Haemodynamic benefit of a rate-adapted A-V delay in dual chamber pacing

In dual chamber pacing, an improvement of exercise capacityis expected when the atrial refractory period is shortened,because the 2/1 point is increased. This objective can be achievedby greatly reducing atrio-ventricular delay (AVD) on exercise.Are such variations (up to 100–120 ms) detrimental froma haemodynamic standpoint? This study was performed to analysethis particular aspect of DDD pacing. Three DDD pacing modes,differing by their AVDs (fixed 200 ms AVD, fixed 150 ms AVD,and rate-adapted AVD) were tested in random order, with a haemodynamicprotocol including ten patients with chronic atrio-ventricular(A-V) block. For the rate-adapted AVD pacing mode, AVD was reducedby 20 ms every 10beats min^–1 increment (from 220 ms at90 beats min^–1 to 100 ms at 150 beats min^–1). Pacingrate was increased from 90 to 150 beats min^–1 by incrementsof 10 beats min^–1 every 5 min. Cardiac performance was significantly improved with the rate-adaptedAVD above the two fixed AVDs, despite a large A VD variation.When A VD was rate adapted, cardiac index, stroke volume indexand left ventricular systolic work index were generally higherand pulmonary capillary wedge pressure, pulmonary arterial pressureand systemic vascular resistances were generally lower, especiallyat 120, 130 and 140 beats min^–1. Comparing the two fixedAVDs, 200 AVD improved cardiac function more at lower heartrates, whereas 150 AVD improved cardiac function more at higherheart rates. Despite its limitations, this study demonstratesthat the potential benefits of reducing AVD with increasingheart rates should be twofold in dual chamber pacing:

1. haemodynamic,optimizing cardiac performance on exercise forall heart rates,especially in cases of organic heart disease;
2. electrophysiologic,permitting a sufficiently rapid maximaltracking rate in caseswith long post-ventricular atrial refractoryperiods, allowinga satisfactory level of exercise.

     

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.     

External counterpulsation: Coronary hemodynamics and use in treatment of patients with stable angina pectoris

External pressure counterpulsation (ECP) has been reported to improve the clinical status of patients with angina pectoris. To document the mechanisms for such an improvement left ventricular oxygen consumption and lactate metabolism, coronary sinus blood flow, and cardiac index were studied in 10 patients with angina pectoris 1) prior to and during ECP; and 2) during right atrial pacing before and after 4 consecutive 2-hour sessions of ECP treatment. During ECP peak early and mean arterial diastolic pressures were significantly raised above control values by 32 and 13% respectively. However, coronary sinus blood flow, left ventricular oxygen consumption and left ventricular lactate extraction, mean systolic arterial pressure and cardiac index were not significantly altered by ECP. Right atrial pacing at 140 beats/min increased coronary sinus blood flow 70% over control values and induced angina and ischemic ST segment changes in 8 patients before and after 4 consecutive treatments of ECP. ECP treatment did not significantly modify the above metabolic and hemodynamic responses at rest or during atrial pacing. Although 5 patients reported improvement in angina symptoms the effect was transitory. No significant improvement over pre ECP-treatment exercise angina threshold was observed immediately following or at 1 and 3 months post treatment. This method of noninvasive circulatory assistance appears to be of doubtful value in the management of patients with stable angina pectoris.     

Beneficial effect of adding nifedipine to beta-adrenergic blocking therapy in angina pectoris

To evaluate the effects of adding nifedipine, a calcium antagonist,to chronic beta-blocking therapy, 10 patients with angiographicallyproven coronary artery disease underwent atrial pacing beforeand after sublingual administration of 20 mg nifedipine. Symptomatic,metabolic and haemodynamic responses were monitored at restand during each pacing period. Nifedipine prolonged pacing timeto angina (285 to 421 s. P <0.01), increased lactate extractionratio (5.4 to 26.7%, P <0.05) and produced coronary and peripheralvasodilation. The results demonstrate that nifedipine has abeneficial additive effect, and should play an important rolein the treatment of angina pectoris in patients already on beta-blockingtherapy.     

Haemodynamic and cardiac metabolic effects of the new {beta}1 agonist prenalterol in patients with cardiac failure

Prenalterol, a ß₁ selective agonist, exerts a positiveinotropic action in animal studies as well as in human volunteersand is effective when administered orally. To assess its immediatehaemodynamic and myocardial metabolic effects, we studied theresponse to prenalterol (50 and 100 µg kg^–1 givenintravenously by cardiac catheterization) in 15 patients withcongestive heart failure secondary to coronary artery diseaseor non-ischaemic cardiomyopathy. At peak effect, cardiac indexincreased from 2.6 ± 0.5 to 3.2 ± 0.81 min^–1m² (mean ± S.D.) (P <0.001); peak rate of left ventricularpressure development rose from 963 ± 242 to 1335 ±411 mmHg s^–1 (P < 0.001); left ventriuclar end-diastolicpressure fell from 25 ± 6 to 17 ± 7 mgHg (P <0.001);coronary sinus blood flow increased from 113 ± 39 to148 ± 55 ml min^–1 (P <0.01); myocardial oxygenconsumption was augmented from 12.7 ± 3.9 to 16.4 ±5.8 ml min^–1 (P < 0.001); and heart rate increasedslightly (from 76 ± 12 to 86 ± 14 beats min^–1;(P <0.05)). No significant changes occurred in left ventricularsystolic pressure, stroke volume index, myocardial lactate extractionrate and myocardial arteriovenous oxygen difference, and nopatients developed angina, ECG changes or ventricular arrhythmias.Infusion of prenalterol effectively improved haemodynamic functionand cardiac metabolism in cardiomyopathy. Therefore this agentdeserves further investigation to evaluate its possible rolefor the long-term therapy of patients with chronic heart failure.     

Effects of flecainide on termination of atrial flutter by rapid atrial pacing

Rapid atrial pacing is effective in terminating atrial flutter,but often results in transient or permanent atrial fibrillationrather than sinus rhythm. Class Ia antiarrhythmic drugs haveearlier been shown to facilitate the direct conversion of atrialflutter to sinus rhythm. The present study was performed totest the hypothesis that flecainide, a group 1c antiarrhythmicdrug, increases the direct conversion to sinus rhythm. In aseries of 30 consecutive clinical episodes of atrial fluttertreated with rapid atrial pacing, 12 episodes were in patientson flecainide treatment (group A), while in 13 episodes no patientswere on group 1 antiarrhythmic drugs (group B). Direct conversionto sinus rhythm was achieved more often in group A (75%) thanin group B (31%) P = 0.034. Both the flutter rates and the pacingrates used were lower in group A, 240 vs 280 beat. Min^–1and 375 vs 430 b. min^–1, respectively. Patients with atrialflutter in whom rapid atrial pacing is to be performed shouldbe considered for pretreatment with flecainide.     

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting

Aims The aim of the study was to evaluate the effects on systemicand coronary haemodynamics and myocar-dial substrate utilizationof a new calcium sensitizer, levosimendan, after coronary arterybypass grafting. Methods and Results Twenty-three low-risk patients were included in this randomizedand double-blind study. They received placebo (n=8), 8 (n=8)or 24 (n=7) µg.kg^–1of levosimendan after coronaryartery bypass operation. Systemic and coronary sinus haemodynamicswith thermodilution and myocardial substrate utilization weremeasured. The heart rate increased 11 beats.min^–1afterthe higher dose (P<0·05). Cardiac output increasedby 0·7 and 1·6l.min^–1(P<0·05 forboth) after 8 and 24µg.kg^–1of levosimendan, respectively.Systemic and pulmonary vascular resistance decreased significantlyafter both doses. Coronary sinus blood flow increased by 28and 42ml/(P=0·054 for the combined effect) after thelower and higher dose, respectively. Myocardial oxygen consumptionor substrate extractions did not change statistically significantly. Conclusion Despite improved cardiac performance, levosimendan did not increasemyocardial oxygen con-sumption or change myocardial substrateutilization. Thus levosimendan has the potential to treat lowcardiac output states after cardiopulmonary bypass surgery.     

Alteration of peripheral vasodilatory reserve capacity after cardioversion of atrial fibrillation

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

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.     

Ischaemic threshold and haemodynamic changes during angina at rest in patients with unstable angina

To examine whether increases in heart rate might be a commontrigger of angina at rest, changes in heart rate, blood pressureand rate-pressure product during pain were compared with theischaemic threshold (heart rate with ST segment shift >=1 mm), determined by atrial pacing, in 272 patients with unstableangina. During an average of 5.9±5.2 episodes of angina,heart rate was comparable to control values (77.0±14.5vs 75.2±11.5, beats. min^–1, ns) and significantlylower than the ischaemic threshold (147.9±22.9, P <0.00001).The rate-pressure product was also lower (955±183 vs2033±369, x 10, P <0.00001). Heart rate during restangina was lower than the ischaemic threshold even when we consideredonly patients with ST depression during pain (n: 71, 81.4±16.0 vs 132.8±21.4, P<0.00001), those with three-vesseldisease (n: 43, 79.9±15.9 vs 136.9±22.0, P <0.00001), or those with a low ischaemic threshold (= <130beats. min, n: 78, 77.0±14.9 vs 118.3±10.7, P<0.00001).In 154 patients in whom a second pacing test was performed theresponse was reproducible in 137 cases (89%). Thus, heart rate barely changes during angina at rest in patientswith unstable angina and is consistently much lower than theischaemic threshold. These findings support the concept thatincreases in heart rate are an unlikely trigger of ischaemiaat rest, even in patients with markedly reduced coronary reserve.     

Comparison of the acute effects of pacing the atrial septum, right atrial appendage, coronary sinus os, and the latter two sites simultaneously on the duration of atrial activation

OBJECTIVE—To compare the acute effects of right atrial appendage, atrial septal, coronary sinus os, and dual site pacing on the duration of atrial activation.
METHODS—20 patients with a variety of cardiac conditions underwent an intracardiac electrophysiological study. Electrograms were recorded from the right atrial appendage and at multiple sites within the coronary sinus. The duration of atrial activation was measured during pacing at the right atrial appendage, atrial septum, and coronary sinus os, and also during dual site stimulation.
RESULTS—The duration of atrial activation with atrial appendage pacing was notably longer (p < 0.001) than with dual site, septal, or coronary sinus os pacing, but there were no significant differences in atrial activation times between these latter three pacing modes. When stimulating the atria at a cycle length of 500 ms, the mean (SD) duration of atrial activation was 145 (37) ms for right atrial appendage pacing, 93 (26) ms for dual site pacing, 96 (28) ms for septal pacing, and 98 (28) ms for coronary sinus os pacing.
CONCLUSIONS—Assuming that the duration of atrial activation is an important determinant of predisposition to paroxysmal atrial fibrillation, atrial septal pacing or coronary sinus os pacing would appear to offer the same advantage as dual site pacing without the additional complexities associated with the latter pacing mode.


Keywords: atrial septal pacing; dual site pacing; atrial activation; atrial fibrillation     

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.     

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

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

Influence of nifedipine on coronary haemodynamics and myocardial metabolism in coronary artery disease

The effect of 30 mg sublingual nifedipine on cardiac metabolismand haemodynamics was studied during two identical periods ofpacing in 11 patients with chronic coronary artery disease.The pace time to angina pectoris improved after nifedipine in6 patients, deteriorated in 2 and was unchanged in 3. Nifedipinedecreased blood pressure (12%), rate pressure product (10%)and coronary vascular resistance (17%) during pacing. Aorto-coronarysinus (A-Cs) oxygen difference decreased at rest (9%) and postpacing(10%) after nifedipine, although an opposite tendency in coronarysinus blood flow resulted in unchanged myocardial oxygen uptakethroughout the study. Although mean myocardial lactate extractionafter nifedipine was unchanged during pacing in the whole groupof patients, it increased in 9 patients who showed a net lactaterelease at control pacing (from –50.9±33.5% to–35.9±30.2%, P>0.05). Nifedipine increased freefatty acid (FFA) extraction during pacing (from 1.5±12.9%to 17.4±13.1%, P<0.02) and uptake (from 1.8±8.5to 11.1±10.6 µmol min^–1, P<0.05). Nifedipineinfluenced only glucose exchange significantly (46% decreasedextraction) at 5 min postpacing. The A–Cs citrate gradientlessened 30–40% postpacing after nifedipine administration. Since the unloading effects of nifedipine did not alter myocardialoxygen uptake, the most important net haemodynamicfinding wasthe decrease in coronary vascular resistance. Although no significantantianginal effect of a fixed dose of nifedipine was found,the increased uptake of FFA may reflect improved myocardialoxidative metabolism after nifedipine     

Increased coronary sinus lactate concentration during pacing induced angina pectoris after clinical improvement by glyceryl trinitrate.

Ten patients with stable angina pectoris and obstructed coronary arteries (greater than 75% reduction in diameter) were studied before and during two periods of pacing, the second of which was preceded by sublingual administration of glyceryl trinitrate (mean dose 0.78 mg). Coronary sinus blood flow measurements and aortocoronary sinus blood sampling for metabolite determinations were carried out. Although the rate of pacing was increased by 10 beats/minute after glyceryl trinitrate administration, the onset of angina was delayed in eight patients during pacing. Drug administration decreased coronary sinus blood flow by 42% and myocardial oxygen uptake by 41% during pacing and induced a shift in mean lactate extraction towards a net release (from 3.1% to -12.6%). It increased the number of patients producing lactate from three to five. Glyceryl trinitrate administration decreased myocardial glucose uptake throughout the study, decreased lactate extraction during recovery, and increased the aortocoronary sinus citrate gradient at rest and during recovery, while the exchange of free fatty acids remained unchanged. A decrease in aortocoronary sinus lactate difference during pacing after glyceryl trinitrate administration correlated positively with the fall in coronary sinus blood flow. The metabolic data do not indicate an augmented myocardial lactate production after glyceryl trinitrate administration. A decrease in coronary sinus blood flow seems, therefore, to be of primary importance in explaining the elevated coronary sinus lactate concentration. Our finding that coronary sinus lactate concentration increased during pacing after glyceryl trinitrate administration despite clinical improvement questions the validity of its use as a quantitative index of ischaemia.     

Circadian rhythm of angina in patients with unstable angina: relationship with extent of coronary disease, coronary reserve and ECG changes during pain

A circadian distribution of ischaemic events has been identifiedin ambulatory patients with stable angina. However, whethera similar distribution occurs in patients with unstable anginawho remain at bed rest is still uncertain. Therefore, we analysedthe possible circadian presentation of episodes of angina atrest (n=1222) in 193 patients hospitalized consecutively. Theinfluence of extent of coronary disease (number of vessels with>70% stenosis, 0, 1 and 2–3), type of ECG changes duringpain on a 12-lead ECG, and coronary reserve, as assessed byischaemic threshold (atrial pacing), were also evaluated. Therewere two peaks of highest incidence: at 0700–1000h andat 1900–2200h (P<0.0001) which were unrelated to theextent of coronary disease, coronary reserve or type of ECGchange. Patients with 1 or 2-3 vessel disease with a reducedischaemic threshold (=<150 beats. min ^–1), however,had a higher incidence of midnight angina (2300–0200h)than those with a normal threshold or with no vessel disease(P<0001). It is concluded that, in spite of being at bed rest, patientswith unstable angina present a definite circadian distributionof angina, with peaks in the early morning and late evening.Patients with a low coronary reserve seem to have a higher incidenceof midnight angina than others.     

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.     

Beneficial effect of enhanced myocardial carbohydrate utilisation after oxfenicine (L-hydroxyphenylglycine) in angina pectoris

Although the major myocardial energy supply comes from oxidationof lipid, carbohydrate requires less oxygen for the same energyyield. Oxfenicine has been shown experimentally to favour carbohydrateutilisation and its effect in a dose of 3–12 mg/kg wasstudied in 18 patients with obstructive coronary artery disease,both at rest and during angina induced by rapid atrial pacing.No major haemodynamic changes or side effects were observedafter the drug. The mean pacing time to angina was significantlyincreased from 289 ± 33 s to 360 ± 35 s (P <0.05) and during pacing, myocardial oxygen consumption fell.After the drug there was a significant increase in myocardialextraction of carbohydrate in the form of lactate, pyruvateand glucose during pacing and in contrast, the myocardial extractionof free fatty acids fell significantly. This increase in myocardialcarbohydrate extraction associated with a reduced myocardialoxygen consumption, is of potential value not only in the treatmentof angina pectoris, but also in the early phases of acute myocardialinfarction.     

Serial electrophysiologic studies after single chamber atrial pacemaker implantation in patients with symptomatic sinus node dysfunction

After single chamber atrial pacemaker implantation, serial electrophysiologicstudies were performed noninvasively at intervals of 3 monthsover a total period of 3 years in 24 patients with symptomaticsinus node dysfunction. All patients underwent invasive electrophysiologicstudies before pacemaker implantation and demonstrated intactanterograde AV conduction. Patients were divided into 2 groupsgroup I did not require antiarrhythmic drugs during follow-upwhereas group 2 received antiarrhythmic drugs. In group 1(11 patients) the atrial paced heart rate producingAV Wenckebach phenomenon (AVWHR) remained stable during a meanfollow-up of 22±10 months, with a variability not exceeding10 beats min^–1 with respect to the initial AVWHR obtainedduring preoperative electrophysiologic study. In group 2 (13patients) with a mean follow-up of 15±8 months a meandecrease of AVWHR of 19.2±17.5 beats min^–1 waspresent between AVWHR before and 3 months after initiation oforal antiarrhythmic drugs (P<0.01) During chronic (>3months) antiarrhythmic drug therapy the variability of the AVWHRnever exceeded 10 beats min^–1 with respect to the AVWHRobtained 3 months after the initiation of oral drug therapy. Deterioration of anterograde AV conduction during long-termfollow-up of patients with symptomatic sinus node dysfunctionand intact anterograde AV conduction at the time of pacemakerimplantation is a consequence of orally taken antiarrhythmicdrugs, rather than a consequence of degeneration of the AV conductingsystem.     

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.