administration than under room air breathing. Therefore, PAR was used as the index to estimate pulmonary hemodynamics under the condition of oxygen administration. (3) It was possible to measure PAR under oxygen administration (PARO2) in 72 cases. "Emphysematous change" was the most influential X-ray finding on the increase of PARO2. From these results, it was thought that pulmonary circulatory disorder in patients with tuberculosis sequelae was caused by the combination of various chest X-ray findings with the different extent. It was possible to predict pulmonary hypertension to a certain degree from categorized chest X-ray findings. It was suggested that "emphysematous change" less related to hypoxic pulmonary vasoconstriction than "fibrosis" and "pleural thickening" from the results of comparison among the partial correlation coefficients, which were associated with the increase of PAR under room air breathing and oxygen administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Investigation of pulmonary hemodynamics and chest X-ray findings in hypercapnic patients with pulmonary tuberculosis sequelae

We investigated pulmonary hemodynamics and chest X-ray findings to explore pathophysiological significance of chronic hypercapnia in patients with pulmonary tuberculosis sequelae. One hundred and seven patients underwent examinations of blood gases and right cardiac catheterization. The patients were divided into two groups, according to arterial carbon dioxide tension under room air breathing (PaCO2). Group I (n = 35) was defined as 45 Torr or lower of PaCO2, and Group II (n = 72) was the hypercapnic group whose PaCO2 was over 45 Torr. In addition, spirometry was done in 34 patients of Group I and 68 of Group II. First, the values of blood gases, spirometry and pulmonary hemodynamics were compared between the two groups. Secondly, between 22 of Group I and 50 of Group II, the values of pulmonary arteriolar resistance (PAR) before and after 100% oxygen breathing for 10 minutes were compared. These comparisons were made by exploratory data analysis. Lastly, we described in all cases with five items of chest X-ray findings and the extent of each finding we had defined. The items were emphysematous change; fibrosis, bronchiectasis, and/or cavity (hereafter abbreviated as "fibrosis"); lung resection and/or atelectasis; pleural thickening; and thoracoplasty. We explored the items of X-ray findings which may relate to hypercapnia by ridit (abbreviation for "relative to an identified distribution") analysis. The results were as follows. (1) Hypercapnic patients tended to have severer restrictive ventilatory impairment and hypoxemia. Under an even level of arterial oxygen tension (PaO2), tissue oxygenation was not poorer in Group II than in Group I. (2) Hypercapnic patients tended to have more unfavorable pulmonary hemodynamics. More than half of them had pulmonary hypertension defined as 20 mmHg or higher of pulmonary artery mean pressure (PAm). Under an even level of PaO2, PAm was higher in Group II. Although 34 patients of Group II showed PaO2 over 60 Torr, 23 of them had pulmonary hypertension. (3) PAR after oxygen breathing was more likely to decrease in Group II than in Group I. (4) As any mean ridit was standardized and adjusted to 0.5 in Group I, the maximum was the mean ridit of "pleural thickening" (= 0.67), next "fibrosis" (= 0.65) in Group II. The above two items of X-ray findings, in which each mean ridit was higher than in any other item, were more influential on hypercapnia. We conclude as follows. (1) Pulmonary hypertension is severer in hypercapnic patients with pulmonary tuberculosis sequelae; it may be mainly attributable to hypoxic pulmonary vasoconstriction. (2) An important cause of chronic hypercapnia may be pathological changes such as "pleural thickening" and "fibrosis" seen on the radiogram.

Does nocturnal hypoxia relate to acute exacerbation of chronic respiratory failure with right heart failure in late sequelae of pulmonary tuberculosis?

Thirty-eight patients with late sequelae of pulmonary tuberculosis (TB seq.) were studied to clarify whether or not nocturnal oxyhemoglobin desaturation (NOD) could relate to acute exacerbation of chronic respiratory failure (AE). All patients had been untreated with home oxygen therapy, because they were not severely hypoxic. We performed sleep studies, pulmonary function tests and arterial blood gas analysis and investigated past history about AE in each patient. Twelve patients had experienced AE with right heart failure and they were classified as CHF (congestive heart failure) group. The rest was classified as Non-CHF group. These two groups were compared as for each variables examined. There was no difference between the two groups in age, body weight, %VC, FEV1.0%, and awake PaO2. Awake PaCO2 was significantly higher in CHF group. Although no difference was observed in baseline SaO2, the degree of NOD was significantly greater in CHF group when evaluated by lowest SaO2 during sleep and 85% desaturation time (total time spent with SaO2 less than 85%). Moreover, 21 of Non-CHF and 6 of CHF were studied for cardiac parameters using right side cardiac catherization. While the differences of mean pulmonary arterial pressure and cardiac output between the two groups were not significant, pulmonary arteriolar resistance was higher in CHF group. We concluded that NOD in TB seq. had a major role in AE with right heart failure. We speculated that AE might be caused, at least partly, by pulmonary vasopressor response to recurrent NOD.

Relationship between signal intensity of blood flow in the pulmonary artery obtained by magnetic resonance imaging and results of right cardiac catheterization in patients with pulmonary disease

Electrocardiogram-gated spin-echo magnetic resonance (MR) images of the chest were obtained in five normal controls and 35 patients with pulmonary disease (11 chronic obstructive pulmonary disease, 6 pulmonary thromboembolism, 5 primary pulmonary hypertension, 4 interstitial pulmonary disease, 4 pulmonary hypertension with disturbance of portal circulation, and 5 other diseases) who underwent right cardiac catheterization. In transverse images at the level of the right main pulmonary artery (rPA) and sagittal images at the level through the midsternal line and the spinal chord, the signal intensity of blood flow in the rPA was quantitatively evaluated, and the correlations with the MR signal intensity of intravascular flow and the parameters of hemodynamics were studied. In diastole MR images of both normal controls and patients mostly showed a significant signal intensity of flowing blood, but in systole some patients demonstrated significant signals and visible flow images. In systolic MR images, the mean values of hemodynamic parameters (mean pulmonary arterial pressure (mPAP), pulmonary arteriolar resistance (PAR), and cardiac index (CI)) were abnormal in patients with significant signal intensity of flow compared with those in patients without sufficient MR signal. The signal intensity was not correlated with mPAP; however, it significantly increased as PAR increased, and it increased as CI decreased both in diastole and in systole. Especially in systole, there was good correlation between the signal intensity in transverse MR images and CI (r = -0.85, P less than 0.01) and between signal intensity in sagittal MR images and PAR (r = 0.90, P less than 0.01). These results suggest that significant flow signal in the rPA in systole has pathophysiological significance, and signal intensity is considered to be significantly affected by changes of PAR and CI. The signal intensity of blood flow in the rPA on MR images can be used as an index of the severity of right heart failure associated with pulmonary disease. MR imaging is a useful modality to evaluate pulmonary circulation disturbance because of its ability to assess blood flow in the pulmonary artery noninvasively without interference from other structures such as bone and normal lung.

Relation of pulmonary vascular response to pressure-flow relationship during incremental exercise in patients with chronic obstructive pulmonary disease (COPD)

Twenty-eight COPD patients underwent right heart catheterization while in clinically stable condition. Pulmonary vascular response to oxygen was evaluated by the percent change in pulmonary arteriolar resistance after 100% oxygen inhalation (% delta PAR), and its relation to the pressure-flow relationship during incremental exercise was assessed. Mean pulmonary arterial pressure (PPA) during exercise was plotted against the cardiac index (C.I.) from rest to maximal exercise in each patient. In most of the patients, the changes in PPA were nearly linear to the C.I. Therefore, a slope could be obtained from the regression equation in each patient. Patients were divided into two groups according to whether their % delta PAR was greater than 20 defined as a responder (RES), or less than five defined as a non-responder (N-RES). Seven out of 28 patients were RES, nine were N-RES, RES showed a higher %FEV1.0 level, C.I. and stroke volume index (S.I.) at maximal exercise, and a lower level of RV/TLC as well as slope. The slope correlated significantly with %DLCO (r = -0.724, p < 0.01), baseline PAR (r = 0.562, p < 0.01) and % delta PAR (r = -0.522, p < 0.01). These results suggest that the diminished pulmonary vascular bed, and the distensibility of pulmonary vessels, appear to contribute to the steepness of the slope and reduced % delta PAR in patients with COPD.

Effect of nifedipine on hemodynamics in precapillary pulmonary hypertension at rest and during exertion

The effect of sublingual nifedipine (20 mg) on haemodynamics at rest and during bicycle ergometry in supine position was assessed in 22 patients with precapillary pulmonary hypertension (obstructive form: n = 17, restrictive form: n = 2, combined obstructive-restrictive: n = 3). At rest nifedipine resulted in an increase of cardiac frequency from 85 to 89/min, during exercise from 109 to 120/min (P less than 0.05). Concomitantly the mean arterial blood pressure decreased significantly both at rest and during exercise. The mean pulmonary arterial pressure showed significant reduction from 42.9 to 36.2 mm Hg (P less than 0.0005) only during exercise. The total body vascular resistance at rest decreased by 21% (P less than 0.005), during exercise by 15% (P less than 0.1). Pulmonary arteriolar resistance at rest decreased by 9%, during maximum loading by 34% from 312 to 215 dyn X s X cm-5 (P less than 0.05). Nifedipine was shown to be a suitable agent for lowering right ventricular afterload in secondary pulmonary hypertension due to chronic lung disease. The beneficial effect at rest depends on the extent of the pulmonary arteriolar resistance and the mean pulmonary arterial pressure. However, during exercise conditions it can be observed in the majority of patients (93%). Due to the variable response haemodynamic assessment is required prior to routine use in order to establish patients with optimal response.

Sildenafil improves endothelial function in patients with pulmonary hypertension

Background Sildenafil has been shown to be effective in the treatment of pulmonary hypertension, and has favourable effects on endothelial function. Our hypothesis is that a part of the beneficial effects of sildenafil in patients with pulmonary hypertension is due to the improvement of the endothelial function. Methods Nine patients (seven females, age 67±9 years) with thromboembolic pulmonary hypertension were treated with sildenafil, at a mean dose of 150±75 mg/die. At baseline and after 6 months all patients underwent: right-heart catheterization, 6-min walking distance, and a study of endothelial function, including the measure of the flow-mediated vasodilation of the brachial artery, and the dosage of plasma levels of endothelin-1 and von Willebrand factor. Results During follow-up we found a significant reduction of mean pulmonary artery pressure and arteriolar resistances. Accordingly, the functional capacity improved (an average of+37 m). Sildenafil improved endothelial-dependent vasodilation and reduced plasma concentrations of endothelin-1 (from 4.5±0.6 to 3.1±0.7 pg/mL; p<0.0001) and von Willebrand factor (from 183.1±10.1 to 149.1±17.6 mU/mL; p<0.0001). Conclusion Improvement of the endothelial function may represents one of the mechanisms able to explain the favourable effects sildenafil has shown in patients with pulmonary hypertension.

Site of Coronary Sinus Drainage Does Not Significantly Affect Coronary Flow Reserve in Patients Long Term After Fontan Operation

This study was designed to investigate the impact of postoperative coronary sinus drainage pressure on coronary flow reserve (CFR) assessed by Doppler guidewire in patients long term after Fontan operation. Twenty-nine patients (median age, 17.4 years female, 11) at a median of 10.6 years after Fontan operation were examined with intracoronary Doppler guidewire during cardiac catheterization. Fourteen patients had coronary sinus (CS) drainage to the systemic venous atrium and 15 patients had CS drainage to the pulmonary venous atrium after Fontan operation. Median CS drainage pressure was significantly higher in systemic venous CS drainage compared to pulmonary venous CS drainage (11 vs 5 mmHg, p < 0.0001). Median CFR values for the right and left coronary artery did not differ significantly with respect to CS drainage. There was a positive correlation between coronary flow reserve and pulmonary arteriolar resistance (p < 0.05) in multivariate regression analysis. The site of coronary drainage into the systemic atrium or the pulmonary venous atrium did not significantly affect CFR. Our data do not support a surgical strategy of elective redirection of coronary sinus blood to a low-pressure compartment but support an early staged approach. The positive correlation between CFR and pulmonary resistance demands further evaluation.

Correlation between pulmonary vascular change and hemodynamics in patients with complete atrioventricular septal defect.

The study of the pulmonary vasculature in Taiwanese with atrioventricular septal defect has not been reported previously. This study investigated the correlation between pulmonary vascular change and hemodynamics in these patients. Ten children with complete atrioventricular defect, 8 of whom had Down syndrome, underwent open lung biopsy. Their age ranged from 8 months to 6 years (mean, 2 years 7 months). Cardiac catheterization was performed and the systolic pressures of pulmonary and systemic arteries were measured immediately before cardiopulmonary bypass (CPB) and immediately after cardiac repair in 9 patients, and expressed as a ratio of pulmonary to systemic systolic pressure (Pp/Ps). Medial hypertrophy and intimal proliferation were prominent in 7 patients with pulmonary hypertension. The alveolar wall muscular arteries and percent arterial medial thickness increased significantly with increasing post-repair Pp/Ps, preoperative Pp/Ps, pulmonary arteriolar resistance index and pre-CPB Pp/Ps (p < 0.02). The arteries present per 100 alveoli were inversely correlated with the above mentioned hemodynamic parameters (p < 0.02). The results of qualitative and quantitative analyses of the pulmonary vasculature in patients with complete atrioventricular defect correlated well with pre-and postoperative pulmonary arterial pressure and can be used to predict the postoperative pulmonary arterial pressure.

Comparison of the Acute Pulmonary Vasodilating Effect of Beraprost Sodium and Nitric Oxide in Congenital Heart Disease-Thailand Multicenter Study-

Congenital heart disease patients who have pulmonary hypertension (PH) require an evaluation for pulmonary vascular reactivity before surgical repair. In the present study the acute pulmonary vasodilating effects of 100% oxygen (O2), beraprost sodium (BPS) and 40 ppm inhaled nitric oxide (iNO) during cardiac catheterization were compared. There were 90 patients who underwent cardiac catheterization for evaluation of PH (mean age, 16.5+/-16 years). The baseline mean pulmonary artery (mPA) pressure was 69.6+/-14.8 mmHg and the pulmonary arteriolar resistance (Rpa) was 13.8+/-8.3 Wood unit m2. Change in pulmonary vascular reactivity was defined as a decrease in mPA or Rpa>20% from baseline. The response to 100%O2, iNO and BPS during cardiac catheterization was 84%, 72.7% and 64%, respectively. Pair comparisons among each hemodynamic parameter showed no difference between the acute vasodilating effect of BPS and iNO. In some patients BPS showed a stronger effect than iNO in lowering Rpa. BPS has a similar pulmonary vasodilating effect to iNO and can be used as an acute pulmonary vasodilating agent during cardiac catheterization with potential benefits over iNO.

Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure.

Chronic heart failure (CHF) may impair lung gas diffusion, an effect that contributes to exercise limitation. We investigated whether diffusion improvement is a mechanism whereby physical training increases aerobic efficiency in CHF. Patients with CHF (n = 16) were trained (40 min of stationary cycling, 4 times/wk) for 8 wk; similar sedentary patients (n = 15) were used as controls. Training increased lung diffusion (DlCO, +25%), alveolar-capillary conductance (DM, +15%), pulmonary capillary blood volume (VC, +10%), peak exercise O2 uptake (peak VO2, +13%), and VO2 at anaerobic threshold (AT, +20%) and decreased the slope of exercise ventilation to CO2 output (VE/VCO2, -14%). It also improved the flow-mediated brachial artery dilation (BAD, from 4.8 +/- 0.4 to 8.2 +/- 0.4%). These changes were significant compared with baseline and controls. Hemodynamics were obtained in the last 10 patients in each group. Training did not affect hemodynamics at rest and enhanced the increase of cardiac output (+226 vs. +187%) and stroke volume (+59 vs. +49%) and the decrease of pulmonary arteriolar resistance (-28 vs. -13%) at peak exercise. Hemodynamics were unchanged in controls after 8 wk. Increases in DlCO and DM correlated with increases in peak VO2 (r = 0.58, P = 0.019 and r = 0.51, P = 0.04, respectively) and in BAD (r = 0.57, P < 0.021 and r = 0.50, P = 0.04, respectively). After detraining (8 wk), DlCO, DM, VC, peak VO2, VO2 at AT, VE/VCO2 slope, cardiac output, stroke volume, pulmonary arteriolar resistance at peak exercise, and BAD reverted to levels similar to baseline and to levels similar to controls. Results document, for the first time, that training improves DlCO in CHF, and this effect may contribute to enhancement of exercise performance.

Computational fluid dynamics in the evaluation of hemodynamic performance of cavopulmonary connections after the norwood procedure for hypoplastic left heart syndrome

Objective Computational fluid dynamics have been used to study the hemodynamic performance of surgical operations, resulting in improved design. Efficient designs with minimal energy losses are especially important for cavopulmonary connections. The purpose of this study was to compare hydraulic performance between the hemi-Fontan and bidirectional Glenn procedures, as well as the various types of completion Fontan operations. Methods Three-dimensional models were constructed of typical hemi-Fontan and bidirectional Glenn operations according to anatomic data derived from magnetic resonance scans, angiocardiograms, and echocardiograms. Boundary conditions were imposed, and fluid dynamics were calculated from a mathematic code. Power losses, flow distribution to each lung, and pressures were measured at three predetermined levels of pulmonary arteriolar resistance. Models of the lateral tunnel, total cavopulmonary connection, and extracardiac conduit completion Fontan operations were constructed, and power losses, total flow distribution, vena caval and pulmonary arterial pressures, and flow distribution of inferior vena caval return were calculated. Results The hemi-Fontan and bidirectional Glenn procedures performed nearly identically, with similar power losses and nearly equal flow distributions to each lung at all levels of pulmonary arteriolar resistance. However, the lateral tunnel Fontan procedure as performed after the hemi-Fontan operation had lower power losses (6.9 mW, pulmonary arteriolar resistance 3 units) than the total cavopulmonary connection (40.5 mW) or the extracardiac conduit (42.9 mW), although the inclusion of an enlargement patch toward the right in the total cavopulmonary connection was effective in reducing the difference (10.0 mW). Inferior vena caval flow to the right lung was 52% for the lateral tunnel, compared with 19%, 30%, 19%, and 15% for the total cavopulmonary connection, total cavopulmonary connection with right-sided enlargement patch, extracardiac conduit, and extracardiac conduit with a bevel to the left lung, respectively. Conclusions According to these methods, the hemi-Fontan and bidirectional Glenn procedures performed equally well, but important differences in energy losses and flow distribution were found after the completion Fontan procedures. The superior hydraulic performance of the lateral tunnel Fontan operation after the hemi-Fontan procedure relative to any other method may be due to closer to optimal caval offset achieved in the surgical reconstruction.

Mortality after partial left ventriculectomy in relation to contraindications for heart transplantation

OBJECTIVE:To analyze the impact of the contraindications for heart transplantation in mortality and survival time after partial left ventriculectomy. METHOD: A prospective clinical study of a cohort of 43 patients submitted to partial left ventriculectomy, in whom there were contraindications for heart transplantation was performed. The following contraindications were analyzed: psychological, sociocultural, age of 65 years of age and older, elevated pulmonary arteriolar resistance and pulmonary arterial hypertension and the refusal or not for transplantation. These variables were tested for association with postoperative mortality and survival time after partial left ventriculectomy. Statistical analysis included the Chi-square test, Kaplan-Meier survival analysis, non-parametric log-rank test, Cox regression model, 95% confidence intervals and p values (significant if less than 0.05). RESULTS: Higher postoperative mortality rates for partial left ventriculectomy were found when the following contraindications of heart transplantation were present preoperatively: poor sociocultural conditions (p = 0.037), psychological disturbances (p = 0.037) and in patients who accepted heart transplantation even when counseled against this procedure (p = 0.017). Survival time was significantly shortened in the presence of psychological disturbances (p = 0.0466), in patients older than 65 years (p = 0.0397) and in those who did not accept heart transplantation (p = 0.0306). Elevated pulmonary arteriolar resistance and pulmonary arterial hypertension were not associated with higher mortality rates or shortened survival time. CONCLUSION: Some of the contraindications for heart transplantation adversely affected the mortality and survival time after partial left ventriculectomy, thus revealing the ineffectiveness of this alternative procedure in this subset of patients.

PREVENTION OF α-NAPHTHYLTHIOUREA-INDUCED PULMONARY EDEMA WITH FRUCTOSE-1,6-DIPHOSPHATE

Neutrophil-derived oxygen free radicals have been implicated in the pathogenesis of noncardiogenic pulmonary edema. Fructose-1,6-diphosphate (FDP) has been shown to inhibit oxygen free radicals production by activated neutrophils. Thus, we investigated whether FDP would attenuate formation of pulmonary edema in anesthetized dogs injected with α -naphthylthiourea (ANTU). Hemodynamic studies involved measurements of left ventricular systolic and end-diasystolic pressures (LVSP and LVEDP), pulmonary artery pressure (PaP), heart rate (HR), and cardiac output (CO). Mean wet weight to dry weight ratios of lung tissue samples were calculated. Following baseline measurements, dogs were injected intravenously (IV) with ANTU 5 mg / kg (n = 16) and 10 mg / kg (n = 8) and half of the dogs were randomly selected to receive 75 mg / kg FDP (10%) and subsequent infusion of 7 mg / kg / min. The rest were given 0.9% NaCl in the same manner. Four hours after ANTU administration, the animals were euthanatized. Except for decline in the CO (nonsignificant), no significant changes in systemic hemodynamics within and between the groups were noted. In the FDP group, PaP and pulmonary arteriolar resistance (PaR) remained unchanged. In the saline group, PaP increased from 12.5 ± 2.44 to 21.8 ± 3.14 mm Hg (P <. 001) and PaR from 166 ± 29 to 468 ± 74 dynes · cm / sec 5 (P <. 005). During the study LVDEP, PaO 2, PaCO 2, and hematocrit did not change significantly within and between the groups. The lungs mean wet weight to dry weight ratios for the sham-operated dogs were 4.20 ± 0.41, for the FDP group 4.32 ± 0.59 and 6.22 ± 1.37 for the saline group (P <. 0005). These data indicate that FDP protected the lung from ANTU-induced injury.