Coronary vasodilator reserve is impaired in patients with hypertrophic cardiomyopathy and left ventricular dysfunction

PURPOSE: To determine whether low concentrations of glutamate induce cell death in purified rat retinal ganglion cells (RGCs). METHODS: Rat retinal ganglion cells were purified from dissociated retinal cells by a modified two-step panning method and were cultured in serum-free medium containing neurotrophic factors and forskolin. Survival of RGCs after exposure to glutamate, with or without glutamate receptor antagonists, was measured by calcein-acetoxymethyl ester staining after 3 days in culture. To visualize calcium signals, RGCs were loaded with the calcium indicator dye, fluo-3 acetoxymethyl ester, and fluorescence was measured by laser scanning confocal microscope. Electrophysiological properties of RGCs were examined by using the whole-cell, patch-clamp technique. RESULTS: The application of increasing concentrations (5-500 microM) of glutamate caused a dose-dependent increase in RGC death after 3 days in culture. Neurotoxic effects of low doses of glutamate were totally blocked by a specific alpha-amino-3-dihydro-5-methyl-isoxazol-4-propionic acid-kainate (AMPA-KA) receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), but not by a specific N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovalerate (APV). In addition, calcium imaging and patch-clamp recordings showed that intracellular calcium accumulation and glutamate-evoked inward currents were completely blocked by DNQX but not by APV. CONCLUSIONS: Low doses of glutamate can activate AMPA-KA receptors in RGCs, which causes increases in intracellular calcium and decreases in cell survival. This is the first report to show the functional role of calcium-permeable AMPA-KA receptors in cultured RGCs.     

Effects of diltiazem on myocardial perfusion abnormalities during exercise in patients with hypertrophic cardiomyopathy

We developed a novel chemiluminescent assay of beta-D-galactosidase (beta-gal) based on the chemiluminescence of indole. 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) was used as a substrate for beta-gal and also as a light emitter. X-gal was hydrolysed by beta-gal to liberate free indoxyl, followed by oxidation to indigo dye, and simultaneously produces hydrogen peroxide (H2O2). H2O2 reacts with the residual X-gal in the presence of horseradish peroxidase (HRP) to emit light. The measurable range of beta-gal obtained by this method was 6 x 10(-14) mol/L to 6 x 10(-11) mol/L; the detection limit was 3 amol/assay. This chemiluminescent assay could be applied to an enzyme immunoassay of thyroxine using beta-gal as the enzyme label.     

Free radical oxidation in patients with hypertrophic cardiomyopathy

As shown by the study of 27 patients with non-obstructive form of hypertrophic cardiomyopathy (HC), this disease is associated with a significant rise in the production of active oxygen forms by leukocytes, significant changes in the activity of enzyme antioxidant defense, unchanged lipid peroxidation, high total antioxidant activity of blood plasma. The patients received a complex of natural antioxidants varying by mechanism of action and glutaminic acid. Antioxidants produced a subjective clinical response, reduced incidence of cardiac arrhythmia, improved exercise tolerance. The response becomes still better in combination of antioxidants with conventional therapeutic tools.     

Reduced cardiopulmonary baroreflex sensitivity in patients with hypertrophic cardiomyopathy

OBJECTIVES: We sought to assess baroreflex function in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: We have previously demonstrated a specific abnormality in the afferent limb of the cardiopulmonary baroreflex in patients with vasovagal syncope. Patients with HCM exhibit abnormal control of their vasculature during exercise and upright tilt; we therefore hypothesize a similar abnormality in the afferent limb of the cardiopulmonary baroreflex arc. METHODS: We investigated 29 patients with HCM and 32 control subjects. Integrated baroreceptor sensitivity was assessed after administration of phenylephrine. Cardiopulmonary baroreceptor sensitivity was assessed by measuring forearm vascular resistance (FVR) during lower body negative pressure (LBNP). Carotid artery baroreflex sensitivity was assessed by measuring the in RR interval during manipulation of carotid artery transmural pressure. The integrity of the efferent limb of the reflex arc was determined by studying responses to both handgrip and peripheral alpha-receptor sensitivity. RESULTS: During LBNP, FVR increased by only 2.36+/-9 U in patients, compared with an increase of 123+/-8.76 U in control subjects (p=0.001). FVR paradoxically fell in eight patients, but in none of the control subjects. Furthermore, FVR fell by 4.9+/-5.6 U in patients with a history of syncope, compared with an increase of 4.7+/-7.2 U in those without syncope (p=0.014). Integrated and carotid artery baroreflex sensitivities were similar in patients and control subjects (14+/-7 vs. 14+/-6 ms/mm Hg, p=NS and -3+/-2 vs. -4+/-2 ms/mm Hg, p=NS, respectively). Similarly, handgrip responses and the dose/response ratio to phenylephrine were not significantly different. CONCLUSIONS: This study suggests that patients with HCM have a defect in the afferent limb of the cardiopulmonary reflex arc.     

Prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy

OBJECTIVES: We investigated the long-term prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy (HC). Diagnosis of HC was suspected because of an abnormal electrocardiogram and/or cardiac murmur and confirmed by echocardiography and/or left ventricular angiography, and hemodynamic investigation. BACKGROUND: Hypertrophic cardiomyopathy shows marked heterogeneity in clinical expression and prognosis. The prognosis of asymptomatic patients with HC has not been fully defined. METHODS: Of 128 consecutive adult patients with HC, 58 asymptomatic patients (Group 1, mean age 42.8 years) and 70 symptomatic patients (Group 2, mean age 50.4 years) were studied to assess cardiac mortality. Mean follow-up periods were 11.0 years for Group 1 and 9.1 years for Group 2. RESULTS: At presentation, Group 1 patients were younger and had smaller left atrial dimensions than did Group 2 patients. The annual cardiac mortality rate and the rate for sudden death alone in Group 1 were significantly lower than in Group 2 (0.9% vs. 1.9%, p < 0.05, 0.1% vs. 1.4%, p < 0.05, respectively). Although about one-third of the survivors in Group 1 had cardiac symptoms at their most recent evaluation, only one patient died suddenly compared with eight in Group 2. The annual mortality rate due to heart failure was similar in each group. Only a syncopal episode was associated with both cardiac death and sudden death for both groups combined. CONCLUSIONS: The cardiac mortality rate for completely asymptomatic adult patients with HC was very low, significantly lower than that of symptomatic patients, and there was a disproportionately low incidence of sudden death.     

Coronary vasodilatory capacity is impaired in patients with dilated cardiomyopathy

Increases in wall stress because of left ventricular enlargement and/or alterations in coronary vasomotor tone might affect myocardial blood flow and vasodilatory capacity in patients with dilated cardiomyopathy. To test this hypothesis myocardial blood flow was measured at rest and during intravenous administration of dipyridamole (0.56 mg/kg) using dynamic nitrogen 13-ammonia positron emission tomography (two-compartment model) in 10 patients with dilated cardiomyopathy (mean left ventricular ejection fraction 28 +/- 8% 1 woman, 9 men; 47 +/- 13 years of age). Ten age and gender matched healthy volunteers served as controls. Coronary artery disease was ruled out by coronary angiography and left ventricular hypertrophy by two dimensional-echocardiography. Baseline heart rate (70 +/- 13 v 64 +/- 12 bpm), systolic blood pressure (111 +/- 20 v 114 +/- 12 mm Hg) and rate pressure product (7,686 +/- 1264 v 7,306 +/- 1,645) were similar in patients and controls. During dipyridamole administration, the rate pressure product increased similarly in both groups. Myocardial blood flow at rest did not differ between groups of patients and volunteers (0.69 +/ -0.27 v 0.67 +/- 0.17 mL/g/min) but correlated with the rate pressure product only in controls (myocardial blood flow, 0.18 + 0.000068214; rate pressure product, .67; P < .05). Hyperemic myocardial blood flow was lower in patients (1.57 +/- 0.39 v 1.92 +/- 0.31 mL/g/min, p < .05, whereas myocardial flow reserve did not differ between groups of patients and controls (2.57 +/- 1.15 v 3.02 +/- 0.94). Coronary vasodilatory capacity is reduced in patients with severe nonischemic cardiomyopathy. Increases in extravascular compressive forces or increased serum catecholamine levels, which in turn induce coronary vasoconstriction, might account for this finding.     

Analysis of impaired exercise capacity in patients with cirrhosis

Exercise limitation in cirrhosis is typically attributed to a cirrhotic myopathy (without impaired oxygen utilization) and/or a cardiac chronotropic dysfunction. We performed symptom-limited cardiopulmonary exercise testing in 19 cirrhotics without confounding variables (cardiopulmonary disease, beta blockade, anemia, smoking). Twelve concurrently exercised patients without cirrhosis and with normal resting pulmonary function were controls. Oxygen consumption (VO2) at peak exercise, at anaerobic threshold (VO2-AT), work rate (WR), and heart rate (HR) were measured. Cirrhotics had significantly lower peak WR (73+/-4 vs 107+/-7% predicted, p < 0.001), VO2 (72+/-4 vs 98+/-5% predicted, P < 0.001), VO2-AT (53+/-4 vs 71+/-5% predicted peak VO2, P < 0.01), HR (83+/-2 vs 91+/-2% predicted, P < 0.01) and were more likely to have chronotropic dysfunction (peak HR < 85% predicted). Six cirrhotics had normal aerobic capacity (peak VO2 > 80% predicted), while 13 were abnormal. The abnormals had an earlier AT (46+/-2 vs 67+/-3% predicted peak VO2, P < 0.05) but no difference in peak HR percent predicted was found. In conclusion, two thirds of cirrhotics, without confounding factors, have significantly reduced aerobic capacity. Cirrhotic myopathy (without impaired O2 utilization) and cardiac chronotropic dysfunction do not adequately account for the observed decrease in aerobic capacity.     

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy?

OBJECTIVES: This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND: Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS: Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS: There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS: Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.     

Ultrastructural changes of blood capillaries in patients with microvascular angina, hypertrophic cardiomyopathy, and dilated cardiomyopathy

The rat model has been used to present evidence of the effect of surgical damage on the immune system. Syngeneic small bowel transplantation (SBT) has been used to show an increased incidence of graft-versus-host disease (GVHD) as well as thymic atrophy and altered host T cell proliferative response. Syngeneic auxiliary SBT was carried out between (LEW x BN)F1 hybrids. Varying amounts of LEW mesenteric lymphocytes were injected into the last animals to induce GVHD. Results showed that in the SBT recipients the incidence of lethal GVHD was increased when compared with untreated or sham-laparotomy controls. Marked thymic atrophy was also observed, while the number of hepatic lymphocytes increased transiently. Lymphocyte proliferation in response to concanavalin A or interleukin-2 was impaired for up to 21 days postoperatively, whereas the mixed lymphocyte reaction reactivity was not affected. These results show that the number and proliferative activity of thymic T cells were impaired after major small bowel transplantation surgery and that extrathymic lymphocytes were developed in the liver.     

Effects of postural changes on left atrial function in patients with hypertrophic cardiomyopathy

BACKGROUND: We assessed left atrial function in normal subjects and in patients with hypertrophic cardiomyopathy (HCM) by using Doppler echocardiography at the supine position and after sudden standing. METHODS AND RESULTS: Twenty-seven patients with hypertrophic obstructive cardiomyopathy (HOCM), 17 patients with HCM, and 35 normal subjects were studied. From the transmitral Doppler flow velocities, peak early and late (E and A) waves, E/A ratio, and time velocity integrals (Ei and Ai) were calculated. Left atrial active contribution (LAAC) was assessed as the ratio Ei/(Ei + Ai). Furthermore, isovolumetric relaxation time (IVRT) was estimated by means of Doppler echocardiography. In the supine position, the E/A ratio was similar in the 3 groups. Conversely, LAAC was significantly higher in patients with HOCM (24.4 +/- 2.0) and in patients with HCM (23.3 +/- 3.3) compared with normal subjects (20.3 +/- 2.3, P <.001 and P <.05, respectively). After sudden standing, LAAC increased significantly in normal subjects by 11%, in patients with HOCM by 24%, and in patients with HCM by 13% (P <.001). Similarly, IVRT increased significantly in all study groups (P <. 001). By using stepwise forward multiple linear regression analysis, we found that LAAC was associated with age, IVRT, and body mass index in the supine position and with diastolic blood pressure and IVRT in the standing position. CONCLUSIONS: Left atrial contribution to left ventricular filling was increased after sudden changes of posture in normal subjects and in patients with HOCM or HCM.     

Impaired heart rate variability in patients with symptomatic NYHA class II-III hypertrophic cardiomyopathy

Power spectral analysis of heart rate variability was performed to assess cardiac autonomic function using Holter monitoring in 19 hospitalized patients with symptomatic NYHA class II-III hypertrophic cardiomyopathy (sHCM), 20 ambulatory patients with asymptomatic NYHA class I hypertrophic cardiomyopathy (asHCM) and 20 normal control subjects. Power spectral analysis decomposed the heart rate variability into high-frequency power (HF: 0.15-0.40 Hz) and low-frequency power (LF: 0.04-0.15 Hz). HF was corrected by mean RR intervals (CCVHF). CCVHF values and LF/HF ratios were used as indices of vagal and sympathetic modulations, respectively. The sHCM group demonstrated no significant elevation in CCVHF during the nighttime as compared to the daytime, while asHCM and control groups showed significant CCVHF elevation during the nighttime (p < 0.05-0.01). The nighttime CCVHF, therefore, was significantly lower in the sHCM group than in the control or asHCM group (sHCM, 1.08 +/- 0.36%; control, 1.60 +/- 0.57%; asHCM 1.82 +/- 0.77%; sHCM vs. control or sHCM vs. asHCM, p < 0.01). All of these three groups showed significant reduction in LF/HF ratio during the nighttime as compared to the daytime (p < 0.01). However, the reduction in the sHCM group was not as great as that in the control group and there was a significant difference between the sHCM and control group (2.01 +/- 1.58 vs. 1.08 +/- 0.65, p < 0.05). Two patients in the sHCM group, who later died suddenly, demonstrated very low CCVHF throughout a 24-hour period (0.2-0.8%). Both vagal and sympathetic impairment with a predominance of vagal abnormalities is suggested in patients with symptomatic NYHA class II or III hypertrophic cardiomyopathy.     

31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected death in adolescents and young adults. Alterations in myocardial metabolism are considered to be causes for contractile dysfunction. We examined the question of whether metabolic abnormalities antedate the manifestation of symptoms in patients with HCM. METHODS AND RESULTS: Proton-decoupled 31P NMR spectroscopy of the anterior left ventricular wall of the heart of 14 young, asymptomatic patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the phosphate metabolites were compared with those of normal control subjects. The patients exhibited a significantly reduced (P<0.02) ratio of phosphocreatine (PCr) to ATP of 1.98+/-0.37 (mean+/-SD), compared with 2.46+/-0.53 obtained in 11 normal control subjects. In addition, the group of patients with severe hypertrophy of the interventricular septum (n=8) showed a significantly increased (P<0.05) Pi-to-PCr ratio, with a Pi x 100/PCr of 20.0+/-8.3 versus 9.7+/-7.2 in control subjects. Both abnormalities are similar to those found in ischemic myocardium. This view is also supported by a significantly increased (P<0.01) phosphomonoester (PME)-to-PCr ratio, with a PME x 100/PCr of 20.7+/-11.2 compared with 8.4+/-6.7 in control subjects, indicating altered glucose metabolism. CONCLUSIONS: 31P NMR spectroscopy detects alterations of myocardial metabolism in asymptomatic patients with HCM. These alterations may contribute to the understanding of the pathophysiology and natural history of the disease.     

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 [microm2], percent lumen area [%lumen], periarteriolar collagen area [microm2]), myocyte diameter (microm) 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 x min x 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.     

Attenuated cardiac sympathetic responsiveness during dynamic exercise in patients with heart failure

BACKGROUND: Cardiac norepinephrine (NE) spillover is increased in patients with chronic heart failure. This elevation is partly due to augmented NE release but also to reduced capacity for cardiac NE removal processes. In patients with mild to moderate heart failure, it is not known whether the described alteration in cardiac sympathetic function also affects cardiac NE spillover during intense sympathetic activation and whether other organs respond in proportion to the heart. METHODS AND RESULTS: Twenty-two patients with heart failure and 15 age-matched healthy subjects were studied. Whole-body and regional (NE) spillovers from the heart and kidneys were assessed at baseline and during supine cycling exercise (10 minutes) with the use of steady-state infusions of tritiated NE (isotope dilution). Cardiac performance was evaluated by means of catheterization of the right side of the heart. Cardiac NE spillover was higher (P < .05) at baseline in the patient group than in healthy subjects, whereas renal and whole-body NE spillovers were similar between the study groups. During exercise, cardiac NE spillover increased 13-fold (P < .05) in healthy subjects but only 5-fold (P < .05) in the cardiac failure group, the latter reaching a lower peak value (P < .05). In contrast, there was no difference between the study groups in either renal or whole-body NE spillover responsiveness to exercise. CONCLUSIONS: Patients with mild to moderate heart failure demonstrated a selective attenuation of cardiac sympathetic responsiveness during dynamic exercise. This attenuation may convey reduced inotropic and chronotropic support to the failing heart.     

Hypercalcemic cardiomyopathy associated with primary hyperparathyroidism mimicking primary obstructive hypertrophic cardiomyopathy

A 72-year-old woman presented to hospital with rapidly progressive dyspnea and chest pain on exertion. Physical findings included a grade 3/6 systolic murmur increased by the Valsalva manoeuvre. Transthoracic echocardiography revealed concentric left ventricular hypertrophy, systolic anterior motion of the mitral valve and critical dynamic outflow tract obstruction. The myocardium was strikingly heterogeneous with hyperdynamic left ventricular systolic function. Laboratory findings included severe hypercalcemia secondary to primary hyperparathyroidism. The patient's outcome was unfavourable with nephrogenic diabetes insipidus, pancreatitis, shock, severe acidosis and death. Postmortem examination confirmed the presence of severe concentric left ventricular hypertrophy, a narrowed left ventricular outflow tract and localized endocardial fibrosis of the left interventricular septum. Microscopic findings showed diffuse calcium deposits of the myocardium, coronary arteries, kidneys and lungs. This appears to be the first report of two-dimensional and Doppler echocardiographic findings in hypercalcemic cardiomyopathy mimicking obstructive hypertrophic cardiomyopathy.     

QT dispersion and risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy

Growth hormone (GH) treatment is associated with a reduction in fat mass in healthy and GH-deficient (GHD) subjects. This is mainly mediated via a direct GH action on adipose cells and stimulation of lipolysis. Leptin is secreted from adipose tissue and may be involved in signaling information about adipose tissue stores to the brain. Hormonal regulation of leptin is still not fully elucidated, and in the present study, we investigated both the long-term (4-month) and short-term (28-hour) GH effects on serum leptin and leptin gene expression in subcutaneous adipose tissue. In GHD adults (n = 24), leptin correlated with most estimates of adiposity (r = .62 to .86), as previously found in healthy subjects. However, no correlation was observed with intraabdominal fat determined by computed tomographic (CT) scan (INTRA-CT). GH treatment for 4 months had no independent effect on either serum leptin or leptin gene expression. In a short-term study, we found that fasting gradually reduced leptin levels in both healthy men and GHD adults, with a maximum reduction of 58% to 60% (P < .01) after 31 hours. No independent effect of GH suppression or GH substitution on serum leptin was found during fasting. Adipose tissue leptin mRNA correlated with serum leptin (r = .51, P < .01) and the body mass index ([BMI] r = .55, P < .05). Serum leptin levels and gene expression were significantly higher in women compared with men (26.6 +/- 5.8 v 10.0 +/- 1.30 ng/mL, P < .05). However, in regression analysis accounting for the gender differences in subcutaneous femoral adipose tissue (FEM-CT), the difference in serum leptin disappeared, indicating that subcutaneous femoral fat or factors closely related to femoral fat (eg, sex hormones) may be causal factors for the gender difference in leptin.     

Ultrastructural alterations in pigs with naturally occurring hypertrophic cardiomyopathy

Naturally occurring hypertrophic cardiomyopathy (HCM) in pigs in generally characterized by unexplained cardiac hypertrophy with abnormal histological features (Liu et al., 1994; Dai et al., 1995). The histological alterations in HCM-affected hearts are characteristic, and can be used to diagnose the disease (Dai et al., 1995). Briefly, these are marked disorientation of cardiac muscle cells, thickening of the intramural coronary arterial wall with a narrowing of the lumen, endocardial and myocardial fibrosis. A high incidence of HCM in a population of pigs strongly suggests a hereditary basis and the Pig Research Institute, Taiwan has, therefore, endeavoured to produce a specific strain of HCM pigs. The purpose of the present study was to determine the ultrastructural changes occurring in pigs with naturally occurring HCM.