Exercise tolerance assessed by unilateral pulmonary artery occlusion test before and after pulmonary resection

Pre- and post-operative exercise tests and unilateral pulmonary artery occlusion tests were performed on 15 surgical patients with pulmonary cancer. The relationship between these cardio-pulmonary parameters and exercise tolerance was studied, and pulmonary functional resectability was discussed. Pre- and post-operative anaerobic thresholds correlated with driving pressure (D.P: pulmonary artery pressure--pulmonary wedge pressure), and the pulmonary vascular-resistance index (PVRI). From the regression line and post-operative energy metabolic ratio, the standard limitation point of pulmonary resection can be estimated, (D.P = 22.6 mmHg PVRI = 621 dyne.sec.cm-5.m2). These data yielded a pulmonary pressure = 33.4 mmHg, total pulmonary vascular resistance index = 885 dyne.sec.cm-5.m2. These correlations were obtained because D.P and PVRI indicate the over all condition of the pulmonary vascular bed, gas exchange, ventilation and cardiac function. These data were in close agreement with previous results pertaining to the above indications. Unilateral pulmonary occlusion testing predicted the post-operative exercise tolerance of patients undergoing lung resection.     

Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension

BACKGROUND: Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS: Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS: Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS: This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.     

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion

Regional pneumoconstriction induced by alveolar hypocapnia is an important homeostatic mechanism for optimization of ventilation-perfusion matching. We used positron imaging of 13NN-equilibrated lungs to measure the distribution of regional tidal volume (VT), lung volume (VL), and lung impedance (Z) before and after left (L) pulmonary artery occlusion (PAO) in eight anesthetized, open-chest dogs. Measurements were made during eucapnic sinusoidal ventilation at 0.2 Hz with 4-cmH2O positive end expiratory pressure. Right (R) and L lung impedances (ZR and ZL) were determined from carinal pressure and positron imaging of dynamic regional VL. LPAO caused an increase in magnitude of ZL relative to magnitude of ZR, resulting in a shift in VT away from the PAO side, with a L/R magnitude of Z ratio changing from 1.20 +/- 0.07 (mean +/- SE) to 2.79 +/- 0.85 after LPAO (P < 0.05). Although mean L lung VL decreased slightly, the VL normalized parameters specific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% total lung capacity also increased after PAO. We conclude that PAO results in an increase in regional lung Z that shifts ventilation away from the affected area at normal breathing frequencies and that this effect is not due to a change in VL but reflects mechanical constriction at the tissue level.     

Flow-dependent pulmonary vasodilation during acute unilateral pulmonary artery occlusion in Jungle Fowl

Giant Jungle Fowl previously were shown to be highly resistant to the onset of pulmonary hypertension syndrome (PHS, ascites) under conditions that induce a substantial incidence of PHS in broiler chickens. In the present study, lightly anesthetized, clinically healthy 12- to 13-wk-old male Giant Jungle Fowl maintained a lower respiratory rate, a similar hematocrit, and superior arterial blood gas values when compared with 6-wk-old male broilers. Giant Jungle Fowl weighed less than broilers (1,860 +/- 19 vs 2,788 +/- 63 g, respectively) and had equivalent absolute values for pulmonary arterial pressure, cardiac output, and pulmonary vascular resistance. Acute unilateral pulmonary artery occlusion in Giant Jungle Fowl doubled the pulmonary vascular resistance and forced the right ventricle to propel a sustained 60% increase in blood flow through the vasculature of the unoccluded lung. A transient increase in pulmonary arterial pressure initially was required to overcome the vascular resistance of the unoccluded lung; however, flow-dependent vasodilation gradually reduced the pulmonary vascular resistance and permitted pulmonary arterial pressure to return toward control levels. Unilateral pulmonary artery occlusion also triggered an immediate reduction in the partial pressure of oxygen in arterial blood, and the gradual return of pulmonary arterial pressure toward control levels did not eliminate this ventilation-perfusion mismatch, which has been attributed to blood flowing too rapidly through the unoccluded lung to permit diffusive gas equilibration. The inherent capacity for flow-dependent pulmonary vasodilation may reduce the susceptibility of Giant Jungle Fowl to PHS by reducing the increment in pulmonary arterial pressure required to propel an elevated blood flow through the lungs.     

Hemodynamics in an arterial union--simulation study on therapeutic unilateral vertebral artery occlusion

Hemodynamic changes following unilateral vertebral artery (VA) occlusion were investigated in a rat model. The left carotid artery was resected and anastomosed to the right side in an end-to-side fashion to create a half-ring bypass. The distal side of the bypass was regarded as a union of VAs. Changes in the geometry, histology and hemodynamics in the union were investigated after the recipient artery was ligated. Intimal thickening was most prominently observed in the recipient arterial segment distal to the ligation site, where the lumen was obliterated. However, the portion of the lumen within 2.6 +/- 0.6 (mean +/- s.d.) mm, a distance of 2.9 +/- 0.6 times the internal diameter from the union, was not obliterated. The angle of the union was positively related to the length of this residual lumen. The results of this study explain some of the pathogenesis in unsuccessful aneurysmal thrombosis or brain stem infarction after therapeutic unilateral VA occlusion.     

Assessment of right ventricular function and interstitial fibrosis in idiopathic dilated cardiomyopathy: hemodynamic correlates and prognostic value

BACKGROUND: Right ventricular (RV) function and morphometric quantitation of interstitial fibrosis in idiopathic dilated cardiomyopathy (IDC) have not been the subject of specifically designed clinical observations. In particular, their role in routine assessment and prognostic evaluation of patients (pts) with IDC remains to be settled. METHODS: Eighty-one consecutive IDC patients (63 M, 18 F; mean age 52 +/- 11 yrs) with left ventricular (LV) systolic dysfunction (angiographic ejection fraction - EF - < 55%), normal coronary arteries and no histologic evidence of myocarditis were studied. Cardiac catheterization and endomyocardial biopsy (EMB) were routinely performed in all cases. RV volumes and EF were obtained by angiography according to Ferlinz' method and interstitial fibrosis was quantitated by computer-assisted morphometric analysis. These data were analyzed in order to study correlations with hemodynamic parameters and to assess their prognostic value in a long-term follow-up. RESULTS: In the study population, right ventricular EF was significantly lower than in normal controls (35 +/- 11% vs 53 +/- 6%, p < 0.0001) and showed a significant positive correlation with LV EF (r = 0.54; p < 0.0001), and a weak but significant negative correlation with fibrosis (r = -0.29; p = 0.03). RV volumes, but not EF, were significantly related to mean pulmonary pressure. At multivariate analysis, RV end-diastolic volume (EDV) and EF were the two independent predictors of severe heart failure (NYHA class III-IV). After a mean follow-up of 64 +/- 36 months, 20 pts died and 9 had heart transplantation, for a 63% transplant-free survival rate (TFS). Multivariate analysis identified three independent predictors of TFS: LV stroke work index (p < 0.0001), RV stroke work index (p = 0.02) and RV EDV (p = 0.03). Fibrosis was predictive of survival only in the subgroup with LV EF < 20%. CONCLUSIONS: Assessment of RV function provides useful information in the evaluation of hemodynamic profile and prognosis of pts with IDC. Quantitation of interstitial fibrosis by morphometry provides little additional data.     

Evaluation of hemodynamic parameters in patients with right ventricular infarction during rehabilitation

Hemodynamic data in 43 patients with right and left ventricular infarction and 39 with left ventricular infarction were compared. Right atrial pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, left ventricular end-diastolic pressure before and after ventricular angiogram, cardiac index, left ventricular stroke volume index, right ventricular stroke work index were evaluated, as well as ratios of right atrial and pulmonary capillary wedge pressure, right and left ventricular end-diastolic pressure, right ventricular end-diastolic and pulmonary capillary wedge pressure, left ventricular ejection fraction calculated from left ventricular angiogram, Berentey's score, and cardiac volume index. Using ONEWAY analysis there was no significant difference between the two groups in period of rehabilitation. In 15 patients with right ventricular infarction regression of ECG changes was observed in lead V3R also without significant influence on hemodynamic data.     

Sustained right ventricular dyskinesis complicated by right ventricular infarction

We encountered a 66-yr-old man with acute left inferior and right ventricular infarction. Tomographic radionuclide ventriculography and Fourier analysis clearly demonstrated reduced wall motion in the inferior walls of both ventricles and markedly delayed phase angles in the inferior right ventricular segment, indicating dyskinesis, which was confirmed by two-dimensional echocardiography and contrast right ventriculography. Four years later, right ventricular dyskinesis was still present and corresponded to a right ventricular perfusion defect on 99mTc-labeled tetrofosmin tomogram. Right ventricular imaging with tomographic radionuclide ventriculography with Fourier analysis and 99mTc-labeled myocardial tomography demonstrates that, even after improved global function and hemodynamics, right ventricular dyskinesis related to right ventricular perfusion defect can be sustained for several years. Thus, these imaging techniques may contribute to diagnosing right ventricular infarction and investigating the pathophysiology.     

Coronary reserve and right ventricular function in awake newborn lambs with persistent right ventricular hypertension

Right ventricular function curves as measured by right ventricular stroke work were normal in all control lambs, whereas three of five lambs with banded pulmonary arteries had relatively flat curves. Left ventricular function was similarly normal in the control group as compared to a near zero slope function curve in the banded group. Regional myocardial blood flow to the septum and right and left ventricles was similar in control and banded lambs. At rest right ventricular coronary vascular resistance was lower in the banded than in the control group and decreased in both groups during both isoproterenol and dextran stress states. In general, both groups had a similar ratio of right to left ventricular oxygen supply to demand ratio. These results show first that there is minimal, if any, biventricular functional reserve in lambs with persistent right ventricular hypertension, and second, that there is substantial coronary vascular reserve in both normal and banded groups.     

Right ventricular function after aorto-coronary bypass surgery: with relation to the site of right coronary artery occlusion

Postoperative right ventricular function was evaluated serially by thermodilution techniques (REF-1, Edwards Laboratories) in patients who underwent aorto-coronary bypass surgery with uneventful postoperative recovery. The patients were divided into three groups depending on the location of critical stenosis of the right coronary artery. The stenosis was proximal to the right ventricular branch in group I (n = 13), distal to the right ventricular branch but proximal to the acute marginal branch in group II (n = 13) and distal to the acute marginal branch in group III (n = 11). Control (n = 20) consisted of the patients with no significant stenosis of the right coronary artery. Cardiac index, intracardiac pressures and amount of cathecolamin used during postoperative course showed no significant differences among the groups including control. With the use of cathecolamine after surgery, right ventricular ejection fraction (RVEF) rose and right ventricular volumes (RVEDV and RVESV) decreased in all the groups except for group I. These values in group I were unchanged. Thus, there were significant differences in RVEF, RVEDV and RVESV between group I and control. These results mean that right ventricular dysfunction may remain even long after occlusion of the proximal right coronary artery.     

Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing

Septic shock is a dangerous condition with high mortality rates. In sepsis, the inducible form of nitric oxide (NO) synthase is induced, releasing high amounts of NO. Glucocorticoids have potent anti-inflammatory properties and are very effective in inhibiting the induction of this enzyme if administered before the shock onset. It is known that glucocorticoid receptor (GR) has critical cysteine residues for steroid binding in its hormone-binding and DNA-binding domains. It has also been reported that NO reacts with ---SH groups, forming S-nitrosothiols. Therefore, we examined the potential effect of NO on the ligand-binding ability of GR. NO donors (S-nitroso-acetyl-DL-penicillamine, S-nitroso-DL-penicillamine, or S-nitroso-glutathione) decreased, in a time- and dose-dependent manner, the binding of [3H]triamcinolone to immunoprecipitated GR from mouse L929 fibroblasts. The nonnitrosylated parent molecules, N-acetyl-DL-penicillamine, and reduced gluthatione were without effect. Scatchard plots revealed that the number of ligand binding sites and Kd were reduced (50%) by NO donors. Western blot analysis ruled out the possibility that dissociation of GR/heat shock protein 90 heterocomplex or decrease in GR protein would account for the inhibitory effect of NO. Decreased ligand binding to GR was found when NO donors were incubated with intact fibroblasts. Incubation with NO donors also decreased the steroid-induced reduction in [3H]uridine incorporation into RNA. All of these NO effects were inhibited by the thiol-protecting agent dithiothreitol. Therefore, S-nitrosylation of critical ---SH groups in GR by NO with consequent decreases in binding and affinity may be the mechanisms which explain the failure of glucocorticoids to exert their anti-inflammatory effects in septic shock.     

Cardio-pulmonary function during acute unilateral occlusion of the pulmonary artery in broilers fed diets containing normal or high levels of arginine-HCl

Cardio-pulmonary function was measured in male broilers reared on diets formulated to contain 1.5% arginine (NORMAL group) or 2.5% arginine (ARGININE group). A snare placed around the right pulmonary artery permitted acute shunting of the entire cardiac output (CO) through the left pulmonary artery, resulting in sustained increases in blood flow (BF) through the left lung in both groups. The unilateral increase in BF was accompanied by sustained increases in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in the NORMAL group. However, following initial transient increases in PAP and PVR in the ARGININE group, subsequent pulmonary vasodilation gradually reduced PVR, and thus PAP, in spite of the ongoing elevation of BF through the left lung. The capacity of the pulmonary vasculature in the ARGININE group to accommodate an increased BF at a normal PAP accounts for the previously reported lower incidence of pulmonary hypertension syndrome (PHS, ascites) in cold-stressed broilers fed supplemental dietary arginine. Hypoxemia and respiratory acidosis ensued rapidly in both groups after tightening the pulmonary artery snare, in spite of a compensatory increase in the respiratory rate. The gradual return of PVR and PAP to presnare levels in the ARGININE group did not eliminate the concurrent ventilation-perfusion mismatch caused by the increased rate of BF through the left lung. Tightening the pulmonary artery snare caused mean systemic arterial pressure (MAP) to drop from control levels of approximately 98 mm Hg to sustained hypotensive levels of approximately 65 mm Hg in both groups. This systemic hypotension was caused by decreases in CO and total peripheral resistance (TPR). The reduction in CO were caused by reduction in stroke volume (SV) rather than heart rate (HR), suggesting that acutely tightening the pulmonary artery snare increased PVR sufficiently to impede left ventricular filling. Accordingly, the maximum increment in PAP attainable by the right ventricle during acute increases in PVR apparently was inadequate to propel the entire CO through the pulmonary vasculature, setting the stage for the congestive right-sided pooling of blood routinely associated with PHS in broilers.     

Ventricular interdependence: significant left ventricular contributions to right ventricular systolic function

This article reviews diastolic and systolic ventricular interaction, and clinical pathophysiological conditions involving ventricular interaction. Diastolic ventricular interdependence is present on a moment-to-moment, beat-to-beat basis, and the interactions are large enough to be of physiological and pathophysiological importance. Although always present, ventricular interdependence is most apparent with sudden postural and respiratory changes in ventricular volume. Left ventricular function significantly affects right ventricular systolic function. Experimental studies have shown that about 20% to 40% of the right ventricular systolic pressure and volume outflow result from left ventricular contraction. This dependency of the right ventricle on the left ventricle helps to explain the right ventricular response to volume overload, pressure overload, and myocardial ischemia. The septum and its position are not the sole mechanism for ventricular interdependence. Ventricular interdependence causes overall ventricular deformation, and is probably best explained by the balance of forces at the interventricular sulcus, the material properties, and cardiac dimensions.     

Mechanical assistance of the pulmonary circulation after right ventricular exclusion

The Fontan procedure is often associated with elevated right-sided pressures and low cardiac output during the early postoperative period. A dog model was established to test the effect of pulmonary artery counterpulsation after atriopulmonary anastomosis. After exclusion of the right ventricle by a purse-string suture at the right AV orifice, placed during inflow occlusion, a valved conduit was inserted between the right atrial appendage and the pulmonary artery. This created a circulatory pattern comparable to a Fontan procedure. Counterpulsation was achieved by inserting a cannula into the conduit distal to the valve in eight dogs; alternatively, in four, counterpulsation could be achieved through a 10 mm side-arm graft connected to the conduit distal to the valve. Twenty-four observations were made. Without counterpulsation the circulatory status of the dog deteriorated rapidly. Counterpulsation resulted in a mean increase in cardiac output of 48% (p less than 0.0001). Right atrial pressure fell significantly with a mean drop of 4 mm Hg (p less than 0.003). This allowed for a further increase in right-sided filling pressure by transfusion, with a subsequent further increase in cardiac output. Left atrial pressure did not change significantly unless altered by transfusion. Counterpulsation instituted through the 10 mm side-arm graft gave similar results. Pulmonary vascular resistance decreased with counterpulsation (mean decrease 35%; p less than 0.002). The use of a side-arm graft connected to the conduit after a Fontan procedure affords a clinical method of circulatory support without the need for additional surgical intervention for decannulation. These data suggest that mechanical assistance of the failing right atrium after atriopulmonary anastomosis is both feasible and effective.     

Preventive effects of tetrandrine on pulmonary hypertension and right ventricular hypertrophy in rats induced by monocrotaline

Pulmonary hypertension and right ventricular hypertrophy in rats were developed 3 weeks after administration of monocrotaline 50 mg/kg i.p. Tetrandrine 10 mg/kg and 15 mg/kg bid p.o. could prevent the above-said effects produced by monocrotaline.     

MRI evaluation of right ventricular pressure overload in chronic obstructive pulmonary disease

In chronic obstructive pulmonary disease (COPD), the development of pulmonary hypertension is common. This study was performed to assess the signs of right ventricular (RV) pressure overload and RV failure in COPD. In 8 COPD patients without primary cardiac disease, RV wall thickness, mass, and end-diastolic volume were measured by cardiac-triggered cine MRI. MR phase-contrast velocity quantification was used to measure stroke volume and the patterns of flow into and out of the RV. Data of patients were tested versus those of a control group matched for age (n = 8). Results showed that the RV wall thickness was increased (.6 +/- 0.1 vs 0.4 +/- 0.1 cm, P < .001). RV mass was increased (67 +/- 11 vs 57 +/- 5 g, P < .005). RV stroke volume was decreased (57 +/- 13 vs 71 +/- 13 ml, P < .01), but RV ejection fraction was not different. In the main pulmonary artery flow, the quotient of acceleration time divided by ejection time was decreased (33 +/- 5% vs 38 +/- 4%, P < .05), which is indicative of pulmonary hypertension. In conclusion, this MRI protocol provides a tool to assess the effects of RV pressure overload in COPD before heart failure has become manifest.     

Systemic sclerosis with pulmonary involvement and right ventricular failure in a child

We report a very rare case of systemic sclerosis in a 6-year-old girl. She presented with diffuse scleroderma, Raynaud's phenomenon, pulmonary interstitial fibrosis, pulmonary hypertension, and right ventricular failure. The diagnosis was confirmed by skin manifestations, high resolution computed tomography, cardiac catheterization, and anti-nuclear antibodies. Nifedipine, prednisolone, digoxin, and furosemide were given. There was remission of the right ventricular failure and dyspnea, and the skin showed partial improvement. The patient remained asymptomatic for a year. The symptoms of respiratory and right heart failure developed again after an episode of lower respiratory tract infection and she eventually died. We discuss the clinical manifestations, treatment, and outcome.     

Effects of norepinephrine on right ventricular function in septic shock patients

OBJECTIVE: To study the effects of norepinephrine on right ventricular function in patients with hyperdynamic septic shock. DESIGN: Prospective, open study. SETTING: A 15 bed ICU in a university hospital. PATIENTS: 9 patients with hyperdynamic septic shock (SBP < 90 mmHg, Cl > or = 4 l.min-1.m-2, SVRI < or = 850 dynes.s.cm-5m-2 and oliguria). INTERVENTIONS: Plasma volume expansion was used to correct a suspected volume deficit and then, norepinephrine infusion was started and titrated to restore systemic blood pressure to the normal range (mean infusion rate: 1.1 +/- 0.2 mcg.kg-1.min-1). Norepinephrine was the only vasoactive agent used in these patients. MEASUREMENTS AND RESULTS: A modified Swan-Ganz catheter mounted with a fast response thermistor was inserted in each patient, allowing repeated measurements of RVEDVI and RVEF. At time of inclusion to the study, all but one patient had elevated MPAP (23 +/- 4 mmHg) and RVEF < or = 50%, and all patients had RVEDVI > or = 90 ml.m-2. During norepinephrine infusion, MAP increased from 51 +/- 9 to 89 +/- 10 mmHg (p < 0.0001), PVRI increased from 204 +/- 35 to 286 +/- 63 dynes.s.cm-5.m-2 (p < 0.05), and despite this increase in right ventricular afterload, no detrimental effect in RVEF (36 +/- 11 to 36 +/- 10%) or in RVEDVI (116 +/- 30 to 127 +/- 40 ml.m-2) was observed. A Frank-Starling relationship for the right ventricle was constructed by plotting an index of ventricular performance (RVSWI) against an index of ventricular preload (RVEDVI). A significant upward shift to the right of the relationship was observed during norepinephrine infusion. CONCLUSION: It was concluded that norepinephrine exerted a favourable effect on right ventricular function.