Music, music therapy and dementia: a review of literature and the recommendations of the Italian Psychogeriatric Association.

This study reviews the most recent (from 2000 to 2011) Clinical Controlled Trials (CCT) and Randomized Controlled Trials (RCT) concerning the use of music and music-therapy (MT) in the context of dementia and related issues. Studies which explored the efficacy of music and MT on behavioral and psychological symptoms of dementia (BPSD) are prevalent, while those aiming at assessing a potential effect of these approaches on cognitive and physiological aspects are scant. Although with some limitations, the results of these studies are consistent with the efficacy of MT approach on BPSD. In this context, the ability of the music therapist to directly interact with the patients appears to be crucial for the success of the intervention. This review was endorsed by the Italian Psychogeriatric Association (AIP) and represents its view about the criteria to select appropriate music and MT approaches in the field of dementia. Accordingly, we have developed a list of recommendations to facilitate the current use of these techniques in the context of non-pharmacological treatments for patients with dementia.

High prevalence of prolonged QT interval duration in male patients with Cushing's disease.

UNLABELLED: Hypogonadal males have recently been shown to present prolonged QT interval, an electrocardiographic measure indicative of risk for fatal cardiac arrhythmias. Excess cortisol secretion induces low testosterone levels in male patients with Cushing's disease but no study has yet evaluated if this is accompanied by changes in QT interval duration. We therefore decided to evaluate whether male patients with Cushing's disease present changes in QT interval duration. QT interval was measured in electrocardiographic readings from 19 men and 35 women with Cushing's disease and age- and sex-matched controls were used for comparison. QT interval was corrected for heart rate according to Bazett's formula (QTc) and QTc >440 msec and >460 msec were taken as indicative of increased risk for torsade de pointes in men and women, respectively. Mean QTc was significantly longer in male patients compared with healthy controls (426.9±9.27 vs. 389.7±8.31, p<0.05) and 5 men with Cushing's disease presented prolonged QTc (prevalence 26%). By comparison, none of the women with Cushing's disease presented prolonged QTc. Hypokalemia and low testosterone appeared associated with long QTc. CONCLUSIONS: Male patients with Cushing's disease present prolongation of QT interval which may lead to measurements associated with high risk for ventricular arrhythmias. Both low testosterone levels and hypokalemia appear to contribute to long QT in men with Cushing's disease.

Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: a pilot study.

Symptoms and signs of male hypogonadism span all organ systems, including the cardiovascular apparatus. The electrocardiographic QT interval reflects cardiac ventricular repolarization and, if prolonged, increases the risk of malignant arrhythmias. QT interval duration is similar in boys and girls during childhood, but shortens in males after puberty and experimental studies suggest that testosterone is a major contributor to shortening of QT interval in men. The aim of the present pilot study was to assess the duration of ventricular repolarization in adult males with primary or secondary hypogonadism. Standard ECG recordings were performed in 26 men (mean age 39.2 +/- 2.17 years) with pituitary or testicular hypogonadism and repeated in 15 patients during testosterone replacement. Twenty-six age-matched control men were also analysed. Measured QT intervals were corrected for heart rate according to Bazzett's formula (QTc = QT/radical RR interval). The prevalence of prolonged QTc was considerably higher in hypogonadal patients (four of 26 men) than in control men (none, p < 0.05) and in the general, healthy population (<2.5%). QTc interval normalized on hormone replacement therapy in the four patients presenting prolonged QTc in the hypogonadal state. Heart rate and left ventricular mass did not differ among the two groups and no known QT-prolonging factor was apparent in patients with abnormal QTc interval. In conclusion, a high number prolonged QT interval measurements was observed in hypogonadal men who may therefore be at increased risk for cardiac arrhythmias. This observation reveals an additional feature of male hypogonadism, which may benefit from testosterone replacement therapy.

Management of cardiovascular risk in the perimenopausal women: a consensus statement of European cardiologists and gynecologists.

Cardiovascular risk is poorly managed in women, especially during the menopausal transition when susceptibility to cardiovascular events increases. Clear gender differences exist in the epidemiology, symptoms, diagnosis, progression, prognosis and management of cardiovascular risk. Key risk factors that need to be controlled in the perimenopausal woman are hypertension, dyslipidemia, obesity and other components of the metabolic syndrome, with the avoidance and careful control of diabetes. Hypertension is a particularly powerful risk factor and lowering of blood pressure is pivotal. Hormone replacement therapy is acknowledged as the gold standard for the alleviation of the distressing vasomotor symptoms of the menopause, but the findings of the Women's Health Initiative (WHI) study generated concern for the detrimental effect on cardiovascular events. Thus, hormone replacement therapy cannot be recommended for the prevention of cardiovascular disease. Whether the findings of WHI in older postmenopausal women can be applied to younger perimenopausal women is unknown. It is increasingly recognized that hormone therapy is inappropriate for older postmenopausal women no longer displaying menopausal symptoms. Both gynecologists and cardiovascular physicians have an important role to play in identifying perimenopausal women at risk of cardiovascular morbidity and mortality, and should work as a team to identify and manage risk factors, such as hypertension.

Electrocardiographic abnormalities in infants born from mothers with autoimmune diseases--a multicentre prospective study.

OBJECTIVES: To assess the prevalence of congenital heart block (CHB) and electrocardiographic (ECG) abnormalities in infants of anti-Ro/SSA-positive women. METHODS: Sixty anti-Ro-positive and 36 anti-Ro-negative patients were prospectively followed before/during pregnancy and underwent weekly fetal echocardiography from 18th to 26th weeks of gestational age. Infants' ECG and/or ECG-Holter were performed at 1, 3, 6 and 12 months. ECG of 200 consecutive neonates were used as a healthy control group. RESULTS: One of 61 fetuses of anti-Ro-positive mothers developed CHB (20th week); another anti-Ro-positive baby developed second degree atrioventricular (AV) block (30th week). The prevalence of transient first degree AV block detected post-natally was significantly higher in the anti-Ro-positive group, in comparison with healthy controls (P = 0.002). No differences in corrected QT (QTc) interval prolongation prevalence (>/=440 ms) was observed between the anti-Ro-positive and -negative groups, but both were significantly higher than that of the control population (P < 0.001). ECG-Holter showed QTc prolongation in 59% of infants of anti-Ro-positive and in 60% of infants of anti-Ro-negative mothers. Holter QTc was >/=470 ms in four infants of anti-Ro-positive group and two of anti-Ro-negative group. Known acquired causes of QTc prolongation were excluded. CONCLUSIONS: This prospective study confirms the low occurrence of CHB in newborns from anti-Ro-positive mothers. ECG abnormalities (first degree AV block and QTc interval prolongation) are frequent in infants of mothers with autoimmune diseases, independently of maternal disease, autoantibody profile and treatment during pregnancy.

Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women.

OBJECTIVE: To assess the true prevalence of congenital complete heart block (CCHB) in infants of anti-Ro/SSA-positive women known to have connective tissue disease (CTD) and, secondarily, to evaluate the prevalence of other electrocardiographic abnormalities in these newborns at birth. METHODS: A prospective study was conducted in 4 referral hospitals. One hundred anti-Ro/SSAA-positive mothers were followed up before they became pregnant and during the index pregnancy. Counterimmunoelectrophoresis and immunoblotting were used to test for antibodies to extractable nuclear antigens. RESULTS: Of the 100 women with anti-Ro/SSA antibodies, 2 had infants who developed CCHB in utero (2%). The CCHB was detected at 22 weeks and 20 weeks, respectively. One of the 2 mothers had primary Sjögren's syndrome (SS), and the other had undifferentiated CTD (UCTD). No case of CCHB occurred among the infants of 53 mothers with systemic lupus erythematosus (SLE). No fetal death occurred due to CCHB. In 2 centers, electrocardiography was recorded in 24 unselected newborns, and 4 were found to have sinus bradycardia. CONCLUSION: The prevalence of CCHB in newborns of prospectively followed up women already known to be anti-Ro/SSA positive and with known CTD was 2%. This finding is useful with regard to preconception counseling of these women. The risk of delivering an infant with CCHB may be higher in mothers with primary SS or UCTD than in those with SLE. Additional electrocardiographic abnormalities such as sinus bradycardia and prolongation of the QT interval may be present in their children.

Is systolic pressure a better target for antihypertensive treatment than diastolic pressure?

BACKGROUND: Diastolic blood pressure has been evaluated in different prospective cohort studies and in pharmacological intervention trials, which have shown the increased risk of cardiovascular events in hypertensive patients and the benefits of antihypertensive therapy. AIMS: To show that systolic blood pressure is at least as important as, or even more important than, diastolic blood pressure as a risk factor for cardiovascular complications. METHODS: Review of medical literature. RESULTS: Large epidemiological trials such as the Multiple Risk Factors Intervention Trial (MRFIT) and the Framingham study have shown that systolic blood pressure is an independent, continuous and modifiable risk for all cardiovascular complications, and in elderly subjects isolated systolic hypertension is the most frequent form of hypertension. In elderly subjects the increased stiffness of large arteries is responsible for the early reflection of pulse wave and for the decrease in diastolic blood pressure due to reduced recoil of large arteries. This is summarized in the increase in pulse pressure, which is directly related to the risk of cardiovascular complications. Three large intervention trials in elderly patients with isolated systolic hypertension have shown the relevant cardiovascular benefit of pharmacological reduction of elevated systolic blood pressure and normal diastolic values: the cardiovascular benefit is similar to that found in the general hypertensive population and in elderly patients with systolic-diastolic hypertension. CONCLUSION: Systolic blood pressure represents an important risk factor for cardiovascular events which can be prevented or reduced with pharmacological treatment.

Gene-specific differences in the circadian variation of ventricular repolarization in the long QT syndrome: a key to sudden death during sleep?

BACKGROUND: In the long QT syndrome (LQTS) most life-threatening cardiac events occur in association with physical or emotional stress. However, a minority of patients dies suddenly during sleep; intriguingly, these sleep-related sudden deaths tend to cluster in families. The mechanism(s) underlying this phenomenon and the reason why it occurs in few selected families are unknown. Recently, some of the LQTS genes have been identified leading to three main subgroups (LQT1, LQT2, LQT3) associated respectively with mutations affecting the following ionic currents involved in the control of ventricular repolarization: I(Ks), I(Kr), I(Na). We have recently observed that cardiac events nighttime are rare in LQT1 and frequent in LQT3 patients. METHODS: We studied 26 LQTS patients all genotyped (11 LQT1, 9 LQT2, 6 LQT3) and 26 healthy controls matched by age and gender. Using a specific software, 24-hour ambulatory ECG recordings were performed and the QT interval was measured in order to allow comparison between QTc nighttime and daytime. RESULTS: The main finding is that while LQT1 patients show a trend for modest QTc shortening and LQT2 patients a trend for modest lengthening nighttime versus daytime, LQT3 patients show clear lengthening of the QTc nighttime. These changes are not explained by heart rate changes or by the use of beta-blockers. CONCLUSIONS: The marked tendency for further QT prolongation nighttime, which clearly increases arrhythmic risk, present among LQT3 patients and absent among LQT1 patients, provides an explanation for the gene-specific higher risk for sudden death during sleep for LQT3 compared to LQT1 patients.

QT interval prolongation in asymptomatic anti-SSA/Ro-positive infants without congenital heart block.

OBJECTIVE: To analyze the electrocardiograms (EKGs) of infants born to mothers with anti-SSA/Ro antibodies in order to evaluate the QT interval (the time from the beginning of the QRS complex to the end of the T wave). METHODS: Sera from mothers and children were analyzed for anti-Ro and anti-SSB/La antibodies by enzyme-linked immunosorbent assay (ELISA) and by Western blot analysis. Fine specificity of anti-Ro antibodies was evaluated by solid-phase ELISA against recombinant 52- and 60-kd proteins and by Western blot. A retrospective chart review was conducted for EKG analysis. Twenty-eight EKG tracings (21 from anti-Ro-positive and 7 from anti-Ro-negative infants born to mothers with autoimmune diseases) were analyzed by a single investigator who was blinded to the infant's antibody status. The QT interval was measured and corrected for heart rate according to Bazett's formula. RESULTS: The mean QT interval was significantly longer in anti-Ro-positive than in anti-Ro-negative infants, also after correction for heart rate (QTc) (P = 0.001). Nine of 21 anti-Ro-positive infants and 0 of 7 anti-Ro-negative infants had QTc values above the upper normal limit (440 msec). A 24-hour EKG recording was performed on 5 patients and confirmed the QT prolongation. These infants were subsequently treated with a beta-blocker in order to prevent arrhythmias. CONCLUSION: Infants born to mothers who carry anti-Ro autoantibodies may show QT interval prolongation and should be monitored with EKG during the first months of life.

Prevalence of episodes of ST-segment depression among mild-to-moderate hypertensive patients in northern Italy: the Cardioscreening Study.

OBJECTIVES: To assess the prevalence of episodes of ST-segment depression in a population of consecutive patients with mild-to-moderate essential hypertension who are free of clinical signs of coronary artery disease. METHODS: The study involved 28 Italian centers that enrolled 414 hypertensive patients (aged 50-70 years; diastolic blood pressure > or = 95-115 mmHg or systolic blood pressure > or = 150-220 mmHg, or both, 10 days after withdrawal of medications). Silent myocardial ischemia was assessed by means of exercise stress testing and 48 h Holter monitoring. An ischemic episode was defined as a horizontal or downward sloping ST-segment depression > or = 100 microV, occurring 80 ms after the J point, and lasting for at least 1 min. RESULTS: Of the 414 patients enrolled, 411 completed the exercise stress test. During the test significant ST-segment depression occurred for 25 patients (6.1%) and all episodes but one were asymptomatic and not associated with arrhythmias. Of the 396 patients for whom we analyzed a 48 h Holter recording, 43 (10.9%) had at least one episode of ST-segment depression and seven of these had also had one during the exercise stress test The median number of episodes per patient was five (range 1-19), median duration was 9 min (range 1-20 min), and the mean amplitude of the ST-segment depression was 190 +/- 180 microV. None of these episodes was associated with symptoms and all of them occurred under resting condition. Patients with (n = 61) and without (n = 335) ST-segment depression during Holter monitoring or exercise stress testing had similar ages (59 +/- 6 versus 58 +/- 6 years) and did not differ for tobacco smoking, plasma lipid levels, blood pressure values and prevalence of echocardiographic left ventricular hypertrophy (57% of patients had left ventricular mass indexes > or = 134 g/m2 for men and > or = 110 g/m2 for women in both groups). Women had a higher prevalence of ST-segment depression than did men during Holter monitoring [32 of 183 (17.5%) versus 11 of 213 (5.2%)], whereas the prevalences of ischemia during the exercise stress test were similar. Female sex was the only significant factor associated with the occurrence of silent myocardial ischemia [odds ratio 2.56 (95% confidence interval 1.40-4.71)]. CONCLUSIONS: Our results show that 15% of patients with mild-to-moderate hypertension, who are free of clinical signs of coronary artery disease, experience episodes of ST-segment depression during Holter monitoring or exercise stress testing. Most of these episodes are asymptomatic and are not associated with the severity of hypertension, the presence of left ventricular hypertrophy, and other risk factors for coronary artery disease. Episodes of ST-segment depression are more common for women than they are for men, particularly during Holter monitoring. The early detection of silent myocardial ischemia by Holter monitoring or by the exercise stress test might be useful for the identification of hypertensive patients who should be investigated further and administered a more specific treatment.

Prolongation of the QT interval and the sudden infant death syndrome.

BACKGROUND: The sudden infant death syndrome (SIDS) is multifactorial in origin, but its causes remain unknown. We previously proposed that prolongation of the QT interval on the electrocardiogram, possibly resulting from a developmental abnormality in cardiac sympathetic innervation, may increase the risk of life-threatening ventricular arrhythmias and contribute to this devastating disorder. We prospectively tested this hypothesis. METHODS: Between 1976 and 1994, we recorded electrocardiograms on the third or fourth day of life in 34,442 newborns and followed them prospectively for one year. The QT interval was analyzed with and without correction for the heart rate. RESULTS: One-year follow-up data were available for 33,034 of the infants. There were 34 deaths, of which 24 were due to SIDS. The infants who died of SIDS had a longer corrected QT interval (QTc) than did the survivors (mean [+/-SD], 435+/-45 vs. 400+/-20 msec, P<0.01) and the infants who died from causes other than SIDS (393+/-24 msec, P<0.05). Moreover, 12 of the 24 SIDS victims but none of the other infants had a prolonged QTc (defined as a QTc greater than 440 msec). When the absolute QT interval was determined for similar cardiac-cycle lengths, it was found that 12 of the 24 infants who died of SIDS had a QT value exceeding the 97.5th percentile for the study group as a whole. The odds ratio for SIDS in infants with a prolonged QTc was 41.3 (95 percent confidence interval, 17.3 to 98.4). CONCLUSIONS: Prolongation of the QT interval in the first week of life is strongly associated with SIDS. Neonatal electrocardiographic screening may permit the early identification of a substantial percentage of infants at risk for SIDS, and the institution of preventive measures may therefore be possible.

Effects of beta-adrenergic blockade on dispersion of ventricular repolarization in newborn infants with prolonged QT interval.

A prolonged QT interval in the neonatal period and during infancy is associated with higher mortality rates, independently of the appearance of symptoms. This suggests the opportunity of a prophylaxis with beta-blockers in this population. QT interval dispersion is a useful clinical tool to predict the efficacy of antiadrenergic therapy. However, the effects of antiadrenergic interventions on QT interval and QT interval dispersion in newborns are not known. Standard 12-lead electrocardiograms were recorded in 14 newborns with prolonged QT interval, before and after oral administration of 2 mg/kg propranolol. Two electrocardiograms were also recorded in 14 newborns with normal QT intervals, matched for age and sex. In the control group no differences in heart rate, mean QTc, and QTc dispersion between the two recordings were observed. In the newborns with prolonged QT interval, propranolol did not change mean Qtc (from 467 +/- 21 to 451 +/- 26 msec; difference not significant), whereas it decreased spatial QTc dispersion, measured as the difference between the longest and shortest QTc in 12 different leads (from 69 +/- 23 to 42 +/- 13 msec; -39%; p = 0.001). This reduction was explained mainly by a shortening of the maximum QTc (from 504 +/- 25 to 476 +/- 18 msec; p = 0.005), with no change in the minimum QTc, and was not dependent on the slight change in mean QTc, as shown by the decrease in the coefficient of variation of QTc (standard deviation of QTc/mean QTc x 100) from 6.0 +/- 2.2 to 3.3 +/- 0.8 (p = 0.002). Of note, after propranolol, both measures of QTc dispersion reached the same levels observed in the control newborns. During the follow-up (> 2 years for nine of 14 infants), none of the infants had symptoms or arrhythmias. These results suggest that beta-adrenergic blockade with propranolol slightly affects mean QTc, but it significantly decreases the spatial dispersion of ventricular repolarization in newborn infants with a prolonged QT interval. This effect might modify the arrhythmogenic substrate, leading to a reduction of the susceptibility to life-threatening arrhythmias.

Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings.

AIMS: There are gender-related differences in the QT interval measured from standard ECG tracings. However, these observations are based on a limited number of beats recorded in resting conditions. Computerized Holter techniques enable ventricular repolarization and its relationship with cardiac cycle length to be analysed long term. Previous studies used only the initial portion of the QT interval to the T wave apex (QTa) to measure ventricular repolarization; however, QTa may underestimate the total QT duration (QTe). The aims of this study were to verify whether QTa and QTe had similar rate-dependence in normal subjects and whether gender-related QTe differences observed in the resting ECG were also present in the long-term QT intervalcycle length relationship. METHODS AND RESULTS: Twenty-four hour Holter recordings were obtained in 40 healthy young subjects. 20 females and 20 males (mean age 28 +/- 9 and 26 +/- 5 years, respectively ns). Two-channel ECG digitized signals were processed using new automatic QT analysis software (Ela Medical), which converted the 24-h recordings into 2880 30-s templates. It also measured the QT apex (QTa) QT end (QTe) and the RR interval (ms) of each template, and computed the slopes of the linear regressions of QTe and QTa values plotted against the corresponding RR interval (QTe/RR and QTa/RR). Females had a shorter RR interval than males (803 +/- 129 vs 877 +/- 86 ms. P = 0.037), with longer mean QTc (420 +/- 17 vs 400 +/- 200 ms. P = 0.0005). In both genders. QTa/RR slopes were steeper than QTe/RR slopes (P = 0.0001). Both QTa/RR and QTe/RR slopes were steeper in females than in males (QTa/RR 0.20 +/- 0.04 vs 0.16 +/- 0.03, P = 0.001; QTe/RR 0.16 +/- 0.04 vs 0.13 +/- 0.03, P = 0.027). Of note, QTa and QTe at fixed long cycle lengths (1000 ms) were longer in women than in men (QTa1000 330 +/- 20 vs 309 +/- 18 ms: P = 0.002; QTe1000 410 +/- 17 vs 389 +/- 19 ms: P = 0.002), while they did not differ at fixed short cycle lengths (600 ms). CONCLUSIONS: This study demonstrates that both the initial portion of the QT interval (QTa) and the entire QT interval (QTe) are useful since QTa is more prolonged than QTe at increasing cycle lengths, and thus includes most of the heart rate dependency of ventricular repolarization. In normal subjects, both the QTc and the long-term relationship between ventricular repolarization and heart rate are affected by gender. The differences in QTa and QTe duration between males and females are more marked at long cycle lengths and disappear at short cycle lengths. Finally, this study also proves the clinical feasibility of assessing the long-term relationship between ventricular repolarization and heart rate by utilizing the automatic measurement of the QT interval from 24-h Holter recordings.

QT interval prolongation and risk of life-threatening arrhythmias during toxoplasmosis prophylaxis with spiramycin in neonates.

We recently reported two cases of QT interval prolongation and cardiac arrest in newborns receiving antibiotic therapy with spiramycin, a macrolide agent extensively used for toxoplasmosis prophylaxis. In this study we assessed the effects of this drug on ventricular repolarization and on the potential risk of lethal arrhythmias in eight newborn infants in whom toxoplasmosis prophylaxis after birth was necessary. Electrocardiograms (ECGs) and echocardiograms were recorded during spiramycin therapy (350,000 i.u./kg/ day) and after its withdrawal. In a control group of eight healthy newborns matched for age and sex, no differences were found between two ECGs analogously recorded. The QT interval corrected for heart rate (QTc) was longer during spiramycin therapy than after drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p = 0.021). QTc dispersion, expressed as the difference between the longest and the shortest value in 12 different leads (QTcmax-min), was also higher during spiramycin therapy (60 +/- 32 msec vs 34 +/- 8 msec, +76%, p = 0.021), mainly because of a major lengthening of the longest QTc (QTcmax). QTc and QTc dispersion were markedly increased in the two newborns who experienced cardiac arrest after beginning treatment compared with the six neonates who had no drug-induced symptoms. During therapy seven of eight newborns had a rare abnormality in the thickening of the left ventricular posterior wall similar to that observed in patients with congenital long QT syndrome. This abnormality disappeared after drug withdrawal. Thus antibiotic therapy with spiramycin in the neonatal period may induce QT interval prolongation and increase QT dispersion. When this effect on ventricular repolarization is more marked, it may favor the occurrence of torsades des pointes and lead to cardiac arrest.

Are gender differences in QTc present at birth? MISNES Investigators. Multicenter Italian Study on Neonatal Electrocardiography and Sudden Infant Death Syndrome.

The analysis of 9,725 electrocardiograms recorded on the fourth day of life has shown that gender-related differences in QTc observed in the adult population are not present at birth.

Effects of the potassium channel blocking agent ambasilide on ventricular arrhythmias induced by acute myocardial ischemia and sympathetic activation.

The ineffectiveness of traditional antiarrhythmic agents in preventing sudden cardiac death has increased the interest in drugs that prolong refractoriness. Ambasilide is a new potassium channel blocking agent that appears to prolong refractoriness at short and long cycle lengths. We assessed the effects of ambasilide, 5 mg/kg intravenous (i.v.) bolus plus 5 mg.kg-1.hr-1 i.v. infusion, in 16 anesthetized cats in which ventricular arrhythmias could be induced reproducibly by the combination of acute myocardial ischemia and increased sympathetic activity. Ambasilide decreased heart rate and blood pressure and prolonged QRS duration (26%, p < 0.05), QTc (17%, p < 0.0001), and JTc (16%, p < 0.005). Ambasilide also shifted the strength-interval curve for ventricular refractoriness by 17 to 22 msec to the right (p < 0.001). Ventricular fibrillation was observed in 7 animals and never occurred after ambasilide (p < 0.001); however, 4 (57%) of these cats had sustained ventricular tachycardia requiring cardiac massage. Ambasilide prevented nonsustained ventricular tachycardia in 2 (40%) of 5 animals. The antiarrhythmic effect of ambasilide persisted when heart rate was kept constant by atrial pacing. In no case was proarrhythmia observed. Ambasilide had a significant electrophysiologic effect at the ventricular level in the cat because it did prolong QTc and ventricular refractoriness. Therefore ambasilide showed an antifibrillatory effect but provided only a partial protection against lethal arrhythmias induced by acute myocardial ischemia and sympathetic activation.