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.     

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.     

Effects of early use of captopril on haemodynamics and short-term ventricular remodelling in acute anterior myocardial infarction

To determine whether ventricular short-term enlargement followingacute myocardial infarction is related to increased left fillingpressures and whether early treatment with captopril altersthis process we studied 68 patients with a first acute myocardialinfarction. Forty patients with a pulmonary capillary pressureequal or above 17 mm Hg were randomized to treatment with conventionaltherapy plus captopril(n 20) or placebo(n 20), in a double blindfashion. Tile remaining 28 patients (non-dysfunction group)were treated conventionally. During the first 72 h, afterloadshowed a prompt decrease in the captopril group as comparedto placebo. Changes from baseline to 14 days in end-diastolicand end-systolic left ventricular volume indexes determinedby radionuclide ventriculography were: non-dysfunction, 85.6(± 21) vs 88(±20) and 44(±17) vs 44(±17)ml.m^–2 captopril(n20), 96.6(±18) vs 99(±19)and 66(±22) vs 65(±22)ml. m^–2; placebo(n20), 96(±25) vs 113(±19) (P <0.001) and 63(±18)vs 74(±22)ml. m^–2 (P <0.01) This study indicates that short-term ventricular enlargementis related to the degree of ventricular dysfunction and thatcaptopril may improve this process.     

Right atrial contractile performance in patients with myocardial infarction

To evaluate right atrial (RA) contractile performance in patientswith myocardial infarction, we validated a cineangiographicmethod of RA volume measurement, and investigated RA volumechange in ‘normal’ individuals and patients witha previous myocardial infarction. Sixteen silicone rubber RAcasts made from human cadavers were filmed in the postero-anteriorand left lateral projections. The cast volumes calculated followingSimpson's rule were in good agreement with those measured bywater replacement (r=0.992, P<.001). At cardiac catheterization,biplane RA cineangiography was performed in 19 ‘normal’individuals (N group), in 14 patients with a previous antero-septalinfarction (AM1 group) and in seven patients with apreviousinferior infarction (IMI group). The RA volume-time curve wasconstructed at 20–40 ms intervals for one cardiac cycle.RA volume at the beginning of the atrial contraction (RAVd),which was defined as the ‘preload’ of the RA, tendedto be larger in both the AMI and IMI groups compared with ‘normal’individuals. The RA ejection volume was significantly largerin both the AMI (18.4 ± 2.1 ml. m^–2, P <0.01)and IMI groups (l9.4±2.8, P<0.01) than in the N group(14.5±1.9), even for a comparable level of RAVd (rangefrom 26 to 36ml.m^–2) (18.6±2.1, P<0.01, 18.2±2.0,P<0.01, 14.7±1.9, respectively). These results suggestthat RA contraction increases in patients with myocardial infarctionby increasing both the ‘preload’ and ‘contractility’of the RA.     

Reversal of ischaemic systolic and diastolic left ventricular dysfunction by successful coronary angioplasty in patients with non-Q wave anterior myocardial infarction

The effect of PTCA on global and regional left ventricular systolicfunction, isovolumic relaxation, chamber and muscle stiffnesswere studied in 30 patients with angina pectoris, previous non-Qwave anterior myocardial infarction (AMI) and significant stenosisof the left anterior descending coronary artery (LAD). In 11of the 30 patients the condition was stable, but it was unstablein 19. Left ventricular angiograms were obtained before and4. 85± 3.67 months after PTCA. The RAO was in the 30^°projection, with the silhouette of the left ventricle slicedinto 90 regions; changes in left ventricular volume, pressureand anterior wall thickness during the full cardiac cycle, togetherwith dpldt were demonstrated. After PTCA, global ejection fractionincreased from 68. 77 ± 5.96% to 76.57 ±3.18%,P<0.001. Impaired contractility was found in 29190 (32.2%)regions before PTCA and in 5190 (5.6%) after PTCA, P<0.001.The time constant of the isovolumic pressure fall decreasedafter PTCA (52.56 ± 17. 40 ms vs 39. 61 ± 11.26ms, P<0.01). Elastic chamber stiffness coefficient decreased(0.022 ± 0.003 vs 0.008 ± 0.004, P<0001) andpeak rate of left ventricular filling increased (319.0 ±107.9 ml. min^–1 vs 396.8 ±201.4 ml. min^–1,P<0.05) after PTCA. The muscle stiffness coefficient waswithin normal values before and did not change after PTCA. Thestudy findings show that in patients with persistent anginapectoris after non-Q wave AMI, complex systolic and diastolicischaemic dysfunction occurs. This dysfunction can be reversedafter successful PTCA of LAD.     

Radionuclide assessment of a normal left ventricular response to exercise in patients without evidence of heart disease

The aim of this study was to define normal left ventricularperformance at rest and during supine bicycle exercise withequilibrium radionuclide ventriculography in a normal populationother than young healthy volunteers. Thirty-one patients (meanage 45 years ± 9 SD) with chest pain of varying originandno evidence of heart disease proven by means of noninvasiveand invasive techniques were studied. Left ventricular ejectionfraction (LVEF) at rest averaged 0.64 ± 007 SD and increasedwith peak exercise to 0.73 ± 008 SD (P<0.005). Changein LVEF from rest to maximum exercise ranged within 0–0.19.Six patients (19%) failed to augment LVEF with exercise to morethan 0.05; none of the patients dropped LVEF during exercise.Multivariate analysis revealed no significant predictors ofLVEF response to exercise. However, there was a tendency thatresting LVEF and enddiastolic volume index with exercise mightinfluence LVEF response to exercise. Peak left ventricular ejectionrate (LVER) at rest averaged 3.3s^–1 ± 0.6 SD andincreased to 51 s^–1 ± 11 SD (P<0.005) with exercise.Peak left ventricular early filling rate (LVFR) was 2.8s^–1± 0.6 SD at rest and was measured 5.5 s^–1 ±l.3 SD at maximum exercise (P<0.005). Left ventricular enddiastolicvolume (EDV) did not change significantly from rest to maximumexercise, whereas left ventricular endsystolic volume (ESV)decreased to 79% ± 19 SD (P<0.01) of the value atrest. In conclusion, in a normal population other than healthy youngvolunteers LVEF does not necessarily have to increase with exercise.Moreover, besides an augmentation of heart rate a normal leftventricular response to supine exercise is associated with anincrease of LVER and LVFR, a decrease in ESV and no significantchange in EDV, suggesting augmented contractility and a virtuallynegligible role of the Frank-Starling mechanism during exercise.     

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.     

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.     

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.     

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.     

Effect of flecainide on left ventricular ejection fraction

Antiarrhythmic agents may depress cardiac contractility andworsen heart failure. Flecainide is an effective antiarrhythmicdrug, but when administered orally in patients with left ventricular(LV) dysfunction, its effect on LV function is unknown. To assessthe effects of flecainide on cardiac function, LV ejection fraction(LVEF) was measured by radionuclide ventriculography in 36 patientswith LV dysfunction (LVEF 40%), prior to and 7 days after drugtherapy was initiated. To analyse the possibility of a dose-dependenteffect on LVEF, 18 patients received 200 mg day^–1 of flecainideand 18 patients with an identical initial LVEF (27±8vs 27±9) (NS) received 300 mg day^–1. The studywas stopped in 7 patients because of severe cardiac adverseeffects; in these patients the LVEF was significantly lower(15±7) than that of the 29 patients who completed theprotocol (27±8) (P<0.01). In patients who completedthe protocol, there was no significant change in LVEF eitherwith a daily dosage of flecainide of 200 mg day^–1 (27±8vs 27±8) or with 300 mg day^–1 (27±9 vs 28±13).Thus, in the patients with LV dysfunction studied, oral flecainidedid not significantly affect LV function either with a low orwith the ususal daily dosage. However in patients with severeimpairment of LV function (LVEF<30%) flecainide must be usedcarefully owing to a higher incidence of adverse effects oncardiac rhythm.     

Left ventricular function after total correction of tetralogy of Fallot

Conflicting data are available concerning left ventricular (LV)function in patients after total correction of tetralogy ofFallot (TOF). The response to afterload stress determined bymethoxamine challenge and the peak systolic blood pressure-end-systolicvolume relationship were evaluated echocardiographically in20 postoperative TOF patients (age range 9 to 15 years, mean12±2). All patients were without significant residualshunts or pulmonary stenosis. Results were compared with thosein 10 control subjects (age range 9 to 15 years, mean 11±2).The TOF group had higher mean end- diastolic (76·9±14·4vs 66·2±7·2 ml. m P<0·05) andmean end-systolic (36·7±8 vs 29·6±3·9ml. m^–2 P<0·05 volumes than controls. Strokevolume index (SVI) and LV ejection fraction were similar inthe two groups. In normal subjects, mnethoxamine caused a decreasein SVI in seven Out of 10 patients and a mild increase in three;the mean value of SVI at rest was not significantly differentfrom the mean value at peak pressor effect (36·5±4·4vs 35·9±4·0 ml. m^–2, P=NS). In theTOF group, methoxamine induceda reduction in SVI in all patients,the mean value of SVl at peak pressor effect was significantlylower than the mean value at rest (31·3±5·4vs 40·2±6·9 ml. m^–2 P<0·001).Ejection fraction decreased in both groups with the afterloadchallenge, but in the TOF patients the reduction was significantlyhigher than in the normal subjects (from 53±4 to 38±5%vs from 55±3 to 49±3%, P<0·001). Peaksystolic blood pressure-end- systolic volume relationships wereconstructed. The slope (m) of the relationship was significantlylower in the TOF group than in the control subjects (2·85±0·77vs 6·21+0·58, p<0·001);in the TOE groupm was below the 95% confidence limit in all studied patients.There was a significant correlation between aortic oxygen saturationpreoperatively and the slope of the peak systolic pressure-end-systolicvolume relation. Thus, LV function after successful total correctionof TOFmay be abnormal, with larger than normal LV size and decreasedcontractile function.     

Captopril versus placebo in congestive heart failure: effects on oxygen delivery to exercising skeletal muscle

The effects of captopril versus placebo on oxygen consumptionin the exercising leg have been examined Doppler measurementsof femoral flow and arteriovenous oxygen difference. Twentypatients with heart failure were randomized to captopril 25mg (N =10) or placebo (N =10). Maximal supine exercise of onewas performed before treatment and again 1 h and 4 h afterwards.Systemic haemodynamic variables were unaffected by placebo,but captopril increased stroke index at peak exercise from 26±3to 34±3 ml beat^-1 m^-2 and reduced pulmonary artery wedgepressure from 26±3 to 16±3 mmHg (P<0.05). Despitecaptopril-induced improvement in left ventricular function,exercise duration did not increase significantly peak valuesfor femoral flow (1059±178 to 938±134 ml min ^-1,P = NS), and oxygen consumption (134±26 to 111±18ml min^-1, P = NS) in the exercising leg were unaffected. Cutaneousflow, as reflected skin temperature (27.5±0.4 to 27.6±0.4°C,P = NS), was also unaffected. In the patients randomized captopril,the acute improvement in left ventricular function was abbreviatedand, after 4 h, all variables had returned towards baseline.Moreover, when the invasive studies were repeated after fourweeks chronic treatment responsiveness to converting enzymeinhibition had attenuated and there were no detectable differencesbetween the captopril and placebo groups.These data have demonstratedan acute captopril-induced improvement in left ventricular functionpatients with congestive heart failure. Nevertheless the beneficialacute response was abbreviated predicting the development ofearly tolerance. Oxygen delivery to the exercising leg showedno tendency to increase acutely when left ventricular functionwas significantly improved, or chronically when systemic responsivenesshad attenuated. Thus irrespective of its effects on left ventricularfunction, captopril does not increase nutritive flow to exercisingskeletal muscle in congestive heart failure.     

Captopril versus placebo in congestive heart failure: effects on oxygen delivery to exercising skeletal muscle

The effects of captopril versus placebo on oxygen consumptionin the exercising leg have been examined Doppler measurementsof femoral flow and arteriovenous oxygen difference. Twentypatients with heart failure were randomized to captopril 25mg (N =10) or placebo (N =10). Maximal supine exercise of onewas performed before treatment and again 1 h and 4 h afterwards.Systemic haemodynamic variables were unaffected by placebo,but captopril increased stroke index at peak exercise from 26±3to 34±3 ml beat^-1 m^-2 and reduced pulmonary artery wedgepressure from 26±3 to 16±3 mmHg (P<0.05). Despitecaptopril-induced improvement in left ventricular function,exercise duration did not increase significantly peak valuesfor femoral flow (1059±178 to 938±134 ml min ^-1,P = NS), and oxygen consumption (134±26 to 111±18ml min^-1, P = NS) in the exercising leg were unaffected. Cutaneousflow, as reflected skin temperature (27.5±0.4 to 27.6±0.4°C,P = NS), was also unaffected. In the patients randomized captopril,the acute improvement in left ventricular function was abbreviatedand, after 4 h, all variables had returned towards baseline.Moreover, when the invasive studies were repeated after fourweeks chronic treatment responsiveness to converting enzymeinhibition had attenuated and there were no detectable differencesbetween the captopril and placebo groups.These data have demonstratedan acute captopril-induced improvement in left ventricular functionpatients with congestive heart failure. Nevertheless the beneficialacute response was abbreviated predicting the development ofearly tolerance. Oxygen delivery to the exercising leg showedno tendency to increase acutely when left ventricular functionwas significantly improved, or chronically when systemic responsivenesshad attenuated. Thus irrespective of its effects on left ventricularfunction, captopril does not increase nutritive flow to exercisingskeletal muscle in congestive heart failure.     

Left ventricular end-systolic pressure volume relations in healthy young men

The purpose of the present study was to establish the relationshipof left ventricular end-systolic volume vs. mean systemic pressurein variously afterloaded beats in a group of healthy, young,men (n=6, age 24±0.9 years). The relationship was expressedby the slope (E_max) of the line connecting pressure-volume co-ordinatesand its extrapolated intercept (V_d) of the volume axis. Theslope was calculated by linear regression of mean systemic arterialpressure (mean SAP, measured by catheter in the radial artery)vs. end-systolic left ventricular volume (ESV, estimated fromcross-sectional, 4-chamber echocardiographic images). Recordingswere obtained at resting, reduced (nitroglycerin infusion),and elevated (metaoxedrin infusion) blood pressure. IndividualE_max values ranged from 1.05 to 2.01 mmHg ml^–1; Vd wasconsistently found to be negative, ranging from –4.7 to–54.8 ml. All individual relations were statisticallysignificant (P<005 to P<0001). Group values were E_max=1.27±0.25(SE) mmHg ml^–1, V_d=–43.3±7.5 (SE) ml, andE_max indexed for body surface area, E_{max ind} ±=2.54±0.49(SE) mmHg ml^–1 m^–2. We further examined the validityof proposed optimal relations among E_max, heart rate (HR) andsystemic resistance (R_s): E^max/HR=R_s, and among ejection fraction(EF), EDV and V_d: EF=0.5 (1–EDV/V_d). For the group E_max/HR/0023±0.003and R_s=0016±0004 (mmHg ml^–1 min^–1), i.e.,a deviation from equivalence of 30% (P<0.001). EF (=0.72±0.02)deviated by 18% (P<0001) from its proposed optimum (0.5 (1–V_d/EDV)=0.61=006).     

Reciprocal ST segment changes in acute inferior myocardial infarction: clinical, haemodynamic and angiographic implications

Reciprocal ST segment changes are frequent during acute inferiormyocardial infarction, yet their significance remains controversial. In order to investigate the implications of these changes, theECG obtained on admission for 83 patients with acute inferiormyocardial infarction was compared with the clinical courseand the results of angiographic and coronary arteriographicstudies performed an average of 3 weeks after the onset of symptoms. Group 1 consisted of 59 patients with at least 1 mm of horizontalon downsloping ST segment depression in at least 1 of leadsV₁ to V₄. Group 2 consisted of 24 patients without precordialST depression in this area. Group 1 patients were generally older than group 2 patients(59.6 ± 6.4 versus 54 ± 5.3 yr, P<0.01) hadhigher total creatine kinase (CK) levels and MB fractions (1835± 940 versus 875 ± 305, P < 001, 269 ±102 versus 95 ± 35 for MB fraction) and more complicationsduring the hospital course (80% versus 38% P<0.01) and greaterleft ventricular dysfunction (ejection fraction 52.2 ±6% for group I versus 59.2±7% for group 2; cardiac index2.75±0.41min^–1 m^–2 for group 1 versus 3.25± 0.3 lmin^–1 m^–2 for group 2 P<0.005). No difference was observed on biplane angiography as far asleft ventricular wall kinesis was concerned. By contrast, coronaryarteriography revealed more frequent left coronary artery diseasein group 1 patients (84%) than in group 2 patients (37%) P<0.005,the left anterior descending and circumflex arteries being equallyoften affected. Finally, the persistence of ST segment depression for more than48 hours was associated with a more severe depression of theejection fraction than transient depression (less than 48 hours). In summary, the presence of ST segment depression in the precordialleads during the acute phase of inferior myocardial infarctionwas associated with greater myocardial necrosis and more frequentleft coronary artery disease, thus identifying a subset of highrisk patients.     

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.     

Influence of captopril on the arterial baroreceptor reflex in patients with heart failure

In 16 male patients with heart failure (NYHA II-III), the influenceof a single dose of 25 mg captopril on the carotid sinus baroreceptorreflex was examined. Blood presure fell significantly by 11± 1.7 mm Hg (P < 0.001), whereas heart rate remainedunchanged (85 ± 3 vs. 83 ± 3 beats min^–1).Carotid sinus baroreceptors were stimulated by means of an airtightneck chamber. Two indices of baroreflex sensitivity were calculated.(1) The sensitivity to reflex heart rate slowing was increasedby captopril from –2.9 ± 0.7 to –5.0 ±1.3 ms mmHg^–1 (P <0.002). The higher the initial sensitivitythe more pronounced was the change after captopril with an increaseof sensitivity by 46% (y = 1.46x –0.17, P <0.01). Thisincrease in sensitivity cannot be explained by haemodynamicchanges induced by captopril. (2) In eight patients the sensitivityof the baroreflex to increased transmural pressure gradientsof the carotid sinus was evaluated by registration of the bloodpressure response to neck suction; this demonstrated an unchangedresponsiveness following captopril administration. From thesedata it can be concluded that captopril selectively augmentsa reflex bradycardia which is mediated by an increase in vagalefferent tone. The change in the reflex response depends onthe initial reflex sensitivity and cannot be explained by haemodynamicchanges caused by captopril.     

Combination of high-dose furosemide and hydrochlorothiazide in the treatment of refractory congestive heart failure

OBJECTIVE: We studied the synergism between high-dose furosemide and hydrochlorothiazidein patients with severe congestive heart failure and impairedrenal function showing diuretic resistance to a daily dose offurosemide of at least 250 mg. DESIGN AND SETTING: An open study A general hospital in The Netherlands. METHODS: In 20 patients with severe congestive heart failure (stage III–IVaccording to the New York Heart Association) with an oedematousmass of more than 5 kg and a proven diuretic resistance to high-dosefurosemide, hydrochlorothiazide (25–100 mg daily) wasadded to the medication for 3–12 days, leaving the othermedication unchanged. After correction of the hydration state,hydrochlorothiazide was withdrawn. Variables included body weight,serum electrolytes, renal function and natriuresis. RESULTS: Addition of hydrochlorothiazide resulted in a mean (±standard deviation) body weight reduction of 6.7 ± 3.3kg per patient. Mean daily urine volume increased from 1899± 958 ml to 3065 ± 925 ml (P<0.001). Fractionalsodium excretion increased significantly from 3.5 ± 3.2%to 11.5 ± 9.0% (P<0.001). The most important sideeffect of this combination therapy appeared to be hypokalaemia.Mean endogenous creatinine clearance decreased (not significantly)from 32.7 ± 22.5 ml . min^–1 . 1.73 m^–2 to27.6 ± 22.5 ml . min^–1. 1.73 m^–2 CONCLUSIONS: Addition of hydrochlorothiazide to high-dose furosemide is apowerful diuretic tool, even in patients with a significantlyreduced renal function. Because of its potentially dangerousside effects (hypokalaemia), it should be used in a carefullycontrolled setting.     

Relationship between ventilatory threshold and onset of ischaemia in ECG during stress testing

The study was carried out to determine the relationship betweenventilatory threshold and the onset of ischaemia, as shown onthe ECG (horizontal and/or descending ST depression of 0.05mV, on average). Twenty-seven male patients (aged 58 ±7 years) with angiographically documented coronary artery disease(CAD) were assessed by cardiopul-monary exercise testing withoutmedication. Oxygen uptake (VO₂), heart rate (HR), rate-pressure-product(RPP) and blood lactate were measured and/or calculated every30 s during exercise. In addition, 10 patients, comparable withthe above group, were examined to find out the acute effectsof isosorbide dinitrate (ISDN) at ventilatory threshold in relationto ischaemic threshold. The first cardiopulmonary exercise testwas carried out without medication, the second 1 h later with5 mg ISDN, taken sublingually 30 min before the test. RESULTS: (x SD): (1) The mean ventilatory threshold preceded the ischaemicthreshold in relation to exercise capacity (48 ±14 vs55±20 watts; P<0.05), VO₂. kg^–1 (10.0 ±2.2vs 12.0 ±2.9 ml. kg^–1. min; P<0.05), HR (93± 15 vs 100 ± 16. min ^–1; P<0.01), RPP(15095 ± 4424 vs 17166 ± 5245; P<0.01) andblood lactate (1.28 ± 0.53 vs 1.44 ±0.60 mmol.l^–1; P<0.05). (2) This relationship was observed moreoften in the subgroup of patients with angina during cardiopulmonaryexercise testing or with myocardial infarction or with three-vesseldisease than in patients without angina or infarction or withone- and two-vessel disease. (3) ISDN improved the ischaemicthreshold from 55 ±26 watts (without medication) to 81±32 watts (P<0.01) but not the ventilatory threshold(56 ±23 vs 59 ±21 watts, ns). CONCLUSION: The ventilatory threshold seems to precede the ischaemic thresholdbecause of impaired aerobic capacity of the leg muscles, causedby deconditioning on account of the disease. However, ischaemia-inducedleft ventricular dysfunction did not seem to have a direct influenceon ventilatory threshold as ISDN improved the ischaemic threshold,but not the ventilatory threshold.