Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

BACKGROUND: Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM: To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS: The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS: Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction.

Regional sympathetic innervation of the heart by means of metaiodobenzylguanidine imaging in silent ischemia.

Metaiodobenzylguanidine was used to determine regional cardiac sympathetic innervation and whether it is reduced in silent ischemia. Patients with silent ischemia (group 1, n = 6) and angina (group 2, n = 5) and normal subjects (n = 6) underwent single-photon emission tomography at 4 hours. From base to midventricle, uptake increased in group 1 (p < 0.006), group 2 (p < 0.01), and the normal subjects (p < 0.004). In group 1 anterior ventricular uptake was greater than inferior uptake at the midventricle (p < 0.03) and apex (p < 0.05). In group 2 the same relationship was demonstrated at midventricle (p < 0.01) and apex (p < 0.05). Group 2 uptake was only significantly greater than group 1 at midventricle (p < 0.05). Innervation is greatest in midventricle and the apex of the left ventricle and greater in the anterior wall compared with the inferior wall. There is no evidence of reduced innervation in silent ischemia.

Initial experience with excimer laser angioplasty for coronary ostial stenoses.

The excimer laser has several potential advantages over conventional balloon angioplasty in the management of stenoses of the native coronary arteries and of the ostia of saphenous vein grafts. Its use in nine patients, eight of whom were classed as high risk, is described. Four lesions involved the ostia of saphenous vein grafts, three of protected left main stems, and two of native right coronary arteries. Stand alone laser was used in seven cases and laser with additional balloon angioplasty was used in two vein graft stenoses. Acute laser success was achieved in all cases, with a mean reduction of stenosis from 82% to 34% after laser alone and to 28% when balloon angioplasty was used as well. One patient died during laser angioplasty to a non-ostial lesion (procedural success rate 89%) and a second died ten weeks after the procedure. In one patient recurrent angina developed (clinical recurrence rate 25%) and restenosis was confirmed on angiography. Follow up angiography was also performed on the other six surviving patients, all of whom were symptom free and none of whom showed evidence of significant restenosis (restenosis rate 14%). With a mean follow up of 19.7 months the overall success rate was 67%.

Mechanical restitution of isolated human ventricular myocardium subjected to in vivo pressure and volume overload.

OBJECTIVE: The aim was to make a comparison of the mechanical and electrical refractory properties of isolated strips of human ventricular myocardium obtained from patients with either left ventricular pressure overload, volume overload, or normal left ventricular function. METHODS: Strips of ventricular myocardium were obtained at the time of cardiac surgery from 17 patients with aortic stenosis, representing pressure overload, 14 patients with aortic regurgitation, representing volume overload, and nine patients with mitral stenosis, representing normal left ventricular function. Muscle strips were mounted isometrically in a tissue bath, superfused with physiological saline at 37 degrees C, and stimulated at 1 Hz. Mechanical restitution curves were constructed from the isometric twitch tension obtained from extrastimuli during a special stimulus protocol. Transmembrane action potentials were recorded using glass microelectrodes and restitution of the upstroke velocity of action potentials studied in the presence of high external potassium concentration. RESULTS: The aortic stenosis group was older and had higher left ventricular systolic pressures and thicker left ventricular walls than the other groups. Electrocardiographic evidence of left ventricular hypertrophy was present in both the aortic stenosis and aortic regurgitation groups. Peak tension, time to peak tension, and the maximum rates of rise and fall of tension were not significantly different between groups. The time constant of the initial rapid recovery phase of mechanical restitution (tau 1) was prolonged in the aortic stenosis group, at 603(SEM 80) ms v 367(53) ms in the aortic regurgitation group (p < 0.005), and 259(70) ms in the mitral stenosis group (p < 0.005). There was a positive correlation between tau 1 and left ventricular wall thickness (p < 0.05). Neither "normal" nor "slow" (in the presence of raised external potassium) transmembrane action potentials differed in the groups studied. The mean time constant of recovery of "slow" action potential dV/dtmax was slower in the aortic stenosis group, but this difference was not significant. CONCLUSIONS: These data are consistent with the hypothesis that the rate of recovery of calcium release from the sarcoplasmic reticulum is slowed in myocardial hypertrophy due to pressure overload in man and provides a possible explanation of the occurrence of mechanical alternans in such patients.

Mechanical restitution in isolated mammalian myocardium: species differences and underlying mechanisms.

Ventricular myocardium was obtained from guinea-pig, ferret and human hearts. In each case small strips were mounted isometrically in a tissue bath and superfused with a physiological saline at 37 degrees C. The preparations were stimulated at 1 Hz and ectopic stimuli of different preceding intervals were given. The relationship between the force produced by the ectopic contraction and the duration of the preceding interval was plotted to form mechanical restitution curves (MRC). In the guinea-pig the MRC is described by a rapid recovery phase with an exponential time constant of 220 +/- 22.7 ms (mean +/- S.E.M.) followed by a decay (28.5 +/- 8.4 s). In ferret and man the rising phase is described by two exponentials (192.5 +/- 43.2 ms and 4.4 +/- 1.5 s in the ferret; 259.7 +/- 45.2 ms and 3.0 +/- 1.0 s in man). The decay phase is slower in ferret (22 +/- 156 s, P less than 0.02) and man (177 +/- 70 s, P less than 0.002) than in guinea-pig. There was no significant difference between the time constants of the rapid recovery phase of mechanical restitution in each species. The time constant of the rapid recovery phase (tau 1) was abbreviated by ryanodine, ouabain and adrenaline in human myocardium and by ryanodine alone in guinea-pig. Verapamil increased tau 1 in both species. The decay time constant (tau 3) was prolonged by ouabain, verapamil and by increasing extracellular [Ca2+] in human myocardium and by ouabain and verapamil in guinea-pig. The recovery of the second inward current in human myocardium was not correlated to the recovery of mechanical function. It is suggested that tau 1 is dependent on the recycling of Ca2+ within the cell as well as the reactivation of the second inward current. The decay phase, tau 3, is dependent on the rate of Ca2+ efflux from the cell, possibly via a Na+/Ca2+ exchange mechanism. The mechanisms underlying the slow recovery time constant, tau 2, are unclear but it is important to calculate tau 2 for the proper evaluation of tau 1.

Assessment of coronary angioplasty by an automated digital angiographic method.

Digital subtraction coronary angiograms (DSA) of 63 patients who had undergone coronary angioplasty (PTCA) for a total of 73 lesions were analyzed with an automated border-detecting computer program capable of simultaneous geometric and densitometric cross-sectional area estimation. The computer measurements were compared with visual interpretation of the 35 mm cineangiograms. The results indicated that visual reports of cineangiograms tend to overestimate the pre-PTCA diameter percent stenosis and to underestimate the post-PTCA residual stenosis in comparison with the computer (p less than 0.001 in bot cases). There was good agreement between geometric and densitometric area percent stenoses calculated by the program on the pre-PTCA digital angiograms (r = 0.82, p less than 0.001, mean of their differences = -0.2 with standard deviation = 6.1). Following PTCA, however, important discrepancies between the two methods existed (r = 0.71, p less than 0.001, mean of their differences = 1.0 with standard deviation = 18.6). Following PTCA (but not pre-PTCA), densitometric evaluation demonstrated a significantly greater mean coefficient of variation between different views (69%) than did the geometric evaluation on the same views (24%). We conclude (1) that visual interpretation of cine coronary angiograms compares poorly with quantitative methods for both the selection of PTCA candidates and the assessment of the results; (2) that the geometric and densitometric characteristics do not agree in describing the degree of post-PTCA residual stenosis; and (3) that after angioplasty, important discrepancies between densitometric evaluation in different views are observed.

Assessment of coronary angioplasty: comparison of visual assessment, hand-held caliper measurement and automated digital quantitation.

Digital subtraction coronary angiograms (DSA) of 27 patients who had undergone coronary angioplasty (PTCA) to a total of 32 lesions were analyzed using an automated border-detecting computer program and hand-held caliper measurement of diameter percent stenosis. The results were compared with visual interpretation of the 35-mm cineangiograms. Visual reports significantly overestimated the pre-PTCA diameter percent stenosis (P less than .001) and underestimated the residual post-PTCA narrowing compared with the automatic computer program (P less than .001). Caliper measurements overestimated significantly the pre-PTCA stenosis in comparison with the computer (P less than .01), but post-PTCA the two methods did not differ significantly (P = .105). There was a positive but poor correlation between caliper and computer measurements (r = .43, P less than .05) performed on the pre-PTCA digital angiograms. Post-PTCA the two methods correlated better (r = 0.78, P less than .001), but further statistical analysis showed important discrepancies between them. The correlation of visual reports and computer measurements was poor pre-PTCA (Kendall's tau = 0.32, P less than .05) and not statistically significant post-PTCA (tau = 0.64, P = .5). We conclude that there is observer bias in the visual reporting of angioplasty results, so that pre-PTCA lesions are overestimated, whereas post-PTCA are underestimated. Hand-held caliper measurement improves the assessment of coronary stenoses in comparison with the visual report but still may not altogether eliminate observer bias; it may overestimate the pre-PTCA stenoses compared with automated border detection.