Coronary artery thrombosis and thrombolysis in baboons: the effect of atenolol treatment on myocardial infarct size

The effect of the beta-blocker atenolol on experimental infarctsize was studied in a non-human primate model. In 12 baboonsthrombosis of the left anterior descending coronary artery (LAD)was induced and atenolol (0·1 to 0·2 mg . kg^–1intravenously, sufficient to lower the heart rate by 20%) wasadministered 10 mm after the onset of ischaemia in six animals,whereas the others received placebo. Thrombolysis was induced60 mm after the onset of ischaemia by intravenous injectionof rt PA (12 µg. kg^–1. min^–1) in all animals. Heart rate dropped signficantly after atenolol injection (128±9beats . min^–1 versus 163±15 beats . min^–1,P<0001) and was also lower than in the control group (128±9beats. min^–1 versus 158±22 beats.min^–1, p<0·05).Blood pressure remained unchanged after atenolol treatment.As compared to the control group, atenolol limited infarct size,expressed as a percentage of left ventricular mass (4·6±1·9%versus 7·9±1·3%, P<0·05 or asa percentage of the perfusion area (26±8% versus 43%8%,P<0·05).     

Assessment of coronary reserve by transoesophageal Doppler echocardiography: Direct comparison between different modalities of dipyridamole and adenosine administration

BACKGROUND: This study was undertaken to compare the coronary vasodilatorresponse to different application modalities of intravenousvasodilators, in order to identify the optimal pharmacologicalprotocol for the evaluation of coronary reserve by means oftransoesophageal Doppler echocardiography. METHODS: Blood flow velocity in the left anterior descending artery,coronary vascular resistance and left main coronary artery cross-sectionalarea were assessed by transoesophageal echo-Doppler during ani.v. adenosine bolus (5 mg), a 5-min adenosine infusion (infusionrate 140µg.kg^–1.min^–1), and low (0·56mg.kg^–1.min^–1),and high-dose (0·84mg.kg^–1.9min^–1) dipyridamoleinfusions in 10 healthy normals (Group 1) and in 20 patients(Group 2) with either coronary microvascular disease (11 patients)or coronary artery disease (nine patients). RESULTS: In both groups, the highest flow velocity and the lowest coronaryvascular resistance were observed during the adenosine infusion.Flow velocity values and indices of coronary vasodilator capacityobserved after the adenosine bolus and the high-dose dipyridamoleinfusion were very close to those obtained during the adenosineinfusion, especially in Group 1. Coronary flow velocity waslower and coronary vascular resistance higher after low-dosedipyridamole, significantly in Group 2. The maximal flow responseto the adenosine bolus was observed within a few seconds afterthe injection, and was very short. The peak response to theadenosine infusion was observed 57±27 s after its start.The coronary flow velocity response to dipyridamole was dosedependent and differed between Groups 1 and 2. CONCLUSION: In combination with transoesophageal Doppler echocardiography,a short-lasting adenosine infusion at a rate of 140µg.kg^–1.min^–1seems to be preferable to an adenosine bolus and dipyridamoleinfusion. The effect of the bolus is too short for an accuratemeasurement of coronary flow velocity, while the dipyridamoleinfusion, especially at a low dose, induces a submaximal vasodilatorresponse.     

Inotropic and vasodilating properties of amrinone depend on the mode of administration

Intravenous infusion of amrinone at increasing rates (10–100µg kg^–1 min^–1,N= 8) caused dose dependentdecreases in left ventricular filling pressure (up to 22%, P<0.05)andcardiac output (up to 16%,P<0.05), but had no effect onheart rate, max L VdP/dt or total systemic vascular resistancein anaesthetized open-chest pigs. Despite unchanged total systemicvascular resistance, tissue vascular resistance decreased significantlyin the heart, stomach, adrenals and kidneys. Although transmuralleft ventricular perfusion was not influenced by amrinone, coronaryblood flow was redistributed in favour of the epicardium, asendo-epi blood flow ratio decreased from 0.95±0.03 to0.82±0.03 (P<0.05). In the same model an intravenousbolus of 1 mg kg^–1 followed by a continuous infusion of50 µg kg^–1 min^–1 (N<8), caused immediatechanges (P<0.05) in left ventricular filling pressure (–35%),max LVdP/dt (+55%), heart rate (+15%) and total systemic vascularresistance (–15%). The changes in filling pressure andsystemic vascular resistance persisted during the next 25 minutes,but maxLVdP/dt returned gradually to baseline in spite of increasingplasma concentrations of the drug. In the conscious pig (N=4),administration of a 1 mg kg^–1 bolus in the pulmonary arteryled to similar increases in heart rate (15%) and max LVdP/dt(26%), while systolic left ventricular pressure was not affected.Direct infusion into the left anterior descending coronary artery(10–40 µg kg^ndash;1 min^–1, N=5) had negligibleeffects on overall haemodynamics and regional myocardial function.The only significant changes were a vasodilation in the coronaryvascular bed accompanied by dose dependent increases in thecoronary venous O₂-content. From our study it appears that abolus injection, as given in the clinical setting, is requiredto elicit an increase in max LVdP/dt and arterial vasodilationbut that the effect on left ventricular preload is not sensitiveto different modes of administration.     

Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure

This study was undertaken to assess the haemodynamic effectsof the combined infusion of prostacyclin and piroximone, a phosphodiesteraseinhibitor, in 18 patients with severe congestive heart failure.Right heart catheterization was performed with a Swan-Ganz thermodilutioncatheter and arterial blood pressure was monitored using a radialline. After baseline haemodynamic measurements, prostacyclinwas administered in all patients at the incremental infusionrate of 2, 4, 6 and 8 and 10 ng. kg^–1. min^–1 during15min each. After recovery of baseline haemodynamics, patientswere randomly assigned to the piroximone infusion rate of 5or 10µg. kg^–1. min^–1 or placebo. After 24h piroximone or placebo infusion, the same prostacyclin protocolwas applied. Prostacyclin infusion added to piroximone resultedin a significant improvement in haemodynamics, as compared tothe group receiving prostacyclin added to placebo. As comparedto the curve observed with the placebo infusion, 10 ng. kg^–1.min^–1 prostacyclin infusion resulted in a further increasein cardiac index, by 41 and 38% (P<0·01) at the piroximone-infusionrates of 5 and 10 ng. kg^–1. min^–1, respectively,whereas systemic vascular resistance decreased by 25 and 21%,respectively (P<0·01). Additionally, a further decreasein pulmonary capillary wedge pressure by 13 and 11% (P<0·05)and in pulmonary vascular resistance by 21 and 19% (P<0·05)was observed at the piroximone-infusion rates of 5 and 10µig.Kg^–1. min^–1, respectively. Consequently, strokework index increased significantly, as compared to the groupreceiving prostacyclin added to placebo. This haemodynamic improvementoccurred without significant changes in heart rate and meanarterial pressure. Thus, this study shows that in patients withsevere congestive heart failure, short-term infusion of prostacyclinis safe and has additive haemodynamic effects on phosphodiesteraseinhibitors.     

Prostaglandin E1--bridge to cardiac transplantation: Technique, dosage, results

BACKGROUND: Heart transplantation candidates who remain severely symptomaticdespite therapy are normally hospitalized. Continuous infusionof intravenous drugs from a portable pump may allow such patientsto live a fairly active life until a donor heart is found. AIM: To investigate in an open pilot study if heart transplantationcan be safely accomplished if these patients are continuouslybridged with various regimens including inotropic support withlow-dose dobutamine in conjunction with dopamine and prostaglandinE1. METHODS: We report on 5 years' experience with prostaglandin E1, a potentvasodilator with proven efficacy in severe heart failure whencoupled with catecholamines. From 1990 to 1995 54 heart transplantationcandidates were bridged with prostaglandin E1 in addition todobutamine 5 µg.kg^–1.min^–1 and dopamine 3µg.kg^–1.min^–1 (group A; n=32) or in additionto 3 µg.kg^–1.min^–1 dopamine alone (group B;n=22), and 11 heart transplantation candidates were bridgedwith dobutamine 5 µg.kg^–1.min^–1 and dopamine3 µg.kg^–1.min^–1 only (group C; n=11). In aninitial dose-ranging test, prostaglandin E1 was uptitrated toside effect limit (29±1 ng.kg^–1.min^–1). Haemodynamics,except for stroke volume index, were similar in all patientsat baseline and a sufficient haemodynamic response (20% increasein stroke volume) was observed during the acute study. Fiftypercent of the peak dose was used for initiating chronic therapy;the dose of prostaglandin E1 was further reduced if side effectsrecurred. RESULTS: Twenty-nine (54%) patients in groups A and B and six in groupC could be discharged home with chronic therapy via a Hickmancatheter connected to a portable pump. After 4 weeks in sixpatients in group A and in 13 patients in group B, when prostaglandinE1 had been reduced from 15±2 ng.kg^–1.min^–1to 8±1 ng.kg^–1.min^–1, increases in cardiacindex and decreases in systemic vascular resistance were sustained,and a permanent decrease in pulmonary vascular resistance indexwas observed in group B. Intravenous therapy was changed innine patients (3/1/5) because of side effects and worseningheart failure. Prostaglandin E1 was withdrawn in three of thesepatients because of an increase in serum creatinine (3 mg.100ml^–1), and in one because of noncompliance. In total,there were 17 cardiac deaths (9/6/2), 42 heart transplants (22/14/6)and six (1/2/3) weaned survivors (including one non-cardiacdeath) in this study. Overall outcome was similar in groupsA and B, but distribution after 2 months appeared to be different(P<0·05) based on more transplantations in group A. CONCLUSION: We concluded that chronic infusions with prostaglandin E1 atreduced dosages is a feasible and safe therapeutic adjunct tobridge end-stage heart failure patients and may yield desirableeffects in a subset of patients in the absence of inotropicsupport by dobutamine.     

Recombinant hirudin as a periprocedural antithrombotic in coronary angioplasty for unstable angina pectoris

Percutaneous transluminal coronary angioplasty is often complicatedby thrombotic abrupt vessel closure in patients with unstableangina pectoris. The present multicentre trial was performedto determine the feasibility of two-dose regimens of recombinanthirudin (r-hirudin) compared to standard heparin in patientsundergoing coronary angioplasty for unstable angina, and toinvestigate the effects of the different treatment regimen onmarkers of coagulation activation. At five participating centres,61 patients were randomly enrolled in one of two sequentialgroups of r-hirudin (group 1: 0-3mg.kg^–1 i.v. bolus, 0·12mg. kg^–1 h^–1 i.v. infusion; 21 patients; group 2:0·5 mg. kg^–1 i.v. bolus, 0·24 mg. kg^–1h^–1 i.v. infusion; 19 patients) or in a heparin controlgroup (150 IU . kg^–1 i.v. bolus, 20 IU . kg^–1. h^–1i.v. infusion; 21 patients). Antithrombotic therapy was startedimmediately before coronary angioplasty and continued for 24h. This was followed by a low-dose anticoagulant infusion foranother 24 h (r-hirudin: 004 mg . kg^–1. h^–1; heparin:7 IU . kg^–1. h^–1). Activated partial thromboplastintime, r-hirudin plasma concentrations by both immunologicaland functional assay, thrombin-hirudin complex, thrombin-antithrombinIII complex, soluble fibrin, and prothrombin fragment 1+2 wereclosely monitored. The median partial thromboplastin time prolongationsat 24 h vs baseline were found to be 1·9-fold and 2·3-foldin r-hirudin group 1 and dose group 2, respectively, and 3·0-foldin the heparin group. There was a dose-dependent correlationbetween partial thromboplastin time and the r-hirudin plasmalevels (r=0·61). In five of 21 patients of dose group1, three of 19 patients of dose group 2, and 10/21 patientsof the heparin group, partial thromboplastin time values exceedingthe predefined target range prompted an interruption of theinfusion. One major bleeding complication occurred in dose group2. The functional assay for the estimation of r-hirudin plasmaconcentrations showed excellent correlations to the immunologicaltechnique (r=0·99). Differences between the thrombin-hirudincomplex levels could not be observed. Increased concentrationsof thrombin-antithrombin III complex, soluble fibrin, and prothrombinfragment 1+2 were seen 4–8 h after coronary angioplastyand after reduction of the high-dose therapy in dose group 1when compared with dose group 2 and the heparin group, respectively.Based on coagulation tests the present study showed the feasibilityof a periprocedural antithrombotic regimen with r-hirudin forpatients undergoing coronary angioplasty for unstable angina.In addition to the partial thromboplastin time the determinationof r-hirudin plasma levels by a chromogenic substrate assayconsiderably improves the monitoring of therapy. The lower doser-hirudin regimen seems to be suboptimal as periprocedural anticoagulationin coronary angioplasty patients as indicated by markers ofthrombin generation and thrombin activity.     

Dipyridamole stress thallium-201 perfusion abnormalities in patients with hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome

Aims Thallium-201 perfusion abnormalities are common in patientswith hypertrophic cardiomyopathy and may be associated withan adverse prognosis in the young. The aim of this study wasto prospectively determine the relationship between thallium-201defects during dipyridamole stress to clinical presentationand outcome in a large consecutive series of patients with hypertrophiccardiomyopathy. Methods/Results Thallium-201 single photon computed tomography was performedin 216 patients with hypertrophic cardiomyopathy during dipyridamolestress (0·5mg.kg^–1). Fixed perfusion defects occurredin 25%, and reversible defects in 22%. A combination of defectswas present in 7%. Fixed defects were associated with: a historyof syncope (17 of 46 with, vs 36 of 170 without syncope, P=0·03);larger left ventricular end-diastolic (46·9±7·4mmvs 43·3±6·4mm; P=0·001) and end-systolicdimension (30·2±8·4mm vs 24·5±5·9mm,P<0·0001); increased left atrial diameter (46·1±8·1mmvs 40·5±7·7mm, P<0·0001); lowerfractional shortening (35·9±10·4% vs 43·8±8·6%,P<0·0001); and lower maximal exercise oxygen consumption(24·2±8·1ml.min^–1.kg^–1vs 29·4±8·8ml.min^–1.kg^–1,P<0·0003). Reversible defects did not correlate withsymptomatic status, but were associated with: larger left atrialdimensions (44·5±8·1mm vs 41·0±8·0mm;P=0·009) and greater maximal left ventricular wall thickness(24·0±7·0mm vs 20·6±7·0mm,P=0·003). The mean follow up time was 41±21 months,range 0·6–124. There was no association betweenany thallium-201 abnormality and disease related death in youngor adult patients. Conclusion The present study shows that fixed thallium-201 perfusion defectsdetected during dipyridamole stress in patients with hypertrophiccardiomyopathy are associated with syncope, larger left ventricularcavity dimensions and reduced exercise capacity. Although theevent rate was relatively small, there was no evidence for anassociation between thallium-201 defects and survival.     

Cardiovascular physiology: The deletion polymorphism of the angiotensin-converting enzyme gene is related to phenotypic differences in human arteries

We hypothesized that angiotensin-converting enzyme (ACE) insertion/deletionpolymorphism may be related to arterial phenotypic differencesthat could explain the adverse effects of deletion polymorphism. Accordingly, contractile responses to angiotensin I and II (0·1nmol .1^–1 µmol. 1^–1), endothelium-dependentrelaxation to methacholine (0·0–100 µmol. 1^–1), and the effect of N^G (L-NMMA; 100 .µmol. 1^–1) on phenylephrine (10 µmol .1^–1) inducedcontraction, were studied in isolated rings of internal mammary arteries obtained from patients undergoing coronary bypasssurgery. The results were analysed according to the ACE genotypeof the patient (II, n=8; ID, n=11; DD, n=9) as well as the presence/absenceof either allele. The arteries from patients with the D allele (IDIDD) displayeda lower sensitivity to methacholine (P<0·05 vs II),which suggested that the capacity of the endothelium for nitricoxide release in response to stimulation was also lower. Bycontrast, the increase in phenylephrine-induced contraction,by pre-incubation with L-NMMA, was more pronounced in the groupwith the DD allele (31±5%) than with the ID (11±11%)and II alleles (1±11%, P<0·05 vs DD), whichsuggested a higher level of basal nitric oxide release. Finally,the differences in the responses to angiotensin I and II, whichwere used to evaluate the vascular conversion of angiotensin1, indicated that the level of angiotensin I conversion washigher in patients with the D allele (IDIDD, P<0·05vs II). The findings of this study indicate that ACE insertion/deletionpolymorphism is related to arterial phenotypic differences inendothelial function and angiotensin I conversion.     

Nifedipine versus nitroprusside for controlling hypertensive episodes during coronary artery bypass surgery

Intraoperative hypertensive episodes are a common problem inpatients undergoing coronary artery bypass grafting. Twentypatients who developed acute hypertension (mean arterial pressureincrease to 110 mmHg) were studied. Ten patients received nifedipine(about 3 fig µg^–1 min^–1) and ten patientsnitroprusside (about 0-75 fig/kg^–1 min^–1) to returnarterial blood pressure to control levels. All patients wereanaesthetized with Jlunitrazepam, fentanyl, pancuronium andN₂0/V₂. The study compares the effects of nifedipine and nitroprussideon systemic and pulmonary haemodynamics. Both nifedipine andnitroprusside decreased arterial pressure to baseline valueswithin about 3 min by reducing the elevated systemic vascularresistance. Cardiac filling pressures and pulmonary artery pressuredecreased significantly only with nitroprusside. Following nitroprussidecardiac output remained unchanged whereas nifedipine increasedcardiac output and stroke volume when blood pressure was loweredby a comparable degree. The data suggest that nifedipine primarily affects resistancevessels in the systemic circulation without significantly changingvenous tone as opposed to the effect of nitroprusside. Thus,nifedipine appears to be an appropriate vasodilator for controllingarterial hypertensive episodes in patients with coronary arterydisease and normal left ventricular function.     

Clinical cardiac electrophysiology of indoramin, a post-synaptic alpha blocker

Indoramin is a selective post-synaptic alpha blocker. Animalexperiments had shown that it has antiarrhythmic effects, butwhether this is due to its alpha blocking effect or some othermechanism is not known. Fifteen patients (10 males) underwentelectrophysiological investigations before and 15 minutes afterintravenous indoramin injection (0.2-0.5 mg kg^–l). Theplasma level of indoramin was measured and the patients weredivided into two groups: group 1 (8 patients) whose plasma levelwas less than 100 µg ml^–1 (average 72 µg ml^–l)and group 2 (7 patients) whose plasma level was more than 100µg ml^–1 (average 151 µ ml^–1). In bothgroups there was a significant drop in the systolic blood pressureafter indoramin (129±22 to 111 ±23 mmHg, P<0.001).There was a marked improvement in the sinus node recovery timein group 1 only (253±92 to 163±40ms, P<0.01).Similarly there was a decrease in AH interval during fixed rateatrial pacing in group 1 only (128 ±33 to 100 ±37ms, P<005) and a significant decrease in the Wenckebach cyclelength after indoramin in group 1 only (372 ±85 to 347± 74 ms, P<005). At the atrial level there were nosignificant effects in either group but there was a significantincrease in the ventricular effective refractory period in group2 (231 ± 35 to 264 ± 64 ms, P< 0.05) but nochange in group 1. The QTc prolonged significantly in group2 (407 ±87 to 438 ±67 ms, P>0-05) but not ingroup 1. These findings suggest that indoramin has dual electrophysiologicaleffects: (1) an ‘excitatory’ effect as seen in group1 which is probably due to alpha blockade or enhanced beta stimulation,and (2) a ‘depressive’ effect: seen in group 2,which may be due to a direct effect.     

Dromotropic effects of oral theophylline in patients with atrial fibrillation and a slow ventricular response

Theophylline increases sinus rate, but as yet its use has notbeen investigated in patients with chronic atrio ventricularconduction disturbances. Resting electrocardiogram, 24-h Holterrecording and treadmill test were performed in 17 patients withchronic atrialfibrillation and a slow ventricular response notrelated to drugs (age: 75±8 years). Then slow-releasetheophylline was administered (700mg daily) and after 5 daysthese investigations were repeated with the same methods. Theophyllineincreased mean resting heart rate (51±6 versus 67±13beats.min^–1, P<0·01 mean 24-h heart rate (51±6versus 68±14 beats.min^–1, P<0·01 andminimal 24-h heart rate (32±6 versus 42±11 beats.min^–1,P<0·01 Cardiac pauses >2·5 s were presentin 13 patients during control recording; after theophyllinethey disappeared in 11 and markedly decreased in the remainingtwo. The longest R-R interval decreased in all patients (3218±943versus 2121±518ms, P<0·01). The daily numberof wide QRS complexes increased in 16 out of 17 patients (428±752versus 1146±1464 ms, P<0·01). Exercise heartrate, evaluated at the end offirsi andsecondstage, was higherafter theophylline than during control test (P<0·01). These data suggest that oral theophylline can represent a validtherapy in most patients with atrialfibrillation and a slowventricular response.     

Long-term effect of cardioversion on peak oxygen consumption in chronic atrial fibrillation: A 2-year follow-up

Restoration of sinus rhythm may improve functional capacityin atrial fibrillation in the short-term. Little is known, however,about its long-term effect on functional status. The aim ofthe present study was to evaluate the long-term effect of cardioversionon peak oxygen consumption (VO₂) in patients with chronic atrialfibrillation. Patients with such a condition and due to undergoelectrical cardioversion were eligible for the study. Patients underwent treadmill exercise testing with measurementof peak VO₂ before cardioversion, and at 1 month and 2 yearsthereafter. Based on the rhythm present at those times aftercardioversion, patients were categorized into three groups:those in sinus rhythm after 1 month and 2 years (Group I); thosein sinus rhythm after 1 month, but with atrial fibrillationafter 2 years (Group II); and those who were in atrial fibrillationboth at 1 month and 2 years following cardioversion (Group III).Thirty-nine patients were included, and underlying heart diseasewas present in 24 of them (62%). In the comparison of the baseline characteristics of Group I(n = 17), Group II (n =11), and Group III (n = 11), underlyingheart disease was more frequent in Group I (88%, 45%, and 36%,respectively); otherwise they were similar. In Group I, peakVO₂ showed an insignificant increase from 21.1 ± 50 to22.3 ± 50 ml. min ^–1. kg^–1 1 month aftercardioversion. After 2 years of sinus rhythm, peak VO₂ showeda further increase to 23.8 ±5.0 ml. min^–1. kg^–1(P<0.05). In Group II patients, peak VO₂ improved after 1month of sinus rhythm (from 25.2 ± 7 to 27.8 ±8 ml. min^–1. kg^–1, P<0.05) but returned to baselineafter 2 years, when atrial fibrillation had relapsed. In GroupIII patients, peak VO₂ was unchanged 1 month after cardioversion,when atrial fibrillation had already relapsed. After 2 years,however, peak VO₂ had decreased from 22.1 ± 4.0 to 20.6± 4.0 (P<0.05), when compared to baseline. In conclusion, restoration of sinus rhythm is associated witha modest but significant improvement of peak VO₂, which persistsafter the first month following cardioversion. In addition,in patients with sustained atrial fibrillation functional capacitydecreases during long-term follow-up. These findings suggestthat, to prevent progressive deterioration of functional capacityin atrial fibrillation, a treatment approach aimed at restoringand maintaining sinus rhythm may be warranted.     

Gradient-echo magnetic resonance imaging during incremental dobutamine infusion for the localization of coronary artery stenoses

Dobutamine pharmacological stress testing in conjunction withgradient-echo magnetic resonance imaging (MRI) may be a usefultool for the assessment of haemodynamically significant coronaryartery stenoses. Therefore, 28 patients without previous myocardialinfarction but significant proximal stenoses (70% diameter stenosis)of one or more coronary arteries were selected for dobutamine-MRI.Each patient underwent MRJ at rest and during incremental dobutamineinfusion (5, 10, 15 and 20 µg. kg^–1. min^–1).Additionally, all patients were submitted to exercise stresselectrocardiography (EST). A total of 72 segments per patient obtained from identical shortaxis and transverse tomograms at rest and during dobutamineinfusion were evaluated by two observers. Each segment was gradedas normal, hypokinetic, akinetic or dyskinetic. Dobutamine-MRIwas considered pathological if segmental wall motion deterioratedby at least one grade after dobutamine infusion. For comparisonwith coronary angiography, segmental wall motion gradings wererelated to the respective coronary artery territories. Peakrate-pressure product during steady-state dobutamine infusion(18·493 ± 4·315 mmHg. min^–1) wassignificantly lower (P<0·01) than during EST (21·316± 4·937 mmHg. min^–1). Dobutanine-inducedwall motion abnormalities were observed in 22/26 (85%) MR studiesand 20/26 (77%) patients had a pathological EST. Regional asynergyinduced by dobutamine-MRI occurred in 11/15 (73%) patients withsingle and 11/11 (100%) with multi-vessel disease. Sensitivityand specificity for the detection of a stenosed coronary arterywere 87% and 100% for the left anterior descending, 62% and93% for the left circumflex and 78% and 88% for the right coronaryartery respectively. In conclusion, dobutamine-MRI is a well tolerated, non-exercisedependent test for the detection and localization of hzaemodynamicallysignificant coronary artery stenoses with a diagnostic accuracysimilar to that previously reported for high-dose dipyridamoleMRI but with a better control of stress intensity and duration.     

Influence of haemodynamics and myocardial ischaemia on Doppler transmitral flow in patients undergoing dobutamine echocardiography

To examine whether pulsed Doppler left ventricular filling indicescan reliably detect myocardial ischaemia in patients with coronaryartery disease undergoing dobutamine stress echocardiographywe studied three groups matched for age and global indices ofleft ventricular function. Group 1 patients (n=10) had normalcoronary arteries whereas those in Groups 2 (n=12) and 3 (n=15)had significant coronary disease (70% diameter stenosis) atangiography. After stopping cardiouctive treatment, patientsunderwent incremental dobutamine stress (5, 10, 15 and 20 µg.kg^–1. min^–1) during pulsed Doppler interrogationof diastolic filling with simultaneous heart rate and bloodpressure measurements. Only Group 3 patients developed myocardialischaemia using electrocardiographic and cross sectional echocardiographiccriteria, subset 3A (n=4) comprised those with inducible mitralregurgitation on colour Doppler. Electrocardiographic R-R intervaldecreased (–311 ± 123 ms, P<0·001) andmean blood pressure altered (5±17 mmHg, P=ns) uniformlyacross groups. The respective changes in peak early velocity,peak atrial velocity and their ratio for Groups 1 (0·08± 0·09 m. s^–1, 0·26 ± 0·18m.s^–1 and – 0·32 ± 0·36), 2(0·07 ± 0·07 m.s^–1 0·18±0·15m.s^–1 and –0·13±0·21) and 3(0·09±0·12 m.s^–1, 0·20±0·13m.s^–1 and –0·17±0·21) weresimilar (all P=ns between groups). Corresponding data for subset3A (0·23 ± 0·04 m.s^–1 0·20± 0·10 m.s^–1and 0·00 ± 0·16)revealed a significantly greater increase in peak early velocityand normalized velocity ratio in these patients. Overall, changesin peak early (r= –0·47, P<0·01) andatrial velocity (r–0·65, P<0·001) andtheir ratio (r=0·35, P<0·05) correlated withreduction in R-R interval but not alterations in blood pressure.In conclusion, tachycardia during dobutamine stress masks theeffects of myocardial ischaemia on Doppler diastolic indicesalthough a minority of patients with inducible mitral regurgitationmanifest a relatively distinct filling profile.     

Coronary vasodilation without myocardial erection: Simultaneous haemodynamic, echocardiographic and arteriographic findings during adenosine and dipyridamole infusion

AIM: The aim of this study was to evaluate simultaneously echocardiographic,haemodynamic and angiographic changes that occur during adenosineand dipyridamole infusion, in patients with one-vessel coronaryartery stenosis. This would assess whether deterioration inleft ventricular haemodynamics during vasodilator agent infusionis influenced by vasodilation per se, or the development ofmyocardial ischaemia. METHODS AND RESULTS: We performed adenosine (140 µg.kg^–1.min^–1over 4 min) and dipyridamole (up to 0·84 mg.kg^–1over 10 min) stress echocardiography tests, together with angiographicand haemodynamic assessment, in 26 patients undergoing electivecoronary angioplasty. In 12 of 26 patients, adenosine and dipyridamoletests were repeated 24 h after angioplasty. The criterion forechocardiography test positivity was the appearance of a newtransient regional wall motion abnormality. Coronary angiogramswere analysed with quantitative coronary arteriography. Adenosineand dipyridamole induced regional dysfunction in 18/26 (69%)and 14/26 (54%) patients before angioplasty, respectively (P=ns).In the echocardiography-positive patients, the percent diameterstenosis was significantly (P<0·05) tighter stenosisthan in the echocardiography-negative patients (adenosine, 66·6±8·3%vs 58·0±8·9%; dipyridamole, 69·2±7·1%vs 57·±7·6%). During both tests, left ventricularend-diastolic pressure significantly increased (P<0·05)in echocardiography-positive patients (adenosine, 9·8±2·7mmHg to 13·5±4·1 mmHg; dipyridamole, 10·1±2·8mmHg to 14·1±4·3 mmHg), but not in echocardiography-negativepatients. In the patients who had undergone successful angioplasty(reduction to <50% diameter stenosis), both adenosine anddipyridamole confirmed the arteriographic success of the procedure(echocardiography negative in all patients). In this group ofpatients, no significant change was observed in left ventricularend-diastolic pressure during adenosine or dipyridamole infusion. CONCLUSIONS: Intravenous infusion of either adenosine or dipyridamole wasaccompanied by an obvious increase in left ventricular end-diastolicpressure only in patients with induced wall motion abnormalities.Coronary vasodilation per se has no significant effect on leftventricular end-diastolic pressure when no ischaemia is induced,disproving any clinically significant ‘erectile’and adverse effects of coronary vasodilation per se.     

Physical training improves exercise capacity in patients with mitral stenosis after balloon valvuloplasty

BACKGROUND: Haemodynamic measurements taken at rest and during exerciseshowed that percutaneous transvenous mitral commissurotomy resultsin both acute and long-term improvement. However, the time lagbefore there is an increase in exercise and in peak oxygen uptakeappears to be delayed and irregular. PATIENTS AND METHODS: To assess the potential of physical training to restore betterphysical capacity after percutaneous transvenous mitral commissurotomy,26 patients with mitral stenosis were studied after the procedure.The group was split into two. Thirteen underwent a 3-month rehabilitationprogramme, and the other 13, who did not, acted as controls. RESULTS: The mitral valve orifice area increased similarly, from 1·;12±017to 1·88 ±0·28 cm² in the training groupand from 1·04±0·16 to 1·88±0·19cm² in the control group. Cardiopulmonary parameters were similarbefore percutaneous transvenous mitral commissurotomy (peako₂: 19·9±2·4 vs 18·9±4·5ml. min^–1. kg^–1; peak workload: 94·6±29·3vs 96·1±25 watts; o₂ at anaerobic threshold: 17±3·4vs 16·1±5·2 ml. .min^–1. kg^–1;all P=ns). Three months later the results were higher in thetraining group (peak o₂: 26·6±4·7 vs 21·6±3·8ml. min^–1. kg^–1, P=0·001; peak workload:125·4±26·6 vs 108·5±23 watts,p=0·03; o₂ at anaerobic threshold: 19·6±5·8vs 15·8±2·9 ml. min^–1. kg^–1;P=0·02). CONCLUSION: These results indicate that patients should take up exerciseafter successful percutaneous transvenous mitral commissurotomyfor better functional improvement.     

The use of esmolol to attenuate the haemodynamic response when extubating patients following cardiac surgery -- a double-blind controlled study

We have assessed the cardiovascular changes associated withemergence from anaesthesia, reversal of neuromuscular blockadeand extubation in a group of 14 patients immediately after coronaryartery bypass graft surgery had been completed. Patients wererandomly allocated to receive either esmolol 500µg. kg^–1over 1 min followed by 100 µg . kg^–1. min^–1or placebo starting prior to reversal. Significant hypertensionand tachycardia occurred in the placebo group, whilst thesechanges were prevented by the administration of esmolol.     

Sympathetic deactivation by growth hormone treatment in patients with dilated cardiomyopathy

Aims We examined the effects of growth hormone administration onthe sympathetic nervous system in patients with idiopathic dilatedcardiomyopathy. Background Growth factor therapy is emerging as a new potential optionin the treatment of heart failure. Although growth hormone providesfunctional benefit in the short term, it is unknown whetherit affects the sympathetic nervous system, which plays a rolein the progression of heart failure. Methods Seven patients with idiopathic cardiomyopathy received 3 monthstreatment with recombinant human growth hormone (0·15–0·20IU.kg^–1.week^–1). Standard medical therapy was unchanged.Myocardial norepinephrine release, both at rest and during submaximalphysical exercise, plasma aldosterone, and plasma volume weremeasured before and after growth hormone treatment. Myocardialnorepinephrine release was assessed from arterial and coronaryvenous plasma concentrations of unlabelled and tritiated norepinephrineand coronary plasma flow (thermodilution). Results Growth hormone induced a significant fall in myocardial norepinephrinerelease in response to physical exercise (from 180±64to 99±34ng.min^–1; P<0·05). Basally, plasmaaldosterone was 189±28 and 311±48pg.ml^–1inthe supine and upright position, respectively, and fell to 106±16(P<0·01) and 182±29pg.ml^–1(P<0·05)after growth hormone therapy. Growth hormone increased plasmavolume from 3115±493ml to 3876±336ml (P<0·05),whereas serum sodium and potassium concentrations were unaffected. Conclusions The data demonstrate that growth hormone administration to patientswith idiopathic cardiomyopathy reduces myocardial sympatheticdrive and circulating aldosterone levels. This neurohormonaldeactivation may be relevant to the potential, long-term useof growth hormone in the treatment of patients with heart failure.     

Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone: A randomized, digoxin-controlled study

A 24 h intravenous dosing regimen of amiodarone was designedto reach a peak plasma concentration at 1 h and to maintainthe concentration above a certain level during the infusionperiod A randomized, open-label, digoxin-controlled study wasundertaken to observe the efficacy and safety of the dosingregimen of amiodarone in treating recent-onset, persistent,atrial fibrillation and flutter with ventricular rates above130 beats. min^–1. Fifty patients with a mean age of 70± 7 (SD) years were enrolled and randomly assigned toreceive either amiodarone intravenously (n=26) or digoxin (n=24).Amiodarone HCl was infused over 24 h according to the followingregimen: 5 mg. min^–1, 3 mg. min^–1, 1 mg. min^–1and 0.5 mg. min^–1 for 1, 3, 6 and 14 h, respectively,for a 70-kg subject. Digoxin (0.013 mg. kg^–1) was infusedin three divided doses, each dose 2 h apart and infused over30 min. The mean heart rates in the amiodarone group decreased significantlyfrom 157 ± 20 beats. min^–1 to 122 ± 25 beats.min^–1 after 1 h (P<005 vs baseline), and then decreasedfurther to stabilize at 96 ± 25 beats. min^–1 after6 h (P<0.05). The digoxin group had fewer dramatic alterationsin heart rates, compared to the amiodarone group, in the first8h (P<0.05, respectively). Maximum reduction was reachedonly after 8 h. The amiodarone infusion was prematurely abortedin two patients due to severe bradycardia and death after conversionin one patient and aggravation of heart failure in the other.Overall, 24 of 26 patients (92%) in the amiodarone group and17 of 24 (71%) in the digoxin group were restored to sinus rhythmwithin 24 h. The accumulated rates of conversion over 24 h weresignificantly different between the two groups (P=0.0048). Digoxin,while not as effective as amiodarone in the treatment of recent-onsetatrial fibrillation and flutter, appears to be safer. Therefore,we suggest the use of digoxin as the first line drug for thetype of patients that formed the basis of the current studyand reserve amiodarone for refractory cases or those in whomdigoxin is not suitable.     

Alteration of peripheral vasodilatory reserve capacity after cardioversion of atrial fibrillation

In atrial fibrillation, exercise capacity is often reduced.This is usually ascribed to a decreased cardiac output as comparedwith sinus rhythm. Very few studies, however, have focused onchanges in the peripheral blood flow during atrial fibrillationas a potential mechanism for exercise limitation. The aim ofthe present study was to determine the effect of conversionof atrial fibrillation to sinus rhythm on peripheral blood flow. Calf blood flow, using an electrocardiogram-triggered venousocclusion plethysmograph, and peak oxygen consumption (peakVO₂), using treadmill exercise testing, were studied in 28 patientswith chronic atrial fibrillation eligible for electrical cardioversion.Measurements were performed before cardioversion, and repeated1 day and 1 month thereafter. Calf blood flow at rest, maximalcalf blood flow, and minimal calf vascular resistance duringthe hyperaemic response immediately following 700 J of calfexercise were determined plethysmographically. One day and 1 month after cardioversion, 23 and 14 patientswere still in sinus rhythm, respectively. In patients who stillhad sinus rhythm after 1 month, maximal calf blood flow increasedfrom 33·7±12 to 40·0±13 ml. 100ml ^{–1 min –1} (P<0.01) and minimal calf vascularresistance fell from 3·2±0·9 to 2·7±0·7mmHg.ml^–1. 100 ml^–1. min^–1 (P<0·01);peak VO₂ increased from 21·3±4 to 24·2±5ml. min^–1. kg^–1 (P<0·001). Calf bloodflow at rest did not improve. In contrast, no significant changesin maximal calf blood flow, minimal calf vascular resistanceand peak VO₂ occurred in patients who had atrial fibrillation1 month after cardioversion. A significant correlation was foundbetween changes in maximal calf blood flow and peak VO₂ 1 monthafter cardioversion (r=0·53, P<0·01). One dayafter cardioversion, no changes in calf blood flow or peak VO₂,were found, either in patients with sinus rhythm or atrial fibrillation. In conclusion, transition from chronic atrial fibrillation tosinus rhythm is associated with a (delayed) improvement in maximalcalf blood flow, minimal calf vascular resistance, and peakVO₂. Our findings suggest that increase in vasodilatory reserve capacitymay contribute to the improvement of exercise capacity aftercardioversion of atrial fibrillation.