Coronary Inflow Research Articles

Supravalvar aortic stenosis: Imaging characteristics and associations on multidetector computed tomography angiography.

To evaluate the imaging features and associations in patients with supravalvar aortic stenosis on multidetector computed tomography (CT) angiography. We retrospectively reviewed all CT angiography studies performed for evaluation of congenital heart diseases at our institution through the period from January 2014 to June 2020. Cases with supravalvar aortic stenosis were identified and classified as syndromic and nonsyndromic based on history, physical examination, and relevant investigations. The type and extent of vascular involvement and associated cardiovascular abnormalities were characterized. Supravalvar aortic stenosis was identified in 26/3926 (0.66%) patients (22 males and 4 females; Age range: 2 months to 20 years). Discrete stenosis was seen in 14/26 (53.8%) patients, while diffuse involvement of the ascending aorta to varying degrees was seen in the remaining 12 (46.2%) patients. About 15/26 (57.7%) patients had pulmonary involvement at some level, namely,infundibular, valvar, supravalvar, or peripheral pulmonic stenosiswhile 15/26 (57.7%) patients had coronary arterial involvement either in the form of stenosis, occlusion, or ectasia. Aortic valvular abnormality including thickening, partial fusion, and adhesion of leaflet edges to the sinutubular junction causing reduced coronary inflow was seen in 15/26 (57.7%) patients. Associated ventricular septal defect, patent ductus arteriosus, and mitral valvular prolapse were seen in four (15.4%), five (19.2%), and two (7.7%) patients respectively. Supravalvar aortic stenosis is a rare abnormality showing associated pulmonary arterial involvement, coronary arterial involvement, aortic valvular abnormalities, and associated congenital cardiac defects in the majority of cases, which may influence surgical outcomes.

Quantification of effects of mean blood pressure and left ventricular mass on noninvasive fast fractional flow reserve.

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFRB using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFRB computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow was computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120, and 130% of the measured values. FFRB increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08, and 0.87 ± 0.07, respectively. Conversely, FFRB decreased with incrementally higher inputs value of LVM: 0.86 ± 0.08, 0.85 ± 0.08, 0.84 ± 0.09, 0.84 ± 0.09, 0.83 ± 0.10, 0.83 ± 0.10, and 0.82 ± 0.10, respectively. Noninvasive FFRB calculated using measured MBP and LVM on a total of 30 vessels was 0.84 ± 0.09 and correlated well with invasive FFR (0.83 ± 0.09) (r = 0.92, P < 0.001). Positive association was observed between FFRB and MBP input values (mmHg) and negative association between FFRB and LVM values (g). Respective slopes were 0.0016 and -0.005, respectively, suggesting potential application of FFRB in a clinical setting. Inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions.NEW & NOTEWORTHY While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFRB) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis.

Effect of protein arginine methyltransferase-1 inhibition on hypoxia-induced vasoconstriction

Hypoxia is defined as a decrease in the oxygen supply to a level below physiological levels which is insufficient to maintain cellular function, in the presence of unrestricted coronary inflow. It is one of the leading causes of global mortality and morbidity, due to its association with the pathology of cancer, cardiovascular disease and stroke. The common feature in these pathologies is the limitation of oxygen availability that participates in the development of these conditions. The pulmonary response to hypoxia, when hypoxia is localized, is hypoxic pulmonary vasoconstriction (HPV). HPV is a physiological and self-regulatory mechanism by which pulmonary capillary blood flow is automatically adjusted to alveolar ventilation for maintaining the optimal balance of ventilation and perfusion. In pathological conditions, HPV occurs as an acute episode during progressive critical illness or as a sustained response with vascular remodeling and pulmonary hypertension. Inspite of the hypoxia-induced shift in the redox status to a more oxidized state, the endothelium-dependent mediators of HPV that cause vasoconstrictor response to hypoxia include nitric oxide (NO), endothelin-1 and angiotensin-II. Indeed, in chronic hypoxia, due to the enhanced reactive oxygen species (ROS) generation, inhibition of endothelial nitric oxide synthase (eNOS) activity and reduced nitric oxide (NO) production there is an imbalance in the vasoconstriction–vasodilation status toward constriction. It is our hypothesis that, in hypoxic stress, a key player in initiating this imbalance is the enzyme, protein arginine methyltransferase-1 (PRMT1) which indirectly affects eNOS activity by increased production of asymmetric dimethylarginine (ADMA), a NOS-inhibitor. Thus, pharmacological inhibition of PRMT1 should restore the cellular and vascular homeostasis in hypoxic conditions.

Rare congenital coronary anomaly - unroofed coronary sinus

In this paper we describe a case of an eight-month-old male infant who was diagnosed with an unroofed coronary sinus (UCS) that unusually presented with desaturation and cyanosis after surgical ventricular sep-tal defect (VSD) closure. The patient was initially diagnosed with congenital heart disease (CHD), perimembranous VSD as-sociated with mild stenosis of pulmonary arteries in early newborn period. Although the patient was regularly monitored by a paediatric cardiologist, and was even hos-pitalized twice due to deterioration of the initially diagnosed disease and the devel-opment of congestive heart failure (CHF) and arrhythmias, the UCS went unnoticed. The disease was unveiled completely after VSD was surgically closed and the patient’s condition deteriorated postoperatively with desaturation and cyanosis in the in-tensive care unit (ICU). On that same day the patient was reoperated on. UCS was closed with a pericardial patch, a persistent left superior vena cava ligated (PLSVC) and the patient successfully recovered. This case is an example that UCS is not only rare but is such an insidious congeni-tal heart disease, often masked with associ-ated heart defects. It should prompt every paediatric cardiologist to perform a careful examination of coronary sinus inflow tract or performance of contrast echocardiogra-phy in every suspicious case.

The effects of N-acetylcysteine on cisplatin-induced cardiotoxicity on isolated rat hearts after short-term global ischemia

The aim of this study was to estimate the protective effect of N-acetyl-l-cysteine (NAC) against cisplatin-induced cardiotoxicity under conditions of ischemic-reperfusion injury.Wistar albino rats were randomly divided into three groups (n=8): control, cisplatin (5mg/kg/w, i.p., 5 weeks) and cisplatin+NAC group (cisplatin – 5mg/kg/w, i.p. and NAC – 500mg/kg/w, i.p., 5 weeks). Isolated hearts were perfused according to the modified Langendorff technique at constant pressure (70cmH2O). Following cardiodynamic parameters were measured: maximum rate of left ventricular pressure development, minimum rate of left ventricular pressure development, left ventricular systolic pressure (SLVP), left ventricular diastolic pressure and heart rate. The ischemic vasodilation episodes were induced by the complete interruption of coronary inflow for 30, 60 and 120s. The samples of the coronary venous effluent (CVE) were continuously collected during the reperfusion period for determination of coronary flow (CF) rate and oxidative stress markers (H2O2, O2−, NO2− and thiobarbituric acid reactive substances – TBARS).Cisplatin reduced CF, heart rate and overflow (total, maximal and duration of overflow) during reperfusion, and increased SLVP (under basal conditions and after global ischemias). Cisplatin increased levels of H2O2 (under basal conditions), O2− and TBARS (under basal conditions and after ischemia), but decreased NO2− levels (during reperfusion) in CVE, and decreased superoxide dismutase and reduced glutathione in serum. NAC attenuated cisplatin-induced changes of cardiodynamic parameters (except CF under basal conditions) and oxidative stress parameters.Those results suggest that NAC, by decreasing oxidative stress, may be useful in cardioprotection during cisplatin therapy.

Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs

Reperfusion is mandatory to salvage ischaemic myocardium from infarction, but also induces additional reperfusion injury and contributes to infarct size (IS). Gentle reperfusion (GR) has been proposed to attenuate reperfusion injury, but this remains contentious. We now investigated whether (i) GR reduces IS and (ii) GR is associated with the activation of reperfusion injury salvage kinases (RISK). Anaesthetized pigs were subjected to 90 min left anterior descending coronary artery hypoperfusion and 120 min reperfusion. GR was induced by slowly increasing coronary inflow back to baseline over 30 min, using an exponential algorithm [F(t) = F(i)+e(-(0.1)(t)((min)-3)).(F(b)-F(i)); F(b), coronary inflow at baseline; F(i), coronary inflow during ischaemia; n = 12]. Pigs subjected to immediate full reperfusion (IFR; n = 13) served as controls. IS was determined by triphenyl tetrazolium chloride staining. The expression level of phosphorylated RISK proteins was determined by western blot analysis in myocardial biopsies taken at baseline, after 80-85 min ischaemia and at 10, 30, and 120 min reperfusion. In additional experiments with IFR (n = 3) and GR (n = 3), the PI3-AKT and MEK1/2-ERK1/2 pathways were pharmacologically blocked (BL). IS was 37 +/- 2% (mean +/- SEM) of the area at risk with IFR and 29 +/- 1% (P < 0.05) with GR. RISK phosphorylation was similar between GR and IFR at baseline and 85 min ischaemia. At 10 min reperfusion, RISK phosphorylation was increased with IFR, but not with GR. At 30 and 120 min reperfusion, RISK phosphorylation was still greater with IFR than GR. RISK blockade did not abolish the IS reduction by GR (BL-IFR: 27 +/- 4% of the area at risk; BL-GR: 42 +/- 5%; P < 0.05). Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.

Impairment of coronary flow reserve in aortic stenosis

Coronary flow reserve (CFR) is markedly reduced in patients with severe aortic valve stenosis (AS), but the exact mechanisms underlying this impairment of CFR in AS remain unclear. Reduced CFR is the key mechanism leading to myocardial ischemia symptoms and adverse outcomes in AS patients. The objective of this study was to develop an explicit mathematical model formulated with a limited number of parameters that describes the effect of AS on left coronary inflow patterns and CFR. We combined the mathematical V(3) (ventricular-valvular-vascular) model with a new lumped-parameter model of coronary inflow. One thousand Monte-Carlo computational simulations with AS graded from mild up to very severe were performed within a wide range of physiological conditions. There was a good agreement between the CFR values computed with this new model and those measured in 24 patients with isolated AS (r = 0.77, P < 10(-4)). A global sensitivity analysis showed that the valve effective orifice area (EOA) was the major physiological determinant of CFR (total sensitivity index = 0.87). CFR was markedly reduced when AS became severe, i.e., when EOA was <1.0 cm(2), and was generally exhausted when the EOA was <0.5-0.6 cm(2). The reduction of CFR that is associated with AS can be explained by the concomitance of 1) reduced myocardial supply as a result of decreased coronary perfusion pressure, and 2) increased myocardial metabolic demand as a result of increased left ventricular workload.

Regulation of Coronary Blood Flow During Exercise

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac outpu...

Reduced myocardial calcium responsiveness after coronary microembolization

We have recently reported that the myocardial dysfunction observed several hours after coronary microembolization (ME) is related to an oxidative modification of tropomyosin (Canton et al., Eur Heart J 27:875–881, 2006). We have now investigated the impact of ME on calcium responsiveness at a time when myocardial function is reduced, i.e. 6 h after ME. In 10 anesthetized pigs the LAD was cannulated and perfused by an extracorporeal perfusion system. Regional myocardial function was assessed by sonomicrometry. Five pigs received saline as placebo and served as controls. In 5 pigs, ME was induced by injection of microspheres (Ø42 μ; 3000/ml/min coronary inflow) through the perfusion system. Calcium responsiveness was determined by measuring the increase in myocardial work (pressure vs. wall excursion) in response to a graded intracoronary infusion of CaCl2 at baseline and at 6 h after ME or placebo, respectively. Graded CaCl2 increased myocardial work at baseline stepwise. At any CaCl2 myocardial work was attenuated 6 h after ME, whereas it was not different from baseline after 6 h in controls. The absolute concentration of Ca in coronary blood to achieve the half maximal increase in myocardial work remained unchanged in controls (baseline: 189±18 μg/ml, mean±SEM; 6 h: 212±22 μg/ml) and after ME (baseline: 179±8 μg/ml; 6 h: 175±17 μg/ml).

Dependence of Intramyocardial Pressure and Coronary Flow on Ventricular Loading and Contractility: A Model Study

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

Cross-Talk Between Cardiac Muscle and Coronary Vasculature

The cardiac muscle and the coronary vasculature are in close proximity to each other, and a two-way interaction, called cross-talk, exists. Here we focus on the mechanical aspects of cross-talk including the role of the extracellular matrix. Cardiac muscle affects the coronary vasculature. In diastole, the effect of the cardiac muscle on the coronary vasculature depends on the (changes in) muscle length but appears to be small. In systole, coronary artery inflow is impeded, or even reversed, and venous outflow is augmented. These systolic effects are explained by two mechanisms. The waterfall model and the intramyocardial pump model are based on an intramyocardial pressure, assumed to be proportional to ventricular pressure. They explain the global effects of contraction on coronary flow and the effects of contraction in the layers of the heart wall. The varying elastance model, the muscle shortening and thickening model, and the vascular deformation model are based on direct contact between muscles and vessels. They predict global effects as well as differences on flow in layers and flow heterogeneity due to contraction. The relative contributions of these two mechanisms depend on the wall layer (epi- or endocardial) and type of contraction (isovolumic or shortening). Intramyocardial pressure results from (local) muscle contraction and to what extent the interstitial cavity contracts isovolumically. This explains why small arterioles and venules do not collapse in systole. Coronary vasculature affects the cardiac muscle. In diastole, at physiological ventricular volumes, an increase in coronary perfusion pressure increases ventricular stiffness, but the effect is small. In systole, there are two mechanisms by which coronary perfusion affects cardiac contractility. Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca2+ transient, which is followed by an increase in Ca2+ sensitivity and higher muscle contractility (Gregg effect). Thickening of the shortening cardiac muscle takes place at the expense of the vascular volume, which causes build-up of intracellular pressure. The intracellular pressure counteracts the tension generated by the contractile apparatus, leading to lower net force. Therefore, cardiac muscle contraction is augmented when vascular emptying is facilitated. During autoregulation, the microvasculature is protected against volume changes, and the Gregg effect is negligible. However, the effect is present in the right ventricle, as well as in pathological conditions with ineffective autoregulation. The beneficial effect of vascular emptying may be reduced in the presence of a stenosis. Thus cardiac contraction affects vascular diameters thereby reducing coronary inflow and enhancing venous outflow. Emptying of the vasculature, however, enhances muscle contraction. The extracellular matrix exerts its effect mainly on cardiac properties rather than on the cross-talk between cardiac muscle and coronary circulation.

Ischemic preconditioning increases the bioavailability of cardiac enkephalins

Growing evidence suggests that cardiac enkephalins and their receptors are involved in ischemic preconditioning (IPC). Because there is no evidence for vesicular storage of small bioactive enkephalins in the heart, studies were designed to test the hypothesis that ischemia depletes cardiac enkephalins and that IPC preserves the same enkephalins by accelerating their processing from the larger proenkephalin precursor (PEP) pool. The precursors and two bioactive representatives, Met-enkephalin (ME) and Met-enkephalin-Arg-Phe (MEAP), were separated by size-exclusion chromatography and quantified by radioimmunoassay. Isolated perfused rat hearts were prepared and exposed to global ischemia. After 30 min of global ischemia and 40 min of reflow, the PEP pool was reduced (from 17.99 +/- 1.52 to 14.20 +/- 2.38 pmol/g wet wt), MEAP increased by 53%, and ME declined by 68%. The sum of the two smaller peptides was unchanged (9.78 +/- 0.83 vs. 9.33 +/- 2.81). Thus the total enkephalin peptide content was not altered (27.77 +/- 1.69 vs. 24.10 +/- 4.75). Peptide distribution after ischemia and reflow was also unaltered by pretreatment with peptidase inhibitors. However, when the hearts were preconditioned, the PEP pool remained significantly lower and both of the bioactive peptides, MEAP and ME, were elevated (+49% and +86%, respectively). The decline in the PEP pool was prevented by peptidase inhibition and the rise in MEAP was exaggerated. In separate protocols, synthetic enkephalins (ME, MEAP, and Leu-enkephalin) were added to the coronary inflow before 30 min of global ischemia and throughout the subsequent reflow. The added enkephalins (10(-8) M) had no inotropic effect on baseline function but completely prevented the mechanical dysfunction observed in untreated controls during reflow. Thus IPC appears to increase available bioactive enkephalins (MEAP + ME) within the heart by enhancing synthesis of precursors and their subsequent processing from the PEP pool.

Mathematical modeling of coronary inflow in presence of aortic stenosis

Aortic stenosis (AS) is the most common heart valve disease. AS causes an obstruction to blood flow from the left ventricle (LV) to the aorta, resulting in a compensatory concentric hypertrophy of ...

Nitric oxide and efficiency of the right heart

See article by Setty et al. (pages 431–436) in this issue . Several differences between right and left heart are known: the effect of cardiac contraction on coronary arterial inflow, autoregulation, and oxygen extraction. Setty et al. [1] show in their study the relationships between function and oxygen consumption of the right heart under control and ischemic conditions and the role of nitric oxide (NO). It turns out that these relationships also differ between left and right heart. Coronary flow depends on perfusion pressure and cardiac oxygen consumption [2]. NO decreases vascular smooth muscle tone and thus modulates flow. NO also promotes vascular growth and affects cardiac function in terms of metabolism, contractility, rhythmicity, and growth [3]. Early studies on ischemia and the role of NO mainly emphasized the vasodilatory effect on the coronary vasculature and thus a protective role of NO. At higher concentrations, NO has a cGMP-independent negative inotropic effect [4]. NO synthase inhibition impairs the efficiency of oxidative metabolism and cardiac function, while during moderate ischemia, NO synthase appears not to be involved in cardiac metabolism … *Tel.: +31 20 4448111; fax: +31 20 4448255. Email address: n.westerhof{at}vumc.nl

Coronary Microembolization: the Role of TNF- α in Contractile Dysfunction

Coronary microembolization is a frequent complication of atherosclerotic plaque rupture in acute coronary syndromes and during coronary interventions. Experimental coronary microembolization results in progressive contractile dysfunction associated with a local inflammation. We studied the causal role of tumor necrosis factor-alpha (TNF- α) in the progressive contractile dysfunction resulting from coronary microembolization. Anesthetized dogs were subjected to either coronary microembolization with infusion of 3.000 microspheres (42 μ m diameter) per ml coronary inflow into the left circumflex coronary artery (n=9), or to intracoronary infusion of recombinant human TNF- α without microembolization (n=4), or to treatment with anti-murine TNF- α sheep antibodies prior to microembolization (n=4). Posterior systolic wall thickening (PWT; sonomicrometry) decreased from 21.1±5.3% (s.d.) at baseline to 5.5±2.2% (P<0.05) at 8 h after microembolization. Infarct size (1.8±1.9%; TTC and histology) and the amount of apoptosis (<0.1%; TUNEL and DNA-laddering) were small. TNF- α at the protein level (WEHI cytolytic assay) was increased and localized to leukocytes (immunostaining), which were increased in number (quantitative histology). In situ hybridization for TNF- α mRNA identified viable cardiomyocytes surrounding the microinfarcts as the major source of TNF- α. Supporting the role of TNF- α, infusion of TNF- α without microembolization decreased PWT from 27.3±6.9% at baseline to 10.1±4.9% after 8 h (P<0.05); in contrast, in the presence of TNF- α antibodies, microembolization no longer reduced PWT (19.3±7.0% at baseline v 16.9±5.0% at 8 h). In conclusion, TNF- α is the mediator responsible for the profound contractile dysfunction following coronary microembolization.

MECHANICAL CHARACTERISTICS OF CORONARY CIRCULATION

The phase opposition of velocity waveforms between coronary arteries (predominantly diastolic) and veins (systolic) is the most prominent characteristic of coronary hemodynamics. The phase opposition indicates the importance of intramyocardial capacitance vessels, as a determinant of phasic coronary arterial and venous flows. To investigate the functional characteristics of the intramyocardial capacitance vessels and its physiological significance, we analyzed the change in venous flow following changes in coronary arterial inflow. It was shown that during diastole the intramyocardial capacitance vessels have two functional components, unstressed volume and ordinary capacitance. Unstressed volume is defined as the volume of blood in a vessel at zero transmural pressure, and it was ~5% of the volume of the myocardium. The systolic coronary venous outflow showed a significant, positive correlation with the total displaceable blood volume stored in the intramyocardial unstressed volume and ordinary capacitance. When the unstressed volume was saturated, the coronary inflow was decreased significantly, compared with that for the unsaturated condition. Thus, the increase in intramyocardial blood volume decreases the coronary arterial inflow, whereas it enhances coronary venous outflow. The latter is an interesting analogy to the Starling's law of the heart.

Isoproterenol enhances myofilament Ca(2+) sensitivity during hypothermia in isolated guinea pig beating hearts.

Isoproterenol is often required to treat acute left ventricular dysfunction during separation from cardiopulmonary bypass for cardiac surgery. We hypothesized that heart rate and intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis may be important factors when isoproterenol improves the cardiac function during hypothermia. Accordingly, we investigated the effect of isoproterenol on the cardiac functional variables, [Ca(2+)]i, and myofilament Ca(2+) sensitivity under spontaneous beating during hypothermia. Intact guinea pig hearts were perfused with a modified Krebs-Ringer solution (baseline) and Krebs-Ringer solution containing isoproterenol (1 nM) at 37 degrees C, 32 degrees C, and 27 degrees C while all cardiac variables and [Ca(2+)]i were recorded. Isoproterenol increased developed left ventricular pressure (LVP), maximum rate of increase in LVP, and coronary inflow at 27 degrees C, and it also increased heart rate and maximum rate of decrease in LVP at each temperature (P < 0.05). Isoproterenol produced a leftward shift of the curve of developed LVP as a function of available [Ca(2+)]i at 32 degrees C and 27 degrees C (P < 0.05), without changing available [Ca(2+)]i. Isoproterenol improves the cardiac function, especially systolic ventricular function, by enhancement of myofilament Ca(2+) sensitivity under spontaneous beating during hypothermia in intact guinea pig hearts. Enhancement of myofilament Ca(2+) sensitivity is involved in the improvement of cardiac function by isoproterenol under spontaneous beating during hypothermia.

Perfusion-contraction mismatch with coronary microvascular obstruction: role of inflammation.

A close relationship exists between regional myocardial blood flow (RMBF) and function during acute coronary inflow restriction (perfusion-contraction matching). However, the relationship of flow and function during coronary microvascular obstruction is unknown. In 12 anesthetized dogs, the left circumflex coronary artery was perfused from an extracorporeal circuit. After control measurements, 3,000 microspheres (42 micrometer diameter) per milliliter per minute inflow were injected to cause a microembolism (ME, n = 6). With unchanged systemic hemodynamics and RMBF, posterior systolic wall thickening (PWT) decreased from 19.8 +/- 1.9% SD at control to 13.3 +/- 4.0, 10.3 +/- 3.8, and 6.9 +/- 4.7% (P < 0.05 vs. control) at 1, 4, and 8 h, respectively. For comparison, inflow was progressively reduced to match PWT to that of the ME group at 1, 4, and 8 h (stenosis, STE, n = 6). RMBF in the STE group was reduced in proportion to PWT. Infarct size was not different among groups (6.5 +/- 4.5 vs. 3.4 +/- 3.2%). However, the number of leukocytes infiltrating the area at risk was significantly greater in the ME group than in the STE group. Coronary microembolization results in perfusion-contraction mismatch and is associated with an inflammatory response.

Effects of cardiac contraction and increased coronary sinus pressure on the coronary arterial pressure-flow relationship.

Increased coronary sinus (CS) pressure and cardiac contraction impair coronary inflow independently. However, it has not been determined how the coronary pressure-flow relationship is strongly affected by changes in CS pressure in the beating heart compared to the non-beating heart. The purpose of this study was to evaluate the combined mechanical effects of cardiac contraction and increased CS pressure. Using isolated, perfused canine hearts, coronary perfusion pressure in the left anterior descending coronary artery (LAD) was gradually reduced in beating and non-beating conditions. Measurements were obtained with and without elevation of CS pressure to determine the mean LAD pressure-flow relationships. At normal and elevated CS pressures, the corresponding zero-flow pressures were not significantly different between the beating and non-beating hearts. A rightward shift of the mean coronary perfusion pressure-coronary flow curve for the beating heart compared to the non-beating heart was observed when CS pressure was not elevated. In contrast, the slopes for both beating and non-beating hearts were similar if the CS pressure was increased. There was a smaller increase in the mean intramyocardial pressure (IMP) at elevated CS pressures in the beating heart as compared to the non-beating heart. Moreover, the increase in diastolic IMP with increased CS pressures in the beating heart was significantly less than that in the non-beating heart. These results indicate that cardiac contraction attenuates the inhibitory effects of increased CS pressure on coronary inflow.

Systolic coronary flow impediment in the dog: role of ventricular pressure and contractility

The present study was planned to investigate the effect of left ventricular pressure and inotropic state on coronary arterial inflow in systole in the anaesthetized dog. A wide range of left ventricular systolic pressures, including the physiological range, were studied. Experiments were done under conditions of maximal vasodilatation and low perfusion pressure in order to avoid vascular autoregulative interference and to keep the microvascular pressure within the normal range. In five anaesthetized dogs, perfused with extracorporeal circulation system, ventricular volume was changed from 20 to 50 ml in steps of 10 ml by filling an intraventricular latex balloon, and the related changes in left ventricular pressure and coronary flow were measured. The volume was then extended to 70 ml to obtain an overstretch which induced a transient decrease in cardiac contractility. During the period of low cardiac contractility the volume was brought back to 20 ml in steps of 10 ml. Systolic ventricular pressure changed with volume but was lower during the period of low contractility. For systolic pressures below 100 mmHg there was no significant relationship between pressure and coronary systolic flow, but the relationship shifted to higher flows during low contractility. For systolic pressures above 100 mmHg systolic coronary flow decreased significantly when systolic pressure increased. In this case the slopes of the relationships were not significantly different before and after the reduction in contractility. These findings suggest that for systolic pressures less than 100 mmHg (i.e. below the physiological range) the shielding effect of the contracting ventricle prevents the ventricular pressure from being transmitted in the myocardial wall. When systolic pressure exceeds 100 mmHg the shielding effect is overcome and the amplitude of the systolic flow reduction varies with ventricular pressure.