Electrocardiographic Effects Research Articles

Fresh Gasoline Emissions, Not Paved Road Dust, Alter Cardiac Repolarization in ApoE<sup>−/−</sup> Mice

Fresh vehicular emissions potentially represent a ubiquitous environmental concern for cardiovascular health. We compared electrocardiographic effects of fresh gasoline engine emissions with resuspended paved road dust in a mouse model of coronary insufficiency. Apolipoprotein E (ApoE)-/- mice on a high fat diet were exposed by whole-body inhalation to either gasoline emissions at 60 microg/m3 particulate matter (PM), an equivalent atmosphere with particles filtered out of the whole exhaust, or paved road dust at 0.5 and 3.5 mg /m3 for 6 h/d for 3 d. Radiotelemetry recordings of electrocardiogram (ECG) were analyzed for changes in T-wave morphology (QT interval, T-wave amplitude, and T-wave Area). Following exposures, lung lavage and blood samples were obtained to assay for markers of pulmonary and systemic inflammation. No exposure induced significant changes in heart rate and only the high concentration of road dust induced signs of pulmonary inflammation. T-wave area exhibited significant deviation from baseline values during exposure to gasoline exhaust particulates, but not to either concentration of road dust or gasoline emissions sans particulates. Gasoline-exposed mice demonstrated elevated plasma endothelin-1, but did not cause systemic inflammation. These data support the hypothesis that freshly-generated engine emissions, as opposed to resuspended paved road dust, may drive cardiac effects that have been observed at road-sides in the environment. The absence of ECG effects for both very high concentrations of road dust PM and equivalent concentrations of the vapor/gas phase of gasoline engine exhaust further indicate the specific risk conferred by fresh vehicular PM.

Assessment of electrocardiographic parameters in healthy dogs undergoing dobutamine stress testing

The electrocardiographic effects of dobutamine stress testing (10 to 40 microg/kg/minute) were investigated in five conscious healthy dogs. We studied the changes in the duration and amplitude of P wave, PR interval, duration of QRS complex, R wave amplitude, QT interval, and heart rate. Development of arrhythmias and ST segment abnormalities were also recorded. It was observed that dobutamine significantly affects atrioventricular-nodal conduction and total electrical systole time at higher infusion rates. Only a single episode of sustained ventricular tachycardia was observed, which was promptly restored to sinus rhythm shortly after dobutamine infusion was discontinued. No ST segment abnormalities were detected. Dobutamine stress testing was concluded to play a role in some ECG parameters at higher infusion rates.

Haemodynamic and Electrocardiographic Effects of Xylazine, Ketamine, Lidocaine and their Combinations after Lumbar Epidural Administration in Healthy Buffalo Calves

Singh, P., Pratap, K., Amarpal, Kinjavdekar, P., Aithal, H.P. and Singh G.R. 2005. Haemodynamic and electrocardiographic effects of xylazine, ketamine, lidocaine and their combinations after lumbar epidural administration in healthy buffalo calves. J. Appl. Anim. Res., 28: 101–106. Haemodynamic and electrocardiographic effects of xylazine (0.05 mg/kg), ketamine (2.5 mg/kg), lidocaine (2.0 mg/kg) alone or in combinations viz. xylazine and ketamine and xylazine and lidocaine were evaluated in healthy buffalo calves after epidural administration in 1st lumbar space. Xylazine alone or in combination with others produced transient changes in the haemodynamic and electrocardiographic indices. The combination of xylazine and lidocaine produced more depression of the haemodynamic and electrocardiographic parameters. However, both combinations were safe in healthy buffalo calves as they produced only temporary and transient changes in the haemodynamic and electrocardiographic indices.

Absence of QTc-Interval-Prolonging or Hemodynamic Effects of a Single Dose of Bitter-Orange Extract in Healthy Subjects

To evaluate the hemodynamic and electrocardiographic effects of a single dose of commercially available bitter-orange dried-fruit extract, which is increasingly being used in dietary supplements. Randomized, double-blind, placebo-controlled, crossover study. University of Connecticut, Storrs Campus. Eighteen healthy volunteers aged 18 years or older. Subjects were given either placebo or bitter-orange dried-fruit extract (450 mg standardized to 27 mg of m- or p-synephrine) in phase 1. The opposite treatment was given during phase 2 after a washout period of at least 7 days. The rate-corrected QT (QTc) interval and blood pressure were measured before dosing and at 1, 3, 5, and 8 hours after dosing. Mean+/-SD values of the maximum postdose values were compared between groups. Subjects receiving bitter-orange extract versus those receiving placebo had similar postdose QTc intervals (402+/-29 vs 403+/-24 msec, p=0.653), systolic blood pressure (114+/-10 vs 115+/-8 mm Hg, p=0.686) and diastolic blood pressure (68+/-9 vs 68+/-8, p=0.879). Bitter-orange dried-fruit extract standardized to m- or p-synephrine 27 mg did not significantly alter the QTc interval or blood pressure after a single dose was administered. Future studies are necessary to ensure the safety of this herbal product with multiple doses.

Mechanisms of ischemia-induced ST-segment changes

Many aspects of ischemia-induced changes in the electrocardiogram lack solid biophysical underpinnings although variations in ST segments form the predominant basis for diagnostic and monitoring of patients. This incomplete knowledge certainly plays a role in the poor performance of some forms of electrocardiogram-based detection and characterization of ischemia, especially when it is limited to the subendocardium. The focus of our recent studies has been to develop a comprehensive mechanistic model of the electrocardiographic effects of ischemia. The computational component of this model is based on highly realistic heart geometry with anisotropic fiber structure and allows us to assign ischemic action potentials to contiguous regions that can span a prescribed thickness of the ventricles. A separate, high-resolution model of myocardial tissue provides us with a means of setting electrical characteristics of the heart, including the status of gap junctional coupling between cells. The experimental counterpart of this model consists of dog hearts, either in situ or isolated and perfused with blood, in which we control coronary blood flow by means of a cannula and blood pump. By reducing blood flow through the cannula for various durations, we can replicate any phase of ischemia from hyper acute to early infarction. Based on the results of these models, there is emerging a mechanism of the electrocardiographic response to ischemia that depends strongly on the anisotropic conductivity of the myocardium. Ischemic injury currents flow across the boundary between healthy and ischemic tissue, but it is their interaction with local fiber orientation and the associated conductivity that generates secondary currents that determine epicardial ST-segment potentials. Results from experiments support qualitatively the findings of the simulations and underscore the role of myocardial anisotropy in electrocardiography.

Electrocardiographic Effects of a Dietary Supplement Containing Ephedra and Caffeine—Reply

Electrocardiographic Effects of a Dietary Supplement Containing Ephedra and Caffeine—Reply

Electrocardiographic Effects of a Dietary Supplement Containing Ephedra and Caffeine

Electrocardiographic Effects of a Dietary Supplement Containing Ephedra and Caffeine

Electrocardiographic Effects of an Ephedra-Free, Multicomponent Weight-Loss Supplement in Healthy Volunteers

Metabolife 356, an ephedra-containing weight-loss product, substantially increases the corrected QT (QTc) interval. Metabolife Ephedra Free, a similar supplement, contains caffeine and extracts of green tea, garcinia cambogia, and yerba mate. Its electrocardiographic (ECG) effects are not known. Therefore, we sought to determine the effect of this supplement on the QTc interval. Randomized, double-blind, placebo-controlled, crossover study. University of Connecticut, Storrs Campus. Twenty healthy volunteers. Intervention. A single capsule containing half the normal recommended dose of Metabolife Ephedra Free or matching placebo was administered in crossover fashion, with a 7-day washout period between treatments. Baseline and three postdose ECG measurements were obtained, and QTc intervals were measured over a 5-hour study period. No significant differences in the QTc interval or other ECG variables were observed between the Metabolife Ephedra Free and placebo groups. At half the recommended single dose, Metabolife Ephedra Free does not affect the QTc interval or other ECG variables over 5 hours. Dose-response studies and studies of longer duration should be conducted.

Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits.

Epidemiological studies showed that hypercholesterolemia is associated with higher left ventricular mass. Endothelin signaling is activated in hyperlipidemic animals and may contribute to progressive ventricular hypertrophy. Simvastatin has been shown to inhibit endothelin-1. However, the behavior of simvastatin on ventricular hypertrophy in hyperlipidemic animals is not well understood. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to simvastatin in cholesterol-fed (1%) rabbits. The left ventricular weight increased 8 wk after cholesterol feeding compared with that in normocholesterolemic rabbits. Simvastatin at a clinical therapeutic dose (1.2 mg x kg(-1) x day(-1)) significantly decreased left ventricular weight by 14% and left ventricular myocyte sizes by 14% as isolated by enzymatic dissociation. Hypercholesterolemia upregulated ventricular preproendothelin-1 mRNA as assessed by real-time quantitative RT-PCR and elevated production of cardiac endothelin-1 concentration. The increased endothelin-1 responses can be inhibited after simvastatin administration. Left ventricular mass indexed by body weight positively correlated with tissue endothelin-1 levels (P = 0.0003). In Langendorff-perfused rabbit hearts, hyperlipidemia led to significant QT prolongation compared with normocholesterolemia, which can be reversed by administering simvastatin. In contrast, simvastatin-induced beneficial effects were reversed by the addition of mevalonate. The addition of bosentan, a nonspecific endothelin receptor blocker, improved the response in hypercholesterolemic rabbits and did not have additional beneficial effects in simvastatin-treated rabbits. The results of the present study suggest that the antihypertropic and electrocardiographic effects of simvastatin at a clinical therapeutic dose are mediated through inhibition of tissue endothelin-1 expression, which is linked to mevalonate metabolism, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.

Ondansetron Is Similar to Droperidol in Causing QT Prolongation

Data analyses that have been performed since the FDA’s controversial “black box” warning about droperidol in 2001 have strongly challenged the basis for the warning. Although the adverse cardiac events occurred at doses greatly exceeding those used for postoperative nausea and vomiting (PONV), the warning was issued in blanket fashion, and use of droperidol, an inexpensive and highly effective antiemetic and sedation agent, effectively ceased. In a prospective study from France, researchers evaluated the electrocardiographic effects of standardized doses of droperidol and ondansetron in 85 consecutive patients undergoing elective general anesthesia who experienced PONV in the recovery room. At the attending anesthesiologist’s discretion, patients …

More Bad News About Ephedra

The FDA recently banned ephedra due to adverse effects, including sudden cardiac death and stroke. To identify the mechanism by which ephedra can cause adverse cardiovascular events, investigators studied its electrocardiographic and hemodynamic effects. In a double-blind, randomized, crossover study, 15 healthy volunteers …

A comparison of the electrocardiographic and hemodynamic cardiotoxic effects of bupivacaine and ropivacaine in pregnant rats

A comparison of the electrocardiographic and hemodynamic cardiotoxic effects of bupivacaine and ropivacaine in pregnant rats

A comparison of the electrocardiographic and hemodynamic cardiotoxic effects of bupivacaine and ropivacaine in pregnant rats

A comparison of the electrocardiographic and hemodynamic cardiotoxic effects of bupivacaine and ropivacaine in pregnant rats

Blood pressure and electrocardiographic effects of acepromazine in anaesthetized horses

Acepromazine, a phenothiazine tranquilizer, causes hypotension in standing horses (Parry et al. 1982). However, a retrospective study (Taylor & Young 1993) showed that acepromazine pre-anesthetic medication did not affect arterial blood pressure (MAP) in anaesthetized horses. This study examined the effects of acepromazine on MAP during romifidine–ketamine–halothane anaesthesia in horses anaesthetized for various surgical procedures. Forty-four horses were allocated by block randomization to groups A and B. Group A received acepromazine 0.05 mg kg−1 IM 30 minutes before induction of anaesthesia, group B did not. All horses received romifidine 0.1 mg kg−1 IV 5 minutes before anaesthesia was induced with diazepam 0.05 mg kg−1 and 2.2 mg kg−1 ketamine IV. The horses' trachea were intubated and horses breathed 50% oxygen and 50% nitrous oxide plus halothane (concentration adjusted as required clinically) from a circle breathing system. Nitrous oxide was discontinued after 10 minutes and analgesics, flunixin 1.1 mg kg−1 and either morphine 0.1 mg kg−1 or butorphanol 0.05 mg kg−1 (matched for horses undergoing the same procedure) administered IV. The facial or dorsal metatarsal artery was catheterized for direct measurement of MAP (every 10 min) and withdrawal of blood for gas analysis (every 30 min). The electrocardiogram (ECG) was monitored continuously with a 10 seconds printout obtained every 10 minutes. Intermittent positive pressure ventilation (IPPV) was instigated if PaCO2 exceeded 9.3 kPa (70 mm Hg). Dobutamine was infused (1.0–5.0 kg−1minute−1) if MAP 70 mm Hg. Mean age, weight and duration of anaesthesia were compared between the groups using a t-test for independent samples. Gender distribution and numbers of horses requiring IPPV or dobutamine were compared between groups using a chi-squared test (with Yates correction). To compare MAP over time, the area under the curve (MAPAUC) was calculated and compared between groups using a t-test. Horses receiving dobutamine were excluded from MAPAUC and MAP comparisons. The ECG printouts were examined for arrhythmias. There were no significant differences between groups (p > 0.05). Group A contained three stallions, 10 geldings and nine mares, aged 6.3 years (range 0.75–18). Group B comprised eight stallions, 11 geldings and three mares aged 7.3(1–16) years. Duration of anaesthesia was group A 97 (50–140) minutes, group B 99 (50–160) minutes. Eight horses in group A and three in group B required IPPV. Nine horses in group A and four in group B received dobutamine. Mean arterial pressure ranged from 60 to 128 mm Hg in group A and 58–96 mm Hg in group B. Mean MAPAUC was 5941 mm Hg minute−1 in group A, in B 6000 mm Hg minute−1. Atrial pre-mature complexes were recorded from one horse in group B. No other arrhythmias were detected. Although MAP was lower in the acepromazine group, this appeared unlikely to cause a clinical problem. The incidence of arrhythmias was too low to determine the influence of acepromazine in this study.

Electrocardiographic effects of intravenous cocaine: an experimental study in a canine model.

Cocaine abuse causes cardiac dysfunction. Acute intravenous administration of cocaine may lead to development of severe arrhythmias, conduction abnormalities, ST-T changes, and sudden death. Understanding arrhythmogenesis due to cocaine may provide a therapeutic approach to reduce morbidity and mortality. We studied the arrhythmogenic activity and other electrocardiographic abnormalities resulting from an intravenous bolus of cocaine. Baseline and postanesthetic electrocardiographic findings were compared with those after administration of intravenous bolus of various doses of cocaine hydrochloride in 20 dogs. The study was done in three phases (phase I: low dose of cocaine [1 mg/kg, 15 experiments]; phase II: medium dose [2 mg/kg, 30 experiments]; and phase III: high dose [5-7 mg/kg, 10 experiments]). Plasma levels of cocaine were estimated. The low dose induced sinus bradycardia, sinus arrhythmia, atrial ectopic, wandering pacemaker, unifocal ventricular premature contractions, and ventricular couplets. The medium dose generated moderately severe arrhythmias that were of supraventricular origin. Atrial flutter and atrial fibrillation were observed in two experiments each. Ventricular arrhythmias were manifested as unifocal, multifocal, interpolated ventricular premature contractions as well as bigeminy, trigeminy, couplets, and salvos. The high dose of 5-7 mg/kg increased electrocardiographic intervals and caused ST-segment elevation as well as serious life-threatening arrhythmias. Three of the dogs developed sustained ventricular tachycardia followed by ventricular flutter-fibrillation and death.

THIS MONTH IN ANESTHESIOLOGY

THIS MONTH IN ANESTHESIOLOGY

Hemodynamic and surface electrocardiographic effects of a new aqueous formulation of intravenous amiodarone

Intravenous amiodarone is an effective antiarrhythmic agent. However, the standard formulation (Cordarone IV) frequently causes hypotension. Hemodynamic studies have attributed this adverse effect to the solvents employed. A newly developed aqueous formulation (Amio-Aqueous) lacks solvents and thus may not causes hypotension. This study evaluated the hemodynamic effects in a cardiac catheterization laboratory. Two boluses of 150-mg aqueous amiodarone were administered via a peripheral vein to 32 hemodynamically stable patients who underwent cardiac catheterization. Boluses were administered initially over 2 to 5 minutes and in the last 9 patients over 2 minutes. Hemodynamic evaluation was performed and 12-lead electrocardiograms were obtained at baseline, immediately after each bolus, and following 30 minutes of observation. No patient developed hypotension. There were no significant changes in systolic and diastolic blood pressure (BP) following the boluses. Compared with baseline, heart rate (HR) significantly decreased 5 minutes after the second bolus (73 ± 12 vs 67 ± 11 beats/min, p <0.05). Mean arterial BP increased (90 ± 14 vs 100 ± 16 mm Hg, p <0.05) and dp/dt decreased (1,599 ± 645 vs 1,294 ± 531 mm Hg/s p <0.05), whereas the PR, QT, and JT intervals increased (174 ± 30 vs 182 ± 33; 402 ± 32 vs 424 ± 35; 317 ± 37 vs 336 ± 32 ms, p <0.05, respectively) by the end of the 30-minute observation period. Amio-Aqueous possesses pharmacodynamic effects that have been attributed to amiodarone, whereas it lacks the hypotensive effect of the standard intravenous amiodarone formulation. Amio-Aqueous appears to be a safer alternative to Cordarone IV when rapid administration is indicated.

Tegaserod, a 5-hydroxytryptamine type 4 receptor partial agonist, is devoid of electrocardiographic effects

OBJECTIVES: Certain GI prokinetic agents have been shown to affect cardiac repolarization, which may be associated with life-threatening arrhythmias. The selective 5-hydroxytryptamine type 4 receptor partial agonist tegaserod is a novel promotile agent developed for the treatment of functional motility disorders such as irritable bowel syndrome (IBS). The aim of the study was to investigate the cardiac safety profile of tegaserod through analysis of electrocardiographic data from clinical studies conducted in patients with IBS and a study conducted in healthy male subjects. METHODS: In three randomized, double blind, placebo-controlled, parallel group clinical studies, 2516 IBS patients with symptoms of abdominal pain and constipation received tegaserod 2 or 6 mg b.i.d. (n = 1679) or placebo (n = 837) for 12 wk. In an additional study, 36 healthy male subjects received i.v. single doses of tegaserod (0.8 mg to 20 mg) or placebo. Standard 12-lead electrocardiograms were recorded at baseline and during treatment. Baseline values were compared with data collected during the treatment period. RESULTS: The proportion of patients with prolongation of the QTc interval was the same for placebo and tegaserod, as was the frequency of overall electrocardiographic abnormalities. No ventricular or supraventricular tachycardia was observed. Comparable electrocardiographic results were obtained during placebo and tegaserod treatment. In healthy volunteers, tegaserod at i.v. doses resulting in plasma concentrations up to 100 times those measured after therapeutic doses (6 mg b.i.d.) did not influence electrocardiographic parameters. CONCLUSIONS: Tegaserod is devoid of electrocardiographic effects and is not expected to adversely influence cardiac function. These data confirm preclinical findings.

THIS MONTH IN ANESTHESIOLOGY

THIS MONTH IN ANESTHESIOLOGY

Effects of CNS site-directed carotid arterial infusions of bupivacaine, levobupivacaine, and ropivacaine in sheep.

Previous preclinical safety studies in ewes have found intravenous levobupivacaine and ropivacaine to be less potent toward causing central nervous system (CNS) and cardiac toxicity than bupivacaine. Analogous cardiotoxicity has been demonstrated directly in various cardiac preparations ex vivo. Moreover, drug-related arrhythmogenicity has been demonstrated from direct CNS injection of local anesthetic agents in vivo, suggesting CNS-related cardiotoxicity. This study investigated whether CNS site-directed blood-borne drug administration (with minimal systemic recirculation) would demonstrate drug-related cardiotoxicity. Direct CNS effects and indirect cardiotoxic sequelae were determined after bilateral carotid arterial infusions of levobupivacaine, bupivacaine, or ropivacaine in ewes. After pilot studies to validate the procedures, equimolar doses (24-96 micromol, approximately 7.5-30 mg) were infused over 3 min using a crossover design. Behavioral CNS signs, quantitative electroencephalographic (EEG), cardiovascular, and electrocardiographic effects were recorded. Drug blood concentrations in superior sagittal sinus and aorta were measured serially. Blood drug concentrations in the superior sagittal sinus were 5-10 times those concurrently in the aorta, confirming highly selective CNS delivery with minimal systemic recirculation. Dose-dependent CNS excitatory behavior and EEG changes, with increased mean arterial blood pressure, heart rate, cardiac output, and myocardial contractility, were found, consistent with sympathetic nervous system stimulation. The overall rank order of potency for these effects was ropivacaine < levobupivacaine < bupivacaine. Nonfatal cardiac arrhythmias were observed, but the type or frequency did not differ between drugs. Although CNS site-selective drug delivery produced quantitative differences between bupivacaine, levobupivacaine, and ropivacaine in some CNS effects and cardiac sequelae, no differences were found in their arrhythmogenic potential.