Effects of statins on myocardial and coronary artery response to ischemia-reperfusion

Stephen V. Rendig, J. David Symons, Ezra A Amsterdam

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

This study tested the hypotheses that (i) lipophilic statins (atorvastatin and simvastatin) impair ventricular recovery from myocardial ischemia-reperfusion, owing to their greater myocyte permeability, compared with a hydrophilic statin (pravastatin), and (ii) statins enhance endothelium-dependent vasodilation of isolated coronary arteries from the ischemic region. Farm pigs consumed chow supplemented with atorvastatin (2.5 mg·kg-1·d-1; n = 6), pravastatin (10 (n = 3) or 20 (n = 2) mg·kg-1·d-1), simvastatin (5 mg·kg-1·d-1; n = 6), or no statin (control; n = 6) for 3 weeks. Animals were anesthetized and instrumented to measure regional (% segment shortening) and global (dP/dt max) left ventricular (LV) function during coronary artery occlusion (10 min) and reperfusion (30 min). Coronary resistance (i.d. = 119 ± 3 μm) and conductance (i.d. = 487 ± 11 μm) arteries were isolated from the ischemic region to measure receptor-dependent (acetylcholine (ACh)) and -independent (KCl) vasoconstriction, and endothelium-dependent (bradykinin (BK)) and -independent (sodium nitroprusside (SNP)) vasodilation. At 30 min reperfusion, neither percent recovery of regional ventricular function (atorvastatin, 24% ± 15%; pravastatin, 36% ± 13%; simvastatin, 29% ± 13%; control, 36% ± 13%) nor percent recovery of global LV cardiac function differed among groups. However, BK-induced vasorelaxation of coronary conductance vessels was greater (P < 0.05) in statins versus controls, and ACh-induced vasoconstriction was less in simvastatin-treated animals, suggesting the potential for enhanced coronary arterial blood flow to the jeopardized region. In conclusion, our data suggest that ischemia-induced myocardial stunning is similar among pigs treated for 3 weeks with atorvastatin, pravastatin, or simvastatin, even though statin treatment appears to augment endothelium-dependent vasodilation of conductance, but not resistance, vessels subjected to ischemia-reperfusion.

Original languageEnglish (US)
Pages (from-to)1064-1071
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume81
Issue number11
DOIs
StatePublished - Nov 2003

Fingerprint

Simvastatin
Reperfusion
Coronary Vessels
Ischemia
Pravastatin
Vasodilation
Endothelium
Bradykinin
Vasoconstriction
Left Ventricular Function
Swine
Atorvastatin Calcium
Myocardial Stunning
Myocardial Reperfusion
Ventricular Function
Coronary Occlusion
Nitroprusside
Cholinergic Receptors
Muscle Cells
Acetylcholine

Keywords

  • Ischemia
  • Reperfusion
  • Statins
  • Vascocontriction-dilation
  • Ventricular function

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

Cite this

Effects of statins on myocardial and coronary artery response to ischemia-reperfusion. / Rendig, Stephen V.; Symons, J. David; Amsterdam, Ezra A.

In: Canadian Journal of Physiology and Pharmacology, Vol. 81, No. 11, 11.2003, p. 1064-1071.

Research output: Contribution to journalArticle

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abstract = "This study tested the hypotheses that (i) lipophilic statins (atorvastatin and simvastatin) impair ventricular recovery from myocardial ischemia-reperfusion, owing to their greater myocyte permeability, compared with a hydrophilic statin (pravastatin), and (ii) statins enhance endothelium-dependent vasodilation of isolated coronary arteries from the ischemic region. Farm pigs consumed chow supplemented with atorvastatin (2.5 mg·kg-1·d-1; n = 6), pravastatin (10 (n = 3) or 20 (n = 2) mg·kg-1·d-1), simvastatin (5 mg·kg-1·d-1; n = 6), or no statin (control; n = 6) for 3 weeks. Animals were anesthetized and instrumented to measure regional ({\%} segment shortening) and global (dP/dt max) left ventricular (LV) function during coronary artery occlusion (10 min) and reperfusion (30 min). Coronary resistance (i.d. = 119 ± 3 μm) and conductance (i.d. = 487 ± 11 μm) arteries were isolated from the ischemic region to measure receptor-dependent (acetylcholine (ACh)) and -independent (KCl) vasoconstriction, and endothelium-dependent (bradykinin (BK)) and -independent (sodium nitroprusside (SNP)) vasodilation. At 30 min reperfusion, neither percent recovery of regional ventricular function (atorvastatin, 24{\%} ± 15{\%}; pravastatin, 36{\%} ± 13{\%}; simvastatin, 29{\%} ± 13{\%}; control, 36{\%} ± 13{\%}) nor percent recovery of global LV cardiac function differed among groups. However, BK-induced vasorelaxation of coronary conductance vessels was greater (P < 0.05) in statins versus controls, and ACh-induced vasoconstriction was less in simvastatin-treated animals, suggesting the potential for enhanced coronary arterial blood flow to the jeopardized region. In conclusion, our data suggest that ischemia-induced myocardial stunning is similar among pigs treated for 3 weeks with atorvastatin, pravastatin, or simvastatin, even though statin treatment appears to augment endothelium-dependent vasodilation of conductance, but not resistance, vessels subjected to ischemia-reperfusion.",
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AU - Symons, J. David

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N2 - This study tested the hypotheses that (i) lipophilic statins (atorvastatin and simvastatin) impair ventricular recovery from myocardial ischemia-reperfusion, owing to their greater myocyte permeability, compared with a hydrophilic statin (pravastatin), and (ii) statins enhance endothelium-dependent vasodilation of isolated coronary arteries from the ischemic region. Farm pigs consumed chow supplemented with atorvastatin (2.5 mg·kg-1·d-1; n = 6), pravastatin (10 (n = 3) or 20 (n = 2) mg·kg-1·d-1), simvastatin (5 mg·kg-1·d-1; n = 6), or no statin (control; n = 6) for 3 weeks. Animals were anesthetized and instrumented to measure regional (% segment shortening) and global (dP/dt max) left ventricular (LV) function during coronary artery occlusion (10 min) and reperfusion (30 min). Coronary resistance (i.d. = 119 ± 3 μm) and conductance (i.d. = 487 ± 11 μm) arteries were isolated from the ischemic region to measure receptor-dependent (acetylcholine (ACh)) and -independent (KCl) vasoconstriction, and endothelium-dependent (bradykinin (BK)) and -independent (sodium nitroprusside (SNP)) vasodilation. At 30 min reperfusion, neither percent recovery of regional ventricular function (atorvastatin, 24% ± 15%; pravastatin, 36% ± 13%; simvastatin, 29% ± 13%; control, 36% ± 13%) nor percent recovery of global LV cardiac function differed among groups. However, BK-induced vasorelaxation of coronary conductance vessels was greater (P < 0.05) in statins versus controls, and ACh-induced vasoconstriction was less in simvastatin-treated animals, suggesting the potential for enhanced coronary arterial blood flow to the jeopardized region. In conclusion, our data suggest that ischemia-induced myocardial stunning is similar among pigs treated for 3 weeks with atorvastatin, pravastatin, or simvastatin, even though statin treatment appears to augment endothelium-dependent vasodilation of conductance, but not resistance, vessels subjected to ischemia-reperfusion.

AB - This study tested the hypotheses that (i) lipophilic statins (atorvastatin and simvastatin) impair ventricular recovery from myocardial ischemia-reperfusion, owing to their greater myocyte permeability, compared with a hydrophilic statin (pravastatin), and (ii) statins enhance endothelium-dependent vasodilation of isolated coronary arteries from the ischemic region. Farm pigs consumed chow supplemented with atorvastatin (2.5 mg·kg-1·d-1; n = 6), pravastatin (10 (n = 3) or 20 (n = 2) mg·kg-1·d-1), simvastatin (5 mg·kg-1·d-1; n = 6), or no statin (control; n = 6) for 3 weeks. Animals were anesthetized and instrumented to measure regional (% segment shortening) and global (dP/dt max) left ventricular (LV) function during coronary artery occlusion (10 min) and reperfusion (30 min). Coronary resistance (i.d. = 119 ± 3 μm) and conductance (i.d. = 487 ± 11 μm) arteries were isolated from the ischemic region to measure receptor-dependent (acetylcholine (ACh)) and -independent (KCl) vasoconstriction, and endothelium-dependent (bradykinin (BK)) and -independent (sodium nitroprusside (SNP)) vasodilation. At 30 min reperfusion, neither percent recovery of regional ventricular function (atorvastatin, 24% ± 15%; pravastatin, 36% ± 13%; simvastatin, 29% ± 13%; control, 36% ± 13%) nor percent recovery of global LV cardiac function differed among groups. However, BK-induced vasorelaxation of coronary conductance vessels was greater (P < 0.05) in statins versus controls, and ACh-induced vasoconstriction was less in simvastatin-treated animals, suggesting the potential for enhanced coronary arterial blood flow to the jeopardized region. In conclusion, our data suggest that ischemia-induced myocardial stunning is similar among pigs treated for 3 weeks with atorvastatin, pravastatin, or simvastatin, even though statin treatment appears to augment endothelium-dependent vasodilation of conductance, but not resistance, vessels subjected to ischemia-reperfusion.

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