The effects of carbon monoxide on the heart: An in vitro study

McGrath, James J.

doi:10.1016/0091-3057(84)90171-0

Cited by 9 publications

(6 citation statements)

References 17 publications

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“…However, the notion of a direct negative chronotropic effect of CO on the excitation‐conduction system is supported by the observed positive inotropic effect coinciding with the rate drop, since CO toxicity is associated with depression in myocardial contractility. This also accords with the more rapid decline in heart rate observed by McGrath (1984), in hearts challenged with 95% CO–5% CO 2 compared to 95% N 2 –5% CO 2 . The ability of CO to modulate heart rate is another aspect with similarity to NO.…”

Section: Discussionmentioning

confidence: 99%

“…This effect has not been reported previously with CO gas, probably due to the relatively small number of studies looking at the influence of CO on the myocardium. Most of the previous studies have focused on CO toxicity which causes contractile depression (McGrath, 1984; Chen and McGrath, 1985). Interestingly, none of the CORM‐A1 doses used in this study affected myocardial contractility, despite indications that it was the CO liberated by CORM‐3 which appeared to cause the positive inotropic effect, as suggested by the lack of contractile response to the inactive form of the drug (iCORM‐3).…”

Section: Discussionmentioning

confidence: 99%

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Positive inotropic effects of carbon monoxide‐releasing molecules (CO‐RMs) in the isolated perfused rat heart

Musameh

Fuller

Mann

et al. 2006

British J Pharmacology

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Background and purpose: Carbon monoxide (CO) generated by the enzyme haeme oxygenase-1 (HO-1) during the breakdown of haeme is known to mediate a number of biological effects. Here, we investigated whether CO liberated from two water soluble carbon monoxide-releasing molecules (CO-RMs) exerts inotropic effects on the myocardium. Experimental approach: Rat isolated hearts perfused either at constant flow or constant pressure were used to test the effect of CO-RMs. Key results: CORM-3, a fast CO releaser, produced a direct positive inotropic effect when cumulative doses (3, 10 and 30 mg min À1 ) or a single dose (5 mM) were infused at either constant coronary pressure (CCP) or constant coronary flow (CCF). The inotropic effect mediated by CORM-3 was abolished by blockade of soluble guanylate cyclase or Na þ /H þ exchanger, but not by inhibitors of L-type Ca 2 þ channels and protein kinase C. CORM-3 also caused a slight reduction in heart rate but did not alter coronary flow. In contrast, the slow CO releaser CORM-A1 produced significant coronary vasodilatation when given at the highest concentration (30 mg min À1 ) but exerted no effect on myocardial contractility or heart rate. Conclusion and implications: A rapid CO release from CORM-3 exerts a direct positive inotropic effect on rat isolated perfused hearts, whereas CO slowly released by CORM-A1 had no effect on myocardial contractility but caused significant coronary vasodilatation. Both cGMP and Na þ /H þ exchange appear to be involved in this effect but further work is needed to determine the relative contribution of each pathway in CO-mediated inotropic effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Positive inotropic effects of carbon monoxide‐releasing molecules (CO‐RMs) in the isolated perfused rat heart

Musameh

Fuller

Mann

et al. 2006

British J Pharmacology

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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. Binding of CO to cytochrome oxidase may interfere with cellular respiration even though the affinity of oxygen for cytochrome oxidase is much higher than that for CO. [7][8][9] Another candidate site for CO action on the heart is on myoglobin.…”

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confidence: 99%

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

Suner

Jay

2008

Academic Emergency Medicine

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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

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“…More recently, McGrath and collaborators (83)(84)(85), using a bloodless, isolated perfused heart preparation, demonstrated that CO results in greater coronary vasodilation than nitrogen anoxia, strengthening the con-tention that CO has a direct effect on vascular smooth muscle discrete from an anoxic one.…”

Section: Coronary and Cerebral Blood Flowmentioning

confidence: 98%

Hemodynamic response to carbon monoxide.

Penney

1988

Environ Health Perspect

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Historically, and at present, carbon monoxide is a major gaseous poison responsible for widespread morbidity and mortality. From threshold to maximal nonlethal levels, a variety of cardiovascular changes occur, both immediately and in the long term, whose homeostatic function it is to renormalize tissue oxygen delivery. However, notwithstanding numerous studies over the past century, the literature remains equivocal regarding the hemodynamic responses in animals and humans, although CO hypoxia is clearly different in several respects from hypoxic hypoxia. Factors complicating interpretation of experimental findings include species, CO dose level and rate, route of CO delivery, duration, level of exertion, state of consciousness, and anesthetic agent used. For example, tachycardia is commonly observed, although bradycardia also can result from myocardial and/or central nervous system (CNS) hypoxemia at high carboxyhemoglobin (COHb) saturations, as can electrocardiographic abnormalities. Augmented cardiac output usually observed with moderate COHb may be compromised in more severe poisoning for the same reasons, such that regional or global ischemia result. The hypotension usually seen in most animal studies is thought to be a primary cause of CNS damage resulting from acute CO poisoning, yet the exact mechanism(s) remains unproven in both animals and humans, as does the way in which CO produces hypotension. This review briefly summarizes the literature relevant to the short- and long-term hemodynamic responses reported in animals and humans. It concludes by presenting an overview using data from a single species in which the most complete work has been done to date.

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The effects of carbon monoxide on the heart: An in vitro study

Cited by 9 publications

References 17 publications

Positive inotropic effects of carbon monoxide‐releasing molecules (CO‐RMs) in the isolated perfused rat heart

Positive inotropic effects of carbon monoxide‐releasing molecules (CO‐RMs) in the isolated perfused rat heart

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

Hemodynamic response to carbon monoxide.

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