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PubMed1998

Visualization of clear echocardiographic images with near field noise reduction technique: experimental study and clinical experience.

BACKGROUND: With transthoracic echocardiography, it is sometimes difficult to obtain a clear image of the apical portion of the heart because of noise near the transducer. To reduce this artifact, we have developed a new technique (near field noise reduction, NFNR) based on the digital filtering by using radiofrequency signals. This technique may be useful for the accurate measurement of the wall thickness of the myocardium in the near field. The objectives of these studies were (1) to determine the accuracy of this new technique for the measurement of wall thickness in the experimental study and (2) to determine whether the improvement in the image quality in the apical portion can be obtained in the clinical setting by using the NFNR technique. EXPERIMENTAL STUDY: By using the NFNR technique, we measured wall thickness of three kinds of phantoms (wall thickness 9.0, 14.0, and 21.0 mm) moving at various velocities (5 to 80 mm/sec) in the water bath with artifact produced by a single probe. It was difficult to obtain clear echocardiographic images of the phantom and measure its wall thickness because of the artifact. By using the NFNR technique, on the other hand, the same phantom was clearly imaged. It was possible to measure the wall thickness of each phantom at each moving velocity with the NFNR technique. Mean differences between the echocardiographic measurement and actual value of wall thickness in each phantom model (9.0, 14.0, and 21.0 mm) were 0.04 +/- 0.58 mm, 0.09 +/- 0.58 mm, and -0.02 +/- 0.24 mm, respectively. CLINICAL STUDY: We studied 25 initial patients in whom the near field was not clearly imaged in apical views by conventional echocardiography because of near field noise. Apical four-chamber or two-chamber views were obtained with and without the NFNR technique. Two observers independently graded endocardial visualization for the 50 segments by using a three-point scale (0 = endocardium not seen, 1 = seen in part but not all of the segment, 2 = endocardium seen along entire segment). The mean segment score in the imaging with the NFNR technique was significantly higher than that without the NFNR technique (observer 1: 1.8 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01; observer 2: 1.6 +/- 0.7 vs 1.2 +/- 0.8, p < 0.01). CONCLUSIONS: The newly developed NFNR technique provides clear echocardiographic images and accurate wall thickness measurement in the experimental model even when it is difficult to obtain clear images because of the artifact. This new technique will be useful in the reduction of near field noise in the clinical setting.

Echocardiography↗

PubMed2000

Reversal of metallothionein expression is different throughout the human myocardium after prolonged left-ventricular mechanical support.

OBJECTIVES: We examined the distribution of metallothionein (MT), a stress-inducible protein, and the cardiomyocyte diameter in human hearts after left-ventricular assist device (LVAD) support. BACKGROUND: Remodeling in end-stage heart failure is characterized by myocyte hypertrophy and alterations of several inducible proteins. LVADs used as a bridge to cardiac transplantation unload the left ventricle and may lead to a reversal of the remodeling, but little is known about the pathophysiology of this process. METHODS: The immunoreactivity for MT and the cardiomyocyte diameter was analyzed in left-ventricular tissue specimens of 17 patients with end-stage heart failure before and after LVAD support. RESULTS: MT positive cells were mainly located sub-endocardially in vacuolized cardiomyocytes and in small vessels throughout the myocardium. During LVAD support, MT-positive myocytes decreased in the sub-endocardial (p < 0.008) and sub-epicardial region (p < 0.003), MT-positive vessels decreased similarly (p < 0.003). Cardiomyocyte diameter decreased significantly only in the sub-endocardium (p < 0.03). Hearts of patients supported longer than 88 days (= median) showed substantially lower MT reactivity at the time of LVAD explantation as compared to patients supported less than 88 days. CONCLUSION: Our results suggest that unloading of the left ventricle during prolonged LVAD support leads to regression of cellular hypertrophy and a decrease of MT expression. The preferential reduction of MT-positive vacuolized cardiomyocytes in the sub-endocardium is comparable with the concept of greatest reduction of wall stress in this area of the myocardium and may be due to the improvement of myocardial blood flow and the energy balance.

Adult↗

PubMed1994

Interaction of anesthetics and catecholamines on conduction in the canine His-Purkinje system.

The findings in papillary muscles that epinephrine facilitates conduction at Purkinje fiber-muscle junctions and in the endocardium are consistent with older observations that activation of myocardial beta-adrenergic receptors speeds conduction and activation in the heart and thereby increases the synergy of contraction (46,47). The cellular mechanism underlying this action is probably increased cell-to-cell coupling between muscle fibers secondary to elevation of cyclic AMP (19,48). However, the findings that epinephrine alone or with halothane transiently slows conduction in the Purkinje layer while simultaneously improving conduction across Purkinje-muscle junctions and in the endocardium may represent proarrhythmic actions. These actions could facilitate arrhythmogenesis by transiently increasing regional differences of activation and repolarization times in the conduction system and myocardium and thereby increasing vulnerability to induction of reentry by premature impulses. Such a proarrhythmic effect could explain an older observation that low-dose norepinephrine infusions decrease the threshold for induction of fibrillation by two premature beats in pentobarbital-anesthetized animals (49). The cellular basis underlying the different responses of Purkinje fibers and the endocardial muscle layer to catecholamines, in which velocity decreased and increased, respectively, is not known. Our working hypothesis to explain this action in canine Purkinje fibers is a mechanism involving activation of WB4101-sensitive alpha 1-adrenoceptor, G-protein coupling to phospholipase C and the generation of DAG and IP3 leading to modulation of cell-to-cell coupling, which is potentiated in the presence of partial uncoupling by halothane. The different responses of Purkinje and myocardial fibers are speculated to result from differences in the relative density of this subtype of alpha 1-adrenoceptor, differences in the subcellular effector coupling mechanisms, or differences in the specific connexin proteins forming gap junctions between Purkinje and myocardial fibers (50).

Animals↗

PubMed1997

Alterations in heart rate following radiofrequency ablation in the treatment of reentrant supraventricular arrhythmias: relation to alterations in autonomic tone.

To determine the relation between the creation of endocardial lesions and alterations in autonomic tone, we analyzed heart rate variability in patients undergoing radiofrequency catheter ablation for symptomatic supraventricular tachycardia. Elevated heart rates are frequently noted after radiofrequency catheter ablation for supraventricular arrhythmias. It has been postulated that this elevation may be secondary to alterations in cardiac autonomic tone. Since heart rate variability is a measure of autonomic nervous system activity, we used this technique to examine the heart rate elevation and to characterize postablation autonomic changes. Thirty-eight patients undergoing 44 radiofrequency catheter ablation procedures were included in the study. Total arrhythmic substrates treated included 34 accessory pathways and 13 AV nodes with dual physiology. Twenty-four hour ambulatory electrocardiographic recordings were obtained in a drug-free state prior to, ablation early postablation, and late postablation. Spectral and nonspectral analyses of heart rate variability were performed. Subgroup analyses were also done on specific cohorts. Subgroups included patients undergoing accessory pathway ablations, AV node modifications, and ablation of septal and nonseptal targets. To determine whether the amount of tissue damage was related to changes in heart rate variability, we analyzed the relation between the total energy delivered to the endocardium and the peak change in creatine kinase and heart rate variability. In this population, a significant transient increase in heart rate was noted following radiofrequency ablation. All time and frequency domain parameters of heart rate variability showed significant reversible decreases. These changes were independent of target site and arrhythmia substrate. There was no correlation noted between the changes in heart rate variability and either the total amount of energy applied to the endocardium or the change in creatine kinase. Increased heart rates and decreased heart rate variability occur following radiofrequency catheter ablation for supraventricular tachycardia. Clinically, the predominant effect is that of decreased parasympathetic tone. Since these transient changes are independent of arrhythmic substrate or ablation site in the atria, a rich parasympathetic innervation of the heart is proposed.

Adolescent↗

PubMed2003

Ectopic expression of an embryonic skeletal myosin heavy chain in human fetal and Syrian hamster hearts.

The mammalian heart is known to contain only two isoformic myosin heavy chain (MHC) genes, alpha and beta. A previously uncharacterized MHC gene was isolated in Syrian hamster hearts (McCully et al., JMol Biol 1991). We identified the novel MHC gene as a hamster embryonic skeletal MHC gene based on the developmental stage- and tissue-specific expression pattern: the restricted expression ofmRNA to striated muscles was highest in embryonic skeletal muscle and was developmentally down-regulated. We confirmed that the embryonic skeletal MHC gene exhibited higher expression in cardiomyopathic than in normal hamster hearts, and was up-regulated during the development of cardiomyopathy. The sporadic expression was highly localized in the endocardium. The present study identified that a very small number of undifferentiated myogenic cells existed in adult hamster endocardium. Moreover, using RT-PCR, a homologue of embryonic skeletal MHC mRNA was also expressed in human embryonic, but not adult ventricles. Our data provide a new insight into the regulatory mechanisms of MHCs in the cardiomyopathic hamster heart.

Animals↗

PubMed1998

Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum.

In lymphocytes, the expression of early immune response genes is regulated by NF-AT transcription factors which translocate to the nucleus after dephosphorylation by the Ca2+-dependent phosphatase, calcineurin. We report here that mice bearing a disruption in the NF-ATc gene fail to develop normal cardiac valves and septa and die of circulatory failure before day 14.5 of development. NF-ATc is first expressed in the heart at day 7.5, and is restricted to the endocardium, a specialized endothelium that gives rise to the valves and septum. Within the endocardium, specific inductive events appear to activate NF-ATc: it is localized to the nucleus only in endocardial cells that are adjacent to the interface with the cardiac jelly and myocardium, which are thought to give the inductive stimulus to the valve primordia. Treatment of wild-type embryos with FK506, a specific calcineurin inhibitor, prevents nuclear localization of NF-ATc. These data indicate that the Ca2+/calcineurin/NF-ATc signalling pathway is essential for normal cardiac valve and septum morphogenesis; hence, NF-ATc and its regulatory pathways are candidates for genetic defects underlying congenital human heart disease.

Animals↗

PubMed2002

Characterization of the electroanatomic substrate for monomorphic ventricular tachycardia in patients with nonischemic cardiomyopathy.

Ventricular arrhythmias are common in the setting of nonischemic cardiomyopathy. The etiology for the cardiomyopathy is frequently not identified and the label of "idiopathic" is applied. Interstitial fibrosis with conduction system involvement and associated left bundle branch block characterizes the disease process in some patients and the mechanism for monomorphic ventricular tachycardia is commonly bundle branch reentry. However, most patients with nonischemic cardiomyopathy have VT due to myocardial reentry and demonstrate marked myocardial fibrosis and electrogram abnormalities. Although patient specific, the overall distribution of electroanatomic abnormalities appears to be equal on the endocardium and epicardium. The extent of electrogram abnormalities appears to parallel arrhythmia presentation and/or inducibility. Patients with sustained uniform morphology VT have the most extensive endocardial and epicardial electrogram abnormalities. Magnetic electroanatomic voltage mapping provides a powerful tool to characterize the location and extent of the arrhythmia substrate. Basal left ventricular myocardial involvement, as indexed by the location of contiguous electrogram abnormalities, is common in patients with sustained VT and left ventricular cardiomyopathy. The relatively equal distribution of electrogram abnormalities on the endocardium and epicardium, and the results of mapping and ablation attempts, suggest that critical parts of the reentrant circuit may be epicardial. Unique features of the electroanatomic substrate associated with cardiomyopathy due to Chagas' disease, sarcoidosis, and arrhythmogenic right ventricular dysplasia are also discussed.

Cardiomyopathies↗

PubMed2003

Mechanism of decrease in the atrial potential after implantation of a single-lead VDD pacemaker: atrial histological changes after implantation of a VDD pacemaker lead in dogs.

The single-lead VDD pacemaker system (VDDPS) enables atrial synchronous ventricular pacing with only one lead in patients with an atrioventricular block. There are some cases in which the atrial potential decreases after implantation of a VDDPS, making physiological pacing difficult. The mechanism of this decrease has not been elucidated yet. To elucidate the possible relationship between the decrease of the atrial potential after implantation of a VDDPS and histopathological changes of the atrium. We implanted a VDDPS from the jugular vein under anesthesia in 10 adult dogs. The tip of the pacing lead was fixed in the right ventricular apex of the heart under fluoroscopic guidance. Then, the lead was ligated and fixed to the jugular vein at a point where a favorable atrial potential was obtained. The end of the lead was passed from the neck to the back subcutaneously; then pulled outside and fixed there to measure the atrial potential. The atrial potential was measured using a pacing system analyzer under anesthesia on days 3 (n = 9) and 7 (n = 8), as well as on weeks 2 (n = 6), 3 (n = 4), and 4 (n = 3), after the implantation. The heart was removed from the dogs on day 3 (n = 2), day 7 (n = 2), week 2 (n = 2), and week 4 (n = 4) to examine the atrial histological findings. The atrial potential was 2.7 +/- 0.7 mV at the time of the implantation, 1.7 +/- 1.1 mV (P < 0.05) on day 3, and 1.7 +/- 0.7 mV on week 4 after the implantation. Macroscopically, the pacemaker lead was covered with thrombus, and adhered to the atrial wall in 80% of animals. Microscopically, the endocardium was hypertrophic due to fibrous tissue; besides RBC extravasation, inflammatory cells infiltration and degeneration of myocardial cells, were observed under the endocardium. Inflammatory changes developed in the atrial wall after implantation of the VDDPS, and this seemed to be one of the mechanisms for the decrease of the atrial potential of the VDDPS.

Animals↗

PubMed1998

Nonsurgical infarctectomy in acute experimental myocardial infarction.

This study examines whether a catheter mounted left intraventricular balloon may prevent left ventricular (LV) dysfunction following acute experimental myocardial infarction. In 10 anesthetized pigs, multiple coronary arterial ligations were applied around the apex of the heart. LV end-diastolic pressure (LVEDP), aortic flow (AF), and LV long and short axis fractional shortening (FS) were measured before and at 15 min intervals after ligations. At the 60th min after ligation, the LV long axis FS and AF decreased by 7.2 +/- 2.6% (p < 0.05) and 13.25 +/- 2.68% (p < 0.01), respectively, and the LVEDP increased by 4.3 +/- 1.1 mm Hg (p < 0.01) while no change was noted in the LV short axis FS. An intraventricular catheter mounted nonpulsating balloon was positioned over the endocardium of the infarcted area at the LV apex. Inflation of the nonpulsating balloon to an optimal volume, which was found to be equal to 8-10% of the LV end-diastolic volume, resulted in a reduction (by 3.8 +/- 1.2 mm Hg, p < 0.01) of the already increased LVEDP and in an increase (by 6.6 +/- 2.1%, p < 0.05) in the LV short axis FS while no statistically significant change was noted in the AF and LV long axis FS. It is concluded that an intraventricular catheter mounted balloon patch positioned over the endocardium of the infarcted area may ameliorate early LV dysfunction, possibly by interfering with the functional geometry of the LV contraction.

Animals↗

PubMed2003

Development and validation of an ECG algorithm for identifying the optimal ablation site for idiopathic ventricular outflow tract tachycardia.

INTRODUCTION: Idiopathic ventricular outflow tract tachycardia or premature ventricular contractions (OT-VTs) can originate from several different sites in the outflow tract, including the left ventricular (LV) endocardium and epicardium. The aims of this study were (1) to develop an ECG algorithm to predict the origin of OT-VT and (2) to test prospectively the accuracy of the algorithm. METHODS AND RESULTS: An algorithm was developed by correlating the 12-lead ECG findings with the catheter ablation site in 80 patients with OT-VT. The ECG characteristics of the QRS complex during the arrhythmia were analyzed. The catheter sites were verified by multi-plane fluoroscopy. The outflow tract was classified into six subdivisions: right ventricular (RV) septum, RV free wall, RV near the His-bundle region, LV endocardium, left sinus of Valsalva (LSV), and LV epicardium remote from the LSV. An OT-VT originating from the LV epicardium remote from the LSV was defined as an OT-VT in which the earliest ventricular activation was recorded at the LSV and radiofrequency ablation from the LSV failed. This algorithm subsequently was tested prospectively in 88 patients. Overall sensitivity was 88% and specificity was 95%. The positive and negative predictive values were 88% and 96%, respectively. CONCLUSION: We describe a new ECG algorithm having a high sensitivity and specificity to identify the optimal ablation site for idiopathic ventricular outflow tachycardia or premature ventricular contractions.

Adolescent↗

PubMed2004

Transmural action potential repolarization heterogeneity develops postnatally in the rabbit.

INTRODUCTION: In the hereditary long QT syndrome, arrhythmia risk changes with age despite the presence of an ion channel mutation throughout development. Age-dependent changes in the transmural dispersion of repolarization may modulate this vulnerability. We recorded cardiac action potentials in infant, periadolescent, and adult rabbit myocardium to determine if transmural heterogeneities in repolarization are developmentally determined. METHODS AND RESULTS: Arterially perfused ventricular preparations were studied from 2-week (n = 7), 7-week (n = 7), and adult (n = 6) NZW rabbits. Action potentials were recorded with microelectrodes in five regions: epicardium (epi), subepicardium (subepi), midwall (mid), subendocardium (subendo), and endocardium (endo) during endocardial S1 pacing at cycle lengths of 2,000, 1,000, and 500 ms. At 2 weeks, the transmural APD90 profile was flat. With age, APD prolongation from subepi to endo created a transmural repolarization gradient. At 7 weeks, APD90 was significantly longer at subendo [204 +/- 2 ms (mean +/- SE) 2,000-ms cycle length, P < 0.05] vs both endo (193 +/- 2 ms) and epi (172 +/- 2 ms), causing a heterogeneous transmural APD90 gradient. In adults, the transmural gradient was a smooth continuum such that APD was shortest in epicardium and longest in endocardium. CONCLUSION: The transmural distribution of APD is developmentally determined. Tissue-specific age-dependent changes in APD can result in transmural repolarization heterogeneity. These age-related effects may modulate arrhythmia vulnerability during development.

Action Potentials↗

PubMed1992

Severe type Hunter's syndrome. Polysomnographic and neuropathological study.

The clinico-pathological and polysomnographical findings of an adult male patient with severe type of Hunter's syndrome are presented. He died of respiratory failure aged 19, which was much older than the average in this disease. Mucopolysaccharidosis was suspected at the age of one year, and diagnosed by leucocyte enzyme assay at 4 years of age. Mental and physical activity gradually deteriorated until his death. He often showed central type sleep apnea during the sleep stage 2, in addition to common obstructive apnea in Hunter's syndrome. The autopsy showed marked fibrous thickening of the endocardium and valves, enlargement of the liver and spleen, dilatation of the lateral ventricles and diffuse atrophy of the brain. Histologically, diffuse cytoplasmic vacuolations were found in fibroblast-like cells in the thickened endocardium and vascular walls, in Kupffer cells, and in many neurons of the central and peripheral nervous systems. Most neuronal inclusions were considered to be a ganglioside, and in other cells to be a mucopolysaccharide, by their ultrastructure. Massive accumulation of ganglioside in the neurons in the respiratory center might be reflected on central type sleep apnea.

Adult↗

PubMed2002

Quantitative diagnosis of apical cardiomyopathy using contrast echocardiography.

BACKGROUND: The echocardiographic diagnosis of apical hypertrophic cardiomyopathy (ACM) has been limited by the frequent inability to visualize the apical endocardium. We hypothesized that the use of contrast agents in patients with suspected ACM, but nondiagnostic echocardiographic studies, would allow quantitative diagnosis. METHODS: Contrast enhancement was performed in 26 patients with nondiagnostic transthoracic echocardiograms (TTEs) for the diagnosis of ACM; 6 patients with suspected ACM based on unexplained symmetric precordial T-wave inversions and increased apical tracer uptake on single-photon emission computed tomography (SPECT) scans, 10 patients with normal electrocardiogram (ECG) readings and no history of hypertension (healthy group), and 10 patients with hypertension and ECG criteria for left ventricular hypertrophy (LVH group). Images were obtained with Optison (Mallinckrodt Medical; IV, 1.0 mL) using harmonic imaging and low mechanical index. Posterior (PW) and septal wall (SW) thicknesses were measured at end-diastole in the parasternal long-axis view. Apical wall thickness (A) was measured from the contrast-enhanced apical endocardium to the visceral epicardial surface in the apical 4-chamber view. A/PW and A/SW ratios were calculated for each group. Asymmetric apical hypertrophy was defined as an A/PW ratio greater than 1.5. RESULTS: Contrast-enhanced apical thickness was greater than 2.0 cm in all patients in the suspected ACM group but less than 1.2 cm in all patients in the LVH and healthy groups. In all 6 patients in the suspected ACM group, A/PW and A/SW ratios were greater than 1.5. No patient in the healthy or LVH groups had thickness ratios greater than 0.85. CONCLUSION: Contrast echocardiography allows quantitative diagnosis of ACM in patients with suggestive ECG and SPECT but nondiagnostic TTEs. This study suggests that contrast echocardiography should be performed before using more expensive or invasive diagnostic testing for this condition.

Adult↗

PubMedDate not supplied

Cooled-tip diode laser catheter for improved catheter ablation of ventricular tachycardia.

Catheter ablation for the treatment of arrhythmias has evolved dramatically over the past two decades. Researchers have investigated alternative energy sources and catheter constructs to improve the efficacy and safety of catheter ablation. This study tested the hypothesis that a new prototype cooled-tip laser catheter used with a low-power diode laser would improve catheter ablation of ventricular tachycardias. Four mongrel dogs underwent a median sternotomy. The cooled-tip laser catheter was advanced into the left ventricle via the left carotid artery and positioned adjacent to the endocardium. Laser powers of 3 and 4 W were delivered at four exposure times to select areas of the endocardium. During application of laser energy, room-temperature saline was circulated through the catheter. At necropsy the hearts were examined and fixed in formalin for histologic examination. Gross examination of the endocardial surfaces showed no indication of crater or thrombus formation. Cross-section of the lesions revealed sharply demarcated, circular-shaped areas of coagulative necrosis extending into the mid-myocardium. Areas of coagulative necrosis were identified within the myocardium extending into the mid-myocardium and occasionally the subepicardium. A sharp line of demarcation was observed between the lesions and the surrounding normal myocardium. The results of this study showed that we could use surface cooling during slow laser heating to create large subsurface lesions with characteristics appropriate for treatment of ventricular tachycardia and little to no surface damage. We believe our catheter system addresses many of the previous issues with laser-based approaches.

Animals↗

PubMed1957

Autoradiographic studies of the utilization of S35-sulfate by the chick embryo.

From studies of autoradiograms of various developmental stages of the chick embryo containing S(35) given us sulfate it was determined that as early as Stages 3+ and 4 there is a selective utilization or accumulation of sulfate by the various parts. The earliest accumulation site is the axial portion of the primitive streak and the floor of the groove. Later S(35) was found in the head process, Hensen's node, notochord, amniocardiac vesicle, wall of the omphalomesenteric vein, endocardium, subendocardial jelly, mesenchyme destined to become cartilage, basement membrane area of the gut, and a mucopolysaccharide layer formed on the free surface of the stomach. The early notochordal localizations of S(35) coincide with the region in which a thin ring of chondroitin sulfate is subsequently laid down. However, it is apparent that there is an intracellular accumulation of inorganic sulfate by the chondroitin-forming cells prior to the time they produce sufficient chondroitin sulfate to be demonstrable histochemically. It was interesting to note that the endocardium appears to concentrate sulfate that later apparently finds its way into the subendocardial jelly. The fact that those mesenchymal cells which later form chondroblasts begin to utilize sulfate selectively before histological differentiation is apparent was determined. In addition, the presence of sulfate-containing substances in the forming basement membrane of the gut would seem to indicate that sulfate is important in the histological differentiation of this membrane.

Animals↗

PubMed1999

Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes.

The biophysical characteristics and alpha subunits underlying calcium-independent transient outward potassium current (Ito) phenotypes expressed in ferret left ventricular epicardial (LV epi) and endocardial (LV endo) myocytes were analyzed using patch clamp, fluorescent in situ hybridization (FISH), and immunofluorescent (IF) techniques. Two distinct Ito phenotypes were measured (21-22 degrees C) in the majority of LV epi and LV endo myocytes studied. The two Ito phenotypes displayed marked differences in peak current densities, activation thresholds, inactivation characteristics, and recovery kinetics. Ito,epi recovered rapidly [taurec, -70 mV = 51 +/- 3 ms] with minimal cumulative inactivation, while Ito,endo recovered slowly [taurec, -70 mV = 3,002 +/- 447 ms] with marked cumulative inactivation. Heteropoda toxin 2 (150 nM) blocked Ito,epi in a voltage-dependent manner, but had no effect on Ito,endo. Parallel FISH and IF measurements conducted on isolated LV epi and LV endo myocytes demonstrated that Kv1.4, Kv4.2, and Kv4.3 alpha subunit expression in LV myocyte types was quite heterogenous: (a) Kv4.2 and Kv4.3 were more predominantly expressed in LV epi than LV endo myocytes, and (b) Kv1.4 was expressed in the majority of LV endo myocytes but was essentially absent in LV epi myocytes. In combination with previous measurements on recovery kinetics (Kv1.4, slow; Kv4.2/4.3, relatively rapid) and Heteropoda toxin block (Kv1.4, insensitive; Kv4.2, sensitive), our results strongly support the hypothesis that, in ferret heart, Kv4.2/Kv4.3 and Kv1.4 alpha subunits, respectively, are the molecular substrates underlying the Ito,epi and Ito,endo phenotypes. FISH and IF measurements were also conducted on ferret ventricular tissue sections. The three Ito alpha subunits again showed distinct patterns of distribution: (a) Kv1.4 was localized primarily to the apical portion of the LV septum, LV endocardium, and approximate inner 75% of the LV free wall; (b) Kv4. 2 was localized primarily to the right ventricular free wall, epicardial layers of the LV, and base of the heart; and (c) Kv4.3 was localized primarily to epicardial layers of the LV apex and diffusely distributed in the LV free wall and septum. Therefore, in intact ventricular tissue, a heterogeneous distribution of candidate Ito alpha subunits not only exists from LV epicardium to endocardium but also from apex to base.

Amino Acid Sequence↗

PubMed1980

Myocardial blood flow and capillary density in chronic pressure overload of the feline left ventricle.

The effects of chronic pressure overload hypertrophy on myocardial blood flow and capillary density was measured in the feline left ventricle. Myocardial hypertrophy was produced by and 84% banding constriction of the ascending aorta 2.8 +/- 1.2 months before the experiments. In seven cats with aortic constriction, cardiac hypertrophy produced a 40% increase in left ventricular mass. Seven cats served as normals. Our findings show that, in chronic pressure overload hypertrophy, coronary blood flow at control (resting) levels is increased compared with normals. In both normal and hypertrophy cats endocardial/epicardial flow ratios were equal at the control level. In the hypertrophied hearts, coronary reserve, measured as the percentage increase in myocardial blood flow from control to near maximal flow during adenosine infusion, was reduced. In the hypertrophy group a shift in the transmural distribution of blood flow in the left ventricle was noticed, as indicated by a reduced endo/epi flow ratio, during adenosine infusion. A decreased capillary density in hypertrophy, most marked in endocardial tissue regions, was demonstrated by this study. These findings indicate that capillary growth does not parallel myofibre growth in the endocardium of pressure overload hypertrophied left ventricles. The resultant anatomical imbalance causes a compromise of flow reserve in the endocardium, making this region vulnerable to ischaemia.

Adenosine↗

PubMed1984

Microvascular deterioration: implications for reperfusion.

Beneficial effects of reperfusion or revascularisation on acute myocardial injury may be restricted to the initial few hours due in part to the development of myocardial haemorrhage and "no-reflow". In the present study, the severity of regional myocardial haemorrhage was assessed with Cr-51-RBC and compared with regional flow in the same areas assessed with labelled microspheres in 51 dogs to determine the temporal profile of reperfusion induced haemorrhage and "no-reflow" in relation to the duration of preceding ischaemia. Reperfusion was initiated after selected intervals of coronary occlusion (1 to 7 h) in 31 dogs, and results compared to those in 14 dogs with persistent occlusion and six dogs with no occlusion. Regions of decreased perfusion were outlined grossly with lissamine dye. Heart rate, blood pressure and left atrial pressures were monitored continuously. Haemorrhage was confirmed by histology. The amount of blood in normal regions of the heart was 3.2 +/- 0.4% of wet weight. In tissue ischaemic for 1 h without reperfusion, it was less, ie, 2.3 +/- 0.7; with occlusion of seven hours, it was reduced even further to 1.3%. in dogs subjected to reperfusion after selected intervals of ischaemia, haemorrhage (6.6 +/- 3.8 ml X 100 g-1) occurred in the endocardium after 3 h of ischaemia but in this epicardium only after 5 h of ischaemia (3.9 +/- 1). Regional flow was normal in the endocardium with reperfusion after 1 h of ischaemia (0.9 +/- 0.2 ml X min-1 X g-1) but decreased by 50% with ischaemia of 7 h prior to reperfusion. Thus, haemorrhage occurred earlier than "no-reflow". Results indicate that the severity of microvascular damage is a function of the duration of the interval of ischaemia prior to reperfusion and that it is evident earliest in the subendocardium. Since haemorrhage preceded "no-reflow" extravasation of blood may contribute to the "no-reflow" phenomenon. Adjunctive measures designed to delay microvascular deterioration may be useful to prolong the interval in which lysis or bypass surgery can be implemented effectively.

Animals↗