Inhibitory effect of calcium-binding protein regucalcin on protein kinase activity in the nuclei of regenerating rat liver

PURPOSE: The purpose of this study was to compare the response in contractility of the right (RV) and left (LV) ventricle of the heart to beta-adrenergic stimulation using an echo planar MR technique. METHOD: In six sheep, RV and LV pressure-volume (P-V) relationships were constructed simultaneously using intraventricular pressures and volumes measured with echo planar MRI at rest and during dobutamine stress. Contractility changes were quantified by assessment of the end-systolic P-V relationship (ESPVR) and the preload recruitable stroke work (PRSW). RESULTS: Both the ESPVR the the PRSW showed a significant increase in contractility for both ventricles after dobutamine administration. The increase in contractility was significantly larger for the LV than for the RV, both measured wit the ESPVR (p < 0.0003) and the PRSW (p < 0.007). CONCLUSION: This study shows the usefulness of echo planar MRI to assess myocardial contractility of both ventricles simultaneously. Furthermore, the study shows that beta-adrenergic stimulation has a significantly greater positive inotropic effect on LV contractility than on RV contractility.     

Nonthoracotomy implantation of cardioverter defibrillators: preliminary experience with a defibrillation lead placed at the right ventricular outflow tract

Although morbidity and mortality associated with defibrillator implantation using a nonthoracotomy approach have decreased as compared with a thoracotomy approach, defibrillation thresholds have been higher and fewer patients satisfied implant criteria. It may be possible to improve on the success of nonthoracotomy defibrillator implantation by the placement of a right ventricular (RV) outflow defibrillation lead. Implantable cardioverter defibrillator implantation data of 30 consecutive patients with clinical VT or VF were reviewed. Three defibrillation leads were routinely used. When either pacing threshold at the RV apex was inadequate (n = 2) or 18-J shocks were not successful in terminating VF in 3 of 4 trials (n = 8), the RV apex lead was positioned to the RV outflow tract attaching to the septum. Defibrillation testing was first performed with the RV apex lead in combination with CS, SVC, and/or subcutaneous leads. Twenty patients satisfied implant criteria with a defibrillation threshold of 13.5 +/- 3.6 J. In 7 of the 10 patients, whose RV lead was repositioned to the RV outflow tract, this lead in combination with SVC, CS, or subcutaneous leads produced successful defibrillation at < or = 18 J or in 3 of 4 trials. This approach improved the overall success of nonthoracotomy implantation of defibrillators from 69% to 90%. After a follow-up of 27 +/- 6 months, there was no dislodgment of the RV outflow tract defibrillation leads. CONCLUSIONS: This article reports the preliminary observation that placement of defibrillation leads to the RV outflow tract in humans was possible and without dislodgment. RV outflow tract offers an alternative for placement of defibrillation leads, which may improve on the success of nonthoracotomy defibrillator implantation.     

Mid-ventricular obstruction: a variant of obstructive cardiomyopathy

In two patients with clinical and catheterization findings of hypertrophic obstructive cardiomyopathy, the level of intraventricular obstruction was found to be in the mid-ventricular area rather than at the junction of the inflow and outflow tracts. One patient died suddenly shortly after unsuccessful outflow tract myectomy. In vivo recognition of this probably rare variant form of obstructive cardiomyopathy rests mainly on the angiograhic appearance of the left ventricle and on the recording of pressures in multiple sites of the left ventricular cavity. Surgical relief of the obstruction in these patients is not likely to be obtained by a transaortic left ventricular outflow myectomy but may require either papillary muscle resection by the transatrial or transventricular approach or mid-ventricular septectomy, or both.     

Search for resistances controlling canine gastric emptying of liquid meals

Previous work has indicated that a chemoselective resistance controls gastric emptying. By use of meals of glucose or oleate, which were shown to empty spontaneously from dogs' stomachs half as fast as saline, we sought to locate this resistance by studying flow under controlled pressures in various regions of the gastrointestinal tract. In intact dogs, gastric outflow of glucose or oleate rose one-third as fast as outflow of saline as gastric pressure was raised, and this increased resistance to outflow of nutrients was unaffected by truncal vagotomy and pyloroplasty. In fistula dogs, gastroduodenal outflow rose linearly with gastroduodenal pressure gradients; outflow was markedly inhibited in a dose-related manner by intestinal oleate but not glucose. Inhibition by oleate was abolished by pyloroplasty. Glucose or oleate flowed into the small bowel from a barostat only slightly slower than saline. However, there was a strong inhibition of intestinal inflow of all three meals by gastric distension, an effect unaltered by truncal vagotomy. The findings suggest that gastric emptying is controlled by complex interactions among pressures and resistances, both within and beyond the stomach.     

Effects of halothane on global and regional biventricular performances and on coronary hemodynamics before and during right coronary artery stenosis in the dog

BACKGROUND: Previously, it was suggested that right ventricular (RV) free wall dysfunction does not necessarily elicit global hemodynamic alterations. This was investigated in a canine model of halothane-induced right coronary artery (RCA) insufficiency. METHODS: Two concentrations (0.8% and 1.6% end tidal) of halothane on global and regional RV and left ventricular (LV) performance and on coronary, pulmonary, and systemic hemodynamics were studied in 10 open-chest dogs first before and, subsequently, during critical RCA stenosis. RESULTS: In the absence of stenosis, halothane caused progressive and comparable depression of regional and global RV and LV function and reduction of RCA flow. Halothane administered during RCA stenosis caused disproportionate decreases in RCA flow and segment shortening and increases in systolic segment lengths in the area supplied by the stenosed RCA that were approximately twice as great as before stenosis. Such severe regional RV dysfunction was not accompanied by greater depression of global RV and LV pump function (systolic pressures and stroke volume). CONCLUSIONS: In the canine heart with its dominant left coronary system, RCA insufficiency (on the basis of halothane-induced hypotension) caused regional RV dysfunction suggesting ischemia that was not accompanied by global hemodynamic alteration.     

Efferent sympathetic and vagal innervation of the canine right ventricle

BACKGROUND: The functional pathways of efferent sympathetic and vagal innervation to the right ventricle (RV) might be important in a variety of disease states that involve the RV wall. The purpose of this study was to investigate those pathways. METHODS AND RESULTS: We determined the effects of phenol and endocardial radiofrequency ablation applied to the RV anterolateral wall and outflow tract on effective refractory period (EPR) shortening during bilateral ansae subclaviae stimulation and ERP lengthening during bilateral vagal stimulation. We found that efferent sympathetic axons to the RV are located in the superficial subepicardium and that lateral sites receive sympathetic innervation predominantly from the lateral margin of the RV near the AV groove. Medial sites close to the left anterior descending coronary artery (LAD) receive sympathetic innervation from both the right lateral atrioventricular (AV) groove and regions near the LAD. At the RV outflow tract, some sympathetic fibers are located intramurally. Efferent vagal fibers are located at the RV surface within 10 mm of the right lateral AV groove; they penetrate intramurally and reach to the medial sites of the RV anterior wall. Other vagal fibers originate near the LAD and are intramural. Vagal fibers to the RV outflow tract are located intramurally either from the lateral side (close to the right coronary artery) or medial side (close to the LAD). CONCLUSIONS: Efferent vagal and sympathetic innervation of the right ventricle resembles that of the left ventricle. A major difference is that efferent sympathetic fibers to the right ventricular outflow tract are located not only in the subepicardium but in the subendocardium as well.     

Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection

As the importance of the right ventricle in many diseases and conditions has been realized, the need for quantitative assessment of the motion and contraction of the right ventricular free wall (RVFW) has become apparent. This study applied the myocardial tagging magnetic resonance imaging (MRI) technique to the normal RVFW to elucidate normal heterogeneity in RV motion and contractile patterns. The RVFW was divided into three segments (inferior, mid and superior) in each of three slices (apical, mid and basal) to allow for a detailed analysis of the motion and contraction. Percent segmental shortening (PSS) was used to measure the amount of contraction, and a vector analysis was used to quantitate the trajectory of the RVFW through systole. PSS increased monotonically through time to an average across all segments of 12% in the basal slice, 14% in the mid-ventricular slice, and 16% in the apical slice of the heart. The trajectory of the RVFW was characterized by a wave of motion toward the septum and outflow tract. The data provided in this study provide a better understanding of normal RV kinematics and can serve as a comparison for disease states.     

Segmental right ventricular function after acute myocardial infarction: two-dimensional echocardiographic study in 63 patients

Right ventricular (RV) segmental contraction was studied in 63 patients with acute myocardial infarction (MI), using 2-dimensional (2-D) echocardiography. Group A included 32 patients with ischemic RV dysfunction: 19 had a disproportionate increase in right atrial pressure at the time of the examination (Group AI) and in 13 patients, right atrial pressure was normal when the echocardiogram was obtained (Group AII). Group B included 31 patients without ischemic RV dysfunction. Alkinesia or dyskinesia of the RV wall was found in 30 patients: 19 from Group AI, 8 from Group AII, and 3 from Group B. Asynergy could be identified in all segments of the RV wall including the outflow tract, RV apex, and anterior wall, but was more frequently found in the posterior wall (29 patients), best seen in the transversal subcostal short-axis view. A significant difference was found either in the frequency of wall motion abnormalities or in the number of segments with asynergy among the 3 groups (p less than 0.001). However, asynergy of the RV wall may be present in some patients with normal right heart hemodynamic function, suggesting that asynergy may be more sensitive than hemodynamic function in the diagnosis of acute RV infarction. Paradoxical septal motion was found in 8 patients, all in Group AI, and all had a right atrial pressure equal to or greater than pulmonary capillary pressure.     

MRI semeiology of segmental contraction abnormalities in arrhythmogenic dysplasia of the right ventricle

The diagnosis of localized arrhythmogenic right ventricular dysplasia may be difficult to ascertain. Aside from electrophysiological arguments, visualization of an abnormal right ventricular contraction pattern is of crucial importance for diagnosis. Cine-MR is almost the only examination method which offers detailed informations on the right ventricular contraction pattern. Nine observations of segmental right ventricular contraction abnormalities assessed by cine-MR are described here: dyskinesia of the distal part of the anterior wall (2), of the inferior wall (2), of the right ventricular outflow tract (2); akinesia of the outflow tract (2) and of the inferior wall (1). Morphological abnormalities of the right ventricle are always associated with contraction abnormalities but seem to be less disease specific. Patients should be more readily referred for a cine-MR examination when the diagnosis of localized right ventricular dysplasia is suspected. Cine-MR sequences related to these observations may be reached via Internet at:http:@alsace.u-strasbg.fr/cardio/coeur.htm.     

Significance of morphological abnormalities detected by MRI in patients undergoing successful ablation of right ventricular outflow tract tachycardia

BACKGROUND: MRI can demonstrate subtle morphological changes of the right ventricle in patients with idiopathic right ventricular outflow tract tachycardia (RVOT). The present study examines the incidence and significance of right ventricular (RV) abnormalities detected by MRI with respect to the site of successful radiofrequency catheter ablation of the clinical tachycardia. METHODS AND RESULTS: The study population comprised 20 patients (mean age, 40+/-12 years) undergoing elimination of recurrent RVOT by radiofrequency catheter ablation. MRI studies were performed before ablation to assess RV volumes and function, as well as structural abnormalities of the RV myocardium. Ten healthy age- and sex-matched subjects served as control subjects. The successful ablation sites, as documented by radiographs of the catheter position, were compared with MRI findings. Patients with RVOT showed no difference in respect to RV volumes and ejection fractions compared with control subjects. Whereas RV abnormalities were limited to prominent fatty deposits of the right atrioventricular groove extending into the inlet portion of the RV wall in 2 of 10 control subjects, MRI studies demonstrated morphological changes of the RV free wall in 13 (65%) of 20 patients with RVOT, including presence of fatty tissue (n=5), wall thinning (n=9), and dyskinetic wall segments (n=4). Eight of these patients had additional fat deposits, thinning, or a saccular aneurysm in the RV outflow tract, corresponding with the ablation site in 6 patients. CONCLUSIONS: In RVOT, structural abnormalities of the right ventricle can be detected in a substantial number of patients despite normal RV volumes and global function. MRI abnormalities within the RV outflow tract are significantly associated with the origin of tachycardia.     

An alternative procedure to intra-arterial aortoinfundibuloplasty

Intra-arterial aortoinfundibuloplasty is a newly developed aortic annular enlargement procedure in which, originally, the annulus was split anteriorly via the main pulmonary arteriotomy. An alternative method of aortoinfundibuloplasty was studied experimentally which creates spiral incisions on the free walls of both great arteries descending together into the aortopulmonary and infundibular septum via both commissures of right and left facing cusps of pulmonary and aortic valves. The valve prosthesis is implanted through this three-dimensional incision, followed by patch reconstruction. The ratio of annular augmentation was three sizes in two animals and four sizes in three animals. Immediate postoperative haemodynamics were satisfactory and there was no significant postoperative increase in systolic pressure gradient at the right ventricular outflow tract and in the right ventricular end-diastolic pressure. This alternative procedure could be applied to cases requiring radical annular enlargement and would give a wider view of both ventricular outflow tracts.     

Effect of halothane, isoflurane and desflurane on lower oesophageal sphincter tone

We have studied the effects of volatile anaesthetics on lower oesophageal sphincter (LOS) tone in three groups of eight pigs allocated randomly to receive end-tidal concentrations of 0.5, 1.0 and 1.5 MAC of desflurane, isoflurane or halothane for 15 min. LOS and oesophageal barrier pressures (BrP = LOSP - gastric pressure) were measured using a manometric method. The decrease in BrP paralleled the decrease in LOS pressure and was significant at 0.5 MAC for isoflurane and at 1.0 MAC for halothane. At 1.5 MAC, BrP values were approximately 62% of baseline values for halothane, 37% for isoflurane and 83% for desflurane. Inter-group comparisons showed that BrP did not differ at baseline and at 0.5 MAC. At 1.0 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.001) and halothane (P < 0.02) whereas the effect of desflurane on BrP was not significantly different from halothane. At 1.5 MAC the effect of isoflurane on BrP was significantly different from desflurane (P < 0.01) and halothane (P < 0.05) whereas the effect of desflurane on BrP was not significantly different from halothane. We conclude that desflurane maintained BrP and this may be clinically important in patients at high risk of regurgitation.     

Prior hypothermia attenuates malignant hyperthermia in susceptible swine

This study was designed to determine the extent by which mild or moderate hyperthermia attenuates the triggering of malignant hypothermia (MH) induced by the combined administration of halothane and succinylcholine. Sixteen susceptible swine were initially anesthetized with nontriggering drugs and then either kept normothermic (approximately equal to 38 degrees C, n = 6) or cooled to induce mild (approximately equal to 35 degrees C, n = 6), or moderate (approximately equal to 33 degrees C, n = 4) hypothermia. Next, after a 30-min control period, the normothermic and mildly hypothermic animals were administered 1 minimum alveolar anesthetic concentration (MAC) halothane followed by a bolus dose of succinylcholine (2 mg/kg). Within 10 min all normothermic animals developed fulminant MH, whereas the onset of MH was slowed or was absent in the mildly hypothermic group. To test whether moderate hypothermia could more effectively minimize the signs of a MH episode, this group of animals was exposed to 1.5 MAC halothane followed 10 min later by a 3-mg/kg bolus of succinylcholine. MH was not induced and anesthesia was then changed to nontriggering drugs (ketamine and pancuronium). The animals were then aggressively rewarmed to 38 degrees C: a slight increase in the ETCO2 was detected, but MH episodes did not spontaneously occur. Subsequently, the readministration of halothane and succinylcholine rapidly provoked fulminant MH. We concluded that the induction of mild hypothermia impairs triggering and reduces the progression of MH induced by the combined administration of halothane and succinylcholine, whereas moderate hypothermia was completely protective and thus could be considered for prophylaxis.     

Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies

This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively). The halothane MAC was redetermined after a 60 min infusion of lidocaine or saline. The baseline halothane MAC for the control group was mean +/- s.d. 0.94 +/- 0.03%, and no significant decrease occurred following saline infusion. Lidocaine decreased halothane MAC in a dose-dependent fashion (r = 0.86; P < 0.0003). The results indicate that i.v. lidocaine may have a role in equine anaesthesia.     

Alterations of normal left ventricular performance by general anesthesia

Serial invasive and noninvasive (systolic time interval) measurements of left ventricular performance were obtained in six healthy volunteers during general anesthesia employing the following sequence: thiopental induction, succinylcholine (prior to endotracheal intubation), and halothane--100 per cent oxygen at 1.25 and 1.75 MAC. Heart rate (HR), mean pulmonary arterial "wedge" pressure (PAW) and mean systemic arterial pressure (MAP) were measured continuously; cardiac index and systolic time intervals (STI's) were measured during each intervention. At both levels of halothane, MAP and stroke work index decreased (both P less than 0.02), while HR and systemic vascular resistance did not change. At 1.25 MAC halothane PAW was unchanged, but at 1.75 MAC PAW increased from 8 +/- 4 (SD) to 11 +/- 5 torr (P less than 0.02). Preload was altered at 1.25 MAC by administration of 600-1,000 ml lactated Ringer's solution; PAW increased from 9 +/- 4 to 17 +/- 3 torr (P less than 0.01). At 1.75 MAC halothane, volume expansion increased PAW in a similar manner, but the resultant ventricular function curve was depressed compared with 1.25 MAC halothane. In additon, at each level of halothane anesthesia, the ventricular function curve was depressed compared with results obtained in awake normal subjects. Afterload was altered at 1.25 MAC halothane by infusion of phenylephrine sufficient to raise MAP by 30 per cent. This intervention resulted in a greater depression of cardiac performance than that observed at 1.75 MAC halothane alone. Although alterations in STI's were directionally similar to changes observed in invasive hemodynamic measurements, STI's were sensitive to acute alternations in loading conditions. It is concluded that the levels of halothane commonly employed for general anesthesia significantly depress left ventricular performance in normal subjects, as evidenced by abnormal responses to alterations in preload and afterload, and that STI's should not be employed for routine measurement of left ventricular performance during anesthesia unless both the afterload and the preload on the myocardium are known.     

Roles of Rho-associated kinase in cytokinesis; mutations in Rho-associated kinase phosphorylation sites impair cytokinetic segregation of glial filaments

The effects of sevoflurane on myocardial contraction and relaxation are poorly understood. Therefore, we studied the effects of equianaesthetic concentrations (0.5, 1, 1.5, 2 and 2.5 MAC) of sevoflurane, isoflurane and halothane on inotropic and lusitropic (myocardial relaxation) variables, and post-rest potentiation in rat left ventricular papillary muscles in vitro. Sevoflurane and isoflurane caused comparable concentration-dependent negative inotropic effects which were significantly lower than those induced by halothane (P < 0.05). Sevoflurane and isoflurane did not modify lusitropic variables under low or high load, whereas halothane showed a negative lusitropic effect at high concentrations. Halothane suppressed post-rest potentiation, whereas isoflurane and sevoflurane did not. Post-rest recovery was unaffected by halothane, isoflurane or sevoflurane at any concentration. Thus in rat myocardium, sevoflurane and isoflurane caused comparable negative inotropic effects, had no significant lusitropic effects and did not alter post-rest potentiation, suggesting that they did not significantly modify the functions of the sarcoplasmic reticulum.     

Variants of dysfunction of the upper urinary tract in urolithiasis

Registration of contractility of the upper urinary tracts (UUT) at multichannel impedance ureterography was conducted in 30 patients with concrements in the kidneys and ureters before extracorporeal lithotripsy. By defects in urodynamics, the patients were divided into 4 groups. The most severe affection of urodynamics (low amplitude of the peristalsis, high tonicity of UUT wall) occurred in group 4. From group 1 to 4 contraction arrhythmia, deformity of contraction complexes, retrograde contraction waves were increasing. The index has been calculated for estimation of UUT performance in transporting urine.     

Relationships between Müller cells and neurons in a primitive tetrapod, the Australian lungfish

BACKGROUND: The cardiovascular side effects of volatile anesthetics are one of the chief causes of postoperative complications in children, and infants seem to be at the greatest risk for this. This study compared cardiovascular changes at equipotent concentrations of sevoflurane and halothane in infants. METHODS: Thirty infants classified as American Society of Anesthesiologists physical status I or II who required elective surgery were randomized to receive either halothane or sevoflurane for inhalation induction. Cardiovascular and echocardiographic data were recorded in both groups at baseline and at end-tidal concentrations of 1 and 1.5 minimum alveolar concentration (MAC). RESULTS: Sevoflurane did not alter heart rate or cardiac index at all concentrations compared with awake values. Sevoflurane significantly decreased blood pressure and systemic vascular resistance compared with awake values at all concentrations. Shortening fraction and rate-corrected velocity of circumferential fiber shortening decreased at 1.5 but not at 1 MAC. Myocardial contractility assessed by stress-velocity index and stress-shortening index decreased significantly at all concentrations, but did not fall into the abnormal range at any concentration. Halothane caused a greater decrease in heart rate, shortening fraction, stress-shortening index, velocity of circumferential fiber shortening, stress-velocity index, and cardiac index at all concentrations than did sevoflurane. CONCLUSION: Sevoflurane causes a lesser decrease in cardiac output than does halothane in infants.     

The effect of imidazoline receptors and alpha2-adrenoceptors on the anesthetic requirement (MAC) for halothane in rats

BACKGROUND: Recent evidences have documented that several pharmacologic actions of alpha2-adrenoceptor agonists are mediated via activation of not only alpha2-adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia. METHODS: Seventy-two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 microg/kg, intraperitoneally [IP]), a selective alpha2-adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC-reducing action of dexmedetomidine (30 microg/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 microg/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated. RESULTS: Dexmedetomidine decreased the MAC for halothane dose-dependently, and this MAC-reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane. CONCLUSIONS: The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2- adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.     

Methylmercury intoxication and histochemical demonstration of NADPH-diaphorase activity in the striate cortex of adult cats

Primary pulmonary hypertension is characterized by elevated pulmonary arterial pressure and vascular resistance, frequently producing right heart failure and death. Therefore, the Doppler right ventricular (RV) index, which is a measure of global RV function, could be a useful predictor of outcome in primary pulmonary hypertension. The Doppler RV index, defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by ejection time, was retrospectively measured in 53 patients (38 women, aged 45 +/- 14 years) with primary pulmonary hypertension. Ejection time was measured from the pulmonary outflow velocity signal. The sum of isovolumic contraction time and isovolumic relaxation time was obtained by subtracting ejection time from the duration of tricuspid regurgitation. The Doppler RV index tended to be elevated (median 0.83) compared with normal ranges. Normal Doppler RV index was 0.28 +/- 0.04. After a mean follow-up duration of 2.9 years, 4 patients underwent lung transplantation and 30 patients died; the cause was cardiac in 28, noncardiac in 1, and uncertain in 1. Univariately, the Doppler RV index (chi-square 20.7, p <0.0001), severity of tricuspid regurgitation (chi-square 8.2, p = 0.004), treatment with calcium blockers (chi-square 6.6, p = 0.01), heart rate (chi-square 5.1, p = 0.02), and symptom status (chi-square 4.9, p = 0.03) were associated with adverse outcome (cardiac deaths and lung transplantation). However, only the Doppler RV index and treatment with calcium blockers were independent predictors within the multivariate model. Our results indicate that the Doppler RV index is a useful predictor of adverse outcome in patients with primary pulmonary hypertension.