Response of the isolated heart to carbon monoxide and nitrogen anoxia

Severe peri-ictal respiratory dysfunction is common in Dravet syndrome

“…This led to bradycardia with a time course similar to that seen after seizures in Scn1a R1407X/+ mice ( Figure 8). It also caused a decrease in amplitude of the QRS complex, as also occurred after fatal seizures, presumably a surrogate of decreased cardiac contractility (66). Pretreatment of WT mice with atropine at 1 mg/kg (n = 5) did not prevent the bradycardia induced by anoxia (Figure 8), indicating that the decrease in heart rate was not mediated by an increase in vagal output.…”

Myocardial findings in fatal carbon monoxide poisoning: a human and experimental morphometric study

“…The frequent occurrence of cardiac disturbances during or after exposure to CO, such as increased frequency of anginal attacks, arrhythmia, and increased levels of cardiac enzymes, has led to a search for morphological changes that could be attributed to CO, especially because the myocardium has been shown to bind more CO than skeletal muscle [4,5]. There is a decreased oxidative phosphorylation [6,7] with a parallel decrease of heart rate, pulse pressure [8,9,10,11] and increased coronary blood flow [8,12] with a relative subendocardial underperfusion [13] whereby vasodilatation is the major response to CO hypoxia [14]. The cardiac electrical instability is not influenced by CO exposure in both normal and ischemic dog hearts, without any effect on coronary blood flow and platelet aggregation [15], a finding which apparently contrasts with other studies both in animals and in human coronary artery disease [12,16].…”

Carbon Monoxide Has Direct Toxicity on the Myocardium Distinct from Effects of Hypoxia in an Ex Vivo Rat Heart Model

“…We chose to use LVGP because prior studies evaluating the cardiac hemodynamics using similar models also used this or similar measures (pulse pressure, mean arterial pressure). 4,6,12,13 Unlike some previous studies using this model to elucidate the effects of CO on the myocardium, in which 95% CO and 5% CO 2 were used, 4 we employed a mixture of CO and oxygen, which better simulates conditions of CO poisoning where the environmental conditions contain both gases. We tested various mixtures of CO and oxygen and determined that with 30% (v ⁄ v) CO in oxygen, the ex vivo rat heart preparation showed a significant depression and was able to recover function.…”

“…In some previous experiments, conducted paced hearts did not recover function after 10 minutes of perfusion with 95% CO and 5% CO 2 ; therefore, the delayed effects seen with CO compared to nitrogen control shown in our experiments could not have been appreciated. 4 Although some investigators used very low CO concentrations in their experiments (0.01%-0.05%), these studies were designed to detect biochemical changes related to oxidative stress and did not measure hemodynamic variables other than heart rate. Although one study quotes ''heart failure'' with CO concentrations as low as 0.2%, it is not clear from the data what this represents in terms of hemodynamic variables, since this observation was from unpublished data.…”

“…2,3 Previous animal studies have suggested that CO may produce direct toxicity to the myocardium rather than indirect hypoxic damage. 4 Experimentally, CO has been shown to decrease regional myocardial segment work and increase coronary flow with increasing concentrations; however, the site and mechanism of CO myocardial toxicity has not been elucidated. 5,6 A site of CO toxicity may be cytochrome oxidase at the level of the mitochondria.…”