The Effect of Anoxia on the Ventricular Fibrillation Threshold in the Rabbit Isolated Heart

Murnaghan, Maurice F.

doi:10.1111/j.1476-5381.1975.tb07586.x

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…Serum potassium level was normal in both groups. Hypoxia, the most important causative factor of CA in patients with CP, exerts its effect on action potentials in the heart muscle [18] sinoatrial nodal cells, conducting system [19], mesencephalic ret icular formation [20], and the central ner vous system [21] by reducing the ventricu lar fibrillation threshold [22]. Our study showed that the CA were frequent al though supplemental oxygen was given and patients were sufficiently oxygenated.…”

Section: Discussionmentioning

confidence: 71%

The Effects of Mexiletine on Cardiac Arrhythmias in Patients with Cor Pulmonale

Skwarski¹,

Śliwiński²,

Górecka³

et al. 1989

Respiration

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Cardiac arrhythmias (CA) are a frequent and dangerous complication of respiratory and cardiac failure in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to investigate the effects of mexiletine on CA in patients with cor pulmonale in a state of cardio-respiratory decompensation. We studied 32 COPD patients with severe airways obstruction; mean VC 2.3510.53 litres; FEV₁, 0.92 ± 0.3 litres and respiratory failure, PaO₂ = 56 ± 5 mm Hg, PaCO₂ = 47 ± 9 mm Hg allocated by random numbers to 20 treated and 12 controls. Continuous 24-hour Holter monitoring was performed for 3 consecutive days after admission to the department following routine treatment which consisted of low-flow oxygen, antibiotic, bronchodilators and diuretics. On the first day, the type and frequency of CA were analysed. Then the treated patients were given mexiletine 250 mg i.v. + 200 mg orally followed by 200 mg every 8 h for the next 48 h. Controls continued the routine treatment only. Mexiletine treatment resulted in a highly significant reduction in the mean number of premature ventricular beats from 163 to 28 and 30/24 h, respectively (p < 0.01). Episodes of ventricular tachycardia were abolished. The mean number of premature supraventricular beats also fell from 85 to 67 and 48/24h (p < 0.01). Number of episodes of sinus tachycardia fell from 17 during the first day to 13 and 10 on the 2nd and 3rd days, respectively. In the controls, the frequency and type of CA remained unchanged. Our results demonstrate that mexiletine has a beneficial effect in limiting CA in patients with right heart and respiratory failure.

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Section: Discussionmentioning

confidence: 71%

The Effects of Mexiletine on Cardiac Arrhythmias in Patients with Cor Pulmonale

Skwarski¹,

Śliwiński²,

Górecka³

et al. 1989

Respiration

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“…Since a high concentration of free fatty acids (FFA) cause an increased demand for oxygen (Mj0s, 1971;Kjekshus & Mj0s, 1972) they would be expected to increase the degree of hypoxia so that it would approach that of the anoxic state. Since anoxia is more arrhythmogenic than hypoxia in so far as it lowers the VAT more (Murnaghan, 1975), then FFA when combined with hypoxia would be expected to increase the incidence of an arrhythmia.…”

Section: Discussionmentioning

confidence: 99%

Effect of Fatty Acids on the Ventricular Arrhythmia Threshold in the Isolated Heart of the Rabbit

Murnaghan

1981

British J Pharmacology

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1 The ventricular arrhythmia threshold (VAT) was measured in the isolated Ringer-perfused rabbit heart (Langendorff preparation) by applying a single 10 ms square-wave pulse of current to the left ventricle during the vulnerable period of late systole under normoxic and hypoxic conditions. 2 The sodium salt of the fatty acid was bound to albumen and incorporated in the Krebs-Henseleit solution which was maintained at 37°C and gassed with 95 %02 and 5% CO2 (normoxia) or 5% CO2 in air (hypoxia). 3 Saturated fatty acids failed to alter the VAT under normoxia. 4 Naturally occurring long-chained saturated and mono-unsaturated fatty acids with chain lengths varying from 14 to 20 carbons, but not the 12 carbon lauric acid, potentiated the effect of the hypoxia in lowering the VAT.5 Short-chained 8 and 10 carbon saturated and long-chained polyunsaturated fatty acids antagonized the effect of hypoxia on the VAT.6 In addition the polyunsaturated acids antagonized the potentiating effect of the long-chained saturated and mono-unsaturated acids on the hypoxia in lowering the VAT.7 The fatty acids did not alter the duration or type of the induced arrhythmia.

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“…Ischemia and hypoxia during cardioplegic arrest result in respiratory chain failure and might finally initiate cell death (Luo et al, 2015 ). Hypoxic conditions during cardioplegia as well as reperfusion injury may result in reduced contractile function and promote arrhythmia, a situation in which catecholamine treatment is usually necessary with additional antiarrhythmic medication or electrical defibrillation and which has a negative impact on patient outcome (Murnaghan, 1975 ; Casthely et al, 1994 ).…”

Section: Introductionmentioning

confidence: 99%

Olesoxime Inhibits Cardioplegia-Induced Ischemia/Reperfusion Injury. A Study in Langendorff-Perfused Rabbit Hearts

et al. 2017

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Objective: During cardioplegia, which is often used in cardiac surgery, the heart is subjected to global ischemia/reperfusion injury, which can result in a post-operative impairment of cardiac function. Mitochondria permeability transition pores (MPTP) play a key role in cardiomyocyte survival after ischemia/reperfusion injury. It was shown in clinical settings that blockers of MPTP like cyclosporine might have a positive influence on cardiac function after cardioplegic arrest. Olesoxime, which is a new drug with MPTP blocking activity, has been introduced as a neuroprotective therapeutic agent. This drug has not been investigated on a possible positive effect in ischemia/reperfusion injury in hearts. Therefore, the aim of our study was to investigate possible effects of olesoxime on cardiac recovery after cardioplegic arrest.Methods: We evaluated 14 mature Chinchilla bastard rabbits of 1,500–2,000 g. Rabbit hearts were isolated and perfused with constant pressure according to Langendorff. After induction of cardioplegic arrest (30 ml 4°C cold Custodiol cardioplegia without and with 5 μmol/L olesoxime, n = 7 each) the hearts maintained arrested for 90-min. Thereafter, the hearts were re-perfused for 60 min. At the end of each experiment left ventricular samples were frozen in liquid nitrogen for ATP measurements. Furthermore, heart slices were embedded in paraffin for histological analysis. During the entire experiment hemodynamic and functional data such as left ventricular pressure (LVP), dp/dt(max) and (min), pressure rate product (PRP), coronary flow, pO2, and pCO2 were also assessed.Results: Histological analysis revealed that despite the same ischemic burden for both groups markers of nitrosative and oxidative stress were significantly lower in the olesoxime group. Moreover, hearts of the olesoxime-group showed a significantly faster and better hemodynamic recovery during reperfusion. In addition, tissue ATP-levels were significantly higher in the olesoxime treated hearts.Conclusions: Olesoxime significantly protected the cardiac muscle from ischemia/reperfusion injury.

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The Effect of Anoxia on the Ventricular Fibrillation Threshold in the Rabbit Isolated Heart

Cited by 6 publications

References 37 publications

The Effects of Mexiletine on Cardiac Arrhythmias in Patients with Cor Pulmonale

The Effects of Mexiletine on Cardiac Arrhythmias in Patients with Cor Pulmonale

Effect of Fatty Acids on the Ventricular Arrhythmia Threshold in the Isolated Heart of the Rabbit

Olesoxime Inhibits Cardioplegia-Induced Ischemia/Reperfusion Injury. A Study in Langendorff-Perfused Rabbit Hearts

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