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.     

Acute myocardial ischaemia induces cardiac carnitine release in man

In animal studies, prolonged periods of ischaemia decrease thecardiac carnitine content. However, whether in humans the heartloses carnitine during short-term ischaemia, and whether thisis related to ischaemia-induced cardiac dysfunction, is as yetunknown. Carnitine kinetics were investigated in 28 normotensivepatients with significant left coronary artery disease, duringand after incremental atrial pacing. To evaluate carnitine kineticsfrom the ischaemic area, patients were grouped as those with(n=22) or without (n=6) myocardial lactate production. Atrialpacing resulted in a comparable maximal heart rate and ST depressionin both groups. Carnitine kinetics did not change in those withoutlactate production. In contrast, coronary venous free carnitinelevels increased significantly by 9% during pacing in thosewith lactate production. Cardiac free carnitine balance changedfrom uptake (255 ± 107 pmol. min^–1, mean ±SEM) to release (–150 ± 66 pmol. min^–1) at30 min after pacing in the group with lactate production. Arterialand coronary venous differences in free carnitine were significantlycorrelated with myocardial lactate extraction immediately afterpacing. The change in coronary venous free carnitine was significantlycorrelated with the change in left ventricular ejection fractionat 10 min after pacing. Thus, in patients with coronary arterydisease, short-term mild myocardial ischaemia results in significantcardiac free carnitine loss.     

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.     

Nocturnal angina in patients with fixed coronary stenosis. Increased coronary vasoconstrictive sensitivity with independence of pacing ischaemic threshold

Atrial pacing and ergonovine tests were performed in 18 consecutivepatients with unstable angina at rest and significant coronaryartery stenosis ( 90% in one vessel in 16 patients). 13 ofthem also had exertional angina. 14 patients presented at leastone positive response (1.0 mm ST-segment shift) to pacing, witha heart rate (144±11 vs 75±13 beats min^–1,P<0.001) and double product (195±26 vs 108±32x 10^–2 P<0.001) significantly higher than during anginaat rest. In the ten patients who presented nocturnal angina,the incidence of positive response to pacing and the pacingischaemic threshold, tested on three different days, were similarto those seen in the remaining patients. In contrast, the ergonovinetest was positive in all patients with nocturnal angina (100%),who required a low dose (0.28±0.2 mg), but it was positivein only four (50%) of those without nocturnal angina, who neededa higher dose (0.55±0.12 mg, P<0.005). Therefore, in patients with severe coronary stenosis and exertionalangina, spontaneous episodes, including nocturnal angina, arenot related to increases in heart rate. The increased coronaryvasoconstrictive sensitivity found in these patients, particularlythose with nocturnal angina, was not dependent on the statusof the coronary reserve, which strongly suggests that changesin coronary tone, focal or diffuse, are involved in the mechanismsof these ischaemic events.     

Modification of left ventricular response to pacing tachycardia by nifedipine in patients with coronary artery disease

The calcium blocking agent nifedipine was shown to protect the isolated left ventricle against the development of altered diastolic compliance during severe global ischemia. To assess the influence of nifedipine during myocardial ischemia in human subjects, we studied the effect of nifedipine (20 mg sublingually) on the hemodynamic response to pacing tachycardia (heart rate 66 ± 4 to 143 ± 4 beats per minute) in 17 patients with multivessel coronary artery disease. Typical anginal pain occurred in all patients during pacing tachycardia before nifedipine, but in only 3 of 17 patients during pacing after nifedipine. In 11 patients a significant (≥ 5 mm Hg) increase in postpacing left ventricular end-diastolic pressure (LVEDP, 15 ± 2 mm Hg to 28 ± 2 mm Hg, p < 0.01) developed, and was associated with an upward shift of the left ventricular diastolic pressure-volume curve. In these patients, pretreatment with nifedipine did not alter resting LVEDP or aortic pressure, but did attenuate or abolish the increase in LVEDP and the shift in left ventricular diastolic pressure-volume curves after pacing tachycardia to the same rate and for the same duration. The antianginal effect of nifedipine was not associated with a reduction in contractility, because there was no change in LV + dp/dt after nifedipine. However, the increase in left ventricular systolic pressure achieved in response to pacing tachycardia was less after nifedipine. We conclude that nifedipine favorably modifies the symptomatic and hemodynamic response to pacing tachycardia in patients with coronary artery disease. The mechanism is uncertain and could involve a direct myocardial effect, peripheral vasodilation, coronary vasodilation or a combination of these effects.     

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.     

Functional characteristics of myocardial bridging: A combined angiographic and intracoronary Doppler flow study

AIMS: Combined quantitative coronary angiography and intracoronaryDoppler flow velocity measurements were performed to study theunderlying haemodynamic mechanisms leading to myocardial ischaemiain patients with myocardial bridging in the absence of coronaryartery disease. METHODS AND RESULTS: In 42 symptomatic patients with myocardial bridging of the leftanterior descending coronary artery, quantitative coronary angiographywas used to measure absolute and relative vessel diameters duringsystole and diastole. In 14 patients, serial frame-by-framediameter quantification during a complete cardiac cycle wasperformed. Intracoronary blood flow velocities were determinedusing a 0·014 inch Doppler flow guide wire proximal,within, and distal to myocardial bridges, and coronary flowreserve was calculated. Quantitative coronary angiography revealeda maximal systolic lumen diameter reduction of 71 ± 16%with a persistent diameter reduction of 35 ± 13% duringmid-diastole. Flow velocities revealed increased average diastolicpeak flow velocities within myocardial bridges of 38·6± 19 cm. s^–1 vs 22·4 ± 7·7cm. s^–1 proximal and 18·6±4·6cm.s^–1 distal (P<0·001), which increased duringrapid pacing (64·7 ± 25 cm. s^–1, P<0·001vs baseline). Coronary flow reserve distal to myocardial bridgeswas 2·3 ± 0·9 (vs 2·9 ± 0·9proximal, P<0·05). There was a characteristic Dopplerflow profile within myocardial bridges with an early diastolicovershoot, which was further augmented during rapid pacing. CONCLUSION: Myocardial bridging is characterized by a delay in diastoliclumen gain and a concomitant increase in diastolic intracoronaryDoppler flow velocities, which are enhanced by rapid pacing.In combination with a reduced coronary flow reserve and anginalsymptoms these findings support the concept of a haemodynamicallysignificant obstruction to coronary flow due to myocardial bridgingin a selected subset of patients.     

Serum triglycerides and HDL cholesterol -- major predictors of long-term survival after coronary surgery

The influence of pre-operative serum lipid levels on late clinicaloutcome after coronary artery bypass surgery was analysed in83 patients undergoing coronary bypass surgery for stable anginapectoris. The mean follow-up period for surviving patients was105±33 months (range 65–133). Twenty-two patients(27%) had died during follow-upt of whom 14 had sustained afatal myocardial infarction and four had succumbed to othercardiovascular causes. Thirty-one patients sustained 35 cardiacevents, defined as either fatal or non-fatal myocardial infarction,or reoperation, or PTCA during the follow-up period. With univariateanalysis, pre-operative serum levels of total cholesterol andtriglycerides were significantly related to cardiac events,P<0.05 and P<0.05, respectively. In a Cox proportionalanalysis, cardiac mortality and total mortality were relatedto serum triglycerides and HDL cholesterol (P<0.05 and P<0.01respectively). Eighty-five percent of the patients with triglycerides<2.0 mm. l^–1 survived for 10 years, while only 48%of patients with triglycerides >2.0 mM. 1^–1 remainedalive for that period. Figures were similar for subjects withHDL cholesterol >1.0mM. I^–1 or HDL cholesterol <1.0mM. I^–1, at 89 and 38%, respectively. Only 28% of the patients with the combination triglycerides>2.0 mM. I^–1 and HDL cholesterol <1.0 mM. I^–1were alive 10 years after surgery. These data suggest that dyslipidaemia,especially the combination of high serum triglycerides and lowHDL cholesterol, is an important factor influencing long-termclinical outcome after coronary bypass surgery.     

The link between acute haemodynamic adrenergic beta-blockade and long-term effects in patients with heart failure: A study on diastolic function, heart rate and myocardial metabolism following intravenous metoprolol

The present study was performed to find possible mechanismslinking the early effects of beta-blockade with the observedlong-term effects in patients with heart failure. In 57 patients with heart failure, 13±3.1 mg of metoprololwas given intravenously. The patients were investigated by invasivehaemodynamics (n = 34), including collection of myocardial metabolicdata during atrial pacing stress (n = 16), by radionuclide angiographyduring physiological atrial pacing (n = 13), and by a bedsideevaluation (n = 10). Diastolic function, measured by early peak filling rate, followedchanges in heart rate, but was similar when heart rate was heldconstant by atrial pacing before and after beta-blockade. Followingbeta-blockade and slower heart rates, diastolic filling volumeswere redistributed to late diastole. Metoprolol induced a paralleldecrease in coronary sinus flow and myocardial oxygen consumption.Myocardial oxygen consumption following beta-blockade decreasedboth during spontaneous rhythm (25±15 to 16±8.8ml. min^–1; P = 0.006), and during atrial pacing stress(30±13 to 23±11 ml.min^–1; P = 0.004). Cardiacindex decreased owing to reduction of heart rate (2.3±1.0to 1.9±0.64 l.min^–1.m²; P = 0.0003), while leftventricular filling pressure was unchanged. Ejection fractionand ventricular volumes were unaltered following atrial pacingor beta-blockade. There was a reflex increase in noradenalineconcentration after beta-blockade injection (0.96±0.66to 1.20±0.91 nmol.l^–1; P = 0.002), whereas myocardialnoradrenaline overflow was unchanged. There was a trend towardsan increase in myocardial lactate consumption after beta-blockadeadministration during atrial pacing stress. It is suggested that the surprisingly good tolerability seenafter acute administration of beta-blockers to patients withsevere heart failure may be explained by prolongation of thediastolic filling phase, which outweighs the negative ino tropiceffects. The reduced myocardial metabolic demand may allow thefailing myocardium to recover and explain the excellent long-termeffect on heart function following beta-blockade treatment.     

Risk factors for myocardial infarction during coronary artery bypass graft surgery

Patients with a particular thrombotic profile may be at greaterrisk of myocardial infarction during coronary artery bypassgraft surgery. The thrombotic profile of 50 patients admitted to hospital withstable angina pectoris was determined prior to haemodynamicinvestigation. ECG results and determination of cardiac enzymesshowed that 12 patients had suffered a perioperative myocardialinfarction. These patients had a higher mean atheroscleroticscore (42.1 ± 10.5 vs 32.9 ± 13, P<0.02), alonger aortic cross clamp time (59 ± 15.2 vs 45.7 ±16.3 min, P < 0.05), lower serum levels of protein C (101.2±26vs 124.7+ 31.4%, P<0.05) and tissue plasminogen activator(322 ± 580 vs 2307±2830 IU ml^–1, P<0.01). There were no differences between the two groups in Jenkin'scoronary score, the number and type of grafts, ejection fraction,left ventricular end-diastolic pressure, lipid profile or levelsof markers of platelet release. In addition to a more severe distal coronary atheroma and alonger aortic cross-clamp time, patients with impaired endothelialfibrinolytic activity appeared to be at greater risk of myocardialinfarction during coronary artery bypass graft surgery.     

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.     

Effect of early treatment with nifedipine in suspected acute myocardial infarction

In this single centre prospective, double blind study, 98 patientswith suspected acute myocardial infarction (AMI) were randomized,within six hours, to nifedipine 10 mg (46 patients) or placebo(52 patients) both administered sublingually. The delay timefrom onset of chest pain to treatment was 3.33±0.2 hours(mean±SEM) and 3.28±0.18 hours for the nifedipineand placebo treated groups, respectively. Treatment was continuedorally for 3 days. AMI was confirmed in 28 patients given nifedipineand 23 patients given placebo. Infarct sizing by CK-MB isoenzymerelease was possible, for technical reasons, in only 23 patientsnifedipine and 17 patients on placebo. CK-M B isoenzyme releasewas 710±104IUI^–1 and 655±118IUI^–1for the nifedipine and placebo treated groups respectively (P>0.05).In the acute coronary insufficiency (ACI) group—18 patientsgiven nifedipine and 29 patients given placebo—there wasno significant difference in duration of admission, urgent cardiacreadmission or progression to AMI within one month. Study withdrawaloccurred in 15.3%—8 nifedipine and 7 placebo. Overall,one month mortality was 10.2% with 5 deaths in both the nifedipineand placebo treated groups. Early treatment with nifedipinedid not reduce enzymatically determined infarct size or onemonth mortality in patients with AMI, or reduce one month morbidityor mortality in patients with ACI.     

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.     

The effect of verapamil on myocardial exchange of free fatty acids, citrate, lactate and glucose in coronary artery disease

Twelve patients with coronary artery stenosis (> 50% diameterreduction) underwent two identical periods of atrial pacingbefore and after i. v. verapamil (0.1 mg/kg). Myocardial exchangesof free fatty acids (FFA), citrate, lactate and glucose wereevaluated from measurements of arterio-coronary sinus differences(n = 12) and coronary sinus blood flow (CSBF) (n = 9). Beforeverapamil 11 patients developed angina. Verapamil abolishedpain in seven and improved pacing time to angina in four patients.After verapamil, aortic pressure decreased (P < 0.05), whilethe rate pressure product remained unchanged during rest andpacing. Verapamil decreased CSBF by 20% (P<0.05) during pacing,and increased oxygen extraction both during pacing and recovery.During pacing verapamil increased net FFA extraction (P<0.01)and uptake (1 to 8 µmol/min P<0.05), and decreasedglucose extraction (P<0.05) and uptake (22 to 11 µmol/min P< 0.02. Verapamil increased myocardial citrate releaseduring pacing (P < 0.05), suggesting a citrate inhibitionof glycolysis as a possible mechanism of the inhibited glucoseuptake. During pacing, verapamil reduced lactate release inseven patients (P<0.05) and decreased lactate extractionin five patients (P<0.05). The results suggest that verapamilmediates its beneficial effect on pacing-induced angina, inpart by changing substrate utilization of the ischaemic myocardiumin man towards that of normal heart.     

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.     

Afterload reduction by nifedipine--the acute haemodynamic response to exercise in hypertensive subjects

In 16 people with essential hypertension, heart rate (HR), bloodpressure (BP) and relative cardiac volumes were measured atrest and during submaximal upright exercise before and after10 mg of sublingual nifedipine using radionuclide ventriculography. In 10 patients who had had no previous therapy (BP 152/103±5/3mmHg) nifedipine produced a fall in BP of 6/12±3/3 mmHg(SEM) and a rise in HR of 15±5 bpm (P<0.001). Thiswas associated with a rise in LVEF of 0.07±0.02 (P<0.005)and in cardiac output of 44±9%, presumably as a resultof ventricular offloading. The cardiac response to exercisegiven the different starting values, was unchanged by nifedipine.Thus the HR was 101±6 bpm at rest after nifedipine andon exercise rose to 124±6 bpm (P<0.001): stroke volumewas +22±8% at rest after nifedipine and rose to +43±12%on exercise. Thus cardiac output which had increased by 44±9%after nifedipine increased by 100±10% from the initialvalue. In 6 patients pre-treated with atenolol (100 mg) and with similarresting BP (158/101±5/4 mmHg) there was a fall in BPof 32/15±3/2 mmHg after nifedipine which was greaterthan in the previously untreated group (P<0.01). In thisgroup HR increased by 8±3 bpm (P<0.05). Followingnifedipine the exercise response was similar given the differentstarting values. The combination of nifedipine and a beta adrenoceptor antagonistcan depress myocardial function and the difference between pressure–volumeratios in the two groups supports this view but there was noimportant depressant effect. We conclude that the combinationof beta blocker and nifedipine therapy is effective and safein hypertensive subjects without significant myocardial dysfunction.     

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.     

Short-term effects of atrial versus atrio-ventricular pacing on myocardial ischaemia in coronary artery disease patients

This investigation was undertaken to evaluate the effects ofshort-term atrial vs atrio-ventricular pacing on myocardialischaemia. The study was in two parts. In part one, 12 coronary arterydisease patients were studied to investigate the effects ofthe two pacing modes on angina pectoris, coronary sinus O₂ saturationand lactate. The two pacing modes were each applied for 5 minat 25 beats. min^–1 more than the maximum heart rate ofthe exercise test. Coronary sinus O₂ saturation and lactatewere estimated before and after pacing. In part two, 13 patientswith left anterior descending coronary artery disease were studiedto investigate the effects of the two pacing modes on coronaryflow reserve, using a Doppler catheter in the above mentionedbranch after the administration of 10 mg intracoronary papaverine.The pacing rate was 15 beats . min^–1 greater than theresting heart rate. Coronary sinus lactate and O₂ saturation changes were the sameand angina pectoris developed at about the same time from thebeginning of pacing under both modes. Coronary flow reservewas 2.1±0.7 during atrial pacing and 2.1±1.1 duringatrio-ventricular pacing (ns). It is concluded that short-term atrial and atrio-ventricularpacing have the same effects on myocardial ischaemia in coronaryartery disease patients.     

Altered left ventricular diastolic function post-atrial pacing in coronary artery disease and left ventricular hypertrophy: further insights by pulmonary venous flow analysis

Left ventricular filling dynamics during acute pacing-inducedmyocardial ischaemia were assessed using trans-oesophageal atrialpacing and simultaneous Doppler measurements of pulmonary venousand mitral flow. All patients (10 with CAD and 12 with leftventricular hypertrophy due to hypertrophic cardiomyopathy;HCM) were in sinus rhythm and patients with mitral insufficiencywere excluded. Data were compared with those of a control group(n=10). Measurements were obtained at baseline (heart rate 84± 14 beats. min ^–1) and immediately after atrialpacing via the same transoesophageal echocardiography (TEE)probe after stepwise increase of the pacing rate to 133 ±12 beats. min ^–1. Heart rate immediately after pacingwas 83 ± 13 beats. min ^–1. Time velocity integrals(TVI) were calculated at baseline and after pacing for the followingflows: early (E) and late (A) mitral flows, as well as antegradesystolic (S), diastolic (D) and retrograde diastolic (R) pulmonaryvenous flows. In the control group none of the flow parameters changed significantlyafter pacing compared with baseline data. In contrast, in CADpatients, the TVI of the E wave, the TVI El A ratio as wellas the pulmonary venous flow changed significantly after pacing(7.3 to 5.5 cm, P<0.05, 1.7 to 11, P<0.01 and 10 to 21cm,P<0.001, respectively). HCM patients also showed significantchanges: TVI El A ratio post-pacing decreased from 1.9 to 1.4(P<005), and the pulmonary venous reverse flow integral increasedfrom 1.3 to 2.8 cm (P<0.0001). Analysis of variance showedthe TVI ElA ratio to be significantly dependent on pacing (P=0.012).The pulmonary venous retrograde flow was found to be influencedby the presence of disease (P=0.033 before and P=0.0001 afterpacing) and in all cases by pacing (before vs after pacing;P=0.0001). Pacing resulted in significantly different changesin the TVI ElA ratio and the TVI of the retrograde pulmonaryvenous flow for CAD and HCM patients compared with those ofcontrol subjects. In patients with CAD and HCM, rapid atrial pacing results ina decreased early to late ventricular filling ratio becauseof impaired relaxation, despite presumably increased fillingpressure. Retrograde pulmonary venous flow increased becauseof increased filling pressure and operating left ventricularstiffness.