Major racial differences in coronary constrictor response between japanese and caucasians with recent myocardial infarction.

BACKGROUND: Enhanced coronary vasomotion may contribute to acute coronary occlusion during the acute phase of myocardial infarction (AMI). Japanese have a higher incidence of variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial. METHODS AND RESULTS: The same team studied 15 Japanese and 19 Caucasian patients within 14 days of AMI by acetylcholine injection into non-infarct-related (NIRA) and infarct-related (IRA) coronary arteries followed by nitroglycerin. Incidence of vasodilation, vasoconstriction, spasm, and basal tone were assessed in proximal, middle, and distal segments after each drug bolus by quantitative angiography. Japanese patients had much lower cholesterol levels than Caucasians (183+/-59 versus 247+/-53 mg/dL, P<0.006) but showed a lower incidence of vasodilation (2% versus 9% of coronary segments) and a greater incidence of spasm after acetylcholine (47% versus 15% of arteries, P<0.00001). Incidence of spasm was higher in IRAs than in NIRAs in both populations (67% versus 39% and 23% versus 11%, respectively). Multivessel spasm was more common (64% versus 17%, P<0.02) and vasoconstriction of nonspastic segments was greater in Japanese patients (-23.4+/-14.9% versus -20.1+/-15.7%, P<0.02) in the presence of similar average basal coronary tone with respect to post-nitroglycerin dilation and of nonsignificant differences of coronary atherosclerotic score. CONCLUSIONS: Soon after AMI, Japanese patients exhibited a 3-fold-greater incidence of spasm and greater vasoconstriction of nonspastic segments after acetylcholine than Caucasians. The causes of such differences warrant further investigation because they may have relevant pathophysiological and therapeutic implications.

Mechanisms of adenosine-induced epicardial coronary artery dilatation.

BACKGROUND: In order to ascertain whether human adenosine-induced dilatation of epicardial arteries is direct or flow-mediated, we compared the effects of intracoronary adenosine infusion on epicardial coronary arteries with those produced by dipiridamole, a selective arteriolar vasodilator. METHODS AND RESULTS: In 24 patients with angiographically normal coronary arteries, coronary blood flow velocity was measured by a Doppler wire during intracoronary infusion of adenosine or dipyridamole, which is known to increase intramyocardial adenosine concentration. Coronary angiograms were obtained at baseline and immediately after the end of each infusion period; coronary diameters 5 mm distal to the wire tip were measured by computer-assisted quantitative coronary angiography. Peak coronary blood flow velocities during adenosine or dipyridamole infusions were similar (52.0 +/- 15.5 and 47.9 +/- 24.2 cm.s-1, P = ns). Coronary diameters immediately after adenosine and dipyridamole infusions were similar and both higher than that at baseline (2.80 +/- 0.63 and 2.86 +/- 0.64 vs 2.44 +/- 0.69 mm, P < 0.05). The absolute and percentage increases of coronary artery diameters in response to adenosine were highly correlated to coronary blood flow velocity (R = 0.622, intercept -0.10 +/- 0.14, P = 0.002 and R = 0.617, intercept -15.2 +/- 9.9, P = 0.001, respectively); similar correlations were found in response to dipyridamole (R = 0.708, intercept -0.44 +/- 0.19, P < 0.001 and R = 0.649, intercept -13.5 +/- 8.7, P < 0.001, respectively). Finally the absolute and percentage changes of coronary artery diameters caused by adenosine were highly correlated to those caused by dipyridamole (R = 0.840 P < 0.001 and R = 0.836, P < 0.001 respectively). CONCLUSIONS: A significant correlation exists between epicardial coronary vasodilation and coronary blood flow velocity during intracoronary adenosine infusion, thus suggesting that epicardial coronary vasodilation induced by adenosine is predominantly flow-mediated rather than direct. This conclusion is supported by the observation that similar findings were obtained using dipyridamole, which can only dilate epicardial coronary arteries indirectly, through the increase in coronary blood flow velocity caused by the inhibition of intramyocardial adenosine re-uptake.

Low incidence of serotonin-induced occlusive coronary artery spasm in patients with recent myocardial infarction.

Intracoronary infusion of serotonin has been reported to induce varying degrees of coronary vasoconstriction in different coronary syndromes, but it has never been studied in patients after myocardial infarction. In patients with recent myocardial infarction, we found a low incidence (11%) of serotonin-induced occlusive spasm only in the infarct-related artery (IRA), and a significantly higher vasoconstriction in the distal segment of the IRA than in the same segment of the non-IRA.

Electrograms for identification of the atrial ablation site during catheter ablation of accessory pathways.

BACKGROUND: Catheter ablation of accessory pathways using radiofrequency current has been shown to be effective in patients with Wolff-Parkinson-White syndrome, by using either the ventricular or atrial approach. However, the unipolar electrogram criteria for identifying a successful ablation at the atrial site are not well established. METHODS AND RESULTS: One hundred patients with Wolff-Parkinson-White were treated by delivering radiofrequency energy at the atrial site. Attempts were considered successful when ablation (disappearance of the delta wave) occurred in < 10 seconds. In eight patients with concealed pathway, the accessory pathway location was obtained by measuring the shortest V-A interval either during ventricular pacing or spontaneous or induced reciprocating tachycardia. In 92 patients both atrioventricular valve annuli were mapped during sinus rhythm, in order to identify the accessory pathway (K) potential before starting the ablation procedure. When a stable filtered (30-250 Hz) "unipolar" electrogram was recorded, the following time intervals were measured: (1) from the onset of the atrial to the onset of the K potential (A-K); (2) from the onset of the delta wave to the onset of the K potential (delta-K); and (3) from the onset of the K potential to the onset of the ventricular deflection (K-V). During unsuccessful versus successful attempts, A-K (51 +/- 11 ms vs 28 +/- 8 ms, P < 0.0001 for left pathways [LPs]; and 44 +/- 8 ms vs 31 +/- 8 ms, P < 0.02 for right pathways [RPs]) and delta-K intervals (2 +/- 9 ms vs -18 +/- 10 ms, P < 0.0001 for LPs; and 13 +/- 7 ms vs 5 +/- 8 ms, P < 0.02 ms for RPs) were significantly longer. CONCLUSIONS: Short A-K interval (< 40 ms), and a negative delta-K interval recorded from the catheter positioned in the atrium are strong predictors of successful ablation of LPs and RPs. Therefore, the identification of the K potential appears to be of paramount importance for positioning of the ablation catheter, followed by analysis of A-K and delta-K unipolar electrogram intervals. However, it appears that the mere recording of K potential is not, per se, predictive of successful outcome, but rather the A-K and delta-K interval.

Thrombogenesis in acute coronary syndromes.

It is well-established that intracoronary thrombosis, which may be associated with plaque fissure and enhanced coronary vasoconstriction, is the immediate cause of a sudden impairment of regional myocardial perfusion, which is transient in unstable angina and is, eventually, irreversible in acute myocardial infarction. It is also well-known that increased platelet reactivity, increased procoagulant activity, and reduced endogenous fibrinolysis are risk factors for acute coronary events. Nevertheless, the primary causes responsible for sudden intracoronary thrombosis and for coronary vasoconstriction causing acute coronary syndromes are still largely speculative. Recent studies have shown activated inflammatory cells both in the coronary arterial wall and in the systemic circulation of patients with unstable angina. Furthermore, the intensity of the inflammatory response is correlated with an adverse prognosis. This inflammatory component may have important pathogenetic and prognostic roles because an outburst of inflammatory cytokines has the potential to increase the sensitivity of platelets to agonists, to turn the anticoagulant and vasodilator physiological properties of the endothelium into procoagulant and vasoconstrictor properties, and to cause plaque fissure by the release of proteolytic enzymes.

Comparison of coronary angiographic narrowing in stable angina pectoris, unstable angina pectoris, and in acute myocardial infarction.

Coronary angiographic findings were compared in patients who presented with acute myocardial infarction (AMI, n = 75), unstable angina pectoris (UAP, n = 36), or stable angina pectoris (SAP, n = 36) for > or = 2 years without evidence of any previous acute event and with an angiogram within 2 years of the initial symptoms. Angiograms were evaluated blindly for severity, extent (depending on the percentage of each coronary segment showing atherosclerosis), and pattern (discrete, < 3 loci of narrowings involving < 50% of any segment; diffuse, anything exceeding this). Patients in the SAP group had more narrowed arteries (2.4 +/- 0.7 vs 1.3 +/- 0.6 [p < 0.02] and 1.4 +/- 0.6 [p < 0.02]), more stenoses (6.0 +/- 3.3 vs 2.1 +/- 1.5 [p < 0.01] and 2.6 +/- 1.7 [p < 0.05]) and occlusions (1.3 +/- 1.1 vs 0.7 +/- 0.6 [p = 0.05] and 0.3 +/- 0.5 [p < 0.02]), and a greater extent index (0.9 +/- 0.5 vs 0.5 +/- 0.3 [p < 0.02] and 0.5 +/- 0.3 [p < 0.02]) than those in the AMI and UAP groups. Furthermore, a discrete pattern was less prevalent in patients with UAP than in those with SAP or AMI (3% vs 40% [p < 0.02] and 25% [p < 0.05], respectively). In conclusion, patients who present with acute coronary syndromes have less extensive atherosclerosis than those who present with chronic stable angina. Therefore, in the former group, coronary atherosclerosis appears to be more susceptible to ischemic stimuli responsible for acute coronary syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in vasodilatory response to dipyridamole between patients with angina and normal coronary arteries and patients with successful coronary angioplasty.

BACKGROUND: Previous studies reported a reduced coronary blood flow reserve, assessed by the intravenous administration of dipyridamole, in patients with angina and normal coronary arteries, and early after successful coronary angioplasty, which suggests the presence of small coronary vessel dysfunction. This study aimed to establish whether the mechanisms of small coronary vessel disease in these two groups of patients are similar. METHODS: The effects of the intracoronary infusion of adenosine and dipyridamole (maximum dose 2.7 and 7.5 mg/min, respectively) on coronary blood flow velocity were assessed in 11 patients with angina and normal coronary arteries (group A) and in 12 patients immediately after successful coronary angioplasty (group B) using a 0.018" Doppler wire. RESULTS: Baseline coronary blood flow velocity was significantly higher in group B than group A (34 +/- 14 versus 19 +/- 8 cm/s; P = 0.001). In group A, coronary blood flow velocity was higher during adenosine than dipyridamole infusion (74 +/- 17 versus 58 +/- 21 cm/s; P < 0.001), whereas in group B velocities were similar (85 +/- 30 versus 78 +/- 32 cm/s; NS). CONCLUSIONS: In patients with angina and normal coronary arteries, a maximal dose of adenosine causes a greater coronary dilation than that of dipyridamole. Given that dipyridamole operates mainly through an inhibition of adenosine re-uptake, it can only dilate the arteriolar segments exposed to endogenous adenosine. Therefore, the lower response to dipyridamole than to exogenous adenosine observed in patients with angina and normal coronary arteries suggests an impairment of the pre-arterioles that are not influenced by endogenous adenosine, resulting in a limited flow-mediated dilation in response to arteriolar dilation. Such an impairment is not apparent immediately after successful coronary angioplasty, where the most obvious abnormality is an increase of baseline coronary blood flow velocity.

Relation between myocardial infarction site and pain location in Q-wave acute myocardial infarction.

Location, severity, duration, and time course of pain were assessed in 104 consecutive patients with either first or second, anterior or inferior Q-wave acute myocardial infarction (AMI). Pain severity was assessed using a visual analog scale. Pain location and radiation were similar in 48 patients with anterior and 56 patients with inferior wall AMI. Pain duration (6.1 +/- 6.4 vs 6.5 +/- 5.4 hours, p = NS) and severity (68 +/- 21 vs 61 +/- 21 mm, p = NS) were also similar. The pain was continuous in 34 patients with anterior (71%) and in 42 with inferior (75%) wall AMI. Among the 41 patients who did not receive thrombolytic therapy, 18 patients with continuous pain had a higher creatine kinase peak level than the remaining 23 patients with intermittent pain or preinfarction angina, or both (2,065 +/- 1,017 vs 1,162 +/- 994 IU, p < 0.01). The incidence of gastrointestinal symptoms was slightly higher in patients with inferior than anterior wall AMI (70% vs 48%, p < 0.05). Among 32 patients admitted with a second AMI, pain location was similar in 14 who had both infarcts in the same myocardial region, but was different in 12 of 18 (67%) who had a first and second infarct in different regions (p < 0.001). Thus, patients with anterior or inferior wall AMI experienced pain in similar body regions. However, in patients who presented with > 1 AMI, different locations of the infarction pain were highly predictive of ischemia occurring in different myocardial regions. Finally, patients with preinfarction angina or intermittent pain tended to have smaller infarcts.

[Mechanisms of coronary microvascular dysfunction]. / Meccanismi della disfunzione microvascolare coronarica.

Abnormal constriction of coronary resistive vessels can induce angina and myocardial ischemia. The possibility that a microvascular vasomotor dysfunction could cause ischemia is in contrast with the well-known traditional notion that a metabolically induced vasodilation could compensate for the effect of an epicardial coronary stenosis. Vasoconstrictor stimuli can plausibly act on vessels situated immediately proximal (prearterioles) to those that can be dilated by ischemia metabolites (arterioles). This functional 2-compartment model of resistive vessels is based on the ability of different substances to cause opposite actions on resistive vessels with different sizes. The possible mechanisms of prearteriolar dysfunction, observed in patients with syndrome X, single vessel disease after a successful PTCA and in a subset of chronic stable patients include: an organic reduction of total vascular section; vascular smooth muscle hyperreactivity to heterogeneous constrictor stimuli; an impaired flow-mediated endothelium-dependent vasodilation (possibly due to a reduced NO and/or EDHF synthesis). The first and third hypothesis can only account for anginal episodes at effort while the second model could explain episodes occurring at rest and without an increase in heart rate. Those mechanisms causing an imbalance between myocardial oxygen supply and demand, induce an increased release of adenosine in order to promote a compensating vasodilation. Adenosine can possibly avoid the occurrence of ischemia but, being a powerful algogenic stimulus, causes pain. It is worth noting that the presence of patchy prearteriolar dysfunction induces areas with excessive release of adenosine. Since total vascular section is extremely large a massive adenosine spill-over can occur with a consequential boosting of algogenic and vasodilatory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of captopril on sympathetic preganglionic efferent activity in cats.

In 13 decerebrate cats, we studied the effects of captopril (10 mg/kg iv bolus) on the background discharge of thoracic preganglionic sympathetic fibers. After drug administration there was an initial reduction in systolic arterial pressure (SAP), which was followed by a later inhibition of sympathetic discharge (from 2.7 +/- 0.5 to 0.79 +/- 0.1 imp/0.1 s; P < 0.01). Captopril significantly reduced the excitatory response of sympathetic fibers to premature ventricular contraction (70 +/- 17 vs. 257 +/- 30%), inferior vena cava obstruction (176 +/- 56 vs. 315 +/- 85%) and asphyxia (143 +/- 20 vs. 245 +/- 51%). Vice versa the sympathetic response to aortic occlusion was unaffected (-58 +/- 8 vs. -62 +/- 6%). A similar reduction in sympathetic discharge was observed after captopril administration in anesthetized cats (n = 3). On the contrary, no changes in background neural discharge were noticed in decerebrate-spinalized cats (n = 5), despite comparable hemodynamic effects. These data indicate that captopril reduces sympathetic efferent activity and its responsiveness to excitatory stimuli. The lack of neural effects in decerebrate-spinalized cats is consistent with a brain stem site of action of captopril.

Beta-blocking effect of propafenone based on spectral analysis of heart rate variability.

RR variability was analyzed in 15 patients with ventricular arrhythmias to evaluate whether the antiarrhythmic action of propafenone is associated with alteration of neural control mechanisms. Before drug administration, spectral analysis of RR variability was characterized by 2 major components at low and high frequency, which are considered to reflect sympathetic and parasympathetic modulation of the heart period. After propafenone (600 to 900 mg/day), there was a marked reduction in RR variance (826 +/- 184 to 412 +/- 77 ms2; p < 0.05), although the mean RR interval was unchanged. The drug significantly reduced the low-frequency component (52 +/- 6 to 28 +/- 4 nu) and augmented the high-frequency component (39 +/- 6 to 55 +/- 5 nu). As a result, the low-/high-frequency ratio (an index of sympathovagal balance) decreased from 2.0 +/- 0.4 to 0.6 +/- 0.1. A positive correlation between serum levels and drug-induced changes in the low-frequency component was also observed. Furthermore, the increase in the low-frequency component induced by tilt (53 +/- 5 to 79 +/- 3 nu) was markedly attenuated after drug administration (27 +/- 5 to 54 +/- 7 nu). Thus, propafenone administration is associated with changes in spectral components that are consistent with a beta-blocking effect of the drug.

Spectral analysis of sympathetic discharge, R-R interval and systolic arterial pressure in decerebrate cats.

In 19 decerebrate and artificially ventilated cats, we analyzed, with a power spectral methodology, the variability simultaneously present in R-R interval and in thoracic preganglionic sympathetic outflow. R-R interval was characterized, as already described in humans and other experimental preparations, by two rhythmic components occurring at a frequency of about 0.1 Hz (low-frequency, LF) and at one corresponding to respiratory rate (high-frequency, HF) which, in these experiments, was set at 0.32 Hz. Two similar rhythmic components were also present in the sympathetic discharge. Arterial pressure changes were produced by aorta or vena cava flow obstruction in order to produce reflex responses in sympathetic activity. Reflex sympathetic excitations induced an increase in the LF component of both R-R interval and sympathetic discharge variabilities, while the HF components were simultaneously reduced. In contrast, reflex sympathetic inhibitions were accompanied by a decrease in LF components of both variability signals, while the HF components were simultaneously increased. A significant and positive correlation was found between changes in impulse activity and the amplitude of LF component of either R-R interval or sympathetic discharge variabilities. These data support the hypothesis that the low-frequency component of R-R variability can be used as a marker of sympathetic modulation.

Effects of mexiletine, propafenone and flecainide on signal-averaged electrocardiogram.

The effects of mexiletine, propafenone and flecainide on the parameters of signal-averaged electrocardiogram in 40 subjects with symptomatic and repetitive ventricular arrhythmias were studied. Mexiletine (n = 16) suppressed ventricular arrhythmias in 10 patients and did not produce any significant changes in filtered QRS duration (fQRS), root mean square voltage of the final 40 ms of filtered QRS (RMS40) or low amplitude terminal component duration (LAS40). Acute (n = 8, 450 mg) and chronic (n = 16, 600-1200 mg.day-1) administration of propafenone determined a significant increase in fQRS (from 123 +/- 2.2 to 139 +/- 3 ms) and a reduction in RMS40 (from 54 +/- 8.8 to 34 +/- 6.7 microV); as a consequence the incidence of ventricular late potentials rose from 43 to 62%. The observed effects were independent of anti-arrhythmic efficacy, which was 86% for this drug. Acute (n = 8, 200 mg) and chronic (n = 13, 200-300 mg.day-1) administration of flecainide was associated with a marked prolongation in fQRS (from 123 +/- 2.8 to 138 +/- 4.1 ms) and a reduction in RMS40 (from 69 +/- 11.5 to 47 +/- 11 microV); thus determining an increase in the incidence of ventricular late potentials from 29 to 48%. Changes in signal-averaged electrocardiogram were not related to drug efficacy, which was 81%. These data indicate that 1c anti-arrhythmic drugs consistently modified the parameters of signal-averaged electrocardiogram; the observed changes might reflect an inhomogeneous slowing of intramyocardial impulse propagation.

Signal averaging of pre- and post-extrasystolic beats in patients with ventricular arrhythmias.

To evaluate the effects of premature ventricular beats on the impulse conduction of adjacent sinus cycles, we compared the high amplification signal-averaged electrocardiogram parameters of the pre- and post-extrasystolic beats with those of the remaining sinus cycle. According to the duration of filtered QRS (fQRS), to the voltage of root mean square of the terminal 40 ms (RMS 40) and to the duration of low amplitude terminal components of the sinus cycles, ventricular late potentials were detected in nine out of 29 subjects. Patients with an abnormal signal-averaged electrocardiogram exhibited a longer fQRS (146 +/- 6 versus 116 +/- 2 ms), a reduced RMS40 voltage (18 +/- 2 versus 80 +/- 10 microV) and a prolonged duration of less than 40 microV components (42 +/- 4 versus 17 +/- 2 ms). Analysis of the pre-extrasystolic beats did not reveal any significant variation in the above parameters, showing a mean difference of 0.44 +/- 2.4 ms; 0.02 +/- 1.14 microV; 1 +/- 1.9 ms and of -1.45 +/- 1.02 ms; 3.5 +/- 8.6 microV; -0.7 +/- 0.84 ms respectively, for patients with and without ventricular late potentials. In addition, no significant variation was observed when the post-extrasystolic beats were considered. These results indicate that the sinus cycles adjacent to premature ventricular discharges do not present variations of signal-averaged electrocardiogram parameters that may suggest an influence of the ectopic beats on their intramyocardial impulse propagation.

Spectral analysis of sympathetic discharge in decerebrate cats.

To evaluate if the 0.1-Hz low-frequency oscillations of R-R interval are a reflection of rhythmical pattern of discharge of the sympathetic outflow, we analysed in 10 decerebrate cats heart rate and cardiac sympathetic efferent discharge variability. A predominant low-frequency component was present in both signals, thus suggesting that the 0.1-Hz rhythm indeed reflects a rhythmical pattern of discharge of sympathetic outflow.

Effects of tilt and exercise on signal-averaged electrocardiogram after acute myocardial infarction.

To determine whether enhanced sympathetic activity could alter a non-invasive index of cardiac instability, we analysed the effects of 90 degrees head-up tilt and submaximal exercise stress test on high amplification signal-averaged electrocardiogram in 64 patients after acute myocardial infarction. At rest, ventricular late potentials were detected in 25% of patients, characterized by a significant prolongation of filtered QRS complex (137 +/- 3 vs 115 +/- 2 ms) and of its components smaller than 40 microV (38 +/- 2 vs 16 +/- 1 ms), as well as by a reduced root mean square voltage calculated for the terminal 40 ms of QRS complex (RMS40 voltage) (19 +/- 1 vs 75 +/- 9 microV) in comparison to patients without micropotentials. Sympathetic activation induced by tilt caused a significant increase in heart rate (from 67 +/- 3 to 79 +/- 3 beats min-1) but did not modify either the incidence of ventricular late potentials or the values of any of the signal-averaged electrocardiogram parameters considered. In 19 patients, recordings were also obtained during a submaximal bicycle exercise stress test at a heart rate of 114 +/- 4 beats min-1 and with systolic arterial blood pressure at 153 +/- 6 mmHg. No effect on signal-averaged electrocardiogram parameters was detectable during this experimental intervention. These data indicate that after myocardial infarction, sympathetic activation does not seem to modify signal-averaged electrocardiogram parameters.

Restraining effect of captopril on cardiovascular sympathetic efferent neural activity.

In 13 decerebrate cats we studied the effects of captopril (10 mg/kg, intravenous bolus) on the background cardiac preganglionic sympathetic discharge and on its responsiveness to brief baroreceptor deactivations induced by premature ventricular contractions. Captopril caused a significant reduction of 57 +/- 7% (from 2.4 +/- 0.4 impulses/0.1s) in sympathetic discharge, with a mean latency of 35 +/- 3 min from the time of drug administration. In addition, the increase in cardiac sympathetic firing during premature ventricular contractions was markedly reduced, from 257 +/- 30% to 70 +/- 17%, before and after administration of captopril. These data indicate that captopril is not only likely to inhibit sympathetic discharge to the heart, but is also likely to restrain the excitatory sympathetic responses to baroreceptor deactivation.