Ventricular interaction and external constraint accountfor decreased stroke work during volume loading in CHF THOMAS D. MOORE,1 MICHAEL P. FRENNEAUX,1 ROZSA SAS,2J. J. ATHERTON,3 JAYNE A. MORRIS-THURGOOD,1 ELDON R. SMITH,2JOHN V. TYBERG,2 AND ISRAEL BELENKIE22Departments of Medicine and Physiology and Biophysics, University of Calgary,Calgary, Alberta T2N 4N1, Canada; 3University of Queensland, Brisbane Q4029, Australia;and 1Department of Cardiology, Wales Heart Research Institute,University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom Received 26 April 2001; accepted in final form 13 August 2001 Moore, Thomas D., Michael P. Frenneaux, Rozsa Sas,
capillary wedge pressure (PCWP) is reduced (4, 28) at J. J. Atherton, Jayne A. Morris-Thurgood, Eldon R.
first sight seem to suggest that volume manipulation Smith, John V. Tyberg, and Israel Belenkie. Ventricular
may alter contractility and that there is a descending interaction and external constraint account for decreased limb of the SW-LVEDV (Starling) relation.
stroke work during volume loading in CHF. Am J Physiol The effective LV distending pressure is transmural LV Heart Circ Physiol 281: H2385–H2391, 2001.—The slope of end-diastolic pressure (LVEDP), which is LVEDP minus the stroke work (SW)-pulmonary capillary wedge pressure the surrounding [pericardial and right ventricular (RV)] (PCWP) relation may be negative in congestive heart failure pressure. Normally, pericardial pressure and RV end- (CHF), implying decreased contractility based on the premisethat PCWP is simply related to left ventricular (LV) end- diastolic pressure (EDP) are low, but in some conditions, diastolic volume. We hypothesized that the negative slope is may be markedly elevated. In these situations, the pres- explained by decreased transmural LV end-diastolic pressure sure surrounding the LV may contribute substantially to (LVEDP), despite the increased LVEDP, and that contractil- measured LVEDP (7), and the effective distending pres- ity remains unchanged. Rapid pacing produced CHF in six sure may be considerably lower than the measured dogs. Hemodynamic and dimension changes were then mea- LVEDP. It is now also clear that in these situations, sured under anesthesia during volume manipulation. Vol- changes in LVEDP may not accurately reflect changes in ume loading increased pericardial pressure and LVEDP but the effective distending pressure (transmural LVEDP).
decreased transmural LVEDP and SW. Right ventricular In a model of acute pulmonary embolism (4, 5), volume diameter increased and septum-to-LV free wall diameter loading decreased SW despite the increased LVEDP; the decreased. Although the slopes of the SW-LVEDP relations opposite occurred during volume removal. This apparent were negative, the SW-transmural LVEDP relations re- paradox of decreased cardiac function when filling pres- mained positive, indicating unchanged contractility. Simi- sure is increased did not represent decreased contractil- larly, the SW-segment length relations suggested unchanged ity; rather, it was explained by a greater increase in contractility. Pressure surrounding the LV must be sub- pericardial pressure and RVEDP than the increase in tracted from LVEDP to calculate transmural LVEDP accu-rately. When this was done in this model, the apparent LVEDP. This resulted in a reduction in transmural decrease in contractility was no longer evident. Despite the LVEDP and thus decreased LVEDV; the decreased increased LVEDP during volume loading, transmural LVEDV was responsible for the reduced SW in keeping LVEDP and therefore SW decreased and contractility re- with Starling’s Law despite the increased intracavitary LVEDP. The reverse was true during volume removal.
Similar observations were made in patients with chronic congestive heart failure; hemodynamics; pericardium obstructive pulmonary disease in whom volume loadingdecreased LVEDV despite increased PCWP (17).
Data from two studies suggest that a similar phe- IT IS IMPORTANT TO ASSESS the hemodynamic status accu- nomenon may also occur in congestive heart failure. In rately in congestive heart failure and to understand some patients, LVEDV increased during nitroglycerin how treatment affects left ventricular (LV) end-dia- administration or when central blood volume was re- stolic volume (LVEDV) because cardiac function is in duced with lower body negative pressure, despite the part dependent on preload. The old observation that fact that both interventions decrease LVEDP (3, 9). We phlebotomy increased cardiac output as central venous suggested previously (2) that these findings can be pressure fell (16) and the more recent observations explained by decreased constraint to LV filling and that stroke work (SW) may increase as pulmonary The costs of publication of this article were defrayed in part by the Address for reprint requests and other correspondence: I. Belen- payment of page charges. The article must therefore be hereby kie, Health Sciences Center, 3330 Hospital Dr. NW, Calgary, Al- marked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734 berta, Canada T2N4N1 (E-mail: [email protected]).
0363-6135/01 $5.00 Copyright 2001 the American Physiological Society direct ventricular interaction. However, there are no five animals, four from over the LV; pressure from over the RV published studies in which simultaneous cardiac func- was used in one animal because of unsuitable tracings over the tion, pressures, and dimensions were measured to ver- LV. In dog 6, pericardial pressures were technically unaccept- ify that constraint to filling and ventricular interaction able, and right atrial pressure was used as an approximation tocalculate transmural LVEDP. In dog 1, catheter whip from the are responsible for the apparent paradoxical response pericardial transducer sometimes caused too much artifact so to volume loading in congestive heart failure.
that only the cardiac cycles just before, at, and just after end Using the canine rapid-pacing congestive heart fail- expiration were used to calculate transmural LVEDP. Data ure model, we tested the hypothesis that volume load- collected during volume removal in three dogs were excluded ing may decrease and volume removal may increase because of severe hemodynamic deterioration (systolic aortic transmural LVEDP, despite opposite changes in intra- pressure decreased rapidly to Ͻ70 mmHg and SV decreased to cavitary LVEDP, and that changes in SW would par- Ͻ50%). Transmural LVEDP was calculated as LVEDP Ϫ peri- allel changes in transmural LVEDP. We also hypoth- cardial pressure. The transseptal pressure gradient was calcu- esized that, as in pulmonary embolism and chronic lated as LVEDP Ϫ RVEDP. SW was calculated as SV ϫ (LV pulmonary disease, ventricular interaction would ac- end-systolic pressure Ϫ LVEDP) (expressed in mmHg⅐ml). End-diastolic dimensions were measured at the peak of the R wave count for the associated changes in ventricular dimen- sions. Our results confirm that changes in intracavitary Statistical analysis. Hemodynamic and dimension changes LVEDP may not reliably predict changes in transmural during volume loading were compared with the Student’s LVEDP in severe congestive heart failure; our results paired t-test. A probability Ͻ0.05 was considered to be sta- also clarify the mechanism by which this occurs.
In the four awake dogs in which PCWP was mea- Experimental model. Rapid ventricular pacing (220–250 beats/min for 4–6 wk) produced severe congestive heart failure sured, mean PCWP fell from a mean of 25 (range (severe LV dysfunction observed echocardiographically, associ- 16–37) mmHg before anesthesia to 16 (range 5–34) ated with lassitude, dyspnea, and ascites) in six dogs (both mmHg when first measured under anesthesia with the sexes, 20–25 kg) as previously described (2, 11, 14, 15, 29, 32).
chest open and the pericardium closed. After instru- The pacemakers were then turned off, and the dogs were stud- mentation and stabilization with variable amounts of ied acutely. (Four were first placed in a supporting sling and, fluid in all six anesthetized animals, LVEDP was with the use of local anesthesia, a catheter was advanced to the pulmonary artery to measure PCWP.) Anesthesia was then Volume loading. Table 1 lists the hemodynamic and induced with intravenous fentanyl citrate (0.1 mg/ml) followed dimension data at baseline and during volume manip- by ϳ2 mg/kg Pentothal Sodium. The animals were then venti-lated with a 70% nitrous oxide-30% oxygen mixture with aconstant-volume respirator. Anesthesia was maintained with Table 1. Hemodynamic and dimension changes fentanyl at a rate of ϳ4 mg/h. A midline sternotomy was during volume manipulation in heart failure performed, the pericardium was incised along the base of theventricles, and the heart was removed from the sac for instru- mentation (4). LV, aortic, and RV pressures were measured with 8-Fr catheter-tipped transducers (model SPC-485A, MillarInstruments; Houston, TX) inserted through a carotid artery and a femoral artery and vein, respectively. Right atrial pres- sure was measured with a fluid-filled catheter inserted through a jugular vein. Pericardial pressure was measured over the lateral surface of both ventricles with flat, fluid-filled balloon transducers (13). Septum-to-LV free wall, LV anteroposterior, and septum-to-RV free wall diameters, as well as LV free wall segment length were measured by sonomicrometry (Sonomet- rics, London, Ontario, Canada). An ultrasonic flow probe (Tran- sonic Systems; Ithaca, NY) was implanted on the aorta to measure stroke volume (SV). A signal from the respirator was used to identify end-expiratory cardiac cycles, and a single lead electrocardiogram was recorded. The pericardium and chest were closed, and the animals were stabilized.
Data are means Ϯ SD from all dogs are available during volume Experimental protocol. While data were continuously col- loading but in only 3 animals during volume removal because of hemo- lected, volume loading was performed with 200–750 ml hep- dynamic instability in the two remaining dogs. HR, heart rate (beats/ arinized saline or a solution of 25 mg/l albumin over 1–4 min min); LVAP, left ventricular (LV) anteroposterior diameter (mm); until the LVEDP was at least 35 mmHg or hemodynamic LVEDP, LV end-diastolic pressure (mmHg); LVSP, peak LV systolic instability developed. Volume was then removed over a sim- pressure (mmHg); PerP, pericardial pressure (mmHg); RVEDP, right ilar period of time to either reduce the LVEDP to 12 mmHg ventricular (RV) end-diastolic pressure (mmHg); RVSP, peak RV sys-tolic pressure (mmHg); SegL, Segment length (mm); SLVFW, septum- or the systolic aortic pressure to Ͻ75 mmHg. The blood- to-LV free wall diameter (mm); SRVFW, septum-to-RV free wall diam- saline mixture was then reinfused until the LVEDP was the eter (mm); SV, stroke volume (ml); SW, stroke work (ml⅐mmHg).
same as at the start of the protocol.
TLVEDP, transmural LVEDP (mmHg); TSG, transseptal pressure gra- Data analysis. Data collected throughout respiration were dient (mmHg); Data collected during volume removal were not sub- analyzed. Pericardial pressure measurements were available in jected to statistical analysis. *P Ͻ 0.01; †P Ͻ 0.05.
AJP-Heart Circ Physiol • VOL 281 • DECEMBER 2001 • ulation. Figure 1 illustrates the changes in pressures,LV performance, and dimensions during volume load-ing and removal in a representative dog (dog 5). Vol-ume loading increased LVEDP (from 20.9 Ϯ 1.8 to26.8 Ϯ 2.9 mmHg) but increased RVEDP more (from15.1 Ϯ 1.6 to 24.3 Ϯ 2.3 mmHg), thus decreasing thetransseptal pressure gradient (from 6.4 Ϯ 1.1 to 3.0 Ϯ1.1 mmHg). As shown in Fig. 2, the increase in peri-cardial pressure during volume loading (from 13.6 Ϯ1.9 to 21.8 Ϯ 3.2 mmHg) was similar to the increase inRVEDP. The decrease in transmural LVEDP (from6.6 Ϯ 0.7 to 4.5 Ϯ 1.1 mmHg) was similar to thedecrease in the transseptal pressure gradient. Thedecreased transseptal pressure gradient and transmu-ral LVEDP were associated with a decreased SV (from11.7 Ϯ 2.8 to 10.1 Ϯ 2.6 ml) and SW (from 418 Ϯ 101 to291 Ϯ 78 ml ⅐ mmHg). All of the above changes werestatistically significant. The changes in peak LV sys-tolic pressure, peak RV systolic pressure, and heartrate were not significant.
Volume removal. The data are from the three ani- mals that remained hemodynamically stable duringvolume removal. As illustrated in Fig. 1 and listed inTable 1, volume removal reversed the changes causedby volume loading. As LVEDP decreased (from 29.3 Ϯ Fig. 2. Plots of PerP versus RVEDP. PerP measurements over bothventricles were available and similar in 3 dogs (dogs 1, 3 and 4) asindicated by open and closed circles. Changes in PerP were closelyrelated to changes in RVEDP. PerP was not available in dog 6. SeeFig. 1 for abbreviations.
2.6 to 23.3 Ϯ 2.6 mmHg), there was also a decrease inRVEDP (from 22.7 Ϯ 1.9 to 14.7 Ϯ 2.7 mmHg), result-ing in an increased transseptal pressure gradient (from6.7 Ϯ 4.3 to 8.7 Ϯ 3.5 mmHg). The decrease in pericar-dial pressure (24.7 Ϯ 0.3 to 16.7 Ϯ 2.4 mmHg) wassimilar to that in RVEDP. Transmural LVEDP in-creased (from 4.7 Ϯ 2.9 to 6.7 Ϯ 2.0 mmHg) and SV andSW increased from 15.3 Ϯ 4.0 to 16.5 Ϯ 5.2 ml and483 Ϯ 143 to 593 Ϯ 167 mmHg ⅐ ml, respectively. PeakLV systolic pressure and heart rate remained un-changed, and peak RV systolic pressure decreasedslightly from 37.3 Ϯ 1.5 to 35.0 Ϯ 1.7 mmHg.
Effects of volume manipulation on dimensions. As illustrated in Fig. 1 and listed in Table 1, changes inthe transseptal pressure gradient caused the septum toshift predictably. During volume loading, the de-creased transseptal pressure gradient caused a left-ward septal shift [the septum-to-LV free wall diameter Fig. 1. Hemodynamic and dimension changes during volume loading decreased from 50.5 Ϯ 1.4 to 49.8 Ϯ 1.3 mm (P Ͻ 0.05), and removal in a representative animal (dog 5). Top: changes in left and the septum-to-RV free wall diameter increased ventricular (LV) and right ventricular (RV) end-diastolic pressure from 42.7 Ϯ 4.8 to 44.4 Ϯ 4.7 mm (P Ͻ 0.01)]. The (EDP), pericardial pressure (PerP), transseptal pressure gradient increased transseptal pressure gradient during volume (TSG), and transmural LVEDP (TLVEDP). Middle: changes instroke volume (SV) and stroke work (SW). Bottom: changes in cham- removal caused a rightward septal shift in all three ber dimensions. As LVEDP increased during loading, RVEDP and animals (septum-to-LV free wall diameter increased PerP increased more so that the TSG and TLVEDP decreased. These from 51.0 Ϯ 2.1 to 51.5 Ϯ 1.7 mm and the RV dimen- changes were associated with a decrease in SV and SW, decreased sion decreased from 45.5 Ϯ 8.7 to 43.9 Ϯ 8.8 mm).
septum-to-LV free wall diameter (SLVFW), and increased septum- There was no significant change in segment length to-RV free wall diameter (SRVFW). Changes were reversed duringvolume removal.
AJP-Heart Circ Physiol • VOL 281 • DECEMBER 2001 • LV segment length. Figure 3 shows the LVEDP- and transmural LVEDP-segment length relations in eachanimal. As can be seen, transmural LVEDP was con-sistently lower than LVEDP and segment length wasmore closely related to transmural LVEDP thanLVEDP. There was little change in segment length indog 4, and there was little change in pressure in dog 1.
In four dogs (dogs 3–6), there was considerably morescatter in the LVEDP-segment length relations.
LV function. The SW-LVEDP relations (Fig. 4A) in each animal were negative and, if interpreted in theconventional manner, imply that contractility de-creased as LVEDP increased. However, the SW-trans-mural LVEDP relations were positive in all animals,SW consistently increasing as a function of increasingtransmural LVEDP. Figure 4B shows the summarydata from all animals in which SW was normalized(100% equals the average of the highest and lowestvalue for each dog). The SW-LVEDP plots showedconsiderably more scatter than the SW-transmuralLVEDP plots. Figure 5 shows the SW-end-diastolicsegment length relations in each dog. In three dogs, theSW-segment length relations had a positive slope,whereas there was little change in segment length inone dog (dog 4) and in SW in another dog (dog 1).
Pericardial constraint. Pericardial pressure varied considerably between animals and during volume ma-nipulation (Table 1). However, as illustrated in Fig. 2,pericardial pressure was similar to RVEDP, andchanges in pericardial pressure (from 13.6 Ϯ 1.9 to21.8 Ϯ 3.2 mmHg, P Ͻ 0.01) during volume loadingwere similar to those in RVEDP (from 15.1 Ϯ 1.6 to24.3 Ϯ 2.3 mmHg, P Ͻ 0.01) throughout the range offilling pressures in the five animals in which it wasobtained. Transmural RVEDP was low throughout (2.5 Fig. 4. A: plots of SW versus LVEDP and TLVEDP during volumeloading in all animals and unloading (3 animals). Relations betweenSW and LVEDP all had a negative slope over at least part of thecurves. In all animals, there was a single positive SW-TLVEDPrelation during both volume loading and removal, suggesting thatpreload determined LV performance throughout volume manipula-tion and that there was no change in contractility. Right atrialpressure was used instead of PerP to estimate TLVEDP in dog 6. B:summary plot of the data from all the animals. Because PerP in dog2 (see Fig. 2) was much lower than RVEDP, RVEDP was usedinstead to calculate transmural LVEDP for this summary plot only.
See Fig. 1 for abbreviations.
mmHg). Pericardial pressure was similar (Fig. 2, openand closed circles) over both ventricles in the threedogs in which both measurements were available.
The most important findings of the present study are as follows. First, change in LVEDP (or PCWP) is not areliable surrogate for estimating change in LVEDV in Fig. 3. Plots of LVEDP and transmural LVEDP versus end-diastolic severe congestive heart failure. Second, when trans- segment length (SegL) during both volume loading in all animals mural LVEDP was used to reflect LV distending pres- (dogs 1–6) and unloading (3 animals). SegL was more closely relatedto transmural LVEDP than LVEDP.
sure, the negative slope of the SW-PCWP (apparent AJP-Heart Circ Physiol • VOL 281 • DECEMBER 2001 • observed changes, the mechanism being similar to thatwhich was previously described in pulmonary embo-lism and chronic pulmonary disease (4, 5, 17). Commonto the three conditions is the presence of both pulmo-nary hypertension and constraint to LV filling.
LVEDP-LVEDV relation and LV function. According to Starling’s Law, SW increases as end-diastolic fiberlength or volume increases. Because volume is difficultto measure, LVEDP (or PCWP) is widely used as itssurrogate. This is based on the premise that LVEDVchanges in the same direction as LVEDP and that, atevery LVEDV, there is one value of LVEDP. SW shouldtherefore change in the same direction as LVEDP pro-vided there is no change in contractility or the amountof mitral regurgitation. This is normally a reasonableapproximation. In severe congestive heart failure, SWmay decrease as LVEDP increases; this “descendinglimb” of the Starling curve has therefore been attrib-uted to decreased contractility, each observation on thedescending limb representing different, progressivelydownward-displaced ventricular function curves (16,18). However, this interpretation presupposes thatLVEDP is the effective distending pressure and that Fig. 5. Plots of SW versus SegL during volume loading in all animals changes in LVEDP reflect changes in LVEDV. As ob- and unloading in 3 animals. In 3 dogs, there is a positive slope of therelation and in 2, there was too little change in one or the other served by Katz in 1955 (19), intracavitary and trans- mural LVEDP are equal only when the pressure sur-rounding the LV is negligible. When the pressuresurrounding the LV is not negligible, external pressure descending limb of the Starling curve, which implies must be subtracted from LVEDP to calculate transmu- decreased contractility) was eliminated. Thus contrac- ral LVEDP accurately (the effective distending pres- tility was not altered by volume manipulation in this sure), which determines diastolic fiber length. Thus, if model of congestive heart failure. This is the first volume loading increases pressure around the LV more demonstration of the potential effect of constraint to than it increases intracavitary LVEDP, transmural LV filling and ventricular interaction during volume LVEDP will decrease (22). This will result in a de- loading in congestive heart failure. Although our pre- creased LVEDV and therefore, reduced SW in accor- vious clinical study (26) had suggested that ventricular dance with the Frank-Starling mechanism.
interaction might explain the previously observed as- We demonstrated these principles previously in a sociation of improved cardiac function when filling pulmonary embolism model in which volume loading pressure was reduced, it has not been previously veri- shifted the LVEDP-LVEDV relation upward and left- fied with simultaneous pressure and dimension mea- ward, suggesting decreased compliance, and the SW- LVEDP relation downward and rightward, suggesting decreased contractility (4, 5). These apparent changes LVEDP, which determines LVEDV) is equal to mea- in compliance and contractility were eliminated when sured LVEDP minus the surrounding pressure. We transmural LVEDP was substituted for LVEDP: com- have shown that intracavitary and transmural LVEDP pliance and contractility remained unchanged. Jardin may even change in opposite directions in acute pul- et al. (17) demonstrated similar ventricular interaction monary embolism (5). The results from the present during volume loading in patients with chronic pulmo- study show that the same phenomena may also occur nary disease. The observation by Dupuis et al. (9) that in congestive heart failure. Thus, although the nega- SW increased as PCWP was reduced by nitroglycerin tive slope of the SW-LVEDP relations at high LVEDPs in some of their patients with heart failure can be suggested that contractility decreased with volume explained by the same mechanism, but this was not loading, when transmural LVEDP was plotted instead, addressed in their report. Whereas one might attribute the apparent decrease in contractility was no longer the improved SW to decreased systemic vascular resis- evident. Indeed, there was a positive SW-transmural tance and/or mitral regurgitation (10), that would not LVEDP relation, indicating that systolic performance account for the associated increase in LVEDV in these was reliably predicted by the effective filling pressure, patients. We recently demonstrated that lower body consistent with Starling’s Law. The SW-segment negative pressure (which decreases LVEDP) reduced length relations provide additional support for the sug- right atrial pressure and increased LVEDV in almost gestion that contractility is not decreased during vol- half of our study patients with severe heart failure (3).
ume loading. Our results also demonstrate that ven- In the present study, we have now demonstrated that tricular interaction contributes importantly to the ventricular interaction explains the apparent paradox- AJP-Heart Circ Physiol • VOL 281 • DECEMBER 2001 • ical responses in SW to volume manipulation in con- and decrease LVEDV. This occurred during volume gestive heart failure; the SW-LVEDP relation implied loading in the present study; the transseptal pressure that a descending limb of the Starling curve was gradient decreased, RV diameter increased, and sep- present, but ventricular performance was faithfully tum-to-LV free wall diameter decreased.
predicted by the changes in transmural LVEDP. The Implications. Our results suggest that the use of SW-segment length relations provide additional sup- LVEDP (or PCWP) to estimate changes in LV preload port for our position that there is no descending limb of in congestive heart failure may be quite misleading, the curve, at least in this model of congestive failure.
particularly because the two may even change in op- Pericardial pressure in congestive heart failure. Vol- posite directions. The presence of increased jugular ume loading normally increases LVEDV substantially venous pressure suggests that pericardial pressure is only until LVEDP reaches ϳ10–15 mmHg, after which increased and therefore should alert the clinician to the LVEDP-LVEDV relation becomes much steeper the possibility that changes in PCWP may not reliably because the pericardium limits further increases in predict changes in LVEDV and, therefore, perfor- cardiac volume (12, 24). Clearly, the pericardium can mance. In fact, function may improve as PCWP is grow in a time-dependent manner, as reported by reduced (28), and the present study clarifies the mech- LeWinter and Pavelec (21), who showed that con- anism by which this can occur. To optimize benefit straint became negligible several weeks after creation from volume manipulation, transmural LVEDP or of an arteriovenous shunt. Because the RV is thinwalled, transmural RVEDP is low, and as RVEDP LVEDV should be assessed. Because of the close rela- increases above 2–4 mmHg, pericardial pressure in- tion between changes in right atrial and pericardial creases in a parallel fashion (1). The thicker LV has a pressures (7, 30), PCWP minus right atrial pressure higher transmural pressure. In patients with and with- might provide a reasonable estimate of transmural out LV disease, ϳ30–40% of measured LVEDP is due LVEDP, but this would have to be validated in clinical to external constraint (8). In the present study, volume studies. Because improved LV performance is the goal loading increased the contribution of external pressure of therapy, perhaps measuring cardiac output directly to the measured LVEDP from ϳ50 to 80%.
is a better strategy. However, it is most important to We recently reported that pericardial pressure var- understand the potential for diastolic constraint and ied widely among animals in the rapid-pacing model of ventricular interaction and that changes in filling pres- congestive failure (14) as it did in the present study. Of sure alone should not be relied upon to predict re- greater importance and in keeping with previous re- ports, changes in RVEDP paralleled those in pericar- Limitations. Our model does not completely mimic dial pressure in both studies (4, 5, 25–27). Because chronic severe congestive heart failure. Failure was of there was no change in transmural RVEDP, we spec- relatively short duration, and pulmonary artery pres- ulate that when central venous pressure is acutely sure was lower than is commonly observed in severe increased, this implies increased pericardial con- failure. We therefore speculate that there is potential straint, a situation in which changes in filling pressure for even greater ventricular interaction (and therefore, may not accurately reflect changes in LVEDV. This is “paradoxical” response to volume manipulation) in se- consistent with studies in chronically instrumented vere heart failure than was observed in the present normal dogs and patients with heart failure; volume study. That this may be true is suggested by much loading increased LVEDV and SV only up to LVEDPs greater increases in SW observed during tailored ther- of 10–12 mmHg (6, 23, 31), after which there was no apy in patients than in the present study (28).
further increase or even a decrease in SV (6).
Another potential limitation was the presence of a Ventricular interaction. Whereas changes in trans- variable amount of pericardial fluid that was drained mural LVEDP explain the observed changes in SW during instrumentation. This probably resulted in during volume manipulation, consideration of the as- some slackness of the pericardium and might have minimized pericardial constraint and therefore, ven- changes provides additional insight into the mecha- tricular interaction. Reproducibility between experi- nisms involved. Because the ventricles share the sep-tum and are surrounded by the poorly distensible peri- ments might have been even better if it had been cardium, in the presence of pericardial constraint, the possible to control for this factor.
volume of one ventricle can increase substantially only In conclusion, we have demonstrated substantial ex- if the volume of the other decreases. The transseptal ternal constraint in this model of pacing-induced con- pressure gradient determines end-diastolic septal po- gestive heart failure. The observed changes in LV per- sition; changes in the transseptal pressure gradient formance during volume manipulation were fully shift the septum and, in the presence of constraint, can explained by changes in the effective distending pres- cause reciprocal changes in the volumes of the ventri- sure and Starling’s Law when preload was appropri- cles. In the presence of pulmonary hypertension, vol- ately assessed. These results underscore the need to ume loading is likely to increase RVEDP more than consider the potential effects of pericardial constraint LVEDP (5, 17). If this occurs, the resulting decrease in and ventricular interaction on LV filling when assess- the transseptal pressure gradient will shift the septum ing the effects of therapy on cardiac function in heart leftward (4, 20) thereby tending to increase RVEDV AJP-Heart Circ Physiol • VOL 281 • DECEMBER 2001 • This study was supported in part by grants-in-aid from the Al- 16. Howarth S, McMichael J, and Sharpey-Schafer EP. Effects
berta Heart and Stroke Foundation (Calgary) held by I. Belenkie and of venesection in low output heart failure. Clin Sci (Colch) 6: by J. V. Tyberg and by grants from the British Heart Foundation (to M. P. Frenneaux, J. A. Morris-Thurgood, and T. D. Moore).
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