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Intensive Care

Medicine

9 Springer-Verlag 1994

Effects of piroximone on the right ventricular function in severe heart failure patients

J.P. Saal, R. Habbal, P. Estagnasie, D. Lellouche, A. Castaigne, J.L. Dubois-Rand6

D~partement de Cardiologie and INSERM U2, H6pital Henri Mondor, F-94010 Cr6teil, France Received: 26 February 1993/Accepted: 24 June 1993

Abstract. Objectives: To assess the effects of piroximone, a phosphodiesterase inhibitor, on right ventricular func- tion in patients with heart failure.

Design: Randomized study: patients were randomly assigned to the piroximone infusion rate of 5 or 10 gg/kg/min.

Setting: Cardiologic intensive care unit.

Patients: 12 consecutive patients with severe heart failure.

Interventions: Right heart catheterization was performed using a Swan-Ganz ejection fraction thermodilution catheter.

Measurements and results: Measurements of right ven- tricular ejection fraction (RVEF), end-diastolic and end- systolic right ventricular volumes were obtained using the thermodilution principle. To determine contractility in- dexes, the relationships between end-systolic pulmonary arterial pressure (ESPAP) over right ventricular end-sys- tolic volume (RVESV) and ESPAP over RVEF were calcu- lated during the infusion of prostacyclin at incremental infusion rates of 2, 4, 6 and 8 ng/kg/min. The slope of the relation between ESPAP over RVESV shifted during piroximone therapy from 7.635_+1.632 to 1.975_+0.432 (p<0.01) and from 6.092_+1.99 to 1.028+0.853 (p <0.05) at 5 and 10 gg/kg/min piroximone infusion, respectively. The slope of the relation between ESPAP over RVEF decreased from -0.414-+0.296 to -0.821-+0.257 (p<0.01) and from -0.127_+0.048 to -0.533+0.135 (p <0.05) at 5 and 10 gg/kg/min pirox- imone infusion, respectively.

Conclusions: This study suggests a positive action of piroximone on right ventricular contractility at these 2 dosages. This approach using this type of catheter al- lowed us to determine right ventricular inotropic indexes.

Key words: Right ventricular function - Heart failure - Thermodilution

Correspondence to: Dr. J.L. Dubois-Rand6

It has been shown that right ventricular function is ex- tremely important in many disease states [1, 2]. However, in human studies the assessment of right ventricular function is difficult, mostly due to the fact that imaging techniques used to measure left ventricular function are not applicable to the right ventricle. Recently, the mea- surements of right ventricular ejection fraction (RVEF) and volumes by a thermodilution technique have brought the analysis of the right ventricular function to the bed- side of the practicing physician [3, 4]. This potentially al- lows the evaluation of drug effects on the right ventricle especially in patients with severe cardiac disease in whom the assessment of right ventricular function is not cur- rently investigated. This study was designed to evaluate the effect on right ventricular function of a new inotropic agent, piroximone, whose action is mediated by phosphodiesterase inhibition. This drug has been studied in experimental and human settings demonstrating both inotropic and vasodilating effects [5-8]. To further as- sess the pyhsiologic effect of this drug on the right ventri- cle and especially to determinate the inotropic action of piroximone, we studied the action of piroximone after afterload changes obtained by infusing incremental doses of prostacyclin, a known vasodilating agent of the pulmonary circulation [9, 101.

Patient and methods Study population

The study group consisted of 12 consecutive patients admitted to the in- tensive care unit with New York Heart Association functional class IV congestive heart failure despite optimal standard therapy with diuretics and vasodilators with a cardiac index <2.5 l . m i n - l m -2 and pulmo- nary capillary wedge pressure > 15 mmHg. Mean age was 57_+8 years (31-69), there were 10 males and 2 females. All patients had a dilated cardiomyopathy as documented by echocardiograpby measurements (mean end-diastolic diameter = 67_+ 14 ram) without major tricuspid re- gurgitation (small spacial distribution < half the right atrium) and no pulmonary regurgitation. Radionuclide left ventricular ejection fraction was 18.8 _+ 3.2% and all patients had sinus rhythm. The cause of conges- tive heart failure was idiopathic dilated cardiomyopathy in 10 cases and

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ischaemic cardiomyopathy in 2 cases. All vasodilators and digitalis were withheld at least 36 h before the time of the study. Diuretics were con- tinued at the previous dosage throughout the study. For patients who required inotropic support, dobntamine infusion was withdrawn at least 2 h before the start of the study. Assessment of the local Ethics Com- mittee was obtained and patients signed an informed consent.

Haemodynamic measurements

Right heart catheterization was performed with a Swan-Ganz Ejection Fraction Thermodilntion Catheter (Model 93A-431 H-7.5F: Baxter-Ed- wards Laboratory, Irvine, CA). This heparin-coated catheter (Throm- boshield) is constructed from a quadruple lumen radio-opaque polyvinylchloride extrusion with a fast-response (95 ms) thermistor and atrial and ventrieular electrodes for intracardiac ECG recordings. The catheter was introduced 12 h before entering the study via a jugular or antecubital vein. The position of the catheter was controlled by fluoroscopy. Its proximal injectate lumen terminates in a multihole port, which was positioned in the right atrium just above the tricuspid valve. Cardiac output and RVEF were measured by successive injections of four 10-ml boluses of iced 5~ glucose solution. Right atrial, pulmo- nary artery, and pulmonary wedge pressures were measured simulta- neously at end expiration. For RVEF determination, the thermodilution signal was coupled with and ejection fraction and cardiac output calculating computer (REF-l:Baxter-Edwards Laboratory, Irvine, CA) allowing measurements of end-diastolic and end-systolic right ven- tricniar volumes, using thermodilution principle. The catheter's rapid response thermistor gives a high fidelity thermodilution curve with characteristic steps or plateaus that represent beat-to-beat changes in blood temperature. The ECG electrodes sense the R-wave, thus identify- ing actual ventricular contractions. R-waves are synchronized with the thermodilntion curve plateaus to calculate RVEF by an exponential technique [3, 4]. Arterial blood pressure was monitored invasively using a radial lannula. All pressure tracings were recorded on a multichannel recorder (Gould TA 2000, Cleveland, OH).

Two recordings of 1 h baseline haemodynamic measurements were made, at least 10 min apart within 1 h prior to drug administration.

Both baseline measurements had to be reproductible and within 1007o of each other. The following variables were measured at baseline: heart rate; mean arterial blood pressure; end-systolic (dicrotic notch pressure) (ESPAP) and mean pulmonary arterial pressure; mean right atrial pressure and mean pulmonary capillary wedge pressure; cardiac output and RVEF.

The following haemodynamic variables were calculated: cardiac in- dex (1/min/m2-cardiac outpnt/body surface area), systemic vascular resistance dynes-s.cm -5 - 8 0 x (mean arterial blood pressure minus

mean right atrial pressure/cardiac output) and pulmonary vascular re- sistance d y n e s . s . c m - 5 _ 80 x (mean pulmonary artery pressure minus mean pulmonary capillary wedge pressure/cardiac output). Right ven- tricular end-diastolic volume (cardiac outpnt/(heart rate•

right ventricular end-systolic volume (RVESV)- (end-diastolic ventricu- lar volume minus (cardiac output/heart rate)) and stroke volume (cardi- ac output/heart rate) were obtained directly from the RVEF and cardiac output calculating computer.

Calculation of end-systolic relationship

To determine inotropic indices, 2 end-systolic relations were calculated for each patient. The relationships between ESPAP over RVESV and ESPAP over RVEE To measure the slope of these relations, a large range of right ventricular afterload changes were obtained by infusing prostacyclin at the incremental infusion rate of 2, 4, 6 and 8 ng/kg/min during 15 min each. During this period, haemodynamic parameters were recorded every 5 rain resulting in the tracings for each patient of an average of 13 (10-18) end-systolic relationships.

Protocol and piroximone administration regimen

After baseline haemodynamic measurements, the prostacyclin test was performed for all patients. After recovery of baseline hemodyuamics, patients received piroximoue 50 gg/kg i.v. bolus and then were random- ly assigned to the piroximone infusion rate of 5 or 10 ~g/kg/min. At 6 h piroximone infusion, when haemodynamics were stable, the same pro- stacyclin test was performed and the slopes of end-systolic relationship traced.

Statistical analysis

Results are expressed as m e a n i S E M . Pairwise comparisons were made using a non-parametric Wilcoxon test. Comparisons between groups were done using the Mann Whitney test. For each subject simple regres- sion by the least squares method was used to calculate the slope of end- systolic relationships. A p < 0.05 level was considered as significant.

Results

Effects of piroximone infusion on cardiac performance The 2 groups o f patients did not differ significantly as re- gard to age, aetiology of the cardiomyopathy and baseline haemodynamir parameters (Table 1). Figure 1

Table 1. Patient characteristics at baseline in group 1 and group 2 randomly assigned to receive either 5 Ixg/kg/min or 10 ~tg/kg/min piroximone Number Age Aetiology Left VEF Right VEF Heart rate Cardiac Mean Capillary Right

(Years) 070 o7o (beats min) index Arterial Wedge Atrial

(1/min/m 2) Pressure Pressure Pressure

(mmHg) (mmHg) (mmHg)

Group 1 5 gg/kg/min

Group 2 10 Ixg/kg/min

1 57 ISCH 18 9 92 1.67 87 40 12

2 53 DCM 16 10 90 1.12 88 38 10

3 44 DCM 15 5 90 1.14 85 20 15

4 52 DCM 23 13 95 2.63 68 15 1

5 56 DCM 24 9 97 2.16 84 28 3

6 62 DCM 21 9 119 1.75 89 28 9

M e a n • 54• 19.5• 9.2• 97• 1.74• 83.5• 2 8 • 8.3•

7 56 DCM 16 9 93 2.09 73 16 5

8 68 ISCH 18 9 87 1.79 66 18 10

9 70 DCM 22 18 70 1.56 99 23 10

10 43 DCM 21 19 100 1.86 85 23 12

11 61 DCM 15 11 81 1.84 77 19 16

12 58 DCM 17 5 130 1.21 76 29 22

Mean• SEM 59 • 18 • 1.14 11.8 • 2.25 93.5 • 8.4 1.73 • 79.3 • 4.7 21.3 • 1.9 12.5 • 2.4 VEF: ventricular ejection fraction

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Fig. 1. Haemodynamic effects of piroximone. Haemodynamic improve- ment at 6 h piroximone infusion at the infusion rate of 5 and 10 ~tg/kg/min. CI, cardiac index; PCWP, pulmonary capillary wedge pressure; RAP, mean right atrial pressure, PAP, mean pulmonary arteri- al pressure; PI/'R, pulmonary vascular resistance; SVR, systemic vascu- lar resistance. *p < 0.05 vs baseline

showed the haemodynamic improvement at 6 h pirox- imone infusion in both groups. An increase in cardiac in- dex was observed associated with a decrease in filling pressures, systemic and pulmonary vascular resistances.

Heart rate remained unchanged in both groups while mean arterial pressure decreased by 7-+4% and by 10.5_+5% at 5 and 10 l~g/kg/min infusion rate, respec- tively (NS). There was no difference in the magnitude of the haemodynamic effects between the 2 piroximone in- fusion rates.

Effects of prostacyclin infusion before and at 6 h piroximone infusion (Fig. 2)

The decrease of mean pulmonary artery pressure and resistance were significant from the infusion rate of 4 ng/kg/min. At 8 ng/kg/min, a slight decrease in mean arterial blood pressure was observed while heart rate remained unchanged.

Effect of piroximone on the right ventricular function:

end-systolic relationship

During piroximone infusion, RVEF and stroke volume increased while end-diastolic and end-systolic volumes decreased (Fig. 3). For each patient there was a positive relationship (Fig. 4) between ESPAP and RVESV during prostacyclin infusion as well as during piroximone thera- py. The average slope of ESPAP over RVESV shifted dur- ing piroximone therapy resulting in smaller values for RVESV at any ESPAP which suggests a positive inotropic effect of piroximone. This slope decreased from 7.635+1.632 to 1.975+0.432 (p<0.01) and from 6.092_+1.99 to 1.028_+0.853 (,o<0.05) at 5 and 10 pg/kg/min piroximone infusion, respectively. There was a negative relationship between ESPAP and RVEF (Fig. 4) both before and during piroximone therapy.

There was a shift of the slope of ESPAP over RVEF from -0.414+0.296 to -0.821+0.257 (p <0.01) a n d from -0.127-+0.048 to -0.533-+0.135 (p<0.05) at 5 and 10 ~tg/kg/min piroximone infusion, respectively. This in- dicates that for any ESPAP, piroximone increased RVEE

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Effects of prostacyclin at the infusion rate of 8 ng/kg/min on mean pulmonary arteri- al pressure, pulmonary vascular resistance, mean arterial blood pressure and heart rate before and during piroximone infusion.

Since there was no difference in the magni- tude of the haemodynamic effects of the piroximone infusion rates of 5 and 10 gg/kg/min, the results of both infusion rates were combined. *p <0.05, **p <0.01 vs baseline

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Fig. 3. Effect of piroximone on right ventricular function. Improvement of right ventricular function at 6 h piroximone infusion at the infusion rate of 5 and 10 Ixg/kg/min. Since there was no difference in the magni- tude of the haemodynamic effects of the piroximone infusion rates of 5 and 10 ~tg/kg/min, theresults of both infusion rates were combined.

*p <0.01 vs baseline

There was no significant difference in the magnitude of the changes of these relationships between the 2 pirox- imone infusion rates. Individual data concerning the changes of the slopes of the relationships between ESPAP over RVESV and ESPAP over RVEF obtained during prostacyclin infusion both before and during piroximone infusion are shown in Table 2. When the re- suits of the 2 different piroximone infusion rates are com- bined, the shift of both end-systolic slopes was highly sig- nificant (p < 0.001, Table 2).

Discussion

The present study shows a direct inotropic action of piroximone on the right ventricle both at the infusion rates of 5 and 10 gg/kg/min. These results were obtained from the use of a thermodilution-right ventricular ejec- tion catheter and from the tracing of end-systolic rela- tionships. In recent years, the importance of right heart disorders has been emphasized in acutely ill patients. A

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Fig. 4. Data from patient no. 3 (5 gg/kg/min). End-systolic relation- ships. RVEF, right ventricular ejection fraction; ESPAP, end-systolic pulmonary arterial pressure; RVESV, right ventricular end-systolic vol- ume. Prostacyclin infusion allowed tracing of end-systolic relationships.

This figure shows and example of end-systolic relationships in one pa, tient. Top: End-systolic pulmonary arterial pressures and right ven- tricular ejection fractions were negatively correlated. During pirox- imone infusion, the slope of this relationship shifted resulting in higher RVEF at any ESPAP. Baltons." End-systolic pulmonary arterial pres- sures and RVESVs were negatively correlated. During piroximone infu- sion, the slope of these relation shifted resulting in lower RVESV at any ESPAP

major problem in assessing right ventricular function arose from difficulties in measuring right ventricular vol- umes. Imaging techniques routinely used to measure left ventricular volumes are not compatible with the right ventricular shape and the orientation of the right ventri- cle relative to inflow and outflow tracts. Among them, ra- dionuclide techniques are the current gold standard for measurement of RVEF for they allow measurements to be made from proportional changes in right ventricular vol- umes without assumptions concerning the complex shape of the right ventricle [ll]. However, it is not a simple ex- amination which can be done and repeated for critically ill patients. Echocardiography is able to estimate fight ventricular function but measurements of volume are hampered by several limitations [12]. In contrast, ther- modilution measurements permits potentially repeated determinations of the RVEF [3, 4]. Since neither shape nor overlying structure affects estimates of ejection frac- tion by indicator dilution techniques, no assumption about either cavity shape or orientation is necessary.

The present study was designed to measure RVEF and right ventricular volumes by thermodilution in severe heart failure patients and its ability to assess the effect of dugs on the right ventricular function. Indeed, it has been shown that at any level of contractility, end-systolic fiber length is a direct function of and varies inversely with

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345 Table 2. Individual end-systolic relationships obtained during prostacyclin infusion at baseline and during piroximone infusion

Number ESPAP/RVEF ESPAP/RVEF ESPAP/RVESV ESPAP/RVESV

Base Piroximone Base Piroximone

1 -0.124 -0.519 10.7 2.67

2 - 0.007 - 0.425 5.61 1,58

3 -0.186 -0.656 12.4 2.44

4 - 1.890 - 2.080 1.09 0.69

5 - 0.157 - 0.782 7.45 1.02

6 - 0.117 - 0.465 8.56 3.45

7 -0.024 - i.010 11.3 4.36

8 - 0.056 - 0.229 3.92 0.29

9 -0.318 -0.848 13 0.10

10 - 0.090 - 0.540 0.84 - 1.89

11 - 0.223 - 0.320 4.54 1.78

12 - 0.050 - 0.452 2.95 1.53

Mean - 0.270 - 0.694 6.86 1.50

SEM 0.148 0.142 1.25 0.48

p value < 0.001 < 0.001

ESPAP: end-systolic pulmonary arterial pressure; RVEF: right ventricular ejection fraction; RVESV: right ventricular end-systolic volume

afterload [13]. In humans, by focusing attention on the relation between the end-systolic volume and the ventric- ular pressure at that instant, it is possible to assess con- tractility [14, 15]. At a given level o f contractility, there is a unique line relating end-systolic pressure to end-systolic volume which is independent of load. The slope o f this line defines contractility. In the present study, incremen- tal prostacyclin infusion rates has been p e r f o r m e d to in- duce afterload changes o f the right ventricle and then ob- tain a wide range o f end-systolic relationships for tracing the slopes o f the relationships between end-systolic vol- umes or ejection fraction and end-systolic pressures. In- deed, in our patients, the infusion o f prostacyclin resulted in b o t h a decrease in p u l m o n a r y pressures and resistance.

The relatively low infusion rates o f prostacyclin used in this study were given only to induce right ventricular afterload changes without inducing i m p o r t a n t systemic effects which by themselves m a y induce changes in con- tractility. Indeed, other studies using protacyclin in heart failure patients with infusion rates up to 10 n g / k g / m i n showed an i m p o r t a n t hypotensive action o f prostacyclin and increased catecholamines [16]. In the present study, due to the low dosages o f prostacyclin used, only slight changes in m e a n arterial pressure and heart rate occurred.

Phosphodiesterase inhibitors that are selective for adenosine 3': Y-cyclic p h o s p h a t e (cAMP)-specific cardiac and vascular phosphodiesterase isozyme I I I comprise a new groups of agents for the treatment o f heart failure [17]. Previous studies have demonstrated that these agents have b o t h left ventricular inotropic effect and sys- temic vasodilating action. However, in contrast to the left ventricle, clinically relevant right ventricular inotropic contribution to drug effect in patients with congestive heart failure has been less documented. Indeed, phosphodiesterase inhibitors administration could im- prove right ventricular p e r f o r m a n c e by combining an in- crease in right ventricular contractility associated with a reduced right ventricular afterload due to augmented left ventricular p e r f o r m a n c e and decreased in p u l m o n a r y ar-

teriolar resistance. Additionally, direct effects o f these agents on p u l m o n a r y vascular s m o o t h muscle have been shown which m a y also participate to the h a e m o d y n a m i c benefit of these drugs on the right ventricular function [18]. Potential improvement o f the right ventricular func- tion by phosphodiesterase inhibitor agents has been pre- viously examined with amrinone and milrinone using ra- dionuclide ventriculography suggesting a direct inotropic action on the right ventricular function [19, 20]. The authors found that the inotropic action o f these agents on the right ventricle appeared to be modest suggesting that the improvement of right ventricular p e r f o r m a n c e was mainly explained on the basis o f right ventricular afterload reduction. Recently, we showed in an experi- mental model, that in contrast to prostacyclin, enox- imone had no or little direct effect on the p u l m o n a r y vascular bed which m a y suggest that the action o f phosphodiesterase inhibitors on right v e n t r i c u l a r afterload is not due to a direct action on p u l m o n a r y vas- cular bed [10]. Piroximone is a n o t h e r phosphodiestase inhibitor. Its h e m o d y n a m i c effects have been examined previously and piroximone improves h a e m o d y n a m i c s by combining b o t h inotropic and systemic vasodilating properties [ 5 - 8 ] . In previous studies, different dosages were evaluated and the infusion rates o f 5 and 10 g g / k g / m i n improved h a e m o d y n a m i c s generally in pa- tients with severe heart failure. In the present study, these 2 infusion rates o f piroximone were administered to as- sess their potential inotropic action on right ventricular function. The effects o f piroximone on right ventricular function was examined when h a e m o d y n a m i c improve- ment was stable and not during the bolus injection phase.

The h a e m o d y n a m i c effects o f piroximone observed in the present study were consistent with those found in other studies with an increase in cardiac index and a decrease in b o t h filling pressures and systemic vascular resistance.

No difference in h a e m o d y n a m i c effects were observed be- tween the 2 infusion rates. In the present study, pirox- imone induced a decrease in end-systolic volumes and in-

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346

crease in stroke volume and RVEE This improvement in right ventricular performance which has been described with other phosphodiesterase inhibitors [19, 20] cannot be interpreted as an inotropic action since it is mainly de- pendent on loading conditions. The analysis of end- systolic relationships at the level of the right ventricle al- lowed to delineate the direct inotropic action of the drug.

In contrast to baseline, the slopes of the relationships be- tween ESPAP and RVEF and volume shifted during piroximone infusion showing that for the same ESPAP, the RVESV was lower and the RVEF was higher with piroximone. No significant difference in the magnitude of the end-systolic relationships changes was observed be- tween 5 and 10 ~g/kg/min. These results suggest that right ventricular positive inotropic effect occurred partic- ipating to the improvement in right ventricular perfor- mance observed with this drug.

Limitation of the study

Thermoclilution-ejection fraction catheter

Several limitations of this technique must be pointed out.

The use of thermodilution ejection fraction catheter to measure RVEF is hampered by serious limitations which have been discussed previously [2t]. Indeed, it requires both adequate mixing of the cold bolus in the right ven- tricle and precise detection of temperature changes in the pulmonary artery. However, with the catheter used in the present study, mixing of the cold indicator was facilitated by its injection via a multihole port located just above the tricuspid valve, as measurements from the right atrial in- jections are more reproducible than those from the right ventricular injections. Using a fast-response thermistor for determining precise temperature changes in the pul- monary artery, identifying the plateaus on the thermal washout curve might be limited by inadequate stabilisa- tion of temperatures between successive cardiac beats, es- pecially in cases of low RVEF and cardiac output which was the case in our study. The new algorhythm method does not require identification of these plateaus; instead, it can directly and acuretaly determine presystolic param- eters. T h i s thermodilution catheter has been validated previously with a variability of 7%, showing that al- though there is some discrepancies between RVEF and ra- dionuclear techniques, thermodilution technique allow simple, accurate and repetitive bedside measurements of right ventricular function in the critically ill [3, 4].

Right ventricular function assessment

Additionally, care must be taken when describing right ventricular function and its determinants using knowl- edge gleamed from left ventricular physiology and data acquired using this ejection fraction catheter system. In- deed, the right ventricle may operate by a unique set of rules not previously defined [22, 23]. Systolic contraction prior to ejection results in initial conformational changes in the right ventricle, which probably reduce wall stress rather than increase it, despite increasing intra-cavitary pressure. Similarly, right ventricular ejection continues

well into the descending phase of the pulmonary arterial pressure signal, thus making estimates of end-systolic pressure-volume relations difficult [24]. However, despite several methodological limitations, the linearity of the right ventricular end-systolic pressure-volume relation- ships during vasodilator administration has been demon- strated previously in different pathological states and es- pecially in heart failure patients [25, 26]. In the present study, we approximated acute drug-induced changes in right ventricular afterload from changes in pulmonary dicrotic notch pressure using methodology analogous to previous investigators [19, 20, 25]. In the present study, 2 end-systolic relationships were calculated: ESPAP over RVESV and ESPAP over RVEF [27]. Both calculations are hampered by methodological limitations. Measuring the extent of cardiac muscle shortening and relating this shortening to end-systolic pressure has been shown to be an index of contractility [27]. However, one caution con- cerning the relation pressure over ejection fraction is that it is preload dependent [27, 28]. Additionally, the right ventricular ejection catheter measures only forward flow as residual thermal volume. Therefore, if tricuspid insuf- ficiency exists, ejection fraction measurements may change during drug administration. During piroximone infusion, unloaded right ventricle related to left ventricu- lar function improvement could have decreased tricuspid regurgitation. Consequently, this would have changed RVEF which in turn would lead to modification of the estimation of end-systolic volumes and finally of end- systolic relationships. Despite this the last point was care- fully limited by assessing tricuspid insufficiency by echographic analysis and excluding patients with severe regurgitation although this is obviously the major limit- ing factor of this method.

Interaction piroximone and prostacyclin

An interaction between prostacyclin and piroximone can- not be excluded since both agents act by increasing cAMP at the cellular level [9]. Indeed, in the present study the effects of piroximone on the right ventricular function have been evaluated during prostacyclin infusion. Addi- tionally, it is likely that an additive action of prostacyclin to piroximone occurred in our patients since both mean arterial blood pressure and mean pulmonary arterial pressure were lower during prostacyclin infusion combin- ed with piroximone than during piroximone infusion alone which suggests an additive vascular action of pro- stacyclin both on the systemic and pulmonary vascular beds.

Clinical implications

The major problem in assessing the right ventricular function arose from difficulties in measuring right ven- tricular volumes. The use of thermodilution despite sev- eral limitations offers a bedside approach to the measure- ment of the right ventricular function in patients with congestive heart failure. Additionally, by using end-sys- tolic data obtained during afterload changes, an ap- proach of the inotropic action of phosphodiesterase in-

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hibitor agents was possible. This relatively simple evalua- tion might have important clinical implications in differ- ent cardiac diseases where right ventricular dysfunction is critical [29]. Additionally this catheter allows the evalua- tion of the efficacy of therapeutical agents.

References

1. Sibbald WJ, Driedger A A (1983) Right ventricular function in acute disease states: pathophysiologic considerations. Crit Care Med 11:339-345

2. Hurford WE, Zapol WM (1988) The right ventricle and critical ill- ness: a review of anatomy, physiology, and clinical evaluation of its function. Intensive Care Med 14:448-457

3. Vincent JL, Thirion M, Brimioulle S, Lejeune P, Kahn RJ (1986) Thermodilution measurement of RVEF with a modified pulmonary artery catheter. Intensive Care Med 12:33-38

4. Dhainaut JF, Brunet F, Monsallier JF, Villemant D, Devaux JY, Konno M, De Gournay JM, Armaganidis A, Iotti G, Huyghebaert M J, Lanore JJ (1987) Bedside evaluation of right ventricular per- formance using rapid computerized thermodilution method. Crit Care Med 15:148-152

5. Petein M, Levine B, Cohn JN (1984) Hemodynamic effects of a new inotropic agent, piroximone (MDL 19205), in patients with chronic heart failure. J Am Coil Cardiol 4:364-371

6. Arbogast R, Brandt CM, Fincker JL, Schechter PJ (1986) Acute hemodynamic effects of piroximone in patients with moderate con- gestive heart failure: comparison with sodium nitroprusside. J Car- diovascular Pharm 8:82-89

7. Axelrod RJ, De Marco T, Dae M, Botvinick EH, Chatterjee K (1987) Hemodynamic and clinical evaluation of Piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure. J Am Coll Cardiol 9:1124-1130

8. Miller WE, Kennedy GT, Ruberg S J, O'Rourke RA, Crawford MH (1988) Hemodynamic effects of a constant intravenous infusion of piroximone in patients with severe congestive heart failure. J Car- diovascular Pharm 12:72-77

9. Kerins DM, Murray R, FitzGerald GA (1991) Prostacyclin and pro- staglandin El: molecular mechanisms and therapeutic utility. Prog Hemost Thromb 10:307-337

10. Deleuze P, Dubois-Rand6 JL, Loisance D, Cachera JP (1992) Eval- uation of enoximone vasodilating effects on animals implanted with a total artifical heart. J Thorac Cardiovasc Surg 103:589-594 11. Helier GV, Treves ST, Parker A (1986) Comparison of ultrashortliv- ed Iridium 191m with technetium 99m for first pass radionuclide angiographic evaluation of right and left function in adults. J Am Coll Cardiol 7:1295-1302

12. Levine RA, Gibson TC, Aretz T, Gillan LD, Guyer DE, King ME, Weyman AE (1984) Echocardiographic measurement of right ven- tricular volume. Circulation 69:497-505

13. Kass DA, Mangham WL, Guo ZM, Kono A, Sunagawa K, Sagawa K (1987) Comparative influence of load versus inotropic states on indexes of ventricular contractility: experimental and theoretical analysis based on pressure-volume relationship. Circulation 6:1422-1436

14. Grossman W, Braunwald E, Mann T, Mc Laurin LP, Green LH (1977) Contractile state of the left ventricle in man as evaluated from end-systolic pressure-volume relation. Circulation 56:

8 4 5 - 852

15. Dubois-Rand6 JL, Duval AM, Saal JP, Merlet P, Lellouche D, Deleuze Ph, Dupouy P, Brun Ph, Loisance D, Castaigne A (1991) Physiologic assessment of milrinone therapy in severe heart failure patients. J Cardiovasc Pharmacol 17:941-948

16. Yoshika Y, Nakajima H, Kawai C, Murakami T (1982) Prostacyclin therapy in patients with congestive heart failure. Am J Cardiol 50:320- 324

17. DiBianco R (1991) Acute positive inotropic intervention: the phosphodiesterase inhibitors. Am Heart J 121:1871-1875 18. Hill NS, Rounds S (1983) Amrinone dilates pulmonary vessels and

blunts hypoxic vasoconstriction in isolated rat lungs. Proc Soc Exp Biol Meal 173205-213

19. Konstam MA, Cohen SR, Salem DN, Das D, Aronovitz M J, Brockway BA (1986) Effect of amrinone on right ventricular func- tion: predominance of afterload reduction. Circulation 74:359-366 20. Eichhorn E J, Konstam MA, Weiland DS, Roberts DJ, Martin TT, Stransky NB, Salem DN (1987) Differential effects of milrinone and dobutamine on right ventricular preload, afterload and systolic performance in congestive heart failure secondary to ischemic or id- iopathic dilated cardiomyopathy. Am J Cardiol 60:1329-1333 21. Maruschak GF, Schauble JF (1985) Limitations of thermodilution

ejection fraction: Degradation of frequency response by catheter mounting of fast-response thermistors. Crit Care Med 13:679-682 22. Weber KT, Janicki JS, Shroff S, Fishman AP (1981) Contractile mechanisms and interaction of the right and left ventricle. Am J Cardiol 47:686-695

23. Weber KT, Janicki JS, Shroff SG, Likoff M J, St John Sutton MG (1983) The right ventricle: Physiologic and pathophysiologic con- siderations. Crit Care Med 11:323-328

24. Brown KA, Ditchey RV (1988) Human right ventricular end-systolic pressure-volume relation defined by maximal elastance. Circulation 78:81-91

25. Konstam MA, Cohen SR, Salem DN, Conlon TP, Isner JM, Das D, Zile MR, Levine H J, Kahn PC (1985) Comparison of left and right ventricular end-systolic pressure-volume relations in con- gestive heart failure] J Am Coll Cardiol 5:1326-1334

26. Mc Kay RG, Spears JR, Aroesty JM, Baim DS, Royal HD, Heller GV, Lincoln W, Salo RW, Braunwald E, Grossman W (1984) In- stantaneous measurement of left and right ventricular stroke vol- ume and pressure-volume relationships with an impedance catheter.

Circulation 69:703-710

27. Borow KM, Come PC, Neuman A, Bairn DS, Braunwald E, Gross- man W (1985) Physiologic assessment of the inotropic, vasodilator and afterload reducing effects of miMnone in subjects without cardiac disease. Am J Cardiol 55:1204-1209

28. Kass DA, Mangham WL, Guo ZM, Kono A, Sunagawa K, Sagawa K (1987) Comparative influence of load versus inotropic states on indexes of ventricular contractility: experimental and theoretical analysis based on pressure-volume relationship. Circulation 6:1422-1436

29. Hines RL (1990) Management of acute right ventricular failure.

J Cardiol Surg 5:285-287

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