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Am J Physiol Heart Circ Physiol 289: H549-H557, 2005. First published March 25, 2005; doi:10.1152/ajpheart.01180.2004
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RV filling modulates LV function by direct ventricular interaction during mechanical ventilation

Jamie R. Mitchell, William A. Whitelaw, Rozsa Sas, Eldon R. Smith, John V. Tyberg, and Israel Belenkie

Departments of Cardiac Sciences, Medicine, and Physiology and Biophysics, The Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada

Submitted 23 November 2004 ; accepted in final form 17 March 2005


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
During mechanical ventilation, phasic changes in systemic venous return modulate right ventricular output but may also affect left ventricular function by direct ventricular interaction. In 13 anesthetized, closed-chest, normal dogs, we measured inferior vena cava flow and left and right ventricular dimensions and output during mechanical ventilation, during an inspiratory hold, and (during apnea) vena caval constriction and abdominal compression. During a single ventilation cycle preceded by apnea, positive pressure inspiration decreased caval flow and right ventricular dimension; the transseptal pressure gradient increased, the septum shifted rightward, reflecting an increased left ventricular volume (the anteroposterior diameter did not change); and stroke volume increased. The opposite occurred during expiration. Similarly, the maneuvers that decreased venous return shifted the septum rightward, and left ventricular volume and stroke volume increased. Increased venous return had opposite effects. Changes in left ventricular function caused by changes in venous return alone were similar to those during mechanical ventilation except for minor quantitative differences. We conclude that phasic changes in systemic venous return during mechanical ventilation modulate left ventricular function by direct ventricular interaction.

right ventricle; left ventricle

MECHANICAL VENTILATION CAN affect cardiac function through a number of mechanisms (7, 9, 12, 14, 16–18, 23, 24, 27, 29–31, 34, 39–41, 46, 49). Direct ventricular interaction (by which we mean that a change in the volume of one ventricle causes a simultaneous and opposite change in the volume of the other ventricle) is one of the mechanisms by which positive end-expiratory pressure (PEEP) may decrease left ventricular (LV) end-diastolic volume and output during mechanical ventilation (4, 9–11, 28, 29, 35, 40, 47). We recently studied direct ventricular interaction in dogs and showed that it was dependent on the presence of pericardial constraint (20). Thus a sudden decrease in right ventricular (RV) end-diastolic volume was associated with a simultaneous increase in LV end-diastolic volume, whereas a sudden increase in RV end-diastolic volume was associated with a decrease in LV end-diastolic volume. During positive pressure inspiration, RV filling and stroke volume are transiently decreased (27, 35, 38, 39). In another recent canine study, we observed that LV end-diastolic volume and stroke volume increased at the same time that RV end-diastolic volume decreased during positive pressure inspiration (the reverse occurred during expiration), consistent with the mechanism being direct ventricular interaction (35). However, this increase was not necessarily caused by the decreased RV volume. An increase in LV stroke volume could have also been caused by an increased RV stroke volume during the expiratory phase of the preceding ventilator cycle or increased LV filling resulting from the increased airway pressure propelling blood from the lungs to the LV (7).

The present study was performed to assess how phasic changes in venous inflow to the right heart during mechanical ventilation and apnea affect LV function by direct ventricular interaction. We measured inferior vena cava flow and ventricular dimensions and performance during transient changes in RV inflow in normal dogs to assess the instantaneous effects of those changes on LV end-diastolic volume and stroke volume and compared the findings with those observed during mechanical ventilation. To obviate any residual effects of preceding ventilator cycles, a single ventilation cycle was introduced during apnea. To study the specific effects of positive-pressure inspiration and expiration, inspiration and expiration were separated with an inspiratory hold. To study the effects of changes in RV inflow independent of ventilation, the inferior vena cava was occluded during apnea and then released. Sustained pressure was also applied to the abdomen during apnea and then released. Our results show that changes in RV end-diastolic volume during apnea cause reciprocal changes in LV end-diastolic volume (and stroke volume) by direct ventricular interaction (septal shift; see Ref. 32) that are similar to those observed during mechanical ventilation.


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
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Animal preparation. Thirteen mongrel dogs of both sexes, weighing 15–33 kg, were premedicated with 25 mg/kg thiopental sodium. Anesthesia was maintained with intravenous fentanyl citrate (0.04 mg/ml; given to effect), followed by an infusion of ~4 mg/h, which was adjusted as necessary to ensure deep sedation without spontaneous respiratory effort. Heparinized saline was infused to maintain adequate filling pressures and avoid hypotension. The animals were intubated with a cuffed endotracheal tube and ventilated with a constant-volume ventilator (inspiratory-to-expiratory ratio of 1:1; model 607; Harvard Apparatus, Natick, MA) with 50% O2-50% nitrous oxide. After instrumentation, the animals were ventilated with 100% O2. The end-expiratory pressure was 0 cmH2O, the tidal volume was 17–23 ml/kg [mean, 19.8 ml/kg (8, 42)], and the respiratory rate was 15–20 breaths/min (mean, 17/min). These parameters were adjusted to maintain a baseline PCO2 of no less than 33 mmHg and pH between 7.2 and 7.4.

A median sternotomy was performed with the animals in the supine position. For instrumentation purposes, the hearts were delivered from the pericardium through a base-to-apex incision. Sonomicrometry (Sonometrics, London, Ontario, Canada) was used to measure the minor-axis septum-to-LV free wall, septum-to-RV free wall, and LV anteroposterior dimensions (1–3, 15, 19, 36). The crystals were placed endocardially in the free walls of the ventricles and midwall in the septum. Flat, fluid-filled balloon transducers, connected to pressure transducers (model P23 ID; Statham Gould, Oxnard, CA), were used to measure pericardial pressure over the lateral surface of the LV (21). After instrumentation, the heart was returned to the pericardium, which was closed with individual sutures taking care not to compromise the pericardial volume (43). Ultrasonic flow probes (Transonic Systems, Ithaca, NY) were placed on the main pulmonary artery, ascending aorta, and inferior vena cava above the diaphragm. An inflatable silicone occluder (In Vivo Metric, Healdsburg, CA) was placed on the inferior vena cava between the heart and the flow probe. Catheter-tipped manometers (8-F, model SPC-484A; Millar Instruments, Houston, TX) were inserted in the LV (through a carotid artery), RV (through an external jugular vein) and aorta (through a femoral artery). The right atrium was paced at a rate slightly greater than the intrinsic rate to eliminate spontaneous variations in heart rate. A single-lead electrocardiogram was recorded. Airway pressure was measured near the endotracheal tube with an air-filled tube connected to a Statham Gould transducer. A femoral arterial line was to obtain samples for blood-gas analysis (Instrumentation Laboratories; 1312 Blood Gas Manager). Body temperature was monitored with either a rectal or vaginal thermometer. The chest was closed under ~5 cmH2O suction.

The conditioned signals were amplified (model VR16; Electronics for Medicine/Honeywell, White Plains, NY), passed through a low-pass filter (100 Hz), and digitized at 200 Hz. The inferior vena cava flow signal was filtered retrospectively (1 Hz filter; Sigma Plot). The digitized data were analyzed on a personal computer using software developed in our laboratory (CVSOFT; Odessa Computer Systems, Calgary, Alberta, Canada).

Experimental protocol. After instrumentation, the dogs were stabilized for ~30 min. To study the hemodynamic effects of a single ventilatory cycle unaffected by preceding ventilatory cycles, the ventilator was stopped at end-expiration for ~5 s, a single ventilatory cycle was performed, and the ventilator remained in an end-expiratory position for ~5 s. To study the onset and offset of increased inspiratory pressure separately, after 5 s of end-expiratory apnea, an inspiratory hold maneuver was performed for one ventilatory cycle by stopping the ventilator at peak airway pressure where it was maintained for 4–5 s and then released. To study the independent effects of changes in RV filling, the inferior vena cava was constricted for ~5–7 s during apnea with the airway disconnected and then the constriction was released. Similarly, to study the independent effects of changing RV inflow without changing airway pressure, the abdomen was manually compressed during apnea with a partially inflated blood pressure cuff for ~5 s and then released. The animals were then killed, and crystal positions were verified.

Data analysis. Transmural LV end-diastolic pressure was calculated as intracavitary-pericardial pressure. The end-diastolic transseptal pressure gradient was calculated as LV end-diastolic pressure-RV end-diastolic pressure. With the exception of when pericardial pressure decreased, such as during sustained caval constriction, LV anteroposterior diameter did not change. We therefore used changes in the septum-to-LV free wall diameter to reflect changes in LV end-diastolic volume. When LV anteroposterior diameter did change, we described the associated changes in LV area, our index of LV end-diastolic volume, which was calculated as the product of the two minor-axis LV dimensions (1–3, 5, 37, 45); RV end-diastolic diameter reflected RV end-diastolic volume (15). In the steady state, average RV and LV stroke volumes were assumed to be equal over time so that RV stroke volume was multiplied by a factor to make both equal. Repeated-measures ANOVA was used to test for significance of changes; a P value <0.05 was considered statistically significant.


   RESULTS
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 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Hemodynamic and dimension changes during ventilation. Figure 1, left, shows a representative example of airway pressure, inferior vena caval flow, and beat-to-beat ventricular dimension and hemodynamic changes during apnea interrupted by a single ventilatory cycle; Fig. 1, right, shows the pooled data from all the animals. As airway pressure increased during inspiration, vena caval flow decreased but began to increase while airway pressure was still increasing. As airway pressure decreased during expiration, caval flow increased above baseline. During inspiration, the transseptal pressure gradient and transmural LV end-diastolic pressure increased. RV diameter decreased and the septum-to-LV free wall diameter increased while the LV anteroposterior diameter did not change. LV area (data not shown) increased despite the decreased sum of the septum-to-free wall diameters. These dimension changes were associated with increased LV and decreased RV stroke volumes. All changes were statistically significant.



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  		Fig. 1. Left: example of hemodynamic and dimension changes during apnea interrupted by a single ventilation cycle. Right: pooled data from all the animals. As airway pressure increased, inferior vena caval (IVC) flow decreased transiently, the transseptal pressure gradient increased, the right ventricular (RV) diameter decreased, and the septum-to-left ventricular (LV) free wall diameter increased despite the decreased sum of the septum-to-free wall diameters, with no change in the LV anteroposterior diameter. LV and RV stroke volumes increased and decreased, respectively. Values for this and Figs. 2–5 are means ± SE. With respect to vena caval flow, the broken lines and open symbols compare peak changes with the baseline value. Dtc, sum of the septum-to-free wall diameters; LVAP, LV anteroposterior diameter; Pair, airway pressure; Qivc, IVC flow; SLVFW, septum-to-LV free wall diameter; SRVFW, septum-to-RV free wall diameter; SV, stroke volume; TLVEDP, transmural LV end-diastolic pressure; TSG, transseptal pressure gradient; SVlv, LV stroke volume; SVrv, RV stroke volume; {Delta}, change.

 
Inspiratory hold. Figure 2 shows a representative example of the responses to an inspiratory hold after 5 s of apnea and the subsequent decrease in airway pressure (left) and the pooled data from all the animals (right). The changes during inspiration were qualitatively similar to those during a single ventilatory cycle (Fig. 1). However, although the increased airway pressure was sustained, vena caval flow increased toward baseline, there was a progressive decrease in the transseptal pressure gradient (no apparent change in transmural LV end-diastolic pressure), the sum of the septum-to-free wall diameters decreased, and there was a progressive increase in RV dimension and decrease in septum-to-LV free wall diameter (and LV area) toward baseline. The dimension changes were associated with parallel changes in RV and LV stroke volumes. As airway pressure fell rapidly at the end of the inspiratory hold, vena caval flow increased above baseline. This was associated with a decreased transseptal pressure gradient (no change in transmural LV end-diastolic pressure), increased RV diameter, decreased septum-to-LV free wall diameter, and no change in the LV anteroposterior diameter. LV stroke volume decreased and RV stroke volume increased. All changes were statistically significant unless otherwise stated.



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  		Fig. 2. Effects of an inspiratory hold. Left: data from a representative example. Right: pooled data from all the animals. During the inspiratory phase, the changes were similar to those shown in Fig. 1. During the sustained increase in airway pressure, caval flow remained similar to that at baseline, transmural LV end-diastolic pressure returned toward baseline, the transseptal pressure gradient decreased, and LV dimensions and stroke volume tended toward baseline without a change in the sum of the septum-to-free wall diameters; RV dimension and stroke volume only partially returned toward baseline values. Release of the inspiratory hold caused changes opposite to those during the inspiratory phase. See Fig. 1 for abbreviations.

 
Inferior vena cava constriction. Figure 3 illustrates the changes caused by inferior vena caval constriction and subsequent release of the constriction during apnea in a representative example (left) and the pooled data from all animals (right). Inferior vena caval constriction decreased caval flow, RV diameter, and stroke volume and transiently increased the transseptal pressure gradient and transmural LV end-diastolic pressure. The septum-to-LV free wall diameter and stroke volume increased; there was a trend for LV area (data not shown) to increase (P = 0.085), and LV anteroposterior diameter was unchanged. Continued vena caval constriction then progressively decreased both RV and LV dimensions (and therefore the sum of the septal-to-free wall diameters and LV area) and stroke volumes as well as pericardial pressure. Release of the constriction increased caval flow, which decreased the transseptal pressure gradient and transmural LV end-diastolic pressure. RV diameter and stroke volume increased. The septum-to-LV free wall diameter, LV area (data not shown), and LV stroke volume decreased. LV anteroposterior diameter increased, at a time when external constraint was still decreased.



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  		Fig. 3. Effects of IVC occlusion. Left: representative example. Right: pooled data from all the animals. The vertical broken line on the left side of the example indicates the time of IVC constriction, and the line on the right shows the time of release of the constriction. For the pooled data on the right, the initial data are just before caval constriction (indicated by the 1st arrow on right), and the second arrow indicates the release of the constriction. The delta symbols indicate the differences compared with baseline (before constriction and before release of the constrictor) values. Caval occlusion reduced caval flow, increased transmural LVEDP, the transseptal pressure gradient, the septum-to-LV free wall diameter, and LV stroke volume. LV anteroposterior diameter did not change, and the sum of the septum-to-free wall diameters, RV dimension, and stroke volume decreased. Pericardial pressure decreased, in keeping with the decreased volume of the ventricles. Sustained constriction decreased end-diastolic pressures, dimensions, and LV and RV stroke volume. Release of the constrictor had transient effects that were opposite to those during constriction. Pperi, pericardial pressure; see Fig. 1 for the other abbreviations.

 
Abdominal compression. Abdominal compression frequently caused arrhythmias that precluded analysis in all but three of the animals. Figure 4 illustrates the changes during abdominal compression in a representative example (left) and the combined data (right). Abdominal compression transiently increased vena caval flow, which then returned to baseline or below within six beats. LV and RV end-diastolic pressures increased; transmural LV end-diastolic pressure changed little; and the transseptal pressure gradient tended to decrease for approximately three beats before returning toward baseline. RV diameter increased, the septum-to-LV free wall diameter decreased, the LV anteroposterior diameter remained unchanged, and the sum of the septal-to-free wall diameters increased. LV stroke volume decreased, and RV stroke volume increased. When abdominal compression was released, vena caval flow decreased transiently; this was associated with decreased LV and RV end-diastolic pressures, a slightly increased septum-to-LV free wall diameter, and a slight decrease in RV diameter. The other measurements changed little. It is noteworthy that, despite the maintained compression, caval flow only increased for ~3 s and, when the compression was released, caval flow decreased to a level below precompression values for ~1 s.



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  		Fig. 4. Effects of abdominal compression in 3 animals. Left: an example of the effects of abdominal compression. Right: pooled data. The broken vertical lines indicate application and removal of abdominal compression. The delta symbols indicate the differences compared with baseline. The initial values after the break in the horizontal axis are from just before release of the compression. During compression, caval flow increased, LV and RV end-diastolic pressures (LVEDP and RVEDP, respectively) increased, and the transseptal pressure gradient and transmural LVEDP decreased. RV diameter increased, the septum-to-LV free wall diameter decreased, and LV anteroposterior diameter did not change. RV stroke volume increased and LV stroke volume decreased. Immediately after release of the compression, the changes tended to be in the opposite direction. Pcuff, cuff compression pressure; see Fig. 1 for other abbreviations.

 

   DISCUSSION
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
In the present study, we focused on how transient changes in RV inflow similar to those observed during mechanical ventilation can affect LV end-diastolic volume and function by direct ventricular interaction. We found that, regardless how we manipulated inferior vena caval flow, transient decreases in RV inflow caused similar direct ventricular interaction to that seen with positive pressure inspiration (Fig. 5); RV end-diastolic volume and output decreased, the transseptal pressure gradient increased, the septum shifted rightward, LV end-diastolic volume increased, and LV stroke volume increased. (During caval constriction, when pericardial pressure decreased, the increase in LV volume was not statistically significant.) The opposite was also observed; transient increases in RV inflow simultaneously increased RV end-diastolic volume and stroke volume and decreased LV end-diastolic volume and stroke volume. The LV anteroposterior diameter did not change during any of the maneuvers (except when pericardial constraint was decreased during caval constriction). Therefore, in the presence of external constraint to LV filling, the changes in LV end-diastolic volume were the result of septal shift alone, similar to those observed in acute pulmonary hypertension and chronic severe heart failure (2, 3, 36).



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  		Fig. 5. Effects of changes in RV inflow on LV function. Decreased RV inflow during positive pressure inspiration or vena cava constriction transiently decreased RV end-diastolic volume and increased the transseptal pressure gradient, which caused the septum to shift to the right. LV end-diastolic volume (no change in the anteroposterior diameter) and stroke volume increased as a result. When RV inflow increased, the opposite occurred. Thus, during the expiratory phase of mechanical ventilation, when the inspiratory hold was released, when caval constriction was released or during abdominal compression, the transseptal pressure gradient decreased, which caused the septum to shift to the left. LV end-diastolic pressure and stroke volume decreased as a result.

 
Previous studies have shown that PEEP may contribute substantially to decreased LV preload during mechanical ventilation by direct ventricular interaction (4, 10, 11, 13, 28, 29, 40, 47). In a recent study, we observed that the phasic changes in RV filling that occur during mechanical ventilation (27, 38, 39) with PEEP levels between 2 and 11 cmH2O were associated with instantaneous, opposite changes in LV end-diastolic volume and that direct ventricular interaction (septal shift) was involved (35). However, many factors, including RV inflow and afterload (48), LV inflow and output, and external constraint contribute to the complex interaction; therefore, the independent contribution of phasic changes in RV inflow to LV function was unclear.

Effects of changes in RV inflow. The present study demonstrates that transient changes in RV inflow, produced by either positive pressure ventilation or by various maneuvers during apnea, caused simultaneous and opposite changes in LV end-diastolic volume and, consequently, LV stroke volume by direct ventricular interaction. The increased LV end-diastolic volume associated with decreased RV inflow implies that inflow to the LV increased, although this was not measured; however, the increase in both end-diastolic volume and stroke volume is consistent only with increased LV inflow. Vena caval constriction decreased the LV end-diastolic pressure (5.4 ± 2.8 to 4.8 ± 2.4 mmHg, P = 0.06), which presumably increased the pressure gradient from the pulmonary veins to the LV. Persistent caval constriction decreased RV and LV dimensions and output as well as pericardial pressure, in keeping with decreased total cardiac volume; we did not measure atrial volumes, which we presume decreased. The transient increase in RV inflow caused by release of the constriction increased LV end-diastolic pressure (from 1.8 to 4.1 mmHg, P < 0.025), which presumably decreased the pressure gradient from the pulmonary veins to the LV. Our experimental protocol did not provide data regarding the progression of changes of a sustained increase in RV inflow.

It is important to note that, during positive pressure inspiration, the increased LV end-diastolic volume occurred despite the decreased sum of the septum-to-free wall diameters. Thus LV end-diastolic volume increased despite the decreased total volume of the ventricles. When RV inflow reached a plateau during the respiratory cycle and the inspiratory hold maneuver, the septum-to-free wall diameters returned toward baseline, which highlights the transient nature of this interaction.

The results from the present study therefore indicate that the cyclic changes in LV end-diastolic volume and output during mechanical ventilation are not simply the result of a phase delay related to the changes in RV output (series interaction) since they were observed during apnea. It is also apparent that the changes in LV end-diastolic volume are not simply the result of squeezing blood from the lungs during inspiration, since the sum of the ventricular volumes decreased (this implies that LV end-diastolic volume could increase because RV end-diastolic volume decreased).

Hemodynamic changes during mechanical ventilation. In principle, positive pressure inspiration might increase LV end-diastolic volume by squeezing blood from the lungs and/or by reducing RV inflow. Inferior vena cava constriction isolated the effects of decreased RV inflow (the transseptal gradient increased, the septum shifted rightward, LV transmural pressure increased, and LV stroke volume increased), all without squeezing any blood from the lungs. Compared with the results of a single ventilation cycle, the responses were in the same direction and similar in magnitude. (As shown in Figs. 1 and 3, the reduction in flow with vena cava constriction seems somewhat greater than that produced by a single ventilatory cycle, but, in terms of the augmentation of LV stroke volume and the changes in dimensions, the results were similar.) During positive pressure inspiration, LV end-diastolic pressure increased (5.4 ± 2.6 to 8.3 ± 2.8 mmHg, P < 0.001). Thus increased LV inflow could only have occurred if a pressure gradient was maintained between the pulmonary veins and the LV. We therefore suggest that the lung-squeezing effect of positive pressure inspiration is an integral component of the mechanism by which LV filling is increased during mechanical ventilation. However, when one considers that LV end-diastolic volume may decrease in some circumstances during inspiration (14), the lung squeezing effect alone may not be sufficient to increase LV filling; we suggest that RV end-diastolic volume may need to decrease for LV end-diastolic volume to increase.

Although the present study demonstrates an independent contribution of RV filling to LV function by direct ventricular interaction when RV inflow is manipulated during apnea, this mechanism can only be considered as one facet of the more complex heart-lung interaction during mechanical ventilation. Series interaction is clearly an important determinant of LV filling; a change in RV output would be expected to be followed by a similar change in LV filling after a delay of several cardiac cycles. In addition, because intrathoracic pressure and lung volume vary during ventilation, the associated changes in RV inflow (27, 38, 39) tend to have the opposite effect on LV end-diastolic volume and stroke volume. This interaction is illustrated by the inspiratory hold maneuver, during which left and RV end-diastolic volumes returned toward baseline after several cardiac cycles, which is consistent with the short-lived decrease and return toward baseline in inferior vena cava flow. After an initial increase in the transseptal pressure gradient, it decreased toward baseline with held inspiration. This resulted in a septal shift such that RV end-diastolic volume increased and LV end-diastolic volume decreased, whereas the sum of the septum-to-free wall diameters remained unchanged (this indicates that septal shift was responsible for these changes).

Thus RV hemodynamics may affect LV filling by several, sometimes counteracting, mechanisms during mechanical ventilation. To add to the complexity of the heart-lung interaction, any increase in pulmonary vascular resistance (common with higher levels of PEEP) can reduce RV output, increase RV end-diastolic pressure, and shift the septum leftward. This can result in either an unchanged or even increased (instead of decreased) RV end-diastolic volume at end-expiration (9, 27, 28, 35). Thus increased pulmonary vascular resistance may decrease LV preload by both series and direct ventricular interaction.

Although LV end-diastolic volume and stroke volume increased during positive pressure inspiration in this and our previous study (35), the opposite has been observed under some circumstances, as illustrated in the report by Denault et al. (14). Although the mechanism by which this may occur has not been clarified, we and others (35, 48) speculate that zone 2 conditions may result in increased pulmonary vascular resistance during inspiration when LV filling pressure is low (as was the case in the study by Denault et al.); such an increase in pulmonary vascular resistance might cause a decreased transseptal pressure gradient that would shift the septum leftward and decrease LV volume. The results of this and our recent studies are more consistent with zone 3 conditions since LV end-diastolic pressure was higher. Thus an inspiratory increase in lung volume was less likely to cause a substantial increase in pulmonary vascular resistance, in which case there would be a lower tendency for the septum to be shifted leftward. It is therefore clear that the contribution of RV inflow to LV function should be assessed in context of other important factors that may also affect LV filling. The different responses to similar increases in airway pressure on LV filling at end-expiration compared with during inspiration (35) underscore the importance of near-constant RV inflow at end-expiration compared with the transient decrease in RV inflow during inspiration.

Mechanisms of ventricular interaction. In this, as in our previous studies, we have studied ventricular interaction by relating changes in ventricular and pericardial pressures to changes in (2-dimensional) minor-axis dimensions. We have done this for several reasons. First, in the presence of the pericardium, the reciprocal changes in LV and RV septum-to-free-wall dimensions provide a sensitive indicator of ventricular interaction (20, 32). Second, pericardial pressure is nonuniform (26, 44) and, although difficult to measure, would seem to be substantially less near the apex of the heart than in the equatorial plane, where it is likely to be maximal. Finally, minor-axis dimensions are easier to measure than the total "vertical" dimension of the heart, and they correspond well to conventional echocardiographic views, thus facilitating clinical correlations between experimental studies and observations in patients. However, all of these reasons notwithstanding, none of our observations imply that three-dimensional, atrioventricular interaction is unimportant or negligible. Indeed, Linderer et al. (33) previously demonstrated in arteriovenous-blocked dogs that, during manipulation of the (paced) P-R interval, when the atria did not empty, pericardial pressure increased, causing diminished LV compliance and stroke volume. In addition, Hamilton et al. (22) recently demonstrated that pericardial pressures over the right atrium and ventricle, although similar during ventricular diastole, diverge during systole, with pericardial pressure over the right ventricle decreasing as systolic contraction increases elastance and transmural pressure. Such three-dimensional interaction is predictable theoretically, based on the virtually constant-volume property of the four-chambered heart, as demonstrated experimentally by Hoffman and Ritman (25) and recently confirmed in patients by Bowman and Kovacs (6).

Limitations of the study. The present work focused on the independent effects of changes in RV filling on LV filling and performance. Although isolation of the effects of this single factor may help explain the contribution of RV inflow to complex heart-lung interaction during mechanical ventilation, we cannot provide a comprehensive or quantitative account of all the factors involved and the relative contribution of changes in RV end-diastolic volume. However, the magnitude of the changes in LV function caused by changes in RV end-diastolic volume was not substantially different from those observed during mechanical ventilation, which suggests that RV volume does have an important effect on LV performance in the intact, ventilated model. Because we did not vary LV end-diastolic pressure systematically, we cannot address the question of how different filling pressures might have affected changes in pulmonary vascular resistance and thus direct ventricular interaction during mechanical ventilation. The study was also performed in normal animals so that the results cannot be extrapolated to disease states without further testing.

In conclusion, the present study indicates that changes in RV end-diastolic volume, in and of themselves, may substantially modulate LV performance by direct ventricular interaction. The magnitude of isolated changes in RV inflow was similar to those observed during continuous mechanical ventilation. This suggests that transient changes in RV filling modulate LV performance by direct ventricular interaction during mechanical ventilation as well.


   GRANTS
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This work was supported in part by grants-in-aid from the Alberta Heart and Stroke Foundation (Calgary) held by I. Belenkie and by J. V. Tyberg.


   FOOTNOTES
 

Address for reprint requests and other correspondence: I. Belenkie, Health Sciences Centre, 3330 Hospital Dr. N.W., Calgary, Alberta, Canada T2N 4N1 (e-mail: belenkie{at}ucalgary.ca)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

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