Myocardial kinetics of thallium-201 after dipyridamole infusion in normal canine myocardium and in myocardium distal to a stenosis.

The purpose of the present study was to define myocardial and blood thallium-201 (Tl-201) kinetics after infusion of dipyridamole in normal canine myocardium and in myocardium distal to a coronary artery stenosis. Miniature radiation detector probes were implanted in the left ventricle in 39 open-chest dogs. A balloon constrictor was placed around the proximal left circumflex coronary artery. Electromagnetic flow probes were positioned proximally around both the left circumflex and left anterior descending coronary arteries. In five control dogs (group 1) the balloon occluder was not inflated; in 12 dogs (group 2) a mild stenosis was created such that resting flow was not reduced, yet the hyperemic response after 10 s of total occlusion was partially attenuated; in nine dogs (group 3) a moderate stenosis was created such that resting flow was not reduced, yet the hyperemic response was completely eliminated; and in 13 dogs (group 4) a severe stenosis was created such that resting flow was reduced. After intravenous dipyridamole (0.08 mg/kg . min-1 x 4 min), 1.5 mCi Tl-201 was injected intravenously and probe counts were collected continuously for 4 h. The mean 4-h fractional myocardial Tl-201 clearance for nonstenotic zones was 0.35, 0.27 for group 2 stenotic zones, 0.19 for group 3 stenotic zones, and 0.05 for group 4 stenotic zones (P less than 0.0001). After reaching peak activity, myocardial Tl-201 activity cleared biexponentially with a final decay constant lambda 2 = 0.0017 +/- 0.0001 min-1 (SE) for nonstenotic zones, 0.0011 +/- 0.0001 min-1 for group 2 stenotic zones, and 0.0006 +/- 0.0001 min-1 for group 3 stenotic zones (P less than 0.01). Group 4 stenotic zone Tl-201 clearances were negligible (decay constant essentially zero). Blood Tl-201 activity decayed triexponentially with a final blood lambda 3 = 0.0018 +/- 0.0001 min-1, which was almost identical to the final myocardial lambda 2 decay constant. Thus, the rate of myocardial Tl-201 clearance can distinguish between coronary stenoses of graded hemodynamic severity. These results may be applicable to quantitative techniques for determining myocardial Tl-201 clearance rates on serial clinical images after dipyridamole administration.     

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.     

潘生丁心肌声学造影估价冠脉储备的实验研究

将８条犬左旋支冠脉（ＬＣＸ）临床缩窄，于主动脉根部快速注入声振７６％复方泛影葡胺行心肌声学造影（ＭＣＥ），并结合潘生丁试验，探讨播生丁ＭＣＥ定量指标估价冠脉储备的价值。结果提示：潘生丁试验后ＬＣＸ血流量及后壁峰值呈下降趋势，而前壁峰值则呈上升趋势（Ｐ＞０．０５）；前、后壁潘生丁试验后与试验前峰值比间有显著差异；潘生丁试验后与试验前ＬＣＸ血流量比与后壁峰值比间无显著差异，两者间相关系数为０．６５。结论：ＭＣＥ潘生丁试验后与试验前峰值比能作为一项估价冠脉储备的指标。     

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.     

心肌声学造影估测冠脉血流储备的实验研究

建立13条开胸犬冠脉左旋支临界狭窄模型，静脉注射潘生丁前后，主动脉根部注射声振Renografin-76行心肌声学造影，分析左室乳头肌短轴切面不同区域造影效应，并与放射性微球所测该部位区域性心肌血流量对比。结果显示静注潘生丁后左前降支灌注区心肌血流量及造影时间-强度曲线指标中的曲线下面积、峰值强度、最大上升斜率均明显增加，P＜0．01或p＜0．05；而左旋支灌区心肌血流量及造影分析指标在给潘生丁前后无明显变化，p＞0．05。说明心肌声学造影可定性、定量评价冠脉血流储备，有较理想的临床应用前景。     

多巴芬酊胺超声心动图与心肌缺血

与冠脉造影及铊－２０１心肌ＳＰＥＣＴ显像对照研究疑冠心病患者２３例，评估多巴芬酊胺超声心动图在心肌缺血中的应用价值。结果表明多巴芬酊胺超声心动图检测冠脉狭窄及缺血后存活心肌的敏感度、特异度及符合率分别为７３％，７６％；７２％，８８％及７２％，８３％。评估左前降支供血节段缺血及缺血后存活心肌的能力较左旋支和右冠脉支供血节段强。     

实时心肌造影评价犬腺苷预适应的心肌保护作用

目的 探讨腺苷预适应对犬心肌缺血再灌注后收缩功能及危险区心肌血流量的保护作用。 方法 健康犬13只,随机分为2组:腺苷预适应组(n=7):缺血前静脉滴注腺苷0.3 mg/min,30 ml;对照组(n=6):缺血前静脉滴注生理盐水30 ml作为平衡对照。阻断左冠状动脉前降支,制作心肌缺血再灌注模型(缺血3 h,再灌注1 h),于阻断前基础状态、缺血3 h、再灌注1 h各时间点经股静脉注入造影剂声诺维,分别采集左心室乳头肌水平短轴图像。同步记录左心室压力曲线。 结果 腺苷预适应组再灌注1 h的左心室内压峰值(LVSP)高于对照组(P＜0.05);缺血3 h、再灌注1 h的左心室内压最大上升速率高于对照组(P均＜0.05);心肌缺血再灌注后,坏死区、危险区心肌血流量低于正常区,其中坏死区最低(P均＜0.05),腺苷预适应组危险区心肌血流量较对照组增加(P＜0.05)。 结论 腺苷预适应能够有效改善犬心肌缺血再灌注后收缩功能,增加危险区心肌血流灌注,改善心肌微循环。     

Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1.     

Assessment of flow mismatch with pharmacologic stress test on myocardial contrast echocardiography in a model of critical stenosis: adenosine triphosphate and dipyridamole.

Although adenosine triphosphate (ATP) is a favorable vasodilator because of its short-acting duration, the agent's effectiveness in facilitating the diagnosis of myocardial ischemia with myocardial contrast echocardiography (MCE) is not fully understood. The goal of this study was to examine the efficacy of intravenous ATP administration (0.15 to 0.30 mg/kg/min for 5 minutes) in diagnosing the flow mismatch with MCE. To achieve this, a critical stenosis was produced in the left circumflex artery in 10 anesthetized dogs. The peak intensity ratio of risk area to control area was reduced by ATP from 0.51 +/- 0.19 to 0.31 +/- 0.12 (P <.05). Systolic wall thickening of the risk area did not change significantly (32.8% +/- 9.8% to 27.5% +/- 12.8%). These changes did not differ from those obtained after dipyridamole. We conclude that MCE with intravenous ATP administration is as useful as the dipyridamole method for diagnosing critical coronary stenosis.     

应用冠脉血流显像技术检测猪心外膜和心肌内冠脉血流特征的实验研究

目的：应用冠脉血流显像技术检测猪的冠脉血流，初步探讨心外膜和心肌内冠脉的时相性灌注特点及其在冠脉扩张状态下的变化。方法：5条实验小型猪，在麻醉状态下应用超声冠脉血流显像技术探测不同节段心外膜冠脉和左室心肌内的冠脉血流信号，记录其血流频谱曲线。观察心外膜及心肌内冠脉的时相灌注特点，测定冠脉血流速度，计算右冠脉和前降支的舒张期／收缩期峰值血流速度比值。观察静脉推注潘生丁（0．56mg/kg）后前降支和心肌内冠脉血流信号及其频谱曲线特点的变化。结果：所有动物均可检测较清晰的心外膜和心肌内冠脉血流信号；心外膜冠脉为全心动周期前向灌注，右 冠脉的收缩期血流速度明显高于前降支；心肌内冠脉的时相灌注特点为收缩期出现低速的逆向血流；静 注潘生丁使心外膜与心肌内冠脉的血流均明显增强，但灌注模式未变。结论：彩色多普勒冠脉血流显像技术为研究冠脉血流的时相性灌注特点提供了很好的无创性检测手段。     

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.     

The flow-function relationship in patients with chronic coronary artery disease and reduced regional function: a Doppler transesophageal and bidimensional transthoracic echocardiography study

Background: Infra-low dose dipyridamole allows one to selectively explore myocardial viability. Transesophageal echocardiography Doppler measurement of left anterior descending coronary artery flow at baseline and following dipyridamole is an efficient tool to assess coronary flow response. Aim of this study was to determine the flow-function relationship during coronary vasodilatory stress in patients with coronary artery disease and baseline dysfunction. Methods and results: Twelve patients with resting dyssynergies and 6 controls underwent assessment of regional function and of left anterior descending blood flow velocity. Flow and function were evaluated at rest and following infra-low dose dipyridamole (0.28?mg/Kg over 4?min). Controls showed a normal function at rest and after dipyridamole. Six patients (‘Responders’) with resting dyssynergies showed an improvement in segments of left anterior descending artery territory, whereas the other six ones (‘Non-responders’) showed no functional change. Controls and ‘Responders’ had similar values of resting peak diastolic left anterior descending artery flow velocity both at rest and after dipyridamole, whereas ‘Non-responders’ showed a blunted flow response to dipyridamole. Conclusion: Myocardial segments with a resting dysfunction and a contractile reserve more often exhibit a residual flow response, whereas segments with fixed pattern show a flat flow response during coronary vasodilator stress.     

Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines

We have recently demonstrated the benefits of glucagon-like peptide-1 (GLP-1) in enhancing regional and global myocardial function after reperfusion in the clinical setting of acute myocardial infarction. We hypothesized that GLP-1 facilitates recovery from myocardial stunning after an ischemic event. To investigate this, we administered GLP-1 (1.5 pmol/kg/min) to six dogs undergoing 10-min occlusion of the left circumflex coronary artery, followed by 24-h reperfusion. We compared the responses of coronary blood flow and regional thickening of the posterior wall with a group of eight vehicle-treated dogs undergoing the same occlusion-reperfusion protocol. Although recovery of coronary blood flow was identical, regional wall motion recovery occurred significantly ((*)p < 0.05) earlier (92 +/- 4 versus 57 +/- 5%(*) at 15 min) and was complete in the GLP-1-treated dogs, whereas residual contractile dysfunction persisted in the control group (99 +/- 4 versus 78 +/- 3%(*) at 24 h). This phenomenon was independent of changes in systemic hemodynamics or global systolic function. However, isovolumic left ventricular relaxation improved significantly in GLP-1-treated dogs. GLP-1 caused an insulinotropic effect, but no hypoglycemia. We conclude that GLP-1 enhances recovery from ischemic myocardial stunning after successful reperfusion.     

Myocardial Blood Flow Distribution during Ischemia-Induced Coronary Vasodilation in the Unanesthetized Dog

This study was designed to determine whether coronary vasodilation distal to a flow-limiting coronary artery stenosis could result in redistribution of myocardial blood flow to produce subendocardial underperfusion. Studies were performed in 10 awake dogs chronically prepared with electromagnetic flow-meters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was measured using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. A 5(-s) coronary artery occlusion was followed by reactive hyperemia with excess inflow of arterial blood effecting 375+/-20% repayment of the blood flow debt incurred during occlusion. When, after a 5(-s) occlusion, the occluder was only partially released to hold arterial inflow to the preocclusion level for 20 s before complete release, the delayed reactive hyperemia was augmented (mean blood flow repayment = 610+/-45%, P < 0.01). This augmentation of the reactive hyperemia suggested that ischemia was continuing during the interval of coronary vasodilation when coronary inflow was at the preocclusion level. Measurements of regional myocardial blood flow demonstrated that endocardial flow slightly exceeded epicardial flow during control conditions. When arterial inflow was limited to the preocclusion rate during vasodilation after a 5(-s) total coronary artery occlusion, however, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium. Thus, in the presence of a flow-limiting proximal coronary artery stenosis, ischemia-induced coronary vasodilation resulted in redistribution of myocardial blood flow with production of subendocardial ischemia in the presence of a net volume of arterial inflow which, if properly distributed, would have been adequate to prevent myocardial ischemia.     

Comparative effects of alpha-1 and alpha-2 adrenoceptors in modulation of coronary flow during exercise

During submaximal exercise, an alpha adrenergic vasoconstriction that opposes metabolic dilation exists in the coronary circulation. Fifteen dogs were given i.c. injections of prazosin (0.5 mg) or yohimbine (0.7 mg) to determine the participation of alpha 1 and alpha 2 adrenoceptors in the vasoconstriction during exercise. All dogs were chronically instrumented to measure left circumflex blood flow, heart rate, regional left ventricular function and global left ventricular function. The experimental protocol consisted of a graded exercise regimen during which, at the highest level of exercise an alpha antagonist was given i.c. Exercise significantly increased heart rate, left ventricular pressure, dP/dt, systolic shortening and rate of shortening, and coronary blood flow. After the prazosin injection there was an increase in circumflex blood flow (25 +/- 3%) as well as regional (38 +/- 6%) and global (20 +/- 3%) contractile function. However, there was no change in circumflex blood flow or myocardial function after yohimbine. These data indicate that during exercise the sympathetic constrictor tone in the coronary circulation is mediated primarily by alpha 1 adrenoceptors, with little or no involvement from alpha 2 adrenoceptors.     

Difference in site and time course of coronary dilating effects of trapidil, nitroglycerin and dipyridamole in anesthetized dogs

Effects of trapidil, a non-nitrate type coronary vasodilator, nitroglycerin and dipyridamole on epicardial coronary diameter and total coronary resistance were studied in anesthetized open-chest dogs. The epicardial coronary diameter of the left circumflex coronary artery was measured by sonomicrometry and total coronary resistance was calculated by aortic pressure and coronary blood flow. Intravenous administration of Trapidil, as well as nitroglycerin, produced transient decreases in total coronary resistance followed by sustained dilation of the large coronary artery. Dipyridamole increased coronary blood flow by 2.7-fold, whereas diameter of the large coronary artery decreased along with the reduction of aortic pressure. The first peak of the biphasic increases in coronary blood flow and subsequent dilation of the large coronary artery appeared after an i.v. bolus administration of trapidil or nitroglycerin and remained even after beta adrenergic blockade. Intracoronary administration of either drug produced monophasic increases in coronary blood flow along with subsequent dilation of the large coronary artery. Thus, trapidil, like nitroglycerin, directly dilates the large and small coronary arteries.     

Prostacyclin and regional coronary blood flow in experimental myocardial infarction

Infusion of prostacyclin (PGI₂) has been reported to affect infarct size and myocardial blood flow favourably in various animal models of myocardial ischaemia. Recent data suggest that a similar effect of PGI₂ may occur also in humans with acute myocardial infarction. We addressed the hypothesis that PGI₂ redistributes myocardial blood flow following coronary ligation, and that this effect favours perfusion of myocardium at risk and thereby limits infarct size. Following ligation of a distal branch of the left coronary artery in anaesthetized dogs, PGI₂ (2–4 ng/kg/min) was infused for 72 h. Regional myocardial blood flow was assessed immediately after the coronary ligation and at the end of the drug infusion, by injection of ⁵⁷Co- and ¹¹³Sn-labelled microspheres, respectively. Coronary ligation reduced regional coronary blood flow by 40–70%. During the subsequent 72 h the blood flow increased, being at the end of the period 50–70% of the flow in the non-ischaemic myocardium. PGI₂ did not affect the spontaneous improvement of regional myocardial blood flow, as assessed at the end of the infusion. PGI₂ also failed to affect infarct size, either when expressed in relation to total left ventricular mass, or in relation to area at risk. We conclude that PGI₂, when infused immediately after coronary ligation in dogs in a clinically relevant dose, neither affects regional myocardial blood flow in the ischaemic regions, nor the size of the myocardial infarction.     

Comparison of thallium-201 SPECT redistribution patterns and rubidium-82 PET rest-stress myocardial blood flow imaging

To compare regional thallium-201 SPECT redistribution patterns with rubidium-82 PET, we studied 81 patients with both imaging modalities. Sixty patients had significant coronary artery disease. All patients underwent PET imaging after dipyridamole infusion, while SPECT imaging was performed after exercise stress (38 patients) and dipyridamole (43 patients). Sixty-eight percent of patients with prior infarct had fixed defects on SPECT, compared to 39% with PET. Sixty-one percent of patients with prior infarct had PET perfusion defects which exhibited ‘reflow’ or normal rubidium-82 tracer uptake (p < 0.05 vs. SPECT). Similar results were seen in patients without prior infarct (26% fixed defects on SPECT vs. 12% for PET, p < 0.05). Regional analysis showed that 57% of fixed SPECT defects corresponded to PET defects with reflow or normal rubidium-82 uptake, while 78% of ‘fixed’ PET defects corresponded to fixed SPECT defects. PET reflow and normal rubidium-82 uptake in sites of fixed thallium-201 SPECT perfusion defects suggest that imaging modalities employing separate tracer injections at rest and after stress, such as rubidium-82 PET, may be more specific in the assessment of myocardial viability, especially in patients with prior myocardial infarction.     

Nitroglycerin and Heterogeneity of Myocardial Blood Flow REDUCED SUBENDOCARDIAL BLOOD FLOW AND VENTRICULAR CONTRACTILE FORCE

The effects of both intracoronary and intravenous administration of nitroglycerin on transmural distribution of blood flow in the left ventricle after partial coronary artery occlusion was investigated using two independent methods. In 16 open chest, anesthetized dogs, tubing supplying the cannulated left coronary artery was partially occluded. Strain gauges sutured paralled to superficial and deep fibers of the myocardium separately recorded the contractile force of each layer. With occlusion set so that depression of the deep contractile force was imminent. 12 mug intracoronary nitroglycerin in seven dogs depressed only the deep contractile force without changing systemic hemodynamics. Intravenous administration of 180 mug nitroglycerin in nine dogs resulted in a decrease of deep contractile force and aortic pressure often associated with an increase in superficial contractile force. Distribution of myocardial blood flow during peak coronary flow after intracoronary administration of nitroglycerin or during a decrease in aortic pressure after intravenous nitroglycerin administration was determined by the tissue uptake of an intracoronary bolus of rubidium-(80). This was compared with the uptake of potassium-(42) injected before nitroglycerin. Intravenous or intracoronary administration of nitroglycerin caused a significant reduction in subendocardial blood flow with a decrease in the subendocardial/subepicardial ratio of isotope.These experiments suggest that under conditions of acute partial coronary occlusion, the autoregulatory response results in more fully dilated subendocardial vessels causing them to be less responsive to nitroglycerin. Nitroglycerin may then reduce the vascular resistance in the subepicardial more than the subendocardial vessels, resulting in a "steal" of blood flow from deep to superficial myocardium.     

Cardiac effects of beta-2 adrenoceptor stimulation with intracoronary procaterol in the absence and presence of regional myocardial ischemia in dogs.

To evaluate consequences of cardiac beta-2 adrenoceptor stimulation on coronary hemodynamics and regional myocardial function assessed by sonomicrometry in the normal and regionally ischemic heart, the effects of administration of procaterol, a selective beta-2 adrenoceptor agonist, into the left circumflex coronary artery (LCX) were examined in the absence and presence of a stenosis of the LCX in anesthetized open-chest dogs. The stenosis of the LCX was made sufficient to decrease percent segment shortening in the LCX-perfused region to around 2 to 3%. When coronary stenosis was absent, intracoronary infusion of procaterol (6.7 ng/min for 15 min) produced significant increases in LCX flow and myocardial segment shortening in the infused region without changes in global hemodynamics. During coronary stenosis, on the contrary, intracoronary procaterol at the same dose significantly deteriorated regional myocardial dysfunction without changing LCX flow, global hemodynamics and cardiac lactate metabolism. These changes induced by procaterol were not observed in the dogs treated with a selective beta-2 antagonist, erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylaminob utan-2-ol. These results suggest the presence of functional beta-2 adrenoceptors in the canine heart both with and without myocardial ischemia.