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

Abstract

Objectives: Carbon monoxide (CO) toxicity causes significant central nervous system and cardiac injury. Although the neurological damage caused by CO toxicity is extensively described, the mechanisms underlying myocardial insult are unclear. The authors used an externally perfused isolated rat heart model to examine the effects of a physiological saline solution (Krebs Henseleit HEPES, KHH) aerated with CO on cardiac function.Methods: Fifteen rats were equally divided into three groups: the control group (KHH + 100% O 2 ), the nitrogen control group (KHH + 70% O 2 , 30% N 2 ), and the CO group (KHH + 70% oxygen, 30% CO). Left ventricular peak systolic pressure (LVPsP), end diastolic pressure (LVEdP), and coronary perfusion pressure were measured while the isolated heart was paced and perfused on a modified Langendorf apparatus.Results: Left ventricular generated pressure (LVGP = LVPsP ) LVEdP) decreased in the nitrogen control and CO groups compared to the control group. There was higher LVGP in the recovery phase between the nitrogen control group compared to the CO group. Both groups had increased lactic acid levels in the experimental phase.Conclusions: Carbon monoxide with hypoxia and hypoxemic hypoxia both result in similar depression of cardiac function. Hearts poisoned with CO with hypoxia do not recover function to the extent that hearts rendered hypoxic with nitrogen do when perfused with 100% oxygen after the insult. This suggests that CO causes direct myocardial toxicity distinct from the effects of hypoxia.ACADEMIC EMERGENCY MEDICINE 2008; 15:59-65 ª

Mechanisms of toxic cardiomyopathy

“…The classical hypothesis is that the binding of CO to intracellular myoglobin in the myocardium impairs oxygen delivery to the mitochondria, and that subsequent energy disorders lead to cardiac contractile decrease [58][59][60][61][62]. Carbon monoxide is also directly toxic for mitochondria, with impairment of mitochondrial respiratory chain at the cytochrome c oxidase level, decrease of glutathione concentrations and of ATP generation [63][64][65]. Finally, a catecholamine surge is also likely involved, mainly for the takotsubo pattern [55].…”

A Prospective Comparative Study between Three Chemical Markers for Predicting Delayed Neurological Sequelae in Patients with Acute Carbon Monoxide Poisoning of Poison Control Center in Minia University Hospital.

“…CO has a significant affinity for all iron or copper containing sites and competes with oxygen at these active sites. The affinity of hemoglobin for CO is 250 times higher than that for oxygen , the result is the formation of carboxy hemoglobin (CO-Hb) which is a molecule incapable of carrying O2 to tissue sites resulting in tissue hypoxia (Suner and Jay, 2008).…”

Magnesium sulfate protects the heart against carbon monoxide-induced cardiotoxicity in rats

“…Furthermore, in this study, MS decreased pathological insults induced by CO. Also, histopathological results showed that MS-treated rats exert reduced necrosis rates in cardiomyocytes as compared to the control group. Cardiac ischemia is the hallmark of cardiotoxicity of CO poisoning ( 17 ). The main mechanism underlying CO poisoning is binding of CO to hemoglobin, resulting in a left-ward shift of oxyhemoglobin curve and tissue hypoxia ( 17 ).…”

“…Cardiac ischemia is the hallmark of cardiotoxicity of CO poisoning ( 17 ). The main mechanism underlying CO poisoning is binding of CO to hemoglobin, resulting in a left-ward shift of oxyhemoglobin curve and tissue hypoxia ( 17 ). Hemoglobin affinity to CO is about 200-250 times higher than its affinity to O2 ( 17 ).…”

“…Many studies confirmed that intravenous (i.v.) administration of MS before and even after ischemia/reperfusion (I/R) ameliorates deleterious effects of ischemia on the heart ( 15 16 17 18 ). Some of these studies did not show significant reduction in infarct size while others showed that MS reduces infarct size, improves vasodilation and nitric oxide (NO) production and exerts Ca 2+ antagonistic effects ( 15 ).…”