High-fat diet alters prostanoid balance and perfusion in ischemic myocardium of naproxen-treated swine

Louis M. Chu; Michael P. Robich; Antonio D. Lassaletta; Jun Feng; Shu Hua Xu; Robert Heinl; Yuhong Liu; Eric Sellke; Frank W. Sellke

doi:10.1016/j.surg.2011.07.022

High-fat diet alters prostanoid balance and perfusion in ischemic myocardium of naproxen-treated swine

Louis M. Chu, Michael P. Robich, Antonio D. Lassaletta, Jun Feng, Shu Hua Xu, Robert Heinl, Yuhong Liu, Eric Sellke, Frank W. Sellke

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the cardiovascular system remains controversial, especially in patients with cardiovascular comorbidities. We used a swine model of chronic myocardial ischemia to investigate whether hypercholesterolemia alters the cardiovascular effects of the nonselective NSAID naproxen. Methods: Yorkshire swine were fed normal chow (NAP; n = 7) or a high-fat diet (HF-NAP; n = 8). Chronic myocardial ischemia was created in all animals by left circumflex ameroid constrictor placement. All swine were started on oral naproxen (440 mg/day) at the time of ameroid placement. After 7 weeks, myocardial perfusion and microvessel reactivity in the ischemic territory were assessed. Tissue levels of prostanoid metabolites 11-dehydrothromboxane B2 (11-d-TXB₂) and 6-keto-prostaglandin F1-α (6-k-PGF_1α) were measured. Tissue was analyzed for capillary density and protein expression. Results: Myocardial perfusion was significantly decreased in the HF-NAP group both at rest and during ventricular pacing. Microvessel relaxation responses to sodium nitroprusside and adenosine 5′-diphosphate were similar between groups. Tissue 11-d-TXB₂ levels were similar between groups, but tissue 6-k-PGF_1α was significantly decreased in the HF-NAP group (P =.001). Expression of thromboxane synthase was significantly higher in the HF-NAP group (P =.02), while prostacyclin synthase expression was significantly decreased in the HF-NAP group (P =.04). Capillary density was higher in the HF-NAP group (P =.005). Proangiogenic vascular endothelial growth factor (VEGF; P =.0002) and Akt (P =.01) were downregulated in the HF-NAP group. Conclusion: A high-fat diet impairs tissue perfusion in ischemic myocardium of naproxen-treated swine by shifting the prostanoid balance to favor production of thromboxane over prostacyclin. Dietary modification may improve myocardial blood flow and alter the safety profile in chronically ischemic cardiac patients taking naproxen.

Original language	English (US)
Pages (from-to)	490-496
Number of pages	7
Journal	Surgery
Volume	150
Issue number	3
DOIs	https://doi.org/10.1016/j.surg.2011.07.022
State	Published - Sep 2011
Externally published	Yes

ASJC Scopus subject areas

Surgery

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10.1016/j.surg.2011.07.022

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@article{65d7996ac5b046c7b1d874ff9987b971,

title = "High-fat diet alters prostanoid balance and perfusion in ischemic myocardium of naproxen-treated swine",

abstract = "Background: The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the cardiovascular system remains controversial, especially in patients with cardiovascular comorbidities. We used a swine model of chronic myocardial ischemia to investigate whether hypercholesterolemia alters the cardiovascular effects of the nonselective NSAID naproxen. Methods: Yorkshire swine were fed normal chow (NAP; n = 7) or a high-fat diet (HF-NAP; n = 8). Chronic myocardial ischemia was created in all animals by left circumflex ameroid constrictor placement. All swine were started on oral naproxen (440 mg/day) at the time of ameroid placement. After 7 weeks, myocardial perfusion and microvessel reactivity in the ischemic territory were assessed. Tissue levels of prostanoid metabolites 11-dehydrothromboxane B2 (11-d-TXB2) and 6-keto-prostaglandin F1-α (6-k-PGF1α) were measured. Tissue was analyzed for capillary density and protein expression. Results: Myocardial perfusion was significantly decreased in the HF-NAP group both at rest and during ventricular pacing. Microvessel relaxation responses to sodium nitroprusside and adenosine 5′-diphosphate were similar between groups. Tissue 11-d-TXB2 levels were similar between groups, but tissue 6-k-PGF1α was significantly decreased in the HF-NAP group (P =.001). Expression of thromboxane synthase was significantly higher in the HF-NAP group (P =.02), while prostacyclin synthase expression was significantly decreased in the HF-NAP group (P =.04). Capillary density was higher in the HF-NAP group (P =.005). Proangiogenic vascular endothelial growth factor (VEGF; P =.0002) and Akt (P =.01) were downregulated in the HF-NAP group. Conclusion: A high-fat diet impairs tissue perfusion in ischemic myocardium of naproxen-treated swine by shifting the prostanoid balance to favor production of thromboxane over prostacyclin. Dietary modification may improve myocardial blood flow and alter the safety profile in chronically ischemic cardiac patients taking naproxen.",

author = "Chu, {Louis M.} and Robich, {Michael P.} and Lassaletta, {Antonio D.} and Jun Feng and Xu, {Shu Hua} and Robert Heinl and Yuhong Liu and Eric Sellke and Sellke, {Frank W.}",

note = "Funding Information: Supported by grants from the National Heart, Lung, and Blood Institute ( RO1HL46716, RO1HL69024, and RO1HL85647 , Dr F. Sellke), a National Institutes of Health (NIH) training grant 5T32-HL094300 (Dr Chu), the Irving Bard Memorial Fellowship (Drs Chu and Robich), NIH training grants 5T32-HL0074 and 5T32-HL007734 (Dr Robich), and NIH training grant 5T32-HL076134 (Dr Lassaletta). ",

year = "2011",

month = sep,

doi = "10.1016/j.surg.2011.07.022",

language = "English (US)",

volume = "150",

pages = "490--496",

journal = "Surgery",

issn = "0039-6060",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - High-fat diet alters prostanoid balance and perfusion in ischemic myocardium of naproxen-treated swine

AU - Chu, Louis M.

AU - Robich, Michael P.

AU - Lassaletta, Antonio D.

AU - Feng, Jun

AU - Xu, Shu Hua

AU - Heinl, Robert

AU - Liu, Yuhong

AU - Sellke, Eric

AU - Sellke, Frank W.

N1 - Funding Information: Supported by grants from the National Heart, Lung, and Blood Institute ( RO1HL46716, RO1HL69024, and RO1HL85647 , Dr F. Sellke), a National Institutes of Health (NIH) training grant 5T32-HL094300 (Dr Chu), the Irving Bard Memorial Fellowship (Drs Chu and Robich), NIH training grants 5T32-HL0074 and 5T32-HL007734 (Dr Robich), and NIH training grant 5T32-HL076134 (Dr Lassaletta).

PY - 2011/9

Y1 - 2011/9

N2 - Background: The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the cardiovascular system remains controversial, especially in patients with cardiovascular comorbidities. We used a swine model of chronic myocardial ischemia to investigate whether hypercholesterolemia alters the cardiovascular effects of the nonselective NSAID naproxen. Methods: Yorkshire swine were fed normal chow (NAP; n = 7) or a high-fat diet (HF-NAP; n = 8). Chronic myocardial ischemia was created in all animals by left circumflex ameroid constrictor placement. All swine were started on oral naproxen (440 mg/day) at the time of ameroid placement. After 7 weeks, myocardial perfusion and microvessel reactivity in the ischemic territory were assessed. Tissue levels of prostanoid metabolites 11-dehydrothromboxane B2 (11-d-TXB2) and 6-keto-prostaglandin F1-α (6-k-PGF1α) were measured. Tissue was analyzed for capillary density and protein expression. Results: Myocardial perfusion was significantly decreased in the HF-NAP group both at rest and during ventricular pacing. Microvessel relaxation responses to sodium nitroprusside and adenosine 5′-diphosphate were similar between groups. Tissue 11-d-TXB2 levels were similar between groups, but tissue 6-k-PGF1α was significantly decreased in the HF-NAP group (P =.001). Expression of thromboxane synthase was significantly higher in the HF-NAP group (P =.02), while prostacyclin synthase expression was significantly decreased in the HF-NAP group (P =.04). Capillary density was higher in the HF-NAP group (P =.005). Proangiogenic vascular endothelial growth factor (VEGF; P =.0002) and Akt (P =.01) were downregulated in the HF-NAP group. Conclusion: A high-fat diet impairs tissue perfusion in ischemic myocardium of naproxen-treated swine by shifting the prostanoid balance to favor production of thromboxane over prostacyclin. Dietary modification may improve myocardial blood flow and alter the safety profile in chronically ischemic cardiac patients taking naproxen.

AB - Background: The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the cardiovascular system remains controversial, especially in patients with cardiovascular comorbidities. We used a swine model of chronic myocardial ischemia to investigate whether hypercholesterolemia alters the cardiovascular effects of the nonselective NSAID naproxen. Methods: Yorkshire swine were fed normal chow (NAP; n = 7) or a high-fat diet (HF-NAP; n = 8). Chronic myocardial ischemia was created in all animals by left circumflex ameroid constrictor placement. All swine were started on oral naproxen (440 mg/day) at the time of ameroid placement. After 7 weeks, myocardial perfusion and microvessel reactivity in the ischemic territory were assessed. Tissue levels of prostanoid metabolites 11-dehydrothromboxane B2 (11-d-TXB2) and 6-keto-prostaglandin F1-α (6-k-PGF1α) were measured. Tissue was analyzed for capillary density and protein expression. Results: Myocardial perfusion was significantly decreased in the HF-NAP group both at rest and during ventricular pacing. Microvessel relaxation responses to sodium nitroprusside and adenosine 5′-diphosphate were similar between groups. Tissue 11-d-TXB2 levels were similar between groups, but tissue 6-k-PGF1α was significantly decreased in the HF-NAP group (P =.001). Expression of thromboxane synthase was significantly higher in the HF-NAP group (P =.02), while prostacyclin synthase expression was significantly decreased in the HF-NAP group (P =.04). Capillary density was higher in the HF-NAP group (P =.005). Proangiogenic vascular endothelial growth factor (VEGF; P =.0002) and Akt (P =.01) were downregulated in the HF-NAP group. Conclusion: A high-fat diet impairs tissue perfusion in ischemic myocardium of naproxen-treated swine by shifting the prostanoid balance to favor production of thromboxane over prostacyclin. Dietary modification may improve myocardial blood flow and alter the safety profile in chronically ischemic cardiac patients taking naproxen.

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U2 - 10.1016/j.surg.2011.07.022

DO - 10.1016/j.surg.2011.07.022

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AN - SCOPUS:80052300804

SN - 0039-6060

VL - 150

SP - 490

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JO - Surgery

JF - Surgery

IS - 3

ER -

High-fat diet alters prostanoid balance and perfusion in ischemic myocardium of naproxen-treated swine

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