[Above and beyond BMI : Alternative methods of measuring body fat and muscle mass in critically ill patients and their clinical significance]. / Jenseits des BMI : Alternative Methoden zur Erfassung von Körperfett und Muskelmasse in der Intensivmedizin und deren klinischer Stellenwert.

Obesity leads to better survival in critically ill patients. Although there are several studies confirming this thesis, the "obesity paradox" is still surprising from the clinician's perspective. One explanation for the "obesity paradox" is the fact that the body mass index (BMI), which is used in almost all clinical evaluations to determine weight categories, is not an appropriate measure of fat and skeletal muscle mass and its distribution in critically ill patients. In addition, height and weight are frequently estimated rather than measured. Central obesity has been identified in many disorders as an independent risk factor for an unfavourable outcome. The first clues are to be found in intensive care. Along with obesity, an individual's entire muscle mass is a variable that has an influence on outcome. Central obesity can be measured relatively easily with an abdominal calliper, but the calculation of muscle mass is more complex. A valid and detailed measurement of this can be obtained using computed tomography (CT) images, acquired during routine care. For future clinical observation or interventional studies, single cross-sectional CT is a more sophisticated tool for measuring patients' anthropometry than a measuring tape and callipers. Patients with sarcopenic obesity, for example, who may be at a particular risk, can only be identified using imaging procedures such as single cross-sectional CT. Thus, BMI should take a back seat as an anthropometric tool, both in the clinic and in research.

Quantification of propionaldehyde in breath of patients after lung transplantation.

Oxygen-derived free radicals (ROS) have been identified to contribute significantly to ischemia-reperfusion (I/R) injury by initiating chain reactions with polyunsaturated membrane lipids (lipid peroxidation, LPO) resulting in the generation of several aldehydes and ketones. Due to their volatile nature these LPO products can be measured noninvasively in breath. We hypothesized that one of these markers, namely propionaldehyde, will be increased in lung and heart-lung transplant patients where severe oxidative stress due to I/R injury with early graft dysfunction represents one of the major postoperative complications resulting in prolonged ventilation and increased in-hospital morbidity and mortality. Expiratory air measurements for acetone, isoprene, and propionaldehyde were performed in seven patients after lung (n = 5) or heart-lung (n = 2) transplantation, ventilated patients (n = 12), and healthy volunteers (n = 17) using online ion-molecule reaction mass spectrometry. Increased concentrations of acetone (transplanted: 3812 [2347-12498]; ventilated: 1255 [276-1959]; healthy: 631 [520-784] ppbv; P < .001) and propionaldehyde (transplanted: 270 [70-424]; ventilated: 82 [41.8-142]; healthy: 1.7 [0.1-11.8] ppbv; P < .001) were found in expiratory air of transplanted and ventilated patients. Propionaldehyde resulting from spontaneous fragmentation of peroxides due to free radical-induced LPO after I/R injury in patients after lung or heart-lung transplantation can be quantified in expired breath.

[Quality of results of therapy of acute respiratory failure : changes over a period of two decades]. / Ergebnisqualität der Therapie des akuten Lungenversagens : Veränderungen über einen Zeitraum von 2 Jahrzehnten.

Progress in intensive care (ICU) treatment of acute respiratory distress syndrome (ARDS) over the last 20 years includes the introduction of extracorporeal membrane oxygenation (ECMO) for CO2 removal and the widespread use of evidence-based lung-protective ventilatory strategies. Little is known, however, about whether these changes have resulted in improvements in short-term and long-term outcome of acute respiratory distress syndrome (ARDS) within the two decades after introduction. In a retrospective study 167 long-term survivors of severe ARDS who were transferred to the clinic for anesthesiology of the University of Munich, Campus Großhadern by means of specialized intensive care unit (ICU) transport teams and treated over a period of 20 years (1985-2005) were evaluated to investigate whether significant improvements in outcome as a consequence of the above mentioned progress in ARDS therapy have occurred. The ARDS patient cohort studied was characterized with regard to demographic variables, initial acute physiology and chronic health evaluation (APACHE) II score, duration of ICU treatment, the duration of mechanical ventilation and mortality. Data on long-term outcome were collected in a subcohort (n = 125) of patients who responded to mailed questionnaires and included health-related quality of life (HRQL, SF-36 questionnaire), symptoms of post-traumatic stress disorder (PTSD), traumatic memories from ICU treatment (PTSS-10 instrument) and current state of employment. During the observation period no significant changes regarding patient age (39 ± 16 years, mean ± SD), disease severity on admission to the ICU (APACHE II scores 22 ± 5), duration of ICU treatment (47 ± 39 days) or duration of mechanical ventilation (39 ± 38 days) were found. Overall ICU mortality during the two decades was 37.3 % (range 25.0 %-38.1 %) between 1995 and 2001 and a non-significant increase in values between 36.8 % and 58.3 % during the time interval from 2002 und 2005. The paO2/FIO2-ratio on ICU admittance improved significantly between 1990 and 2000 (69 ± 5 between 1990 and 1994 versus 101 ± 12 between 1995 and 2000, p < 0.01) and remained nearly unchanged thereafter. Long-term outcome was evaluated on average 5.0 ± 3.1 years after discharge from the ICU. During the time period between 1985 and 1994 survivors of ARDS showed significant impairments in all 8 categories of the SF-36 HRQL instrument when compared to an age and sex-matched normal population with maximal differences regarding physical function (z = -1.01), general health perception (z = -1.17) and mental health (z = -1.3). Patients who were treated from 1995 to 2005 were still impaired in 7 out of 8 categories of HRQL but reported significantly better mental health (49.6 ± 16.5 vs. 68.6 ± 17.8, p < 0,01) and better physical function than individuals from the previous decade (49.6 ± 16.5 vs. 73.4 ± 27.5, p = 0,03). The difference of mental health was no longer significant when compared to a healthy age and sex matched control group (p = 0.14) but the difference in physical function still was (z = -0.48, p < 0.01). The incidence of severe post-traumatic stress defined as a PTSS-10 score ≥ 35 was 20.4 % and remained unchanged throughout the 2 decades of observation. The PTSS-10 scores correlated with the number of traumatic memories present (r = 0.43, p < 0.01, n = 125). More than 50 % of long-term survivors were able to return to full time work with no significant changes during the 2 decades of observation. The introduction of new modalities of ARDS treatment were associated with higher paO2/FIO2-ratios on ICU admittance but had no effect on short-term outcomes including duration of ICU therapy, mechanical ventilation or mortality. The ARDS patients are still at risk for post-traumatic stress and persistent impairments in HRQL. Apart from some improvements in HRQL, the outcome of ARDS therapy remained largely unchanged during two decades.

The effect of inhaled nitric oxide and inhaled iloprost on hypoxaemia in a patient with pulmonary hypertension after pulmonary thrombarterectomy.

Acute pulmonary hypertension with life-threatening right heart failure may complicate the postoperative course following cardiothoracic surgery. Both inhaled nitric oxide and inhaled iloprost, a stable analogue of prostacyclin, have been used frequently for this purpose in acute pulmonary hypertension of various origins. We present a case of a patient with acute pulmonary hypertension and severely impaired gas exchange following pulmonary thrombo-endarterectomy. Therapy with one inhaled vasodilator alone did not satisfactorily abort a postoperative pulmonary hypertensive crisis and low-output syndrome due to right heart failure. Combined inhaled nitric oxide and inhaled iloprost, however, showed additive effects. Hence, the combination of both drugs may be reasonable in cases where the standard therapy fails. The effect has been demonstrated by means of continuous blood gas monitoring.

Acute respiratory distress syndrome with transiently impaired left ventricular function and Torsades de Pointes arrhythmia unmasking congenital long QT syndrome in a 25-yr-old woman.

We report a case of recurrent episodes of Torsades de Pointes arrhythmia in the setting of transiently impaired left ventricular ejection fraction, acute respiratory distress syndrome, transient hypokalaemia and QT-prolonging drugs, in a previously healthy 25-yr-old female patient. In the course of the clinical and genetic work-up this patient was newly diagnosed with a mutation in KCNH2 encoding the alpha-subunit of the human repolarizing potassium channel I(Kr). This case report illustrates the multivariate nature of long-QT syndrome, and emphasizes the usefulness of a pharmacological test for repolarization abnormalities.

Differential effects of angiotensin II receptor blockade on pressure-induced left ventricular hypertrophy and fibrosis in rats.

The effects of the angiotensin II receptor type 1 (AT1) antagonist losartan on pressure overload-induced left ventricular (LV) hypertrophy were studied in female Sprague-Dawley rats. Starting on the day of surgery, losartan (L, 12 mg/kg/day) was administered as continuous intraperitoneal infusion for 2 weeks by using alzet mini-osmotic-pumps (model 2002). This dose of losartan shifted the in vivo dose-response curve of the angiotensin II-induced elevation of left ventricular systolic pressure (LVSP) to the right. Pressure overload was achieved by placing a band around the aortic arch. This caused an aortic stenosis (AS) with an outer diameter of 1.0 mm. The hemodynamic effects were measured in the intact, anesthetized rats (n = 15). The hearts were excised, and the weights of the left (LV) and right ventricle (RV) were determined. Some of these hearts (n = 7) were perfused with collagenase to obtain isolated cardiac myocytes for the measurement of cell volume. Other hearts (n = 8) were examined for morphological changes. In the animals with AS, LVSP was markedly elevated. Furthermore, LV weight and LV myocyte cell volume were increased in this group, while RV weight and RV myocyte cell volume remained stable in all the groups. L had no significant effect on the AS-induced increase in LVSP and cell size parameters, nor on the weight gain of the LV. Histological analysis revealed that the AS-induced enlargement of the mean myocyte diameter was not affected by L. The interstitial collagen fraction was increased in the AS rats and became normalized by L. These data suggest that the renin-angiotensin system might not be involved in the development of pressure-induced cardiac hypertrophy within the time-frame of these experiments, but that it does play a major role in the genesis of the interstitial fibrosis which is a typical feature of this pathophysiological condition.

Measurement of left ventricular maximal isovolumetric pressure in rats: effects of antihypertensive drugs and diabetes mellitus.

We developed a method for measuring left ventricular maximal isovolumetric pressure (LVMIP) in intact rats and applied it in the presence of acutely administered antihypertensive drugs and in experimental diabetes mellitus. The combination of a 2 French Fogarty arterial embolectomy balloon catheter with a new ultra-thin shaft (0.25 mm diameter) Millar ultra-miniature pressure tip catheter was used. Closed-chest, thiopental anaesthetized female Sprague-Dawley rats received the beta-adrenoceptor blocker metoprolol (1 mg/kg/h), the alpha-adrenoceptor blocker prazosin (0.1 mg/kg/h), and the calcium antagonist nifedipine (0.5 mg/kg/h). They were applied as continuous i.v. infusion for 30 minutes. The angiotensin II type 1 (AT1) receptor antagonist losartan (3 mg/kg) was applied as bolus i.v. injection. Diabetes mellitus was induced by a single tail vein injection of streptozotocin (60 mg/kg) five weeks prior to hemodynamic measurements. Under control conditions, left ventricular systolic pressure (LVSP) was 136.5 +/- 3.7 mmHg and increased to 263 +/- 5.4 mmHg when the balloon was inflated (LVMIP). LVSP was significantly lower in the presence of prazosin, metoprolol, nifedipine, and in diabetic rats. However, LVMIP was significantly reduced only in the metoprolol-treated and diabetic rats. Both LVSP and LVMIP did not change significantly in losartan-treated rats. The degree of the increase in left ventricular maximal isovolumetric pressure during balloon inflation (LVMIP-LVSP) was not significantly different in any experimental condition. These results suggest that the mechanism for evoking LVMIP is not dependent on the acute stimulation of cardiac alpha- and beta-adrenergic receptors, on calcium channels, nor on the AT1 receptors. In addition, the intrinsic mechanism for the generation of LVMIP seems not to be influenced in the diabetic state.

Effects of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats.

It was the aim of the present study to characterize the hemodynamic, biochemical and morphologic effect of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats. Isolated right ventricular hypertrophy was induced in female Sprague-Dawley rats by intermittent hypoxia (IH; 10% O2, 8 h/day, 5 days/week, 20 days of exposition, n=15). After completion of IH, left- (LV) and right-ventricular (RV) hemodynamic parameters were measured under room air conditions in the intact, thiopental-anesthetized animals with special Millar ultraminiature tipcatheter-manometers. Cardiac output was determined using the thermodilution method. Cell volume (CV) of isolated cardiomyocytes was measured with a Coulter Channellyzer after collagenase cell isolation. The specific activities of the myocardial pentose phosphate pathway enzymes glucose-6-phosphate-dehydrogenase (G-6-PD) and 6-phosphogluconate-dehydrogenase (6-PGD) were determined using a spectrophotometric assay. IH caused a rise in right ventricular systolic pressure (RVSP) from 38.1+/-0.83 to 58.1+/-1.42 mmHg and an increase in the RV weight/body weight ratio (RVW/BW) from 0.884+/-0. 053 to 1.166+/-0.049 mg/g. The activities of G-6-PD and 6-PGD were significantly increased after IH in the RV, but not in the LV. CV was increased from 24 248+/-1193 to 29 541+/-1765 micrometer 3, myocardial cell length was unchanged. IH had no influence on the LV parameters or cardiac output. Co-infusion of the angiotensin II receptor antagonist losartan (LO; 12 mg/kg/d i.p., n=14) during the IH period reduced the rises in RVSP (49.4+/-2.06 mmHg), RVW/BW (0. 99+/-0.072 mg/g), G-6-PD and 6-PGD significantly, but not completely. The increase in CV, however, was prevented (24 524+/-2370 micrometer 3) entirely. We conclude from these data that the IH-induced RV-hypertrophy was primarily of the concentric type. LO attenuated the hypoxia-induced isolated RV hypertrophy and significantly reduced the metabolic response of the RV. The LO effect was most potent with regard to the increase in cardiomyocyte volume.

Functional responses of the left and right heart of diabetic rats to alpha- and beta-adrenergic receptor stimulation.

It was the aim of the present study to examine the influence of alpha-and beta-receptor stimulation on the function of the right (RV) and left (LV) ventricle of streptozotocin-diabetic rats (STZ; 60 mg.kg-1; n = 14). Phenylephrine (PE; 3 mg.kg-1.h-1) or isoproterenol (ISO; 24 micrograms.kg-1.h-1) were infused intravenously for 20 min 4 weeks after STZ injection. The hemodynamic parameters were measured on intact, anaesthetized animals with special Millar ultraminiature tipcatheter manometers. In the non-diabetic animals (n = 15), PE caused a significant elevation of left ventricular systolic pressure (LVSP) from 138.5 +/- 3.2 to 205.4 +/- 7.5 mmHg and raised heart rate (HR) from 362 +/- 12.6 to 399 +/- 17.2 beats.min-1 (mean +/- S.E.M.; P < 0.05). LVSP and HR were significantly lower in the diabetic animals under control conditions (110.5 +/- 6.4 mmHg and 273 +/- 16.0 beats.min-1, respectively) and not affected by PE. ISO induced a significant and comparable decrease in diastolic aortic pressure (DAP) and an increase in HR in both the non-diabetic and diabetic group. The PE-induced enhancements of LV dP/dtmax and RV dP/dtmax from 10533 +/- 805 to 21533 +/- 1386 and from 2044 +/- 262 to 3867 +/- 733 mmHg.s-1 were significant in the control animals. In the diabetic rats, LV dP/dtmax was lower (5971 +/- 901 mmHg.s-1) and was increased by PE to the range of control rats (11171 +/- 1591 mmHg.s-1). The PE-induced elevation of RV dP/dtmax from 2028 +/- 284 to 2771 +/- 391 mmHg.s-1 was less pronounced in the diabetic rats than in the controls. Under the influence of ISO, the increase of dP/dtmax in both ventricles was comparable to the effect of PE and fully preserved in the diabetic animals. Right ventricular systolic pressure (RVSP) was increased under PE and ISO in both groups to comparable values. These results demonstrate that the in vivo response to beta-adrenoceptor stimulation is well preserved in the diabetic rat, while the effects of alpha-stimulation are markedly reduced, especially in the left ventricle and systemic circulation.

Different response of the rat left and right heart to norepinephrine.

The in vivo hemodynamic and morphologic responses of the rat left (LV) and right (RV) ventricle to continuous long-term i.v. infusion of norepinephrine (NE) at different dosages and for different durations of infusion were studied. Female Sprague-Dawley rats received continuous intravenous infusion of norepinephrine from infors syringe pumps for 24, 48 and 72 h at a dose of 200 mu g center dot kg-1 x h-1. Furthermore, NE was infused for 72 h at dosages of 50, 100 and 200 mu g center dot kg-1 x h-1. The beta-adrenergic blocker and vasodilator with alpha1-blocking activity carvedilol (0.5 mg x kg-1 x h-1) was coinfused with NE for 72 h. The hemodynamic effects were measured on intact, anesthetized rats with special Millar ultraminiature pressure tip catheters, and the weights of the left and right ventricles were measured. NE increased heart rate at any time or dose, whereas cardiac output and total peripheral resistance remained unchanged. LV and RV dP/dtmax were nearly doubled as compared to control values and RVSP was elevated by more than 100%. The effect of NE on LVSP was much less pronounced (< 20%) and only significant at 50 mu g x kg-1 x h-1 for 72 h. Neither LV nor RV end-diastolic pressures were elevated, indicating that cardiac failure had not occurred. The LV developed hypertrophy with an increase of the ventricular weight/body weight ratio (LVW/BW) of 22% even after only 2 days of NE (200 mu g x kg-1 center dot h-1). The RV showed no hypertrophy at any time of the experiments. The NE-induced changes in HR, dP/dtmax, RVSP and LVW/BW were completely prevented by the coinfusion of carvedilol. These studies show that the hemodynamic responses to continuous infusion of NE are more pronounced in the RV than in the LV. Conversely, NE induced hypertrophy only in the LV, not in the RV. The hemodynamic effects of chronic NE infusion did not change significantly between 1 and 3 days of infusion. The in vivo responses to exogenous NE therefore were unaffected by adaptive effects such as downregulation of adrenergic receptors.

[Continuous measurement of cardiac output with pulse contour analysis]. / Die kontinuierliche Messung des Herzzeitvolumens mit der Pulskonturanalyse.

Pulse contour cardiac output (PCCO) is an easily applicable method for continuous measurement of cardiac output in critically ill patients. Calculation of stroke volume is possible by analysing the area under the systolic part of the arterial pulse pressure waveform together with an individual calibration factor (Zao) to account for the individually variable vascular impedance. Since vascular impedance is potentially affected by altered vascular tone, it was the aim of the present study to examine the validity of PCCO in ICU patients receiving various dosages of a variety of vasoactive drugs. PATIENTS AND METHODS. Continuous cardiac output was measured in 20 ICU patients for a total of 110 h using the pulse contour method. The precision of PCCO was determined in comparison with its calibration reference, the thermodilution method (TDCO): (1) during administration of vasoactive drugs at a constant rate and (2) during conditions with altered vascular tone and haemodynamics elicited by changes in vasoactive drug dosage. For this purpose, the patients received varying dosages of vasoactive drugs (dopamine, dobutamine, epinephrine, norepinephrine, nitroglycerin, prostacyclin and urapidil). RESULTS. A total of 165 data sets was obtained, each consisting of the average of four capnometrically triggered TDCO measurements and the corresponding PCCO values. The relative difference between methods (+/- 2 SD) was +/- 23.9% (SD 0.85 l.min-1; r = 0.93) if a single calibration at the beginning of measurement series was performed (Fig. 2). The bias of the mean cardiac output values of both methods was -0.09 l.min-1. The precision of PCCO improved to +/- 15.7% by additional calibrations (SD 0.56.min-1; r = 0.96; bias 0.003 l.min-1). Data of two patients showed that recalibration may be necessary after extreme haemodynamic changes due to septic shock or cooling. Alteration of vascular tone by clinically used dosage of vasoactive drugs, however, had no destabilizing effect on the pulse contour method. CONCLUSIONS. It could be demonstrated that PCCO provides a valuable method for continuous cardiac output measurement in the intensive care setting with a precision comparable to that of thermodilution.

The functional and metabolic responses of the heart to catecholamines are attenuated in diabetic rats.

Many studies have shown that the contractile response of the rat left ventricle is impaired in diabetes mellitus. Few studies have examined the acute in vivo effects of catecholamines on the right ventricle of diabetic rats. The present study investigates the acute in vivo effects of norepinephrine (100 micrograms.kg-1.h-1 continuous intravenous infusion for 15 minutes) on the function of the right and left ventricle of diabetic rats. The effects of isoproterenol (25 mg.kg-1, subcutaneously) on the activity of glucose-6-phosphate dehydrogenase, the first and rate limiting enzyme of the oxidative pentose phosphate pathway, and on adenine nucleotide biosynthesis of the diabetic heart were also examined. Diabetes mellitus was induced by a single intravenous injection of streptozotocin (60 mg.kg-1) 4 weeks before measurements. The hemodynamic measurements were made on intact, anesthetized rats with Millard ultraminiature pressure tip catheters. The basal hemodynamic measurements (left ventricular systolic pressure, diastolic aortic pressure, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax) as well as glucose-6-phosphate dehydrogenase activity and adenine nucleotide biosynthesis were the same in the diabetic animals as in the controls. Heart rate was slower in the diabetics. Norepinephrine, after 15 minutes of intravenous infusion, induced a marked increase in heart rate, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax; whereas left ventricular systolic pressure and diastolic aortic pressure remained unchanged. Isoproterenol caused a pronounced stimulation of both cardiac glucose-6-phosphate dehydrogenase activity (after 24 hours) and adenine nucleotide biosynthesis (after 5 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

Response of the rat heart to catecholamines and thyroid hormones.

Catecholamines and thyroid hormones have a similar influence on heart function and metabolism, but this may occur in a differential manner and to a different extent. In this study, the effects of norepinephrine (NE) and of triiodothyronine (T3) were studied in regard to the function of the left (LV) and right ventricle (RV) and to the oxidative pentose phosphate pathway (PPP). NE was applied in rats as continuous i.v. infusion (0.2 mg/kg/h) for three days. T3 was given as daily s.c. injections (0.2 mg/kg) for the same period of time. LV and RV function was measured in the closed-chest trapanal-anesthetized animals using special Millar ultraminature catheter pressure transducers. NE induced an increase in heart rate, in mean arterial pressure, and in total peripheral resistance (TPR). The cardiac RNA/DNA and the left ventricular weight/body weight ratios were increased by about 40%. These effects were prevented by simultaneous alpha- and beta-receptor blockade with prazosin and metoprolol, respectively, but not by verapamil which abolished the hemodynamic effects. RVSP was significantly elevated by NE in a dose-dependent manner. The functional effects of T3 on the LV were not as pronounced as those induced by NE. Heart rate and LV dp/dtmax were increased by T3, and this increase was prevented by concomitant beta-receptor blockade with metoprolol. In contrast to NE, T3 induced an increase in cardiac output and a concomitant decrease in TPR. The RNA/DNA ratio was elevated and cardiac hypertrophy had developed after treatment for three days with T3. These changes were not affected by beta-receptor blockade with metoprolol. RVSP was increased by T3 to a lesser extent than with NE. In metabolic terms it turned out that only NE, but not T3 had a stimulating effect on the cardiac PPP. NE increased the mRNA and activity of glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of this pathway. However, there was no effect of T3 on G-6-PD activity nor on 6-phosphogluconate dehydrogenase activity, one of the following enzymes in the pathway within the first 5 days of T3 treatment. These results demonstrate that the functional effects of T3 were not as pronounced as or even different from those of NE, and that T3 lacked a stimulating effect on the cardiac PPP.

Acute effects of catecholamines on function of the rat right heart.

OBJECTIVE: Although the haemodynamic effects of catecholamines on the rat left ventricle have been investigated extensively, only few systematic in vivo studies have been performed on the right ventricle. The aim was to examine the acute effects of noradrenaline and isoproterenol on rat right ventricular function. METHODS: Haemodynamic variables were measured during acute, 20 minute infusion of noradrenaline (0.1 mg.kg-1 x h-1) or isoproterenol (12 micrograms.kg-1 x h-1) in female Sprague Dawley rats. To estimate the contribution of alpha and beta receptor stimulation to these effects, eight rats each were infused with prazosin (0.1 mg.kg-1 x h-1), metoprolol (1.0 mg.kg-1 x h-1), or the alpha and beta antagonist carvedilol (0.5 and 1.0 mg.kg-1 x h-1) alone and in combination with noradrenaline or isoproterenol. RESULTS: Noradrenaline and isoproterenol increased right ventricular systolic pressure (RVSP) from 30.3 (SEM 0.5) (n = 32) to 72.7(2.7) (n = 24) and 72.3(4.4) (n = 8) mm Hg, right ventricular (RV) dP/dtmax from 1848(70.3) to 4058(301) and 3612(366) mm Hg.s-1, and heart rate from 329(6) to 371(6) and 420(8) beats.min-1, respectively. Metoprolol completely prevented the isoproterenol induced haemodynamic changes, but neither metoprolol nor prazosin was able to significantly affect the pressure effect of noradrenaline (noradrenaline + metoprolol: 67.3(6.9) mm Hg, noradrenaline + prazosin: 67.0(3.8) mm Hg). The combination of both blockers, however, prevented the noradrenaline induced rise in RVSP (noradrenaline + metoprolol + prazosin: 36.5(5.1), and noradrenaline + prazosin + metoprolol: 30.0(1.2) mm Hg). Carvedilol (1.0 mg.kg-1 x h-1) significantly attenuated the noradrenaline induced RVSP increase (39.1(3.0) mm Hg), but not to the control range. Metoprolol or carvedilol completely prevented the noradrenaline elicited increases in heart rate (254(7) and 287(20) min-1) and RVdP/dtmax, but prazosin alone had no effect on the heart rate and RVdP/dtmax increase. Thus beta receptor blockade alone failed to significantly influence the noradrenaline induced increase of RVSP despite prevention of the increase in heart rate and RVdP/dtmax. Prazosin had a significant effect on RVSP only in combination with metoprolol. CONCLUSIONS: The combined effect of both alpha and beta blockade exceeds the pure addition of the single effects in the rat right ventricle. Moreover, we speculate that the failure to reduce the noradrenaline induced increase in RVSP by either alpha or beta blockade alone is due to the stimulation of the receptor that is not affected by the respective blocker.