Class III antiarrhythmic action of d-sotalol during hypothermia

Bjørnstad, Hanne; Tande, Pål M.; Refsum, Helge

doi:10.1016/0002-8703(91)90149-c

Cited by 13 publications

(5 citation statements)

References 27 publications

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“…Although intravenous D-sotalol comparisons were not within the scope of the present research, the results of others have demonstrated that D-sotalol is an effective antiarrhythmic agent when administered intravenously. Nevertheless, the dosages (8 to 10 mg/kg) used in these previous investigations (7)(8)(9)(10)(16)(17)(18), and the resulting peripheral plasma levels (peak level, 50 000 ng/ml) (7-l 0,16-18 ), were significantly higher than those reported in the present study. However, the coronary venous D-sotalol levels in the present study were comparable to therapeutic levels reported by others (7)(8)(9)(10)(16)(17)(18)(19) .…”

Section: Discussioncontrasting

confidence: 71%

“…Nevertheless, the dosages (8 to 10 mg/kg) used in these previous investigations (7)(8)(9)(10)(16)(17)(18), and the resulting peripheral plasma levels (peak level, 50 000 ng/ml) (7-l 0,16-18 ), were significantly higher than those reported in the present study. However, the coronary venous D-sotalol levels in the present study were comparable to therapeutic levels reported by others (7)(8)(9)(10)(16)(17)(18)(19) . Furthermore, Lynch et al, [ 271 demonstrated that in a multiple dose (8 mg/kg intravenously every 8 hours) pretreatment regimen, Dsotolal suppressed the induction of ventricular tachycardia in an infarction model system, and also provided significant protection against the development of ventricular fibrillation in response to further acute ischemia in conscious post-infarction dogs.…”

Section: Discussioncontrasting

confidence: 71%

See 1 more Smart Citation

The efficacy of controlled release D-sotalol-polyurethane epicardial implants for ventricular arrhythmias due to acute ischemia in dogs

Labhasetwar¹,

Kadish²,

Underwood³

et al. 1993

Journal of Controlled Release

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Epicardially implanted Dsotalol polyurethane composite matrices for preventing ischemic ventricular arrhythmias were studied in open chest dogs under general anesthesia. D-sotalol was combined with a polyureapolyurethane (3:7) in solvent-cast films, which were characterized in vitro for their drug release at 37°C at pH 7.4 (0.05 M K2HP04). D-sotalol in vitro release occurred rapidly in an initial burst phase, with roughly 20% released within the first five min, and 90% by 60 min. Thereafter, an exponentially decreasing release rate was observed with matrix depletion by live hours. In the animal studies, the left anterior descending coronary artery (LAD) was occluded for 10 min on an hourly basis for up to live occlusions. 10 min prior to the third LAD occlusion, either a D-sotalol matrix or a vehicle matrix (control) was placed on either the ischemic or nonischemic left ventricular epicardium. The study was then continued observing the effects of matrix placement on occlusions 3,4, and 5.200 mg D-SOtdO matrices, which delivered a net dose of 1.2 mg/kg, effectively inhibited ventricular arrhythmias only if placed on the left ventricular ischemic zone. Placement of 200 mg D-sotalol matrices in the nonischemic zone was ineffective for significantly reducing the occurrence of ventricular arrhythmias. Furthermore, D-sotalol controlled release matrices were ineffective for preventing ventricular fibrillation (VF) regardless of dose or placement site. 200 mg ischemic zone D-sotalol matrices resulted in plasma sotalol levels in regional coronary venous samples ranging from 3.5 pg/ml to 10.4 &ml. However, peripheral sotalol levels obtained simultaneously ranged from 0.23 pg/ml to 0.78 ,ug/ ml. It is concluded that epicardial D-sotalol controlled release matrices inhibited ischemic ventricular arrhythmias, but not VF, if placed in the left ventricular ischemic zone during repeated LAD occlusions.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussioncontrasting

confidence: 71%

The efficacy of controlled release D-sotalol-polyurethane epicardial implants for ventricular arrhythmias due to acute ischemia in dogs

Labhasetwar¹,

Kadish²,

Underwood³

et al. 1993

Journal of Controlled Release

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“…This indicates that pharmacological APD prolongation during hypothermia is unfavourable. A study on K + -channel blocker sotalol gave the same outcome; sotaloltreatment was more effective in prolonging APD during hypothermic than normothermic conditions and authors thought this effect to be pro-arrhythmic (11,107)…”

Section: Class III Antiarrhythmic Agentsmentioning

confidence: 93%

Hypothermia and cardiac electrophysiology: a systematic review of clinical and experimental data

Dietrichs

Tveita

Smith

2018

Cardiovascular Research

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Moderate therapeutic hypothermia procedures are used in post-cardiac arrest care, while in surgical procedures, lower core temperatures are often utilized to provide cerebral protection. Involuntary reduction of core body temperature takes place in accidental hypothermia and ventricular arrhythmias are recognized as a principal cause for a high mortality rate in these patients. We assessed both clinical and experimental literature through a systematic literature search in the PubMed database, to review the effect of hypothermia on cardiac electrophysiology. From included studies, there is common experimental and clinical evidence that progressive cooling will induce changes in cardiac electrophysiology. The QT interval is prolonged and appears more sensitive to decreases in temperature than the QRS interval. Severe hypothermia is associated with more pronounced changes, some of which are proarrhythmic. This is supported clinically where severe accidental hypothermia is commonly associated with ventricular fibrillation or asystole. J-waves in human electrocardiogram recordings are regularly but not always observed in hypothermia. Its relation to ventricular repolarization and arrhythmias is not obvious. Little clinical data exist on efficacy of anti-arrhythmic drugs in hypothermia, while experimental data show the potential of some agents, such as the class III antiarrhythmic bretylium. It is apparent that QT-prolonging drugs should be avoided.

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“…Establishment of baseline values under standardized conditions is necessary because RMP directly depends on the extracellular K + concentration (21), APD in guinea-pig papillary muscles is markedly affected by the temperature (22), and agerelated changes in APD are observed in various cardiac tissues (23,24).…”

Section: Discussionmentioning

confidence: 99%

QT PRODACT: A Multi-site Study of In Vitro Action Potential Assays on 21 Compounds in Isolated Guinea-Pig Papillary Muscles

et al. 2005

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Abstract. To construct a non-clinical database for drug-induced QT interval prolongation, the electrophysiological effects of 11 positive and 10 negative compounds on action potentials (AP) in guinea-pig papillary muscles were investigated in a multi-site study according to a standard protocol. Compounds with a selective inhibitory effect on the rapidly activated delayed rectifier potassium current (I Kr ) prolonged action potential duration at 90% repolarization (APD 90 ) in a concentration-dependent manner, those showing Ca 2+ current (I Ca ) inhibition shortened APD 30 , and those showing Na + current (I Na ) inhibition decreased action potential amplitude (APA) and V max . Some of the mixed ion-channel blockers showed a bell-shaped concentration-response curve for APD 90 , probably due to their blockade of I Na and / or I Ca , sometimes leading to a falsenegative result in the assay. In contrast, all positive compounds except for terfenadine and all negative compounds with I Kr -blocking activity prolonged APD 30-90 regardless of their I Na -and / or I Ca -blocking activities, suggesting that APD 30-90 is a useful parameter for evaluating the I Krblocking activity of test compounds. Furthermore, the assay is highly informative regarding the modulation of cardiac ion channels by test compounds. Therefore, when APD 90 and APD 30-90 are both measured, the action potential assay can be considered a useful method for assessing the risk of QT interval prolongation in humans in non-clinical safety pharmacology studies. Supplementary material (Appendix): available only at http://dx

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Class III antiarrhythmic action of d-sotalol during hypothermia

Cited by 13 publications

References 27 publications

The efficacy of controlled release D-sotalol-polyurethane epicardial implants for ventricular arrhythmias due to acute ischemia in dogs

The efficacy of controlled release D-sotalol-polyurethane epicardial implants for ventricular arrhythmias due to acute ischemia in dogs

Hypothermia and cardiac electrophysiology: a systematic review of clinical and experimental data

QT PRODACT: A Multi-site Study of In Vitro Action Potential Assays on 21 Compounds in Isolated Guinea-Pig Papillary Muscles

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