Right Ventricular Pressure Overload Research Articles

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.

Estimation of Right Atrial Volume and Function by an Online Echocardiographic Edge Detection System.

To define the accuracy of real-time two-dimensional echocardiographic imaging with automatic border detection (ABD) for the assessment of right atrial volume and function, we studied with ABD echocardiography 29 healthy subjects and 43 patients with sinus rhythm and various forms of heart disease. Twenty-three patients had right ventricular (RV) dysfunction (fractional area change < 45%), and 20 had RV hypertrophy from pressure overload. Doppler color flow imaging disclosed moderate-to-severe tricuspid regurgitation (TR) in 20 patients and trivial or no TR in 23. The ABD-derived end-diastolic (EDV) and end-systolic (ESV) volumes by the method of discs were used to compute fractional indexes of right atrial (RA) volume changes. Right atrial emptying fraction (RAEF) percent [(ESV - EDV)/ESV x 100] was calculated. The ABD-derived EDV and ESV correlated well with conventional offline measurements of two-dimensional echocardiographic images in the 43 patients (r = 0.94 for the end-diastolic values; r = 0.93 for the end-systolic values). Intraobserver and interobserver variability showed a high correlation between different measurements (r = 0.97 and 0.90, respectively). RA volumes were significantly higher in the patient population than in the control subjects (148.9 +/- 66.7 ml vs 43.1 +/- 9.2 ml, P < 0.0001). The right atrial emptying fraction (RAEF) was higher in patients with RV pressure overload than in normal subjects (61% +/- 11% vs 46% +/- 9%, P < 0.05) and lower in those with RV dysfunction than in the control subjects (29% +/- 7% vs 46% +/- 9%, P < 0.01). In both groups (RV pressure overload and RV dysfunction), RAEF was higher in patients without or with trivial TR compared with those with significant TR (29% +/- 7% vs 23% +/- 6%; 61% +/- 11% vs 42% +/- 7%; P < 0.05). Thus, changes in right atrial volume and function can be measured noninvasively by the ABD method. This imaging technique may prove to be useful for assessing right atrial size and function under different physiological and pathological conditions and for identifying factors that influence atrial function in right ventricular diseases.

Plasma Brain Natriuretic Peptide Levels Increase in Proportion to the Extent of Right Ventricular Dysfunction in Pulmonary Hypertension

Objectives. This study sought to investigate the influence of right ventricular (RV) hemodynamic variables and function on the secretion of brain natriuretic peptide (BNP) in patients with isolated RV overload.Background. Plasma BNP is known to increase in proportion to the degree of left ventricular (LV) overload. However, whether BNP secretion is also regulated in the presence of RV overload remains unknown.Methods. Plasma BNP and atrial natriuretic peptide (ANP) levels in the pulmonary artery were measured in 44 patients with RV overload: 18 with RV volume overload (RVVO) due to atrial septal defect and 26 with RV pressure overload (RVPO) due to primary or thromboembolic pulmonary hypertension. Right heart catheterization was performed in all patients. RV and LV ejection fraction, myocardial mass and volume of the four chambers were determined by using electron beam computed tomography.Results. Although both plasma BNP and ANP levels were significantly elevated in patients with RV overload compared with values in control subjects, plasma BNP and the BNP/ANP ratio were significantly higher in patients with RVPO than with RVVO (BNP 294 ± 72 vs. 48 ± 14 pg/ml; BNP/ANP 1.6 ± 0.2 vs. 0.8 ± 0.2, both p < 0.05). Plasma BNP correlated positively with mean pulmonary artery pressure (r = 0.73), total pulmonary resistance (r = 0.79), mean right atrial pressure (r = 0.79), RV end-diastolic pressure (r = 0.76) and RV myocardial mass (r = 0.71); it correlated negatively with cardiac output (r = −0.33) and RV ejection fraction (r = −0.71). Plasma BNP significantly decreased from 315 ± 120 to 144 ± 54 pg/ml with long-term vasodilator therapy (total pulmonary resistance decreased from 23 ± 4 to 15 ± 3 Wood U).Conclusions. Plasma BNP increases in proportion to the extent of RV dysfunction in pulmonary hypertension.

Intraaortic Balloon Counterpulsation Improves Right Ventricular Failure Resulting From Pressure Overload

Background. Right ventricular (RV) dysfunction is common after heart transplantation, and myocardial ischemia is considered to be a significant contributor. We studied whether intraaortic balloon counterpulsation would improve cardiac function using a model of acute RV pressure overload. Methods. In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres. Results. After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 ± 2 to 60 ± 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 ± 4 to 49 ± 2 mm Hg; p < 0.01), RV ejection fraction (0.51 ± 0.04 to 0.16 ± 0.02; p < 0.01), and cardiac index (2.48 ± 0.04 to 1.02 ± 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 ± 2 to 61 ± 3 mm Hg; p < 0.01), cardiac index (1.02 ± 0.11 to 1.45 ± 0.14; p < 0.05), RV ejection fraction (0.16 ± 0.02 to 0.23 ± 0.02; p < 0.01), and blood flow to the left ventricle. Conclusions. In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.

A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program.

During cardiac hypertrophy, the chief myocardial energy source switches from fatty acid beta-oxidation (FAO) to glycolysis-a reversion to fetal metabolism. The expression of genes encoding myocardial FAO enzymes was delineated in a murine ventricular pressure overload preparation to characterize the molecular regulatory events involved in the alteration of energy substrate utilization during cardiac hypertrophy. Expression of genes involved in the thioesterification, mitochondrial import, and beta-oxidation of fatty acids was coordinately down-regulated after 7 days of right ventricular (RV) pressure overload. Results of RV pressure overload studies in mice transgenic for the promoter region of the gene encoding human medium-chain acyl-CoA dehydrogenase (MCAD, which catalyzes a rate-limiting step in the FAO cycle) fused to a chloramphenicol acetyltransferase reporter confirmed that repression of MCAD gene expression in the hypertrophied ventricle occurred at the transcriptional level. Electrophoretic mobility-shift assays performed with MCAD promoter fragments and nuclear protein extracts prepared from hypertrophied and control RV identified pressure overload-induced protein/DNA interactions at a regulatory unit shown previously to confer control of MCAD gene transcription during cardiac development. Antibody "supershift" studies demonstrated that members of the Sp (Sp1, Sp3) and nuclear hormone receptor [chicken ovalbumin upstream promoter transcription factor (COUP-TF)/erbA-related protein 3] families interact with the pressure overload-responsive unit. Cardiomyocyte transfection studies confirmed that COUP-TF repressed the transcriptional activity of the MCAD promoter. The DNA binding activities and nuclear expression of Sp1/3 and COUP-TF in normal fetal mouse heart were similar to those in the hypertrophied adult heart. These results identify a transcriptional regulatory mechanism involved in the reinduction of a fetal metabolic program during pressure overload-induced cardiac hypertrophy.

Right ventricular dysfunction persists following brief right ventricular pressure overload.

Acute pulmonary hypertension may cause right ventricular (RV) contractile failure. While it has been assumed that restoration of normal loading conditions after acute pulmonary hypertension is sufficient for complete recovery of RV function, this has not been rigorously examined. The purpose of this study was to test the hypothesis that acute RV pressure overload produces RV contractile dysfunction that persists following restoration of control loading conditions. We subjected 18 autonomically-blocked, chloralose-anesthetized, open-chest pigs to 1 h of pulmonary artery constriction to increase RV systolic pressure from 35 +/- 1 to 55 +/- 1 mmHg, followed by 2 h of measurements after pulmonary artery constriction release. We determined regional RV free wall function from pressure-segment length loops and preload recruitable stroke work relations, and global RV function from stroke work vs. end-diastolic pressure relations. As expected, RV free wall systolic shortening diminished during pulmonary artery constriction, but the endo/epi blood flow ratio, lactate uptake, and coronary venous pH were not significantly changed. Following release of pulmonary artery constriction, RV systolic and diastolic pressure returned to control values. Nonetheless, contractile dysfunction persisted, with depressed RV free wall systolic shortening (70 +/- 22% of control), RV regional external work (59 +/- 11% of control at control end-diastolic length), and global RV stroke work (56 +/- 14% of control at control end-diastolic pressure). Depressed regional work was due to a parallel, rightward shift of the preload recruitable stroke work relation. Five pigs identically instrumented but not subjected to pulmonary artery constriction showed no significant over 3 h. Acute pulmonary hypertension causes RV contractile dysfunction that persists at least 2 h after restoration of control loading conditions. Contractile dysfunction is not attributable to RV ischemia during pressure overload.

Echo-Doppler Evaluation of Left Ventricular Impairment in Chronic Cor Pulmonale

The effects of acute right ventricular (RV) pressure and volume overloads on left ventricular (LV) filling are well known, while the significance of chronic RV pressure overload on LV function has been less studied. To evaluate the LV impairment, 30 patients with chronic cor pulmonale and pulmonary arterial hypertension secondary to chronic obstructive lung diseases (COLDs) were studied. All patients underwent respiratory tests and arterial blood gas assessment. An echo-Doppler examination was made to measure LV ejection fraction (EF), RV and LV end-diastolic and end-systolic diameters and areas, RV/LV area indexes, LV diastolic and systolic eccentricity indexes, mitral and tricuspid flow patterns, and mitral flow velocity in late and early diastole (A/E) indexes. A right heart catheterization was carried out to determine the resting mean pulmonary arterial pressure (mPAP). The data showed a marked enlargement of RV, compressing the left through a leftward shift of interventricular septum. A linear regression analysis detected a significant correlation between mPAP and the following parameters: RV/LV diastolic and systolic area indexes (r=0.75, p<0.0001; r=0.84, p<0.000, respectively), mitral A/E index (r=0.61, p<0.0005), and LV diastolic and systolic eccentricity indexes (r=0.93, p<0.0001; and r=0.83, p<0.0001). No correlations were found between echo-Doppler data and functional respiratory parameters. From these results, we conclude that chronic RV pressure overload induces LV filling impairment despite a normal systolic phase, due to septal leftward shift. In fact, chronic RV pressure overload distorts early diastolic LV geometry delaying LV filling phase, and the functional diastolic impairment of the LV is closely correlated to pulmonary hypertension levels.

10 The pulmonary circulation in lung diseases

Summary In most cases of pulmonary hypertension, the pulmonary circulation retains its ability to dilate or to contract further, because of the release of vasoconstrictor as well as vasodilator mediators. The vascular endothelium synthesizes vasoconstrictor and vasodilator mediators, thereby playing a major role in the control of pulmonary vascular tone. Whether endogenous NO is involved in the maintenance of the normally low basal pulmonary vascular tone remains unsettled. However, many studies indicate that NO is released during hypoxia and lung injury, and counteracts the increase in P pa. Many data suggest that endogenous ETs could mediate pulmonary hypertension. ET receptor antagonists may prove valuable therapy for lung diseases associated with pulmonary hypertension. Inhaled NO selectively reduces P pa in various pulmonary hypertensive states and improves gas exchange in many patients with acute lung injury. Inhaled NO may therefore play a role in the treatment of pulmonary hypertension and/or lung injury. However, its long-term toxicity is not yet defined, and its clinical value needs to be evaluated in controlled trials. Complex interactions exist between the pulmonary circulation, the RV and the LV in health and disease. A better understanding of these interactions could promote valuable therapeutic strategies for RV pressure overload.

Pressure and Volume Loading of the Right Ventricle Have Opposite Effects on Left Ventricular Ejection Fraction

Left ventricular ejection fraction has been reported to be depressed in patients with right ventricular volume overload (RVVO) due to Ebstein's anomaly and uncomplicated atrial septal defect, whereas it is usually preserved in right ventricular pressure overload (RVPO) due to congenital pulmonic stenosis. In the present study, we examined the hypothesis that the differential timing of active displacement of the ventricular septum into the left ventricle in RVPO (end systole) and RVVO (end diastole) results in opposite effects of RVPO and RVVO on left ventricular ejection fraction. Ten patients with severe tricuspid regurgitation after tricuspid valve resection for endocarditis and 10 patients with primary pulmonary hypertension were studied as models of isolated RVVO and RVPO, respectively. Left ventricular ejection fraction, end-diastolic volume, and regional systolic shortening were measured with the use of echocardiographic techniques in these 20 patients and 10 healthy control subjects. In RVPO, despite marked underfilling of the left ventricle relative to the healthy control subjects (end-diastolic volume, 48 +/- 26 versus 77 +/- 20 mL; P < .02), left ventricular ejection fraction was similar to that of the control subjects (56 +/- 5% versus 60 +/- 4%; P = .07) and only 1 of 10 RVPO patients had an ejection fraction of less than 50%. In contrast, in RVVO the left ventricle was volume replete (end-diastolic volume, 84 +/- 26 versus 77 +/- 20 mL; P = NS), but left ventricular ejection fraction was significantly depressed (51 +/- 4% versus 60 +/- 4%, P < .001) compared with the control subjects, and 4 of 10 RVVO patients had an ejection fraction of less than 50%. Analysis of systolic fractional shortening along two perpendicular short-axis diameters and the mutually orthogonal long axis demonstrated isolated augmentation of fractional shortening in the ventricular septal-to-posterolateral free wall dimension in RVPO (47.4 +/- 13.7% versus 34.2 +/- 13.1%, P < .05) and isolated depression of fractional shortening along that same dimension in RVVO (13.7 +/- 11.8% versus 34.2 +/- 13.1%, P < .001) compared with the control subjects. End-systolic leftward ventricular septal shift in RVPO results in isolated augmentation of systolic shortening in the septal-to-free wall dimension, whereas end-diastolic leftward ventricular septal shift in RVVO results in isolated reduction in systolic shortening in the septal-to-free wall dimension. As a result, despite relative underfilling of the left ventricle in RVPO, resting left ventricular ejection fraction is preserved, whereas ejection fraction is depressed for the volume-replete left ventricle of patients with RVVO.

Regional Left Ventricular Systolic Function in Relation to the Cavity Geometry in Patients With Chronic Right Ventricular Pressure Overload

Distortion of the left ventricular (LV) cavity in patients with right ventricular pressure overload (RVPO) is well known. However, no direct measurements of regional myocardial function in terms of myocardial shortening and wall thickening are available; therefore, exactly how RVPO disturbs LV regional performance remains unclear. By using three-dimensional (3D) tagged magnetic resonance imaging, we were able to measure regional systolic function directly. Our objective was to study the relation between the distortion of the LV circular shape and regional LV function. In nine patients with RVPO and six healthy volunteers, four parallel short-axis images (with 12 radial tags) and two mutually orthogonal long-axis images (with four parallel tags) were generated, and endocardial and epicardial borders were manually traced. By integration of the short- and long-axis images, 3D reconstruction of the LV tracking points from end diastole to end systole was obtained. Data from the midventricular two short-axis image slices were analyzed. These were then divided into anterior, lateral, posterior, and septal regions. Circumferential and longitudinal shortening were then calculated from the endocardial and epicardial tag intersection points. Wall thickness and thickening were calculated by the 3D volume-element approach. An eccentricity index (EI), the ratio of septum-to-free-wall to anteroposterior diameters, was used to describe the shape of the LV cavity. The regional curvature was also measured. The RVPO group was characterized by flattening of the septum and LV lateral wall, decreased EI reflecting the distorted LV shape, altered distribution of endocardial circumferential shortening, and preserved ejection fraction. Changes in EI closely correlated with the septal curvature. The EI was smaller at end systole, reflecting further shape distortion relative to end diastole. Reduced myocardial performance, as measured by wall thickening and circumferential and longitudinal shortening fractions, was observed for the septum. A reduction in endocardial circumferential shortening of the septal and lateral walls was directly related to the end-systolic EI. In addition, whereas for healthy subjects a linear relation between area ejection fraction and endocardial circumferential shortening was observed, in RVPO patients a curvilinear (quadratic) relation was observed. In patients with RVPO, compared with healthy subjects, the septal function was reduced, as evidenced by reduced thickening and shortening fractions. The distortion in LV cavity at end systole due to the flattening of the septum contributes to preserved systolic ventricular function and nonuniform distribution in endocardial circumferential shortening.

Midterm outcome after pulmonary balloon valvuloplasty in patients younger than one year of age

In conclusion, pulmonary balloon valvuloplasty is a useful, safe, and probably definitive procedure in the treatment of isolated PS in patients <1 year of age. Because RV pressure overload can also be effectively reduced in neonates and infants, with a low incidence of complications and low risk of restenosis, we see no reason to delay valvuloplasty until a later stage of life.

978-122 Ultra Exercise Induces Right Ventricular Dysfunction

There is concern that very extensive ″ultra exercise″ might lead to left ventricular (LV) dysfunction and cardiac damage. Accordingly, we studied 23 runners participating in a 100 mile race (Hardrock 100, Silverton, Colorado) at high altitude (9318 feet). Subjects had baseline echocardiograms, finger tip oximeter readings and bloods for cardiac troponin I (cTnl) and MB creatine kinase (CK). In the 14 subjects (mean age = 43 ± 8 years) who finished the race, an immediate (20–30 min after finishing) post race echocardiogram, oximeter reading and blood sample for cTnl and MBCK were obtained. Studies were repeated 24 hours later. At baseline, all oximeter readings, echocardiograms, cTnl and MBCK values were normal. Post race and at 24 hours, oximeter readings were unchanged and all cTnl values were normal except for one subject with a minor elevation. MBCK was elevated in all finishers (mean 52 ± 28 ng/ml post race) and was not related to echocardiographic abnormalities. In 5 patients with bronchospasm post race, right ventricular (RV) dilation, depressed function of the RV free wall and paradoxical septal motion was observed (a pattern of ″RV pressure and volume overload″). In these subjects, systolic pulmonary artery pressure estimated from the tricuspid regurgitant jet had increased from 28 ± 2 to 55 ± 10 mmHg, p &lt; 0.005. The subject with the elevated value of cTnl had severe RV dysfunction and the highest pulmonary artery pressure, 65 mmHg. No new LV wall motion abnormalities were observed. RV dysfunction resolved completely in all subjects by 24 hours post race. Subjects with bronchospasm indicated that it had occurred previously during long races. These data do not support studies that contend that ultra exercise damages the left ventricle. They do suggest that in susceptible subjects, ultra exercise can induce pulmonary hypertension that is severe enough to cause reversible RV dysfunction.

Load effects on gene expression during cardiac hypertrophy

Hemodynamic load is a primary regulator of cardiac mass. A potential proximal event in this regulatory pathway is thought to be the induction of immediate early genes, and markers of this process include the re-expression of genes for fetal sarcomeric proteins and the ventricular expression of atrial natriuretic factor (ANF). Previous in vivo models which have examined these questions have often neither quantified myocardial loading nor accounted for covariables which may affect gene expression such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, or baroreceptors. Thus, whether load alone is sufficient to induce immediate early genes, which may ultimately result in cardiac hypertrophy, remains unknown. In the present study two models of right ventricular (RV) pressure overload were created by partially occluding the pulmonary artery (PA), either with a balloon catheter for 1 or 4 h, or with a surgically placed PA band for 12, 24, or 48 h. Serum catecholamine concentrations were determined in a subset of RV pressure overload cats at basal state, after 5 min of balloon inflation, and after 1 h of balloon inflation to examine the effects of this systemic trophic factor on IEG induction. Northern blot analysis for c-fos, egr-1, alpha-skeletal actin, and ANF from paired RV and left ventricular (LV) RNA allowed the effect of load (selectively increased in the RV) to be separated from other systemic variables (present in both ventricles). The relative signal intensities of the optical density of RV and LV mRNA autoradiograms were determined from northern blots, alternate lanes of which were loaded with 7.5 micrograms of total RNA from RV and LV tissue from the same cat. Partial PA occlusion caused RV systolic pressure to increase from a control value of 22 +/- 1 mmHg to 57 +/- 6 mmHg after 1 h, 59 +/- 5 mmHg after 4 h, and 58 +/- 5 mmHg after 48 h of RV pressure overload (RVPO). Serum norepinephrine and epinephrine levels at both 5 and 60 min of RVPO were not significantly different from basal levels. The RV/LV ratios of mRNA for both egr-1 and c-fos were equal in control and 48 h PA banded animals, but were increased in the 1 and 4 h balloon RVPO cats. The RV/LV ratio of mRNA for alpha-skeletal actin was equal in the basal state and did not increase after 12, 24, or 48 h of RVPO. After 48 h of RVPO, total RNA was increased in the RV compared with the LV (1.9 +/- 0.1 v 1.1 +/- 0.1 micrograms/g tissue, P < 0.05). ANF expression was present in the RV after 48 h of RVPO, but absent in same-animal LV and all control ventricles. Thus, while increased load alone did not alter the expression of alpha-skeletal actin, it was sufficient both to induce increased expression of two distinct classes of immediate early genes, as well as ANF, and to increase total RNA, indicating hypertrophic growth initiation.

Canine pulmonary hypertension model induced by pulmonary artery embolization of gelatin sponges.

We attempted to develop a pulmonary hypertension model in dogs by gelatin sponge embolization. We then monitored right-ventricular pressure overload by echocardiography. Gelatin sponges (Spongel, Yamanouchi, Tokyo) were homogenized and mixed in normal saline (0.6 mg/ml). The mixture was administered via the jugular vein to general pulmonary emboli. Repeated administration of the sponges increased the mean pulmonary arterial pressure and caused right ventricular pressure overload. The degree of pulmonary hypertension was proportional to the volume of gelatin sponge injected. Echocardiography, performed both before and after embolization, proved useful assessing for the degree of right-ventricular pressure overload.

Significance of the right ventricular free wall in dogs with and without pulmonary constriction.

To evaluate the role of the right ventricular (RV) free wall in cardiac function, RV and left ventricular (LV) wall segment lengths were measured by ultrasonic crystals in 10 open chest dogs with the pericardium preserved. Right coronary artery (RCA) was perfused separately by own blood and the flow was reduced stepwise until active shortening (delta L) of the RV segment disappeared or RCA flow became zero (Ischemia). The experiment was repeated with and without pulmonary stenosis (PS). At Ischemia, RV and LV systolic pressures decreased. RV end-diastolic length increased and RV delta L decreased. LV end-diastolic length and LV delta L were reduced. LV stroke volume concurrently fell. These changes became more prominent with PS. The critical level of RCA flow, at which RV delta L began to change, was higher with PS (5.27 +/- 2.85 ml/min, mean +/- S.D.) than without PS (1.44 +/- 1.16, p < 0.01). Based on the relationships between RV delta L and percent changes in RV developed pressure and stroke volume, the degree of the decreases in RV developed pressure and stroke volume at RV delta L of zero were estimated to be about 20%. These results indicate that the RV free wall partly contributes to maintaining the RV function, especially during RV pressure overload.

The renin-angiotensin system and volume overload-induced changes in cardiac collagen and elastin.

Besides cardiac load, the renin-angiotensin system (RAS) and aldosterone may regulate collagen accumulation during maturation or hypertrophic growth. The effect of cardiac volume overload on both left ventricular (LV) and right ventricular (RV) collagen and elastin and the possible role of the RAS in such changes have not yet been assessed. In the present study we assessed (1) the effects of 4 to 10 weeks of volume overload by an aortocaval shunt or minoxidil on LV and RV collagen and elastin and (2) the potential of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan to prevent and regress volume overload-induced changes in cardiac collagen and elastin. Cardiac volume overload by aortocaval shunt or minoxidil treatment decreased LV collagen accumulation as compared with control rats. In contrast, RV collagen accumulation was potentiated during the initial weeks but not during chronic aortocaval shunt. Enalapril and losartan prevented the relative decreases in LV collagen content and concentration induced by a shunt. Losartan also reversed the decrease in LV collagen content by aortocaval shunt. Neither blocker significantly affected the enhanced RV collagen accumulation during the initial weeks of shunt, but both blockers further potentiated RV collagen accumulation during chronic volume overload. Aortocaval shunt for 4 weeks but not 10 weeks enhanced LV and RV elastin accumulation. This initial increase in LV and RV elastin content was blocked by both enalapril and losartan. Cardiac volume overload, even when accompanied by increased plasma renin activity, decreases LV collagen accumulation, suggesting that in contrast to the stimulatory effect of systolic wall stress, increased diastolic wall stress inhibits collagen accumulation. In support of this concept, enalapril and losartan decreased LV preload and maintained LV collagen accumulation. In contrast to LV collagen, RV collagen accumulation was potentiated during the initial weeks of volume overload, possibly related to acute RV pressure overload shortly after aortocaval shunt and its decrease with chronic shunt. Enalapril and losartan had minimal effect on the enhanced RV collagen during the initial weeks of aortocaval shunt but potentiated RV collagen during chronic shunt, possibly by decreasing RV diastolic pressures. Altogether, these data suggest that during cardiac volume overload, the RAS affects cardiac collagen primarily by its hemodynamic effects. The RAS, however, may potentiate RV and LV elastin accumulation during the initial weeks of volume overload since both enalapril and losartan block this increase.

Left ventricular systolic performance is depressed in chronic pulmonary emphysema in dogs

The effect of chronic right ventricular (RV) pressure overload on left ventricular (LV) systolic function in chronic obstructive lung disease is unclear. To examine LV systolic performance in pulmonary emphysema, a chronic canine model was developed in which pulmonary artery pressure could be elevated to a level found in human disease. Severe emphysema was produced by the repeated instillations of the enzyme papain into the lung. Sonomicrometry was used to assess LV dimensions along the septal-lateral, apex-base, and anterior-posterior orthogonal axes of the LV. With the animal conscious, measurements of LV systolic function were obtained over a wide range of LV circumferential end-ejection stresses at baseline and after 1 yr of emphysema (post-1-yr study). In the emphysema group (n = 5), the results showed that at the post-1-yr study, measurements of LV ejection fraction, mean velocity of circumferential shortening, and rate of anterior-posterior dimensional shortening were reduced compared with those obtained at the baseline study. In the emphysema group, end-systolic volume was increased for a given end-systolic pressure or stress at the post-1-yr study compared with baseline values, while fractional shortening measured along the three axes was decreased. There were no similar changes in systolic parameters in control groups. We conclude that chronic RV pressure overload may cause an impairment in LV systolic performance in chronic emphysema.

Effects of chronic right ventricular pressure overload on left ventricular diastolic function

Right ventricular (RV) function influences left ventricular (LV) diastolic filling in various clinical and experimental models. The influence of RV systolic function on LV diastolic performance was examined in patients with severe RV pressure overload. Eighty-two patients with pulmonary vascular or parenchymal disease who were referred for heartlung or lung transplant evaluation were studied. All patients had radionuclide angiography from which RV ejection fraction and LV peak filling rate were measured. Most patients (n = 51) had rightsided cardiac catheterization. In 24 patients (group 1), RV ejection fraction was <30%, whereas in 58 (group 2), it was >30%. Mean pulmonary artery pressure was greater in group 1 than in 2 (57 ± 16 vs 34 ± 20 mm Hg; p < 0.0001). Pulmonary artery wedge pressure was also greater in group 1 than in 2 (14 ± 9 vs 7 ± 2 mm Hg; p < 0.0001), whereas peak filling rate was decreased (2.16 ± 0.88 vs 2.97 ± 0.79 end-diastolic volumes/s; p < 0.0001). LV ejection fraction was normal in all patients. There was an inverse relation between RV ejection fraction and pulmonary artery wedge pressure (r = −0.45; p < 0.001; SEE 5.3). There was a direct relation between RV ejection fraction and LV peak filling rate (r = 0.49; p < 0.0001; SEE 1.34). In patients with RV pressure overload, RV systolic function is related to LV diastolic performance. This effect is most likely mediated by ventricular interdependence.

Energetics of acute pressure overload of the porcine right ventricle. In vivo 31P nuclear magnetic resonance.

In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of the right ventricular (RV) free wall was employed to determine (a) whether phosphorus energy metabolites vary reciprocally with workload in the RV and (b) the mechanisms that limit RV contractile function in acute pressure overload. In 20 open-chest pigs, phosphocreatine (PCr)/ATP ratio (an index of energy metabolism inversely related to free ADP concentration), myocardial blood flow (microspheres), and segment shortening (sonomicrometry, n = 14) were measured at control (RV systolic pressure 31 +/- 1 mm Hg), and with pulmonary artery constriction to produce moderate pressure overload (RV systolic pressure 45 +/- 1 mm Hg), and maximal pressure overload before overt RV failure and systemic hypotension (RV systolic pressure 60 +/- 1 mm Hg). With moderate pressure overload, PCr/ATP declined to 89% of control (P = 0.01), while contractile function increased. Adenosine (n = 10, mean dose 0.16 mg/kg-min) increased RV blood flow by an additional 41% without increasing PCr/ATP, indicating that coronary reserve was not depleted and that the decrease in PCr/ATP from control was not due to ischemia. With maximal pressure overload and incipient RV failure, PCr/ATP fell further to 81% of control and RV blood flow did not increase further, even with adenosine. Thus: (a) The decline in PCr/ATP with moderate RV pressure overload, without evident ischemia or contractile dysfunction, supports the positive regulation of oxidative phosphorylation by ATP hydrolysis products. (b) Depletion of RV coronary flow reserve accompanies the onset of RV failure at maximal pressure overload.

Theoretical validity of predicting right ventricular systolic pressure by a quantitative index of interventricular septal displacement in acute right ventricular pressure overload.

A leftward shift of the interventricular septum (IVS) of the heart is observed in patients with right ventricular pressure overload (RVPO). We simulated the leftward displacement of IVS in a modified ellipsoidal model on the assumption that the IVS generates the same tension as the left ventricular (LV) free-wall in acute RVPO, and derived the relational equations between ventricular pressures (RVP, LVP) and eccentricity index (EI = LVAPD/LVSLD, LVAPD: left ventricular anterior-posterior diameter, LVSLD: left ventricular septal-lateral diameter). The equations indicate that RVP/LVP correlates with simultaneous EI, independent of the absolute LV wall tensions and the LV size. To confirm this result, we undertook recurrent pulmonary embolizations in anesthetized open-chest dogs, and analyzed the relationship between RVP/LVP and EI at four phases in systole through the course of RVPO and shock. The advance of RVPO shifted the peak of RVP toward late-systole and made the values of RVP/LVP and EI significantly greater at late-systole than at early-systole. There were significant linear relationships between instantaneous EI and RVP/LVP at each phase, expect for the early systole in the shock stage, and the regression lines on all phases were similar to one another. These results are consistent with our theoretical ones. Therefore we conclude that it is reasonable to predict RVP by using EI, theoretically and experimentally.