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PubMed2003

Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia.

BACKGROUND: Although catheter mapping has been used to define the endocardial electrogram characteristics in patients with ventricular tachycardia (VT) and coronary disease, characterization of the electrophysiological substrate in patients with VT and nonischemic cardiomyopathy is limited. METHODS AND RESULTS: Left ventricular endocardial electroanatomical mapping was performed in 19 patients with nonischemic cardiomyopathy and monomorphic VT with an average of 178+/-83 sites per chamber mapped. Abnormal bipolar electrogram was defined as endocardial voltage signal amplitude of <1.8 mV. The extent and location of abnormal endocardium was estimated by measuring areas of abnormal electrogram recordings from 3D voltage maps. The origin of VT was approximated by identifying sites of entrainment with concealed fusion or early presystolic activity and/or by pace mapping. Abnormal electrograms were recorded over a 41+/-28 cm2 area that represented 20+/-12% of total endocardial surface. The majority of patients (14/19 patients) had only a modest area (<25%) of endocardial abnormality. All patients had abnormal low-voltage endocardial areas located near the ventricular base in the perivalvular region. There were 3+/-1 VT morphologies per patient. The majority (88%) of the 57 mapped VTs originated from the ventricular base, corresponding to regions with abnormal endocardial electrograms. CONCLUSIONS: Electroanatomical mapping in patients with monomorphic VT and nonischemic cardiomyopathy typically demonstrates a modest-sized basal area of endocardial electrogram abnormalities. The VT site of origin corresponds to these basal electrogram abnormalities. These findings have important implications regarding strategies for VT ablation in this setting.

Adult↗
PubMed2004

Epicardial activation of left ventricular wall prolongs QT interval and transmural dispersion of repolarization: implications for biventricular pacing.

BACKGROUND: Epicardial pacing of the left ventricle (LV) has been shown to prolong the QT interval and predispose to the development of torsade de pointes arrhythmias. The present study examines the cellular basis for QT prolongation and arrhythmogenesis after reversal of the direction of activation of the LV wall. METHODS AND RESULTS: A transmural ECG and transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial cells of arterially perfused canine LV wedge preparations. QT interval increased from 297.6+/-3.9 to 314.0+/-5.7 ms (n=12; P<0.001) and transmural dispersion of repolarization (TDR) increased from 35.5+/-5.2 to 70.3+/-6.2 ms (n=12; P<0.001) as pacing was shifted from endocardium to epicardium. Conduction time between M and epicardial cells increased from 12.1+/-1.2 to 24.2+/-1.5 ms (n=12; P<0.001). Amplification of TDR was further accentuated in the presence of rapidly activating delayed rectifier potassium current blockers (E-4031 and cisapride), increasing from 50.5+/-7.6 to 86.1+/-6.2 ms (n=8; P<0.01). Torsade de pointes arrhythmias could be induced during epicardial, but not endocardial, pacing of LV in the presence of rapidly activating delayed rectifier potassium current blockade. CONCLUSIONS: Reversal of the direction of activation of the LV wall, as occurs during biventricular pacing, leads to a prominent increase in QT and TDR as a result of earlier repolarization of epicardium and delayed activation and repolarization of the midmyocardial M cells. The increase in TDR creates the substrate for the development of torsade de pointes under long-QT conditions.

Action Potentials↗
PubMed1999

Endothelial growth factor receptors in human fetal heart.

BACKGROUND: Endothelial receptor tyrosine kinases include 3 members of the vascular endothelial growth factor receptor (VEGFR) family and 2 members of the angiopoietin receptor (Tie) family. In addition, the VEGF(165) isoform binds to neuropilin-1 (NP-1), a receptor for collapsins/semaphorins. The importance of these receptors for vasculogenesis and angiogenesis has been shown in gene-targeted mice, but so far, little is known about their exact expression patterns in the human vasculature. METHODS AND RESULTS: Frozen sections of human fetal heart were stained immunohistochemically with receptor-specific monoclonal (VEGFR, Tie) or polyclonal (NP-1) antibodies. The following patterns were observed: The endocardium was positive for VEGFR-1, VEGFR-2, NP-1, Tie-1, and Tie-2 but negative for VEGFR-3. The coronary vessels were positive for Tie-1, Tie-2, VEGFR-1, and NP-1 and negative for VEGFR-2 and VEGFR-3. Myocardial capillaries and epicardial blood vessels stained for VEGFR-1, VEGFR-2, NP-1, and Tie-1; myocardial capillaries and epicardial veins weakly for Tie-2; and epicardial lymphatic vessels for VEGFR-2 and VEGFR-3, weakly for Tie-1 and Tie-2, but not for VEGFR-1 or NP-1. CONCLUSIONS: The results demonstrate differential expression of the endothelial growth factor receptors in distinct types of vessels in the human heart. This information is useful for the understanding of their roles in physiological and pathological processes and for their diagnostic and therapeutic application in cardiovascular medicine.

Capillaries↗
PubMed2001

Impact of sex and gonadal steroids on prolongation of ventricular repolarization and arrhythmias induced by I(K)-blocking drugs.

BACKGROUND: Mechanisms for longer rate-corrected QT intervals and higher incidences of drug-induced torsade de pointes in women than in men are incompletely defined, although gonadal steroids are assumed to be important determinants of these differences. METHODS AND RESULTS: We used microelectrode techniques to study isolated rabbit right ventricular endocardium from control male and female and castrated male (ORCH) and female (OVX) rabbits. Action potential duration to 30% repolarization (APD(30)) was significantly shorter in male than female and in ORCH than OVX at a cycle length of 500 ms. The I(Ks) blocker chromanol 293B had no effect on APD in males or females. The I(Kr) blocker dofetilide prolonged APD in female and ORCH more than in male and OVX. At 10(-)(6) mol/L dofetilide (cycle length=1 second), the incidence of early afterdepolarizations was: female, 67%; ORCH, 56%; male, 40%; and OVX, 28%. Serum 17beta-estradiol levels were unrelated to the effects of dofetilide, but as testosterone levels increased, the dofetilide effect to increase APD diminished, as did early afterdepolarization incidence. CONCLUSIONS: Sex-related differences in basal right ventricular endocardial AP configuration persist in castrated rabbits, suggesting that extragonadal factors contribute to the differences in ventricular repolarization. In this model, drugs that block I(Kr) but not I(Ks) prolong repolarization in a way that suggests that protection from excess prolongation in males is attributable to testosterone, whereas the risk of excess prolongation of repolarization in females is related to sex-determined factors in addition to estrogen.

Action Potentials↗
PubMed1975

The sequence of normal recovery of excitability in the dog heart.

The sequence with which 18 to 70 ventricular sites recovered excitability after normal excitation was determined in 15 dogs. At the epicardial level the recovery sequence was similar to that of normal activation. The sequence of excitation and recovery differed at the endocardium with some basal areas recovering excitability earlier than the apex despite later activation. Evidence of a normal epicardial to endocardial recovery sequence was also obtained. The findings are compatible with and provide a tentative explanation of some features of T waves in human body surface electrocardiograms.

Animals↗
PubMed1979

Endocardial excision: a new surgical technique for the treatment of recurrent ventricular tachycardia.

Twelve patients with medically refractory ventricular tachycardia secondary to ischemic heart disease underwent surgery for cure of their arrhythmia. Preoperatively, the tachycardia could be reproducibly initiated and terminated in each patient by programmed stimulation. In all instances, intraoperative mapping localized the tachycardia to the border of the aneurysm, a site not routinely resected during aneurysmectomy. In nine instances, the area of origin involved the septum. During bypass the tachycardia could still be induced after standard aneurysmectomy or ventriculotomy in 11 of 12 patients. On the basis of intraoperative mapping, resection of endocardium in the area of origin (25--40% the circumference of the aneurysmectomy) up to normal muscle was performed. In one patient without a discrete aneurysm, endocardial excision alone through a ventriculotomy was performed. There was one operative death due to cardiogenic shock (preoperative ejection fraction 5%) and one late death due to rupture of a mycotic aneurysm in the pulmonary artery. Before discharge, all patients underwent a repeat relectrophysiologic study off antiarrhythmic agents and in none could ventricular tachycardia be initiated. Hemodynamic and angiographic catheterization showed improved hemodynamics and ejection fractions in all. The 10 survivors remained free of sustained ventricular tachycardia for 9--20 months, with one late nonarrhythmic death.

Adult↗
PubMed1980

Successful surgical excision of focal paroxysmal atrial tachycardia. Observations in vivo and in vitro.

A 41-year-old man had chronic, recurrent, drug-resistant paroxysmal right atrial tachycardia. Electrophysiologic studies revealed features suggesting atrial reentrance, including induction and termination of tachycardia with rapid atrial pacing and atrial extrastimuli. Endocardial catheter mapping localized the origin of tachycardia to the right atrial appendage. Intraoperative epicardial mapping refined the localization to the posterolateral rim of the appendage. The appendage was excised and the tachycardia was permanently cured. Microelectrode studies on the excised tissue revealed an inducible rhythm localized to a small area of the atrial endocardium, characterized by rapid pacing induction, rhythmicity generated from a suprathreshold afterdepolarization, low maximum diastolic potential, low overshoot potential and a smooth transition from phase 4 to phase 0, suggesting triggered automaticity. This is the first observation in man of probable triggerable atrial automaticity, which may be a direct counterpart of the clinical arrhythmia. The successful surgical outcome indicates that a focal atrial tachycardia can be excised in selected patients.

Adult↗
PubMed1983

Acute myocardial infarct extension into a previously preserved subendocardial region at risk in dogs and patients.

In this study we quantitated the region of preserved myocardium between a subendocardial myocardial infarct (SEMI) and the endocardium in dogs and determined whether this preserved zone was within the region at risk and whether infarct extension could occur in this region. We also evaluated whether a similar subendocardial region exists in patients with SEMI. A 40-minute temporary occlusion of the left anterior descending coronary artery (LAD) in eight dogs resulted in a 35 +/- 5% transmural infarct with 8 +/- 1% subendocardial preservation as assessed by point-counting of the histologic specimens. In vivo perfusion of coronary vessels with Microfil showed that this preserved subendocardial zone was within the region at risk. The preserved subendocardial zone had significantly fewer cell layers in the dogs ventilated with room air than in dogs ventilated with 100% oxygen (8 +/- 4 vs 19 +/- 4, p less than 0.001), which suggests that diffusion from the ventricular cavity was the mechanism of cell preservation. In contrast, the inspired oxygen concentration did not influence the size of the SEMI. Reocclusion of the LAD for 24 hours in an additional eight dogs, 1 week after a SEMI had been created by a 40-minute temporary occlusion, resulted in both subendocardial and subepicardial extension involving 5 +/- % and 29 +/- 9%, respectively, of the transmural myocardium at the infarct center. Subendocardial infarct extension of a similar dimension to that in dogs ventilated on 100% oxygen was observed in postmortem material from eight patients with infarct extension. The preserved layers of subendocardium presumably receive sufficient nutrients from the ventricular cavity to maintain the viability of this region during temporary, but not permanent, reduction of blood supply from the coronary arteries.

Aged↗
PubMed1985

Transcatheter ablation: comparison between laser photoablation and electrode shock ablation in the dog.

To characterize and compare the effects of transcatheter laser and electrical energy on endocardium, 35 laser pulses were delivered to the endocardial surfaces of isolated canine hearts, and 33 endocardial lesions were produced by the transarterial delivery of either transcatheter laser irradiation or electrical shock in closed-chest anesthetized dogs. Laser-induced lesion dimensions in vitro and in vivo increased with increased total dose of energy; however, the lesions produced in vivo were different in morphology and were significantly larger than lesions produced by equivalent doses of energy delivered in vitro (p less than .05). Endocardial lesions produced in vivo by laser at 40 and 80 J (7.9 X 5.4 X 6.6 and 7.9 X 5.1 X 7.5 mm) were comparable in gross morphology and size to those produced by electrical shock at 100 and 200 J (8.5 X 6.6 X 6.6 and 10.0 X 8.5 X 8.2 mm, respectively; p = NS), but transcatheter electrode shock produced significantly more ventricular tachycardia (p less than .003), premature ventricular beats in the 7 min after energy discharge (p less than .05), and wall motion abnormality (p less than .005). Transcatheter laser photoablation can create controlled endocardial lesions with less energy and fewer deleterious effects than transcatheter electrode shock.

Animals↗
PubMed1986

The subendocardial border zone during acute ischemia of the rabbit heart: an electrophysiologic, metabolic, and morphologic correlative study.

Isolated preparations of rabbit interventricular septum were perfused through the coronary arteries with oxygenated Tyrode's solution and placed in a tissue bath where they were superfused as well. Transmembrane potentials were simultaneously recorded from the subendocardium with two flexibly mounted microelectrodes, one from a superficial cell, and the other from a deep cell. Ischemia was produced by stopping coronary flow while superfusion with oxygenated Tyrode's solution was maintained. After a 7 to 12 min ischemic period, the preparation was fixed by coronary perfusion with fixative while the microelectrodes remained in place. After fixation, the microelectrodes were withdrawn. Appropriate tissue blocks were cut in 4 micron serial sections and the microelectrode track was followed until the tip position was identified. Transmembrane potentials during ischemia were divided into two categories: "border zone" potentials (resting membrane potential [RMP] 73 +/- 3 mVe, action potential amplitude [APA] 81 +/- 13 mV, action potential duration [APD] 116 +/- 48 msec, n = 12) and "ischemic" potentials (RMP 53 +/- 4 mV, APA 44 +/- 11 mV, APD 102 +/- 42 msec, n = 8). Ischemic potentials were recorded from cells at depths greater than 560 micron below the endocardial surface and border zone potentials were recorded in a layer at between 130 and 650 micron below the surface. In a separate series of experiments, extracellular concentrations of K+ and pH were measured with ion-sensitive electrodes at different depths and, after a 10 min period of ischemia, part of the septum was placed in liquid nitrogen to allow determination of phosphocreatine (PC) levels in successive 50 to 100 micron layers. After 10 min of ischemia, extracellular K+ gradually increased from 4 to 9 mM in endocardium to a depth of 600 micron, pH fell from 7.4 to 6.6 over the same distance, and PC decreased to very low, stable levels at only 800 micron. It is concluded that in the first 10 min of acute ischemia, an endocardial border zone exists of 40 to 60 cell layers in which transmembrane potentials are affected relatively little by ischemia. Within this electrophysiologic border zone extracellular K+ was lower than 9 mM, pH was higher than 6.6, and tissue content of PC was not lower than 40% of normal. In layers deeper than 600 micron, with further development of a metabolic gradient, action potentials became markedly depressed. This electrophysiologic inhomogeneity within the ischemic subendocardium could be a factor in arrhythmogenesis during the first minutes of ischemia.

Action Potentials↗
PubMed1987

Regional effects of verapamil on recovery of excitability and conduction time in experimental ischemia.

This study was designed to test the hypothesis that verapamil has an effect on ischemia-initiated arrhythmias related to its regional influences on recovery of excitability and conduction time. Using a coronary perfused preparation of cat left ventricle that allows simultaneous electrophysiologic monitoring of both endocardium and epicardium, we studied the effect of verapamil on ischemia-induced changes in transmembrane action potentials, conduction properties, and refractory periods of endocardial and epicardial muscle cells. Oxygenated Tyrode's solution was perfused through the left anterior descending coronary artery, while the preparation was superfused with Tyrode's solution gassed with 95% N2 and 5% CO2. "Ischemia" was produced by stopping coronary perfusion. During 30 min of ischemia, resting potential, action potential amplitude (APA), and action potential duration (APD) were reduced, and conduction time was prolonged in both endocardial and epicardial cells, but the changes were greater in the epicardial cells. Endocardial refractory periods shortened in parallel with APD shortening throughout 30 min of ischemia, whereas epicardial refractory periods shortened for the first 10 min and then increased due to development of longer postrepolarization refractoriness. As a result, there were significant differences in refractory periods between endocardial and epicardial cells at 10 and 30 min of ischemia, and rapid ventricular activity could be induced at these times. Exposure to verapamil (1 mg/liter) before cessation of coronary perfusion significantly limited the reduction of APA and the prolongation of conduction time during the first 10 min of ischemia in epicardial cells, but did not influence endocardial cells. During the remaining 20 min of ischemia, verapamil enhanced the reduction of APD of both epicardial and endocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Control of radiofrequency lesion size by power regulation.

The influence of power and exposure duration on lesion size in radiofrequency catheter ablation was investigated in 15 closed-chest dogs. Radiofrequency energy was delivered to the right ventricular endocardium between the tip of a standard 6F electrode catheter and a large W and durations of 5, 10, 20, 30, and 60 seconds. At necropsy 1 week later, well-demarcated homogeneous lesions were found when power had exceeded a threshold level that decreased from 1.8 W at 5 seconds to 0.7 W at 60 seconds. Lesion size ranged from 0 to 7.5 mm in depth and 0 to 9 mm in diameter. For the 5, 10, and 20 second ablations, lesion size was determined by exposure duration and power level. However, after a 20 second exposure, lesion size had reached maturity and was related to delivered power only. Therefore, a gradual, controlled growth of the lesion can be obtained by a stepwise increase of the radiofrequency power level with ample exposure duration at each level to allow for stabilization. At levels exceeding 7 W, the formation of a thin insulating layer of blood coagulum on the electrode surface caused an abrupt increase of impedance within approximately 30 seconds. Therefore, lesion size is limited to 8.5 mm in radiofrequency ablation with a standard 6F endocardial electrode catheter.

Animals↗
PubMed1990

Effect of nontransmural necrosis on epicardial potential fields. Correlation with fiber direction.

The effect of nontransmural necrosis on epicardial potential distributions was studied in 13 dogs. In previous studies, left ventricular epicardial pacing generated epicardial potential maps at QRS onset with a negative central area and two positive areas that faced the portions of the wavefront propagating along fibers. Subsequently, the positive areas expanded in a counterclockwise direction by 90 degrees to 120 degrees. In those studies, the rotatory expansion of the positive areas was tentatively attributed to the spread of excitation through deep myocardial layers, where fiber direction rotated counterclockwise from epicardium to endocardium. To test this hypothesis, we tried to interrupt the counterclockwise expansion of the positive area by creating localized, nontransmural necrosis at various depths in the left ventricular wall by injection of formalin or application of laser energy. Epicardial potential maps were obtained from a grid of 12 x 15 electrodes on a 44 x 56-mm area. Epicardial pacing from selected sites generated epicardial maps in which some positive areas were missing compared with controls. The direction of the straight line joining the pacing site to the site of missing positivity correlated well with the average fiber direction in the necrotic mass (r = 0.82, p less than 0.01). Angle between epicardial fiber direction and the straight line described above correlated well with the average depth of the necrosis, expressed as percent of the wall thickness (r = 0.95, p less than 0.01). These data support the hypothesis that the counterclockwise expansion of the epicardial positivity occurring after epicardial pacing results from excitation spreading along deep fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Repolarizing K+ currents in nonfailing human hearts. Similarities between right septal subendocardial and left subepicardial ventricular myocytes.

BACKGROUND: Studies of cardiac K+ channels from animal models have documented tissue-dependent and species-dependent diversity in the types and properties of K+ channels responsible for the repolarization of cardiac action potentials. Recent reports of human ventricular K+ currents emphasized differences in transient outward K+ current (Ito1) recorded from left ventricular (LV) subendocardial and subepicardial myocytes. These myocytes are usually isolated only from the LV free wall. The surface of the interventricular septum is continuous with the endocardium of both ventricular chambers. However, the septum contracts in unison with the left ventricle and therefore might have electric properties consonant with this function. In this study, we compare the characteristics of human cardiac K+ currents (Ito1 and inward rectifier K+ current [IK1]) of myocytes isolated from either the LV subepicardium or subendocardium of the right ventricular (RV) septum. METHODS AND RESULTS: Subendocardial tissues were obtained during routine biopsies of the right interventricular septum of seven heart transplant recipients. Subepicardial tissues were obtained from five patients with normal LV function during open heart surgery. IK1 amplitude was the same in myocytes isolated from both regions. Delayed rectifier K+ currents were small or absent in these cells. Ito1 was only slightly larger in LV subepicardial versus RV septal subendocardial myocytes. For example, at +60 mV, Ito1 was 7.2 +/- 0.4 pA/pF (n = 33) in subepicardial cells compared with 6.0 +/- 0.5 pA/pF (n = 36) in subendocardial cells. All characteristics of Ito1 examined, including the voltage dependence of activation and inactivation, rate of inactivation, and percent decline of peak current during repetitive pulsing, were similar in myocytes isolated from both regions. These findings are in contrast to previous studies that demonstrated that Ito1 of subendocardial myocytes isolated from the LV free wall of human hearts was smaller and that recovery from inactivation of this current was much slower compared with that observed in subepicardial myocytes. CONCLUSIONS: We conclude that the major repolarizing K+ currents in normal human ventricular myocytes are IK1 and Ito1 and that the properties of Ito1 of subendocardial cells isolated from the right interventricular septum are more similar to subepicardial cells than to subendocardial cells of the LV free wall. The similar electric properties shared by myocytes from these two regions may be functionally important inasmuch as the right side of the interventricular septum functions as an extension of the subepicardium of the left ventricle during the contractile cycle.

Action Potentials↗
PubMed1997

Guidance of radiofrequency endocardial ablation with real-time three-dimensional magnetic navigation system.

BACKGROUND: Ablation therapy for certain arrhythmias requires the formation of complex lesions based on electrical and anatomic mapping. We tested the accuracy and reproducibility of a nonfluoroscopic mapping and navigation (NFM) system to guide delivery of radiofrequency (RF) energy in the right atrium (RA) of swine. METHODS AND RESULTS: The NFM system uses an ultralow magnetic field to measure the real-time three-dimensional (3D) location of the tip of the locatable catheter. While in stable contact with the endocardium, between 30 and 40 consecutive tip locations were sampled and used for the 3D reconstruction of the RA geometry. The location of the catheter tip was presented in real time, superimposed over the RA geometry. We selected a point on the 3D reconstruction and delivered RF energy to that site via the tip of the locatable catheter. The catheter was then completely withdrawn and renavigated twice to the same point, at which RF energy was delivered again. At autopsy, the distance between the centers of the three ablation points (mean+/-SEM) was 2.3+/-0.5 mm (n=27). Similarly, we used the NFM system to guide the generation of linear lesions. The measured length of the linear lesions on the NFM 3D view was close to the actual lesion length measured at autopsy (correlation coefficient, .96; P=.002; n=6). Furthermore, the location, shape, and continuity of the linear lesions corresponded to the autopsy findings. CONCLUSIONS: We conclude that the NFM system can guide the application of RF energy without the use of fluoroscopy in a highly accurate and reproducible manner.

Animals↗
PubMed1998

Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome.

BACKGROUND: This study probes the cellular basis for the T wave under baseline and long-QT (LQT) conditions using an arterially perfused canine left ventricular (LV) wedge preparation, which permits direct temporal correlation of cellular transmembrane and ECG events. METHODS AND RESULTS: Floating microelectrodes were used to record transmembrane action potentials (APs) simultaneously from epicardial, M-region, and endocardial sites or subendocardial Purkinje fibers. A transmural ECG was recorded concurrently. Under baseline and LQT conditions, repolarization of the epicardial action potential, the earliest to repolarize, coincided with the peak of the T wave; repolarization of the M cells, the last to repolarize, coincided with the end of the T wave. Thus, the action potential duration (APD) of the longest M cells determine the QT interval and the Tpeak-Tend interval serves as an index of transmural dispersion of repolarization. Repolarization of Purkinje fibers outlasted that of the M cell but failed to register on the ECG. The morphology of the T wave appeared to be due to currents flowing down voltage gradients on either side of the M region during phase 2 and phase 3 of the ventricular action potential. The interplay between these opposing forces determined the height of the T wave as well as the degree to which the ascending or descending limb of the T wave was interrupted, giving rise to bifurcated T waves and "apparent T-U complexes" under LQT conditions. Spontaneous and stimulation-induced polymorphic ventricular tachycardia with characteristics of torsade de pointes (TdP) developed in the presence of dl-sotalol. CONCLUSIONS: Our results provide the first direct evidence that opposing voltage gradients between epicardium and the M region and endocardium and the M region contribute prominently to the inscription of the ECG T wave under normal conditions and to the widened or bifurcated T wave and long-QT interval observed under LQT conditions. Our data suggest that the "pathophysiological U" wave observed in acquired or congenital LQTS is more likely to be a second component of an interrupted T wave, and argue for use of the term T2 in place of U to describe this event.

4-Aminopyridine↗
PubMed2000

Improvement in midwall myocardial shortening with regression of left ventricular hypertrophy.

Despite normal indices of left ventricular (LV) chamber function, patients with LV hypertrophy (LVH) due to hypertension are thought to have depressed midwall systolic shortening compared with normotensives. The aims of the present study were (1) to confirm this observation and (2) to assess the effects of antihypertensive therapy that cause regression of LVH on LV systolic function assessed at both the midwall and endocardium. Thirty-eight previously untreated hypertensive subjects with LVH underwent echocardiography and were compared with 38 normotensive control subjects. Comparisons between the group with LVH and the control group revealed no significant differences in cardiac output (4. 32+/-0.23 versus 4.55+/-0.21 L/min), ejection fraction (62.5+/-2% versus 66.4+/-1.07%), or endocardial fractional shortening (34.5+/-1.45% versus 37.0+/-0.82%), but shortening assessed at the midwall was significantly less in the group with LVH (17.9+/-1.11% versus 21.6+/-0.63%, P<0.01). Subsequently, 32 patients with uncontrolled hypertension (24 previously untreated and 8 on existing antihypertensive therapy) underwent treatment with ramipril, with the addition of felodipine and bendrofluazide if required, to reduce blood pressure to <140/90 mm Hg. These 32 patients underwent echocardiography at baseline, after blood pressure control, and after an additional 6 months of tight blood pressure control. Good blood pressure control was achieved after 6 months compared with baseline (143/86+/-2.8/1.4 versus 174/103+/-4.1/1.9 mm Hg; P<0.01) with significant regression of LV mass index (124+/-3.4 versus 145+/-3.8 g/m(2), P<0.01). LV fractional shortening assessed at the midwall improved with regression of LVH (21.9+/-0.84 and 18.7+/-1. 19%, P<0.05), with posttreatment midwall shortening being similar to that of the normal control subjects evaluated in the first study. Hypertensive patients with LVH have depressed midwall systolic shortening despite normal indices of LV chamber function. Regression of LVH after good blood pressure control improved midwall shortening to normal levels.

Adult↗
PubMed2004

Lineage and morphogenetic analysis of the cardiac valves.

We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development.

Animals↗