unstable angina Coronary microcirculatory vasoconstriction during ischemia in patients with (original) (raw)
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Circulation, 2001
Background —The pathophysiology of microvascular response to a severe coronary stenosis has not been conclusively identified. The aim of this study was to characterize the human vasomotor response to pacing-induced ischemia of both the stenotic arterial segment and the distal microcirculation. Methods and Results —Sixteen patients with stable angina and single-vessel disease were studied. Blood flow velocity and transstenotic pressure gradient were monitored at baseline, after intracoronary adenosine (2 mg), and during ischemia induced by atrial pacing with and without adenosine. At the end of this protocol, the study was repeated after intracoronary phentolamine in 7 patients and after angioplasty in 9. Stenosis resistance was calculated as the ratio between mean pressure gradient and mean flow, and microvascular resistance as the ratio between mean distal pressure and mean flow; values were expressed as percent of baseline. Adenosine decreased ( P <0.05) baseline microvascular ...
Circulation, 2002
Background-Development of left ventricular hypertrophy in aortic stenosis (AS) is accompanied by coronary microcirculatory dysfunction, demonstrated by an impaired coronary vasodilator reserve (CVR). However, evidence for regional abnormalities in myocardial blood flow (MBF) and the potential mechanisms is limited. The aims of this study were to quantitatively demonstrate differences in subendocardial and subepicardial microcirculation and to investigate the relative contribution of myocyte hypertrophy, hemodynamic load, severity of AS, and coronary perfusion to impairment in microcirculatory function. Methods and Results-Twenty patients with isolated moderate to severe AS were studied using echocardiography to assess severity of AS, cardiovascular magnetic resonance to measure left ventricular mass (LVM), and PET to quantify resting and hyperemic (dipyridamole 0.56 mg/kg) MBF and CVR in both the subendocardium and subepicardium. In the patients with most severe AS (nϭ15), the subendocardial to subepicardial MBF ratio decreased from 1.14Ϯ0.17 at rest to 0.92Ϯ0.17 during hyperemia (PϽ0.005), and subendocardial CVR (1.43Ϯ0.33) was lower than subepicardial CVR (1.78Ϯ0.35; Pϭ0.01). Resting total LV blood flow was linearly related to LVM, whereas CVR was not. Increase of total LV blood flow during hyperemia (mean value, 89.6Ϯ59.6%; range, 17% to 233%) was linearly related to aortic valve area. The decrease in CVR was related to severity of AS, increase in hemodynamic load, and reduction in diastolic perfusion time, particularly in the subendocardium. Conclusions-CVR was more severely impaired in the subendocardium in patients with LVH attributable to severe AS.
Circulation. Cardiovascular interventions, 2013
The use of fractional flow reserve in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) is a controversial issue. We undertook a study to assess the vasodilatory capacity of the coronary microcirculation in patients with NSTEMI when compared with a model of preserved microcirculation (stable angina [SA] cohort: culprit and nonculprit vessel) and acute microcirculatory dysfunction (ST-segment-elevation myocardial infarction [STEMI] cohort). We hypothesized that the vasodilatory response of the microcirculation would be preserved in NSTEMI. A total of 140 patients undergoing single vessel percutaneous coronary intervention were included: 50 stable angina, 50 NSTEMI, and 40 STEMI. The index of microvascular resistance (IMR), fractional flow reserve, and coronary flow reserve were measured before stenting in the culprit vessel and in an angiographically normal nonculprit vessel in patients with SA. The resistive reserve ratio, a measure of the vasodilatory capacity o...
Cardiovascular Research
Although myocardial ischaemia usually manifests as a consequence of atherosclerosis-dependent obstructive epicardial coronary artery disease, a significant percentage of patients suffer ischaemic events in the absence of epicardial coronary artery obstruction. Experimental and clinical evidence highlight the abnormalities of the coronary microcirculation as a main cause of myocardial ischaemia in patients with ‘normal or near normal’ coronary arteries on angiography. Coronary microvascular disturbances have been associated with early stages of atherosclerosis even prior to any angiographic evidence of epicardial coronary stenosis, as well as to other cardiac pathologies such as myocardial hypertrophy and heart failure. The main objectives of the manuscript are (i) to provide updated evidence in our current understanding of the pathophysiological consequences of microvascular dysfunction in the heart; (ii) to report on the current knowledge on the relevance of cardiovascular risk fac...
Circulation: Cardiovascular Interventions, 2014
Background— Intravenous adenosine infusion produces coronary and systemic vasodilatation, generally leading to systemic hypotension. However, adenosine-induced hypotension during stable hyperemia is heterogeneous, and its relevance to coronary stenoses assessment with fractional flow reserve (FFR) remains largely unknown. Methods and Results— FFR, coronary flow reserve, and index of microcirculatory resistance were measured in 93 stenosed arteries (79 patients). Clinical and intracoronary measurements were analyzed among tertiles of the percentage degree of adenosine-induced hypotension, defined as follows: %ΔP a =–[100–(hyperemic aortic pressure×100/baseline aortic pressure)]. Overall, %ΔP a was –13.6±12.0%. Body mass index was associated with %ΔP a ( r =0.258; P =0.025) and obesity, an independent predictor of profound adenosine-induced hypotension (tertile 3 of %ΔP a ; odds ratio, 3.95 [95% confidence interval, 1.48–10.54]; P =0.006). %ΔP a was associated with index of microcircu...
Journal of the American College of Cardiology, 2019
Background: Hemodynamic instability with hypotension in acute coronary syndromes leads to profound and irreversible ischemia. While exact mechanisms are unclear, coronary microvascular dysfunction likely plays a major role in these dangerous syndromes. This study examined microvascular function during STEMI in a pig model in states of abnormal coronary blood pressure and flow. The purpose was to characterize microvascular dysfunction in clinical syndromes such as STEMI/NSTEMI, cardiogenic shock, no-reflow, and stress cardiomyopathy. Methods: STEMI was induced in 7 normal pigs by balloon LAD occlusion for 90 minutes. Controlled flow infusion assessed microvascular resistance pre-and post-reperfusion using an occlusive balloon catheter and distal crystalloid infusion via precision pump. Distal coronary pressure (P) generated by the controlled flow (Q) was measured during stepped flow sequencing (0-40 ml/min at 5, 10, 20, 30 and 40 ml/ min). The resulting P-Q relationship yielded absolute dMVR as the derivative function dP/dQ. Results: The P-Q relationship was highly linear across physiologic and pathologically low levels. Profound microvascular instability developed at mean intracoronary pressure 30 mmHg, with rapidly rising resistance above baseline, Microvascular Resistance (pre-vs. post reperfusion STEMI) Ratio 1.27 + 0.21, suggesting partial microvascular collapse remained after reperfusion. Conclusion: Cardiac microvascular instability associated with hypoperfusion is rapid and progressive, and in this study showed a mean 27% resistance increase remaining even after reperfusion. This phenomenon is likely induced by partial hydrodynamic microvascular collapse when intra-coronary pressures decrease to mean 30 mmHg or less. The progressive feedback cycle is self-perpetuating with rising microvascular resistance inducing progressively lower flow, ischemia and worsening hypotension. This cycle may explain serious clinical coronary syndromes such as STEMI/NSTEMI, cardiogenic shock and no-reflow. Real time absolute microvascular resistance is easily and precisely measured using controlled flow infusion methods.
Pharmacology & Therapeutics, 2000
Ischemia generally has been assumed to cause maximal vasodilation of the coronary resistance vessels. However, recent observations have demonstrated that during ischemia, the coronary microvessels can retain some degree of vasodilator reserve and remain responsive to vasoconstrictor stimuli. Traditional understanding of coronary blood flow regulation envisioned an array of resistance vessels that respond homogeneously to local myocardial metabolic needs. Although coronary arterioles (Ͻ 100 m) do respond to myocardial metabolic activity, recent studies have demonstrated that up to 40% of total coronary resistance resides in small arteries 100-400 m in diameter. Vasoconstriction of these small arteries is capable of decreasing blood flow, but they are minimally responsive to the metabolic effects of the resultant flow reduction. The lack of metabolic vasoregulation of the resistance arteries explains, at least in part, the observation that myocardial ischemia does not predictably cause maximal resistance vessel dilation. In addition, vasoconstrictor influences can compete with metabolic vasodilator activity in coronary arterioles. These findings suggest that pharmacologic vasodilators acting at the microvascular level might be therapeutically useful in patients with ischemic heart disease. Unfortunately, when myocardial ischemia results from a flow-limiting coronary stenosis, nonselective pharmacologic vasodilation of the resistance vessels can worsen subendocardial ischemia by decreasing intravascular pressure to produce coronary steal and by worsening of stenosis severity. Selective dilation of small arteries in ischemic regions might have potential for enhancing blood flow. A critical property of an effective agent is that it not interfere with metabolic vasoregulation at the arteriole level, so that dilation of small arteries in adequately perfused regions would be countered by compensatory vasoconstriction of the arterioles to prevent coronary steal.
American Journal of Physiology-Heart and Circulatory Physiology, 2006
A paradoxical microcirculatory constriction has been observed in hearts of patients with ischemia, secondary to coronary stenosis. Here, using the isolated mouse heart (Langendorff), we examined the mechanism of this response, assuming involvement of nitric oxide (NO) and endothelin-1 (ET-1) systems. Perfusion pressure was maintained at 65 mmHg for 70 min ( protocol 1), or it was reduced to 30 mmHg over two intervals, between the 20- and 40-min marks ( protocol 2) or from the 20-min mark onward ( protocol 3). In protocol 1, coronary resistance (CR) remained steady in untreated heart, whereas it progressively increased during treatment with the NO synthesis inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (2.7-fold) or the ETA antagonist BQ-610 (2.8 fold). The ETB antagonist BQ-788 had instead no effect by itself but curtailed vasoconstriction to BQ-610. In protocol 2, hypotension raised CR by 2.2-fold. This response was blunted by reactive oxygen species (ROS) scavengers (mannito...
American Heart Journal, 1983
ABSTRACT This study tested the hypothesis that vasodilation of coronary arterioles distal to a fixed, artificial intraluminal coronary stenosis may result in a local, intramural “steal” of blood from endocardium distal to the stenosis. Seven closed-chest conscious pigs were instrumented for the study by placing an artificial plastic stenosis (7.5 mm long, 82% luminal diameter reduction) into the animal's left anterior descending coronary artery. The distal end of a 70 cm long 1.4 mm inner diameter plastic catheter was embedded inside the stenosis with its end open to the distal end of the stenosis. The catheter was used to record distal coronary artery pressure and to infuse adenosine (200 μg · min−1 × 10 minutes) into the distal coronary bed. Regional myocardial blood flow (microsphere technique) and pressure distal to the stenosis was measured before, during, and 15 to 30 minutes after adenosine infusion. The animal was then killed and the heart was sectioned for determination of microsphere activity in endocardial (ENDO) and epicardial (EPI) layers distal to the stenosis (distal zone) and in ENDO and EPI layers perfused by the unobstructed circumflex coronary artery (circumflex [CX] zone). Under resting conditions both ENDO and EPI blood flows (ml · min−1; mean ± 1 SD) distal to the stenosis (1.15 ± 0.23 and 1.30 ± 2.26, respectively, were reduced in comparison with flow in the CX zone (ENDO: 1.53 ± 0.30, p < .005; and EPI: 1.44 ± 0.26, p < 0.02). Distal mean coronary pressure (mm Hg) declined significantly (p < 0.01) versus control (69.7 ± 17.1) during adenosine infusion (46.1 ± 7.2). At the same time distal zone epicardial blood flow increased significantly (1.30 ± 0.26 ml · min−1 · gm−1 to 1.88 ± 0.50, p < 0.01), whereas endocardial blood flow declined (1.15 ± 0.23 to 0.95 ± 0.21, p < 0.05). After discontinuation of adenosine, distal zone ENDO and EPI flow returned to preinfusion levels. Flows in the CX zone did not change significantly during the study. Calculated distal zone EPI resistance (mm Hg/ml · min−1 · gm−1) declined in each animal in response to adenosine (54.7 ± 17.9 to 25.4 ± 4.9, p < 0.01). Thus we observed (1) persistent vasodilatory reserve in epicardium distal to a severe fixed coronary artery stenosis and (2) redistribution of blood flow away from endocardium distal to the stenosis (i.e., an intramural “steal”) when vasodilation was produced by local administration of adenosine.