Effect of nifedipine on physiologic shunting and oxygenation in chronic obstructive pulmonary disease

Kalra, Lalit; Bone, Michael

doi:10.1016/0002-9343(93)90154-h

Cited by 25 publications

(11 citation statements)

References 24 publications

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“…3,4,21,22 Despite the significant advances in the therapy for PAH in recent years, the prognosis remains poor. [8][9][10][11][12][13][14] Cilostazol, a type 3 phosphodiesterase inhibitor, has been proven to have anti-platelet and anti-thromboembolic effects as well as inhibiting smooth muscle proliferation. 18,23,24 Accordingly, the administration of cilostazol to MCT-induced PAH in rats was expected to offer additional benefits of improving pulmonary blood flow and reduced PAH.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] Strategic managements for PAH include long-term oxygen or inhaled nitric oxide therapy, diuretic therapy, anticoagulant agents, vasodilators, calcium channel blocker agents, intravenous prostacyclin, phosphodiesterase inhibitors and endothelin antagonists. [8][9][10][11][12][13][14] However, all of these therapies remain problematic due to either high cost, limited effectiveness or serious side effects.Regarding the mechanistic basis of PAH, inhibiting the abnormal proliferation of vascular endothelial and smooth muscle cells may be an effective therapeutic strategy for preventing progressive PAH. 15,16 Cilostazol, a phosphodiesterase III inhibitor approved by the US Food and Drug…”

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confidence: 99%

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Cilostazol Therapy Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat Model

Chang

Sun

Sheu

et al. 2008

Circ J

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ulmonary arterial hypertension (PAH) is caused by various pathophysiological mechanisms and characterized by a progressive increase in pulmonary vascular resistance caused by vascular cell proliferation and obliteration of pulmonary microvasculature, leading to severe pulmonary hypertension, right side heart failure and death. [1][2][3][4][5][6][7] Strategic managements for PAH include long-term oxygen or inhaled nitric oxide therapy, diuretic therapy, anticoagulant agents, vasodilators, calcium channel blocker agents, intravenous prostacyclin, phosphodiesterase inhibitors and endothelin antagonists. [8][9][10][11][12][13][14] However, all of these therapies remain problematic due to either high cost, limited effectiveness or serious side effects.Regarding the mechanistic basis of PAH, inhibiting the abnormal proliferation of vascular endothelial and smooth muscle cells may be an effective therapeutic strategy for preventing progressive PAH. 15,16 Cilostazol, a phosphodiesterase III inhibitor approved by the US Food and Drug Circulation Journal Vol.72, May 2008Administration (FDA) for treatment of intermittent claudication, reduces smooth muscle proliferation and intimal hyperplasia after endothelial injury and lowers restenosis after coronary artery stenting. [17][18][19][20] However, whether cilostazol therapy can reverse PAH through inhibition of endothelial and smooth muscle cell proliferation has not been reported. Therefore, the present study tested the hypothesis that cilostazol therapy can effectively attenuate PAH after the administration of monocrotaline (MCT), which is well known to induce selective pulmonary endothelial injury in the rat. Methods Ethics, Experimental ProceduresAll animal experimental procedures were approved by the Institute of Animal Care and Use Committee at our hospital and were performed in accordance with the Guide for the Care and Use of Laboratory Animals (NIH publication No. 85-23, National Academy Press, Washington, DC, USA, revised 1996).All animal experimental procedures were done by investigators who blinded to the experimental conditions of all rats. Animal Models of PAH and Study SampleOn day 0, pathogen-free, adult male Sprague-Dawley (SD) rats (n=20), weighing 300-320 g (Charles River Technology, BioLASCO Taiwan Co, Ltd, Taiwan) were given 1 subcutaneous injection of MCT (75 mg/kg; Sigma, St. Louis, MO, USA).On day 28, after right ventricular systolic blood pressure (RVSBP) was measured in each rat, MCT-treated rats were assigned to 2 experimental groups: group 1 (MCT alone, Methods and ResultsMale Sprague -Dawley rats (n=10/each group) were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus cilostazol (20 mg·kg -1 ·day -1 ) (group 2) and saline injection only (group 3). Hemodynamic measurement on day 28 following MCT treatment indicated the development of significant PAH on MCT-treated groups (p<0.0001). Cilostazol was given to group 2 orally on days 28-90. By day 90 following MCT treatment, the right ventricular (RV) systolic blood pressure and RV hyper...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Cilostazol Therapy Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat Model

Chang

Sun

Sheu

et al. 2008

Circ J

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“…Calcium antagonists have been shown to be effective in the treatment of pulmonary hypertension secondary to connective tissue vascular disease (67), but not in patients with COPD (68), where treatment was limited because of the deleterious effects on venous admixture (69). The effectiveness of therapy with calcium antagonists in secondary pulmonary hypertension seems to depend on the initial level of PAP, i.e., the higher the initial level of PAP, the less effective the drug (67,68).…”

Section: Specific Treatmentmentioning

confidence: 98%

Management of Pulmonary Hypertension: Physiological and Pharmacological Considerations for Anesthesiologists

Fischer¹,

Aken²,

Rkle³

2003

Anesthesia & Analgesia

171

108

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F or decades the pulmonary circulation was not considered as important as the systemic ("greater") circulation. However, pulmonary hypertension can arise because of many diseases of the heart and lung. Therefore, increasing efforts in research have been undertaken leading to a profound increase in understanding pulmonary vascular physiology and pathophysiology. This review discusses basic physiology, clinical concepts, and treatment options for pulmonary hypertension and the related right ventricular heart failure focusing on secondary pulmonary hypertension in patients during anesthetic procedures. Physiology of Pulmonary CirculationThe pulmonary vascular bed is a high-flow, lowpressure circulation system. Pulmonary vessels have less resistance in comparison to the systemic circulation under normal conditions because of higher compliance of pulmonary precapillary arterioles with a thinner media and less smooth muscle cells (SMCs) compared with the corresponding systemic arterioles. In addition, the cross-sectional area of the pulmonary vascular bed is large and highly distensible with recruitable vessels available to accommodate increase in flow resulting in low pressure and low resistance.In contrast to the systemic arteries, pulmonary vessels constrict with hypoxia (Euler-Liljestrand reflex) and relax in the presence of hyperoxia. Furthermore, changes in cardiac output (CO), airway pressure, and gravity affect the pulmonary more than the systemic circulation. Increases in CO distend open vessels and recruit previously closed vessels. Therefore, the crosssectional area of pulmonary circulation enlarges and results in a decrease in pulmonary vascular resistance (PVR). An increase in CO has very little effect on pulmonary arterial pressure (PAP) because of the recruitment and distension of pulmonary vessels. An increased PAP or left atrial pressure (LAP) may also distend and recruit pulmonary vessels. Clinically, this means that enhanced CO caused by the administration of inotropic drugs or enlarged blood volume will passively decrease PVR.

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“…Although several management strategies have been proposed, including long-term therapy with oxygen or inhaled nitric oxide (Anand et al, 1998), diuretic therapy, anticoagulants, vasodilators (Barst et al, 1999), calcium channel blockers (Kalra and Bone, 1993), intravenous prostacyclin (Barst et al, 1996;Badesch et al, 2000), phosphodiesterase inhibitors, and endothelin antagonists (Badesch et al, 2000;Channick et al, 2001;Rubin et al, 2002), these regimens remain unsatisfactory due to either limited efficacy or serious side effects. In view of the mechanistic basis of vascular cell proliferation and vascular occlusion, inhibition of vascular smooth muscle proliferation, together with restoration of endothelial function and integrity of pulmonary microvasculature, may be a novel and effective therapeutic strategy for the re-establishment of normal pulmonary hemodynamics in patients with PAH.…”

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confidence: 99%

Early Combined Treatment with Cilostazol and Bone Marrow-Derived Endothelial Progenitor Cells Markedly Attenuates Pulmonary Arterial Hypertension in Rats

Sun¹,

Lee²,

Sheu³

et al. 2009

J Pharmacol Exp Ther

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We investigated whether early combined cilostazol and bone marrow-derived endothelial progenitor cell (BMDEPC) treatment offers synergistic benefit in ameliorating monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Male Sprague-Dawley rats (n ϭ 10/group) were randomized to receive saline injection only (group 1), MCT (70 mg/kg) (group 2), and MCT plus cilostazol (20 mg/kg/day) (group 3), MCT plus BMDEPCs (2.0 ϫ 10 6 cells) (group 4), and MCT plus combined cilostazol/BMDEPCs (group 5). Intravenous BMDEPCs and oral cilostazol were given on day 3 after MCT administration. By day 42, connexin43 protein expression in right ventricle (RV) was reduced in group 2 compared with other groups and also was decreased in groups 3 and 4 compared with groups 1 and 5 (all p Ͻ 0.05). In addition, mRNA expressions of matrix metalloproteinase-9, tumor necrosis factor-␣, and caspase-3 were higher, whereas Bcl-2 and endothelial nitric-oxide synthase were lower in lung and RV in group 2 compared with the other groups (all p Ͻ 0.05). The number of alveolar sacs and lung arterioles was lower in group 2 than in other groups and lower in groups 3 and 4 than in group 5 (all p Ͻ 0.05). RV systolic pressure (RVSP) and weight were increased in group 2 compared with the other groups (all p Ͻ 0.0001). Moreover, RVSP and RV-to-left ventricle plus septum weight ratio were higher in groups 3 and 4 than in groups 1 and 5 (p Ͻ 0.001) but showed no difference between groups 1 and 5. In conclusion, early combined autologous BMDEPC/cilostazol treatment is superior to BMDEPC or cilostazol only for preventing MCT-induced PAH.

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Effect of nifedipine on physiologic shunting and oxygenation in chronic obstructive pulmonary disease

Cited by 25 publications

References 24 publications

Cilostazol Therapy Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat Model

Cilostazol Therapy Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat Model

Management of Pulmonary Hypertension: Physiological and Pharmacological Considerations for Anesthesiologists

Early Combined Treatment with Cilostazol and Bone Marrow-Derived Endothelial Progenitor Cells Markedly Attenuates Pulmonary Arterial Hypertension in Rats

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