Microvascular and systemic effects following top load administration of saturated carbon monoxide-saline solution*

Hangai-Hoger, Nanae; Tsai, Amy G.; Cabrales, Pedro; Suematsu, Makoto; Intaglietta, Marcos

doi:10.1097/01.ccm.0000259533.84180.c7

Cited by 25 publications

(22 citation statements)

References 48 publications

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“…We contemplated several approaches to hinder the intrinsic NO-scavenging capacity of Hb, and chose Hb oxidation as the least likely to introduce artefacts, and suitable for short-duration experiments. We considered carboxyhemoglobin (COHb); however, carbon monoxide is released from Hb and the presence of CO in the circulation could be potent vasodilator in the hamster model, as shown by Hangai-Hoger and colleagues (24). Another alternative was inactivation of Hb gas transport carrying capacity using cyanide to form cyanomethemoglobin; however, this reaction affects RBCs membrane (increases fragility) and the cyanide cannot be removed 100% from the treated blood.…”

Section: Discussionmentioning

confidence: 99%

Lowering of Blood Pressure by Increasing Hematocrit with Non–Nitric Oxide–Scavenging Red Blood Cells

Vázquez¹,

Cabrales²,

Tsai³

et al. 2008

Am J Respir Cell Mol Biol

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Isovolemic exchange transfusion of 40% of the blood volume in awake hamsters was used to replace native red blood cells (RBCs) with RBCs whose hemoglobin (Hb) was oxidized to methemoglobin (MetHb), MetRBCs. The exchange maintained constant blood volume and produced different final hematocrits (Hcts), varying from 48 to 62% Hct. Mean arterial pressure (MAP) did not change after exchange transfusion, in which 40% of the native RBCs were replaced with MetRBCs, without increasing Hct. Increasing Hct with MetRBCs lowered MAP by 12 mm Hg when Hct was increased 12% above baseline. Further increases of Hct with MetRBCs progressively returned MAP to baseline, which occurred at 62% Hct, a 30% increase in Hct from baseline. These observations show a parabolic ''U'' shaped distribution of MAP against the change in Hct. Cardiac index, cardiac output divided by body weight, increased between 2 and 17% above baseline for the range of Hcts tested. Peripheral vascular resistance (VR) was decreased 18% from baseline when Hct was increased 12% from baseline. VR and MAP were above baseline for increases in Hct higher than 30%. However, vascular hindrance, VR normalized by blood viscosity (which reflects the contribution of vascular geometry), was lower than baseline for all the increases in Hct tested with MetRBC, indicating prevalence of vasodilation. These suggest that acute increases in Hct with MetRBCs increase endothelium shear stress and stimulate the production of vasoactive factors (e.g., nitric oxide [NO]). When MetRBCs were compared with functional RBCs, vasodilation was augmented for MetRBCs probably due to the lower NO scavenging of MetHb. Consequently, MetRBCs increased the viscosity related hypotension range compared with functional RBCs as NO shear stress vasodilation mediated responses are greater.Keywords: blood pressure; shear stress; NO bioavailability; hematocrit; plasma layer Increased hematocrit (Hct) above baseline is usually associated with elevation of systemic blood pressure due to the increase in blood viscosity. These effects were found in studies in which Hct was increased 40% or more above baseline (1-3). However, a recent study by Martini and coworkers (4) showed that mean arterial pressure (MAP) increases only when Hct is increased 20% above baseline using functional RBCs, and that MAP decreased when the change in Hct were less than 20%. In this range, cardiac output (CO) also increased and peripheral vascular resistance (VR) decreased (4, 5).According to Martini and colleagues (4), the cause of this paradoxical effect is that acute augmentation in Hct directly increases shear stress on the endothelium. This phenomenon may be due, in part, to the increase in viscosity and the decrease in cell-free layer (plasma layer) width, affecting blood properties and the endothelium interface, where shear signals are produced.Increased endothelial shear stress promotes production of endothelium vasoactive and nonvasoactive factors (6). Knockout mice deficient in endothelial nitric oxide (NO) synthases, and ham...

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Section: Discussionmentioning

confidence: 99%

Lowering of Blood Pressure by Increasing Hematocrit with Non–Nitric Oxide–Scavenging Red Blood Cells

Vázquez¹,

Cabrales²,

Tsai³

et al. 2008

Am J Respir Cell Mol Biol

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show abstract

“…In contrast, CO stimulates sGC and cGMP in conditions in which NO is diminished. Therefore, CO may act as a partial agonist for sGC activation to regulate vascular function and response Suematsu et al, 2005;Hangai-Hoger et al, 2007). CO acts as a 86 guardian against hepatic dysfunction and regulates NOmediated activation of cGMP Wu and Wang, 2005).…”

Section: Carbon Monoxide Production Ho-dependent Ho-independentmentioning

confidence: 99%

Pharmacological and Clinical Aspects of Heme Oxygenase

Abraham

Kappas²

2008

Pharmacol Rev

1,012

988

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“…In smooth muscle and endothelial tissue, CO mimics the effects of NO by causing relaxation and vasodilatation, respectively (Hangai-Hoger et al, 2007;Patel et al, 1993). CO also has anti-apoptotic and anti-inflammatory effects mediated through mitogen-activated protein kinases (MAPK) and not guanylyl cyclase (Piantadosi and Zhang, 1996).…”

Section: Functions Of Ho-2mentioning

confidence: 99%

“…In vascular tissue, CO has also been shown to stimulate relaxation of endothelial smooth muscle cells by activation of calcium-dependent potassium channels (Williams et al, 2004) via a poorly-understood mechanism that does not involve guanylyl cyclase. CO has been shown to serve as a partial agonist to nitric oxide synthetase (NOS) and thus, may down-regulate the level of NOSdependent signaling (Hangai-Hoger et al, 2007;Ishikawa et al, 2005).…”

Section: Protective Roles Of Co: Cell Signaling Mediated By Comentioning

confidence: 99%

Elucidating the Role of Biliverdin Reductase in the Expression of Heme Oxygenase-1 as a Cytoprotective Response to Stress

Reed¹

2012

Pharmacology

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Microvascular and systemic effects following top load administration of saturated carbon monoxide-saline solution*

Cited by 25 publications

References 48 publications

Lowering of Blood Pressure by Increasing Hematocrit with Non–Nitric Oxide–Scavenging Red Blood Cells

Lowering of Blood Pressure by Increasing Hematocrit with Non–Nitric Oxide–Scavenging Red Blood Cells

Pharmacological and Clinical Aspects of Heme Oxygenase

Elucidating the Role of Biliverdin Reductase in the Expression of Heme Oxygenase-1 as a Cytoprotective Response to Stress

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