Resistance to ventricular fibrillation predicted by the QRS/QTc - Ratio in an intact rat model of hypothermia/rewarming

Dietrichs, Erik Sveberg; Selli, Anders Lund; Kondratiev, Timofei; McGlynn, Karen; Smith, Godfrey L.; Tveita, Torkjel

doi:10.1016/j.cryobiol.2021.01.003

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…Recent studies find that dispersion of repolarization and a depolarization/repolarization mismatch is associated with increased risk for ventricular fibrillation at 31-32°C (Piktel et al, 2010;Dietrichs et al, 2020a). These pro-arrhythmic changes can be detected by low values of a novel ECG marker for hypothermia-induced cardiac arrest; QRS/QTc (Dietrichs et al, 2020b(Dietrichs et al, , 2021Ref). Hypothermic pigs in the present study were cooled to the same temperature and given β 1 -receptor stimulating Epi infusions.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32°C) With Spontaneous Circulation in an Intact Porcine Model

et al. 2021

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Aims: Rewarming from accidental hypothermia and therapeutic temperature management could be complicated by cardiac dysfunction. Although pharmacologic support is often applied when rewarming these patients, updated treatment recommendations are lacking. There is an underlying deficiency of clinical and experimental data to support such interventions and this prevents the development of clinical guidelines. Accordingly, we explored the clinical effects of epinephrine during hypothermic conditions.Materials and methods: Anesthetized pigs were immersion cooled to 32°C. Predetermined variables were compared at temperature/time-point baseline, after receiving 30 ng/kg/min and 90 ng/kg/min epinephrine infusions: (1) before and during hypothermia at 32°C, and after rewarming to 38°C (n = 7) and (2) a time-matched (5 h) normothermic control group (n = 5).Results: At 32°C, both stroke volume and cardiac output were elevated after 30 ng/kg/min administration, while systemic vascular resistance was reduced after 90 ng/kg/min. Epinephrine infusion did not alter blood flow in observed organs, except small intestine flow, and global O2 extraction rate was significantly reduced in response to 90 ng/kg/min infusion. Electrocardiographic measurements were unaffected by epinephrine infusion.Conclusion: Administration of both 30 ng/kg/min and 90 ng/kg/min at 32°C had a positive inotropic effect and reduced afterload. We found no evidence of increased pro-arrhythmic activity after epinephrine infusion in hypothermic pigs. Our experiment therefore suggests that β₁-receptor stimulation with epinephrine could be a favorable strategy for providing cardiovascular support in hypothermic patients, at core temperatures >32°C.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32°C) With Spontaneous Circulation in an Intact Porcine Model

et al. 2021

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“…The accompanying reduced myocardial excitability and potentially conduction velocity may contribute to the anti-arrhythmic properties under the same principle as Vaughan-Williams Class I anti-arrhythmic drugs ( 30 ). A similar logic can be used to explain the anti-arrhythmic effects of profound hypothermia where both QRS and QT are increased ( 5 – 7 , 31 ). A mild reduction of excitability by inhibition of the VGSC and the associated reduced TdP-risk would not be detected by monitoring QTc-interval, which is prolonged predominately by effects on repolarization.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Ventricular Arrhythmias by QRS/QTc - Ratio in Citalopram or Escitalopram Intoxication

Dietrichs

Smith

2022

Front. Med.

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BackgroundThe U.S. Food and Drug Administration (FDA) has stated that citalopram and escitalopram should not be used at daily doses above 40 mg/20 mg due to risk for development of fatal ventricular arrhythmias like torsade de pointes (TdP). Yet, supratherapeutic serum concentrations of citalopram are common and predicting patients at risk for TdP is of high clinical value. Accordingly, we investigated whether QRS/QTc; developed for predicting TdP in hypothermic patients could be used in citalopram intoxication.MethodsA total of 16 publications describing patients suffering from complications due to citalopram or escitalopram treatment, or intoxication with the same substances, were included after a systematic search. The main criterion for inclusion was admission ECG, either with given QRS and QTc values or with attached ECG-files that enabled calculation.ResultsQRS/QTc rather that QTc alone emerged as a marker of ventricular arrhythmia in the 16 included case reports, with highly significant (p < 0.0005) lower values in patients displaying ventricular arrhythmias.ConclusionCitalopram and escitalopram are extensively used in treatment of depressive disorders, and a large proportion of patients have supratherapeutic serum concentrations. Calculation of QRS/QTc in available case reports show that this novel ECG-marker has potential to predict patients at risk for developing ventricular arrhythmias.

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“…Such complications are not uncommon in hypothermia per se [29], and it is possible that administering pentoxifylline to hypothermic patients, could lead to increased risk. Both in vivo, ex vivo and human data show that there is an increased risk of ventricular fibrillation (VF) in hypothermia, when the core temperature is around 30 °C [32][33][34]. Potential aggravation of such lethal side effects should be further assessed in the experimental setting before clinical implementation of pentoxifylline for treatment of hypothermic patients is considered.…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic properties for inhibition of cAMP- and cGMP elimination by pentoxifylline remain unaltered in vitro during hypothermia

Selli

Kuzmiszyn

Smaglyukova

et al. 2022

Scand J Trauma Resusc Emerg Med

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Background Rewarming from hypothermia is associated with severe complications, one of which is hypothermia-induced cardiac dysfunction. This condition is characterized by decreased cardiac output accompanied by increased total peripheral resistance. This contributes to mortality rate approaching 40%. Despite this, no pharmacological interventions are recommended for these patients below 30 °C. Raising the intracellular levels of cAMP and/or cGMP, through PDE3- and PDE5-inhibitors respectively, have showed the ability to alleviate hypothermia-induced cardiac dysfunction in vivo. Drugs that raise levels of both cAMP and cGMP could therefore prove beneficial in patients suffering from hypothermia-induced cardiac dysfunction. Methods The unselective PDE-inhibitor pentoxifylline was investigated to determine its ability to reach the intracellular space, inhibit PDE3 and PDE5 and inhibit cellular efflux of cAMP and cGMP at temperatures 37, 34, 30, 28, 24 and 20 °C. Recombinant human PDE-enzymes and human erythrocytes were used in the experiments. IC50-values were calculated at all temperatures to determine temperature-dependent changes. Results At 20 °C, the IC50-value for PDE5-mediated enzymatic breakdown of cGMP was significantly increased compared to normothermia (IC50: 39.4 µM ± 10.9 µM vs. 7.70 µM ± 0.265 µM, p-value = 0.011). No other significant changes in IC50-values were observed during hypothermia. Conclusions This study shows that pentoxifylline has minimal temperature-dependent pharmacodynamic changes, and that it can inhibit elimination of both cAMP and cGMP at low temperatures. This can potentially be effective treatment of hypothermia-induced cardiac dysfunction. Trial registration: Not applicable.

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Resistance to ventricular fibrillation predicted by the QRS/QTc - Ratio in an intact rat model of hypothermia/rewarming

Cited by 6 publications

References 23 publications

Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32°C) With Spontaneous Circulation in an Intact Porcine Model

Cardiovascular Effects of Epinephrine During Experimental Hypothermia (32°C) With Spontaneous Circulation in an Intact Porcine Model

Prediction of Ventricular Arrhythmias by QRS/QTc - Ratio in Citalopram or Escitalopram Intoxication

Pharmacodynamic properties for inhibition of cAMP- and cGMP elimination by pentoxifylline remain unaltered in vitro during hypothermia

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