Gradual reduction of coronary perfusion pressure in cats: changes in transmural distribution of blood flow

We evaluated a model for regional myocardial hypoperfusion in cats with an extracorporeal shunt line to the left main coronary artery, and investigated the effects of reduced coronary perfusion pressure on the transmural distribution of left ventricular blood flow measured with radioactive microspheres. Shunt establishment did not alter cardiac function, myocardial tissue blood flow, or its transmural distribution. An artificial shunt stenosis, which clearly reduced coronary perfusion pressure without changing cardiac function, caused reduced endocardial blood flow, slight flow reduction in mid-myocardium, and no flow change in the epicardium. When a severe stenosis was applied, causing increased end-diastolic pressure and reduced shunt flow, endocardial and mid-myocardial flow further decreased whereas epicardial blood flow remained essentially unchanged. These results demonstrate a transmural profile of the coronary autoregulation capacity.     

Does α1-adrenergic blockade influence regional blood flow regulation in hearts with coronary artery occlusion?

Summary. The effects of selective α₁-adrenergic blockade with doxazosin on regional myocardial tissue blood flow was studied in anaesthetized cats with acute coronary artery occlusion. Reflex tachycardia was prevented by selective β₁-adrenergic blockade with atenolol and coronary perfusion pressure was kept constant by partial stenosis of the descending aorta. Administration of atenolol reduced cardiac mechanical work-load by its negative inotropic and chronotropic effects, and reduced myocardial tissue blood flow in normally perfused myocardium. This reduction was most pronounced in the endocardial half-layer of the myocardium adjacent to the ischaemic region. Administration of doxazosin in this situation clearly reduced peak systolic and coronary perfusion pressure. But when coronary perfusion pressure was raised to pre-administration values, measurements of regional blood flow revealed no changes either in ischaemic or non-ischaemic myocardium. Also, there was no sign of redistribution of blood flow between endocardial and epicardial tissue in any area. This study, therefore, indicates that α₁-adrenoceptors play a minor role in the regulation of coronary blood flow in normal myocardium as well as ischaemic myocardium.     

Effects of KB-944, a novel calcium antagonist, in several models of canine myocardial ischemia

The actions of KB-944 ([4-(2-benzothiazolyl)-phenylmethyl]phosphonic acid diethylester) on hemodynamics and regional myocardial blood flow during partial or total coronary artery occlusion were studied in anesthetized dogs. In one series of experiments a severe stenosis, that reduced distal diastolic coronary perfusion pressure to 40 mm Hg, was applied to the left anterior descending coronary artery whereas in another series of experiments the left anterior descending was ligated to produce a total occlusion. Intravenous infusion of KB-944 (100 and 200 micrograms/kg/min) decreased heart rate and left ventricular systolic and aortic blood pressure. Total coronary artery blood flow and regional perfusion of normal myocardium were increased by KB-944 in both models. KB-944 increased regional segment function in normal and ischemic regions and maintained distal coronary artery perfusion pressure, coronary flow and transmural regional myocardial blood flow during partial coronary artery occlusion despite a reduction in aortic pressure. In a model of total coronary artery occlusion, KB-944 had no effect on the indirect indices of collateral function, retrograde flow and retrograde pressure. However, when diastolic aortic pressure was maintained, KB-944 produced transmural increases in myocardial blood flow to normal and collateral dependent zones. Thus, KB-944 maintains ischemic zone blood flow despite decreases in coronary perfusion pressure and increases in tissue flow in the collateral dependent region when aortic pressure is prevented from decreasing.     

Effect of practolol on blood flow distribution in the myocardium during acute regional ischaemia in cats

The β-adrenergic blocking agent practolol was given to 11 cats with acute coronary artery ligation, and regional myocardial tissue blood flow was measured by the distribution of 15 μm labelled microspheres. Practolol reduced heart rate and cardiac contractility, but left ventricular end-diastolic pressure rose in eight animals. In three animals, however, the haemodynamics were essentially unchanged and these are referred to as non-responders. No changes in regional myocardial blood flow were observed after practolol administration, either in ischaemic, border or normal areas of the left ventricle. This indicates less serious imbalance between oxygen demand and delivery in ischaemic tissue. There was no endocardial/epicardial redistribution of tissue flow. Practolol did not appear to improve coronary perfusion, and beneficial clinical effects of practolol are therefore probably related to reduction of myocardial oxygen demands.     

Myocardial Blood Flow Distribution in Concentric Left Ventricular Hypertrophy

Regional myocardial blood flow during both control conditions and ischemia-induced vasodilatation was studied in eight chronically instrumented awake dogs. Seven of these animals had coarctation-banding of the ascending aorta performed at 6 wk of age, and the other dog had congenital subvalvular aortic stenosis. The mean left ventricular weight for the group was 157+/-7.6 g, and the left ventricular body weight ratio was 8.76+/-0.47 g/kg. None of the animals exhibited signs of congestive heart failure.During the control state, the mean left ventricular systolic pressure was 249+/-12 mm Hg and the left ventricular end-diastolic pressure was 11.5+/-0.5 mm Hg. The aortic diastolic pressure was 74+/-6 mm Hg. Mean left circumflex coronary artery blood flow was 71+/-6 cm(3)/min. In the animals with coarctation-banding, 52+/-6% of the flow occurred during systole. In the dog with congenital subvalvular aortic stenosis, 5% of the coronary flow was systolic. Mean transmural blood flow during resting conditions was 0.97+/-0.08 cm(3)/min per g, and the ratio of endocardial to epicardial flow (endo/epi) was 0.88+/-0.07. During reactive hyperemia, the mean transmural blood flow increased to 3.5+/-0.30 cm(3)/min per g; however, the endo/epi decreased to 0.52+/-0.06.THESE STUDIES DOCUMENT A DIFFERENCE IN TRANSMURAL BLOOD FLOW DISTRIBUTION BETWEEN THE NORMAL AND THE HYPERTROPHIED LEFT VENTRICLE: during resting conditions, in the normal ventricle, the highest flow occurs in the endocardial layer, whereas in the hypertrophied ventricle, the highest flow is in the middle layers with the endocardial flow less than the epicardial flow. During ischemia-induced vasodilatation, the abnormal endo/epi becomes accentuated markedly. These data demonstrate that, in situations requiring high flow, the endocardial layer of a heart with marked concentric left ventricular hypertrophy may not be perfused adequately.     

Regional perfusion in hearts with acute coronary artery occlusion and subsequent β2- and α1-adrenergic blockade

Summary. Blockade of cardiac adrenoceptor subtypes, coronary or myocardial, might elicit compensatory interaction from remaining unblocked subtypes. An attempt to explore this interplay was made by studying regional myocardial blood flow alterations associated with β₂-adrenergic blockade followed by β₁-adrenergic blockade in anaesthetized cats with acute coronary occlusion. In order to maintain constant needs for perfusion, atrial pacing was established and the aortic blood pressure was kept constant. In myocardium remote from the ischaemic region, β₂-adrenergic blockade produced higher endocardial blood flow whereas no flow changes were observed close to the ischaemic region. With subsequent β₁-adrenergic blockade, blood flow increased endocardially in non-ischaemic regions, but remained unchanged in epicardial tissue. Control experiments without coronary ligation revealed no increase in left ventricular oxygen consumption during the experiments and support the theory that the observed blood flow increase in the coronary ligation group, following drug interventions, was not caused by increased cardiac work. This study indicates that combined β₂- and α₁-adrenergic blockade alters the balance between receptor subtypes. Unopposed β₁-mediated vasodilation is the most likely candidate to explain why endocardial flow was increased.     

Balance and imbalance of regional myocardial contractile function and blood flow

Summary During normoperfusion, both contractile function and myocardial blood flow are heterogeneously distributed throughout the left ventricle. Midwall segment shortening is greater at the apex than at the base of the left ventricle, and it is greater in the anterior than in the posterior wall. Also, transmural heterogeneity of myocardial deformation exists, with greater segment shortening and wall thickening in inner than in outer myocardial layers. Myocardial blood flow is greater in inner than in outer myocardial layers. Apart from transmural heterogeneities, there are adjacent regions with largely different resting flow in the same heart. While an increase in myocardial contractile function will lead to a metabolically mediated increase in myocardial blood flow, an increase in regional coronary perfusion within or above the autoregulatory range does not, in turn, increase regional myocardial contractile function. During hypoperfusion induced by a proximal coronary stenosis, the reduction in subendocardial blood flow is more pronounced than that in subepicardial blood flow, and contractile function in the inner myocardial layers ceases more rapidly than that in outer myocardial layers. The reduced regional myocardial contractile function is closely matched to the reduced regional myocardial blood flow; however, such coupling between reduced flow and function is lost when ischemia is prolonged for several hours, i.e., function for a given flow is further reduced. Acute embolization of the coronary microcirculation induces a progressive loss of regional myocardial function at unchanged regional myocardial blood flow, i.e., perfusion-contraction mismatch. During reperfusion, regional myocardial contractile function remains depressed for a prolonged period of time, depending on the severity, duration and location of the preceding ischemic epsiode, while regional myocardial blood flow is restored. Eingegangen: 24. Oktober 2000 /Akzeptiert: 22. M?rz 2001     

Quantification of myocardial blood flow and assessment of its transmural distribution with real-time power modulation myocardial contrast echocardiography.

BACKGROUND: The purpose of this study was to examine the ability of real-time myocardial contrast echocardiography (MCE) with power modulation to quantitate myocardial blood flow (MBF) and to assess its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses. METHODS AND RESULTS: MBF was measured in 12 dogs instrumented with a cuff occluder around the left anterior descending coronary artery at rest, during partial coronary stenosis (during infusion of adenosine), and during coronary occlusion. The MCE-derived rate of microbubble velocity, beta, and myocardial blood volume, A, were obtained by curve fitting of videointensity versus time plots, after the transient destruction of microbubbles by high-energy ultrasound. The data were compared with MBF measured with radiolabeled microspheres. Significant correlations were found between radiolabeled microsphere-derived MBF and both beta (r = 0.93) and the product of A x beta (r = 0.91). MCE beta reserve also correlated well with microsphere-derived flow reserve. Comparing endocardial/epicardial MCE ratios and microsphere-derived MBF ratios, significant correlation was also found between endomicropsheres/epimicrospheres MBF ratio and both endo/epi beta (r = 0.90) and endo/epi A x beta (r = 0.88). CONCLUSIONS: Real-time power modulation MCE allows for an accurate quantification of MBF and of its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses.     

Effects of nitroglycerin on transmural myocardial blood flow in the unanesthetized dog.

This study was designed to determin the effect of nitroglycerin upon transmural distribution of myocardial blood flow in the awake dog during normal conditions and in the presence of ischemia-induced coronary vasodilation. Studies were performed in chronically prepared dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was estimated by using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. During control conditions endocardial flow (0.86 plus or minus SEM 0.05 ml/min per g) slightly exceeded epicardial flow (0.72 plus or minus 0.03 ml/min per g, P smaller than 0.05), and this distribution of flow was not significantly altered by nitroglycerin. After a 5-s coronary artery occlusion, reactive hyperemia occurred with excess inflow of arterial blood effecting 360 plus or minus 15% repayment of the blood flow debt incurred during occlusion. When arterial inflow was limited to the preocclusion rate during coronary vasodilation after a 5-s total coronary artery occlusion, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium, and the delayed reactive hyperemia was markedly augmented (mean blood flow debt repayment =775plus or minus 105%, P smaller than 0.01). Tese data suggested that subendocardial underperfusion during the interval of coronary vasodilation in the presence of a flow-limiting proximal coronary artery stenosis caused continuing subendocardial ischemia which resulted in augmentation of the reactive hyperemic response. In this experimental model both the redistribution of myocardial blood flow which occurred during an interval of restricted arterial inflow after a 5-s coronary artery occlusion and augmentation of the subsequent reactive hyperemic response were returned toward normal by nitroglycerin. This effect of nitroglycerin may have resulted, at least in part, from its ability to vasodilate the penetrating arteries which deliver blood from the epicardial surface to the subendocardium.     

Effects of Increasing Heart Rate Induced by Efferent Sympathetic Neuronal Stimulation, Isoproterenol or Cardiac Pacing on Myocardial Function and Oxygen Utilization

The effects of increasing heart rate by six different methods on cardiac /unction were investigated in 17 open-chest anesthetized dogs. Heart rate was increased approximately 30% by (1) right interganglionic nerve stimulation, (2) atrial pacing, (3) ventricular pacing, (4) atriovenfricular sequential pacing, (5) right stellate ganglion stimulntion, and (6) isoproterenoi administration. During heart rate increases induced by atrial pacing left ventricular intramyocardial pressure, coronary Wood flow, oxygen delivery per unit of myocardial oxygen consumption, and myocardial efficiency were unchanged. Ventricular pacing reduced left ventricular cavity and septal intramyocardial pressure, while circumflex coronary flow increased, resulting in reduced oxygen delivery relative to myocardial oxygen consumption. Similarly, atrioventricu-lar sequential pacing increased circumflex coronary artery flow and myocardial oxygen consumption, and decreased septal intramyocardial pressure and oxygen delivery per unit of myocardial oxygen consumption. Right stellate ganglion stimulation and isoproterenol increased left anterior descending and circumflex coronary artery blood flow, intramyocardial pressure, and myocardial oxygen consumption. Estimated myocardial efficiency (left ventricle) was decreased by ventricular pacing and isoproterenol, and was unchanged by atrial pacing and right interganglionic nerve stimulation. Increases in heart rate induced by right interganglionic nerve stimulation did not alter myocardial oxygen consumption, or the index of cardiac efficiency. It is concluded that augmentation of heart rate by either ventricular or atrioventricular pacing impairs myocardial function so that there is a decrease of left ventricular efficiency, and isoproterenol augments chronotropism and myocardial force relative to cardiac external work so there is a reduction in cardiac efficiency. In contrast, atrial pacing or right interganglionic nerve stimulation augments chronotropism such that myocardial oxygen consumption and efficiency are unchanged.     

The effects of glyceryl trinitrate,isosorbide dinitrate and sodium nitroprusside on haemodynamics,coronary blood flow and myocardial oxygen consumption — An experimental study

The influences of glyceryl trinitrate, isosorbide dinitrate and sodium nitroprusside intravenously on haemodynamics, coronary circulation and myocardial oxygen consumption were investigated in closed chest dogs (n=8). In an attempt to simulate heart failure the dogs received blood transfusion (15 ml/kg) in the presence of halothane-induced myocardial depression. All three nitrates reduced the loads for the left ventricle. With isosorbide dinitrate and sodium nitroprusside the preload and pulmonary pressure decreased to a greater extent than with glyceryl trinitrate. The haemodynamic results suggest that sodium nitroprusside is the favourable nitrate in left ventricular failure because it produces a balanced reduction in the ratio of pre- and afterload. Four μg/kg·min sodium nitroprusside induced marked coronary dilatation; glyceryl trinitrate had only a slight coronary vasodilating effect. With isosorbide dinitrate the myocardial blood flow remained well adapted to oxygen demand, the coronary vascular resistance did not change. Sodium nitroprusside produced a significant change of the transmural myocardial blood distribution-expressed as the epi/endocardial blood flow ratio. The ratio was increased by sodium nitroprusside, much more than by glyceryl trinitrate or isosorbide dinitrate.     

Alpha-adrenoceptor subtypes and regional myocardial blood flow distribution during coronary occlusion in dogs

The involvement of postsynaptic alpha-adrenoceptors in the distribution of regional myocardial blood flows (RMBFs, microsphere technique) within the left ventricle has been investigated during intermittent coronary artery occlusion in open-chest anesthetized dogs. Two types of RMBFs distribution were assessed: (1) between endocardial (endo) and epicardial (epi) layers (endo/epi ratio) and (2) between nonischemic (NIZ) and ischemic zones (IZ) (IZ/NIZ ratio). Equipressor does of selective alpha 1-(cirazoline after rauwolscine) and alpha 2-(UK-14,304 after prazosin) adrenoceptor agonists were infused in dogs previously submitted to ganglionic and muscarinic blockade. In a control group, aortic pressure was mechanically raised by aortic stenosis to levels similar to those reached with both alpha-adrenoceptor agonists. Cirazoline and aortic stenosis increased RMBFs in IZ and NIZ but did not alter the calculated coronary resistance in NIZ and did not affect endo/epi and IZ/NIZ ratios. In contrast, UK-14,304 preferentially augmented coronary resistance in NIZ, increased IZ/NIZ ratio (both P less than 0.05) but did not affect endo/epi ratio in IZ and NIZ. Thus, we conclude that if transmural distribution of RMBFs (endo/epi ratio) is not preferentially controlled by any alpha-adrenoceptor subtype, postsynaptic alpha 2-adrenoceptors are of importance during coronary occlusion in promoting a favorable redistribution of RMBFs from NIZ towards IZ by inducing a selective NIZ coronary vasoconstriction (ie a "reverse coronary steal").     

MR first pass imaging: quantitative assessment of transmural perfusion and collateral flow

Recent advances with fast switching gradient coils, and the optimization of magnetic resonance techniques for multi-slice imaging have made it possible to apply models of contrast agent transit for the quantification of myocardial perfusion, and determination of the transmural distribution of blood flow. This article summarizes some of these recent developments and presents examples of quantitative, multi-slice myocardial perfusion imaging studies in patients and animal models. Multi-slice, true first pass imaging, with high temporal resolution, and T1-weighted, arrhythmia insensitive contrast enhancement is used for the quantification of perfusion changes accompanying mild to severe ischemia. The first pass imaging technique and the modeling approach are sufficiently robust for fitting of tissue residue curves corresponding to a wide, physiologically realistic range of myocardial blood flows. In animals this was validated by comparison to blood flow measurements with radiolabeled microspheres as gold standard. It is demonstrated that with the proposed modeling approach one can determine the myocardial perfusion reserve from two consecutive MR first pass measurements under resting and hyperemic conditions. In patients with microvascular dysfunction the MR studies show for the first time that the myocardial perfusion reserve correlates with Doppler flow measurements (linear regression with slope of 1.02±0.09; r=0.80). Since perfusion limitations usually begin in the subendocardium as coronary flow is gradually reduced, first pass imaging with the prerequisitie spatial and temporal resolution allows early detection of a mild coronary stenosis.     

STEMI患者PCI术中注射前列地尔对心肌灌注恢复的影响

目的 探讨在急性ST段抬高型心肌梗死患者经皮冠状动脉介入术中注射前列地尔对患者心功能、心肌灌注、氧化应激和预后的影响.方法 将78例急性S T段抬高型心肌梗死患者按随机数字表法分为两组,各39例.两组均予以经皮冠状动脉介入术和常规支持治疗,观察组在术中冠脉注射前列地尔.比较两组术后梗死相关动脉心肌梗死溶栓试验血流分级和...     

Transmural distribution of metabolites and blood flow in the canine left ventricle following isoproterenol infusions.

The effects of intravenous infusions of isoproterenol (0.1, 1.0 or 2.5 micrograms/kg/min for 1 hr) on the transmural distribution of myocardial high-energy phosphates and glycolytic intermediates were determined in anesthetized, open chested dogs. The transmural distribution of blood flow across the left ventricular wall was determined after serial injections of 15 mu radioactively labeled microspheres. A biopsy of the posterolateral wall was frozen in liquid nitrogen, divided into epicardial, midmyocardial and endocardial thirds, and assayed for metabolites. The remainder of the heart was processed for light and electron microscopy. At the infusion rate of 2.5 micrograms/kg/min, isoproterenol caused nonuniform reductions in ATP, phosphocreatine, total adenine nucleotides and glycogen, which were particularly depleted in the endocardium. Isoproterenol also caused nonuniform increases above baseline in blood flow (epicardial, 492%; midmyocardial, 197%; and endocardial, 131%). The endocardial/epicardial blood flow ratios, however, were reduced. Evidence of cellular damage was demonstrated by the presence of numerous contraction band lesions along with mitochondrial swelling and the appearance of electron-dense deposits. It is concluded that necrogenic infusions of isoproterenol impair myocardial energy production in all myocardial layers despite an overall increase in blood flow. There appears to be a link between the gradients in metabolites and the distribution of blood flow such that the endocardium becomes more vulnerable to injury.     

Long-term follow-up of coronary artery dissection due to blunt chest trauma with spontaneous healing in a young woman

We report a previously healthy 17-year-old woman who experienced coronary artery dissection with an acute transmural anterior myocardial infarction and myocardial contusion following blunt chest trauma in a motorcycle accident. A chest roentgenogram on admission was normal, and an electrocardiogram showed an acute transmural anterior myocardial infarction with complete right-bundle-branch block. A 2D echocardiogram revealed an akinesis of the anterior wall and a hypokinesis of the posterior wall in the left ventricle. Initial coronary angiography demonstrated severe stenosis with delayed antegrade filling in the proximal left anterior descending artery. Technetium-99m pyrophosphate myocardial scintigraphy demonstrated diffuse tracer uptake in the left ventricular wall. Follow-up coronary angiography performed 1 year after the accident showed a minor stenosis without any filling defects. We describe long-term follow-up of the coronary artery dissection following blunt chest trauma with spontaneous healing.     

SonoVue心肌声学造影结合冠状动脉造影早期诊断冠心病的临床研究

目的采用外周静脉注射声学造影剂声诺维,观察心肌灌注及心内膜缘显像,并且与患者的冠状动脉造影结果进行对比研究,评价声诺维对冠心病的早期诊断价值。方法分别在基础和非线性成像条件下,对28例患者经静脉注射声诺维2 ml,并与冠状动脉造影检查结果作对比分析。结果注射造影剂之前心内膜显示欠清的左室心内膜缘得到满意的显影;声诺维能很好显示心肌灌注情况。结论声诺维可以增强心内膜缘的显影,能显示心肌灌注,有助于冠心病的早期诊断。     

Quantification of transmural gradient of blood flow in myocardial ischemia with real-time myocardial contrast echocardiography and dipyridamole stress test

Transmural redistribution of myocardial blood flow (MBF) is the earliest sign of myocardial ischemia. We aimed to evaluate the ability of real-time myocardial contrast echocardiography (MCE) combined with dipyridamole stress to quantify the transmural gradient of MBF during graded coronary stenosis. Real-time MCE was performed in 14 open-chest dogs at seven experimental stages: baseline; hyperemia induced by 6-min infusion of dipyridamole; 50%, 75% and 90% reduction of hyperemic flow after constriction in each stage for 10 min; reperfusion for 10 min; and subtotal occlusion of the left anterior descending coronary artery (LAD) for 90 min. We obtained MCE perfusion parameters from subendocardial (A-endo, beta-endo and A x beta-endo) and subepicardial (A-epi, beta-epi and A x beta-epi) layers of the ventricular septum and calculated their transmural gradients (A-EER, beta-EER and A x beta-EER) and systolic wall thickening (SWT). The sensitivity and specificity of each parameter for predicting 75% reduction of hyperemic flow, which was defined as mild myocardial ischemia, were derived by receiver operating characteristic (ROC) curve analysis. No transmural gradients were found at baseline; during maximal hyperemia and 50% reduction of hyperemic flow. beta-endo, A x beta-endo, beta-EER and A x beta-EER decreased significantly when the hyperemic flow was reduced by 75% or more. In contrast, SWT remained unchanged until the hyperemic flow was reduced by 90%. Among all parameters measured, beta-EER and A x beta-EER had the highest and SWT the lowest sensitivity and specificity in predicting mild myocardial ischemia. In conclusion, real-time MCE combined with dipyridamole stress allows for quantification of the transmural gradient of MBF. beta-EER and A x beta-EER are more sensitive than SWT and other MCE parameters in detecting mild myocardial ischemia.     

Acute graded hypercapnia increases collateral coronary blood flow in a swine model of chronic coronary artery obstruction

OBJECTIVE: To evaluate the effect of acute hypercapnia on regional myocardial blood flow in a swine model of chronic, single-vessel coronary artery obstruction. Permissive hypercapnia is being used frequently in critical care settings. One possible detrimental effect of hypercapnia is the initiation of coronary "steal" in patients with coronary artery disease. The effects of hypercapnia on collateral coronary blood flow in the setting of coronary obstruction have not been defined. DESIGN: Prospective controlled experimental study. SETTING: Institutional animal research facility. SUBJECTS: Eight juvenile swine weighing 25-30 kg. INTERVENTIONS: Collateral coronary circulation was induced in eight piglets by banding the proximal left anterior descending coronary artery for 8-10 wks followed by total ligation. Graded hypercapnia (mean Paco2, 81 torr [10.80 kPa; Paco2 = 81 torr] and 127 torr [16.93 kPa; Paco2 = 127 torr]) was induced by increasing inspiratory carbon dioxide under isoflurane anesthesia (1 minimum alveolar concentration). MEASUREMENTS AND MAIN RESULTS: Animals were attached to instruments to measure pulmonary and systemic hemodynamics, regional myocardial blood flow, and cardiac output. Regional myocardial blood flow was determined using radiolabeled microspheres. Cardiac output, mean arterial pressure, and coronary perfusion pressure were unchanged at both levels of hypercapnia compared with baseline values. Heart rate was increased at Paco2 [HI] (p < .05). Regional blood flow was increased at both levels of hypercapnia in the collateral-dependent and normally perfused myocardium (p < .05; as high as 56% for subendocardium and as high as 106% for subepicardium at Paco2 [HI]). The intercoronary blood flow ratio remained unaltered. The transmural flow ratio was reduced at Paco2 [HI] (P < .05). During hypercapnia, regional lactate extraction remained unaltered, and regional oxygen extraction was unchanged or reduced despite the increase in oxygen consumption. CONCLUSIONS: In this swine model of chronic single-vessel coronary artery obstruction, acute hypercapnia does not induce coronary steal from collateral-dependent myocardium, but it does increase global coronary blood flow.     

Myocardial adenine nucleotide depletion within 1 h of acute coronary artery occlusion.

In anaesthetized open-chest casts with occlusion of the left anterior descending coronary artery (LAD), adenine nucleotides and degradation products were studied in small myocardial tissue samples (10-20 mg) with high-pressure liquid chromatography, and tissue blood flow was measured with radioactive microspheres 5, 10, 20, 40, and 60 min after LAD occlusion. There was a rapid and parallel decrease of myocardial ATP and accumulation of adenosine, inosine, hypoxanthine, and xanthine both in epicardial and endocardial half-layers of the ischaemic myocardium within the first 20 min of coronary occlusion. After 40 and 60 min, myocardial ATP content decreased and degradation products accumulated further in the endocardium but stabilized epicardially. Analysis of covariance showed that the slightly higher blood flow in ischaemic epicardial layers, did not explain the transmural difference in ATP content after 40 and 60 min. Adenosine decreased after 40 min of ischaemia in both wall layers reaching negligible amounts after 60 min. It is concluded that breakdown of energy stores is less severe in epicardial than in endocardial wall layers during the first hour after acute coronary occlusion in the cat heart. This transmural difference cannot be explained entirely by less severe epicardial ischaemia. Therefore, transmural heterogeneity in metabolic function during severe ischaemia may also be important.