ABSTRACT
Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA antiarrhythmic, it has been reported that NAPA is a pure class III antiarrhythmic that affects only the repolarizing phase of the cardiac action potential. This last concept, observed exclusively in dogs, gained wide acceptance, appearing in classic pharmacology textbooks. However, evidence in species such as mice and rats indicates that NAPA can affect cardiac Na+ channels, which is unexpected for a pure class III antiarrhythmic drug. To further clarify this issue, the effects of PA (used as a reference drug) and NAPA on the maximum upstroke velocity (Vmax) and half-decay time (HDT) of the cardiac action potential were examined in the isolated right papillaris magnus of the guinea pig heart. Both PA and NAPA affected Vmax at lower concentrations than required to affect HDT, and NAPA had weaker effects on both variables. Thus, NAPA displayed typical class IA antiarrhythmic behavior. Therefore, the concept that NAPA is a pure class III antiarrhythmic drug is more species-dependent than previously envisioned. In addition, we demonstrated that the differential pharmacology of PA and NAPA is explainable, in molecular terms, by steric hindrance of the effects of NAPA and the greater number of potent aromatic-aromatic and cation π interactions with Na+ or K+ cardiac channels for PA.
ABSTRACT
Interaction of procainamide hydrochloride (PAH) with human serum albumin (HSA) is of great significance in understanding the pharmacokinetic and pharmacodynamic mechanisms of the drug. Multi-spectroscopic techniques were used to investigate the binding mode of PAH to HSA and results revealed the presence of static type of quenching mechanism. The number of binding sites, binding constants and thermodynamic parameters were calculated. The results showed a spontaneous binding of PAH to HSA and hydrophobic interactions played a major role. In addition, the distance between PAH and the Trp–214 was estimated employing the F?rster's theory. Site marker competitive experiments indicated that the binding of PAH to HSA primarily took place in subdomain ⅡA (Sudlow's site I). The influence of interference of some common metal ions on the binding of PAH to HSA was studied. Synchronous fluorescence spectra (SFS), 3D fluorescence spectra and circular dichroism (CD) results indicated the conformational changes in the structure of HSA.
ABSTRACT
An 82-year-old female, with left femoral neck fracture was scheduled for left hip hemiarthroplasty, under spinal anaesthesia. She had been suffering from diabetes, hypertension, lung cancer and was previously treated with IV aminophylline for respiratory insufficiency. She was given spinal anaesthesia with 10 mg of 0.5% hyperbaric bupivacaine, and T6 sensory block level was established. After 10 minutes, her blood pressure dropped to 80/60 mmHg, so intravenous ephedrine was given. At that moment, multifocal atrial tachycardia (MAT) appeared on electrocardiogram (ECG). Intravenous infusion of phenylephrine and procainamide was given and conversion of MAT to sinus rhythm was successfully achieved. We report a case of MAT after spinal anaesthesia, in a patient with respiratory insufficiency previously treated with IV aminophylline, which was successfully treated by intravenous infusion of phenylephrine and procainamide.
Subject(s)
Aged, 80 and over , Female , Humans , Aminophylline , Blood Pressure , Bupivacaine , Electrocardiography , Ephedrine , Femoral Neck Fractures , Hemiarthroplasty , Hip , Hypertension , Infusions, Intravenous , Lung Neoplasms , Phenylephrine , Procainamide , Respiratory Insufficiency , Stress, Psychological , TachycardiaABSTRACT
0.05),respectively.Conclusions Sodium channel blocker procainamide results in a similar repolarisation prolongation in the epicardium,midmyocardium and endocardium of the left ventricle.
ABSTRACT
A canine model of sudden coronary death was established by intimal sur-face anodal direct current stimulation of the left circumflex coronary artery (LCX)on 5-8 days after the left anterior descending coronary artery (LAD) infarction. TheLCX intimal injury and subsequent thrombus formation produced ECG ST segment chan-ges at 104?30 minutes (X?SD), followed by premature ventricular beats, ventriculartachycardia (VT), and ventricular fibrillation (VF) in all normal saline (NS) treated dogs(n=6), in procainamide (PA) treated dogs (n=6), ECG ST segment changes appearedat 110?40 minutes, followed by VT and VF in only one dog (P
ABSTRACT
A canine model of electro-physiologic-electropharmacologic testing on ischemic ventricular tachyarrhythmias were established in the open-chest dogs subjected to programmed electrical stimulation (PES) on 5~8days after acute my-ocardial infarction produced with two -stage occlusion of left anteriol decending coronary artery (LAD) followed by partly reperfusion. The electrophysiologic -electropharmacologic effects of pro-cainamide (PA ) were observed in this canine model. pA distinctly lengthened the QTc interval and the effective refractory period ( ERP) of normal and infarct myocardium in both ventricles and decreasedthe dispersion of ERP in infarct myocardium (IDR) as well as the dispersion of ERP in left ventricle (VDR). The PES - induced ventricular tachycardia (VT) or ventricular fibrillation (VF) was prevented in 5 out of 6 PA treated dogs (n = 6),Normal saline (NS) did not prevented PES- induced VT/VF. The results suggest that PA may be effective in preventing the onset of reentrant ventricular tachyarrhythmias after myocardium ischemic damage.