Ischemia-reperfusion impairs endothelium-dependent relaxation of coronary microvessels but does not affect large arteries.

Quillen, James E.; Sellke, Frank W.; Brooks, Leonard; Harrison, David G.

doi:10.1161/01.cir.82.2.586

Cited by 148 publications

(59 citation statements)

References 17 publications

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“…There are several studies that have demonstrated that myocardial ischaemia and reperfusion selectively impairs endothelium-dependent relaxation of isolated coronary arteries (for reviews Hearse et al, 1993;Sobey & Woodman 1993) although there are also reports that the coronary conductance arteries are una ected by ischaemia (Quillen et al, 1990;Winn & Ku, 1992). In the present study ischaemia/ reperfusion did not a ect the absolute response to ACh even though we employed a protocol similar to previous studies from this laboratory where endothelium-dependent relaxation was impaired (Sobey et al, 1990;.…”

Section: Discussionmentioning

confidence: 68%

“…However, Quillen et al, (1990) and Winn & Ku (1992) both reported that ACh-induced relaxation of dog coronary arteries was una ected by ischaemia and reperfusion. This then raises the question as to whether EDHF might contribute to endothelium-dependent relaxation after ischaemia and reperfusion to help to maintain responses to endothelium-dependent dilators, however the mechanism of endothelium-dependent relaxation has not previously been investigated in ischaemic arteries.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced role for the opening of potassium channels in relaxant responses to acetylcholine after myocardial ischaemia and reperfusion in dog coronary arteries

Chan

Woodman

1999

British J Pharmacology

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1 Anaesthetized dogs were subjected to 1 h occlusion of the left circum¯ex coronary artery followed by 2 h of reperfusion. Relaxant responses were examined in coronary artery rings removed proximal (nonischaemic) or distal (ischaemic) to the site of occlusion. 2 Relaxant responses to acetylcholine (ACh) were similar in nonischaemic and ischaemic artery rings. In addition ACh-induced relaxation of nonischaemic and ischaemic artery rings was equally susceptible to inhibition of nitric oxide (NO) synthase using L-N G -nitroarginine (L-NOARG, 10 74 M), or to inhibition of soluble guanylate cyclase using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 75 M). 3 In nonischaemic arteries, the relaxation to ACh was una ected by high K + (67 mM) but in ischaemic arteries, the maximum relaxation to ACh was signi®cantly reduced from 113+6 to 60+2% (ANOVA, P50.05). Tetraethylammonium (TEA, 10 73 M), an inhibitor of large conductance calcium activated potassium (BK Ca ) channels did not inhibit the response to ACh in nonischaemic arteries but in ischaemic arteries TEA signi®cantly shifted the concentration response curve to ACh to the right (pEC 50 ; nonischaemic, 7.07+0.25; ischaemic, 6.54+0.21, P50.01, ANOVA) without decreasing the maximum relaxation. TEA did not a ect the responses to sodium nitroprusside in either nonischaemic or ischaemic arteries. 4 In conclusion, ischaemia/reperfusion did not change the sensitivity of endothelium-dependent relaxation to L-NOARG or ODQ indicating that ischaemia did not a ect the contribution of NO or cyclic GMP to ACh-induced relaxation. However, in ischaemic arteries the opening of the BK Ca channels contributed to relaxation caused by ACh whereas TEA had no e ect in nonischaemic arteries. The factor responsible for the opening of this potassium channel was a factor other than NO and may be endothelium derived hyperpolarizing factor (EDHF).

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Enhanced role for the opening of potassium channels in relaxant responses to acetylcholine after myocardial ischaemia and reperfusion in dog coronary arteries

Chan

Woodman

1999

British J Pharmacology

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“…Recent studies have demonstrated that ischemic or hypoxic injury to vital organs, including brain, lung, heart, and kidney, not only damages parenchymal cells but also affects the function and reactivity of the vasculature serving these organs (1)(2)(3)(4)(5)(6)(7). A general feature of the altered vasoreactivity is an augmented sensitivity to vasoconstrictor stimuli which, in turn, increases the vulnerability of the affected organ to additional ischemic attacks.…”

Section: Introductionmentioning

confidence: 99%

“…A general feature of the altered vasoreactivity is an augmented sensitivity to vasoconstrictor stimuli which, in turn, increases the vulnerability of the affected organ to additional ischemic attacks. Prinzmetal's and postinfarction angina, accelerating transient cerebral ischemic attacks, vasoconstriction after limb ischemia, and prolonged acute renal failure, at least in part, are thought to be clinical examples of postischemic hypersensitivity of the resistance vasculature (1)(2)(3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Conger

Robinette²,

Villar³

et al. 1995

J. Clin. Invest.

113

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Lack of response to endothelium-dependent vasodilators generally has been considered to be evidence for decreased nitric oxide synthase (NOS) activity and NO generation after ischemic or hypoxic injury to vital organs including the kidney. In this study, renal blood flow (RBF) responses to endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator prostacyclin, the nonselective NOS inhibitor L-NAME (without and with L-arginine), the inducible NOS inhibitor aminoguanidine, and the NO-donor sodium nitroprusside were examined in 1-wk norepinephrine-induced (NE) and sham-induced acute renal failure (ARF) rats. Compared with sham-ARF, there was no increase in RBF to intrarenal acetylcholine and bradykinin, but a comparable RBF increase to prostacyclin in NE-ARF kidneys. However, there was a signiflcantiy greater decline in RBF to intravenous L-NAME in NE-than sham-ARF rats (-65±8 vs. -37±5%, P < 0.001) which was completely blocked by prior L-arginine infusion. There was no change in RBF to the inducible NOS specific inhibitor aminoguanidine. Unlike sham-ARF, there was no increase in RBF to intrarenal sodium nitroprusside in NE-ARF. Immunohistochemistry and immunofluorescence detection of constitutive (c) NOS using mouse monoclonal antibody were carried out to positively determine the presence of cNOS in NE-ARF. 90% of renal resistance vessels showed evidence of endothelial cNOS in both sham-and NE-ARF. Taken together, results of these experiments are consistent with the conclusion that NOS/NO activity is, in fact, maximal at baseline in 1-wk NE-ARF and cannot be increased further by exogenous stimuli of NOS activity. The increased NOS is likely of the constitutive form and of endothelial origin. It is suggested that the increased NOS activity Clin. Invest. 1995. 96:631-638.)

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“…19) Previous studies have shown that microvessels exhibit detectable dysfunction earlier than larger epicardial vessels after ischemic injury. 20) Leukocyte depletion during reperfusion has been shown to attenuate endothelial reperfusion injury. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] Endothelial function is mediated via nitric oxide.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte-depleted Continuous Blood Cardioplegia for Coronary Artery Bypass Grafting

Murai¹,

Imazeki²,

Shioguchi³

et al. 2000

Jpn Heart J

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SUMMARYMany cardiac surgeries are performed with blood cardioplegia. However, some studies suggest that activated neutrophils form blood cardioplegia can cause reperfusion injury. In this study we assessed myocardial protection using a leukocyte-depleted cardioplegic solution.Patients undergoing elective coronary artery bypass grafting (CABG) with continuous blood cardioplegia were divided into two groups: the LD group, which received leukocyte-depleted blood cardioplegia (n = 11); and the control group, which received nonfiltered blood cardioplegia (n = 11). IL-6, IL-8, CK-MB, and troponin T were measured in the coronary sinus blood immediately after the release of the aortic cross-clamp. Cytokine concentrations were also measured upon the patient's return to the ICU. The total dopamine and dobutamine doses, hemodynamic measurements after surgery, and the leukocyte filtration rate were also measured.During antegrade cardioplegia infusion, leukocytes were almost completely removed (filtration rate: 85.8 ± 4.0%). However, during terminal warm cardioplegia, leukocyte removal decreased (filtration rate: 39.9 ± 7.8%). Immediately after the release of the aortic cross-clamp, plasma CK-MB and troponin T concentrations were significantly lower in the LD group (17.7 ± 1.9 U / l and 0.017 ± 0.002 ng / ml, respectively) than in the control group (30.3 ± 3.6 U / l and 0.072 ± 0.029 ng / ml, respectively). The IL-6 and IL-8 concentrations were similar in the LD group and the control group. After the return to the ICU, the CK-MB and troponin T concentrations were similar in the two groups. No significant differences were found in the total doses of dopamine or dobutamine after surgery in the two groups (99 ± 77 vs 101 ± 128 µg / kg / min). No significant differences were found in the hemodynamic parameters after surgery in the two groups.In patients undergoing CABG with continuous blood cardioplegia, leukocytedepleted blood cardioplegic solution may attenuate reperfusion injury. (Jpn Heart J 2000; 41: 425-433)

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Ischemia-reperfusion impairs endothelium-dependent relaxation of coronary microvessels but does not affect large arteries.

Cited by 148 publications

References 17 publications

Enhanced role for the opening of potassium channels in relaxant responses to acetylcholine after myocardial ischaemia and reperfusion in dog coronary arteries

Enhanced role for the opening of potassium channels in relaxant responses to acetylcholine after myocardial ischaemia and reperfusion in dog coronary arteries

Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Leukocyte-depleted Continuous Blood Cardioplegia for Coronary Artery Bypass Grafting

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