Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

OBJECTIVE--The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS--Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS--23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING--Tertiary referral centre for cardiology. RESULTS--In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal, and four showed no clear change. In those with myocardial infarction four out of five patients had changes that resembled those with normal ventricles but the changes were less pronounced. There were no differences in any of the three groups between the changes in monophasic action potential duration in patients taking beta blockers and those who were not. The changes in monophasic action potential duration in the transplanted heart resembled those in the group with normal ventricles. Inflections on the repolarisation phase of the monophasic action potential consistent with early afterdepolarisations were seen in three of the patients with abnormal wall motion and in none of those with normal wall motion. CONCLUSIONS--These results are further evidence that changes in ventricular loading influence repolarisation. When wall motion was abnormal the effects on regional endocardial repolarisation were often opposite in direction to those when it was normal. Thus regional differences in wall motion could generate local electrophysiological inhomogeneity which may be relevant to the association of arrhythmia with impaired left ventricular function.     

Inhaled nitric oxide (iNO) delivery with high-frequency jet ventilation (HFJV).

OBJECTIVE: To determine if nitric oxide (NO) therapy can be reliably administered during high-frequency jet ventilation (HFJV) using the INOvent delivery system. STUDY DESIGN: NO concentrations were measured just proximal to the endotracheal (ET) tube and at the distal tip of the ET tube during a bench evaluation. Measurements were taken over a wide range of airway pressure settings and NO concentrations with both high- and low- resistance lung models. Percent changes in set versus proximal and proximal versus distal iNO concentrations were tabulated. RESULTS: Differences between proximal and distal NO concentrations were 10% or less. In the therapeutic range of up to 20 p.p.m., differences in concentration were 1 p.p.m. or less. There was no consistent effect on NO concentration when airway resistance was increased by 500%. CONCLUSION: Nitric oxide therapy can be reliably administered during HFJV with the INOvent delivery system when NO is injected exclusively via the HFJV circuit.     

Simultaneous endocardial and epicardial monophasic action potential recordings during brief periods of coronary artery ligation in the dog: influence of adrenaline, beta blockade and alpha blockade

Local differences in the time course of recovery of excitability during the early phase of myocardial ischaemia are important in the genesis of arrhythmias. Catecholamines are known to encourage the formation of arrhythmias and adrenergic blockade is a recognised therapeutic regime. The purpose of this study was to compare the effect of short periods of coronary artery ligation on endocardial and epicardial repolarisation time, to assess any disparity between the two surfaces, and investigate the influence of catecholamines and adrenergic blockade. Simultaneous left ventricular endocardial and epicardial monophasic action potentials (MAPs) were recorded during short periods of left anterior descending coronary artery (LAD) ligation in 9 open chested dogs. Recordings were made during two 90 s periods of LAD ligation. Two further ligations were made during infusion of adrenaline (1 microgram.kg-1.min-1). Subsequently ligations were made after beta blockade with propranolol (0.25 mg.kg-1) and then in the presence of a combination of alpha blockade (phentolamine, 0.15 mg.kg-1) and beta blockade. MAP duration was measured at 90% repolarisation. LAD ligation produced a marked shortening of MAP duration epicardially with only minimal shortening endocardially, which resulted in a highly significant difference between the repolarisation times on the two surfaces. The disparity between surfaces tended to be augmented by adrenaline and was significantly minimised by either beta blockade alone or in combination with alpha blockade. Our results show rapid development of substantial regional differences in repolarisation time between endocardium and epicardium in response to "ischaemia".(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct effect of dobutamine on action potential duration in ischemic compared with normal areas in the human ventricle.

BACKGROUND AND OBJECTIVES. The arrhythmogenic effect of beta-adrenoceptor stimulation is complex and may differ in ischemic and normal myocardium. In this study we examined the differential effect of beta-adrenergic stimulation on ventricular action potential duration and, hence, dispersion of repolarization in potentially ischemic versus nonischemic human ventricular myocardium. METHODS. Simultaneous biventricular monophasic action potentials were recorded in 14 patients (28 recording sites) during infusion of dobutamine in incremental doses (low dose 5 micrograms/kg per min, high dose 10 to 15 micrograms/kg per min) during atrial pacing. Perfusion at the action potential recording site was assessed by incorporating myocardial perfusion scintigraphy with injection of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile during the recording at peak doses of dobutamine. Action potential duration during dobutamine infusion was compared with that during atrial pacing to identical rates in the absence of dobutamine. RESULTS. In 21 normal zone recordings, dobutamine produced a variable effect over that produced by atrial pacing to identical heart rates, either lengthening or shortening the action potential duration. The mean (+/- SEM) value for the additional effect of dobutamine was 0.9 +/- 2.5 ms with low doses and -4 +/- 2.6 ms with high doses (p = NS). In seven recordings from potentially ischemic zones, low dose dobutamine had a similar effect (mean change -3.4 +/- 6.5 ms; p = NS vs. normal zone values). However, the high dose dobutamine invariably shortened the action potential duration by a mean of -22.9 +/- 2.9 ms. (p less than 0.05 vs. low dose in ischemic areas, p less than 0.01 vs. normal zone recordings). Pacing alone or the addition of dobutamine had no significant effect on the normal dispersion of action potential duration between two nonischemic recording sites. In recordings in a normal and an abnormally perfused site, high dose dobutamine significantly altered the dispersion of action potential duration. CONCLUSIONS. These results suggest a different effect of beta adrenergic stimulation in potentially ischemic compared with nonischemic human ventricular myocardium. The abnormal dispersion of repolarization thus created may well be important in beta-receptor-mediated arrhythmogenesis during myocardial ischemia.     

Monophasic action potentials at discontinuation of cardiopulmonary bypass: evidence for contraction-excitation feedback in man

Mechanical dysfunction is the strongest predictor of sudden cardiac death due to arrhythmia. Contraction-excitation feedback whereby changes in myocardial length/tension influence the time course of repolarization and excitability would provide a possible mechanism. Such a relationship has been shown in animals but has yet to be demonstrated in man. A useful model for studying this relationship is provided by the process of weaning off cardiopulmonary bypass after routine coronary artery surgery. During this weaning period of approximately 1 min, the heart is converted from being partially empty and flaccid (i.e., a "nonworking" state) to being filled and stretched to support the circulation (i.e., a "working" state). Monophasic action potentials (MAPs) were recorded from the left ventricular epicardium as a measure of repolarization time in 16 patients at discontinuation of cardiopulmonary bypass. Systolic pressure was recorded from the radial artery line. Measurements were made at three stages that related to different dynamic states of the heart: (1) starting to come off bypass ("minimally working"), defined as the time of first appearance of an inflection on the arterial pressure trace indicating the start of left ventricular ejection and valve opening, when arterial pressures represent left ventricular pressure, (2) half off bypass ("partially working"), and (3) off bypass ("wholly working"). During the process of discontinuing bypass MAP duration shortened, while systolic pressure increased. MAP duration at 90% and 60% repolarization (MAP D90, MAP D60) decreased from 288.0 +/- 29.5 msec (mean +/- SEM) and 235.0 +/- 27.9 msec in the minimally working heart to 274.5 +/- 30.2 msec and 224.2 +/- 27.3 msec in the partially working heart (p less than .001), with a subsequent decrease to 261.0 +/- 28.8 and 214.0 +/- 28.7 when the heart was wholly working (p less than .001). Systolic pressure increased from 54.1 +/- 9.3 mm Hg in the minimally working heart to 65.9 +/- 13.8 mm Hg in the partially working heart (p less than .001) and subsequently increased to 75.5 +/- 13.3 mm Hg when the heart was wholly working (p less than .001). Mean heart rates did not change significantly. A strong correlation was obtained between absolute MAP duration and systolic pressure. Regression analysis revealed: MAP D90 vs systolic pressure (p less than .001) and MAP D60 vs systolic pressure (p less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)     

Vasodilator myocardial perfusion imaging: demonstration of local electrophysiological changes of ischaemia.

OBJECTIVE--To examine the incidence and severity of myocardial ischaemia provoked in the course of perfusion scintigraphy by coronary vasodilators using endocardial recordings of steady state monophasic action potentials as an independent marker of early localised myocardial ischaemia. PATIENTS--31 men undergoing routine cardiac catheterisation for investigation of chest pain were studied. SETTING--A tertiary cardiac referral centre. DESIGN--Single site monophasic action potentials were recorded from the left or right ventricle or both (50 recording sites) during intravenous infusion of dipyridamole (0.015 mg/kg/min) for four minutes. Heart rate was held constant with atrial pacing at 20% above the patient's resting rate. Technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (MIBI) was administered four minutes after dipyridamole, and single photon emission tomographic imaging was performed an hour later. Rest images were obtained the next day (two day, two dose protocol). Recordings were divided into three groups based on the scintigraphic perfusion characteristics and coronary anatomical data for the action potential recording site: group 1--recordings from areas with a normal perfusion pattern (n = 30), group 2--recordings from areas with a perfusion defect and subtended by significantly narrowed coronary arteries without obvious angiographic collateral supply (n = 10), and group 3--recordings from areas with a perfusion defect and subtended by occluded arteries with angiographically evident collaterals from adjacent vessels (n = 10). RESULTS--There were changes in the duration of the monophasic action potential indicative of ischaemia--that is, shortening of duration of steady state action potential--in 18 of the 20 recordings from areas of abnormal perfusion. Peak changes were apparent eight minutes from the start of the dipyridamole infusion. Mean (SEM) values for duration of the action potential between control and peak effect at eight minutes were 276.5 (5.3) ms v 276.6 (5.4) for group 1 (NS), 289.6 (4.7) ms v 278.4 (4.9) ms for group 2 (p less than 0.001), and 269.6 (5.7) ms v 242.0 (4.4) for group 3 (p less than 0.0001). These changes were significantly different between the three groups (p less than 0.01). ST segment changes on the surface electrocardiogram were seen in only eight patients, all with areas of viable myocardium supplied by collateral vessels. CONCLUSIONS--These data provide strong evidence for the presence of myocardial ischaemia in regions of reversible perfusion defects induced by dipyridamole. This study also shows that such ischaemia is more intense and more likely to be seen when myocardial viability is dependent on collateral circulation.     

An analysis of pulsus alternans in aortic stenosis.

Pulsus alternans was studied hemodynamically in 5 patients with calcific aortic stenosis. Left ventricular function was assessed by angiographic volume analysis and by force-velocity analysis. All cases showed alternation of max and min dP/dt and kVmax. Inconsistent factors were an alternating left ventricular enddiastolic pressure, alternating left ventricular enddiastolic volume, alternating left ventricular endsystolic volume, ejection fraction, enddiastolic wall stress and wall stiffness. All cases had a high ventricular mass, but the critical value of ventricular mass or the ratio of mass to left ventricular enddiastolic volume were also inconsistent. Pulses alternans is primarily due to alternating contractility.     

Effect of intermittent left anterior hemiblock on left ventricular function.

Studies of left ventricular function were performed during intermittent left anterior hemiblock, Max dP/dt and Vmax fell during left anterior hemiblock, with a rise in left ventricular end-diastolic pressure compared with a normally conducted beat.     

Pseudoxanthoma elasticum presenting with myocardial infarction

A 31 year old man presented with an anterior myocardial infarction. He had a history of recurrent gastrointestinal bleeding of obscure cause since childhood and peripheral vascular disease. A clinical diagnosis of the type 1 dominant form of pseudoxanthoma elasticum was supported by histological data from skin biopsy.