Influence of thrombolytic therapy on the evolution of baroreflex sensitivity after myocardial infarction

Influence of thrombolytic therapy evolution of baroreflex sensitivity myocardial infarction

on the after

Depressed baroreceptor sensitivity (BRS) has been associated with an increased risk of ventricular arrhythmias and sudden cardiac death after myocardial infarction, but the influence of thrombolytic therapy on BRS has not been examined. To determine the effect of thrombolytic therapy on the evolution of BRS after myocardial infarction, BRS was assessed at 6 days, 6 weeks, and 3 months in 76 patients, 53 (70%) of whom had received thrombolytic therapy. The mean age (57 vs 57 years), sites of infarction, and the proportion of patients taking ,&blockers (66% vs 52%) did not differ between patients who did and those who did not receive thrombolytic therapy. There was no difference in predischarge mean left ventricular ejection fractions (42% vs 46%) between the two groups of patients, but mean baseline BRS was 9.2 (0.6) mseclmm Hg in patients who were treated with thrombolysis and 5.9 (1.3) msec/mm Hg in those who were not (p = 0.03). At 6 weeks the corresponding values were 9.7 (1.1) and 11.1 (2.6) mseclmm Hg @ = 0.6) and at 3 months 9.1 (1.0) and 6.5 (1.1) mseclmm Hg (p = 0.07). At baseline 13% of patients who were treated with thrombolysis and 13% of those who were not had BRS C3.0 mseclmm Hg, but at 3 months 9% of patients who were treated with thrombolytic agents compared with 17% of those who had BRS ~3.0 msec/mm Hg. In conclusion, early after myocardial infarction mean BRS was higher in patients treated with thrombolysis compared with nontreated patients. Similar trends were noted 3 months later, and the proportion of patients with low BRS was smaller in those given thrombolytic therapy compared with those who were not. Thrombolytic therapy should reduce the incidence of early and late sudden cardiac death after myocardial infarction. (AM HEART J 1993;125:285.)

Olusola Odemuyiwa, MD, Thomas Farrell, MRCP, Anne Staunton, SRN, James Sneddon, MRCP, Jan Poloniecki, DPhil, David Bennett, MD, Marek Malik, MD, and John Camm, MD London, England

Thrombolytic agents reduce the number of deaths from circulatory failure in acute myocardial infarctionly 2 presumably by reperfusing the infarct-related artery, reducing infarct size, and thus preserving ventricular function.3-5 However, the influence of thrombolytic therapy on the incidence and predictors of out-of-hospital sudden death and other aspects of cardiac function have been relatively ignored. Results of recent studies have shown that baroreceptor sensitivity (BRS) is depressed during the first 3 months after myocardial infarction,7,s the period of

*

From the Department of Cardiological Sciences, St. George’s Hospital Medical School. Received for publication July 7,1992; accepted August 24, 1992. Reprint requests: Dr. 0. Odemuyiwa, Department of Cardiological Sciences, St. George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE. Copyright @ 1993 by Mosby-Year Book, Inc. 0002-8703/93/$1.00 + .lO 4/l/42541

greatest risk of sudden death. However, markedly depressed BRS early after infarction also identifies patients who remain at high risk for development of serious ventricular arrhythmias or sudden death up to several months after infarction.g-ll These preliminary findings indicate that either BRS remains depressed long after infarction in such patients or markedly depressed BRS early after myocardial infarction may identify patients with a long-term predisposition to sudden death, which is not altered by any subsequent changes in BRS itself. Thrombolytic therapy may therefore influence the incidence of sudden death by affecting either the evolution of BRS or the proportion of patients with markedly depressed BRS. Alternatively, if thrombolytic therapy reduced the incidence of sudden death without affecting BRS, this would have an impact on the practical value of routine BRS assessment in postinfarction patients. This prospective study examines the influence of thrombolytic therapy on the evolu285

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Table 1. Reasonsfor excluding 33 patients Reasons

for exclusion

Refused to take part Heart failure Administrative reasons Sinus node disease/atria1 fibrillation Unstable angina/reinfarction Insulin-dependent diabetes mellitus Change of treatment during study History of hypertension Total

n

8 7 2 3 7 3 2 1 33

tion of BRS during the first 3 months after myocardial infarction. METHODS Between April and November 1991, a total of 109 consecutive patients were admitted directly to our hospital with acute myocardial infarction and survived to the fifth hospital day. Myocardial infarction wasdiagnosedaccording to standard criteria. lo,l1 Intravenous streptokinase (1.5 million units) was administered to 78 (72%) of these patients within 6 hours (mean 3.5 hours) of the onset of major symptoms. Thirty-one patients did not receive thrombolytic therapy either becausethey arrived too late at the hospital or becauseof conventional contraindications to thrombolytic therapy. The most important contraindications to streptokinase in the study were active peptic ulceration and suspectedaortic dissection.Patients were admitted to the study on the fifth hospital day, and BRS tests were carried out on the sixth hospital day and repeated 6 weeksand 3 months after infarction. The study was approved by the district ethics committee, and each patient gave informed consent. Baroreceptor sensitivity testing. BRS testing wascarried out based on the method of Smyth et a1.12Patients were studied in the fasting state and in the supineposition. Continuous noninvasive arterial pressurewasrecorded by meansof infrared digital plethysmography (Ohmeda2300 Finapres blood pressuremonitor, Ohmeda Canada, Mississauga,Canada).This method hasbeenvalidated for the measurementof arterial blood pressure,13, l4 and in our laboratory the correlation coefficient between invasive and noninvasive arterial pressuresis 0.9. When the heart rate and blood pressurewere stable, an intravenous bolusof 0.2 mg of phenylephrine was given to attain a rise in systolic blood pressureof between15 and 40 mm Hp. If this wasnot achieved, a rest period was observed until the heart rate and blood pressurereturned to baselinelevels,and a higher doseof phenylephrine wasthen given. This target increase in blood pressure was achieved even in patients taking P-blockers. The test was repeated until at least three recordings were made at the optimum dose. Baroreflex sensitivity wascalculated from the first sustainedincrease in blood pressure.The beat-to-beat variation in systolic blood pressure(systolic blood pressureminusbaselinesystolic pressure)was plotted againstthe beat-to-beat varia-

February 1993 Heart Journal

tions in eachimmediately ensuingR-R interval. The slope of the regressionline of this plot with a correlation coeficient >0.8 wastaken asbaroreflex sensitivity. The meanof three such slopeswastaken asthe final result in msec/mm Hg. As suggestedby La Rovere et a1.,ga BRS value of less than 3.0msec/mmHg wasconsideredmarkedly depressed. The mean changein blood pressurewas25 mm Hg (range 15to 35 mm Hg), and the meandoseof phenylephrine used was 0.25 mg. As we reported in a different group of patients,” there was no correlation between BRS and either the doseof phenylephrine or the phenylephrine-induced changein systolic blood pressure.Left ventricular ejection fraction wasdetermined by the multiple gated acquisition technique, before or shortly after patients were dischargedfrom the hospital. Statistical analysis. Data are presented as mean values & SD and when appropriate as mean values with standard errors in parentheses. Single comparisons of mean values were made by a two-tailed paired t test for paired observations, but comparisonsbetween groups of the differences betweenthe meanvalues of BRS were carried out by analysisof variance with ageand ejection fraction ascovariates. The 95“; confidencelimits of the differencesbetween two meanswere calculated as appropriate. Relationships between continuous variables were examined by means of Pearson’sproduct-moment correlation coefficient with one-tailed significance. Categorical variableswere compared by meansof chi-square analysis.A p value <0.05 wasconsideredsignificant. As in the study by Schwartz et al.,; to examine any contribution that the unequal sizesof the patient groupsmay have madeto our results, the patients treated with thrombolysis were assigned by date of admissionto one of two groups eachcomprising 26 patients. The two subgroupshad similar mean BRS values at baseline,9.6 (0.3) msec/mmHg versus 8.9 (0.3) msec/mm

Hg (p = NS) and at 6 weeks and 3 months.

Exclusions (Table I). Patients with insulin-dependent diabetesmellitus, heart failure (New York Heart Association class or higher

2), sinus or atrioventricular

node dys-

function, or a history of systemic arterial hypertension at baselinewere excluded from the study, as were those who subsequently had a reinfarction, heart failure, or unstable angina and those who required revascularization. Also excluded from the study were two patients who were given fi-blockers after the start of baselineBRS testing. Of the 78 patients who received thrombolytic therapy, 25 (32I’;,) were excluded from the study comparedwith 8 (26”;’ ) of 31 who did not receive thrombolytic

therapy

(NS). Data from 76

patients are presented. RESULTS

BRS 5 to 11 of 90 f ence in

was assessed a mean of 6.5 + 2.3 days (range days) and then a mean of 40 f 9 and a mean 20 days after infarction. There was no differthe interval between infarction and BRS as-

sessment between patients who did and those who

did not receive thrombolytic therapy (Table II). Clinical characteristics (Table III). There were 62

Vduma

125

Number

Thrombolysis

2, Part 1

Table II. Interval between infarction and BRS test during follow-up in each group Test

interval

Characteristics

test

Baseline 6 weeks

3 months

TT* 6.8 (2.1) 41 (8.7) 95 (10)

TT*

No TTf

p Value

53 56.5 24 (45 %%) 38 (72%) 3 (6%) 44 (83%) 42 36 (68%)

23 56.5 12 (52%) 14 (61%) 6 (3%)) 18 (78%) 46 (14) 12 (52%)

NS NS NS NS NS 0.2 NS

(days) No TTj 7.3 (2.6) 39 (15) 86 (28)

p Value NS NS NS

Standard arrora in parentheses; NS, not significant. *Received thrombolytic therapy. tDid not receive thrombolytic therapy.

(82%) male patients, 36 (47 %) patients with an anterior infarction, 40 (53 % ) with an inferior infarction, and 24 (32%) with a non-Q wave infarction. Treatment was determined by the attending physician. Among the 76 patients, 48 were taking ,&blockers, five of whom were also taking oral nitrates and a dihydropyridine calcium antagonist. Nitrates and calcium antagonists were combined in three other patients, six other patients were receiving nitrate monotherapy, and three were on a single-therapy regimen of calcium antagonist; five patients were taking diuretics. None of the patients studied was taking angiotensin converting enzyme inhibitors. Medication was not altered during follow-up. As we have reported in a different group of patients,lO, l1 there were no significant complications associated with BRS testing. Clinical events. Among the 78 patients who received streptokinase three (4 % ), compared with four (13 % ) of 31 patients who did not receive streptokinase, had heart failure in the hospital; six (8%) patients who received streptokinase and one (3 % ) patient who did not receive streptokinase had unstable angina in the hospital. One patient who had received streptokinase had a reinfarction. A 54-year-old man with two-vessel disease and an ejection fraction of 44 % , but BRS values of 5.1 msec/mm Hg at baseline, 8.2 msec/mm Hg at 6 weeks, and 3.1 msec/mm Hg at 3 months, died suddenly 6 months after infarction. This patient had received streptokinase. Influence of age and left ventricular function on BRS. Baseline BRS correlated inversely with age (r = -0.47, p < O.OOl), but the influence of age on BRS at 6 weeks (r = -0.25, NS) and at 3 months (r = -0.14, NS) was less marked. There were 45 (60 % ) patients aged <60 years; 4 (9%) of them and 6 (20%) of the remaining 31 patients had markedly depressed BRS at baseline (NS). Age was used as a covariate in between-group comparisons of mean BRS. Baseline BRS correlated with BRS at 6 weeks (r = 0.8, p < 0.001) but not with BRS at 3 months. BRS at 6

207

Table Ill. Clinical characteristics of the patients studied

Number BRS

on baroreflex sensitivity

Meanage(yr) Anterior MI Q-wave MI Previous MI Males Mean LVEF @Blockers

MI, Myocardial infarction; LVEF, left ventricular significant. *Received thrombolytic therapy. tDid not receive thrombolytic therapy.

ejection fraction;

NS, not

days did not correlate with left ventricular ejection fraction (r = 0.2) and neither did BRS at 6 weeks (r = 0.14) or at 3 months (r = 0.11). Evolution of BRS in the whole patient population. The evolution of BRS is represented in Fig. 1. Mean ejection fraction was 42 + 14 in patients treated with streptokinase and 46 f 13 in patients not treated with streptokinase (p = 0.2). BRS at baseline ranged from 1.4 to 35 msec/mm Hg and rose from a mean of 8.6 (0.9) msec/mm Hg to a mean of 10.1 (1.1) msec/mm Hg at 6 weeks (p = 0.09, 95% confidence interval = -2.5 to 0.5). Mean BRS at 3 months was 8.4 (0.8), with a range of 0.5 to 29.3 msec/mm Hg, but was not significantly different from the mean baseline BRS or the mean BRS at 6 weeks. Mean baseline BRS was 5.9 (1.3) msec/mm Hg in patients who did not receive thrombolytic therapy and 9.2 (0.8) msec/mm Hg in patients who did (p = 0.03). At 6 weeks the corresponding values were 11.1 (2.8) msec/mm Hg and 9.7 (1.1) (p = 0.6) and at 3 months 6.5 (1.1) and 9.1 (1.0) (p = 0.07, 95% confidence interval = 1.4 to 3.8). Predischarge proportion of patients with markedly depressed BRS. Thrombolytic therapy had a less discernible influence on the number of patients with markedly depressed BRS. At baseline 7 (13 % ) of the 53 patients who had been treated with streptokinase and 3 (13%) of the 23 who had not received streptokinase had markedly depressed BRS (i.e., <3.0 msec/mm Hg). At 6 weeks 6 (11%) of the patients who had been treated with streptokinase and 2 (9 % ) of the 23 who had not had a BRS value <3.0 mseclmm Hg. At 3 months 5 (9%) of the 53 patients who had been treated with streptokinase but 4 (17 % ) of the 23 patients who had not received thrombolytic therapy had BRS <3.0 msec/mm Hg. The most important predictor of markedly depressed BRS at 3 months was a BRS value <3.0 msec/mm Hg at 6 days; 4 (40 % ) of the 10 patients with BRS <3.0 msec/mm Hg at

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February 1993 Heall Journal

Fig. 1. Evolution of baroreceptor sensitivity (BRS). In patients who did not receive thrombolytic therapy mean BRS rose from 5.9 msec/mm Hg to 11.1 msec/mm Hg (p = 0.031,from which it fell to 6.5 (p = 0.07). There was little change in mean BRS in patients treated with thrombolysis. BRSZ, BRSB, BRSS, Mean baroreceptor sensitivity at 6 days, 6 weeks, and 3 months, respectively.

baseline, compared with only 5 (8%) of 66 patients with BRS >3.0 msec/mm Hg at baseline, had BRS <3.0 msec/mm Hg at 3 months (p < 0.05, Fig. 2). Influence of low ejection fraction on the evolution of BRS. Mean ejection fraction was 52 * 8% in patients with an ejection fraction ~40 ‘% and 29 f 7 % in the 27 patients with an ejection fraction <40%. Mean BRS at baseline was 9.9 (1.0) msec/mm Hg and 6.3 (0.7) msec/mm Hg in the respective groups (p = 0.01). The corresponding figures were 10.7 and 8.2 msec/mm Hg at 6 weeks (p = 0.2) and 9.3 and 7.6 msec/mm Hg at 3 months (p = 0.4). Of the 27 patients with an ejection fraction <40 70, six (22% ) had BRS <3.0 msec/mm Hg at baseline compared with four (8 ‘T;i) with an ejection fraction 140%. At 6 weeks four (15 % ) of those with an ejection fraction <40 SCand two (4%) with an ejection fraction ~40% had BRS <3.0 msec/mm Hg. The corresponding figures at 3 months were 3 (11% ) and 6 (12 % ). There was no important difference in baseline clinical characteristics between patients who were and those who were not

taking P-blockers (Table IV); neither were there any differences in the evolution of BRS between the two groups. DISCUSSION Background. The central nervous system receives and integrates input from the sensory endings of afferent sympathetic and vagal fibers, and an increase in cardiac sympathetic activity in particular has been shown to impair the baroreceptor reflex.15 Myocardial infarction may result in mechanical distortion of these sympathetic fibers and disruption of vagal afferent fibers,16-l8 leading to depressed BRS. The subsequent improvement in BRS has been attributed to receptor necrosis and adaptation of the receptors to continuing mechanical and chemical stimuli.lg, 2o Compensation by one pathway for the disruption of another, as in dogs with chronic denervation of the aortic arch baroreceptors21 may also account for the recovery of BRS after myocardial infarction. Evolution of BRS. Schwartz et a1.7found that com-

Volume Number

125 2, Parl

Thrombolysis

1

on

baroreflex sensitivity

289

BRS (msec/mmHg) 16

r

l-

14 12 10 8 6

6 Days

6 Weeks

3 Months

Fig. 2. Individual courseof baroreceptor sensitivity (‘RS) in patients with markedly depressedBRS at

6 days and 3 months.

pared with normal control values, BRS was depressed 18 days after infarction and returned to normal and achieved stability only after 3 months. However, Osculati et a1.8found that BRS returned to normal as early as 10 days after infarction. This discrepancy may be due to differences between the respective control groups. In the study by Schwartz et a1.,714 of the 21 control subjects were healthy volunteers, whereas in the latter study8 the five control subjects had been admitted to the hospital with atypical chest pain and may well have had relatively depressed BRS. Neither study considered the potential effect of thrombolytic therapy on BRS. The timing of BRS assessmentwas different in the present study. We found, however, that when the patient group was taken together, BRS values at 6 days and 3 months were similar. These findings are consistent with those reported by Osculati et a1.8 However, we found that the baseline BRS was lower in patients not treated with streptokinase, even though the mean baseline left ventricular ejection fraction was similar in the two groups of patients. It is unlikely that these differences in mean BRS between the patient groups existed before infarction, because the patients did not differ in any other im-

Table

IV. Relationship between P-blocker therapy and

BRS p-blockers

Number Mean EF Mean BRSl Mean BRS2 Mean BRS3

No P-blockers

p Value

48 42 f 14 7.6 10.2

28 44 * 13 9.1

0.5 0.3 0.8

8.3

8.5

0.9

BRSI, BRSZ, BRS3, Baroreceptor sensitivity months, respectively; EF, ejection fraction.

9.1

at baseline, 6 weeks, and 3

portant clinical respect either on admission to the hospital or at the time they were recruited for the study. Alternatively, because thrombolysis reduces infarct size, patients treated with thrombolysis may have sustained less disruption of ventricular vagal and sympathetic afferent fibers than patients who did not receive streptokinase. Moreover, a patent infarct-related artery patency may wash out ischemic catabolites and prevent aneurysm formation and ventricular remodeling. 22We speculate that the decline in BRS in the patients who did not receive thrombolytic therapy may be the result of autonomic imbalance consequent to progressive infarct expan-

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sion and left ventricular dysfunction. The relationship between the subsequent evolution of BRS and prognosis in these patients requires further study. One patient in whom BRS fell from 8.2 msec/mm Hg at 6 weeks to 3.1 msec/mm Hg has died suddenly. Proportion

of patients

with markedly

depressed

BRS.

The proportion of patients with markedly depressed BRS at baseline was similar to that previously reported9 and was the same in patients who did and those who did not receive thrombolytic therapy. There was also a tendency for markedly depressed BRS early after infarction to remain depressed. However, at 3 months proportionally twice as many patients who did not receive thrombolytic therapy compared with BRS those whodid had <3.0 msec/mm Hg. Although statistical significance was not reached because of the small numbers, this finding mirrors the trends in mean BRS and may be clinically important. Study limitations. It may be argued that the BRS in the study population should have been compared with that in a normal control group. However, the study aimed to examine the effect of thrombolytic therapy on BRS and not to repeat previous studies, which have established that BRS is depressed in infarct patients compared with normal control subjects. 7,8 Indeed, to be protective in postinfarction patients, BRS may need to be higher than in agematched control subjects. A randomized study of thrombolytic therapy in acute myocardial infarction is now unethical, and we believe that because the study was prospective and based on a consecutive series of patients, it is likely to closely reflect the population found in a clinical practice. The difference in sample size also reflects the relative numbers of patients currently being treated with streptokinase. Nevertheless, when the group that received thrombolytic therapy was divided into two, similar differences in mean BRS were found between each group treated with thrombolysis and the patients receiving thrombolytic therapy. Another potential criticism is that the patency of the infarct-related artery was not assessed.However, the time from the onset of symptoms to the administration of streptokinase in the present study is similar to that in clinical practice and in studies showing the benefits of thrombolytic therapy with regard to mortality’. 2 and artery patency.23 Finally, apart from excluding patients with a history of hypertension or diabetes, it was impossible to estimate and correct for any differences in BRS between patient groups that might have existed even before infarction. We believe, however, that this potential shortcoming is a feature of any such study and does not materially affect our conclusions.

February 1993 Heart Journal

Clinical implications. If, as in postinfarction animals, depressed BRS is an important correlate of the risk of ventricular fibrillation during acute coronary occlusion,z4 results of the present study indicate that thrombolytic therapy should reduce the number of sudden cardiac deaths early after myocardial infarction. Thrombolytic therapy also appears to have an effect on the subsequent course of BRS and may thus reduce the incidence of sudden deaths late after infarction. If this is confirmed, the assessmentof BRS should still be of prognostic value in the thrombolytic era. We have also shown that markedly depressed BRS early after infarction tends to remain depressed during follow-up. This explains why low BRS early after infarction predicts arrhythmic events even late after infarction. Whether measures designed to improve vagal reserve, such as exercise training,25 will improve BRS and reduce the risk of sudden death in such patients is unclear. REFERENCES

Italian0perlo StudiodellaStreptochinasi nell’Infarto Miocardico (GISSI). Effectivenessof intravenousthrom-

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bolytic treatment in acute myocardial infarction. Lancet 1986;1:397-402. ISIS2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-60. Jeremy RW, Hackworthy RA, Bautovich G, Hutton BF, Harris PJ. Infarct artery perfusion and changes in left ventricular volume in the month after myocardial infarction. J Am Co11 Cardiol 1987:9:989-95. White HD, Norris RM, Brown MA, et al. Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987;317: 850-5. Martin GV, Sheehan FH, Stadius M, et al. Intravenous streptokinase for acute myocardial infarction: effects on global and regional systolic function. Circulation 1988;78:258-66. Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival. Should the paradigm be expanded? Circulation 1989;79:441-4. Schwartz PJ, Zaza A, Pala M, Locati E, Beria G, Zanchetti A. Baroreflex sensitivity and its evolution during the first year after myocardial infarction. J Am Co11 Cardiol1988;12:629-36. Osculati G, Grassi G, Giannattasio C, Seravalle G, Valagussa F. Zanchetti A, Mancia G. Early alterations of the baroreceptor control of heart rate in patient with acute myocardial infarction. Circulation 1990;81:939-48. La Rovere MT, Zaza A, Stone HL, Specchia G, Schwartz PJ. Baroreflex sensitivity, clinical correlates and cardiovascular mortalitv among patients with a first myocardial infarction: a prospective study. Circulation 1988,78:816-24. Farrell TG. Paul V. Crinns TR. Malik M. Bennett DE. Ward DE, Camm’AJ. Barbreflex sensitivity and’electrophysidlogical correlates in patients after acute myocardial infarction. Circulation 1991;83:945-52. Farrell T, Odemuviwa 0, Bashir Y, Cripps T, Malik M, Ward D, Camm AJ. Theprognostic value of baroreceptor sensitivity in acute mvocardial infarction. Br Heart J 1992:67:129-37. Smyth HS: Sleight P, Pickering GW. Reflex regulation of arterial pressure during sleep in man. Circ Res 1969;24:109-21. Parati G, Casadei R, Groppelli A, Rienzo M, Mancia G. Com-

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parison of finger and intraarterial blood pressure monitoring at rest and during laboratory testing. Hypertension 1989;13: 647-55. Imholz BPM, Settels JJ, van den Meiracker AH, Wesseling KH, Wieling W. Noninvasive beat to beat finger blood pressure measurement during orthostatic stress compared to arterial pressure. Cardiovasc Res 1990;24:214-21. Schwartz PJ, Pagani M, Lombardi F, Malliani A, Brown AM. A cardio-cardiac sympathovagal reflex in the cat. Circ Res 1973;72:215-20. Thoren PN. Activation of left ventricular receptors with nonmedullated vagal afferent fibers during occlusion of a coronary artery in the cat. Am J Cardiol 1976;37:1046-51. Malliani A, Recordati G, Schwartz PJ. Nervous activity of afferent cardiac sympathetic fibers with atria1 and ventricular endings. J Physiol 1973;229:457-69. Barber MJ, Mueller TM, Davies BG, Gill RM, Zipes DP. Interruption of sympathetic and vagal-mediated afferent responses by transmural myocardial infarction. Circulation 1985;72:623-31. Barber MJ, Mueller TM, Henry DD, Fetten SJ, Zipes DP. Transmural myocardial infarction in the dog produces sym-

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Estimation of anterior infarct size with body surface QRST integral maps in the presence of abnormal ventricular activation sequence in dogs The possibility of estimating infarct size with body surface QRST integral (lo& maps was investigated in dogs. iQxsT maps were constructed from 874ead body surface ECGs, which were recorded 1 week after the production of anterior myocardial infarction during artificial pacing that simulated normal conduction, left bundle branch block, and Wolff-Parkinson-White syndrome in 11 dogs. Small differences were observed between the l~xsr maps of the normal conduction and left bundle branch block models (I = 0.93, root mean square difference = 8.71 mVmsec) and between the normal conduction and Wolff-Parkinson-White models (r = 0.96, root mean square difference = 6.03 mvmsec). Summation of the QRST integral values over the body surface leads (QRST index) inversely correlated with infarct size in all three conductions models: r = -0.91 (p < 0.001) in the normal conduction model; r = -0.81 @ < 0.001) in the left bundle branch block model; and r = -0.86 (p < 0.001) in the Wolff-Parkinson-White model. These results show that lossr maps permit noninvasive estimation of infarct size, even in the presence of abnormal activation sequences. (AM HEART J 1993;125:291.)

Yoshio Ichihara, MD, Makoto Hirai, MD, Hiroshi Hayashi, MD, Yasushi Tomita, MD, Masayoshi Adachi, MD, Akira Suzuki, MD, Makoto Tsuda, MD, Makoto Nagasaka, MD, and Hidehiko Saito, MD Nagoya, Japan

From the Division of Cardiology, First Department of Internal Nagoya University School of Medicine, Nagoya, Japan. Received for publication Feb. ‘7, 1992; accepted Aug. 10, 1992. Reprint requests: Makoto Hirai, MD, Division ment of Internal Medicine, Nagoya University rumai-cho Showa-ku, Nagoya 466, Japan. Copyright

Q 1993

000%8703/93/$1.00

by Mosby-Year + .lO

4/l/42653

Book,

of Cardiology, First School of Medicine,

Medicine,

Depart65 Tsu-

A variety of methods have been used to assessinfarct size and cardiac function after an infarction. They include cardiac enzyme measurements, radionuclide imaging, two-dimensional echocardiography, conventional ECG, chest x-ray studies, right heart catheterization, and left heart catheterization. Among

Inc.

291