Hanne Bjørnstad

Rate-dependent class III antiarrhythmic action, negative chronotropy, and positive inotropy of a novel IK blocking drug, UK-68,798 : potent in guinea pig but no effect in rat myocardium

The electromechanical effects of UK-68,798 (UK), a novel class III antiarrhythmic drug, were studied in guinea pig and rat papillary muscles (PMs) and atria in vitro using conventional microelectrode technique. UK (10−8-10−6 M) prolonged the action potential duration (APD) by 21–58% and effective refractory period in parallel, without affecting the resting potential or maximum rate of depolarization in guinea pig PM stimulated at 1 Hz. UK increased the contractile force without prolonging the time to peak force or relaxation. In comparison, 5 ± 10−5 M d-sotalol was needed to induce the same electrophysiological effects as 10−8 M UK. UK prolonged the APD significantly less at 2 Hz than at 1 and 0.5 Hz. Early afterdepolarizations (EADs) developed in 2 of 11 preparations after 10–6 M at 0.5 Hz. No reversal of drug effect was seen after up to 2 h washout. UK (10−9-10−3 M) reduced the spontaneous heart rate and prolonged the sinus node recovery time of guinea pig right atria. No effects on rat PM or atria, even after 10−5 M, indicate a selective action of UK on the delayed rectifying outward potassium current, Ik. These results indicate a potent and selective, rate-dependent class III antiarrhythmic action of UK-68,798 linked with positive inotropy. Increased APD, bradycardia, and induction of EADs, however, represent a potential arrhythmogenic combination.

Anti-Inflammatory Effect of Cardiac Resynchronization Therapy

Background: Congestive heart failure (CHF) is associated with persistent immune activation. Medical therapy has been shown to exert only limited anti‐inflammatory effects. Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in a subset of patients with heart failure, but it is not known whether this treatment affects the immune system as well. To test this hypothesis, eight patients with heart failure scheduled for CRT were investigated for immune activation before and 6 months after CRT treatment.

A young man with acute dilated cardiomyopathy associated with methylphenidate.

An 18-year-old obese man with a body mass index of 40, diagnosed with attention-deficit hyperactivity disorder and treated with methylphenidate (Concerta®) was acutely admitted to hospital with hypoxia and dyspnoea. On investigation signs of liver-, renal-, and heart-failure were found. Noradrenalin infusion was started. Echocardiography showed dilated left ventricle and an ejection fraction (EF) of 25%. Liver function improved, noradrenalin and dobutamine were tapered, but three days after admission a new echocardiography showed an EF of 10%. The patient was transferred to the National Hospital (Rikshospitalet, Oslo), where intensified treatment including intra aortic balloon pump (IABP) was instituted. Cardiac function improved, and 3 weeks later the IABP was disconnected. EF at this point was 15%. The patient was denied heart transplantation due to various cofactors. The investigation concluded with a probable relationship between his cardiomyopathy and the use of methylphenidate (Concerta).

Effect of bretylium tosylate on ventricular fibrillation threshold during hypothermia in dogs

How bretylium tosylate affected the ventricular fibrillation threshold, electrophysiological parameters, and plasma catecholamine levels during hypothermia in dogs was studied. Threshold for ventricular fibrillation was determined by programmed electrical stimulation using a stimulation protocol that involved applying a maximum of five extrastimuli at body temperatures 37, 34, 31, 28, and 25 degrees C, and at the same temperatures during rewarming. Electrocardiogram, epicardial monophasic action potentials (MAP), and electrograms were recorded, and ventricular effective refractory period (VERP) was determined at each of the above temperatures. In one group (n = 7), a bolus dosage of bretylium tosylate (BT), 6 mg/kg body wt, was administered at 25 degrees C before rewarming. Another group (n = 4) was exposed to cooling and rewarming without addition of BT. Cooling to 25 degrees C reduced ventricular fibrillation threshold linearly, reduced heart rate, increased VERP and MAP, and slowed myocardial conduction velocity in both groups. There was no overall increase in plasma catecholamine levels during cooling. Addition of BT at 25 degrees C increased ventricular fibrillation threshold during rewarming compared with cooling. Addition of BT at 25 degrees C increased VERP by +/- 32 milliseconds and the corrected JT time by 0.06 +/- 0.02 seconds. VERP and JTc increased during rewarming with BT compared with cooling with no drug. BT had no effect on conduction velocity, and plasma catecholamine levels were not reduced. The antiarrhythmic effect of BT during hypothermia was attributed to an increased wavelength of refractoriness by its increase in the refractory period. This increased wavelength of refractoriness may prevent excitable gaps or increase circuit pathway in the setting of reentry arrhythmias.

Class III antiarrhythmic action of d-sotalol during hypothermia

To investigate whether changes in temperature influence the electrophysiologic effects of the class III antiarrhythmic agent d-sotalol, we studied its effects on propranolol-pretreated guinea pig papillary muscles at temperatures ranging from 37 degrees to 27 degrees C by means of conventional microelectrode techniques. We also examined the rate-dependent effect of d-sotalol at 37 degrees and 27 degrees C. Before the addition of d-sotalol, reducing the temperature from 37 degrees to 27 degrees C increased the action potential duration recorded at 50% repolarization (APD50) from 112 +/- 7 msec to 271 +/- 15 msec and action potential duration recorded at 90% repolarization (APD90) from 136 +/- 7 msec to 325 +/- 10 msec. d-Sotalol (50 mumol/L) lengthened APD50 and APD90 to a greater degree at low temperatures. Thus at 37 degrees C d-sotalol lengthened APD50 and APD90 by 12 +/- 6 msec and 19 +/- 5 msec, and at 27 degrees C by 37 +/- 5 msec and 52 +/- 7 msec, respectively. d-Sotalol produced its greatest effect on APD at long pacing cycle lengths, thus demonstrating reverse dependence. This rate-dependent effect was more marked at 27 degrees C than at 37 degrees C. The greater effect of d-sotalol on APD at long pacing cycle lengths may be explained by the modulated receptor hypothesis, assuming that the drug has a higher affinity for closed potassium channels. Such a mechanism may also explain the accentuated class III antiarrhythmic action of d-sotalol observed during hypothermia.

Gated SPECT offers improved interobserver agreement compared with echocardiography.

Purpose: Left ventricular ejection fraction (EF) is a powerful predictor of prognosis in coronary artery disease. The purpose of the present study was to measure interobserver differences for gated SPECT (GSPECT) software and echocardiography, and to compare these modalities regarding left ventricular volumes and EF. Materials and Methods: Eighty-four patients scheduled for nuclear imaging underwent a 1-day GSPECT with Tc-99m-tetrofosmin. Images were processed by 2 raters who calculated volumes and EF using Cedar-Sinai quantitative gated-SPECT (QGS), Emory Cardiac Toolbox (ECT), and 4D-MSPECT of the University of Michigan. Echocardiographic volumes were measured by 2 raters. Interobserver reliability was assessed by intraclass correlation coefficient (ICC). Differences in volumes and EF between echocardiography and GSPECT were compared with t-tests. Results: ICC was 0.61 for echocardiography, 0.94 for QGS, 0.88 for ECT, and 0.91 for 4D-MSPECT (P < 0.0001 compared with echocardiography). For small ventricles (ESV ≤30 mL), ICC was 0.58 for echocardiography and 0.90 for QGS (P = 0.008 compared with echocardiography); 0.77 and 0.73 for ECT and 4D-MSPECT, respectively (P = ns). End-diastolic and end-systolic volumes were significantly larger with GSPECT than with echocardiography, also echocardiographic ejection fraction was significantly different from GSPECT. Conclusions: There is better interobserver reliability in GSPECT as compared with echocardiography, and QGS seems more robust in this study especially when it comes to small ventricles.

Transient ST elevation due to coronary spasm in a young woman

A 43-year-old woman was admitted to the coronary care unit at Nordland Hospital (Bodo, Norway) because of a two-week history of transient chest pain. Her total cholesterol level was 8.0 mmol/L and she was a heavy cigarette smoker. On arrival, her vital signs were stable and she was pain-free. An electrocardiogram (ECG) showed inverted and biphasic T waves in the precordial leads (Figure 1A), but after 30 min, she developed intense pressing chest pain and an ECG indicated severe anterior transmural ischemia (Figure 1B). She was immediately transferred to the coronary care unit where the pain subsided in 5 min to 10 min. Echocardiography showed normal contractility in all coronary territories. A control ECG showed regression of the ST elevation (Figure 1C). She was transferred to the University Hospital of North Norway (Tromso, Norway) for coronary angiography. Troponin T values were all below 0.01 μg/L. Coronary angiography showed a small plaque in the proximal left anterior descending artery (Figure 2) but the flow was unobstructed Thrombolysis In Myocardial Infarction (TIMI) grade 3. Coronary spasm was suspected and she was started on a calcium blocker. She remained symptom-free after six months. Figure 1) A Electrocardiogram (ECG) on arrival (precordial leads V1 to V6 only). There are widespread T inversions. B ECG demonstrating ST elevations in the anterior leads during chest pain. C ECG showing regression of ST elevation after the chest pain resolved ... Figure 2) Angiogram of the left coronary artery. The arrow depicts a plaque in the proximal left anterior descending artery, just before the diagonal branch Coronary spasm (variant angina or Prinzmetal’s angina) is believed to be caused by a transient increase in the coronary artery vasomotor tone (1). Spasm may also occur in proximity to atherosclerotic lesions including small lesions (2). Patients are often heavy cigarette smokers (3). Treatment includes nitrates and calcium antagonists.

Pericardial Effusion in a Patient with Lymphangioleiomyomatosis

A 60-y-old woman with known lymphangioleiomyomatosis presented with a pericardial effusion. Chylous fluid was drained by pericardiocentesis, and EBV was demonstrated in the pericardial effusion. Treatment with a systemic antiviral agent removed the virus from the effusion. The effusion itself was treated surgically.

Effect of Cardiac Resynchronization Therapy on Inflammation in Congestive Heart Failure: A Review.

Congestive heart failure is associated with increased levels of several inflammatory mediators, and animal studies have shown that infusion of a number of cytokines can induce heart failure. However, several drugs with proven efficacy in heart failure have failed to affect inflammatory mediators, and anti‐inflammatory therapy in heart failure patients has thus far been disappointing. Hence, to what extent heart failure is caused by or responsible for the increased inflammatory burden in the patient is still unclear. Over the past couple of decades, resynchronization therapy with a biventricular pacemaker has emerged as an effective treatment in a subset of heart failure patients, reducing both morbidity and mortality. Such treatment has also been shown to affect the inflammation associated with heart failure. In this study, we review recent data on the association between heart failure and inflammation, and in particular how resynchronization therapy can affect the inflammatory process.

Feasibility of using tissue Doppler velocities in stress echo during upright bicycle exercise.

Background and Aim: There are several studies on myocardial tissue Doppler velocities during dobutamine stress, but few studies on the same parameters during bicycle exercise. We wanted to examine how sample sites affected velocities, beat‐to‐beat variability and segments eligible for analysis. Methods: Twenty patients with normal coronary arteries were included in the study. Echocardiograms were obtained at rest and at peak exercise on the exercise bike and were analyzed off line by two independent raters. Results and Conclusions: Tissue velocities decreased from base to apex. Mean difference between the raters was−0.02 cm/sec at rest and 0.45 cm/sec during exercise. Peak‐to‐peak variability was lowest in the mitral ring during rest (10–14%) and increased at peak exercise (15–21%). The proportion of segments eligible for analysis was 84% in the septum and 67% in the anterior wall during exercise. Thus, in patients with normal coronary arteries, tissue Doppler velocities decrease from base toward the apex during bicycle exercise. Interrater agreement is reduced during exercise and beat‐to‐beat variability is lowest in the mitral ring.