Background
Search strategy
Impact of smoking on coronary microvasculature
Impact of smoking on coronary microvasculature and stable CMD
Smoking pattern impact on the coronary microvascular function
Mechanistic studies on the effects of smoking on coronary microvasculature in human subjects
Mechanistic ex vivo and in vitro evidence on the effects of nicotine on coronary microvasculature
Impact of smoking on post-ischemic and PCI-induced coronary microvascular injury
Clinical studies on the impact of smoking on coronary microvasculature injury by reperfused myocardial infarction
Ex vivo and in vitro effects of smoking on post ischemic and PCI-induced microvascular injury
Impact of alcohol on coronary microvasculature
Impact of alcohol on coronary microvasculature and stable CMD
Clinical impact of alcohol on the coronary microvascular function
Mechanistic studies on the effects of alcohol on coronary microvasculature in human subjects
Mechanistic ex vivo and in vitro evidence on the effects of alcohol on coronary microvasculature
Impact of alcohol on post-ischemic and PCI-induced coronary microvascular injury
Clinical studies on the impact of alcohol on coronary microvasculature injury by reperfused myocardial infarction
Ex vivo and in vitro effects of alcohol on post ischemic and PCI-induced microvascular injury
Opioids and coronary microvascular function
Clinical effect of opioids on coronary microvasculature and CMD
Impact of opioids on coronary microvasculature and stable CMD
Mechanistic ex vivo and in vitro evidence on the effects of opioid on coronary microvasculature
Impact of opioid on post-ischemic and PCI-induced coronary microvascular injury
Clinical studies on the impact of opioid on coronary microvasculature injury by reperfused myocardial infarction
Ex vivo and in vitro effects of opioid on post ischemic and PCI-induced microvascular injury
Patient or animal model | Study population | Substance | Administration duration/dose | Clinical test/experiment | Observed effect on coronary microcirculation | References |
---|---|---|---|---|---|---|
Young healthy smokers | 30 | Cigarette Smoking | Short-term chronic | Positron emission tomography measuring myocardial perfusion during rest, cold stress and dipyridamole-induced hyperemia | Impaired myocardial microcirculation function and regulation at cold stress (endothelial-dependent) | [184] |
Male healthy twins | 360 | Cigarette Smoking | Chronic smokers | Positron emission tomography measuring myocardial perfusion at rest and adenosine vasodilation | Lowered CFR in smokers, even after adjusting for oxidative stress and inflammatory markers | [185] |
Inflammation markers: IL-6, CRP | ||||||
Oxidative stress markers: hydroperoxides, GSH,/GSSG ratio | ||||||
Healthy young male smokers | 30 | Cigarette Smoking | Short-term chronic | Positron emission tomography measuring Myocardial blood flow (MBF) at rest, adenosine and cold stress | Reduced ratio of cold MBF to rest MBF (endothelium-dependent) | [186] |
Healthy smokers | 19 | Cigarette Smoking | Chronic smokers | Positron emission tomography measuring coronary flow reserve (CFR), before and after vitamin C administration | Vitamin C restored CFR and the responsiveness of coronary microvessels | [187] |
Angina patients, female, no CAD | 3568 | Cigarette Smoking | Chronic smokers | Doppler echocardiography measuring coronary flow velocity reserve (CFVR) at rest and high dose dipyridamole | Current smoking was identified as a predictor of impaired CFVR | [188] |
Vasospastic angina pectoris (VSA) patients | 22 | Cigarette Smoking | Chronic smokers | Doppler echocardiography measuring coronary flow reserve (CFR), at rest and adenosine administration | Lowers CFR in smokers | [189] |
CAD patients | 97 | Cigarette Smoking | Chronic smokers | Coronary angiography measuring CFR, index of microcirculatory resistance (IMR), and fractional flow reserve (FFR); at rest and adenosine-induced hyperemia | Higher IMR in current smokers, no difference in CFR or FFR | [190] |
Healthy young volunteers | 20 | Cigarette smoking | Chronic and acute effect (chronic smokers with 4 h abstinence, smoking 2 cigarettes) | Doppler echocardiography measuring coronary flow velocity (CFV), and coronary vascular resistance index (CVRI) | No difference in CFR and CVRI at baseline, lower CFR and higher CVRI after smoking 2 cigarettes | [191] |
Healthy young volunteers | 20 | Cigarette smoking | Acute (2 cigarette) | Doppler echocardiography measuring coronary flow reserve (CFR) | Similar reduction in CFR after light and regular cigarette smoking | [192] |
Healthy young smokers | 62 | Cigarette smoking | Chronic and acute effect of light cigarette smoking vs. regular cigarette smoking | Doppler echocardiography measuring coronary flow velocity reserve (CFVR) | Both chronic and acute effects of regular and light cigarettes were similar, reducing the CFVR | [193] |
Healthy smokers | 21 | Cigarette smoking | Acute, cigarettes with either > 1 mg, or < 1 mg nicotine content | Doppler echocardiography measuring coronary flow reserve (CFR) | Reduced CFR only in group smoking > 1 mg content cigarettes | [194] |
Healthy smokers | 51 | Cigarette smoking | Chronic | Measuring plasma and urine biomarkers of inflammation ( IL-6, IL-8, ILβ1 and TNFα), endothelial injury (Intracellular adhesion molecule 1, metalloproteinase-9) and oxidative stress (myeloperoxidase, 8-isoprostane) | Biomarkers of inflammation, oxidative stress, immunity and tissue injury were increased in smokers | [195] |
Human coronary arterioles (HCAs) | - | Cigarette Smoking | Chronic smokers | Dissected human coronary arterioles obtained from cardiac surgery; reactivity and responsiveness of microcirculation was tested by video microscopy | Smoking impaired Na+/K+ ATPase mediated vasodilation | [196] |
PCI patients | 2765 | Cigarette Smoking | Chronic current or past smokers | Health related quality of life(HRQOL) and disease specific health status analyzed by questionnaires | Better cardiac health related outcomes in non-smokers and past smokers, compared to current smokers | [119] |
Alcoholic patients expired for advanced liver disease, with no CAD symptoms | 18 | EtOH | Chronic (alcoholic) | Histology of endomyocardial biopsies | Endothelial cell degeneration, small lumen size, thickened micro-vessel walls with edema, perivascular fibrosis, vascular, subendothelial humps, and vascular wall inflammation | [129] |
Rat model | 21 animals in each test group | EtOH | Chronic, 36% ethanol containing diet (4 weeks) | Histology | Thickened walls of micro-vessels and smaller lumen size, increased endothelial proliferation | [121] |
Rabbit model | 10 animals per group | EtOH | Chronic ( diet containing 20% ethanol) 3 weeks | Histology and ultra-structural analysis of the myocardium and cardiac capillaries | Increased numerical density of the micro-vessels | [120] |
Alcoholic patients | 40 | EtOH | Chronic (alcoholic patients) | Histopathology analysis on cardiac biopsies obtained | Increased capillary density with enhanced endothelial proliferation | [122] |
C57BL/6 J mice | 7 animals per group | EtOH | Chronic (diet containing 36% ethanol) 12 weeks | Histology | Remodeling of the microcirculation, capillaries with widened peri-capillary distances | [125] |
Rats preconditioned before myocardial infarction induction | 8 animals per group | EtOH | Chronic (preconditioned with low-dose ethanol (0.5 g/kg/day), high-dose ethanol (5 g/kg/day) of alcohol 4 weeks before MI induction | Immunohistochemistry | High dose: endostatin increased, no change in VEGF | [126] |
Low dose: increased VEGF, lowered endostatin | ||||||
Cultured small-vessel murine endothelial cells 4–10 (SVEC4-10) | - | EtOH | Acute, 100 mg/dl | In vitro angiogenesis assay, Endothelial cell tube formation assay | Impaired angiogenesis and reduction in VEGF receptors | [127] |
Yorkshire swine | 14 | EtOH | Chronic 7 weeks after MI induction, 90 ml ethanol daily, | Dissected micro-vessels /vasodilator response and histopathology analysis | Increased angiogenesis, improved microvascular reactivity, endothelial function and myocardial perfusion in the ischemic regions of the myocardium | [155] |
Yorkshire swine | 16 | EtOH | Chronic, 90 ml ethanol daily, 7 weeks | Dissected micro-vessels /vasodilator response and histopathology analysis | Increased capillary density, increased VEGF, no change in microvessel reactivity and myocardial perfusion | [156] |
Coronary artery vascular smooth muscle cells | EtOH | Acute, 10–20 mM | protein and mRNA analysis | Increased VEGF | [166] | |
Human umbilical vein endothelial cells (HUVECs) | EtOH | Acute, 24 h, 1–100 mM | Matrigel network formation assay, proliferation and migration assay, protein and mRNA analysis | Activation of CBF-1/RBP-Jk mediated angiogenesis | [23] | |
Human coronary artery endothelial cells (HCAECs) | - | EtOH | Acute, 24 h, 1–50 mM | Matrigel network formation assay, protein and mRNA analysis | Activation of Flk-1/Notch mediated angiogenesis | [24] |
Rat model | 26 | EtOH | Chronic, 3–24 month age, 12% in drinking water | mRNA extraction from left ventricles of the heart, qRT-PCR | Higher expression of p53 | [23] |
Patients with chest pain, positive ETT, normal angiography | 250 | Opium | Chronic (addicted patients) | Coronary angiography | Opium addicted patients are more likely to develop CMD | [24] |
Patients with CAD, scheduled to undergo coronary artery bypass grafting surgery | 35 | Opioid-based anesthetic (fentanyl) | Acute anesthetic dose of fentanyl up to 5 mg kg-1, 30 min) | Vascular occlusion testing (VOT) and near-infrared spectroscopy | Impaired coronary microvascular reactivity | [156] |
Cultured cells: mouse endothelial cells and cardiac myocytes | - | Morphine | 1–100 ng/ml | Biomolecular tests for analysis of VEGF expression (qPCR, ELISA) | Reduced VEGF expression by cardiomyocytes and endothelial cells | [166] |