Ischemia-induced action potential shortening is blunted by d-sotalol in a pig model of reversible myocardial ischemia.

The purpose of this study was to investigate, in an anesthetized pig model of low-flow myocardial ischemia, the electrophysiologic effects of the class III drug d-sotalol during myocardial ischemia. Serial monophasic action potential (MAPD90) recordings and refractory period determinations from the anterior and posterior left ventricular wall were taken in 25 pigs during baseline, after low-flow posterior wall ischemia, after d-sotalol infusion under nonischemic conditions, and after repeated posterior wall ischemia while continuing the drug. Measurements were done at 60 and 150 beats/min after radiofrequency ablation of atrioventricular conduction.

Impact of left ventricular diastolic dysfunction on maximal treadmill performance in normotensive subjects with well-controlled type 2 diabetes mellitus.

Patients with type 2 diabetes often have impaired exercise capacity compared with nondiabetic subjects. Left ventricular (LV) diastolic dysfunction has been shown to limit exercise performance in nondiabetic subjects. Men with well-controlled type 2 diabetes were divided into 2 groups: normal LV diastolic function (group 1, n = 9) or LV diastolic dysfunction (group 2, n = 10) based on standard echocardiographic criteria using pulmonary veins and transmitral flow recordings.

Concomitant Block of the Rapid (I(Kr)) and Slow (I(Ks)) Components of the Delayed Rectifier Potassium Current is Associated With Additional Drug Effects on Lengthening of Cardiac Repolarization.

BACKGROUND: The delayed rectifier potassium current, which comprises both a rapid (I(Kr)) and as slow (I(Ks)) component, is a major outward current involved in repolarization of cardiac myocytes. I(Kr) is the target of most drugs that prolong repolarization, whereas electrophysiological effects resulting from combined block of I(Kr) and I(Ks) still need to be characterized. METHODS AND RESULTS: Studies in isolated, buffer-perfused guinea pig hearts were undertaken to compare lengthening of cardiac repolarization under conditions of I(Kr) block alone, I(Ks) Block alone, or combined block of I(Kr) and I(Ks).

Midterm follow-up of unstented biological valves.

We have used the stentless aortic biosprosthesis for aortic valve replacement during the last 10 years. Since 1988, 647 stentless aortic prosthesis were implanted: 384 unstented heterografts, 176 Ross procedures, and 87 homografts. Patients up to age 50 were offered the Ross procedure, those between the ages of 50 and 60 a homograft, and patients 60 years old and older received heterografts.

Droperidol lengthens cardiac repolarization due to block of the rapid component of the delayed rectifier potassium current.

Introduction: Torsades de pointes have been observed during treatment with droperidol, a butyrophenone neuroleptic agent. Our objectives were (1) to characterize the effects of droperidol on cardiac repolarization and (2) to evaluate effects of droperidol on a major time-dependent outward potassium current involved in cardiac repolarization (I(K)r).

Methods And Results: Isolated, buffer-perfused guinea pig hearts (n = 32) were stimulated at different pacing cycle lengths (150 to 250 msec) and exposed to droperidol in concentrations ranging from 10 to 300 nmol/L.

Involvement of CYP2D6 activity in the N-oxidation of procainamide in man.

Occurrence of a lupus-like syndrome in a significant number of patients treated with procainamide has limited the clinical use of this antiarrhythmic drug. In-vitro studies conducted in our laboratory have demonstrated that CYP2D6 is the major cytochrome P450 isozyme involved in the formation of N-hydroxyprocainamide, a metabolite potentially involved in the drug-induced lupus erythematosus syndrome observed with procainamide. In the current study, we evaluated the role of CYP2D6 activity in the in-vivo oxidation of procainamide in man.

Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs.

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied.

Clinical pharmacokinetics of mexiletine.

Mexiletine, a class Ib antiarrhythmic agent, is rapidly and completely absorbed following oral administration with a bioavailability of about 90%. Peak plasma concentrations following oral administration occur within 1 to 4 hours and a linear relationship between dose and plasma concentration is observed in the dose range of 100 to 600 mg. Mexiletine is weakly bound to plasma proteins (70%).

Changes in left ventricular mass and function after aortic valve replacement: a comparison between stentless and stented bioprosthetic valves.

The objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to the postoperative changes in left ventricular (LV) mass and function. Forty patients with aortic stenosis undergoing valve replacement with a stentless (20 patients) or a stented (20 patients) bioprosthesis were evaluated early (baseline), 1 year, and 2 years after operation. Left ventricular mass index was calculated with the corrected American Society of Echocardiography formula.

Hemodynamic and physical performance during maximal exercise in patients with an aortic bioprosthetic valve: comparison of stentless versus stented bioprostheses.

Objectives: The objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to their hemodynamic behavior during exercise.

Background: Stentless aortic bioprostheses have better hemodynamic performances at rest than stented bioprostheses, but very few comparisons were performed during exercise.

Methods: Thirty-eight patients with normally functioning stentless (n = 19) or stented (n = 19) bioprostheses were submitted to a maximal ramp upright bicycle exercise test.

Comparison of propafenone versus procainamide for the acute treatment of atrial fibrillation after cardiac surgery.

A prospective, randomized, double-blind study to compare the efficacy in terminating postoperative atrial fibrillation of the class Ic drug propafenone versus class Ia drug procainamide was conducted. Intravenous propafenone was superior to procainamide in achieving rapid cardioversion and a better rate control with a lower incidence of symptomatic hypotension.

Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes.

Venlafaxine is a newly introduced antidepressant agent. The drug causes selective inhibition of neuronal reuptake of serotonine and norepinephrine with little effect on other neurotransmitter systems. Cases of seizures, tachycardia, and QRS prolongation have been observed following drug overdose in humans.

Lysophosphatidylcholine, a metabolite which accumulates early in myocardium during ischemia, reduces gap junctional coupling in cardiac cells.

Lysophosphatidylcholine (LPC) is a metabolite that accumulates rapidly during cardiac ischemia in animal and human hearts. LPC induces electrophysiological changes including action potential alterations and cardiac arrhythmias. Since there is increasing evidence that disrupted cell coupling can contribute to the generation of cardiac arrhythmias under ischemic conditions, this study was designed to assess the effects of LPC on gap junction coupling between cardiac cell pairs using the dual whole-cell voltage-clamp technique.

Modulation of HERG potassium channel properties by external pH.

We expressed the human eag-related gene (HERG), known to encode for the cardiac potassium channel IKr, in Chinese hamster ovary (CHO) cells. This study investigated effects of external pH (pHo) on HERG current properties using the whole-cell patch-clamp technique. We observed that current amplitude was decreased and kinetics of activation and deactivation were faster when pHo was lowered from 7.

Stereoselective disposition of the antiarrhythmic agent mexiletine during the concomitant administration of caffeine.

Caffeine consumption is extensive in industrialized countries and its role in drug-drug interactions is often overlooked. CYP1A2, the major cytochrome P450 isoform involved in the metabolism of caffeine, has also been implicated in the formation of N-hydroxymexiletine, the major metabolite of mexiletine. Therefore, the objective of this study was to assess the effects of a clinically relevant dosage of caffeine on the stereoselective disposition of mexiletine.

Usefulness of the indexed effective orifice area at rest in predicting an increase in gradient during maximum exercise in patients with a bioprosthesis in the aortic valve position.

This study examines the hemodynamic behavior of aortic bioprosthetic valves during maximum exercise. Nineteen patients with a normally functioning stented bioprosthetic valve and preserved left ventricular function were submitted to maximum ramp bicycle exercise. In 14 of the 19 patients, valve effective orifice area and mean gradient were measured at rest and during exercise using Doppler echocardiography.

Thioridazine lengthens repolarization of cardiac ventricular myocytes by blocking the delayed rectifier potassium current.

Proarrhythmia has been observed with the antipsychotic agent thioridazine (THIO). The mechanisms underlying these effects are unknown. The objectives of this study were 1) to characterize the effects of THIO on cardiac repolarization and 2) to determine whether lengthening of the Q-T interval could be explained by blocking major K+-repolarizing currents.

Hemodynamic features of the freestyle aortic bioprosthesis compared with stented bioprosthesis.

Background: The Freestyle prosthesis is a new stentless aortic bioprosthesis. Anticipated benefits are improved hemodynamics and increased longevity.

Methods: Doppler echocardiograms were performed early and at 3 to 6 months, 1 year, and 2 years after operation in 157 patients (69 men, 88 women, aged 48 to 85 years) with this prosthesis, and results were compared with hemodynamic data in patients with Intact and Mosaic stented bioprostheses.

Rapidly evolving constrictive tuberculous pericarditis: case presentation and review of the literature.

A 69-year-old male presented with a diagnosis of idiopathic pericarditis, first treated with prednisone for a few weeks with resolution of the symptoms. A few days after stopping the medication, he presented with malaise, cough and signs of pericardial constriction confirmed by echocardiography. He was diagnosed with pulmonary tuberculosis with pericardial involvement and treated accordingly.

Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine.

Treatment with second generation histamine H1 receptor antagonists has been associated with lengthening of the Q-T interval and proarrhythmia. Similarly, lengthening of the Q-T interval has been reported in patients after overdosing with diphenhydramine (DPH), a first generation agent. Therefore, our study was designed 1) to assess effects of DPH on cardiac repolarization and 2) to characterize effects of the drug on major voltage-dependent cardiac K+ currents.

Attenuation of myocardial ischemia with repeated exercise in subjects with chronic stable angina: relation to myocardial contractility, intensity of exercise and the adenosine triphosphate-sensitive potassium channel.

Objectives: This study characterized the attenuation of myocardial ischemia observed with re-exercise to determine whether: 1) a differing exercise intensity modifies this attenuation; 2) it could be explained by contractile down-regulation or stunning; 3) it is mediated by activation of ATP-sensitive potassium channels (K+-ATP).

Background: Subjects with ischemic heart disease (IHD) frequently note less angina with re-exercise after a brief rest. Potential mechanisms of this 'warm-up' phenomenon have been little explored.

Atherogenic, hemostatic, and other potential risk markers in subjects with previous isolated myocardial infarction compared with long-standing uncomplicated stable angina.

Background: Several atherogenic, hemostatic, inflammatory, and genetic parameters and markers have been implicated as risk factors in coronary artery disease, although whether they are risk factors for acute as opposed to chronic coronary disease is unclear.

Methods And Results: Fifty subjects with an isolated myocardial infarction >3 months previously were compared with 50 subjects with a minimum 3-year history of stable angina, documented coronary artery disease, normal electrocardiogram and normal ventricular wall motion, and no episode suggesting infarction or unstable angina. Biologic variables analyzed included apolipoprotein B (apo B), lipoprotein (a), C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (TPA) and inhibitor (PAI-1), thrombin-antithrombin (TAT), fragment 1+2 (F1+2), von Willebrand factor (vWF), activated protein C resistance, homocyst(e)ine, anticardiolipin antibodies, blood group, and the angiotensin-converting enzyme insertion/deletion (I/D) and angiotensin II receptor gene polymorphisms.

In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists.

Classic antihistamines, namely diphenhydramine, chlorpheniramine, clemastine, perphenazine, hydroxyzine, and tripelennamine, share structural features with substrates and inhibitors of the polymorphic cytochrome P450 (CYP) isozyme CYP2D6. Therefore, the current study was undertaken to characterize the in vitro inhibition of CYP2D6 by these commonly used, histamine H1 receptor antagonists. Microsomal incubations were performed using bufuralol as a specific CYP2D6 substrate and microsomes derived from human cells transfected with CYP2D6 cDNA.

Impact of prosthesis-patient mismatch on hemodynamic and symptomatic status, morbidity and mortality after aortic valve replacement with a bioprosthetic heart valve.

Background And Aims Of The Study: Previous studies have shown that the effective orifice area of an aortic prosthetic valve may be too small in relation to the patient's body surface area, resulting in abnormally high gradients. The consequences of this condition, termed prosthesis-patient mismatch, have not been fully studied. The study objective was to determine if the condition has a detrimental effect on symptomatic and hemodynamic status, morbidity and mortality of patients undergoing aortic valve replacement.