Vagal Enhancement Linking Abnormal Blood Pressure Response and Subendocardial Ischemia in Hypertrophic Cardiomyopathy

An abnormal blood pressure response to exercise has been reported to be associated with left ventricular subendocardial ischemia in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism remains unclear. We report a case of HCM with an abnormal blood pressure response and subendocardial ischemia, in which the analysis of heart rate variability revealed exercise‐induced vagal enhancement. The present case highlights the possible mechanism linking abnormal blood pressure response and left ventricular subendocardial ischemia in patients with HCM.     

Electrocardiographic changes as a marker of improved subendocardial ischemia in a patient with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) patients sometimes develop subendocardial ischemia without coronary artery stenosis. We report a case of non-obstructive HCM, in which electrocardiographic changes were observed with improvement of subendocardial ischemia. A 76-year-old man presented with chest pain on exertion. The electrocardiogram revealed left ventricular (LV) hypertrophy with repolarization abnormalities. No coronary stenosis was found on computed tomography angiography, but thallium-201 exercise scintigraphy revealed transient LV cavity dilation after exercise, consistent with subendocardial ischemia. His chest symptoms disappeared after starting verapamil. Transient LV cavity dilation improved without a reduction in exercise tolerance, as did electrocardiographic abnormalities without any changes on echocardiography.     

Septal Q wave as a marker of septal ischemia in hypertrophic cardiomyopathy.

BACKGROUND: Small Q waves in the left lateral leads are termed septal q waves, and their response to exercise has been reported to be a marker of septal ischemia in coronary artery disease. Patients with hypertrophic cardiomyopathy (HCM) sometimes develop septal ischemia in the absence of coronary stenosis, but little data are available concerning the association of the septal q wave response with septal ischemia. METHODS AND RESULTS: Exercise electrocardiography and Tc-99m-tetrofosmin myocardial scintigraphy were recorded to detect myocardial ischemia in 29 HCM patients with asymmetric septal hypertrophy. The septal q wave amplitude was summed up in V(5) and V(6) during exercise testing, and the results were correlated with septal ischemia defined as a regional septal ischemia or a part of diffuse subendocardial ischemia. A decrease in the sum of the septal q wave amplitude during exercise testing yielded a sensitivity of 100% and specificity 33% for regional septal ischemia, and a sensitivity of 100% and specificity of 43% for diffuse subendocardial ischemia, although an absent septal q wave at rest provided a low sensitivity for the detection of regional septal ischemia (43%) and diffuse subendocardial ischemia (33%). CONCLUSIONS: The septal q wave response to exercise is a useful marker of septal ischemia in HCM with asymmetric septal hypertrophy.     

Exercise-induced ST-segment depression and myocardial ischemia in patients with hypertrophic cardiomyopathy: myocardial scintigraphic study

OBJECTIVES: Patients with hypertrophic cardiomyopathy (HCM) sometimes develop myocardial ischemia during exercise in the absence of coronary lesions. The relationship between myocardial ischemia and ST-segment depression was investigated during exercise testing in patients with HCM. METHODS: Regional hypoperfusion and/or transient left ventricular cavity dilation, a parameter of subendocardial hypoperfusion, were assessed on exercise 99mTc-tetrofosmin myocardial scintigraphy in 42 patients with non-obstructive HCM. The scintigraphic results were further correlated with the ST-segment responses to exercise. RESULTS: Regional hypoperfusion or transient left ventricular cavity dilation were observed in 19 (45%) or 16(38%)patients with HCM, respectively. The incidence of ST-segment depression > or = 0.1 mV during exercise testing was similar in HCM patients with regional hypoperfusion, with transient left ventricular cavity dilation, and without hypoperfusion (42%, 38%, 38%, p = 0.95). Furthermore, exercise-induced ST-segment depression > or = 0.1 mV occurred similarly irrespective of symptoms, exercise tolerance, the degree or the site of hypertrophy, or the presence or absence of resting ST-segment depression. CONCLUSIONS: ST-segment depression during exercise testing was common in patients with HCM, but seems to be an unreliable marker of myocardial ischemia as assessed by exercise scintigraphy.     

R-wave amplitude response to myocardial ischemia in hypertrophic cardiomyopathy

Background and Purpose

R-wave amplitude change during exercise has been reported to enhance diagnostic value for myocardial ischemia in coronary heart disease.

Methods

We summed up R-wave amplitude in all the 12 leads during exercise testing and correlated the results with regional myocardial ischemia or diffuse subendocardial ischemia as detected by scintigraphy in 49 patients with hypertrophic cardiomyopathy (HCM) and 16 controls.

Results

The sum of R-wave amplitude decreased during exercise in patients with HCM (mean, 12.4 mV to 11.7 mV, P < .01) as well as in controls (8.0 mV to 7.7 mV, P < .05). Percent changes in the sum of R-wave amplitude did not differ between 4 subgroups of patients with HCM: one having both regional and subendocardial ischemia, one only the former, one only the latter, and one neither of them (mean, 6.5%, 7.7%, 4.6%, and 5.1%; P = .79).

Conclusions

R-wave amplitude response to exercise failed to demonstrate myocardial ischemia in our patients with HCM.     

Exercise-induced abnormal blood pressure responses are related to subendocardial ischemia in hypertrophic cardiomyopathy

Objectives. We examined by thallium-201 scintigraphy whether exercise-induced abnormal blood pressure response (BPR) is related to myocardial ischemia.

Background. Hemodynamic instabilities during exercise in patients with hypertrophic cardiomyopathy (HCM) are considered to be caused by abnormal reflex control of vascular resistance.

Methods. In 105 patients with HCM, exercise thallium scintigraphy was performed by means of a multistage, symptom-limited bicycle ergometer exercise test.

Results. Eighty-eight patients had normal BPR (≥25 mm Hg from baseline to peak exercise), and 17 had abnormal BPR (<25 mm Hg). Clinical characteristics including age, the prevalence of obstruction, New York Heart Association functional class and echocardiographic measurements were similar between the two groups. Left ventricular end-diastolic pressure was significantly higher in patients with abnormal BPR than in those with normal BPR (18 ± 8 vs. 14 ± 5 mm Hg, p < 0.05). Exercise-induced perfusion abnormalities including fixed and reversible perfusion defects, and left ventricular cavity dilatation (LVCD) were identified in 72 (69%) of 105 study patients. Left ventricular cavity dilatation indicates subendocardial hypoperfusion and is a marker of diffuse subendocardial ischemia. The prevalence of fixed or reversible perfusion defects was similar between the two groups. Patients with abnormal BPR had the higher prevalence of LVCD as compared to those with normal BPR (47.1 vs. 10%, p < 0.0002). Multiple logistic regression analysis revealed that LVCD was independently associated with abnormal BPR (odds ratio 3.76, 95% confidence interval 1.61 to 8.76).

Conclusions. Exercise-induced abnormal BPRs in patients with HCM are related to subendocardial ischemia during exercise.     

Opposite effects of coronary artery disease and hypertrophic cardiomyopathy on left ventricular long axis function during dobutamine stress

BACKGROUND: The mechanism for reduced early diastolic long axis lengthening velocity in hypertrophic cardiomyopathy (HCM) is not known. METHODS: We measured simultaneous septal long axis amplitude and early lengthening velocity in 23 patients with HCM, 23 normal subjects and 22 patients with coronary artery disease (CAD) of left anterior descending artery. RESULTS: Resting amplitude and lengthening velocity were reduced in HCM 0.9+/-0.2 cm, 3.5+/-1.9 cm/s but equally in CAD 1.0+/-0.3 cm, 4.1+/-2.5 cm/s vs. 1.3+/-0.2 cm, 6.3+/-1.7 cm/s in normals, p < 0.01 for both vs. normal. With dobutamine stress, lengthening velocity increased by 2.7+/-1.9 cm/s (p < 0.001) in normals, by 2.8+/-2.5 cm/s (p < 0.001) in HCM but not in patients with CAD 0.5+/-2.1, p = NS. Increment in total long axis amplitude was subnormal in CAD and HCM. However, increment in lengthening velocity was higher with stress for corresponding change in amplitude in HCM compared with CAD (chi2) = 16.5, p < 0.001). An increase in early lengthening velocity by 2 cm/s was 77% sensitive and 70% specific in discriminating between HCM and CAD. Post-ejection shortening developed or worsened in all CAD patients indicating ischemia but not in any with HCM. CONCLUSIONS: Reduced peak early lengthening velocity is not specific for HCM but also occurs in CAD. Unlike CAD, lengthening velocity increases in HCM with stress and there is no aggravation of post-ejection shortening, suggesting that the abnormal relaxation is not due to subendocardial ischemia in HCM. The greater recoil velocity per unit deformation in HCM compared with CAD, indicates elastic mechanism with increased passive muscle stiffness due to fibrosis or fibre disarray.     

Gated single-photon emission computed tomography detects subendocardial ischemia in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) sometimes develop subendocardial ischemia (SEI) in the left ventricle (LV). In the present study it was examined whether volumetric variables obtained by gated single-photon emission computed tomography (SPECT) are useful in detecting exercise-induced SEI in patients with HCM. METHODS AND RESULTS: Exercise 99mTc-tetrofosmin myocardial scintigraphy was performed in 26 HCM patients having non-obstruction and mild hypertrophy with a ventricular septal thickness < or = 20 mm. SEI was quantified using software developed previously, and the results were correlated with volumetric variables obtained using Quantitative Gated SPECT software. Exercise-induced percentage change in LV end-systolic volume was higher in 9 HCM patients with SEI (25.8+/-3.1%) than in 17 patients without (10.0+/-2.5%, p=0.009), although the percentage change in LV end-diastolic volume was similar in the 2 groups. The receiver-operator characteristics curve of the percentage changes in LV end-systolic volume for the detection of SEI showed that the optimal cutoff was 17%. This cutoff point yielded a good diagnostic value for the presence of SEI with a sensitivity of 89%, specificity 82%, and likelihood ratio 5.04. CONCLUSIONS: Gated SPECT technique is useful in detecting SEI during exercise in a select population of HCM patients.     

Alterations of the Architecture of Subendocardial Arterioles in Patients With Hypertrophic Cardiomyopathy and Impaired Coronary Vasodilator Reserve: A Possible Cause for Myocardial Ischemia

Objectives. The study was designed to investigate the architecture of subendocardial arterioles of patients with hypertrophic cardiomyopathy (HCM) and angina pectoris with respect to coronary vasodilator reserve.Background. There is growing evidence that the coronary microvasculature is abnormal in HCM. Arterioles, which mainly regulate intramyocardial blood flow, are especially suspect.Methods. Thirteen patients with HCM (50.1 ± 12.6 years old, mean value ± SD) were studied after exclusion of any relevant coronary stenoses. Subendocardial arterioles (density [n/mm²], wall area [μm²], percent lumen area [%lumen], periarteriolar collagen area [μm²]), myocyte diameter (μm) and interstitial collagen fraction (Vv%) were evaluated by means of stereologic morphometry of transvenous biopsy samples. Coronary blood flow was measured quantitatively with the inert chromatographic argon method at basal conditions and after dipyridamole (0.5 mg/kg body weight over 4 min intravenously), and coronary vasodilator reserve was calculated as the ratio of coronary resistance at basal conditions and after pharmacologic vasodilation. Data from five normotensive subjects (45.4 ± 11 years old, p = NS) served as control data.Results. Arteriolar density was diminished by 38% (p = 0.004) and %lumen by 13% (p = 0.009) in patients with HCM compared with control subjects. Coronary reserve was impaired in patients with HCM (2.28 ± 0.6 vs. 5.34 ± 1.49, p = 0.003) because of higher coronary resistance after vasodilation (0.48 ± 0.14 vs. 0.22 ± 0.06 mm Hg × min × 100 g/ml, p = 0.004). Coronary vasodilator reserve correlated with arteriolar density (r = +0.47, p = 0.045) and with %lumen (r = 0.65, p = 0.003).Conclusions. In HCM, the architecture of preterminal subendocardial arterioles is altered by a reduced total cross-sectional lumen area, corresponding to an impaired coronary vasodilator capacity that may predispose to myocardial ischemia.     

Relationship of exercise or pacing induced ST segment depression and myocardial lactate metabolism in patients with hypertrophic cardiomyopathy

To elucidate a mechanism and clinical implications of chest pain and ST segment depression during exercise in patients with hypertrophic cardiomyopathy (HCM), we investigated myocardial lactate metabolism during atrial pacing in 18 patients with HCM and 7 control subjects with normal coronary arteriograms. At an average peak pacing rate of 146 beats/min, 11 patients with HCM showed the lactate extraction ratio decreasing to less than 5%, and 6 of them produced lactate, suggesting the development of myocardial ischemia. These 11 patients with abnormal lactate metabolism demonstrated ST segment depression (82%) and chest pain (73%) during pacing and also presented abnormal results (55%) on an exercise stress test. These abnormal findings were not observed in the other 7 patients who had ratios of 5% or more at peak pacing. These observations suggest that ST segment depression and chest pain are manifestations of myocardial ischemia even in patients with HCM who have normal coronary arteriograms, and that patients with pacing induced abnormal lactate metabolism are at an increased risk of developing myocardial ischemia during exercise.     

Coronary microvascular dysfunction and ischemia in hypertrophic cardiomyopathy. Mechanisms and clinical consequences.

Symptoms and signs of myocardial ischemia are often found in patients with hypertrophic cardiomyopathy (HCM) despite angiographically normal coronary arteries. Myocardial ischemia is deemed responsible for some of the lethal complications of HCM including ventricular arrhythmias, sudden death, progressive left ventricular remodeling, and systolic dysfunction. In the past decade, a number of studies using positron emission tomography have demonstrated severe impairment of the vasodilator response to dipyridamole in the majority of HCM patients, not only in the hypertrophied septum but also in the non-hypertrophied left ventricular free wall. In the absence of coronary stenoses, this finding is indicative of diffuse microvascular dysfunction, in line with the autoptic evidence of widespread abnormalities of the intramural coronary arterioles. In turn, microvascular dysfunction represents a very likely substrate for recurrent ischemia. This may account for the fact that microvascular dysfunction has recently been shown to represent an early and powerful predictor of an unfavorable outcome in HCM. The aim of this article is to provide a concise overview of the available evidence of microvascular dysfunction and ischemia in HCM, and to speculate on the potential implications for management.     

正电子发射断层成像术在肥厚型心肌病中的应用:发现微血管功能异常所致的心肌低灌注

Hypertrophic cardiomyopathy (HCM) is characterized by extreme clinical heterogeneity, ranging from sudden cardiac death to long-term disease progression and heart failure-related complications. Myocardial ischemia, occurring at the microvascular level, is a major determinant of clinical expression and outcome. Accordingly, the severity of this microvascular dysfunction has been shown to represent an early and powerful predictor of unfavorable outcome in HCM. The assessment of microvascular function in vivo is technically challenging, although critical to a truly comprehensive evaluation and risk stratification of HCM patients. Available technologies include positron emission tomography and cardiac magnetic resonance (CMR). Studies of regional myocardial blood flow using positron emission tomography have demonstrated that the vasodilator response to dipyridamole is impaired in most HCM patients, not only in the hypertrophied ventricular septum but also in the less hypertrophied or non-thickened left ventricular free wall. CMR also allows measurement of myocardial flow, although the technique is currently time-consuming and largely limited to research situations. CMR provides further insight into the effects of ischemia in HCM patients, by visualizing the distribution and extent of fibrosis at the intramyocardial level. Late gadolinium enhancement ( LGE) is a potential predictor of risk in HCM patients, and is believed to largely reflect replacement fibrosis resulting from recurrent microvascular ischemia. LCE is associated with increased prevalence of ventricular arrhythmias, and associated with microvascular dysfunction. The present review is to provide a concise overview for the available evidence of microvascular ischemia and its consequences in HCM.     

Prevention of myocardial ischemia during coronary angioplasty: a simple new method for distal antegrade arterial blood perfusion

The nature and cause of the striking regional dilatation of the microvasculature of the subendocardial myocardium seen in some patients with ischemic heart disease are unknown. To examine this question, we reviewed nine patients in whom regions of the left ventricular free wall had marked prominence of subendocardial vasculature on postmortem arteriography. All hearts had severe diffuse atherosclerosis of major epicardial coronary arteries. Histologic findings, including serial transmural sections, showed extreme dilatation of arterioles, capillaries, and venules of the subendocardial third of the myocardium. In this same region myocytes showed atrophy, vacuolization (a marker of chronic ischemia), and small foci of necrosis and fibrosis. The generalized small-vessel dilatation with adjacent ischemic myocytes makes it improbable that the vascular changes are caused by collateral flow. Previous anatomic studies have shown artery-vein arrangements in the myocardium providing for countercurrent regulation of regional blood flow. This mechanism, which produces vascular enlargement on the basis of metabolic need, may explain the regional variceal transformation of the subendocardial microvasculature seen with chronic ischemia.     

Significance of subendocardial S-T segment elevation caused by coronary stenosis in the dog: Epicardial S-T segment depression,local ischemia and subsequent necrosis

A model of partial thickness ischemia has been developed using subendocardial S-T elevation without epicardial S-T elevation to detect partial thickness ischemia which is sufficient to cause subsequent necrosis. Subendocardial blood flow in this model (measured with radioactive microsphere techniques) may be reduced to 25 percent of normal (P < 0.001) by coronary stenosis and tachycardia while subepicardial flow remains normal. Epicardial S-T depression seems to indicate reciprocally subendocardial S-T elevation as long as a layer of nonischemic epicardial muscle is present, but when ischemia becomes transmural, epicardial S-T elevation occurs. Regional pressure-flow relations were determined as distal coronary pressure was reduced at a constant aortic pressure, heart rate and cardiac output. These relations revealed remarkably effective autoregulation of epicardial blood flow concomitant with progressive subendocardial ischemia.     

Increased plasma brain natriuretic peptide level as a guide for silent myocardial ischemia in patients with non-obstructive hypertrophic cardiomyopathy

OBJECTIVES: We measured plasma atrial/brain natriuretic peptide (ANP/BNP) levels at rest and during exercise and correlated the results with various clinical findings, particularly with myocardial ischemia, in asymptomatic hypertrophic cardiomyopathy (HCM). BACKGROUND: In patients with HCM, ANP and BNP levels are elevated and exercise-induced myocardial ischemia is common. However, it has not yet been elucidated how these levels at rest and their change with dynamic exercise are related to ischemia. METHODS: Levels of ANP and BNP were measured at rest and at peak exercise during (99m)Tc-tetrofosmin scintigraphy in 31 asymptomatic patients with non-obstructive HCM and in 10 control subjects. RESULTS: Levels of ANP and BNP at rest and the change of ANP and BNP levels (PG/ML) from rest to exercise were significantly greater in HCM than in control subjects (ANP: rest, 53.2 +/- 31.8 vs. 11.6 +/- 6.1; exercise, 114.5 +/- 74.8 vs. 28.3 +/- 23.4. BNP: rest, 156.7 +/- 104.1 vs. 9.8 +/- 9.6; exercise, 201.6 +/- 131.5 vs. 13.2 +/- 14.5). Septal perforator compression (SPC) and exercise-induced ischemia were observed, respectively, in 20 (64.5%) and in 19 (61.3%) patients with HCM. The increment of ANP during exercise was similar between HCM subgroups with or without inducible ischemia. However, BNP levels at rest and BNP increments during exercise were significantly greater in the HCM subgroup with inducible ischemia than in the subgroup without (rest, 190.5 +/- 116.2 vs. 103.1 +/- 48.3; exercise, 250.5 +/- 142.2 vs. 124.2 +/- 58.6). Multiple logistic regression analysis revealed that SPC and BNP levels at rest were independently associated with exercise-induced ischemia. CONCLUSIONS: Measurement of plasma BNP levels at rest may be useful in predicting silent myocardial ischemia in HCM.     

Energy metabolism and contractile function after 15 beats of moderate myocardial ischemia.

Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50% reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (+/- 1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p less than 0.05) and 84% (p less than 0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions.     

Fabry's disease cardiomyopathy: echocardiographic detection of endomyocardial glycosphingolipid compartmentalization.

OBJECTIVES: We sought to identify echocardiographic hallmarks of Fabry's disease cardiomyopathy (FC). BACKGROUND: The recognition of FC from other forms of left ventricular hypertrophy (LVH) by noninvasive imaging techniques is not yet available, and diagnosis, mostly in the absence of systemic manifestations, still relies on genetic and invasive studies. METHODS: Forty consecutive patients (mean age 39 +/- 15 years, 22 men and 18 women) with an established diagnosis of Fabry's disease were submitted to echocardiographic evaluation. Control population consisted of 40 consecutive patients with hypertrophic cardiomyopathy (HCM), 40 hypertensive patients with echocardiographic evidence of LVH, and 40 age- and gender-matched healthy subjects with no LVH. All HCM patients and FC with LVH and/or cardiac symptoms underwent cardiac catheterization with left ventricular endomyocardial biopsy. RESULTS: Echocardiography showed in 83% of FC patients (95% of FC patients with LVH) a binary appearance of endocardial border absent in all HCM, hypertensive, and healthy subjects. The sensitivity and specificity of this echocardiographic feature in detecting Fabry patients in study population were 94% and 100%, respectively. Comparison of echocardiographic with histologic and ultrastructural findings showed the binary appearance to reflect an endomyocardial glycosphingolipids compartmentalization, consisting of thickened glycolipid-rich endocardium, free glycosphingolipid subendocardial storage, and an inner severely affected myocardial layer with a clear subendocardial-midwall layer gradient of disease severity. CONCLUSIONS: Echocardiographic binary appearance of left ventricular endocardial border, reflecting endomyocardial glycosphingolipids compartmentalization, represents a sensitive and specific diagnostic hallmark of Fabry's disease cardiomyopathy.     

Sudden cardiac death in patients with hypertrophic cardiomyopathy: From bench to bedside with an emphasis on genetic markers

Hypertrophic cardiomyopathy (HCM) is the most common cause of death in the young, particularly in young competitive athletes. Death often occurs suddenly in asymptomatic, apparently healthy individuals. Several clinical parameters as well as genetic factors have been characterized that can identify those HCM patients who are at high risk for sudden cardiac death (SCD). The clinical parameters that have some predictive values for SCD in HCM patients are the following: a prior history of SCD, a family history of SCD, history of syncope, symptomatic ventricular tachycardia on Holter monitoring, inducible ventricular tachycardia during electrophysiologic studies, and myocardial ischemia in children with HCM. Recent identification of mutations in the beta myosin heavy chain gene and genotype-phenotype correlation in HCM patients have shown that the beta myosin heavy chain mutations are also prognosticators in HCM families. Several mutations such as Arg⁴⁰³Gln and Arg⁷¹⁹Gln are associated with a high incidence of SCD, while Leu⁹⁰⁸Val mutation is associated with a benign course and a low incidence of SCD in HCM families. Additional genetic factors such as a polymorphism in angiotensin-converting enzyme I gene may also contribute to a high incidence of SCD in HCM families. Identification and characterization of HCM patients at high risk for SCD provide the opportunity to render prophylactic therapeutic interventions, such as implantation of defibrillators, in these individuals.     

Effect of acute subendocardial ischemia on ventricular refractory periods

OBJECTIVES: To investigate the impact of acute subendocardial ischemia on the dispersion of ventricular refractory periods. METHODS: Acute subendocardial ischemia was induced in sheep by partial ligation of the left circumflex coronary artery and rapid pacing of the left atrium. The ventricular effective refractory period (ERP) was measured in five areas of the left ventricle by a programmed premature stimulation technique. RESULTS: The average ERP and ERP dispersion remained unchanged in the control group (n=5, P>0.05). In the study group (n=5), the ERP was shortened following subendocardial ischemia. ERP dispersion decreased significantly from 48+/-9 ms to 36+/-13 ms 30 min after the ischemia (P=0.02). There was neither spontaneous nor stimulation-induced ventricular arrhythmia after ischemia. CONCLUSION: Acute subendocardial ischemia leads to a homogenous reduction of ventricular ERP. This may partially explain why subendocardial ischemia is associated with a low incidence of ventricular arrhythmia.