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Biomedical subjects

Mark S Link

Publications and source records attributed to Mark S Link.

At least 37 records · Page 2Linked to original sources
PubMed2005

Atrioventricular nodal reverse facilitation in connexin40-deficient mice.

BACKGROUND: Facilitation is an important physiologic property of the atrioventricular (AV) node. Previous studies demonstrated abnormal AV conduction in connexin (Cx)40-deficient mice. OBJECTIVES: We hypothesize that Cx40-deficient mice display altered patterns of AV nodal facilitation compared with wild-type mice. METHODS: Sixteen 36-week-old mice (eight Cx40(-/-) mice and eight Cx40(+/+) controls) underwent in vivo closed chest electrophysiologic study. A 2Fr octapolar catheter was advanced into the right ventricle to record a His-bundle electrogram. A special facilitation stimulation protocol was performed in each mouse to evaluate facilitation. Following atrial drive pacing (S1S1) at 150 ms, a facilitating beat S2 was delivered prior to the test beat S3. S3H3 was measured for varying S1S2 values at fixed H2S3 intervals. RESULTS: Progressive shortening of S1S2 (from 150 ms to 130, 110, and 90 ms) resulted in gradual prolongation of S2H2. The prolongation was more pronounced in Cx40(-/-) mice for each S1S2 compared with wild-type mice (P <.001). In each wild-type mouse, for a given H2S3 interval, this gradual increase in S2H2 produced progressive shortening of S3H3, so-called AV nodal facilitation phenomenon. However, in each Cx40(-/-) mouse, facilitation was seen only at S1S2 of 130 ms (P <.001 vs S1S2 of 150 ms). Evidence of reverse facilitation was documented at S1S2 of 110 and 90 ms. CONCLUSION: Facilitation is observed in wild-type mice. With similar S1S2 intervals in Cx40-deficient mice, facilitation is seen only at longer S1S2 intervals, whereas reverse facilitation is seen at shorter S1S2 intervals, suggesting that Cx40 is involved in the generation of AV nodal facilitation.

Animals↗
PubMed2005

Role of streptomycin-sensitive stretch-activated channel in chest wall impact induced sudden death (commotio cordis).

INTRODUCTION: Deaths secondary to low-energy impacts to the precordium in young individuals (commotio cordis) have been reported with increasing frequency. In a swine model, baseball impacts induce ventricular fibrillation when directed at the center of the left ventricle during the vulnerable portion of repolarization just prior to the T-wave peak. It has been hypothesized that activation of stretch-sensitive channels could be crucial for this electrophysiological phenomenon. In this study, a nonselective stretch-activated cation channel was pharmacologically blocked prior to chest blows to determine whether this channel represents a possible pathway by which commotio cordis events occur. METHODS: In a randomized and blinded experiment, 12 swine (mean 17.1 +/- 2.5 kg) received either 2-g streptomycin intramuscularly (mean serum concentration 115 +/- 18 muM) or sterile water prior to chest impact. Each animal received six precordial impacts with a baseball propelled at 40 mph. RESULTS: There was no significant difference in the frequency of induced VF in the animals administered streptomycin (10 of 19 impacts: 53%) compared to those control animals receiving only sterile water (10 of 31: 32%) (P = 0.15). However, the magnitude of ST segment elevation was less in the streptomycin-treated animals (19 +/- 19 mV) versus controls (61 +/- 46 mV) (P = 0.015). CONCLUSION: Streptomycin did not alter the frequency of ventricular fibrillation in our commotio cordis model, indicating that the stretch-activated channel is not implicated in the genesis of chest blow-induced cardiac arrest. However, streptomycin did reduce ST elevation following impact suggesting that the stretch-activated channel may play a role in ST segment elevation following chest wall blows.

Animals↗
PubMed2005

Association of air pollution with increased incidence of ventricular tachyarrhythmias recorded by implanted cardioverter defibrillators.

Epidemiologic studies have demonstrated a consistent link between sudden cardiac deaths and particulate air pollution. We used implanted cardioverter defibrillator (ICD) records of ventricular tachyarrhythmias to assess the role of air pollution as a trigger of these potentially life-threatening events. The study cohort consisted of 203 cardiac patients with ICD devices in the Boston metropolitan area who were followed for an average of 3.1 years between 1995 and 2002. Fine particle mass and gaseous air pollution plus temperature and relative humidity were measured on almost all days, and black carbon, sulfate, and particle number on a subset of days. Date, time, and intracardiac electrograms of ICD-detected arrhythmias were downloaded at the patients' regular follow-up visits (about every 3 months). Ventricular tachyarrhythmias were identified by electrophysiologist review. Risk of ventricular arrhythmias associated with air pollution was estimated with logistic regression, adjusting for season, temperature, relative humidity, day of the week, patient, and a recent prior arrhythmia. We found increased risks of ventricular arrhythmias associated with 2-day mean exposure for all air pollutants considered, although these associations were not statistically significant. We found statistically significant associations between air pollution and ventricular arrhythmias for episodes within 3 days of a previous arrhythmia. The associations of ventricular tachyarrhythmias with fine particle mass, carbon monoxide, nitrogen dioxide, and black carbon suggest a link with motor vehicle pollutants. The associations with sulfate suggest a link with stationary fossil fuel combustion sources.

Adult↗
PubMed2005

Cardiovascular toxicities of performance-enhancing substances in sports.

Athletes commonly use drugs and dietary supplements to improve athletic performance or to assist with weight loss. Some of these substances are obtainable by prescription or by illegal means; others are marketed as supplements, vitamins, or minerals. Nutritional supplements are protected from Food and Drug Administration regulation by the 1994 US Dietary Supplement Health and Education Act, and manufacturers are not required to demonstrate proof of efficacy or safety. Furthermore, the Food and Drug Administration lacks a regulatory body to evaluate such products for purity. Existing scientific data, which consist of case reports and clinical observations, describe serious cardiovascular adverse effects from use of performance-enhancing substances, including sudden death. Although mounting evidence led to the recent ban of ephedra (ma huang), other performance-enhancing substances continue to be used frequently at all levels, from elementary school children to professional athletes. Thus, although the potential for cardiovascular injury is great, few appropriately designed studies have been conducted to assess the benefits and risks of using performance-enhancing substances. We performed an exhaustive OVID MEDLINE search to Identify all existing scientific data, review articles, case reports, and clinical observations that address this subject. In this review, we examine the current evidence regarding cardiovascular risk for persons using anabolic-androgenic steroids including 2 synthetic substances, tetrahydrogestrinone and androstenedione (andro), stimulants such as ephedra, and nonsteroidal agents such as recombinant human erythropoietin, human growth hormone, creatine, and beta-hydroxy-beta-methylbutyrate.

Androstenedione↗
PubMed2005

Particulate air pollution and nonfatal cardiac events. Part II. Association of air pollution with confirmed arrhythmias recorded by implanted defibrillators.

Implanted cardioverter defibrillators (ICDs) monitor patients for episodes of cardiac arrhythmias and can initiate a therapeutic intervention to restore normal heart rhythm. These devices also record dates, times, and electrograms of these episodes. We examined the effects of air pollution on the incidence of arrhythmias in 195 cardiac patients with ICD devices in the Boston metropolitan area between July 1995 and July 2002. Gaseous air pollutant and meteorologic data were measured on essentially all days, fine particle mass on 80% of the days, and black carbon (BC) on 61% of the days. Date and time of detected arrhythmias, intracardiac electrograms, and therapeutic interventions were downloaded during the patients' regular follow-up visits every 3 months on average. A cardiac electrophysiologist reviewed electrograms recorded before, during, and after the arrhythmias and categorized them into ventricular and supraventricular events. Risk of arrhythmias associated with air pollution was estimated using logistic regression with adjustments for season, temperature, relative humidity, day of the week, and patient. We found increased relative risks of ventricular arrhythmias (VAs) associated with an increase in 2-day mean concentrations for all air pollutants considered, although these associations were not statistically significant. The relative risks of supraventricular arrhythmias (SVAs) increased in association with 2-day mean concentrations for all air pollutants, and this association was significant only for sulfur dioxide (SO2) at 4 ppb (odds ratio [OR] = 1.33; 95% confidence interval [CI] = 1.04, 1.70). The positive associations of VAs and SVAs with particulate matter less than 2.5microm in aerodynamic diameter (PM2.5; also referred to as fine particles), carbon monoxide (CO), nitrogen dioxide (NO2), BC, and SO2 suggest a link with motor vehicle pollutants. We explored patient characteristics that may have identified subjects susceptible to the effects of air pollution. The association of air pollution with SVAs was blunted by regularly prescribed beta-blockers. We found stronger associations of air pollution with VAs for episodes within 3 days of a previous arrhythmia, suggesting that VAs were triggered by air pollution episodes in combination with other factors that raised the patient's underlying risk. Although ICDs are specifically designed to monitor and treat only VAs, these results suggest that air pollution may trigger both VAs and SVAs.

Adult↗
PubMed2004

New concepts in pacemaker syndrome.

After implantation of a permanent pacemaker, patients may experience severe symptoms of dyspnea, palpitations, malaise, and syncope resulting from pacemaker syndrome. Although pacemaker syndrome is most often ascribed to the loss of atrioventricular (A-V) synchrony, more recent data may also implicate left ventricular dysynchrony caused by right ventricular pacing. Previous studies have not shown reductions in mortality or stroke with rate-modulated dual-chamber (DDDR) pacing as compared to ventricular-based (VVI) pacing. The benefits in A-V sequential pacing with the DDDR mode are likely mitigated by the interventricular (V-V) dysynchrony imposed by the high percentage of ventricular pacing commonly seen in the DDDR mode. Programming DDDR pacemakers to encourage intrinsic A-V conduction and reduce right ventricular pacing will likely decrease heart failure and pacemaker syndrome. Studies are currently ongoing to address these questions.

Journal Article↗
PubMed2004

Echocardiographic evidence of left atrial abnormality in young patients with lone paroxysmal atrial fibrillation.

Usual assessment of left atrial size by 2-dimensional echocardiography in the anteroposterior dimension often underestimates the true atrial size. We compared 15 young patients (< or =50 years old) with lone paroxysmal atrial fibrillation to age-matched controls, and measured atrial size in the inferosuperior and mediolateral dimensions. These additional measurements and atrial volumes were significantly increased compared with control patients, revealing that patients with apparent "lone" paroxysmal atrial fibrillation may have subtle structural abnormalities of the left atrium.

Adult↗
PubMed2004

High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST).

OBJECTIVES: We evaluated the incidence, predictors, and treatment of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based (VVIR) pacing in the Mode Selection Trial (MOST). BACKGROUND: Pacemaker syndrome, or intolerance to VVIR pacing, consists of cardiovascular signs and symptoms induced by VVIR pacing. METHODS: The definition of pacemaker syndrome required that a patient with single-chamber VVIR pacing develop either congestive signs and symptoms associated with retrograde conduction during VVIR pacing or a >or=20 mm Hg reduction of systolic blood pressure during VVIR pacing, associated with reproducible symptoms of weakness, lightheadedness, or syncope. RESULTS: Of 996 patients randomized to VVIR pacing, 182 (18.3%) met criteria for pacemaker syndrome in follow-up. Pacemaker syndrome occurred early in most patients (13.8% at 6 months, 16.0% at 1 year, increasing to 19.7% at 4 years). Baseline univariate predictors of pacemaker syndrome included a lower sinus rate and higher programmed pacemaker rate. Previous heart failure, ejection fraction, and drop in systolic blood pressure with VVIR pacing at implantation did not predict the development of pacemaker syndrome. Post-implantation predictors of pacemaker syndrome were a higher percentage of paced beats, higher programmed low rate, and slower underlying spontaneous sinus rate. Quality of life decreased at the time of diagnosis of pacemaker syndrome and improved with reprogramming to atrial-based pacing. CONCLUSIONS: Severe pacemaker syndrome developed in nearly 20% of VVIR-paced patients and improved with reprogramming to the dual-chamber pacing mode. Because prediction of pacemaker syndrome is difficult, the only way to prevent pacemaker syndrome is to implant atrial-based pacemakers in all patients.

Aged↗
PubMed2004

Comparison of survival and other complications after heart transplantation in patients taking amiodarone before surgery versus those not taking amiodarone.

Concern exists regarding preoperative amiodarone use and complications occurring after heart transplantation (HT). During a 10-year period of performing HT, we found that patients treated with amiodarone before undergoing HT had decreased overall survival, required longer periods of ventilatory support, and were at increased risk for significant bleeding complications. These findings raise further concern about the use of amiodarone treatment in patients with heart failure before undergoing HT.

Adult↗
PubMed2004

Enalapril treatment and hospitalization with atrial tachyarrhythmias in patients with left ventricular dysfunction.

BACKGROUND: Experimental and clinical evidence suggests a preventive role for agiotensin-coverting enzyme (ACE) inhibitors on the development of atrial fibrillation. However, the effect of ACE inhibition on hospitalization with atrial tachyarrhythmias in patients with left ventricular (LV) dysfunction is not known. We sought to determine whether enalapril treatment reduced hospitalizations with atrial tachyarrhythmias in patients with LV dysfunction. METHODS: We performed a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) trial. Hospitalizations with atrial tachyarrhythmias were noted. RESULTS: A total of 192 hospitalizations with atrial tachyarrhythmias occurred in 158 patients during a follow-up period of 34 months. The time to first hospitalization with atrial tachyarrhythmias or death was significantly lower in the enalapril group (P =.005). In a multivariate analysis adjusting for the presence of atrial fibrillation at study entry, enalapril treatment was associated with a reduction in the rate of hospitalization with atrial tachyarrhythmias or death (RR, 0.87; 95% CI, 0.79-0.96; P =.007). The incidence of hospitalization with atrial tachyarrhythmias was 7.9 hospitalizations per 1000 patient-years of follow-up in the enalapril group, compared with 12.4 per 1000 patient-years in the placebo group (RR, 0.64; 95% CI, 0.48-0.85; P =.002). CONCLUSION: Enalapril is associated with a decreased incidence of hospitalization with atrial tachyarrhythmias in patients with LV dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a condition associated with the risk of sudden death (SD). METHODS AND RESULTS: We conducted a multicenter study of the impact of the implantable cardioverter-defibrillator (ICD) for prevention of SD in 132 patients (93 males and 39 females, age 40+/-15 years) with ARVC/D. Implant indications were a history of cardiac arrest in 13 patients (10%), sustained ventricular tachycardia in 82 (62%), syncope in 21 (16%), and other in 16 (12%). During a mean follow-up of 39+/-25 months, 64 patients (48%) had appropriate ICD interventions, 21 (16%) had inappropriate interventions, and 19 (14%) had ICD-related complications. Fifty-three (83%) of the 64 patients with appropriate interventions received antiarrhythmic drug therapy at the time of first ICD discharge. Programmed ventricular stimulation was of limited value in identifying patients at risk of tachyarrhythmias during the follow-up (positive predictive value 49%, negative predictive value 54%). Four patients (3%) died, and 32 (24%) experienced ventricular fibrillation/flutter that in all likelihood would have been fatal in the absence of the device. At 36 months, the actual patient survival rate was 96% compared with the ventricular fibrillation/flutter-free survival rate of 72% (P<0.001). Patients who received implants because of ventricular tachycardia without hemodynamic compromise had a significantly lower incidence of ventricular fibrillation/flutter (log rank=0.01). History of cardiac arrest or ventricular tachycardia with hemodynamic compromise, younger age, and left ventricular involvement were independent predictors of ventricular fibrillation/flutter. CONCLUSIONS: In patients with ARVC/D, ICD therapy provided life-saving protection by effectively terminating life-threatening ventricular arrhythmias. Patients who were prone to ventricular fibrillation/flutter could be identified on the basis of clinical presentation, irrespective of programmed ventricular stimulation outcome.

Adolescent↗
PubMed2003

Use of antiarrhythmics and implantable cardioverter-defibrillators in congestive heart failure.

As much as half of the mortality in patients with congestive heart failure (CHF) resulting from left ventricular systolic dysfunction is attributable to sudden cardiac death. Thus, the identification of risk and prevention of sudden death are important components of treating this population of patients. Antiarrhythmic drugs have been shown to be either neutral or harmful when studied in patients with prior myocardial infarction and impaired left ventricular function. Amiodarone, when studied in patients with CHF, may be of benefit. This benefit may be more pronounced in patients with nonischemic cardiomyopathy. Implantable cardioverter defibrillators (ICDs) are of clear benefit when used in the primary and secondary prevention of sudden death in selected populations. Studies soon to be completed should clarify the role of the cardioverter-defibrillator in patients with CHF. Antiarrhythmic medications are often used in conjunction with ICDs for a variety of reasons. However, these drugs have the potential to adversely affect defibrillator function, and knowledge of these effects is important when using this strategy.

Anti-Arrhythmia Agents↗