Efficacy of flecainide in pacing-induced sustained ventricular tachyarrhythmias: correlation to clinical parameters and tachycardia-characteristics

Seventy-two patients with sustained ventricular tachycardiaor syncope of unknown origin underwent electrophysiologic evaluationbefore and after therapy with flecainide (200–300 mg day^–1).In all patients, sustained ventricular tachycardia or ventricularfibrillation was inducible during control electrophysiologicstudy. During flecainide therapy, sustained ventricular tachycardia(VT) was no longer inducible in 18 patients (25%) whereas in54 patients, VT was still inducible. In five of the latter patients,VT became more difficult to induce (overall efficacy 32%). Therate of VT decreased from 214±49 beats min^–1 duringthe control electrophysiologic study to 178±48 beatsmin^–1 during flecainide (P<0.01). The ERP of the rightventricle increased from 251±27 ms during the controlstudy to 267±34 ms on flecainide (P<0.01). Mean ejectionfraction and mean LVEDP did not differ between responders andnon-responders, yet the presence of a left ventricular aneurysmcorrelated with a lack of antiarrhythmic response to flecainide.VT rate as well as VT morphology during the control study discriminatedbetween responders and non-responders; 11% of patients withVT-rate 230 beats min^–1 responded to oral flecainidecompared with 31% with a VT rate > 230 beats min^–1at control. 26% with induced monomorphic VT responded, comparedwith 100% with induced VF during the control study. 18 of 23responders were discharged on flecainide. During a mean follow-upof 26±18 months, two patients experienced a recurrenceof VT and in one patient, flecainide had to be discontinueddue to side-effects. Thus, the acute efficacy of flecainide, evaluated by serialdrug testing, correlates with haemodynamic parameters and thecharacteristics of tachycardia.     

Dipyridamole slows the rate of isovolumic pressure fall in patients with normal coronary arteries

Dipyridamole is currently used for thallium imaging and stressechocardiography. The coronary and haemodynamic effects of dipyridamoleare well documented while its effects on left ventricular relaxationremain to be determined. The aim of the present study was toevaluate the effects of dipyridamole on left ventricular relaxationrate in healthy subjects. High fidelity pressure recordingswere obtained at fixed atrial pacing (89 ±2 beats. min^–1)in 10 subjects with normal left ventricular angiography andcoronary arteriograms. Left ventricular pressure was recordedat rest and 5 min after a 4 min infusion of dipyridamole (0.14mg. kg^–1. min^–1). Dipyridamole infusion decreasedleft ventricular systolic pressure (P<0.01) and time to leftventricular systolic pressure (P<0.01)r with no changes inend-diastolic pressure or peak rate of pressure rise. The peakrate of isovolumic pressure fall decreased (from 1957 ±105 to 1488 ± 100 mmHg. s^–1, Y<0.01) and thetime constant of isovolumic relaxation increased (from 37 ±2to 44±3 ms, P<0.02). In conclusion, our study indicatesthat acute administration of clinically relevant doses of dipyridamoledisplays deleterious effects on heart relaxation in healthyhumans.     

Postextrasystolic Repolarization Abnormalities in ST‐U Segment in Patients with Ventricular Arrhythmias

Background: Changes in U‐wave amplitude after premature ventricular contractions (PVC) are known as prognostic markers in the long QT syndrome dependent on bradycardia. The purpose of the study was to find correlation between postextrasystolic ST‐U segment changes and a history of sustained ventricular tachycardia or ventricular fibrillation (VT/VF). Methods: The ST‐U segment configurations were taken from the 24‐hour ambulatory ECG. The comparison of the morphology of these segments was performed between sinus beats preceding PVC's and first postextrasystolic beats. Population: Two groups of patients were evaluated: 1) 32 patients with VT/VF history (VT/VF group), and 2) 36 patients with potentially malignant arrhythmia (structural heart disease with frequent PVCs and/or nonsustained VT‐nsVT) tnon‐VT/VF group). Results: We found T‐wave changes in 8 patients (25%) from the VT/VF group and in 12 patients (33.3%) from the nonVT/VF group (P = NS) and U‐wave changes in 13 patients (40.6%) and 3 patients (8.3%), respectively (P < 0.05). Other ECG indexes related to PVC's were also considered: RR interval, coupling interval (Cl), prematurity index (Pl), and postextrasystolic pause (PP). The analysis of these ECG indices revealed, when compared with patients without T‐U‐wave changes, that the occurrence of U‐wave changes was significantly related to longer RR interval of the sinus rhythm preceding PVC: 1025 ± 211 vs 918 ± 200 ms (P < 0.05). The prematurity index was lowest in patients with U‐wave changes: 0.54 ± 0.12 vs 0.65 ± 0.16 (P < 0.01) while postextrasystolic pauses leading to the postextrasystolic U‐wave changes were significantly longer: 1383 ± 223 vs 1130 ± 247 ms (P < 0.001). Cl did not differentiate patients: 556 ± 108 vs 584 ± 117 ms (P = NS). Conclusions: Postextrasystolic changes in ST‐U segment configuration are dependent on bradycardia, low prematurity index of the PVC, and the lengthening of the postextrasystolic pause. U‐wave changes more frequently appeared in patients with malignant arrhythmias. Follow‐up study is needed to assess if they might be predictive for the occurrence or reoccurrence of arrhythmic episodes. A.N.E. 2002;7(1):17–21     

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).     

Coronary reserve, extent of coronary disease, recurrent angina and ECG changes during pain in the in-hospital prognosis of acute coronary syndromes

The prognostic value of recurrent angina, severity of coronarydisease, ECG changes during pain and coronary reserve (ischaemicthreshold measured by atrial pacing: heart rate with ST segmentshift = 1 mm), was evaluated in 383 consecutive patients withacute coronary syndromes. Univariate analysis showed a significantrelationship between occurrence of complications (death, infarctionor coronary surgery) and number of anginal episodes, extentof coronary disease, ischaemic threshold and ST depression withpain. A multivariate analysis indicated that the first threeparameters were the main independent predictors. Coronary reservewas reduced (threshold 150 beats. min^–1) in 83% of patientswho had a myocardial infarction (40), in 91% of those who died(11), in 87% of those who underwent coronary surgery (52) andin 47% of uncomplicated cases (301). Also, a low ischaemic thresholdwas associated with a larger number of anginal episodes thana high threshold ( 130 beats. min^–1, 6.1 ± 5.6vs > 150 beats. min^–1, 2.9± 4.1, P<0.0001),and in complicated patients with one-, two- or three-vesseldisease ischaemic threshold (137.3± 21.2, 133.3 ±18.9, and 135.1 ± 21.2 beats. min^–1, respectively)was lower than in the uncomplicated ones (153.4±20.1,P < 0.005; 148.2± 19.1 P < 0.005; and 139.2 ±23.0 ns, beats, min^–1). A threshold <150 beats. min^–1and ECG changes during pain identified the subset with the highestrisk for complications (59/137, 45%), whereas a threshold >150 beats. Min^–1 and absence of pain or ECG changes duringpain identified those with the lowest risk (5/109, 5%, p <0.001). Thus, our findings document the prognostic significance of coronaryreserve for in-hospital complications in patients with acutecoronary syndromes and confirm the prognostic value of previouslyknown risk markers. They also indicate that some of them maybe significantly influenced by the status of coronary reserve.     

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.     

Does dobutamine prevent the rise in left ventricular filling pressures observed during exercise after heart transplantation?

The purpose of the study was to evaluate whether infusion ofa beta-adrenergic agonist, prior to and during exercise, couldcompensate for reduced sympathetic stimulation and correct deficientacceleration of left ventricular relaxation, so preventing arise in left ventricular filling pressures during exercise aftercardiac transplantation. Abnormal left ventricular relaxationkinetics can contribute to exercise-induced diastolic dysfunctionof the cardiac allograft. This was demonstrated in transplantrecipients whose acceleration of left ventricular relaxationduring exercise was almost negligible recently and whose elevationof left ventricular end-diastolic pressure was high. Decreasedadrenergic tone due to denervation could be involved in deficientleft ventricular lusitropic response to exercise, because accelerationof left ventricular relaxation during exercise depends on adequatesympathetic stimulation. Serial supine bicycle exercise was performed at an identicalworkload in eight transplant recipients while in the controlstate and during continuous infusion of dobutamine, titratedbefore exercise to achieve a heart rate matching the heart rateat peak exercise in the control state. During control exercise,heart rate rose from 87 ± 8 to 104 ± 12 beats.min^–1 (P<0.05), left ventricular end-diastolic pressurefrom 14 ± 5 to 20 ± 4 mmHg (P<0.05), left ventriculardP/dt_max from 1374 ± 172 to 1854 ± 278 mmHg. s^–1(P<0.05), and cardiac output from 5.8 ± 0.9 to 8.5± 1.11. min^–1 P<0.05). There was a small butsignificant decrease of the time constant of left ventricularpressure decay (T) from 42 ± 6 to 38 ± 6 ms (P<0.05).During dobutamine infusion, exercise resulted in a further increasein heart rate from 108± 11 to 122 ± 17 mmHg (P<0.05),in cardiac output from 7.4 ± 0.9 to 10.3 ± 2.5l. min^–1 (P<0.05), and in left ventricular dP/dt_maxfrom2181 ± 220 to 2620 ± 214 mmHg. s^–1 (P<0.05).These values were higher than the measurements obtained at theend of the control exercise run (P<0.05). T failed to change(29 ± 4 vs 27 ± 5 mmHg, P>0.05) and left ventricularend-diastolic pressure increased from 5 ± 3 to 11 ±5 mmHg (P<0.05) but remained lower than at the end of thecontrol exercise run (11 ± 5 vs 20 ± 4 mmHg, P<0.05). Compensation for reduced sympathetic stimulation by administrationof dobutamine improves exercise haemodynamics in cardiac transplantrecipients, but cannot prevent the exercise-induced rise inleft ventricular end-diastolic pressure and correct deficientacceleration of left ventricular relaxation. Abnormal exercisehaemodynamics after heart transplantation are therefore onlypartly related to deficient sympathetic stimulation.     

Influence of the force--frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy

In isolated human myocardium it was shown that a positive force-frequencyrelationship occurs in non-failing myocardium; however, theforce-frequency relationship was found to be inverse in myocardiumfrom failing human hearts. In order to investigate the clinicalrelevance of these experimental findings, the influence of heartrate changes on haemodynamics and left ventricular functionwas studied in eight patients without heart failure and in ninewith failing dilated cardiomyopathy (NYHA II–III). Rightventricular pacing was performed at a rate slightly above sinusrate and at 100, 120 and 140 beats. min^–1 Haemodynamicparameters were obtained by right heart catheterization andby high-fidelity left ventricular pressure measurements. Leftventricular angiography was performed at basal pacing rate andat 100 and 140 beats. min^–1 With increasing heart rate,cardiac index increased in patients with normal left ventricularfunction from 2·9 ± 0·2 to 3·5 ±0·21. min^–1. m^–2 (P<0·01) and decreasedcontinuously in patients with dilated cardiornyopathy from 2·6± 0·1 to 2·2 ± 0·11. min^–1. m^–2 (P<0·05). With increasing heart rate,the maximum rate of left ventricular pressure rise increasedin non-failing hearts from 1388 ± 86 to 1671 ±88 mmHg. s^–1 (P<0·01) and did not change infailing hearts. Ejection fraction decreased from 27 ± 3% to 19 ±2% in patients with dilated cardiomyopathy (P<0·05)when the pacing rate was changed from 84 ± 2 beats. min^–1to 140 beats. min^–1, which was associated with a significantlyincrease in end-systolic volume without significantly changesin end-diastolic volume. In patients with normal left ventricularfunction, when the pacing rate was changed from 85 ±3 beats. min^–1 to 140 beats. min^–1, end-diastolicvolume decreased significantly by 13%, whereas left ventricularend-systolic volume and ejection fraction did not significantlychange. Left ventricular systolic and end-diastolic pressuresdid not significantly change with pacing tachycardia in eithergroup. The frequency-related changes in left ventricular volumesand pressures indicate that the differrent haemodynamic effectsof pacing tachycardia in both groups of patients result predominantlyfrom frequency effects on myocardial function and not from frequencyeffects on preload or afterload. These data indicate that recentexperimental findings of positive force-frequency effects innon-failing and negative force-frequency effects in failinghuman myocardium are relevant for the intact heart.     

Volume loading in predominant right ventricular infarction: bedside haemodynamics using rapid response thermistors

Intravenous fluid loading is commonly used for the treatmentof low cardiac output (CO) syndrome complicating severe rightventricular infarction (RVMI). We prospectively evaluated theeffectiveness of this method in 11 consecutive patients (age66 ± 14 years) with severe R VMI, using a newer thermodilutionmethod with rapid response thermistors. Volume loading was performeduntil pulmonary wedge pressure (PWP) reached 18 to 24 mmHg.Right atrial pressure (RAP), pressures of the right ventricle(RV) and pulmonary artery (PA), PWP, RV volumes, RV ejectionfraction (RVEF), stroke volume (SV), CO, pulmonary vascularresistance (PVR) and RAP/PWP ratio were measured before andafter volume loading. RAP rose from 12 ± 4 to 19 ±5 mmHg (P<0.0001) and its tracing showed a non-compliantpattern in all patients. RV end-diastolic pressure rose from13 ± 4 to 20 ± 5 mmHg (P<0.0001) and PWP from14 ± 3 to 20 ± 6 mmHg (P<0.0001). Mean PA pressurerose from 20 ± 3 to reach 25 ± 6 mmHg (P<0.001),while PVR did not change significantly (117± 39 vs 101± 49 dyn. s. cm^{– 5}, P ns). RAP/PWP ratio rose from0. 85 ± 0.14 to 1.05 ± 0.07 (P<0.01). The end-diastolicRV volume increased from 95 ± 26 to 113± 24ml.m^{– 2} (P<0.001); however, RV end-systolic volume increasedfrom 65 ± 28 to 83 ± 29 ml. m^{– 2} (P<0.01),thus SV did not change significantly (30± 6 vs 30±8ml. beat^{– 1}m^{– 2}, P ns). RVEF decreased from 32±11 to 28± 11% (P<0.001). CO did not improve significantly(2. 3 ± 0.42 vs 2.4± 0.62 l. min^{– 1}. m^–2, P ns) neither did the clinical status. In conclusion, volumeloading per se is not sufficient to improve CO in patients withsevere R VMI, despite the fact that it increases R V preloadLeft ventricular preload does not increase, but PWP rises becauseof the limiting role of the pericardium.     

The effects of frusemide and angiotensin-converting enzyme inhibitors and their combination on cardiac and renal haemodynamics in heart failure

Few studies exist on the interaction of diuretics and angiotensin-convertingenzyme inhibitors in patients with chronic heart failure. Twelvesubjects with heart failure were studied before and after theirusual oral dose of frusemide in random order on consecutivedays during fixed sodium, potassium and water intake. Patientsthen received 10 mg day ^–1 of enalapril for 5 days andsubsequently restudied before and after their usual dose offrusemide. Frusemide was not observed to have an effect on systemic orrenal haemodynamics prior to enalapril, but urine volume andsodium content rose as expected. Treatment with enalapril, inthe absence of frusemide, was associated with a fall in meanblood pressure from 89 ±5 mmHg to 85 ±4 mmHg (P< 0.02) and a rise in renal blood flow from 424 ±202ml min^–1 to 494±225ml min^–1 (P<0.02),but cardiac output and glomerular filtration rate were againunchanged. Addition of frusemide to enalapril therapy resultedin a greater fall in mean blood pressure (87±5mmHg to79±4 mmHg; P<001) and an increase in cardiac output(3.1 ± 11 lmin-1 to 3.6± 1.01 min^–1; P<0.02).Renal blood flow increased further than after enalapril aloneto 579 ±211 ml min^–1 but the glomerular filtrationrate fell to 63±26 ml min^–1 (P<0.01) and thefiltration fraction fell to 19±5% (P<0.001). Weightgain occurred and the diuretic response to frusemide was reducedduring this early phase of enalapril therapy.     

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.     

Ventricular tachycardia in myocardial infarction: Relation to heart rate and premature ventricular contractions

Analysis of monitored electrocardiograms, recorded in 77 patientsduring the first 48 hours following the onset of myocardialinfarction, revealed 492 episodes of ventricular tachycardiawith rates of 90–220 min^–1. Characteristics of theventricular tachycardia episodes were correlated with heartrate and with the rate and complexity of ventricular arrhythmiasin the 10-min period preceding ventricular tachycardia. Ventriculartachycardia with rates of 140–180 min^–1 and witha QS configuration was the most frequent event. The first ectopiccomplex of VT was R-on-Tin only 17.2%. Sinus tachycardia wasassociated with significantly fewer episodes of VT with ratesof 110–140min^–1 than when the sinus rate was normal.However episodes of ventricular tachycardia with rates of 181to 220 beats min^–1 were more frequent during sinus tachycardia.Analysis of the frequency of premature ventricular contractionsin the 10-min period immediately preceding ventricular tachycardiarevealed no premature ventricular contractions in 24.4% of cases.Multiple premature ventricular contractions with a frequencyof >5 min^-1 were observed in 8.4% of cases, multifocal in30.3%, couplets in 24% and early PVCs in 12.2%. In the minutebefore ventricular tachycardia, only 40.2% of cases displayedpremature ventricular contractions. In that minute, complexpremature ventricular contractions were distributed as follows:multifocal in 10%, couplets in 8.7% and early PVCs in 2.6% ofcases. Out of the total of 492 runs of ventricular tachycardia,5 cases (1%) resulted in ventricular fibrillation. The frequencyand complexity of premature ventricular contractions as wellas the characteristics of ventricular tachycardia were foundto be of little predictive value for the immediate developmentof ventricular fibrillation in patients with acute myocardialinfarction.     

Dopexamine hydrochloride, a {beta}2 adrenergic and dopaminergic agonist; haemodynamic effects following cardiac surgery

Twelve patients recovering from open heart surgery receivedan intravenous infusion of dopexamine hydrochloride, a novelß₂, adrenergic and dopamine receptor agonist. Themean cardiac index increased from 2.58 to a maximum of 3.641 min^–1 m^–2 (P<0401) and the systemic vascularresistance (SVR) decreased from 1527 to 11 I6 dynes cm^–5(P <0.001) at a dose of 3 pg kg^–1 min^–1. Heartrate increased with dose from 85 beats min^–1 to a maximumof 119 beats min^–1 (P<0.001). There was no significantchange in the pulmonary vascular resistance (PVR) with treatmentin the group as a whole. However, PVR decreased (P <0.05)in patients who had aortic-valve replacement ( AVR) only, whereasin patients who had mitral-valve replacement ( MVR) the PVRincreased (P<0.05). We conclude that dopexamine hydrochloridewas well tolerated in patients following cardiac surgery. Itproduced a significant increase in cardiac output with evidenceof afterload reduction and, although the increase in heart ratemay limit its use in some patients, dopexamine hydrochlorideis potentially of value in the treatment of low cardiac outputstate following cardiac surgery.     

Acute haemodynainic effects of the antiarrhythmic agent pirmenol in cardiac patients: a comparison with lidocaine

The acute haemodynamic effects of pirmenol, a new Class 1 antiarrhythmicagent, were investigated in a double-blind comparison with lidocaineand placebo. Three groups of 10 patients each received eitherpirmenol as a 50 mg intravenous injection followed by a 2.5mg min^–1 infusion, or lidocaine as a 75 mg injection followedby a 3 mg min^–1 infusion, or placebo. Mean plasma pirmenolconcentrations during the 30 min infusion period were 2.3–2.5mg l^–1, and were considered to be therapeutically effective. Compared to measurements taken during a baseline phase of 15min duration, pirmenol increased heart rate by 10 beats min^–1(P<0.001) and mean arterial pressure (MAP) by SmmHg (P<0.001).It also increased systemic vascular (P<0.05) and pulmonaryarterial resistances (P<0.01). Left ventricular end-diastolicpressure (LVEDP) was not increased significantly. Cardiac indexand left ventricular work index remained unchanged. Lidocaineinduced a comparable increase in MAP (6mmHg; P<0.001) andelevated LVEDP (2.8 mmHg; P<0.05) and did not affect leftventricular work index. Echocardiographic left ventricular ejectionfraction was reduced more by pirmenol ( – 0.05; P<0.001)than by lidocaine (–003; P<0.05), but the greater reductionmay partly be explained by the increase in heart rate. Pirmenoldid not induce excessive circulatory responses or side-effectsin any patient. Intravenous administration ofpirmenol results in increased heartrate and afterload but has little effect on preload. The myocardialdepressant effect is relatively slight, and comparable to thatof lidocaine.     

Short-term cardiac adaptation to severe haemodilution: an echocardiographic study in normal and hypertensive subjects

In order to avoid transfusion risks and optimize blood bankresources, in recent years many blood sparing techniques havebeen proposed, including severe haemodilution. The aim of thisstudy is to assess the pattern of normal haemodynamic and cardiacadaptation to severe haemodilution in patients undergoing majororthopaedic surgery and refusing blood transfusions for religiousreasons (the patients were Jehovah's Witnesses). Two-dimensionally guided M-mode echocardiograms were performedat baseline and 4 days after major orthopaedic surgery in 26Jehovah's Witnesses (age 61±11 years), with normal regionaland global baseline left ventricular function and no valvulardisease. Left ventricular (LV) volumes were estimated by usingthe Teichholz formula. From the latter, we calculated ejectionfraction and stroke volume, cardiac output (stroke volumex heartrate), and total peripheral resistance estimated as mean arterialpressure by cuff sphygmomanometer x 80/cardiac output. On thebasis of LV mass (ASE-cube corrected by Devereux), two groupswere identified: non-hypertrophic (LV mass index <110 g.m^–2 in women and <130g. m^–2 in males) and hypertrophic. In the 19 patients without LV hypertrophy, haemoglobin decreasedfrom 13.5±1.6 (mean ± standard deviation) g. dl^–1(at baseline) to 8.7 ± 1.3 post-operation (P<0.01),and peripheral vascular resistances fell from 2131 ±450 to 1278±310 (dyne. s. cm^–5) (P<0.01). Therewas an increase in heart rate (from 68±9 to 87±9beats. min^–1, P<0.01) and cardiac output (from 3.8±0.7 to 6.7 ±1.41 min^–1, P<0.01), witha rise in ejection fraction (from 62 ± 5 to 66 ±6%, P<0.01) and a decrease in relative wall thickness (from0.42 ± 0.03 to 0.35 ± 0.04, P<0.01). In theseven hypertensive hypertrophic patients, haemoglobin went from12.4 ± 1 (at baseline) to 8.4 ± 1.5 post-operation(P<0.01) and peripheral vascular resistances fell from 2551± 845 to 1363 ± 413 (P<0.01). There was anincrease in heart rate (+38%) and cardiac output (+46%) comparableto that found in non-hypertrophic patients, but with no significantvariation in LV relative wall thickness (from 0.50 ±0.08 to 0.48 ± 0.05, P=ns) and no increase in ejectionfraction (from 62 ±8 to 62.3 ±9%, P=ns). Therewas an inverse correlation between haemoglobin levels and LVcardiac output in both the normal (r= - 0.74; P<0.01) andthe hypertrophic (r= -0.63, P<0.05) group. In conclusion, severe haemodilution induces a high output statewith a fall in peripheral vascular resistance. This haemodynamicadaptation is accompanied by an eccentric remodelling in normal,but not in hypertrophic, hearts. In normal patients, but muchless so in the hypertrophic ones, LV geometry is a dynamic variablewhich can be profoundly modified by a few days of severe haemodilutionand can thus significantly contribute to the overall adaptationto altered haemodynamics.     

Blood pressure responses in Japanese and Swedish children in the supine and standing position

We investigated the cardiovascular responses to active standingin Swedish and Japanese pre-pubertal children using non-invasivecontinuous beat-to-beat finger blood pressure (BP) monitoring.Seventy-eight Swedish (7–12 years) and 53 Japanese children(6–12 years) were examined. There were no significantdifferences in body weight or height between the two groups(total group). Finger blood pressure and heart rate were continuouslyrecorded in the supine position and during standing. SupineBP was significantly higher in Swedish compared to Japanesechildren (115/65 vs 98/50mmHg, P<0.001), and Swedish childrenshowed a significantly larger initial BP drop upon rising (–28/15 vs –141 –10 mmHg, P<0.05) and alarger increment of heart rate (39 ± 10 vs 29 ±8 beats. min^–1, P<0.05). There were, however, no differencesin the blood pressure and heart rate changes in the followingsteady state period (2–3 min) between the two groups. These results suggest that Swedish pre-pubertal children havea higher basal blood pressure and enhanced cardiovascular autonomicresponses, such as pronounced baroreflex receptor sensitivityand vasoconstrictor mechanisms. These differences in the twocohorts were not related to body dimensions or degree of maturation,indicating that autonomic functions in the cardiovascular systemlargely depend on genetic factors and environmental variables.     

Effects of sympathetic activation on ventricular ectopic beats in subjects with and without evidence of organic heart disease

In a selected group of 10 apparently healthy subjects and 22patients with organic heart disease, all with frequent ventricularectopic beats on Holter monitoring, we assessed the influenceof sympathetic activation by comparing the arrhythmogenic effectsof a symptom-limited bicycle exercise stress test and 90°head up tilt. Tilting reduced ventricular arrhythmias in thenormal subjects (–48±18% from 9±2 beatsmin^-1, P<0.05). Exercise stress testing caused small andinsignificant changes in arrhythmias during the early (50–75W) phases and an almost complete suppression of ventricularectopic beats in the final stages (–99±1%, P<0.01).In six of the 10 subjects, ventricular arrhythmias reappearedin the early recovery phase. In the 22 patients with organicheart disease, tilting increased ventricular ectopic beats (43±17%from 9±3 beats min^-1, P<0.05); augmented repetitiveforms in 12 patients (179±88% from 1.4±0.6 per3 min) and produced repetitive forms in six of the 10 remainingpatients who did not show repetitive forms during control conditions.Exercise stress testing caused a marked increase in ectopicactivity in the early phase (84±35%) while the responseduring the maximal phase of exercise as well as during recoverywas related to the effort capabilities. Arrhythmias were increasedin 12 patients with limited exercise duration and were reducedin 10 patients with good exercise tolerance. These data indicatethat sympathetic activation has different effects on ventriculararrhythmias depending on the clinical setting and that tiltingis a useful manoevre to evaluate the arrhythmogenic effectsof increased sympathetic activity.     

Proarrhythmic and antiarrhythmic effects of intravenous prostacyclin in man

Prostacyclin (PGI2) has been shown to reduce the occurrenceof experimental ventricular arrhythmias. To assess potentialbeneficial effects in man, the electrophysiological action ofPG12 was studied in 16 non medicated patients. The protocolused in incremental pacing and programmed stimulation in theright atrium and ventricle. This protocol and measurement ofeffective refractory periods (ERP) were performed before andduring the injection of 2.5, 5 and 10 ng kg^–1 min^–1of PGI2. The atrial functional refractory period decreased significantly(P<0.05); PGI2 had no influence on the occurrence of induciblenon-sustained (NS) atrial tachycardias and was responsible forthe occurrence of 2 non-sustained atrial tachycardias in 8 patientswith inducible atrial echo beats under basal conditions. Thirteenpatients did not have inducible ventricular tachycardia ( VT)under basal conditions. Non-sustained VT was induced after PGI2in 4 of them but in only 1 of them after the administrationof propranolol. Three patients had inducible VT under basalconditions (1 non-sustained, 2 sustained VT). PG12 did not preventthe occurrence of VT (1 non-sustained, 1 sustained VT), exceptin 1 patient with ischaemic-related VT, who had non-sustainedVT after PGI2. In conclusion, PGI2 does not seem to have a cardiacantiarrhythmic effect and may increase the atrial and ventricularrepetitive response. This effect could be related to an increaseof adrenergic tone.     

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.     

Felodipine in ventricular dysfunction

The systemic and coronary haemodynamic effects of felodipinewere evaluated at rest and during stress induced atrial pacingin fourteen patients with chronic cardiac failure, secondaryto coronary heart disease. Felodipine was an effective arteriolarvasodilator producing increases in cardiac index from 2.6 ±0.l to 3.5 ± 0.2 l min^–1 m^–2 (P<0.001)and stroke volume 35.3 ± 2.7 to 41.4 ± 2.4 mlbeat^–1 m^–2 (P<0.002). Coronary venous flow also increased significantly (126 ±8 to 168 ± 13 ml min^–1) (P<0.005) and this didnot appear to be accompanied by an increase in myocardial oxygenusage, as myocardial oxygen consumption was essentially unchanged.When the myocardium was stressed by atrial pacing the increasein cardiac output and stroke volume was maintained—25%and 23%, respectively (P<0.01). These results suggest thatfelodipine may well have a significant role in the managementof patients with congestive cardiac failure.