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PubMed1993

Comprehensive evaluation of left hemisphere type I schizencephaly.

We report the neuropsychological, magnetic resonance imaging, electroencephalographic telemetry, and sodium amytal test findings of a 32-year-old, left-handed man with unilateral left hemisphere type I schizencephaly. The patient was referred for treatment of medically refractory left temporal complex partial seizures that developed at age 26 years. Sodium amytal testing revealed complete incorporation of speech and language function by the right hemisphere. Detailed neuropsychological evaluation indicated average to above-average performance on all measures of language skills, judgment and reasoning, visuospatial abilities, and memory function. This case demonstrates that extensive but lateralized neuronal migration disorders can be associated with complete reorganization and full recovery of function by the contralateral hemisphere. Furthermore, this case supports the view that the degree of recovery is greatest when compensatory mechanisms are activated antenatally.

Adult↗

PubMed1994

Depression in complex partial seizures. Electroencephalography and cerebral metabolic correlates.

OBJECTIVE: We sought to determine whether the frequency of depressive disorders among patients with complex partial seizures is associated with the laterality of ictal onset or the laterality of interictal cerebral hypometabolism. DESIGN: Fifty-three patients with medically intractable complex partial seizures were assessed for history of interictal depressive disorders meeting strict Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R), criteria with use of a modification of the Structured Clinical Interview for DSM-III-R. All subjects underwent video-electroencephalographic telemetry and fludeoxyglucose F18 positron emission tomographic scanning. The main outcome measure was the frequency of a history of major depressive episodes (MDEs) in subjects with left-sided vs right-sided ictal onset and in subjects with left-sided vs right-sided temporal lobe hypometabolism. RESULTS: Thirty-three subjects (62%) had a history of interictal depressive disorders, 16 (30%) of whom met criteria for one or more MDEs. More of those with left-sided ictal onset had a history of depression. Thirty-six subjects had definite unilateral temporal lobe hypometabolism demonstrated by positron emission tomographic scanning. More of those with left temporal lobe hypometabolism had a history of MDEs, and the combination of left temporal lobe hypometabolism and high-degree hypometabolism was strongly associated with a history of MDEs. Furthermore, among those with right temporal lobe hypometabolism, more of those with high-degree hypometabolism had a history of MDEs. CONCLUSION: Laterality of ictal onset and degree of interictal temporal lobe hypometabolism may be interdependent factors that contribute to the risk of depressive disorder in patients with complex partial seizures.

Adult↗

PubMed2001

Vibrant semi-implantable hearing device with digital sound processing: effective gain and speech perception.

BACKGROUND: The Vibrant Soundbridge (Symphonix Devices, San Jose, Calif) is a semi-implantable hearing device. The transducer is attached directly to the incus and is linked by telemetry to the externally worn audioprocessor. A major advantage of this semi-implantable setup, especially during its experimental phase, is that the audioprocessor can be updated. Recently, we replaced the previous 2-channel analog audioprocessor in 14 patients with a 3-channel digital device. DESIGN: Prospective clinical study. Basic functions were measured, including gain as a function of input level and speech perception in quiet. PATIENTS: Patients (n = 14) had moderate to severe sensorineural hearing impairment (average hearing threshold at 0.5, 1.0, 2.0, and 4.0 kHz of 40- to 76-dB hearing level [HL]) and chronic external otitis, which contraindicated use of an ear mold. RESULTS: Gain of the 3-channel audioprocessor for comfortable listening levels and for conversational levels varied from approximately 15- to 30-dB HL, suggesting that the device is suitable for patients with hearing loss of up to 60- to 70-dB HL. In 5 patients, identical measurements were performed using their conventional hearing aids. The other 9 patients did not use a conventional hearing device because of severe external otitis. On average, results obtained with the Vibrant Soundbridge were not as good as those obtained with the conventional device. Nevertheless, patients were satisfied with the Vibrant Soundbridge because they could use it all day without pain or itching. CONCLUSIONS: The Vibrant Soundbridge is suitable for patients with hearing loss of up to 70-dB HL. Compared with conventional devices, in audiometric terms, a surplus value of the Vibrant Soundbridge was not found.

Adult↗

PubMed1983

Cardiac pacing in children and young adults.

Pacemakers are being used with increasing frequency in children. New pacemakers are smaller, more sophisticated, can be programmed, have output telemetry, are more reliable, and are longer lasting. Implant techniques have been modified, so that they are less traumatic to the patient and result in better electrical measurements. Transvenous implants seem to be the preferred method in children who weigh 13.5 kg or more. Physiologic dual-chamber pacemakers make the patients feel better. The time between hospitalizations for pacemaker replacements or revisions has increased from 14.7 months in 1974 to 22 months in this study.

Adolescent↗

PubMed2002

Impact of a clinical decision rule on hospital triage of patients with suspected acute cardiac ischemia in the emergency department.

CONTEXT: Emergency department (ED) physicians often are uncertain about where in the hospital to triage patients with suspected acute cardiac ischemia. Many patients are triaged unnecessarily to intensive or intermediate cardiac care units. OBJECTIVE: To determine whether use of a clinical decision rule improves physicians' hospital triage decisions for patients with suspected acute cardiac ischemia. DESIGN AND SETTING: Prospective before-after impact analysis conducted at a large, urban, US public hospital. PARTICIPANTS: Consecutive patients admitted from the ED with suspected acute cardiac ischemia during 2 periods: preintervention group (n = 207 patients enrolled in March 1997) and intervention group (n = 1008 patients enrolled in August-November 1999). INTERVENTION: An adaptation of a previously validated clinical decision rule was adopted as the standard of care in the ED after a 3-month period of pilot testing and training. The rule predicts major cardiac complications within 72 hours after evaluation in the ED and stratifies patients' risk of major complications into 4 groups--high, moderate, low, and very low--according to electrocardiographic findings and presence or absence of 3 clinical predictors in the ED. MAIN OUTCOME MEASURES: Safety of physicians' triage decisions, defined as the proportion of patients with major cardiac complications who were admitted to inpatient cardiac care beds (coronary care unit or inpatient telemetry unit); efficiency of decisions, defined as the proportion of patients without major complications who were triaged to an ED observation unit or an unmonitored ward. RESULTS: By intention-to-treat analysis, efficiency was higher in the intervention group (36%) than the preintervention group (21%) (difference, 15%; 95% confidence interval [CI], 8%-21%; P<.001). Safety was not significantly different (94% in the intervention group vs 89%; difference, 5%; 95% CI, -11% to 39%; P =.57). Subgroup analysis of intervention-group patients showed higher efficiency when physicians actually used the decision rule (38% vs 27%; difference, 11%; 95% CI, 3%-18%; P =.01). Improved efficiency was explained solely by different triage decisions for very low-risk patients. Most surveyed physicians (16/19 [84%]) believed that the decision rule improved patient care. CONCLUSIONS: Use of the clinical decision rule had a favorable impact on physicians' hospital triage decisions. Efficiency improved without compromising safety.

Acute Disease↗

PubMed2004

Surveillance of medical device-related hazards and adverse events in hospitalized patients.

CONTEXT: Although adverse drug events have been extensively evaluated by computer-based surveillance, medical device errors have no comparable surveillance techniques. OBJECTIVES: To determine whether computer-based surveillance can reliably identify medical device-related hazards (no known harm to patient) and adverse medical device events (AMDEs; patient experienced harm) and to compare alternative methods of detection of device-related problems. DESIGN, SETTING, AND PARTICIPANTS: This descriptive study was conducted from January through September 2000 at a 520-bed tertiary teaching institution in the United States with experience in using computer tools to detect and prevent adverse drug events. All 20 441 regular and short-stay patients (excluding obstetric and newborn patients) were included. MAIN OUTCOME MEASURES: Medical device events as detected by computer-based flags, telemetry problem checklists, International Classification of Diseases, Ninth Revision (ICD-9) discharge code (which could include AMDEs present at admission), clinical engineering work logs, and patient survey results were compared with each other and with routine voluntary incident reports to determine frequencies, proportions, positive predictive values, and incidence rates by each technique. RESULTS: Of the 7059 flags triggered, 552 (7.8%) indicate a device-related hazard or AMDE. The estimated 9-month incidence rates (number per 1000 admissions [95% confidence intervals]) for AMDEs were 1.6 (0.9-2.5) for incident reports, 27.7 (24.9-30.7) for computer flags, and 64.6 (60.4-69.1) for ICD-9 discharge codes. Few of these events were detected by more than 1 surveillance method, giving an overall incidence of AMDE detected by at least 1 of these methods of 83.7 per 1000 (95% confidence interval, 78.8-88.6) admissions. The positive predictive value of computer flags for detecting device-related hazards and AMDEs ranged from 0% to 38%. CONCLUSIONS: More intensive surveillance methods yielded higher rates of medical device problems than found with traditional voluntary reporting, with little overlap between methods. Several detection methods had low efficiency in detecting AMDEs. The high rate of AMDEs suggests that AMDEs are an important patient safety issue, but additional research is necessary to identify optimal AMDE detection strategies.

Adult↗

PubMed1996

Comparison of the body temperature rhythms of diurnal and nocturnal rodents.

The daily rhythm of body temperature of six rodent species, three of them nocturnal (Rattus norvegicus, Mesocricetus auratus, and Meriones unguiculatus) and three diurnal (Octodon degus, Spermophilus tridecemlineatus, and S. richardsoni), was studied by telemetry under a 14L:10D light-dark cycle. Significant interspecies differences were found in the mean level (range: 36.0-37.4 degrees C), amplitude (range: 2.1 degrees-4.3 degrees C), robustness (range: 115-185 Qp), and acrophase (range: 8.5-16.0 hr) of the temperature rhythm. In addition, a positive correlation (r = 0.79) was found between body mass and robustness of the rhythm across species. However, the only consistent difference between the diurnal and nocturnal species was the acrophase, which occurred during the day in the diurnal species (range: 8.5-11.5 hr) and during the night in the nocturnal species (range: 13.5-16.0 hr).

Animals↗

PubMed1998

Differences in stress reactivity of laboratory macaques measured by heart period and respiratory sinus arrhythmia.

Some laboratory primates are more likely than others to react to anxiety-provoking stressors. Individuals that overreact to stressors may experience diminished psychological well-being and would be inappropriate for some experiments. The differences between reactive and nonreactive individuals may be reflected in heart period and respiratory sinus arrhythmia (RSA). Using surface electrodes and radio telemetry, we measured these two cardiac variables in seven male and ten female singly caged longtailed macaques (Macaca fascicularis) when they were exposed to two stressors, a sudden noise (whistle test) and an unfamiliar technician wearing capture gloves (glove test). Behavior was videotaped during both tests. For the whistle test, cardiac data were recorded before, during, and after two 1 minute whistle blasts separated by 90 min. For the glove test, data were recorded in 1 minute blocks every 8 minutes over 96 minutes before, during, and after 1 minute exposure to the gloved technician. Heart period was decreased and RSA was suppressed during both the whistle and glove exposures. After the whistle test, the cardiac activity of most subjects returned to baseline levels within 10 minutes. The glove test produced more extended suppression, with greater individual differences, than the whistle test. There were greater individual differences in RSA than in heart period. These enhanced individual differences were used to define stress reactors that differed from nonreactors in their cardiac data profiles. Of 16 subjects that completed the glove test, five were identified as reactors.

Animals↗

PubMed1994

A phase I trial of intrahepatic verapamil and doxorubicin. Regional therapy to overcome multidrug resistance.

BACKGROUND: Verapamil can modulate multidrug resistance in vitro, but only at levels that are not tolerable when administered systemically. Regional strategies of drug administration may permit the delivery of high concentrations of a drug to specific areas with lower systemic levels. Colorectal cancers typically express the multidrug resistance phenotype. METHODS: A Phase I trial was performed to determine the maximum tolerable dose (MTD) and dose limiting toxicities of verapamil by hepatic artery infusion, together with doxorubicin, to patients with hepatic metastases of colorectal cancer. Fourteen patients with metastatic colorectal cancer received a 14-hour intrahepatic infusion of verapamil. Six hours after the start of the infusion, a fixed dose of doxorubicin (50 mg/m2) was given, also via the hepatic artery, over a 30-minute period. Patients were followed by cardiac telemetry but were not in an intensive care setting, and no invasive monitoring was used. All patients had received prior intrahepatic chemotherapy. RESULTS: The MTD of intrahepatic verapamil on this schedule in this patient population was 1.2 mg/kg/hour. Hypotension was the dose limiting toxicity. No major objective responses were noted in this heavily pretreated patient population. A dose of 1.0 mg/kg/hour is recommended for Phase II trials. CONCLUSIONS: Based on estimations of normal hepatic artery blood flow, the estimated concentration of verapamil delivered to the hepatic tumors at 1.0 mg/kg/hour is 3.6 micrograms/ml (7.3 microM), which is comparable to concentrations at which an in vitro reversal of MDR is seen. This study demonstrates that the systemic toxicities of an MDR reversal agent can be overcome by regional drug delivery, establishing this approach as an important model system for further study of MDR modulation.

Adenocarcinoma↗

PubMedDate not supplied

Physiology of hot flashes.

Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.

Body Temperature Regulation↗

PubMed1987

Seizures during barbiturate withdrawal: relation to blood level.

We studied 21 patients with complex partial seizures during phenobarbital (PB) or primidone withdrawal. Blood levels were measured daily, and seizure frequency was monitored by nursing staff and EEG-video telemetry. Patients were monitored for one week of baseline and for five weeks after PB tapering was initiated (withdrawal). Most were observed for at least one week after levels were undetectable. When ranked seizure counts were averaged, there was a tendency for seizure rates to be highest as PB levels passed through the range 15 to 20 mg/l, compared with rates at higher or lower PB levels. There was little or no relation between the rate of PB withdrawal, other drug therapy, or initial PB level and the ratio of highest seizure frequency to mean seizure frequency. Patients withdrawing from PB may be most likely to experience an increase in seizure frequency when their PB blood level falls below 20 mg/l.

Humans↗

PubMed1994

Positron emission tomographic measurement of cerebral blood flow and temporal lobectomy.

We used positron emission tomography (PET) and bolus injection of H2(15O) to measure interictal cerebral blood flow (CBF) in 32 patients who had temporal lobectomy for uncontrolled complex partial seizures. Seizure focus localization was confirmed by ictal video-electroencephalographic (video-EEG) telemetry, and patients who had imaging findings suggesting the presence of a tumor were excluded. PET-CBF studies were interpreted using a standard template by raters blinded to EEG and clinical data, and were not used in surgical planning. After surgery, patients were followed for 32 +/- 18 months. Twenty-six patients were seizure free and 6 had persistent seizures. Mean lateral temporal hypoperfusion was 8 +/- 14% in patients who became seizure free and 9 +/- 6% in patients with persistent seizures. Fourteen patients had at least 15%, and 11 at least 20% hypoperfusion, but were not more likely to be seizure free. Three additional patients had 15 to 20% hypoperfusion in the temporal lobe contralateral to their EEG focus. PET measurement of CBF using bolus H2(15O) should not be used to help select patients for temporal lobectomy.

Brain↗

PubMed1998

Angelman syndrome: correlations between epilepsy phenotypes and genotypes.

We compared epilepsy phenotypes with genotypes of Angelman syndrome (AS), including chromosome 15q11-13 deletions (class I), uniparental disomy (class II), methylation imprinting abnormalities (class III), and mutation in the UBE3A gene (class IV). Twenty patients were prospectively selected based on clinical cytogenetic and molecular diagnosis of AS. All patients had 6 to 72 hours of closed-circuit television videotaping and digitized electroencephalogrpahic (EEG) telemetry. Patients from all genotypic classes had characteristic EEGs with diffuse bifrontally dominant high-amplitude 1- to 3-Hz notched or triphasic or polyphasic slow waves, or slow and sharp waves. Class I patients had severe intractable epilepsy, most frequently with atypical absences and myoclonias and less frequently with generalized extensor tonic seizures or flexor spasms. Epileptic spasms were recorded in AS patients as old as 41 years. Aged-matched class II, III, and IV patients had either no epilepsy or drug-responsive mild epilepsy with relatively infrequent atypical absences, myoclonias, or atonic seizures. In conclusion, maternally inherited chromosome 15q11-13 deletions produce severe epilepsy. Loss-of-function UBE3A mutations, uniparental disomy, or methylation imprint abnormalities in AS are associated with relatively mild epilepsy. Involvement of other genes in the chromosome 15q11-13 deletion, such as GABRB3, may explain severe epilepsy in AS.

Adolescent↗

PubMed2005

Venous sphincters in the choroidea of spontaneously hypertensive rats.

Ocular vasculopathy resulting from severe systemic hypertension affects retina, choroidea, and the optic nerve. While the pathologic changes of the arterial system, including luminal narrowing, are well documented, little is known about the ocular venous vessels in hypertension. Adult 18-week-old spontaneously hypertensive rats (SHRs) were untreated (control) or treated with lisinopril for 4 weeks; normotensive Wistar-Kyoto (WKY) rats were additional controls. The mean systemic blood pressure (MSP) was monitored chronically using telemetry. The ocular microvasculature was examined using scanning electron microscopy (SEM) of corrosion casts, histology of serial sections, and computer-based 3D reconstruction. The MSP in control SHRs (145 +/- 11.9 mmHg) was decreased to 68.1 +/- 4.9 mmHg (P < 0.001) following treatment, which was even below the baseline level of WKY (96.7 +/- 5.8) rats (P < 0.05). In addition to media thickening in arteries, the venous plexus of the choroidea in control SHRs revealed multiple tufts of smooth muscle cells (sphincters) that narrowed the lumen. Correlating to histology, SEM of casts and 3D reconstruction showed numerous constrictions and muscular tufts in veins of the choroidea, narrowing the vascular lumen up to 47%. Following antihypertensive treatment, the percentage of sphincter constriction was decreased to 6% (P < 0.001). The depth of venous sphincter contraction correlated significantly with MSP (r = 0.87). To our knowledge, these results indicate for the first time that venous sphincters occur in the choroidea of the SHRs, and that their muscularity correlates with MSP. Venous sphincters might be involved in the pathophysiology of hypertension-related ocular changes.

Animals↗

PubMed1997

Dofetilide in patients with left ventricular dysfunction and either heart failure or acute myocardial infarction: rationale, design, and patient characteristics of the DIAMOND studies. Danish Investigations of Arrhythmia and Mortality ON Dofetilide.

BACKGROUND: Attempts to prolong life with antiarrhythmic drugs in patients at increased risk of sudden cardiac death have so far been disappointing or inconclusive. HYPOTHESIS: The Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) encompass two survival studies testing the prophylactic use of the selective potassium-channel blocker, dofetilide, in patients at high risk of sudden death. METHODS: The first study includes patients admitted to hospital with congestive heart failure (CHF), the other includes patients with acute myocardial infarction (MI) within the previous 7 days. In both studies patients must have left ventricular systolic dysfunction (ejection fraction < or = 35%) determined by echocardiography. Each of the two studies are planned to enroll 1500 patients. Consecutive hospitalized patients with MI or CHF are screened in 37 Danish hospitals. Eligible patients are randomized to receive dofetilide or matching placebo. All patients are continuously monitored by telemetry for the first 3 days of the study to detect possible arrhythmic events and to ensure resuscitation in case of serious arrhythmias. Minimum duration of follow-up is 12 months. RESULTS: Between November 1993 and July 1996, a total of 5812 consecutive patients with CHF and 8688 consecutive patients with MI was screened for entry. Of these, 1518 patients were included in the CHF study and 1510 patients in the MI study. Overall 1-year mortality of randomized patients were 28 and 22%, respectively. CONCLUSION: DIAMOND will provide important data on the safety and efficacy of dofetilide in high-risk patients with left ventricular dysfunction and either CHF or MI, as well as evaluate tolerability in these populations.

Aged↗

PubMed2004

Rapid screening of cardiac patients with a miniaturized hand-held ultrasound imager--comparisons with physical examination and conventional two-dimensional echocardiography.

BACKGROUND: Rapid screening of cardiac patients with a hand-held ultrasound imager (SonoHeart [SH]) could provide valuable clinical information. HYPOTHESIS: Whether the use of this device yields additional information to a carefully conducted physical examination and comparable findings to those of conventional two-dimensional echocardiography (2-D) during inpatient rounds is not well established and is the subject of this study. METHODS: In all, 100 consecutive telemetry patients underwent rapid screening with 2-D and color Doppler SH during inpatient rounds. SonoHeart findings were compared with results from conventional 2-D and physical examination conducted by an attending cardiologist. RESULTS: All patients had interpretable images. Mean scanning time with SH was 5.0 +/- 1.2 min; 2-D and SH findings were comparable. The parameters studied included chamber sizes, left ventricular (LV) systolic function, presence of LV hypertrophy (LVH), wall motion abnormalities (WMA), pericardial effusion (PE), and valvular regurgitations. Mild to moderate valvular regurgitation and LV systolic dysfunction were reliably diagnosed by SH in a number of patients whose symptoms were unrelated to the abnormalities detected. CONCLUSIONS: Rapid screening with SH provides accurate and valuable information that would otherwise be undetected during physical examination. Its introduction into clinical practice may redefine the initial approach to patients with cardiovascular disease.

Cardiovascular Diseases↗

PubMed2006

Cardiac sequelae in Brooklyn after the September 11 terrorist attacks.

BACKGROUND: Terrorism, such as the attacks on the World Trade Center (WTC) on September 11, 2001, result in higher stress-related disorders, especially in those persons in close proximity. HYPOTHESIS: Cardiac events resulting from the September 11, 2001 tragedy have not been detailed near the WTC. METHODS: Patients admitted to the Telemetry and Coronary Care Units at New York Methodist Hospital 4 miles from the WTC 60 days prior to and after the September 11 attacks were analyzed. In all, 1,653 admissions were reviewed: 427 records pre 9/11/2001 and 422, 393, and 411 records in the post-9/11/2001, pre-9/11/2000, and post-9/11/2000 data sets, respectively. Patients were categorized based on diagnosis: acute myocardial infarction (MI), unstable angina (UA), tachyarrhythmia (TA), and others (including syncope and congestive heart failure). RESULTS: There was a significant difference in the proportion of the various cardiac diagnoses post 9/11/01 (p = 0.008 by chi-square analysis). Compared with pre 9/11/2001, there were significantly more patients with acute MI (15.5 vs. 11.2%) and TA (19.9 vs. 13.6%) but fewer with UA (39.6 vs. 47.3%) after the terrorist attacks. The distribution of cardiac events during a similar period of time in 2000 revealed no such pattern. CONCLUSIONS: There was a significant increase in acute MI and TA and a smaller increase in UA after the September 11 attacks. The difference did not appear to be due to temporal variation. It appears that stress likely contributed to an increase in TA by itself or with ischemia, resulting in progression of UA to acute MI.

Aged↗

PubMed2003

Cardiac electrophysiological phenotypes in postnatal expression of Nkx2.5 transgenic mice.

Nkx2.5 is a conserved homeodomain (HD) containing a transcription factor essential for early cardiac development. We generated several mutations modeling some patients with congenital heart disease. Transgenic mice (tg) expressing the wildtype Nkx2.5 under beta-myosin heavy chain (MHC) promoter died during the embryonic stage. However, tg mice expressing this mutation under beta-MHC promoter (beta-MHC-TG(I183P)), the wildtype Nkx2.5 (alpha-MHC-TG(wild)), and a putative transcriptionally active mutant (carboxyl-terminus deletion, alpha-MHC-TG(DeltaC)) under alpha-MHC promoter showed postnatal lethal heart failure. Given the profound atrioventricular conduction abnormalities we recently demonstrated in beta-MHC-TG(I183P) mice, the aim of this study was to determine whether alpha-MHC-TG(wild) and alpha-MHC-TG(DeltaC) mutant mice display similar cardiac electrophysiological phenotypes. Surface ECG recordings and in vivo electrophysiology studies were performed in alpha-MHC-TG(wild) mice and controls at 6 weeks of age, and in alpha-MHC-TG(DeltaC) mice and controls at 10 weeks of age. Ambulatory ECG recordings in alpha-MHC-TG(wild) and controls were obtained using an implantable radiofrequency telemetry system. PR prolongation and atrioventricular nodal dysfunction were detected in alpha-MHC-TG(wild) and alpha-MHC-TG(DeltaC) mice. Bradycardia and prolonged PR interval were seen in ambulatory ECG of alpha-MHC-TG(wild) mice compared to controls. Several alpha-MHC-TG(wild) mice died of bradycardia. Fetal and neonatal mutant Nkx2.5 expression causes severe cardiac conduction failure. Postnatal overexpression of nonmutant (wild) Nkx2.5 also causes conduction abnormalities, although the onset is after the neonatal stage. Bradycardia and AV conduction failure may contribute to the lethal heart failure and early mortality.

Animals↗