The effect of elevated arterial free fatty acid concentrations on hemodynamics and myocardial metabolism and blood flow during ischemia

Summary In the present investigation the effect of elevated arterial free fatty acid (FFA) concentrations on regional myocardial blood flow (MBF), myocardial metabolism and hemodynamics during ischemia was studied in anesthetized dogs.Ischemia was induced by stenosis of the left interventricular coronary artery. Mean poststenotic coronary artery pressure was kept constant during ischemia. FFA concentrations were elevated by intravenous injection of heparin (group I), intralipid (group II) or both substances (group III).After elevation of FFA concentrations by heparin alone or together with intralipid, heart rate gradually increased, while aortic pressure tended to decrease.Slight elevation of arterial FFA levels (up to 0.30 mM, group I, and up to 0.53 mM, group II) had no significant effect on total MBF and uptake of glucose, FFA, and oxygen or release of lactate in the ischemic myocardium. However, elevating arterial FFA levels up to 0.81 mM (Group III), significantly decreased total MBF (6%), endo/epicardial blood flow ratio (13%), and oxygen uptake (34%) in the ischemic myocardium and resulted in release of lactate from this area. The release of potassium, inorganic phosphate and H⁺ as well as plasma CO₂ concentration were not influenced. Neither was the uptake of glucose and FFA.These findings suggest that elevated arterial FFA concentrations can decrease MBF and augment lactate production in the ischemic myocardium.With 2 figures and 4 tablesThe investigations were (partly) supported by the Foundation for Medical Research FUNGO, which is subsidized by the Netherlands Organization for the Advancement of Pure Research (ZWO).     

Myocardial morphology and blood flow distribution in chronic volume-overload hypertrophy in dogs

Summary In this study we investigated myocardial structural alterations and regional myocardial blood flow in chronic volume-overload induced left ventricular hypertrophy in the dog. Moderate hypertrophy (28%) was produced by inserting a shunt between the left subclavian artery and the left atrial appendage in 7 dogs (LVH), while a sham operation was performed on 5 control dogs (C). At a paced heart rate of 100 beats/min there were no differences in blood-flow distribution to the subendocardium (ENDO) mid-myocardium (MYO) or subepicardium (EPI) or in ENDO/EPI ratios between the two groups of dogs. Following adenosine-induced coronary vasodilatation (1 mg/kg/min), there was a relative shift in blood flow away from the ENDO in the LVH dogs so that the ENDO/EPI ratio was reduced. Analysis of the microvascular bed and myocyte cross-sectional area in the same three regions of interest revealed a significant reduction in capillary density in the ENDO region of the hypertrophied hearts when compared to controls (LVH=2463±10, C=2773±75 caps/mm²) and a corresponding increase in myocardial cell cross-sectional area (LVH=262±10, C=233±36 m²). The reduction in capillary density in LVH may be explained on the basis of increased muscle growth without appropriate capillary proliferation indicating an inadequate neovascular response to this form of overload. The results also indicate that blood-flow distribution abnormalities may not be detected at resting flow with moderate LVH produced by volume overload.Work done during tenure as a Fellow of the Southeastern Pennsylvania Heart AssociationWork done during tenure as an established investigator of the American Heart AssociationSupported by USPHS NIH Grants No HL 19425 and HL 07198     

Assessment of regional myocardial blood flow with myocardial contrast echocardiography: an experimental study

OBJECTIVES: The aim of this study was to verify the accuracy of using myocardial contrast echocardiography (MCE), to quantify regional myocardial blood flow (MBF), and to evaluate myocardial viability in comparison to that measured by radiolabeled microsphere and pathologic examination. METHODS: Epicardial MCE was obtained in five myocardial ischemic dogs with constant microbubble intravenous infusion. After the video intensity (VI, y) versus pulsing interval plots derived from each myocardial pixel were fitted to an exponential function: y = A(1 - e(-beta t)), the MBF was calculated as the product of A (microvascular cross-sectional area or myocardial blood volume) and beta (mean myocardial microbubble velocity). The MBF was also obtained by radiolabeled microsphere method. RESULTS: The MBF derived by radiolabeled microsphere method in the normal, ischemic, and infarcted region was 1.5 +/- 0.3, 0.7 +/- 0.3, and 0.3 +/- 0.2 ml/min per gram, respectively; P < 0.01. The product of A and beta in those regions was 52.5 +/- 15.1, 24.4 +/- 3.9, and 3.7 +/- 3.8, respectively; P < 0.01. The normalized product of A and beta correlated well with normalized MBF (r = 0.81, P = 0.001). CONCLUSION: Our initial study demonstrated that MCE has an ability to assess MBF in ischemic myocardium in the experimental model. It may provide a potential capability to detect viable myocardium noninvasively after total persistent coronary occlusion in the clinical setting.     

Cardiac tamponade in dogs with normal coronary arteries. I. Effect of changing intravascular volume on hemodynamics and myocardial blood flow

Summary Intravascular volume expansion has been shown to improve cardiac output in experimental cardiac tamponade. To determine the limitations of intravascular volume manipulation, acute tamponade was created in 20 anesthetized, spontaneously breathing dogs. The intrapericardial volume causing tamponade was determined for each animal, and kept constant. Hemodynamics were recorded with and without tamponade at multiple levels of intravascular volume. During cardiac tamponade, intravascular volume expansion increased cardiac output only in animals which were initially volume-depleted. Volume expansion of normovolemic or hypervolemic animals caused minimal changes in cardiac output, but increased atrial and aortic pressures. Intravascular volume depletion of the normovolemic animal caused a significant decline in cardiac output, in contrast to the trend towards an increased output following phlebotomy of the volume-expanded animals. In general, the benefit of intravascular volume expansion during cardiac tamponade could only be demonstrated when atrial pressures were below 12 mm Hg.Dr. Cohen is the recipient of a Research Career Development award from the National Heart, Lung and Blood Institute, HL-00281.     

Assessment of myocardial blood flow and volume using myocardial contrast echocardiography

The development of new microbubble agents and ultrasound imaging modalities now allows the assessment of myocardial perfusion with echocardiography. Microbubbles also can be administered intravenously as constant infusions, which allows their concentration in blood to reach steady state. If the relation between microbubble concentration and video intensity is within the linear range, then myocardial video intensity will reflect the concentration of microbubbles in that region, which at steady state is the myocardial blood volume. The ability to destroy microbubbles and measure their replenishment into the ultrasound beam provides an opportunity to evaluate microbubble (or red blood cell) velocity. The product of myocardial blood volume and red blood cell velocity represents myocardial blood flow.     

Felodipine in severe chronic congestive heart failure: Acute effects on central hemodynamics and regional blood flow distribution

Summary In order to assess the effect of felodipine, a new calcium antagonist with vascular selectivity, on regional blood flow distribution at rest in chronic congestive heart failure, ten patients were studied during an acute test. Right heart catheterization allowed the evaluation of hemodynamic parameters; renal blood flow was calculated using paraamino-hippuric acid clearance; hepatic blood flow measurement was based on indocyanine green clearance; and limb blood flow was assessed with venous occlusion plethysmography. Blood samples were collected for the analysis of plasma catecholamines, renin, and aldosterone. All parameters were recorded in duplicate under basal conditions and after felodipine infusion.The infusion of felodipine induced a significant increase in cardiac index, stroke work index, and limb blood flow. Systemic and pulmonary arterial blood pressure, pulmonary wedge pressure, and systemic resistance underwent a significant decrease. The heart rate, pulmonary resistance, renal blood flow, and hepatic blood flow were not changed.In conclusion, felodipine was of benefit in congestive heart failure at rest in an acute test, acting through a marked decrease in vascular resistance and a consequent improvement in cardiac output and limb blood flow. No changes in renal and hepatic blood flow were observed.Part of these data have been presented at the Second Cardiovascular Pharmacotherapy International Symposium, San Francisco, CA, 1987.     

Preservation of myocardial blood flow by calcium antagonists does not prevent attenuation of regional myocardial function after repetitive brief periods of myocardial ischaemia in the rat heart

The aim of this study was to assess the effect of two differentcalcium channel blockers on myocardial blood flow and functionin a rat model of myocardial ‘stunning’ by repeatedshort episodes of ischaemia (‘repetitive ischaemia’).In an open chest rat model, the left anterior descending coronaryartery was ligatedfor 10 mm followed by 15 min reperfusion.In total, five periods of ischaemia and reperfusion were performed.Myocardial blood flow was assessed by the hydrogen clearancetechnique and systolic thickening fraction by pulsed Doppler.After five episodes of ischaemia, myocardial blood flow andmyocardial thickening in the ischaemic area were reduced by60±8% and 52±7% (n=9), respectively, as comparedto baseline. Continuous intravenous infusion of the calciumchannel blockers nifedipine (n=6) and gallopamil (n=6), started20 min prior to onset of ischaemia, attenuated the ischaemia-induceddecrease of myocardial perfusion. Nifedipine was the most effectivewith only 5±2% reduction in blood flow after five ischaemicepisodes, whereas reduction of myocardial blood flow was 30±4%in the presence of gallopamil. However, neither nifedipine norgallopamil were able to prevent regional ventricular dysfunctioninduced by repetitive ischaemia. Despite the preservation ofmyocardial blood flow following repetitive ischaemia, calciumchannel blockers do not prevent ischaemia-induced reductionof myocardial function in the ischaemic area.     

硝酸甘油对狗的心表冠状动脉和心肌微循环血流的影响

目的：探讨硝酸甘油(NTG)对狗心表冠状动脉和心肌微血管血流量的影响。方法：对10只雄性杂种狗静脉注射NTG后,应用心肌对比超声心动图测量心肌微血管血流量,动脉血流仪测量冠状动脉前降支血流量,超声心动图测量心脏腔径和容积。结果：NTG对心表冠状动脉和心肌微血管的血流量均无明显影响,注射NTG前后,前降支血流量为(13．91±2．91)ml/min对(14．59±4,63m)1/min；A·β值为：45．57±14．27对80．13±36．63,P均＞0．05；NTG对心率、血压、平均动脉压、中心静脉压和冠状动脉血管阻力也无明显影响。但可明显减少心脏腔径和心腔容积,尤其右心腔径和容积减少更明显；与舒张末期容积比较,NTG对心脏收缩末期容积影响更大。结论：NTG对狗的心表大冠状动脉和心肌微血管的血流量无影响,其抗心绞痛的作用可能是通过减少心脏容积和心室壁张力,减少心肌耗氧量而实现的。     

Measurement of heterogeneous myocardial blood flow

Inert gas measurements of myocardial blood flow have been compared to simultaneous radioactive microsphere flow measurements. Average flow per unit weight agreed within 20% in 20 of 24 comparisons. With the inert gas technique flows up to 580 ml/min/100 g could be measured. Semilogarithmically plotted desaturation curves were distinctively curvilinear. It is concluded that the shape of the washout curve is a function of the underlying flow pattern.     

应用实时心肌超声造影定量评价心功能对急性心肌梗死犬心肌血流量的影响

目的:探讨心功能对心肌梗死犬心肌血流灌注的影响。方法:18只健康杂种犬于前降支分出的第1对角支远端约1cm处结扎3h,应用心肌超声造影(MCE)定量分析左室前壁中间段和下壁中间段心肌血流量(MBF)。结果:17只犬成功建立急性心肌梗死模型。根据结扎3h后左室整体射血分数(EF)分为2组:A组(EF≥50%)7只,B组(EF<50%)10只。B组左室前壁中间段和下壁中间段MBF均低于A组,但2组之间差异无统计学意义;与结扎前相比,2组左室前壁中间段MBF均明显降低,差异有统计学意义(P<0.05),A组左室下壁中间段MBF略升高,B组则降低,但均差异无统计学意义。结论:心功能对MBF有一定的影响,可能会低估冠状动脉血流储备和高估狭窄程度,在以MCE诊断冠心病时应注意心功能对MBF的影响。     

Effects of oral pretreatment with metoprolol on left ventricular wall motion,infarct size,hemodynamics, and regional myocardial blood flow in anesthetized dogs during thrombotic coronary artery occlusion and reperfusion

Summary Objectives. To study the effects of oral pretreatment with metoprolol over 3 days on hemodynamics, left ventricular function, regional myocardial blood flow, and infarct size in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery treated with thrombolysis.Methods. Ten dogs received 200 mg metoprolol (Selozok) orally and 8 dogs received placebo for 3 days twice daily and 1 hour before the experiment. Under general anesthesia, thrombotic occlusion was provoked by the copper-coil technique. Intracardiac pressures and their derivatives, cardiac output (thermodilution method), regional coronary blood flow (microspheres), global and regional left ventricular function (ventriculography), and infarct size (triphenyltetrazolium staining) were measured. Measurements were performed during control, after 60 minutes of occlusion, and after 30 and 90 minutes of reperfusion. Thrombolysis was performed in all dogs 60 minutes after occlusion by intravenous infusion of 10 µg/kg/min of rt-PA for 30 minutes.Results. During control cardiac output was lower, total peripheral resistance higher, and Tau and the left ventricular isovolumic relaxation time greater in the metoprolol group. During occlusion and after reperfusion, there were no significant hemodynamic differences between both groups. Blood flow to the area at risk and circumflex territory during occlusion were, respectively, 12.8±5.80 ml/100 g/min versus 9.65±8.35 ml/100 g/min (p>0.05) and 42.58±7.86 ml/100 g/min versus 61.52±20.43 ml/100 g/min (p=0.01) in the metoprolol- and placebo-treated dogs. The ratios of flow area at risk/circumflex territories in the epicardial, midmyocardial, and endocardial layers were, respectively, 0.44±0.20, 0.19±0.09, and 0.20±0.13 in the metoprolol- versus 0.24±0.16, 0.08±0.06, and 0.06±0.07 (p0.04) in the placebo-treated dogs. The ratio of flow endocardium/epicardium was higher (p0.02) in the active treatment group during the control period, both in the area at risk and circumflex territory; this was also the case in the circumflex territory at the end of the experiment (p=0.003). Thirty minutes after occlusion, blood flow to the three layers of the area at risk rose to 2–3 times control values in both groups; a significant increase above control values also occurred in the circumflex territory. After 90 minutes reperfusion, blood flow to both territories was similar in both groups but was comparable to the control; however, in necrotic tissue of the subendocardial layer of both groups, flow fell below control values (p<0.05). End-systolic volume rose from 21.2±7.4 ml to 36.1±11.5 ml (p<0.05), end-diastolic volume remained constant (46.0±13.8 vs. 47.9±12.1 ml; p>0.05), and ejection fraction fell from 53.9±8.3% to 25.8±10.2% (p<0.05) at the end of the experiment in the metoprolol group. Respective figures for the placebo group were 19.4±7.9 versus 27.9±10.9 (p<0.05), 38.5±13.0 versus 42.1±11.0 (p>0.05), and 50.6±5.7 versus 35.5±11.7 (p<0.05). Fractional shortening of the chords analyzed was similar in both groups during the control period; it fell significantly at the end of the experiment in three chords of the metoprolol group and in five chords of the placebo group. The apical chord in the placebo, but not in the metoprolol, dogs was dyskinetic: fractional shortening was –0.86±9.7 versus 7.5±13.5% (p>0.05). The area at risk was 41.6±10.6 cm² in metoprolol- and 40.5±7.2 cm² in placebo-treated dogs (p>0.05); the infarct size, expressed as a percentage of the area at risk, was 29.0±22.5% and 45.3±23.6% (p=0.02), respectively.Conclusions. Oral pretreatment with metoprolol limited infarct size and improved regional left ventricular function, probably due to its negative chronotropic and inotropic effects, and also due to an enhancement of collateral flow from the circumflex territory to the area at risk.     

New collateral flow increasing early after coronary occlusion prevented myocardial necrosis in dogs

Summary Increases in regional myocardial blood flow (Qm) developing soon after myocardial infarction may minimize myocardial necrosis. To test this hypothesis, Qm in the area surrounding an acutely occluded coronary artery was determined successively over 4 weeks in 11 dogs. Non-radioactive colored microspheres were injected into the left atrium 5s (Qm at this time is referred to as Q1), 3h (Q2), 12h (Q3), and 4 weeks (Q4) after occlusion of the coronary artery. After termination of the experiment, the heart was removed, and Qm and three indices of myocardial necrosis i.e., myocardial creatine kinase activity (CK), infarct size determined by triphenyl tetrazolium chloride stain (TTC), and myocardial fibrosis visualized by Azan-Mallory stain, were determined. Each Qm was expressed as a percentage of normal: Qm (% of normal) = [Q/Qc] ischemic area/[Q/Qc]non-ischemic area × 100, where Qc indicates Qm determined before coronary occlusion. In the ischemic area of the left ventricle, Q1, Q2, Q3, and Q4 were 25 ± 3%, 30 ± 3%, 31 ± 3%, and 42 ± 3% of normal, respectively, in the inner layer, and 31 ± 3%, 52 ± 4%, 52 ± 4%, and 77 ± 6% of normal, respectively, in the outer layer. During the 4-week period, the increase of Qm in the outer layer was greater than that in the inner layer. The inner layer showed a small increase of flow from Q3 to Q4 (9 ± 2%), but in the outer layer there were greater flow increases from Q1 to Q2 (21 ± 3%) and from Q3 to Q4 (24 ± 6%). No consistent flow change from Q2 to Q3 was seen in the inner, middle, or outer layers. Q1 showed good correlation with the three indices of myocardial necrosis, indicating that abundant pre-existing collaterals are important in minimizing myocardial necrosis. The Qm increase within 3h after occlusion (Q2 – Q1) also showed a good correlation with the three indices while that after 12h (Q4 – Q3) showed a variable relationship with these indices. Myocardial necrosis was mild provided that Q2 – Q1 was high. This study demonstrated that there is a considerable flow increase until 3 h after coronary occlusion and that this flow increase may contribute to the reduction of myocardial necrosis.     

Effects of high doses of insulin on regional blood flows during acute left ventricular failure in dogs

This study describes the effects of high doses of insulin onsystemic haemodynamics and regional blood flows during acuteischaemic heart failure in dogs. Left ventricular (LV) dysfunctionwas induced by embolization of the left main coronary artery,and was evidenced by a significant increase in LV end-diastolicpressure and decrease in LVdP/dt_max and cardiac output. Measurementsof femoral, renal, mesenteric and carotid blood flows showeda redistribution of cardiac output during failure. Femoral bloodflow decreased to a greater extent than cardiac output, butcarotid blood flow decreased in proportion to cardiac output,while mesenteric and renal blood flows were moderately reducedin relation to the decrease in cardiac output. Administrationof 300 IU of fast-acting insulin significantly improved theperformance of the failing left ventricle. Cardiac output wasraised to levels observed before failure. The greatest increasesin peripheral flow occurred in the femoral and carotid vascularbeds, while the least occurred in the mesenteric and renal vascularbeds. These observations indicate that insulin at high doselevels significantly improves peripheral circulation by positiveinotropic and vasodilatating effects. There was a tendency tofavour femoral and carotid vascular flows, but not at the expenseof renal and visceral flows. Beta receptor blockade blockedneither the systemic nor regional haemodynamic effects of insulin.Heart failuer, insulin, regional blood flow.     

高渗盐水对心力衰竭犬心脏功能和肾脏血流量的影响

目的探讨高渗盐水对心力衰竭犬心脏结构功能、血流动力学及肾脏血流量的作用。方法用快速心室起搏法建立心衰犬模型,分为假手术组、对照组、盐水组、速尿组、盐水+速尿组,分别在起搏前、起搏6周、盐水治疗2周后观测下列指标:超声心动检查,测量左室舒张末径（LVEDD）,左室收缩末径（LVESD）,左室射血分数（LVEF）、心排出量（CO）、肾脏血流量（RBF）;漂浮导管测量右房压（RAP）、平均肺动脉压（MPAP）、肺毛细血管楔嵌压（PCWP）、平均动脉压（MAP）、左室舒张末压（LVEDP）。结果单纯模型组与假手术组比较,血流动力学变化明显,RAP、PCWP、LVEDP升高,MAP降低,超声观测LVESD、LVEDD增大,LVEF、CO、RBF显著下降（P<0.05或P<0.01）;高渗盐水+速尿组,LVEF、CO、RBF、MAP明显增加,LVEDD、RAP、LVEDP、PCWP降低明显;高渗盐水组RBF较对照组有显著差异（P<0.05或P<0.01）;速尿组各指标与对照组比较均无变化。结论高渗盐水配合速尿能够增加心衰犬肾脏血流量,改善其降低的肾灌注,并改善部分心脏结构和功能指标和血流动力学状况。     

Flow support catheter for prolonged maintenance of coronary blood flow

A newly designed flow support catheter with a supporting wire mesh cage which can be expanded into a tubular configuration and then readily reduced was evaluated in mongrel dogs. Regional myocardial blood flow (RMBF) was measured using the radioactive microsphere technique in the area of both balloon-denuded instrumented and control non-instrumented coronary arteries following placement of either a fixed-wire or a higher profile rapid exchange flow support catheter. At 5, 20, and 180 min following delivery and expansion of either device, RMBF was not significantly different in left ventricular subepicardium and subendocardium perfused by the instrumented vs. the control coronary arteries. Angiography demonstrated widely patent instrumented arteries in 15/18 dogs; in no dog was side branch occlusion observed. Significant cage thrombus deposition was seen angiographically in 3 animals causing temporary total coronary occlusion in 1. Following reduction and removal of the flow support catheter, vessel patency was present in all dogs. The flow support catheter is an effective endovascular stenting device capable of providing structural arterial support, while simultaneously maintaining distal coronary blood flow. It is envisioned that the primary application of this catheter will be to enable primary salvage of vessels acutely injured during coronary angioplasty, by “tacking up” intimal flaps for an extended period. It may also provide a bridge to emergency surgical revascularization.     

Effect of hepatic collateral hemodynamics on gastric mucosal blood flow in patients with liver cirrhosis

The dependence of the gastric mucosal change in liver cirrhosis on the extrahepatic collaterals is still unknown. Therefore we studied the influence of these collateral hemodynamics on gastric mucosal blood flow and gastric mucosal lesions. The subjects were 23 cirrhotic patients and were divided into two groups by the findings of percutaneous transhepatic portography. The first group consisted of 14 cases whose extrahepatic collaterals were via esophageal varices (group I). The second group included 9 cases having collaterals other than esophageal varices (group II). Multiple red spots were observed in 13 of 14 cases in group I, and two of nine cases in group II. Gastric mucosal blood flow was 2.0±0.9 volts (mean±sd) in group I, 4.0±1.2 in group II. A statistically significant difference was observed between groups I and II. Gastric mucosal blood flow was not significantly correlated with portal venous pressure in group I. It is concluded that, in liver cirrhosis, gastric mucosal blood flow is changeable according to the types of the extrahepatic collaterals.     

Studies on the regulation of myocardial blood flow in man II. Effects of acute arterial hypoxia

To determine whether adjustment of myocardial blood flow (MBF), myocardial oxygen consumption (MVO₂) and myocardial substrate uptake (MSU) to acute arterial hypoxia is influenced by training effects on the heart, 7 trained and 7 untrained healthy individuals were investigated. MBF (argon method), MVO₂ and MSU of glucose, lactate and free fatty acids were measured at rest during normoxia and two different stages of acute arterial hypoxia: a) 12.82 vol% O₂; b) 8.74 vol% O₂. Measurements were carried out during hemodynamic and respiratory steady state conditions. Myocardial flow and metabolism of athletes were significantly (p<0.01) lower compared to untrained subjects. In the trained cohort, MBF increased from 65 ± 19 to 73 ± 16 (a) and 98 ± 23 (b) ml/min·100 g. MVO₂ remained at normoxic control level of 8.00 ± 2.27 ml/min·100g. In the untrained group, MBF increased from 77 ± 15 to 84 ± 20 (a) and 108 ± 18 (b) ml/min · 100g. Again, there was no significant deviation in MVO₂ from the normoxic level of 10.11 ± 1.90 ml/min·100g. Decrease in arterial oxygen content was overcompensated by an increase in coronary conductance resulting in a significantly improved efficiency of myocardial perfusion during severe hypoxia. MSU of glucose, lactate and free fatty acids as well as calculated ATP production did not change significantly during hypoxia. It is concluded that training effects on the heart do not influence regulation of MBF, MVO₂ and MSU during moderate or severe acute arterial hypoxia. Reaction of coronary smooth muscle tone to a decrease in oxygen partial pressure is independent from training effects. However, both acute arterial hypoxia and physical training exert synergetic effects on the heart by reducing myocardial oxygen consumption per heart beat. Thus, it is assumed that adaptive properties of myocardial blood flow and metaboüsm to severe hypoxia are more pronounced in trained than in untrained individuals.     

Chronic instrumentation and its lack of effect on the hemodynamics and regional myocardial blood flow of conscious dogs

The effects of chronic instrumentation on regional myocardial performance and regional myocardial blood flow were studied in 8 mongrel dogs. Regional segment lengths were measured by an ultrasonic dimension gauge technique at two areas of the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX). Regional myocardial blood flow was measured by a tracer microsphere technique. These measurements were repeated while the animals were conscious on the 4th, 11th, 21st and 28th days after instrumentation. On the 4th day, the heart rate was rather high and regional shortening at both the LAD and LCX areas remained suppressed. After the 11th day, hemodynamic variables such as heart rate, left ventricular pressure and regional wall motion were fairly constant. Regional myocardial blood flow and its distribution were also constant throughout the experimental period. Fibrosis of the epicardium invariably induced by surgical procedures did not affect the distribution of regional blood flow as compared with that of the interventricular septum. Thus, a stable hemodynamic state was recorded after the 11th day following surgical manipulation and the implantation of sensors and catheters did not affect the level of regional myocardial blood flow or its distribution at rest. Such long term reproducible measurements of regional wall motion and regional myocardial blood flow may facilitate chronic studies of cardiovascular physiology.     

Effects of oxyfedrine on regional myocardial blood flow in patients with coronary artery disease

Summary Medical treatment of angina pectoris is largely based on the use of beta-blocking agents, calcium antagonists, and nitrates. Oxyfedrine, an amino ketone derivative and partial agonist at beta receptors, has been shown to have potent antianginal properties and to increase coronary blood flow in normal and ischemic myocardial regions in experimental studies. We assessed the effects of intravenous oxyfedrine on regional myocardial blood flow, using positron emission tomography (15-oxygen water), in six patients with chronic stable angina, positive exercise tests, and documented coronary artery disease. Myocardial blood flow was measured in all patients before (baseline) and 10 minutes after the intravenous administration of a single bolus (0.11–0.13 mg/kg) of oxyfedrine. Compared to baseline, heart rate and systolic blood pressure remained almost unchanged after the administration of oxyfedrine. Mean baseline myocardial blood flow was 0.90±0.15 ml/g/min in areas supplied by arteries with significant coronary stenosis and 1.08±0.19 ml/g/min in areas supplied by nonstenotic coronary vessels (p<0.05). After the adminsitration of oxyfedrine, myocardial blood flow increased significantly in both the regions supplied by stenotic vessels (by 25%; from 0.90±0.15 to 1.20±0.31 ml/g/min; p=0.002) and in areas supplied by angiographically normal coronary vessels (by 22%; from 1.08±0.19 to 1.38±0.49 ml/g/min; p<0.05). The results of this study indicate that in patients with coronary artery disease, intravenous oxyfedrine significantly increases regional myocardial blood flow, both in areas supplied by critically obstructed vessels and in areas supplied by normal or less severely narrowed coronary arteries.