Autonomic imbalance in the recovery period after myocardial infarction

The aim of the study was to evaluate the responses to autonomicfunction tests during the healing period of myocardial infarction(AMI). In 24 patients, at 2 and 6 weeks after the acute event,Valsalva manoeuvre, deep breathing at 6 breaths per min, isometrichandgrip and cold pressor tests were performed. Responses ofarterial blood pressure (BP) and heart rate (HR) were measured.At 2 weeks post AMI a significant decrease in parasympathetictone was noted: HR reduction during deep breathing: 18.5±5.7beats. min^–1 for controls vs 9.7±2.6 beats. min^–1for AMI, P<0.001. Systolic BP response to handgrip and coldpressortest was only slightly (non signflcantly) increased: 30.6±12.9mmHg (controls) vs 40.0±20.5mmHg (AMI) for the handgriptest and 13.8±8.1 mmHg vs 18.0± 10.1 mmHg respectivelyfor the cold pressor test. At 6 weeks post AMI, the responseto the deep breathing test (15.9±5.6 beats. min^–1)nolonger significantly differed from that in controls. In contrast,the sympathetic stressor tests showed a signficant increasein systolic BP response: 63.8±21.9mmHg, P<0.001 and26.1±14.9 mmHg, P<0.05, respectively for the handgripand cold pressor tests. It appeared that infarct localizationhad no effect on autonomic function tests. There is evidence of autonomic imbalance both at 2 and at 6weeks after AMI, with a rapid but transient decrease in vagalactivity and enhancement of orthosympathetic nervous tone; thiswas markedly more pronounced at 6 weeks post AMI despite treatmentwith beta-blocking agents in all patients.     

Heterogeneity of left ventricular regional wall thickening following dobutamine infusion in normal human subjects: A quantitative two-dimensional echocardiographic study

Background: Pathophysiological data and pragmatic clinical experiencewith stress echocardiography suggest that inotropic stimulationwith simultaneous changes in heart rate and loading conditionscan affect the function of various myocardial regions asymmetrically,inducing heterogeneity in wall motion and thickening, possiblymimicking ‘ischaemic’ regional hypokinesis or lackof hyperkinesis during stress. Objectives: To describe, in a quantitative fashion, the physiologicalcontractile response of different left ventricular regions followingdobutamine infusion. Methods: Two hundred and twenty-three in-hospital patients undergoingdobutamine stress echocardiography and coronary angiographywere initially considered. Of these 223 patients, 18 had angiographicallynormal coronary arteries, normal resting function, negativeergonovine and exercise stress tests, and negative dobutaminestress echo-cardiograms; of the 18, only in 11 patients (sixfemales, age=56 ± 10 years) was it possible to obtainquantitative measurements of the middle segments of the inferior,anterior, lateral, and septa! walls. Two-dimensional echocardio-graphicmeasurements of wall thickness were obtained at the end-diastolic(onset of Q wave) and end-systolic phases, both at baseline(rest) and at the peak of the dobutamine infusion (40 fig. min^–1.kg^–1plus atropine). Results: Dobutamine increased heart rate (rest-69 ±9vs dobutamine=138 ± 13 beats. min^–1; P<0.01),whereas systolic blood pressure did not change significantly(rest-136 ± 75 vs dobutamine.150 ± 25 mmHg, P=ns).During stress, % systolic thickening decreased in the inferiorwall (rest = 73 ± 24 vs dobutamine ± 50 ±9%; P<0.01), whereas it tended to increase to a variableextent in the other regions, i.e. septal (rest=46± 17vs dobutamine=68 ± 13%, P<0.01), anterior (rest 62± 19 vs dobutamine=69 ± 11%, P=ns), and lateralwall (rest=48± 16 vs dobu-tamine=61 ± 18%, P=ns).The decrease in % systolic thickening of the inferior wall wasinversely correlated with the increase in end-diastolic wallthickness (r=– 0.75; P<0.01), but neither with heartrate (r=0.15; P=ns) nor with systolic blood pressure changes(r=0.05; P=ns). Conclusions: Heterogeneity of left ventricular wall thickeningcan be induced or magnified by dobutamine infusion even in subjectswithout coronary artery disease, with the inferior wall showinga lack of hyperkinesis, up to relative hypokinesis, in comparisonwith other myocardial regions. Caution in aggressive dobutaminestress echocardiography reading, especially in the inferiorwall, might be warranted.     

Clinical, adrenergic and heart endocrine measures in chronic atrial fibrillation as predictors of conversion and maintenance of sinus rhythm after direct current cardioversion

The aim of this study was to evaluate clinical, adrenergic andendocrine factors that could predict sinus rhythm maintenanceafter direct current cardioversion in chronic atrial fibrillation. Nineteen patients with chronic non-rheumatic atrial fibrillation(mean duration 6±5 months) were studied. They were exercised24 h before cardioversion at maximum effort with the Naughtonprotocol. Heart rate and blood pressure at rest and exercisewere recorded and blood samples were taken for the assessmentof adrenergic activity, by measuring cyclic adenosine monophosphate,heart endocrine function, atrial natriuretic peptide and itssecond messenger, cyclic guanosine monophosphate. Fifteen ofthe 19 patients were initially converted to sinus rhythm (eightpatients with external and seven patients with internal DC shocks).After 3 months eight patients remained in sinus rhythm and 11had relapsed, most of them within the first month. On exercisethe chronotropic response was lower in the group who remainedin sinus rhythm than in the group in atrial fibrillation (peakheart rate 147±11 beats.min^–1 vs 165±24beats.min^–1 p=0·02). During exercise, the systolicblood pressure in the sinus group reached higher values thanin the group who relapsed (192±17 mmHg vs 176±18mmHg, p=0·03). Cyclic adenosine monophosphate increasedsignificantly from rest to peak exercise in the sinus rhythmgroup (from 23±9 pmol.ml^–1 to 31±15 mol.ml^–1,p=0·02) while it remained unchanged in the atrial fibrillationgroup (25±10 pmol.ml^–1 to 24±8 pmol.ml^–1,p=0·02). For all 19 patients the differ ence in cyclicadenosine monophosphate between rest and exercise was negativelycorrelated with maximum heart rate (r=0·58, p=0·009).Atrial natriuretic peptide increased from rest to peak exercisein the sinus rhythm group (from l29±58 fmol.ml^–1to 140±66fmol.ml^–1 while it remained unchangedin the group in which atrial fibrillation persisted or recurred(from 112±58 fmol.ml^–1 to 111±53 fmol.ml^–1p=0· A significant correlation between atrial natriureticpeptide and cyclic guanosine monophosphate levels at exercisebefore cardioversion was found for the sinus rhythm group only(r=0·76, p=0·02). In patients with non-rheumatic chronic atrial fibrillation evaluationof clinical parameters such as heart rate and blood pressurechanges during maximal exercise can be useful in the choiceof suitable therapy. An inadequate increase in plasma cyclic-adenosinemonophosphate and atrial natriuretic peptide on exercise couldpredict patients with more severe underlying disease, wherecardioversion should not be recommended.     

Utilization of oxygen by the contractile apparatus is disturbed during reperfusion of post-ischaemic myocardium

Post-ischaemic ventricular function remains depressed ( = myocardialstunning) despite nearly normal coronary blood flow during reperfusion.In order to illuminate the causes of this phenomenon, we studiedthe relationship between ventricular function and myocardialoxygen consumption (MVO_2tot) in experiments on 15 isolated rabbithearts perfused with erythrocyte suspension (hct=30%). Leftventricular systolic function was assessed by measuring aorticflow (ml. min ^–1), peak systolic pressure (L VP_max), dPldt_max,and early relaxation in terms of dPldt_min during control and30 min after the onset of reperfusion, following 20 min globalno-flow ischaemia. The pressure-volume area was calculated asa measure of total mechanical energy. The external mechanicalefficiency (E_ext) was assessed from stroke work and MVO_2torBothcontractile efficiency (E_con= inverse slope of the MVO₂-PVArelationship) and MVO₂ of the unloaded contracting heart (MVO_2unl=basal MVO₂ + MVO₂ for excitation-contraction coupling) werecalculated using pressure-volume area and MVO_2tot Results: At matched heart rate (149 ± 30 vs 147 ±31 min ^–1; mean ± SD) and end-diastolic volume(1.3 ± 0.2 ml), the systolic variables were significantlydecreased in the stunned myocardium: aortic flow: 38 ±13 vs9 ± 11 ml. min ^–1, LVP_max: 112 ±19vs 74±18mmHg, and dP/dt_max: 1475 ±400 vs 1075±275 mmHg. s^–1. Likewise, dP/dt_min was significantlyimpaired (– 1275 ±250 vs – 975 ±250).The decrease in pressure-volume area (570 ±280 vs 270±200mmHg.ml. 100g^–1) was not statistically significant. In contrast,both E_ext (0.75±0.29 vs 0.18±0.26 arbitrary units)and E_con (31 ± 18 vs 14± 7%) were significantlydecreased, whereas MVO_2tot (40±9 vs 34±8µl.beat^–1. 100g^–1) and MVO_2unl (26±9 vs22±6µl.beat^–1. 100g^–1) were not. Summary: Ventricular function after brief episodes of ischaemiais decreased whereas MVO_2tot is maintained, i.e. external efficiencyis decreased. MVO₂ for the unloaded contraction remained unchanged,indicating that MVO₂for excitation-contraction coupling is inappropriatelyhigh for the depressed contractile state. The decreased contractileefficiency indicates further that O₂ utilization of the contractileapparatus is disturbed during reperfusion.     

Left ventricular function in children with the Marfan syndrome

Aortic dilatation and heart valve lesions are common in theMarfan syndrome but whether primary alterations occur in leftventricular (LV) function has not been studied hitherto. LVsize, mass and systolic as well as diastolic function were studiedby M-mode and Doppler echocardiography and cine magnetic resonanceimaging in 22 Marfan children aged 3.0–15.4 years andin 22 age-matched healthy children. No child had significantvalve disease. Heart rate and systolic blood pressure were comparablein the groups but diastolic blood pressure was higher in thecontrols (67 ± 7 mmHg vs 62 ± 8 mmHg, P=0.030).No statistically significant differences were found in LV size,mass or systolic function. The Marfan children had slower LVpeak diameter lengthening rates (106 ± 27 mm s^–1vs 132 ± 29 mm. s^–1, P=0.004), prolonged relaxationtimes (155 ± 22 ms vs 140 ± 19ms, P=0.023), slowerdeceleration of the early transmitral velocity (580 ±144 cm.s^–2 vs 720 ± 160 cm. s^–2, P=0.006),and smaller early-to-late peak velocity ratios (1.99 ±0.40 vs 2.29 ± 0.46, P=0.031). These data indicate thatI.V early diastolic function (relaxation) is impaired in theMarfan syndrome. Weakened elastic recoil due to the underlyingconnective tissue abnormality may best explain this novel observation.     

Influence of the postoperative period and surgical procedure on ambulatory blood pressure-determination of hypertension load after successful surgical repair of coarctation of the aorta

Aims This study quantified hypertension load using 24-h ambulatoryblood pressure monitoring after successful repair of coarctationof the aorta less than (1) or more than 10 years previously(2) and examined the influence of the surgical procedure (anastomosisor subclavian flap). Methods and Results Ambulatory blood pressure recordings were obtained using anAccutracker II monitor every 30min during the day and hourly,at night. Day and night systolic and diastolic values were higherin coarctation of the aorta than in controls: (day: systolicblood pressure/diastolic blood pressure: 133/71±6/4 vs115/66±3/2 night: systolic blood pressure/diastolic bloodpressure: 117/61±4/4 vs 107/57±3/2mmHg, P<0·01)and at all times, were higher in coarctation of the aorta (2)than in coarctation of the aorta (1). Clinical daytime systolichypertension was observed in 20% of recordings from coarctationof the aorta (1) and 49% from coarctation of the aorta (2) whilediastolic hypertension was not observed. However, systolic bloodpressure and diastolic blood pressure responses to daily activitieswere significantly higher in coarctation of the aorta than incontrols and this was more marked in coarctation of the aorta(2) than in coarctation of the aorta (1). Type of surgery didnot affect either hypertension prevalence or blood pressurereactivity. Conclusions These observations indicate exaggerated systolic blood pressureand diastolic blood pressure reactivity after repair of coarctationof the aorta, the prevalence of systolic hypertension doubling10 years after surgery.     

Blood volume and right heart haemodynamics in abrupt hypotension following sublingual isosorbide dinitrate in acute myocardial infarction

Arterial blood pressure and heart rate were measured in 43 patientswith acute myocardial infarction and a systolic blood pressure120 mmHg during sublingual administration of 5 mg of isosorbidedinitrate. In 25 of them right heart haemodynamics were alsomeasured. Severe (25%) hypotension developed in 12 patients(Group 1, systolic blood pressure 158 ± 28 to 78 ±17 mmHg, mean ± SD) but not in the remaining 31 (Group2) and was accompanied by a fall in heart rate (82 ±20 to 70 ± 22beats min^-1, P<0.05), in cardiac output(4.3 ± 0.3 to 3.2 ± 0.4l mm^-1, P<0.02, n =5) and in systemic vascular resistances (2326 ± 463 to1532 ± 442 dynes sec^-1 cm^-5, P<0.02) not present inGroup 2. The reduction in right (Group 1,8 ± 3 to 3 ±1, vs. Group 2,10 ± 3 to 6± 3 mmHg, V <0.005)and in left ventricular filling pressures (Group 1,15 ±4 to 8 ± 2, vs. Group 2,18 ± 6 to 13 ±5 mmHg, P<0.001) was more remarkable in Group 1. In thisgroup there was also a high incidence of anterior infarction(9/12, 75%). Blood volume measured in 30 patients was lowerin Group 1 but differences were not significant. A second doseof 5 mg of isosorbide dinitrate 36–48 h later producedneither symptomatic hypotension (Group 1, 147 ± 29 to129 ± 24 mmHg) nor a fall in cardiac output in any patient,whereas changes infilling pressures were comparable to thoseof the first dose. Thus, severe isosorbide dinitrate-induced hypotension in myocardialinfarction is limited to the acute phase and seems more prevalentin anterior infarction but can not be clearly predicted fromresting haemodynamic or blood volume measurements, at leastin non-hypotensive patients. Moreover, it appears to be causedby an excessive ventricular emptying due to a striking venousand arterial vasodilation, probably during a stage of a particularlydepressed ventricular compliance.     

Effects of tilt and exercise on signal-averaged electrocardiogram after acute myocardial infarction

To determine whether enhanced sympathetic activity could altera non-invasive index of cardiac instability, we analysed theeffects of 90° head-up tilt and submaximal exercise stresstest on high amplification signal-averaged electrocardiogramin 64 patients after acute myocardial infarction. At rest, ventricularlate potentials were detected in 25% of patients, characterizedby a significant prolongation of filtered QRS complex (137 ±3vs 115 ±2 ms) and of its components smaller than 40 fiV(38 ±2 vs 16 ±1 ms), as well as by a reduced rootmean square voltage calculated for the terminal 40 ms of QRScomplex (RMS40 voltage) (19 ± 1 vs 75 ± 9µV)in comparison to patients without micropotentials. Sympathetic activation induced by tilt caused a significantincrease in heart rate (from 67 ±3 to 79 ±3 beatsmin^–1) but did not modify either the incidence of ventricularlate potentials or the values of any of the signal-averagedelectrocardiogram parameters considered. In 19 patients, recordingswere also obtained during a submaximal bicycle exercise stresstest at a heart rate of 114 ±4 beats min^–1 andwith systolic arterial blood pressure at 153 ±6 mmHg.No effect on signal-averaged electrocardiogram parameters wasdetectable during this experimental intervention. These data indicate that after myocardial infarction, sympatheticactivation does not seem to modify signal-averaged electrocardiogramparameters.     

Antihypertensive treatment with felodipine but not with a diuretic reduces episodes of myocardial ischaemia in elderly patients with hypertension

Episodes of transient myocardial ischaemia can frequently beobserved in hypertensive patients. To assess the effects ofantihypertensive treatment with the calcium antagonist felodipineor the diuretic combination hydrochlorothiazidel triamtereneon episodes of ischaemic-type ST-segment depression (ST-D),simultaneous ambulatory electrocardio-graphic and blood pressure(BP) monitoring was performed in 42 elderly hypertensives withoutmanifest coronary artery disease. All patients (mean age 79± 6 years, office BP 160/95 mmHg) were evaluated offany antihypertensive or anti-ischaemic therapy and after 3 monthstreatment with either felodipine or the diuretic (randomized,double-blind study) for episodes of significant ST-D (0.1 mV,duration 1 min, interval 1 min). The reduction in office BPand daytime ambulatory BP was similar for both agents, as wasa significant reduction in the heart rate x systolic BP product(DP) over 24 h (felodipine: 12 441 ±2076 vs 11 643 ±1953 mmHg. min^–1; P=0.048; diuretic: 12 366 ± 2782vs 11 062 ± 2012 mmHg. min^–1; P=0.003). While felodipinesignificantly decreased the total number of ST-D (from 40 tosix episodes; P=0.03), the total number of ST-D remained unchangedwith the diuretic (non-significant increase from 31 to 45 episodes;P=0.24). The same trend was observed for the number of patientswith ST-D. The ischaemic threshold, defined as DP at the onsetof the episodes of ST-D, increased with felodipine (12 171 ±340vs 13 770 ± 138 mmHg. min^–1) and decreased withthe diuretic (16 210 ±312 vs 14 092 ± 319 mmHg.min^–1). In conclusion, antihypertensive treatment withfelodipine reduces blood pressure and episodes of transientmyocardial ischaemia in elderly hypertensive patients, whilehydrochlorothiazidel triamterene increases these episodes despitea similar BP reduction. Felodipine may influence structuraland functional factors at the coronary micro circulation level.These mechanisms improve coronary blood flow and increase theischaemic threshold.     

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.     

Systolic blood pressure and (cardiac) mortality over 15 years after venous coronary bypass surgery

OBJECTIVE: The aim of the present study was to determine the influenceof pre-operative systolic blood pressure and systolic bloodpressure 1 and 5 years after venous coronary bypass surgeryon subsequent cardiac and non-cardiac mortality. DESIGN: A prospective 15 years follow-up study. PATIENTS: A series of 446 consecutive coronary bypass surgery patients,operated on between April 1976 and April 1977. According totheir systolic blood pressure, patients were divided into fivegroups. MAIN OUTCOME MESURES: Systolic blood pressure 5 years after surgery, but not pre-operativesystolic blood pressure, was an independent predictor of cardiacmortality. RESULTS: Multivariate Cox proportional hazards analysis revealed thatpre-operative systolic blood pressure was not associated withcardiac mortality, while higher systolic blood pressure 1 yearafter surgery showed a trend towards increased cardiac mortality.Systolic blood pressure 5 years after surgery appeared to bea strong independent predictor of cardiac mortality during thesubsequent follow-up period. Patients with a systolic bloodpressure of 130–139 mmHg had the lowest risk. Comparedto this group, the cardiac mortality risk in patients with asystolic blood pressure 5 years after surgery of 140–149mmHg, 150–159 mmHg and $160 mmHg, was 2·3 (1·2to 4·6), 3·4 (1·6 to 7·1) and 3·1(1·4 to 6·5) times higher. Systolic blood pressure>130 mniHg 5 years after surgery was also associated witha 2·3 times (1·1 to 4·7) times increasedrisk for cardiac mortality, compared to patients with a systolicblood pressure of 130–139 mmHg. CONCLUSIONS: These findings underline the importance of systolic blood pressurecontrol in the initial years after coronary bypass surgery.     

Effect of atrial fibrillation on pulmonary venous flow patterns: transoesophageal pulsed Doppler echocardiographic study

The effect of atrial fibrillation on pulmonary venous flow patternsis still not well known. Twenty-four patients in atrial fibrillationand 21 patients in sinus rhythm were studied by transoesophagealechocardiography. In ninety-five percent (20/21) of sinus rhythmpatients, the early systolic wave due to atrial relaxation orreverse wave due to atrial contraction could be distinguishedon pulsed Doppler tracings by transoesophageal echocardiography.However, there was no early systolic wave and/or reverse atthe end of diastole in any atrial fibrillation patients. Inatrial fibrillation patients without mitral regurgitation (n= 14), the onset of systolic flow was delayed (165±38vs 50±46 ms, P < 0.05), and systolic peak velocities,time-velocity integrals and systolic fractions were reduced(31 ± 13 vs 54±17 cm.s^–1, P < 0.05; 5± 2 vs 13 ± 6 cm, P < 0.05 and 36 ±8 vs 61±15%, P < 0.05, respectively) as compared tothose in sinus rhythm. Significant mitral regurgitation (n =10) reduced systolic velocity parameters considerably in atrialfibrillation patients but the diastolic flow parameters werenot significantly different between sinus rhythm and atrialfibrillation patients. Stepwise multiple regression analysis identified atrial fibrillationas an important independent predictor for changes in systolicflow parameters. The R-R interval is also an important factorfor diastolic flow parameters. Thus, the present study demonstratesthat atrial fibrillation significantly modifies pulmonary venousflow pattern and is an important factor for systolic flow parameters.Significant mitral regurgitation can further modify systolicflow pattern in atrial fibrillation patients.     

Influence of the breathing mode on the time course and amplitude of the cyclic inter-atrial pressure reversal in postoperative coronary bypass surgery patients

The haemodynamic basis for paradoxical embolization in patientswith stroke and decompression sickness has not yet been fullyelucidated. Therefore right and left atrial pressures were measuredsimultaneously with peroperatively placed catheters after coronaryartery bypass grafting in 17 patients with sinus rhythm andnormal left ventricular function. Recordings were made bothduring spontaneous breathing and positive pressure ventilation. A cyclic pressure reversal in which right atrial pressure exceededleft atrial pressure was reproducibly recorded. It started onaverage 215 ± 5 ms (mean ± SEM) after the onsetof the electrocardiographic P-wave, lasted on average 179 ±14 ms and had a maximal amplitude of on average 4.1 ±0.3 mmHg. During the expiration phase of spontaneous breathingand inspiration phase of positive pressure ventilation, theonset of the pressure reversal occurred later, its durationwas shorter and its amplitude smaller. These observations demonstrate the presence of a cyclic inter-atrialpressure reversal and illustrate the importance of the breathingmode for the time course and amplitude of this reversal.     

Acute effect of captopril administration on baroreflex sensitivity in patients with acute myocardial infarction

Depressed baroreflex sensitivity (BRS) after acute myocardialinfarction (AMI) is considered an indication of decreased vagaland/or increased sympathetic tone. To determine the effect ofangiotensin converting enzyme inhibitors (ACEI) on BRS afterAMI we studied 27 patients with a first Q wave AMI, no signsof heart failure and no history of arterial hypertension ordiabetes mellitus. An additional group of10 patients with thesame clinical characteristics served as controls. On the 5thday after the onset of AMI, three consecutive boluses of phenylephrinewere given intravenously and baseline BRS was taken as the meanslope of the linear regression lines of RR intervals over systolicblood pressure. QT interval was also measured and correctedaccording to Bazett's formula (QTc). Consequently, a singleoral dose of captopril 50 mg or placebo was given to treatmentor control group patients, respectively; BRS and QTc were reassessedlh later. One hour after captopril administration BRS increasedfrom 5.95±2.80 to 9.14±3.46ms.mmHg^–1 (P<0.0001);QTc increased from 414±46 to 425± 46 ms (P<0.0001),systolic blood pressure decreased from 125±19 to 115±15mmHg (P=0.0002), while heart rate did not change significantly.Baseline BRS was correlated only with age (r= 0.74, P<0.0001).In the control group, 1 h after placebo, no difference was observedin any variable compared to baseline. Captopril appears to improveBRS immediately in the early phase of AMI.     

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.     

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.     

Magnetic resonance imaging of the pulmonary venous flow pattern in mitral regurgitation: Independence of the investigated vein

Objectives: The aim of the present study was two-fold: first,to quantify characteristic parameters of the pulmonary venousflow pattern in patients with mitral regurgitation by usingmagnetic resonance phase velocity mapping; second, to determinewhether this pattern is dependent on the vein being investigatedand the direction of the regurgitant jet. Background: Echocardiographic findings threw doubt on whetherthe pulmonary venous flow pattern is independent of the veinbeing investigated and whether the flow velocities in the pulmonaryveins have a linear relationship with the volume flow. Subjects and methods: Flow patterns were assessed in all fourpulmonary veins by magnetic resonance velocity mapping in healthyvolunteers and in 17 patients with echocardiographically mildand 13 patients with severe regurgitation. Results: No differences were found between the use of velocityor volume flow for characterizing individual curves. The pulmonaryvenous flow pattern in controls was characterized by six points,a biphasic systolic wave (maximum systolic volume flow: (29± 18 ml. s^–1), and end-systolic descent (24 ±18 ml. s^–1), a biphasic diastolic wave (maximum diastolicvolume flow: 69 ±22 ml. s^–1) and an end-diastolicreversed flow. Reversed end-systolic flow was a characteristicsign of severe regurgitation ( –10 ± 18ml. s^–1).The systolic-to-diastolic flow ratio was lower in severe regurgitation(0.5 ±0.6) than in mild regurgitation (1.4 ±0.9),P<0.0001). In severe regurgitation, the normalized time intervalsfrom Q wave to the highest systolic peak and end-systolic descentwere of less prolonged duration than in mild regurgitation andcontrols (P<0.01). Flow patterns between veins were similarand the median of the correlation coefficients between the curveswas the same in patients with or without an eccentric jet, 0.80and 0.81, respectively. Conclusion: Magnetic resonance velocity mapping is helpful indetermining and understanding pulmonary venous flow characteristics.It is demonstrated that the pulmonary venous flow pattern isindependent of the vein being investigated irrespective of theregurgitant jet direction, and that it is useful in gradingmitral regurgitation.     

Acute antiischaemic properties of high dosages of intravenous diltiazem in humans in relation to its coronary and systemic haemodynamic effects

The antiischaemic properties of intravenous diltiazem in recommendedtherapeutic doses are disputed. In 17 patients with coronaryartery disease the systemic and coronary haemodynamic effectsof diltiazem were assessed during a high-dose infusion (0.4mg kg^-1 per 5 min. followed by 0.4 mg kg^-1 per 10 min). In addition,its potential antiischaemic properties were investigated duringidentical pacing stress tests. 30 minutes before (P₁) and immediatelyafter diltiazem administration (P₂). Diltiazem reduced leftventricular systolic pressure from 133±5 to 116±5mmHg (P<0.005, ±SEM). persisting until after P₂. Itdecreased systemic and coronary resistance by 32% (P<0.001)and 29% (P<0.005), respectively, with a sustained increasein cardiac output from 5.9±0.4 to 7.3±0.61 min^-1(P<0.01), but a brief 20% rise in coronary flow (P<0.05),after the bolus infusion only. Heart rate, contractility, leftventricular filling pressure and myocardial O₂ consumption remainedunchanged. Despite high plasma levels (673±81 µgl^–1)diltiazem was well tolerated. During identical maximal pacingrates diltiazem considerably reduced myocardial O₂ demand (doubleproduct: 16.3±0.8 (P₂) vs 21.1±1.1 (P₁), P<0.005),due to an 18% decrease in left ventricular systolic pressure,resulting in diminished coronary flow and myocardial O₂ consumptionduring P₂ (14% and 15%, respectively, P<0.05 vs P₁). Diltiazemalso significantly reduced pacing-induced ischaemia, indicatedby normalization of myocardial lactate extraction (1±8%(P₂) vs –41±12% (P₁), P<0.05), and left ventricularfilling pressure (13±2 (P₂ vs 27±3 mmHg (P₁),P<0.01). less ST-segment depression (0.12±0.01 (P₂)vs 0.24±0.02 mV (P₁), P<0.01) and improved contractility(V_max 59±5 (P₂) vs 48±3 s^-1 (P₁), P<0.05).Angina was absent or less in 15 patients during pacing afterdiltiazem. Thus, diltiazem, in high dosages, induces continuingsystemic but short lasting coronary vasodilation, improves pumpfunction without negative chronotropic and inotropic effectsand has pronounced antiischaemic properties, predominantly dueto diminished myocardial O₂ demand.     

Acute antiischaemic properties of high dosages of intravenous diltiazem in humans in relation to its coronary and systemic haemodynamic effects

The antiischaemic properties of intravenous diltiazem in recommendedtherapeutic doses are disputed. In 17 patients with coronaryartery disease the systemic and coronary haemodynamic effectsof diltiazem were assessed during a high-dose infusion (0.4mg kg^-1 per 5 min. followed by 0.4 mg kg^-1 per 10 min). In addition,its potential antiischaemic properties were investigated duringidentical pacing stress tests. 30 minutes before (P₁) and immediatelyafter diltiazem administration (P₂). Diltiazem reduced leftventricular systolic pressure from 133±5 to 116±5mmHg (P<0.005, ±SEM). persisting until after P₂. Itdecreased systemic and coronary resistance by 32% (P<0.001)and 29% (P<0.005), respectively, with a sustained increasein cardiac output from 5.9±0.4 to 7.3±0.61 min^-1(P<0.01), but a brief 20% rise in coronary flow (P<0.05),after the bolus infusion only. Heart rate, contractility, leftventricular filling pressure and myocardial O₂ consumption remainedunchanged. Despite high plasma levels (673±81 µgl^–1)diltiazem was well tolerated. During identical maximal pacingrates diltiazem considerably reduced myocardial O₂ demand (doubleproduct: 16.3±0.8 (P₂) vs 21.1±1.1 (P₁), P<0.005),due to an 18% decrease in left ventricular systolic pressure,resulting in diminished coronary flow and myocardial O₂ consumptionduring P₂ (14% and 15%, respectively, P<0.05 vs P₁). Diltiazemalso significantly reduced pacing-induced ischaemia, indicatedby normalization of myocardial lactate extraction (1±8%(P₂) vs –41±12% (P₁), P<0.05), and left ventricularfilling pressure (13±2 (P₂ vs 27±3 mmHg (P₁),P<0.01). less ST-segment depression (0.12±0.01 (P₂)vs 0.24±0.02 mV (P₁), P<0.01) and improved contractility(V_max 59±5 (P₂) vs 48±3 s^-1 (P₁), P<0.05).Angina was absent or less in 15 patients during pacing afterdiltiazem. Thus, diltiazem, in high dosages, induces continuingsystemic but short lasting coronary vasodilation, improves pumpfunction without negative chronotropic and inotropic effectsand has pronounced antiischaemic properties, predominantly dueto diminished myocardial O₂ demand.     

Left ventricle filling abnormalities prior to and following treatment of thyrotoxicosis -- is diastolic dysfunction implicated in thyrotoxic cardiomyopathy?

Despite cardiac failure being a well recognised complicationofthyrotoxicosis, systolic function has generally been reportedas maintained or enhanced. In this study, left ventricular diastolicfunction was assessed in 16 thyrotoxic patients and 18 age-matchedcontrols by pulsed-Doppler echocardiography. Patients were re-studiedafter 3 and 12 months of treatment. Prior to treatment all standardDoppler-;derived indices of diastolic function were significantlydifferent to control (isovolumic relaxation time (IVRT) 63±18.9vs 84.0±14.8 ms, peak early filling velocity (E_max) 79.2±15.2vs 61.9±10.7 cm . s^–1, peak atrial filling velocity(A_max) 68.2±17.9 vs42.2±9.4 cm . s^–1, decelerationof early filling (E/F slope) 6.1±1.8 vs3.7±1.1m . s^–1, thyrotoxic vs control). However, these fillingabnormalities appear likely to reflect the tachycardia and reducedsystemic vascular resistance (SVR) found in the patients (heartrate 102±15 vs 76 ± 9, SVR 874 ± 207 vs1293 ± 362 dynes .s^–1. cm^–5, both P<0.001).After 3 months of treatment haemodynamics were similar in thetwo groups but filling remained abnormal in patients with apattern suggesting increased transmitral pressure gradients(E_max 73.1 ± 15.1 cm.s^–1, A_max 55.8 ± 19.2cm.s^–1,E/F slope 4.9 ± 2.0m . s^–1, all P<0.05 comparedto controls). After 12 months of treatment most parameters hadreturned to normal but the atrial contribution to left ventricularfilling remained high (A_max54.7 ± 13.9 vs control 42.2± 9.4 cm . s^–1 .flow velocity integral of atrialfilling 4.7 ± 1.3 vs 3.6±11 control, both P0.01).Left ventricular filling is therefore highly abnormal beforeand during the treatment ofthyrotoxicosis. However, these changesappear unlikely to reflect an intrinsic thyrotoxic cardiomyopathyand are more likely to represent a combination of prolongedincreases in left ventricular filling pressures along with abnormalitiesof left atrial function. The abnormal Doppler parameters emphasisethe importance of sinus rhythm in maintaining left ventricularfilling in thyrotoxicosis and may explain why marked haemodynamicdeterioration may result from the development of atrial fibrillationin these patients.