Tolerance of isolated rabbit hearts to short ischemic periods is affected by increased LV mass fraction.

Hypertrophied hearts are known for increased risk of arrhythmias and are linked with reduced ischemic tolerance. However, still little is known about state characterized only by increased left ventricle (LV) mass fraction. Seventeen isolated rabbit hearts with various LV mass were divided into two groups according to LV weight/heart weight ratio (LVW/HW ratio), namely group H and L (with higher and lower LVW/HW ratio, respectively) and underwent three short cycles of global ischemia and reperfusion. The differences in electrogram (heart rate, QRS(max), mean number, onset and dominant form of ventricular premature beats) and in biochemical markers of myocardial injury (creatine kinase, lactate dehydrogenase - LDH) and lipid peroxidation (4-hydroxy-2-nonenal - 4-HNE) were studied. As compared to group L, hearts in group H exhibited lower tolerance to ischemia expressed as higher incidence and severity of arrhythmias in the first ischemic period as well as increase of LDH and 4-HNE after the first reperfusion. In the third cycle of ischemia-reperfusion, the preconditioning effect was observed in both electrophysiological parameters and LDH release in group H. Our results showed consistent trends when comparing changes in electrograms and biochemical markers. Moreover, 4-HNE seems to be good potential parameter of moderate membrane alteration following ischemia-reperfusion injury.

Hisian extrasystole mimicking second degree atrioventricular block. a case report.

Hisian extrasystoles originate from the His bundle. They are rare and usually misdiagnosed. In fact, they manifest on the EKG, with a p' wave located before, in or after the QRS complex. More rarely, the extrasystole blocks the propagation of the influx to the ventricles simulating a Mobitz II atrioventricular (AV) block. We report the case of a 36-Year-old woman with no medical History, suffering from presyncope and palpitations at rest. Her physical examination and EKG were normal. The 24-hour Holter monitoring showed some long periods with unexpected blocked p waves but with no significant pause. Considering her young age and the absence of causes of AV block, we performed an intracardiac electrophysiological study which showed hisian extrasystoles with normal conduction tissue properties at baseline and under flecainide. The diagnosis of hisian extrasystoles simulating Mobitz II AV block was made. A simple monitoring with beta-blockers therapy was recommended. Hisian extrasystoles may simulate first or second degree AV block with different therapeutic and prognostic implications. Nevertheless, these hisian extrasystoles may be the marker of a vulnerable AV conduction, long-term follow up should be considered.

Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2.

Extrasystoles lead to several consequences, ranging from uneventful palpitations to lethal ventricular arrhythmias, in the presence of pathologies, such as myocardial ischemia. The role of working versus conducting cardiomyocytes, as well as the tissue requirements (minimal cell number) for the generation of extrasystoles, and the properties leading ectopies to become arrhythmia triggers (topology), in the normal and diseased heart, have not been determined directly in vivo. Here, we used optogenetics in transgenic mice expressing ChannelRhodopsin-2 selectively in either cardiomyocytes or the conduction system to achieve cell type-specific, noninvasive control of heart activity with high spatial and temporal resolution. By combining measurement of optogenetic tissue activation in vivo and epicardial voltage mapping in Langendorff-perfused hearts, we demonstrated that focal ectopies require, in the normal mouse heart, the simultaneous depolarization of at least 1,300-1,800 working cardiomyocytes or 90-160 Purkinje fibers. The optogenetic assay identified specific areas in the heart that were highly susceptible to forming extrasystolic foci, and such properties were correlated to the local organization of the Purkinje fiber network, which was imaged in three dimensions using optical projection tomography. Interestingly, during the acute phase of myocardial ischemia, focal ectopies arising from this location, and including both Purkinje fibers and the surrounding working cardiomyocytes, have the highest propensity to trigger sustained arrhythmias. In conclusion, we used cell-specific optogenetics to determine with high spatial resolution and cell type specificity the requirements for the generation of extrasystoles and the factors causing ectopies to be arrhythmia triggers during myocardial ischemia.

Preliminary study of prospective ECG-gated 320-detector CT coronary angiography in patients with ventricular premature beats.

BACKGROUND: To study the applicability of prospective ECG-gated 320-detector CT coronary angiography (CTCA) in patients with ventricular premature beats (VPB), and determine the scanning mode that best maximizes image quality and reduces radiation dose. METHODS: 110 patients were divided into a VPB group (60 cases) and a control group (50 cases) using CTCA. All the patients then underwent coronary angiography (CAG) within one month. CAG served as a reference standard through which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CTCA in diagnosing significant coronary artery stenosis (luminal stenosis ≥50%) could be analyzed. The two radiologists with more than 3 years' experience in cardiac CT each finished the image analysis after consultation. A personalized scanning mode was adopted to compare image quality and radiation dose between the two groups. METHODOLOGY/PRINCIPAL FINDINGS: At the coronary artery segment level, sensitivity, specificity, PPV, and NPV in the premature beat group were 92.55%, 98.21%, 88.51%, and 98.72% respectively. In the control group these values were found to be 95.79%, 98.42%, 90.11%, and 99.28% respectively. Between the two groups, specificity, sensitivity PPV, NPV was no significant difference. The two groups had no significant difference in image quality score (P>0.05). Heart rate (77.20±12.07 bpm) and radiation dose (14.62±1.37 mSv) in the premature beat group were higher than heart rate (58.72±4.73 bpm) and radiation dose (3.08±2.35 mSv) in the control group. In theVPB group, the radiation dose (34.55±7.12 mSv) for S-field scanning was significantly higher than the radiation dose (15.10±1.12 mSv) for M-field scanning. CONCLUSIONS/SIGNIFICANCE: With prospective ECG-gated scanning for VPB, the diagnostic accuracy of coronary artery stenosis is very high. Scanning field adjustment can reduce radiation dose while maintaining good image quality. For patients with slow heart rates and good rhythm, there was no statistically significant difference in image quality.

Electrocardiographic changes in hospitalized patients with leptospirosis over a 10-year period.

BACKGROUND: The aim of this study was to investigate the incidence and type of ECG changes in patients with leptospirosis regardless of clinical evidence of cardiac involvement. MATERIAL/METHODS: A total of 97 patients with serologically confirmed leptospirosis treated at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" in Zagreb, Croatia, were included in this retrospective study. A 12-lead resting ECG was routinely performed in the first 2 days after hospital admission. Thorough past and current medical history was obtained, and careful physical examination and laboratory tests were performed. RESULTS: Abnormal ECG findings were found in 56 of 97 (58%) patients. Patients with abnormal ECG had significantly elevated values of bilirubin and alanine aminotransferase, lower values of potassium and lower number of platelets, as well as more frequently recorded abnormal chest x-ray. Non-specific ventricular repolarization disturbances were the most common abnormal ECG finding. Other recorded ECG abnormalities were sinus tachycardia, right branch conduction disturbances, low voltage of the QRS complex in standard limb leads, supraventricular and ventricular extrasystoles, intraventricular conduction disturbances, atrioventricular block first-degree and atrial fibrillation. Myopericarditis was identified in 4 patients. Regardless of ECG changes, the most commonly detected infection was with Leptospira interrogans serovar Australis, Leptospira interrogans serovar Saxkoebing and Leptospira kirschneri serovar Grippotyphosa. CONCLUSIONS: The ECG abnormalities are common at the beginning of disease and are possibly caused by the direct effect of leptospires or are the non-specific result of a febrile infection and metabolic and electrolyte abnormalities. New studies are required for better understanding of the mechanism of ECG alterations in leptospirosis.

Global coupling in excitable media provides a simplified description of mechanoelectrical feedback in cardiac tissue.

Cardiac mechanoelectric feedback can play an important role in different heart pathologies. In this paper, we show that mechanoelectric models which describe both the electric propagation and the mechanic contraction of cardiac tissue naturally lead to close systems of equations with global coupling among the variables. This point is exemplified using the Nash-Panfilov model, which reduces to a FitzHugh-Nagumo-type equation with global coupling in the linear elastic regime. We explain the appearance of self-oscillatory regimes in terms of the system nullclines and describe the different dynamical attractors. Finally, we study their basin of attraction in terms of the system size and the strength of the stretch-induced currents.

Extra-sístoles / Premature cardiac complexes

Extra-sístoles são despolarizaçöes cardíacas prematuras que podem se originar em qualquer local do coração. Se originadas nos átrios ou na junção atrio-ventricular, são denominadas extra-sístoles supraventriculares. As extra-sístoles supraventriculares são geralmente benignas, não necessitando de tratamento. Se originadas nos ventrículos, são denominadas extra-sístoles ventriculares, e seu prognóstico está diretamente correlacionado à presença e ao tipo de cardiopatia. Em coraçöes normais, o prognóstico é excelente; na cardiopatia isquêmica, a presença de extra-sístoles ventriculares freqüentes aumenta significativamente o risco de morte súbita. Requerem tratamento apenas quando relacionadas a sintomas limitantes. A supressão das extra-sístoles ventriculares com medicaçöes antiarrítmicas parece não modificar o prognóstico.

[Chronostructure of ectopic heart activity in the acute phase of myocardial infarction]. / Khronostruktura éktopicheskoi aktivnosti serdtsa v ostroi faze infarkta miokarda.

7-day monitoring of cardiac rhythm has been conducted in 42 patients with myocardial infarction (MI) and 15 patients with chronic ischemic heart disease. Hour-by-hour analysis of extrasystole demonstrates that probability of ventricular arrhythmia is maximal in transmural MI, the first 3 days of acute MI are most arrhythmogenic. Follow-up of ventricular ectopic activity (VEA) showed the latter to significantly enhance early in the morning, afternoon and on the first 5 days after midnight. In unpenetrating MI, VEA intensifies in the morning, afternoon and postmidnight hoars. Atrial ectopic activity (AEA) in transmural MI enhances early in the morning, afternoon and at night (on the first 3 days). AEA in unpenetrating MI is more intensive late in the morning and afternoon.

Action potential conduction between guinea pig ventricular cells can be modulated by calcium current.

We used cell pairs electrically coupled with relatively high intercellular resistance to investigate the involvement of calcium current in the origin of the source current during the conduction process of the action potential (AP). Three interventions were used to reduce the calcium current: a specific calcium channel blocker [nifedipine (NIF)], premature stimulation, and increments in the frequency of stimulation of the cell. The ionic membrane current (Iion) after the peak of the AP of the stimulated cell was positive and small when the cell was uncoupled. However, when the stimulated cell was coupled to a cell model or to another cell, Iion during this period became negative and large to supply the coupling current. A rapid early repolarization of the AP occurred in the stimulated cell because of the removal of charge from the stimulated cell. NIF decreased the magnitude of the net negative Iion during this period and caused a more rapid early repolarization in the stimulated cell. NIF increased the delay between the activations of two coupled cells at a given coupling resistance (Rc) but decreased the longest delay that could be produced without conduction failure for a given cell pair. The highest Rc below which conduction of AP occurred was also decreased by NIF. Premature stimulation and an increase of the stimulation frequency also caused an increase in the extent of the early repolarization and increased the delay between two cell activations at a given Rc. Conduction block occurred with sufficient prematurity or at a sufficiently high frequency of stimulation even though activation of the stimulated cell occurred for each stimulus. The Iion that flows during the early plateau phase of the AP in the stimulated cell became negative and significantly large by coupling two cardiac cells together. This current flow is a major component needed to supply the coupling current through the intercellular resistance. The decrease of calcium current caused a decrease in the magnitude of this net inward ionic current, resulting in an increase of the rate of early repolarization and an increase in the conduction delay between two cells at a given Rc. These results suggest the involvement of calcium current in the conduction process when cells are coupled at relatively high Rc.

Cardiomyopathy and myocarditis in children with ventricular ectopic rhythm.

OBJECTIVE: The objective of this study was to evaluate the histologic features of the myocardium in children with abnormal ventricular ectopic rhythm but a structurally normal heart. BACKGROUND: Abnormal ventricular ectopic rhythm in children with a structurally normal heart is an uncommon but serious condition. Previous studies in adults with these findings have shown that approximately 10% have "primary electrical disease" and that 40% to 100% of these have abnormal histologic findings. METHODS: Endomyocardial biopsy samples were obtained prospectively in 33 subjects presenting with ventricular ectopic rhythm but a structurally normal heart by physical examination and noninvasive studies. Biopsy specimens were evaluated for histologic changes consistent with dilated cardiomyopathy or myocarditis and these results were compared with noninvasive and invasive clinical findings. RESULTS: Of the 33 subjects, 16 (48%) had normal myocardial histologic features (Group A), 14 (42%) had changes similar to the histologic features seen with idiopathic dilated cardiomyopathy (Group B) and 3 (9%) had lymphocytic myocarditis (Group C). Presenting clinical symptoms, surface electrocardiograms (ECGs), exercise stress testing and electrophysiologic stimulation tests failed to predict the biopsy results. Twenty-four-hour ambulatory ECGs showed a statistical difference between sustained and nonsustained ventricular tachycardia in Group A versus Group B (p less than 0.007), with Group A having more sustained ventricular tachycardia. Left ventricular function measured by fractional shortening on echocardiography did not differ between groups, but left ventricular end-diastolic dimension was greater in the subjects with abnormal histologic findings (Group B) (p less than 0.03). CONCLUSIONS: These results provide evidence that approximately 50% of children with abnormal ventricular ectopic rhythm but a structurally normal heart may have subclinical cardiomyopathy or unsuspected myocarditis.

Ventricular premature beats in young subjects without evidence of cardiac disease: histological findings.

This report describes the results of right ventricle endomyocardial biopsies from 26 subjects (mean age 27 +/- 10 years) with premature ventricular beats and normal cardiac anatomy and mechanical function. Light microscopy examination revealed normal myocardium in 10 subjects (38%), acute myocarditis in two (7%), borderline myocarditis in one (3.5%), non-specific histological abnormalities including cellular hypertrophy, fibrosis and degenerative changes in 11 (42%), vasculitis in one (3.5%) and findings compatible with right ventricular dysplasia in the final subject (3.5%). The frequency of ventricular premature beats, as assessed by Holter monitoring, and the results of electrophysiological testing did not correlate with histopathological findings and their severity. These data indicate that some young subjects with premature ventricular beats of unknown origin have abnormal right ventricular biopsy findings. Adequate follow-up will probably demonstrate the clinical utility of these observations.

Endomyocardial biopsy approach in cases with ventricular arrhythmias.

Right ventricular endomyocardial biopsies were performed in patients with ventricular tachycardia (VT: n = 20) and idiopathic premature ventricular contraction (PVC: n = 23). Active myocarditis was found in one case and postmyocarditic change in 9 cases. Significant pathology according to our definition was found in 9 out of the total of 43 cases (20.5%). The pathological features of the 9 cases were interstitial fibrosis in 5, disarrangement of muscle bundles in 6, degeneration of myocytes in one and increase in fatty tissue in 7. Increase in fatty tissue was characteristically observed in 6 out of the 20 cases with VT and it was noteworthy that the VT cases with left bundle branch block configuration showed high incidence of the fatty tissue (5/12 cases, 42%).

Evidence for a link between mechanical and electrical alternans in acutely ischaemic myocardium of anaesthetized dogs.

In order to examine the relation between mechanical alternans and associated electrical alternans during acute myocardial ischaemia, we determined the effect of a ventricular premature beat and calcium antagonists on mechanical and electrical alternans during acute coronary occlusion in anaesthetized dogs. Isometric contractions and unipolar electrocardiograms were recorded from ischaemic myocardium. During coronary occlusion, mechanical alternans was accompanied by electrical alternans, which was an alternate change in the ST segment elevation, i.e. the higher ST and the lower ST. Electrical alternans was frequently discordant and in some cases accompanied by discordant mechanical alternans. Both discordant electrical and mechanical alternans became concordant and were potentiated after the ventricular premature beat. In all cases, concordant mechanical alternans was accompanied by concordant electrical alternans and vice versa. In this situation, the higher and the lower ST corresponded to the larger and the smaller contractions respectively. Thus, a fixed correspondence was observed between mechanical and electrical alternans. A fixed correspondence was also observed between mechanical alternans and the variation in the time taken for repolarization of the monophasic action potential. Verapamil and diltiazem inhibited both electrical and mechanical alternans. The present results support the idea that a common mechanism, such as a beat-to-beat cycle of the transmembrane and intracellular movement of calcium ions, may play a role in the mechanisms of electrical and mechanical alternans.

Ventricular ectopy in totally symptom-free subjects with defined coronary artery anatomy.

Ambulatory ECG recordings were obtained from 313 consecutive, totally symptom-free male subjects on whom cardiac catheterization was subsequently performed for occupational reasons. These recordings were examined for ventricular ectopy and the results were studied in relation to the findings on selective coronary angiography. Ventricular ectopy was a common finding, with 58% of those subjects with normal coronary artery anatomy having at least one ventricular premature beat during the period of monitoring (mean 16 1/2 hours), 22% having greater than one such complex per hour, and 10% having greater than 10 per hour. Complex ventricular ectopy was present in 21% of the normal subjects. No association between the extent or complexity of ventricular ectopy and the presence or grade of anatomic coronary artery disease was demonstrated, nor was ventricular ectopy overrepresented in those with both significant coronary artery disease on angiography and evidence of ischemia on provocative testing.

Sites of origin of ventricular premature beats in patients with and without cardiovascular disease evaluated by body surface mapping.

The site of origin of ventricular premature beats (VPBs) was estimated by QRS maps and its distribution in two patient groups was studied. VPB origin was determined by comparing the body surface map of VPBs with that during electrical stimuli applied at various sites of the ventricle. Subjects were 100 patients without obvious underlying cardiovascular disease (Group N) and 289 patients with various heart diseases (Group D). Nine sites of origin of VPB were identified. In group N, VPBs of right ventricular origin were noted in 69%, those of left ventricular origin in 6%. There was a relatively high incidence of VPBs with foci estimated to be the divisions of the left bundle branch, and the age of patients with these VPBs was young. In Group D, VPBs of left ventricular origin showed a higher incidence (34.6%) and those of right ventricular origin a lower incidence (41.2%) than those in group N. The data suggest that VPBs originating from the apex and base of the ventricle strongly indicate the presence of basic heart disease and that VPBs originating in or near the divisions of the left bundle branch in younger subjects do not necessarily indicate cardiac disease.

[Myocardial dysplasia of the right ventricle (Uhl's anomaly) as a possible cause of sudden, unexpected death]. / Myokardiale Dysplasie der rechten Herzkammer (Uhl'sche Anomalie) als mögliche Ursache eines plötzlichen, unerwarteten Todes.

Partial absence and fatty replacement of the myocardial compacta of the right ventricular wall was observed in five young male adults, four of whom died suddenly and unexpectedly and one in a car accident. In one of these cases there was only one coronary orifice. Four cases of the so-called Uhl anomaly had histological findings indicating dysmorphic myocardial cells associated with minimal lymphohistiocytic infiltrates within the fatty tissue. In one case, chronic destructive inflammation was a prominent feature. Marked dysmorphic alterations in the myocardial fibers suggested the occurrence of arrhythmic episodes as the main cause of sudden heart failure and death.