Modeling of mechanical dysfunction in regional stunned myocardium of the left ventricle

Reversible mechanical dysfunction of the myocardium after a single or multiple episode(s) of coronary artery occlusion has been observed in previous studies and is termed myocardial stunning. The hypothesis that stunning could be represented by a decrease in maximum available muscle force in the stunned region was examined by means of a mathematical model that incorporates series viscoelastic elements. A canine experimental model was also employed to demonstrate depressed contractility and a consistent delay of shortening in the stunned region. The mechanical model of the left ventricle was designed to include a normal and stunned region, for which the stunned region was allowed to have variable size. Each region consisted of a volume and time dependent force generator in parallel with a passive elastic force element. The passive elastic element was placed in series with a constant viscosity component and a series elastic component. The model was solved by means of a computer. Passive and active properties of each region could be altered independently. The typical regional measures of muscle performance such as percent shortening, percent bulge, percent thickening, delay of shortening, percent increase in end-diastolic length and other hemodynamic measures were computed. These results were similar to those observed in animal models of stunning. In addition, a nearly linear relationship with end-diastolic length and delay of shortening was predicted by the model. It was concluded that a decrease in the peak isovolumic elastance and augmentation of viscosity effect of creep during stunning can explain mechanical abnormalities of stunned myocardium.     

Effects of pulsatile and nonpulsatile coronary perfusion on performance of the canine left ventricle

This study compares the effect of pulsatile (Group C, Fib/P) and nonpulsatile (Group B, Fib/NP) coronary perfusion on myocardial performance during 2 hours of normothermic ventricular fibrillation. Group A (BH/NP), used as a base-line observation, consisted of 2 hours of nonpulsatile coronary perfusion in beating hearts. The assessment of ventricular performance included diastolic ventricular compliance, myocardial oxygen consumption and lactate extraction, regional myocardial blood flow, and histology. After 120 minutes of ventricular fibrillation, Group C showed normal ventricular diastolic compliance as compared to a 50 per cent decrease in Group B (p less than 0.01). Myocardial oxygen consumption was not significantly different from that in Group B. Because of a 70 per cent increase in oxygen extraction above Group B (p less than 0.05), total left ventricular myocardial blood flow was reduced (103 +/- 23 versus 260 +/- 36 ml. per 100 Gm. per minute, p less than 0.05) and had near-constant resistance. Lactate extraction was significantly greater and more stable as compared to Group B (9.28 +/- 1.33 versus 1.8 +/- 1.08, p less than 0.05). Left ventricular endocardial/epicardial flow ratio was greater in Group C (1.21 +/- 0.08 versus 1.06 +/- 0.06, p less than 0.05). Minimal subendocardial histologic changes were present as compared to the marked patchy subendocardial ischemic changes seen in Group B. The results demonstrate that the addition of pulsatile flow to coronary perfusion minimized the deleterious effects of prolonged ventricular fibrillation on myocardial performance.     

Angiography of left ventricle following volume load and physical work in coronary disease

In order to recognize and quantitate abnormalities in wall segment motion in 22 patients simultaneous measurements of isovolumic and ejection phase parameters were performed with the Millar-angiographic catheter at rest, after leg raising and during bicycle exercise. 6 patients had slight coronary heart disease (CHD) (group I), 16 patients had severe CHD (group II). During volume load in all patients of gr. II a decrease of peak measured velocity (Vpm) and the velocity of circumferential fiber shortening (Vcf from 1.4 to 1.1 circ/s, p less than 0.025) occurred. In gr. I Vcf increased (p less than 0.05). During exercise there was a high increase in Vpm and Vcf in gr. I (from 1.2 to 1.9 circ/s) whereas in gr. II no increase was observed. LVEDP rose to 29 mm Hg and ESV from 58 to 70 ml/1.73 m2. By increasing LVEDP during volume load underperfused areas became ischaemic and akinetic. During physical work the segmental abnormality can be less pronounced possibly due to the higher prestenotic pressure.     

Effects of hypertrophy on regional action potential characteristics in the rat left ventricle: a cellular basis for T-wave inversion?

BACKGROUND: In cardiac hypertrophy, ECG T-wave changes imply an abnormal sequence of ventricular repolarization. We investigated the hypothesis that this is due to changes in the normal regional differences in action potential duration. We assessed the contribution of potassium- and calcium-dependent currents to these differences. Both the altered sequence of ventricular repolarization and the underlying cellular mechanisms may contribute to the increased incidence of ventricular arrhythmias in hypertrophy. METHODS AND RESULTS: Rats received daily isoproterenol injections for 7 days. Myocytes were isolated from basal subendocardial (endo), basal midmyocardial (mid), and apical subepicardial (epi) regions of the left ventricular free wall. Action potentials were stimulated with patch pipettes at 37 degrees C. The ratio of heart weight to body weight and mean cell capacitance are increased by 22% and 18%, respectively, in hypertrophy compared with controls (P<.001). Normal regional differences in action potential duration at 25% repolarization (APD25) are reduced in hypertrophy (control: endo, 11.4+/-0.9 ms; mid, 8.2+/-0.9 ms; epi, 5.1+/-0.4 ms; hypertrophy: endo, 11.6+/-0.9 ms; mid, 10.4+/-0.8 ms; epi, 7.8+/-0.6 ms). The regional differences in APD25 are still present in 3 mmol/L 4-aminopyridine. Hypertrophy affects APD75 differently, depending on the region of origin of myocytes (ANOVA P<.05). APD75 is shortened in subendocardial myocytes but is prolonged in subepicardial myocytes (control: endo, 126+/-7 ms; epi, 96+/-10 ms; hypertrophy: endo, 91+/-6 ms; epi, 108+/-7 ms). These changes in APD75 are altered by intracellular calcium buffering. CONCLUSIONS: Normal regional differences in APD and the changes observed in hypertrophy are only partially explained by differences in I(tol). In hypertrophy, the normal endocardial/epicardial gradient in APD75 appears to be reversed. This may explain the T-wave inversion observed and will have implications for arrhythmogenesis.     

Systolic time intervals of the left ventricle in neuromuscular diseases

In 64 patients having neuromuscular disease and in 11 healthy persons, preejection period (PEP), ejection time index (LVETI) and PEP/LVET ratio of the left ventricle were studied by indirect method. PEP was significantly longer, ejection time index was significantly shorter and PEP/LVET ratio was significantly higher in patients with progressive muscular dystrophy than healthy persons. In 75% of patients having this disease LVETI was shortened and only in 30% of them Ecg abnormalities could be detected. These findings are postulated to be due to diffusely decreased contractility of the left ventricular heart muscle in progressive muscular dystrophy.     

Performance of the lift ventricle in left ventricular obstructive cardiomyopathy

Whether volume expansion influences NaC1 reabsorption by the diluting segment of the nephron remains a matter of controversy. In the present studies this question has been examined in normal unanesthetized dogs, undergoing maximal water diuresis. Free water clearance (CH2O/GFR) has been used as the index of NaC1 reabsorption in the diluting segment. Three expressions have been employed for "distal delivery" of NaC1: a) V/GFR, designated as the "volume term"; b) (CNa/GFR + CH2O/GFR), the "sodium term;" and c) (CC1/GFR + CH2O/GFR), the "chloride term". The validity of these terms is discussed. Three techniques were used to increase distal delivery: 1) the administration of acetazolamide to dogs in which extracellular fluid (ECF) volume was not expanded (grop 1); 2) "moderate" volume expansion (group 2); and 3) "marked" volume expansion (group 3). CH2O/GFR increased progressively with rising values for "distal delivery" regardless of which term was used to calculate the latter. With all three delivery terms, differences in distal NaC1 reabsorption emerged between the two volume-expanded groups, though only with the "chloride" term did substantial differences also emerge between the nonexpanded group 1 dogs and both volume-expanded groups. In group 1, values for CH2O/GFR increased in close to a linear fashion up to distal delivery values equal to 24% of the volume of glomerular filtrate. However, at high rates of distal delivery the rate of rise of CH2O/GFR was less in group 2 than in group 1 and the depression of values was even greater in group 3. Within the limits of the techniques used, the data suggest that volume expansion inhibits fractional NaC1 reabsorption in the diluting segment of the nephron in a dose-related fashion. The "chloride" term was found to be superior to the "volume" and "sodium" terms in revealing these changes.     

Efferent sympathetic and vagal innervation of the canine right ventricle

BACKGROUND: The functional pathways of efferent sympathetic and vagal innervation to the right ventricle (RV) might be important in a variety of disease states that involve the RV wall. The purpose of this study was to investigate those pathways. METHODS AND RESULTS: We determined the effects of phenol and endocardial radiofrequency ablation applied to the RV anterolateral wall and outflow tract on effective refractory period (EPR) shortening during bilateral ansae subclaviae stimulation and ERP lengthening during bilateral vagal stimulation. We found that efferent sympathetic axons to the RV are located in the superficial subepicardium and that lateral sites receive sympathetic innervation predominantly from the lateral margin of the RV near the AV groove. Medial sites close to the left anterior descending coronary artery (LAD) receive sympathetic innervation from both the right lateral atrioventricular (AV) groove and regions near the LAD. At the RV outflow tract, some sympathetic fibers are located intramurally. Efferent vagal fibers are located at the RV surface within 10 mm of the right lateral AV groove; they penetrate intramurally and reach to the medial sites of the RV anterior wall. Other vagal fibers originate near the LAD and are intramural. Vagal fibers to the RV outflow tract are located intramurally either from the lateral side (close to the right coronary artery) or medial side (close to the LAD). CONCLUSIONS: Efferent vagal and sympathetic innervation of the right ventricle resembles that of the left ventricle. A major difference is that efferent sympathetic fibers to the right ventricular outflow tract are located not only in the subepicardium but in the subendocardium as well.     

Adenosine-sensitive ventricular tachycardia from the anterobasal left ventricle

OBJECTIVES: This study demonstrates that exercise-provocable tachycardia resembling right ventricular outflow tract tachycardia may originate from the anterobasal left ventricle. BACKGROUND: Reentry is the operative mechanism of idiopathic left ventricular tachycardia, with a QRS complex of right bundle branch block and superior axis that is responsive to verapamil but not adenosine. Whether some mechanism other than reentry is operative in some idiopathic left ventricular tachycardias is unclear. METHODS: In 4 of 53 consecutive patients with idiopathic left ventricular tachycardia, the tachycardia was sensitive to adenosine. These four patients were women 63, 61, 61 and 31 years old and were the subjects of the present study. RESULTS: In all four patients, spontaneous tachycardia was related to exercise or emotional stress. The tachycardia displayed atypical left (one patient) or right (three patients) bundle branch block with an inferior axis and marked variation in cycle length. An intravenous bolus of adenosine triphosphate (10 to 20 mg) terminated tachycardia in all four patients. Tachycardia was terminated or prevented in three patients given intravenous or oral verapamil. Atrial or ventricular incremental or extrastimulus testing induced tachycardia in all four patients (three with, one without isoproterenol infusion). Electrically induced tachycardia also demonstrated marked variation in cycle length, which ranged from 230 to 390 ms. Entrainment was not demonstrable with overdrive pacing from multiple sites. Endocardial mapping during tachycardia revealed that the earliest activations were registered 25, 40, 35 and 50 ms before onset of the QRS complex, respectively, from the anterior aspect of the left ventricle just below the mitral annulus, adjacent to the left ventricular outflow tract. High frequency Purkinje spikes were not recorded at this site. Radiofrequency current delivered to this site successfully ablated the tachycardia in three of the four patients. CONCLUSIONS: Exercise-provocable, catecholamine-mediated, verapamil-responsive, adenosine-sensitive ventricular tachycardia may arise from the anterobasal left ventricle adjacent to the outflow tract.     

Rotational deformation of the canine left ventricle measured by magnetic resonance tagging: effects of catecholamines, ischaemia, and pacing

OBJECTIVE: The aim was to investigate the generation of rotation of the left ventricular apex with respect to the base by magnetic resonance tagging, a non-invasive method of labelling the myocardium, in a canine model. METHODS: 18 dogs were imaged at baseline and during: (1) inotropic stimulation with dobutamine; (2) chronotropic stimulation with atrial pacing; (3) anterior wall ischaemia; (4) posterior wall ischaemia; and (5) varying left ventricular activation site; six dogs underwent each intervention. Apical rotation of the apex (torsion) was quantified. The epicardium and the endocardium were considered separately, as were the anterior and posterior walls. RESULTS: Mean torsion of the epicardium [anterior 3.1(SEM 1.2) degrees, posterior 9.9(1.0) degrees] was less than that of the endocardium [anterior 8.1(2.6) degrees, posterior 14.9(2.0) degrees, p < 0.05 for both]. Anterior torsion was less than posterior torsion for both the epicardium, p < 0.05, and the endocardium, p < 0.05. Dobutamine increased torsion of both the epicardium [anterior 13.3(2.2) degrees, posterior 12.6(1.7) degrees, p < 0.05 for both] and the endocardium [anterior 24.6(2.3) degrees, posterior 16.5(2.1) degrees, p < 0.05 for both]. Atrial pacing at 160% baseline rate increased torsion of both the anterior wall [epicardium 6.6(1.0) degrees, endocardium 11.3(1.2) degrees, p < 0.05] and the posterior wall [epicardium 13.0(1.3) degrees, endocardium 19.4(1.9) degrees, p < 0.05]. Anterior wall ischaemia reduced torsion of the anterior wall only [epicardium -2.0(1.0) degrees, endocardium 6.7(2.3) degrees, both p < 0.05]. Posterior wall ischaemia reduced torsion of the posterior wall of the epicardium only [7.1(1.2) degrees, p < 0.05] but also reduced torsion of the anterior wall [epicardium 0.7(1.0) degrees, endocardium 2.4(1.6) degrees, p < 0.05 for both]. Altering the pattern of left ventricular activation by atrioventricular pacing reduced torsion of the posterior wall of the epicardium [6.6(1.2) degrees, p < 0.05] and of the anterior [3.6(1.9) degrees, p < 0.05] and posterior [7.1(1.6) degrees, p < 0.05] walls of the endocardium. CONCLUSIONS: Rotational deformation of the left ventricle is dependent on the pattern of left ventricular activation and the contractile state. That a decrease in the contractile state in one area (by ischaemia) can cause a decrease in rotation in another suggests that this rotation depends on the complex fiber arrangement of the whole ventricle.     

DDD pacemaker implantation--cardiac pacemaker tips in the left atrium and ventricle by the left thoracotomy

Recently DDD pacemaker implantation for the children has undergone trials world wide; though regarding the approach, ways and positions of the epicardial lead, a few problems are still remained to be discussed. Now we report 9 cases (5 males, 4 females) of DDD pacemaker implantations by the left anterolateral thoracotomy approach. The 9 patients weighing 6.5 to 33 kg, were aged 11 months to 12 years (mean 6 years) of whom male 5, female 4 with degree of Block; 2 and 7. To all patients the stab-in type epicardial tips were implanted in the left atrium, the screw-in type ventricular epicardial tips were in the left ventricle by the 4th intercostal thoracotomy, and the pacemaker generators were beneath the fascia of the abdominal rectus muscle. We have no sensing and pacing failure, all pacemakers are working in the DDD mode well.     

Angiographic and morphologic features of the left ventricle in Ebstein's malformation

Quantitative and qualitative cineangiographic analysis of the left ventricle (LV) was performed in 26 patients with isolated Ebstein's malformation, having a mean age of 23 +/- 17 years. Nine autopsied hearts with isolated Ebstein's malformation were submitted to morphologic and morphometric analysis. In 4 of the cases, it was possible to make a direct correlation between the angiographic data obtained during life and the autopsy findings. On the basis of the LV end-diastolic volume we identified 3 groups of patients: 7 with volume <60 ml/m2, another 7 with volume between 60 and 80 ml/m2, and 12 with volume >80 ml/m2. The LV ejection fraction was reduced in 2 patients with normal LV end-diastolic volume and in 6 with increased LV end-diastolic volume. The ratio of ventricular mass to LV end-diastolic volume was always adequate, but a reduction of the ventricular contractive performance (end-systolic pressure to end-systolic volume ratio <3 mm Hg/ml/m2) was found only in patients with a dilated left ventricle. No correlation was demonstrated between the extent of the atrialized component of the right ventricle (mean value 67 +/- 31 cm2, range 13 to 133) and the LV dimensions. All but 2 patients showed a leftward diastolic displacement of the ventricular septum, but in only 1 did this produce an elongated shape of the left ventricle. Sixteen had anomalies of LV dynamics: 10 with hypokinesia (3 of the posterior wall, 4 of the apex, 1 of the inferior wall, 1 of the septum, and 1 global), 6 with dyskinesia (1 of the posterior wall, 2 of the apex, 1 of the posterior wall and apex, 1 of the superior part of the septum, and 1 of the anterior wall), and 8 with premature diastolic distension of the anterobasal wall. Morphometric analysis produced mean values for myocytes of 59 +/- 10%, for the interstitium of 21 +/- 4%, and for fibrous tissue of 20 +/- 9% (normal 4 +/- 1%). Five autopsied hearts had a prolapsing and/or dysplastic mitral valve.     

Real-time strain rate imaging of the left ventricle by ultrasound

The regional function of the left ventricle can be visualized in real-time using the new strain rate imaging method. Deformation or strain of a tissue segment occurs over time during the cardiac cycle. The rate of this deformation, the strain rate, is equivalent to the velocity gradient, and can be estimated using the tissue Doppler technique. We present the strain rate as color-coded 2-dimensional cine-loops and color M-modes showing the strain rate component along the ultrasound beam axis. We tested the method in 6 healthy subjects and 6 patients with myocardial infarction. In the healthy hearts, a spatially homogeneous distribution of the strain rate was found. In the infarcted hearts, all the infarcted areas in this study showed up as hypokinetic or akinetic, demonstrating that this method may be used for imaging of regional dysfunction. Shortcomings of the method are discussed, as are some possible future applications of the method.     

Hamartomatous malformation of the left ventricle associated with sudden death

We describe unusual left ventricular cardiac lesions in a 17 year old boy who died suddenly during exertion. These consisted of two grossly evident regions of deficient myocardium, containing cavernous spaces which represented exaggerated intertrabecular regions of the left ventricular cavity. Dense fibro-elastotic tissue was deposited around these spaces along with a variable admixture of mature adipose tissue, fibrous tissue and blood vessels. The etiology of these presumably congenital developmental abnormalities is obscure. The lesions most probably represent a hamartomatous malformation, which is a poorly documented pathological entity.     

Complete unloading alone may not adequately protect the left ventricle

BACKGROUND: The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined. METHODS: We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass. RESULTS: Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP. CONCLUSIONS: These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.     

Ionic mechanisms of regional action potential heterogeneity in the canine right atrium

Atrial action potential heterogeneity is a major determinant of atrial reentrant arrhythmias, but the underlying ionic mechanisms are poorly understood. To evaluate the basis of spatial heterogeneity in canine right atrial repolarization, we isolated cells from 4 regions: the crista terminalis (CT), appendage (APG), atrioventricular ring (AVR) area, and pectinate muscles. Systematic action potential (AP) differences were noted: CT cells had a "spike-and-dome" morphology and the longest AP duration (APD; value to 95% repolarization at 1 Hz, 270+/-10 ms [mean+/-SEM]); APG and pectinate muscle cells had intermediate APDs (180+/-3 and 190+/-3 ms, respectively; P<0.001 versus CT for each), with APG cells having a small phase 1; and AVR cells had the shortest APD (160+/-4 ms, P<0.001 versus other regions). The inward rectifier and the slow and ultrarapid delayed rectifier currents were similar in all regions. The transient outward K+ current was significantly smaller in APG cells, explaining their small phase 1 and high plateau. L-type Ca2+ current was greatest in CT cells and least in AVR cells, contributing to their longer and shorter APD, respectively. The E-4031-sensitive rapid delayed rectifier K+ current was larger in AVR cells compared with other regions. Voltage- and time-dependent current properties were constant across regions. We conclude that myocytes from different right atrial regions of the dog show systematic variations in AP properties and ionic currents and that the spatial variation in ionic current density may explain AP differences. Regional variation in atrial ionic currents may play an important role in atrial arrhythmia generation and may present opportunities for improving antiarrhythmic drug therapy.