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What role does the right side of the heart play in circulation?

Right ventricular failure (RVF) is an underestimated problem in intensive care. This review explores the physiology and pathophysiology of right ventricular function and the pulmonary circulation. When RVF is secondary to an acute increase in afterload, the picture is one of acute cor pulmonale, as occurs in the context of acute respiratory distress syndrome, pulmonary embolism and sepsis. RVF can also be caused by right myocardial dysfunction. Pulmonary arterial catheterization and echocardiography are discussed in terms of their roles in diagnosis and treatment. Treatments include options to reduce right ventricular afterload, specific pulmonary vasodilators and inotropes.

Cardiotonic Agents↗

[Arrhythmogenic right ventricular cardiomyopathy with pulmonary embolism: a case report].

A 50-year-old man complained of dyspnea on exertion. Electrocardiography showed frequent premature ventricular contraction and inverted T wave in leads V1-V6. Echocardiography and right ventriculography showed dilation and systolic dysfunction of the right ventricle. The diagnosis was arrhythmogenic right ventricular cardiomyopathy. In addition, thrombus was also observed in the pulmonary artery on chest computed tomography and pulmonary artery angiography. The final diagnosis was arrhythmogenic right ventricular cardiomyopathy complicated by pulmonary embolism. Pulmonary embolism should be considered in patients with arrhythmogenic right ventricular cardiomyopathy with dyspnea.

Arrhythmias, Cardiac↗

[Pulmonary arterial hypertension in intensive care unit and operating room].

OBJECTIVE: To review the perioperative anaesthetic management of pulmonary arterial hypertension. DATA SOURCES: Extraction from Pubmed database of French and English articles on the perioperative anaesthetic management of pulmonary hypertension for 9 years. DATA SELECTION: The collected articles were reviewed and selected according their quality and originality. The more recent data were selected. DATA SYNTHESIS: Pulmonary arterial hypertension is classically divided in primary and secondary. Primary pulmonary hypertension (familial and sporadic) is relatively severe and rare. Muscularization of the terminal portion of the pulmonary vascular arterial tree, caused by smooth muscle cell hyperplasia is the first change. Pulmonary arterial hypertension linked with disorders of the respiratory system and hypoxemia or pulmonary venous hypertension including mitral valve disease and chronic left ventricular dysfunction are often associated with high morbidity and mortality. The main consequence of pulmonary hypertension development is the occurrence of right-sided circulatory failure. A better understanding of disease pathophysiology will contribute to the development of new therapies increasing then the prognosis of these patients. The management of primary pulmonary hypertension or secondary pulmonary arterial hypertension is a challenge for the anaesthesiologist because the risk of right ventricular failure is markedly increased.

Anesthesia↗

Effects of sequential biventricular pacing during acute right ventricular pressure overload.

Temporary sequential biventricular pacing (BiVP) is a promising treatment for postoperative cardiac dysfunction, but the mechanism for improvement in right ventricular (RV) dysfunction is not understood. In the present study, cardiac output (CO) was optimized by sequential BiVP in six anesthetized, open-chest pigs during control and acute RV pressure overload (RVPO). Ventricular contractility was assessed by the maximum rate of increase of ventricular pressure (dP/dt(max)). Mechanical interventricular synchrony was measured by the area of the normalized RV-left ventricular (LV) pressure diagram (A(PP)). Positive A(PP) indicates RV pressure preceding LV pressure, whereas zero indicates complete synchrony. In the control state, CO was maximized with nearly simultaneous stimulation of the RV and LV, which increased RV (P = 0.006) and LV dP/dt(max) (P = 0.002). During RVPO, CO was maximized with RV-first pacing, which increased RV dP/dt(max) (P = 0.007), but did not affect LV dP/dt(max), and decreased the left-to-right, end-diastolic pressure gradient (P = 0.023). Percent increase of RV dP/dt(max) was greater than LV dP/dt(max) (P = 0.014). There were no increases in end-diastolic pressure to account for increases in dP/dt(max). In control and RVPO, RV dP/dt(max) was linearly related to A(PP) (r = 0.779, P < 0.001). The relation of CO to A(PP) was curvilinear, with a peak in CO with positive A(PP) in the control state (P = 0.004) and with A(PP) approaching zero during RVPO (P = 0.001). These observations imply that, in our model, BiVP optimization improves CO by augmenting RV contractility. This is mediated by changes in mechanical interventricular synchrony. Afterload increases during RVPO exaggerate this effect, making CO critically dependent on simultaneous pressure generation in the RV and LV, with support of RV contractility by transmission of LV pressure across the interventricular septum.

Animals↗

[Usefulness of transesophageal echocardiography in the critical patient].

To assess the usefulness and safety of transesophageal echocardiography in critically ill patients, we analysed the transesophageal echocardiography studies in 60 of such cases (age: 58 +/- 11 and 38 males). Every patient underwent a previous transthoracic echocardiogram, that was considered inadequate for diagnostic purposes. Thirty patients (50%), were on mechanical ventilation and 17 patients (28%) showed hypotension and/or shock. Forty patients (66%) were at special care units and in 31 (52%) of them, pulmonary and systemic pressures, and continuous analysis of venous pressure of oxygen were available. Indications for study were: 17 patients with clinical suspicion of aortic dissection (confirmed in 5 cases): 9 patients infective endocarditis (4 cases showed valvular vegetations); 6 patients with mitral prosthesis dysfunction (confirmed in 4 cases); complicated acute myocardial infarction (MI) in 8 patients (2 cases with mitral insufficiency, 3 with left ventricular dysfunction, 1 with right ventricular MI, 1 with left ventricular pseudoaneurysm and other with isolated inferior MI); in 11 patients the study was performed to evaluate the result of cardiac transplantation immediately (< 4 h) and it showed 2 cases of left ventricular dysfunction; 3 patients were studied for severe cardiac dysfunction of unknown etiology (a dilated cardiomyopathy was confirmed in one and ruled out in the other, and one patient showed signs of restrictive situation); there were other causes in the rest. The procedure could be completely performed in all cases. In conclusion in critically ill patients the transesophageal echocardiography has a great usefulness and minimal complications.

Adolescent↗

ECG-gated 99mTc single-photon emission CT for assessment of right ventricular structure and function: is the information provided similar to echocardiography?

STUDY OBJECTIVE: (99m)Tc single-photon emission CT (SPECT) and ECG-gated SPECT can visualize well the right ventricle (RV) in most patients, but their utility for assessment of the RV has not been formally evaluated. We examined whether (99m)Tc SPECT/ECG-gated SPECT provide similar information to transthoracic two-dimensional Doppler echocardiography (2D-ECHO) regarding RV cavity size, wall thickness, and systolic function. DESIGN: Retrospective analysis. SETTING: A major university teaching hospital. PATIENTS: A consecutive series of 194 patients with good quality stress SPECT and 2D-ECHO studies performed within 1 day of each other and no significant interim cardiac events. MEASUREMENTS AND RESULTS: RV size and function were visually assessed by SPECT/ECG-gated SPECT and 2D-ECHO. RV wall thickness was visually assessed by SPECT and measured in mm in end-diastole by 2D-ECHO. Of 142 patients with normal RV cavity size by SPECT, 134 patients (94%) had normal RV cavity size by 2D-ECHO. However, of 52 patients with RV dilation by SPECT, only 9 patients (17%) had RV dilation by 2D-ECHO. A perfusion abnormality in the right coronary artery territory was significantly associated with RV dilation by SPECT (p < 0.005) and 2D-ECHO (p < 0.05). Among 150 patients with ECG-gated SPECT, only 2 patients had abnormal RV systolic function, as compared with 18 patients by 2D-ECHO. RV wall thickness measurements by SPECT and 2D-ECHO did not correlate. CONCLUSIONS: For normal interpretations regarding RV cavity size, wall thickness, and systolic function, there is good agreement between (99m)Tc stress SPECT/ECG-gated SPECT and 2D-ECHO. However, there is poor overall agreement between gated SPECT/ECG-gated SPECT and 2D-ECHO regarding the presence of RV dilation, hypertrophy, and systolic dysfunction.

Echocardiography, Doppler↗

Myocardial dysfunction in human immunodeficiency virus infection: an echocardiographic study of 157 patients in hospital in Zimbabwe.

OBJECTIVE: To determine the prevalence and characteristics of myocardial dysfunction and other cardiac manifestations in acutely ill hospital patients infected with human immunodeficiency virus (HIV) in Zimbabwe. DESIGN: A prospective echocardiographic survey of acutely ill HIV seropositive patients. SETTING: General medical ward, Harare Central Hospital, Zimbabwe. PATIENTS: One hundred and fifty seven HIV seropositive patients admitted with various acute medical conditions over a 12 month period, January to December 1994. MAIN OUTCOME MEASURES: Detection of myocardial dysfunction and other cardiac abnormalities by cross sectional echocardiography. RESULTS: Eighty (51%) men and 77 women were studied (mean (SD) age 34.4 (8.5), range 15-60 years for males and 31.6 (9.0), range 16-65 years for females). They were all heterosexual. None was haemophiliac or an intravenous drug user. Echocardiographic abnormalities were found in 79 (50%) patients: 14/151 (9%) had dilated cardiomyopathy, 33/151 (22%) left ventricular dysfunction, 9/151 isolated right ventricular dilatation, and 30/157 (19%) pericardial disease (28 with effusions, three having tamponade). There were two cases of constrictive pericarditis and one of ascending aortic aneurysm. CONCLUSIONS: There is a high prevalence of echocardiographically detected myocardial and pericardial disease in this group of acutely ill HIV infected patients. Left ventricular dysfunction without dilatation was common, but its significance was not ascertained.

Acute Disease↗

Assessment of right ventricular contractile function in patients with left ventricular dysfunction by a simplified echocardiographic subtraction method.

A simplified version of the modified echocardiographic subtraction method for measuring right ventricular (RV) volume was used to assess the indices of RV contractile function, the end-systolic pressure-volume (RV Emax) ratio and the +dP/dt(max)-end-diastolic volume (EDV) relationship. RV volumes determined by the simplified subtraction method and the modified subtraction method were compared in 18 patients. Subsequently, RV contractile function was assessed in 13 patients with normal left ventricular (LV) function (control group: ejection fraction > 56%, as determined by left ventriculography), and 10 patients (group F; five with myocardial infarction, three with dilated cardiomyopathy, two with ischemic cardiomyopathy) with depressed LV function (ejection fraction < or = 55% by left ventriculography). During the application of lower body negative pressure of -20 mmHg, B-mode echocardiograms (apical four-chamber view) and RV or pulmonary artery pressure were recorded simultaneously. The regression equation between RV volumes obtained by the simplified subtraction method and the modified subtraction method was y = 0.99x + 4.5, and the correlation coefficient (r) was 0.985 (p < 0.001). The RV Emax of group F was not significantly less than that of the control group (0.40 +/- 0.16 vs 0.44 +/- 0.17 mmHg/ml, not significant). The correlation coefficients of RV Emax in each group were large (control group 0.92 +/- 0.09, group F 0.90 +/- 0.07). The +dP/dtmax-EDV ratio of group F was significantly less than that of the control group (2.05 +/- 0.74 vs 3.40 +/- 1.85 mmHg/ml.sec, p < 0.05). The correlation coefficient of the +dP/dtmax-EDV ratio was 0.91 +/- 0.06 in the control group and 0.85 +/- 0.15 in group F. The indices of RV contractile function could be assessed using the simplified subtraction method. RV function in patients with LV dysfunction appeared to be depressed.

Adult↗

[Right ventricular function in patients with poor left ventricular function: studies in patients undergoing coronary artery bypass surgery].

In many patients, right ventricular (RV) dysfunction is due to RV infarction. In some patients, however, RV dysfunction may be secondary to the left ventricular (LV) dysfunction. In order to clarify the influence of poor LV function on RV function, RV ejection fraction (EF) was evaluated serially by thermodilution techniques (REF-1, Edwards Laboratories) in patients with LVEF less than 40% who underwent aorto-coronary bypass surgery with uneventful postoperative course. The patients were divided into four groups depending on the site of LV infarction; anterior (n = 13), inferior (n = 8), anterior + inferior (n = 16), and no infarction (n = 4). Control (n = 11) consisted of the patients with LVEF more than 60% and with no significant stenosis of the right coronary artery. Cardiac index, intracardiac pressures and amount of catecholamine used during postoperative course showed no significant differences among the groups including control. However, the groups except for the group of anterior infarction showed significantly low pre- and postoperative RVEF compared with control. Only the group of anterior infarction had almost normal RVEF. These results mean that RV dysfunction associated with inferior infarction remain long afterwards and that low LVEF due to anterior infarction caused little effect on RV function.

Aged↗

[Interest of the brain natriuretic peptide as a marker of acute cor pulmonale in acute respiratory distress syndrome].

OBJECTIVE: The aim of this study was to evaluate the accuracy of the BNP as a marker of acute cor pulmonale in patients with ARDS. STUDY DESIGN: Prospective clinical trial. PATIENTS AND METHODS: At day 2 or 3 after the onset of the ARDS, an echocardiography was performed. Patients with left ventricular dysfunction were excluded. Right ventricular area (RVA) and RVA/LVA ratio were measured. ACP was defined as RVA/LVA > 0.6 associated with septal dyskinesia. Simultaneously, 5 ml of blood was collected for BNP measurement. RESULTS: 26 patients were studied. BNP levels were higher in 10 patients with ACP: 585.5 [189-4830] vs 145.5 [36.5-346] pg/ml (P=0.01) but in those with creatinine clearance < 90 ml/min: 602 [331-3530] vs 125 [39-189] pg/ml (P=0.007). BNP was correlated with RVA (r=0.5; p=0.01), RVA/LVA ratio (r=0.61; p=0.001), sPAP (r=0.58; p=0.002) and with age, cardiac index and creatinine clearance (r=0.61; p=0.001). In multivariate analysis, BNP was only correlated with creatinine clearance (p=0.03), and RVA (p=0.06). CONCLUSION: In ARDS patients without left ventricular dysfunction, BNP level is more elevated in patients with acute cor pulmonale than patients without cor pulmonale.

Acute Disease↗

Haemodynamic patterns in patients with scorpion envenomation.

OBJECTIVE: To study cardiovascular haemodynamics following scorpion envenomation. SETTING: Intensive care unit of a university hospital. PATIENTS: Eight patients with Indian red scorpion (Mesobuthus tamulus) stings. INTERVENTION: Captopril (6.25 to 12.5 mg orally) every 30 minutes until pulmonary oedema resolved. MAIN OUTCOME MEASURES: Haemodynamic data obtained by pulmonary artery catheterisation. RESULTS: Two haemodynamic patterns were seen. There was a predominant vascular effect in one patient, with severe hypertension, tachycardia, increased systemic vascular resistance index (SVRI = 5893 dyn.s.cm-5), and normal cardiac index (2.73 l/m2). A predominant myocardial effect with left ventricular dysfunction and normal right ventricular function was seen in the other seven patients, with tachycardia, pulmonary oedema, mild hypotension, reduced stroke volume (mean (SD), 25.9 (8.3) ml/m2), normal SVRI (1812 (831) dyn.s.cm-5), and increased pulmonary artery wedge pressure (PAWP = 25 (4.4) mm Hg). Following mild dehydration pulmonary oedema subsided (PAWP = 14 (8.5) mm Hg) in three of these patients, but hypovolaemic shock developed (right atrial pressure (RAP) = 1.3 (2.1) mm Hg); pulmonary oedema recurred with rehydration. One patient developed fatal cardiogenic shock with raised PAWP (27 mm Hg) and RAP (11 mm Hg), and vasodilatation (SVRI = 1129 dyn.s.cm-5). Stroke volume (30.5 (8.7) ml/m2) and cardiac output (4.3 (1.5) 1/m2) improved with resolution of pulmonary oedema (PAWP = 14.4 (4.2) mm Hg) following afterload reduction with captopril. CONCLUSIONS: Mild envenomation causes severe vasoconstriction and hypertension. Severe envenomation produces predominant left ventricular dysfunction with normal systemic vascular resistance manifesting as pulmonary oedema or severe hypotension depending on the fluid balance. Shock due to biventricular dysfunction and vasodilatation occurs terminally.

Adolescent↗

Left ventricular diastolic dysfunction presenting as ascites: the importance of clinically assessing central venous pressure.

A 66-year-old man without history of heart disease or symptoms of left ventricular (LV) failure was admitted with transudative ascites. Echocardiography showed no valvular or pericardial disease and normal LV function. Gated pool scintigraphy confirmed normal LV systolic function but demonstrated severe right ventricular systolic dysfunction. Catheterization revealed left ventricular diastolic dysfunction as the cause of right-sided failure. The clinician evaluating transudative ascites cannot exclude LV failure on the basis of noninvasive assessment of systolic function alone. Appreciation of an elevated central venous pressure remains the most important evidence of a cardiac source of ascites.

Aged↗

[Functional dynamics of the right ventricle and pulmonary circulation in obstructive sleep apnea. Therapeutic consequences].

Obstructive sleep apnea (OSA) is common with an incidence of at least 500,000 patients in the German population. Typical symptoms are daytime sleepiness, headache in the morning, and snoring. Presumably obstructive sleep apnea via various mechanisms increases cardiovascular morbidity. Hypoxemia causes nocturnal hypertension in most of the patients. Nevertheless, about 20% of the patients develop daytime pulmonary hypertension and right heart dysfunction. Clinical and animal studies demonstrated right ventricular hypertrophy as a consequence of intermittent hypoxemia and pulmonary hypertension. Right ventricular hemodynamics differ essentially from left ventricular hemodynamics. Right ventricular function is substantially influenced by right ventricular afterload, which is mainly determined by pulmonary vascular resistance, and slightly influenced by preload. Application of continuous positive airway pressure (CPAP) via a nose mask normalizes nocturnal breathing disorders and reduces pre- and afterload, especially in patients with cardiomegaly. Therefore, CPAP generates positive effects on the myocardium.

Continuous Positive Airway Pressure↗

Brain natriuretic peptide: diagnostic and therapeutic implications in pulmonary arterial hypertension.

Brain or B-type natriuretic peptide (BNP) is one of the new biomarkers employed within the last decade to help clarify difficult cardiovascular problems. Plasma BNP is elevated in cardiac ventricular dysfunction and plays a key role in protecting the body from volume overload by maintaining renal function and sodium balance. Studies in patients with pulmonary arterial hypertension (PAH) have demonstrated that plasma BNP levels are raised proportionally to the extent of right ventricular (RV) dysfunction. There is growing evidence that BNP may be a potential biomarker for PAH in screening for occult disease, diagnostic evaluation, prognosis, and estimating a response to therapy. Additionally, augmentation of the natriuretic peptide system through exogenous administration of BNP or by preventing its degradation may be a promising option for the management of decompensated RV failure. Because plasma BNP levels rise in a variety of cardiopulmonary conditions and are affected by several physiological factors, BNP interpretation must not occur in isolation but rather within the context of good clinical judgment.

Biomarkers↗

Effects of left ventricular support on right ventricular mechanics during experimental right ventricular ischemia.

BACKGROUND: Left ventricular (LV) assist device (LVAD) support has been associated with right ventricular (RV) failure in humans, but the etiology remains unknown. Mechanical LV support apparently does not induce RV pump failure in normal hearts, but controlled studies of LV assistance in hearts with preexistent RV dysfunction have been limited. Therefore, this study was performed to determine if LVAD support impairs RV systolic mechanics during acute RV ischemia. METHODS AND RESULTS: Five closed-chest, autonomically blocked, sedated dogs were studied after placement of an LVAD (LV-femoral artery bypass), right coronary artery (RCA) occluder, and 27 miniature radiopaque tantalum markers into the LV and RV walls for independent computation of RV and LV volumes. Biplane videofluoroscopic marker images and hemodynamic data were recorded before RCA occlusion with the LVAD off (maximum LV pressure [LVPmax] = 119 +/- 25 mm Hg), after 3 minutes of RCA occlusion with the LVAD off (LVPmax = 84 +/- 18 mm Hg), and then with the LVAD on (LVPmax = 26 +/- 32 mm Hg). Global RV contractility (end-systolic elastance [RV Ees] and preload recruitable stroke work [RV PRSW]), RV power output, and the mechanical (pump) efficiency of converting potential energy to external work (ratio of RV stroke work/total pressure-volume area) were calculated. As expected, with RCA occlusion there were major decreases in RV Ees (from 2.5 +/- 1.2 to 1.4 +/- 0.5 mm Hg/mL, P < .005) and RV PRSW (15 +/- 4 versus 9 +/- 4 mm Hg, P < .001). RV power output (overall pump performance) declined by 39 +/- 20% (P < .025), and mechanical efficiency fell by 38 +/- 13% (P < .001). After initiation of mechanical LV support, however, there was no further impairment of RV contractility or power output (P > .80). Pulmonary artery input impedance (RV afterload) decreased from 848 +/- 628 to 673 +/- 577 dyne.sec-1.cm-5 (P < .01), which led to a 26 +/- 29% improvement in RV pump efficiency (P < .001). CONCLUSIONS: While right coronary artery occlusion significantly reduced RV systolic performance, LVAD support during acute RV ischemia did not further impair RV contractility or power output. Furthermore, since RV afterload fell with LV unloading, the mechanical pump efficiency of the right ventricle actually improved. These observations demonstrate that LVAD support does not directly induce RV failure in canine hearts with acute isolated RV ischemia.

Animals↗

Evaluation of cardiac function by tissue Doppler imaging in children with chronic hepatitis.

OBJECTIVES: Pathoanatomic changes in cirrhosis result in impaired ventricular filling and diastolic dysfunction and were named as cirrhotic cardiomyopathy. However, cardiac functions have not been studied in patients with chronic hepatitis. We hypothesized that such patients might have subclinical ventricular dysfunction, detectable by tissue Doppler echocardiography and related to the severity of hepatic inflammation and fibrosis. METHODS: We studied 63 clinically stable patients, 27 patients with mild chronic hepatitis (group 1), 22 patients with moderate chronic hepatitis (group 2) and 14 patients with severe chronic hepatitis (group 3) according to the scoring system of Knodell, and 36 age-matched healthy subjects. RESULTS: Patients with severe chronic hepatitis had impaired right ventricular diastolic function. The early diastolic velocity of the tricuspid valve annulus was lower in patients from group 3 than in healthy subjects (P < 0.001). Patients in group 3 had a greater isovolumic relaxation time (P < 0.001), indicating right ventricular diastolic dysfunction. Comparing group 3 with the healthy subjects, the ratio of peak early myocardial tissue velocity and peak late (or atrial) myocardial tissue velocity was significantly decreased (P < 0.001), at 1.4 (0.7) and 1.9 (0.7), respectively. There was also a slightly lower peak early myocardial tissue velocity and peak late (or atrial) myocardial tissue velocity ratio and a slightly longer isovolumic relaxation time in patients from group 2 than in healthy subjects (P < 0.05). CONCLUSIONS: We detected subclinical dysfunction of the right ventricle in children with chronic hepatitis in whom hepatic inflammation and fibrosis is prominent. Tissue Doppler echocardiography provides a quantifiable indicator useful for detection and monitoring of disease progression.

Adolescent↗

Left ventricular assist device for right side assistance in patients with transposition.

Right (systemic) ventricular dysfunction is well described after Senning operations for transposition of the great arteries, and patients with congenitally corrected transposition of the great arteries. Transplantation remains the only definitive therapy for refractory heart failure, however patients may deteriorate clinically prior to the availability of a donor heart. This report details the implantation of a TCI Heartmate (Thoratec Corp., Pleaston, CA) as a morphologic right ventricular assist device to bridge these patients to transplantation.

Adolescent↗

[Sick sinus syndrome: comparative study of atrial and ventricular stimulation tests].

Subjects with a ventriculo-atrial block and normal sinus function exhibit acceleration of the sinus rhythm during incremental right ventricular pacing; this acceleration is nor observed or is hardly visible in patients with sinus node dysfunction. Incremental right ventricular pacing up to 150/min was performed in 16 patients with ventriculo-atrial block (Group A) referred for investigation of sinus node dysfunction and the results compared with the classical tests of atrial pacing (Strauss'graph, atrio-sino-atrial conduction time, sinus node recovery time). The same tests were carried out in 19 patients without sinus node dysfunction (Group B). In the latter group, sinus rhythm exceeded 80/min during right ventricular pacing at 150/min and the rate increased with respect to the basal rhythm was always greater than 10/min. In Group A premature atrial pacing gave abnormal results in 4 cases, sinus node recovery times were abnormal in 15 cases, and rapid right ventricular pacing abnormal in all cases (sinus rhythm less than 80/min and/or rate increase of less than 10/min). There was no relation between the increased sinus node recovery time and the degree of rate increase during rapid ventricular pacing. Incremental right ventricular pacing, therefore, seems to be a new method of investigating sinus node function but complementary studies are required to determine its limitations, the exact mechanism and to try to widen its application to subjects without ventriculo-atrial block.

Aged↗