Effects of nicorandil, a new antianginal agent, and nifedipine on collateral blood flow in a chronic coronary occlusion model

The effects of nicorandil and nifedipine on collateral blood flow were compared in anesthetized dogs with a well-developed collateral circulation produced by Ameroid constriction (6-8 weeks) of the left anterior descending (LAD) coronary artery. The radioactive microsphere technique was used to determine myocardial perfusion in the normal left circumflex (LC) region and in the LAD region distal to the Ameroid constrictor. Low and high doses of nicorandil (25 and 50 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min) were infused i.v. to reduce mean arterial and left ventricular systolic pressure approximately 10 and 25 mm Hg, respectively. A low dose of nicorandil had no effect on myocardial perfusion whereas nifedipine increased subepicardial blood flow in both the LC and LAD regions. The high dose of nifedipine further increased both subepicardial and subendocardial perfusion to the LC region and subepicardial blood flow to the LAD region whereas nicorandil had no effect. When aortic blood pressure was returned to control by occluding a snare around the descending thoracic aorta during infusion of the high dose, nicorandil and nifedipine increased subepicardial and subendocardial blood flow to LAD and LC regions. Whereas nicorandil increased flow to both tissue layers equally, nifedipine increased subepicardial perfusion primarily. In summary, nifedipine increased collateral blood flow in a chronic coronary occlusion model despite the presence of systemic hypotension, whereas nicorandil only increased flow when aortic blood pressure was maintained. However, nicorandil increased myocardial blood flow equally across the left ventricular wall, whereas nifedipine primarily increased subepicardial blood flow.     

无创性检测心外膜血流变化评价冠脉侧支循环建立的实验研究

目的：应用冠脉血流显像观察前降支(LAD)近端慢性闭塞后其中远段以及后降支(PDA)血流的变化，探讨无创检测心外膜血流在评价侧支循环方面的意义。方法：24条实验小型猪，在前降支近端放置Ameroid环建立慢性心肌缺血模型。放环6周后做选择性左冠状动脉造影和心肌声学造影，观察放环处是否完全闭塞以及造影剂在左室心肌的分布情况。分别在基础状态及放环6周后，采用左心两腔切面观察前降支远段及后降支的血流信号，记录血流频谱。结果：14条动物成功建立模型。其中6条左室前壁见明显灌注缺损，冠脉血流显像未探及前降支中远段血流信号，后降支的峰值流速与基础状态无明显差异；8条前壁见不同程度造影剂充填，其中4条前降支远端可见前向性血流信号，2条前降支远端见逆向性血流信号，这8条猪的后降支峰值流速较基础时明显增快。结论：冠脉血流显像能直接检测冠脉闭塞后相关心外膜冠脉血流的改变，可作为判断侧支循环建立的重要依据。     

Nicotinic acid, free fatty acids and myocardial function during coronary occlusion and reperfusion in the dog

The effect of nicotinic acid on regional myocardial blood flow, percentage of segment shortening and myocardial uptake of free-fatty acids during a 15-min occlusion of the left anterior descending coronary artery and 3-hr reperfusion period was compared to a saline-treated control group. Nicotinic acid (2.4 mumol/kg/min i.v.) was infused 30 min before and throughout the occlusion period. Heart rate, arterial blood pressure and left ventricular systolic and end diastolic pressures were not different during occlusion and reperfusion in the nicotinic acid or saline-treated groups. However, left ventricular dP/dt, an index of global myocardial function and percentage of segment shortening in the ischemic region were greater during occlusion and reperfusion after nicotinic acid. Even though myocardial blood flow was unaltered in the normal or ischemic region during nicotinic acid infusion, subendocardial blood flow during reperfusion was enhanced significantly when compared to the control group. Nicotinic acid also decreased free-fatty acid uptake by the heart during occlusion which returned gradually to the pretreatment control during 3 hr of reperfusion. Thus, the improvement in percentage of segment shortening, dP/dt and subendocardial blood flow during reperfusion may be related to the ability of nicotinic acid to reduce free-fatty acid uptake by the heart during coronary occlusion.     

Isosorbide dinitrate ameliorates myocardial ischemia after development of collateral function in a canine model

The effects of i.v. administered isosorbide dinitrate (ISDN) on the reduced level of regional myocardial function during coronary occlusion were studied in conscious dogs before and after collateral development and in the absence of persistent coronary stenosis. The animals were instrumented during sterile surgery with a miniature pressure gauge for measuring left ventricular pressure and a cannula for aortic pressure. Two pairs of piezoelectric crystals were placed in normal and ischemic areas to determine regional circumferential length. A hydraulic cuff occluder and a Doppler flow probe were placed around the left circumflex coronary artery. Collaterals were induced to develop by 2 min of coronary occlusion applied repetitively at an interval of 32 min for 2 to 9 days, until the regional dysfunction produced by coronary occlusion had disappeared. Collateral development was estimated according to percentage of systolic shortening and endsystolic length area (ESL area) during the occlusion. Before collateral development, ISDN in a dose of 100 micrograms/kg did not affect the level of regional dysfunction. The ESL area was 250 +/- 54 and 248 +/- 52 mm.sec before and after ISDN, respectively. After collateral development, the ESL area was 51 +/- 13 mm.sec and it decreased by 35% after the i.v. administration of ISDN. The improvement by ISDN of transient myocardial dysfunction was achieved even during electrical tachypacing. Accordingly, the beneficial effects of ISDN on regional wall motion rendered ischemic during transient coronary occlusion were appreciable after coronary collateral development.     

冠脉血流显像无创评估心肌梗死缺血区侧支循环的初步临床观察

目的 观察冠脉血流显像无创技术对心肌梗死缺血区的侧支循环状况,以期建立无创检测缺血区侧支循环新方法。方法 冠心病心肌梗死患者8例,采用心尖两腔切面观察前后降支及心肌内血流,左室短轴切面观察前后室间隔支的血流,频谱多普勒测量血流速度。结果８例患者经冠脉造影证实有不同途径的侧支交通,后降支与前降支末梢相交通者５例,前降支为逆向充盈、冠脉血流显像检查前降支远端可见收缩期为主和舒张期为主的逆向血流各１例,后降支远端测及舒张期反向血流１例;有前后室间隔支相交通的６例（由前间隔支至后室间隔支２例和后间隔至前间隔支４例）,冠脉血流显像检查时可见明显增强的前后室间隔支的血流信号并向缺血区延伸,频谱显示为舒张期为主的反向血流,造影显示由对角支和回旋支与前降支中部相交通的２例,冠脉血流显像仅探测到对角支内血流增快,为１.5m/s。另外,冠脉血流显像在１例前降支起始部闭塞的患者中观察到由左室腔进入缺血的前壁的血流束,频谱以舒张期为主,峰速为０.49m/s。结论 冠脉血流显像技术可直观显示心肌梗死患者的侧支循环血流,可作为冠脉造影的重要补充。     

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.     

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.     

Improvement in Myocardial Function and Coronary Blood Flow in Ischemic Myocardium after Mannitol

The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery.Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005).THUS, INCREASES IN SERUM OSMOLALITY PRODUCED BY MANNITOL RESULT IN THE FOLLOWING BENEFICIAL CHANGES DURING MYOCARDIAL ISCHEMIA: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow.     

Comparison of Nitroglycerin-, Nitroprusside-, and Phentolamine-Induced Changes in Coronary Collateral Function in Dogs

The recent use of vasodilators to improve ventricular function in acute myocardial infarction led us to investigate the effects of nitroglycerin, nitroprusside, and phentolamine on coronary collateral flow. Dogs were studied 2-4 wk after an ameroid constrictor was placed around the left anterior descending (LAD) coronary artery. Retrograde flow and peripheral coronary pressure were measured from a cannula inserted in the LAD distal to the ameroid. Systemic arterial pressure was held constant by an aortic cuff. When administered intracoronary (i.c.), nitroglycerin, 0.3-100 mug/min, or nitroprusside, 3-100 mug/min, produced quantitatively similar, dose-dependent increases in retrograde flow. Neither drug, i.c., changed peripheral coronary pressure. Nitroglycerin, 3-300 mug/min, intravenous (i.v.), produced dose-dependent increases in retrograde flow; nitroprusside, i.v., increased retrograde flow only in high doses (100-300 mug/min). Nitroglycerin and nitroprusside, i.v., produced similar increases in peripheral coronary pressure. Phentolamine, 1-300 mug/min, i.v., decreased retrograde flow, and did not change peripheral coronary pressure. Nitroprusside was considerably more potent than nitroglycerin in decreasing systemic arterial pressure and in reducing total coronary resistance. Thus, (a) although i.c. nitroglycerin and nitroprusside produce similar effects on collateral function, i.v. nitroglycerin is more effective than i.v. nitroprusside in augmenting collateral flow; (b) phentolamine has deleterious effects on collateral function; and (c) the relative vasodilator potencies of nitroglycerin and nitroprusside vary in different vascular beds; thus, for a given reduction in systemic arterial pressure, nitroprusside is less effective in increasing retrograde flow.     

The relationship between regional myocardial perfusion at rest and arteriographic lesions in patients with coronary atherosclerosis.

Measurements of mean left ventricular (LV) and regional myocardial blood flow rates were made at rest in 161 patients with 133Xe and a multiplecrystal scintillation camera. Myocardial perfusion rates were correlated with assessments of the degree of coronary artery disease made from the arteriograms obtained during the same studies. In patients with normal coronary arteries without heart failure, the presence of hypertension, aortic stenosis, or aortic insufficiency was not associated with changes in mean LV perfusion from the control value of 61+/-7 ml/100 g-min. However, mean LV perfusion was significantly reduced in patients with normal coronary arteries who had cariomyopathy and impaired ventricular performance. Mean LV perfusion was not significantly different from control values in patients with "mild" coronary artery disease (less than 50% obstruction) or in patients with significant isolated disease (greater than 50% obstruction) of the left anterior descending (lad) artery. Significant reductions in mean LV perfusion were found in patients with greater than 50% obstruction of two coronary arteries (LAD + right or LAD + circumflex) and in patients with triple-vessel disease. The average perfusion rate for regions distal to LAD obstructions in patients with isolated LAD disease was not lower than the LAD perfusion in control patients, but was significantly reduced in patients with LAD + right coronary artery disease (43+/-14 ml/100 g-min). In the latter group average perfusion distal to the LAD lesion was significantly lower than the average regional perfusion rate for the remainder of the LV. However, the mean blood flow rate for the remainder of the LV was also significantly lower than control values despite the lack of significant circumflex disease. The data demonstrate that the presence of radiographically "mild" or significant isolated LAD coronary disease is not associated with reductions in mean LV perfusion at rest, but that mean LV perfusion is reduced in the presence of significant disease of two or three coronary artieries. None of the patients experienced angina during the resting studies and most had clinical evidence of ventricular failure. The observation of depressed LV perfusion in this group, as in the patients with cardiomyopathy, raises the possibility that a lowered resting blood supply may be adequate for a reduced level of performance of a diseased ventricle. The lack of selective reductions of regional perfusion at rest in the majority of the patients with LAD lesions suggests that regional myocardial blood flow must be measured during an intervention which increases myocardial oxygen consumption in order to assess the physiological significance of lesions which are observed at coronary arteriography.     

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.     

侧支循环对局部缺血心肌节段功能的影响

目的 应用超声斑点追踪二维应变显像技术探讨支循环供血对相应缺血心肌节段功能的影响.方法 121例行冠状动脉(冠脉)造影检查者分为3组:1组,冠状动脉正常者30例;2组,冠状动脉狭窄≥75%且伴有侧支循环者45例;3组,冠状动脉狭窄≥75%且不伴有侧支循环者46例.经胸采集左室心尖四腔观、两腔观和长轴观及二尖瓣、乳头肌、心尖短轴观的二维图像.分析各组相应血管供血心肌节段在纵向(L)、径向(R)、周向(C)上的收缩期峰值应变(Sps)、收缩末期应变(Ses)、收缩期峰值应变率(SRs)、舒张早期应变率(SRe)、舒张晚期应变率(SRa)和扭转(Rot)的角度及扭转率.结果 与1组相比,2组纵向的Sps、Ses、SRs,SRa,径向的SRe、SRa,周向的SRe,舒张早期扭转率、舒张晚期扭转率,3组纵向的Sps、Ses、SRs、SRa、SRe,径向的Ses、SRs、SRe、Sra,周向的Sps、Ses、SRs、SRe、SRs,收缩期扭转的峰角度、收缩期峰值扭转率、舒张早期扭转率的绝对值均减少(P＜0.05);与2组相比,3组纵向的Sps、Ses、SRs,径向的Ses、SRs,周向的Sps、Ses、SRs、Sra,收缩期扭转的峰角度、收缩期峰值扭转率、舒张早期扭转率的绝对值均减少(P＜0.05).结论 侧支循环供血可以改善相应缺血心肌节段在各运动方向上的心功能;二维应变显像技术可以有效地评价缺血心肌节段功能.     

The Effects of Nitroglycerin on Coronary Collaterals and Myocardial Contractility

Nitroglycerin (TNG) causes a prolonged dilatation of coronary collaterals. To demonstrate a functional significance of this dilatation we measured the effect of TNG on myocardial contractile force in dogs 2(1/2)-4 wk after the left anterior descending coronary artery (LAD) had been embolized in closed-chest animals. Development of collaterals was documented by angiography. Via a left thoracotomy the main left coronary artery (LCA) and LAD distal to the embolized plug were cannulated. Coronary flow and perfusion pressure were recorded. Contractile force was measured with gauges sutured to epicardial areas supplied by the left circumflex coronary artery (LCf) and occluded LAD. Coronary perfusion pressure in the LCA was gradually decreased until the contractile force recorded by the LAD gauge diminished while the LCf gauge was unaffected. Under these conditions, with coronary perfusion pressure held constant with the aid of a Starling resistance, TNG (18 mug) injected into the LCA increased peripheral LAD pressure by 3-12 mm Hg and contractile force in the LAD region by 36% (range 20-90%), returning it to near-normal levels, while having minimal effect in the LCf area. These changes persisted for 5 min. When LCf and LAD areas were both ischemic, intracoronary TNG had minimal effect on peripheral LAD pressure and contractile force. Thus, TNG causes prolonged dilatation of coronary collaterals and presumed increased collateral flow with subsequent enhancement of myocardial contractile force in ischemic areas. This effect is seen only when ischemia is limited to an area supplied by the collaterals. When the whole heart is ischemic, collaterals are unresponsive to TNG, suggesting that these collaterals dilate fully when the regions from which they originate become ischemic.     

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 Propranolol on Regional Myocardial Function, Electrograms, and Blood Flow in Conscious Dogs with Myocardial Ischemia

The effects of coronary occlusion and of subsequent propranolol administration were examined in 18 conscious dogs. Overall left ventricular (LV) function was assessed by measurements of LV pressure and dP/dt, and regional myocardial function was assessed by measurements of segment length (SL), velocity of SL shortening and regional myocardial “work”, i.e., pressure-length loops in normal, moderately, and severely ischemic zones. Regional intra-myocardial electrograms were measured from the same sites along with regional myocardial blood flow as determined by the radioactive microsphere technique. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reduction and graded elevation of the ST segment. Propranolol depressed overall LV function, function in the normal zone (work fell by 17±4%), and in the majority of moderately ischemic segments (work fell by 7±3%). In severely ischemic segments the extent of paradoxical motion and post-systolic shortening was reduced by propranolol. After propranolol regional myocardial blood flow fell in the normal zone (11±2%) and rose in the moderately (15±4%) and severely (63±10%) ischemic zones. Thus, in the conscious dog with regional myocardial ischemia, propranolol induces a redistribution of myocardial blood flow, with flow falling in normal zones and rising in moderately and severely ischemic zones. The improvement in perfusion of ischemic tissue was associated with slight but significant depression of shortening, velocity, and work in the moderately ischemic zones and of paradoxical bulging and post-systolic shortening in the severely ischemic zone.     

Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs.

The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods of regional myocardial ischemia, was studied in conscious dogs. Total left vemtricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure (dP/dt), and dP/dt/P. Regional LV function was assessed with measurements of regional segment length and velocity of shortening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 5- and 15-min periods on separate days. A 5-min occlusion depressed overall LV function transiently, but just before release of occlusion overall function had nearly returned to control. At this time regional function in the ischemic zone was still depressed to the point of absent shorteining or paradoxical motion during systole and was associated with marked ST segment elevation (+ 10 +/- 2.2 mV) at the site where function was measured. With release of occlusion and reperfusion the intramyocardial electrogram returned to normal within 1 min, and reactive hyperemia subsided by 5-10 min. In contrast to the rapid return to preocclusion levels for coronary flow and the electrogram, regional mechanical function remained depressed for over 3 h. A 15-min coronary occlusion resulted in an even more prolonged (greater than 6 h) derangement of function in the ischemic zone. Thus, brief periods of coronary occlusion result in prolonged impairement of regional myocardial function which could not have been predicted from the rapid return of the electrogram and coronary flow. These observations indicate that brief interruptions of coronary flow result either in a prolonged period of local ischemia or that alterations of mechanical induced by ischemia far outlast the repayment of the oxygen debt.     

Attenuation by atenolol of myocardial acidosis during ischemia in dogs: contribution of beta-1 adrenoceptors to myocardial acidosis

Coronary artery occlusion produces myocardial acidosis, which can be attenuated by propranolol or sotalol. The present study was undertaken to determine which beta adrenoceptors, beta-1 or beta-2, contribute to the ischemic myocardial acidosis. Dogs anesthetized with pentobarbital were used. In the first series of experiments, blood flow in the left anterior descending coronary artery was reduced by an occluder to about one-third of the original flow. Myocardial pH was measured by means of a micro pH electrode inserted into the left anterior descending coronary artery area at the depth of about 8 mm. The myocardial pH decreased from 7.44 to 7.55 to 6.73 to 6.89, 30 min after partial occlusion being the time immediately before an i.v. injection of drugs. Atenolol (1 mg/kg) attenuated significantly the decrease in myocardial pH that had been induced by partial occlusion, whereas IPS 339 (360 micrograms/kg) and ICI 118,551 (300 micrograms/kg) did not. The pH effect of atenolol was confirmed even in the paced heart. In the second series of experiments, the antagonistic action of these drugs on the isoproterenol-induced increase in heart rate and myocardial contractile force and the decrease in diastolic blood pressure was investigated. By this experiment, it was confirmed that atenolol has the beta-1 adrenoceptor antagonistic action, and the IPS 339 and ICI 118,551 have the beta-2 antagonistic action. These results suggest that the activation of beta-1 adrenoceptors contribute to the myocardial acidosis during ischemia.     

Effects of Nitroglycerin and Propranolol on the Distribution of Transmural Myocardial Blood Flow during Ischemia in the Absence of Hemodynamic Changes in the Unanesthetized Dog

Chronically instrumented awake dogs were used to study the effects of nitroglycerin and propranolol on the transmural distribution of myocardial blood flow during transient ischemia. Studies were carried out 7-14 d after implantation of an electromagnetic flowmeter probe and balloon occluder on the left circumflex coronary artery, placement of epicardial minor axis sonar crystals, and implantation of left atrial, left ventricular, and aortic catheters. The occluder was inflated to completely interrupt flow for 10 s followed by partial release to reestablish flow at 60% of the preocclusion level. During this partial release, which served as the control for the study, regional myocardial blood flow was measured with 7- to 10-mum radioactive microspheres. After control measurements, seven dogs were given nitroglycerin (0.4 mg i.v.) and eight dogs propranolol (0.2 mg/kg i.v.). 5 min later the occlusion and partial release sequence was repeated, and regional myocardial blood flow was measured when heart rate, aortic and left ventricular end-diastolic pressure, and minor axis diameter were unchanged from control values.The data values were selected so that total flow to the ischemic region during partial release after nitroglycerin or propranolol administration was not significantly different from flow during the control partial release. After nitroglycerin administration, endocardial flow (endo) in the ischemic region increased from 0.46+/-0.07 to 0.59+/-0.06 ml/min per g (P < 0.006); epicardial flow (epi) decreased from 0.78+/-0.09 to 0.70+/-0.08 ml/min per g (P < 0.04). The endo:epi ratio increased from 0.65+/-0.07 to 0.92+/-0.10 (P < 0.05). In contrast, administration of propranolol produced no significant change in transmural flow (endo, 0.42+/-0.02 and 0.46+/-0.03 ml/min per g; epi, 0.71+/-0.06 and 0.70+/-0.07 ml/min per g) or in the endo:epi ratio (0.60+/-0.03, 0.66+/-0.06) in the ischemic region.Nitroglycerin and propranolol produce different effects on the transmural distribution of blood flow to ischemic myocardium. Nitroglycerin can increase blood flow to the underperfused endocardium in the absence of alterations in heart size, hemodynamic parameters, and total transmural flow to the ischemic region. Under similar conditions, propranolol has no significant effect on the transmural distribution of blood flow to an ischemic region.     

冠状动脉慢血流现象的冠状动脉血流成像分析

目的 应用冠状动脉血流成像(CFI)无创性评估冠状动脉慢血流现象患者的冠状动脉血流速度变化.方法 冠状动脉无明显狭窄且心肌梗死溶栓试验(TIMI)提示慢血流现象患者21例,冠状动脉造影无明显狭窄且TIMI血流正常者9例作为对照组.采用校正的TIMI血流计帧法(CTFC)评价冠状动脉血流速度.常规超声心动图测量左室舒张末期内径、收缩末期内径、左室射血分数、E峰、A峰、E/A值.CFI测量冠状动脉前降支远端舒张期峰值血流速度(Vmax)、舒张期平均流速(Vmean)和血流速度时间积分(VTI).结果 慢血流组前降支CTFC为(45.37±8.62)帧,对照组为(15.94±4.66)帧,二者差异有统计学意义(t=-9.596,P=0.000).慢血流组与对照组常规超声心动图测值差异均无统计学意义.慢血流组前降支Vmax为(22.86±3.04)cm/s,Vmean为(17.62±2.89)cm/s,VTI为(8.49±2.01)cm;对照组前降支Vmax为(31.78±9.28)cm/s,Vmean为(23.67±7.60)cm/s,VTI为(10.91±4.47)cm,两组差异均有统计学意义(P＜0.05).对照组及慢血流组前降支CTFC与Vmax和Vmean呈负相关,对照组前降支CTFC与VTI呈负相关,慢血流组前降支CTFC与VTI无相关性.结论 冠状动脉慢血流现象患者冠状动脉前降支远端血流速度减慢,CFI能够反映冠状动脉造影TIMI血流的变化,但诊断冠状动脉慢血流现象有局限.

Abstract：

Objective To non-invasive assess coronary blood flow velocity changes of patients with slow coronary flow phenomenon (SCFP) by coronary blood flow imaging (CFI).Methods Twenty-one patients who had no significant coronary artery stenosis but had thrombolysis in myocardial infarction (TIMI) slow-flow phenomenon were the experimental group,nine patients who has no significant coronary stenosis and TIMI flow normal were the control group.Using corrected TIMI frame count(CTFC) assess velocity of coronary artery.The left ventricular end diastolic diameter,end systolic diameter,ejection fraction,E peak velocity,A peak velocity,E/A ratio were measured by conventional echocardiography.The distal anterior descending coronary artery diastolic peak flow velocity(Vmax),mean velocity(Vmean) and blood flow velocity time integral(VTI) were measured by CFI.Results The corrected TIMI frame count (CTFC) of left anterior descending artery blood flow in slow blood group was (45.37 ± 8.62)frame,that in control group was (15.94± 4.66)frame,the difference was statistically significant (t = -9.596,P =0.000).The conventional echocardiographic measurements of two groups were not significantly different.The left anterior descending artery Vmax was (22.86 ± 3.04)cm/s,Vmean was (17.62 ± 2.89)cm/s,VTIwas (8.49± 2.01)cm in the slow blood flow group,the left anterior descending artery Vmax was (31.78 ± 9.28) cm/s,Vmean was (23.67 ± 7.60) cm/s,VTI was (10.91 ± 4.47) cm in the control group.The difference was statistically significant.The left anterior descending artery CTFC with Vmax and Vmean was negative correlation in the control group and the slow blood flow group.The left anterior descending artery CTFC was negatively correlated with VTI in the control group,there was no correlation between left anterior descending artery CTFC and VTI in the slow blood flow group.Conclusions Coronary artery flow velocity in the left anterior descending artery was declined.CFI can reflect changes in coronary TIMI flow,but in the diagnosis of coronary slow flow phenomenon CFI has limitations.     

Contrasting effects of verapamil and nifedipine on pH of ischemic myocardium in the dog

It remains unknown whether the actions of verapamil to depress and nifedipine to enhance contractile function of ischemic myocardium influence the degree of myocardial ischemic injury. Thus, we measured intramyocardial pH using fiberoptic pH probes in 43 anesthetized open-chest dogs pretreated for 30 min with verapamil, or nifedipine in doses that decreased aortic pressure 10 to 15 mm Hg before ligation of the left anterior descending coronary artery for 15 min. Drugs were continued during the 15-min ischemic period until the animals were euthanized without reperfusion: verapamil, 10-20 micrograms/kg/min and nifedipine, 2 to 4 micrograms/kg/min i.v. Verapamil-treated dogs showed higher pH of ischemic subendocardium after 15 min ischemia (6.75 +/- 0.07) than did the nifedipine (6.48 +/- 0.04) or placebo (6.43 +/- 0.05) groups, even if the animals were paced (6.71 +/- 0.11) to prevent the negative chronotropic effect of verapamil (P less than 0.01). Neither verapamil nor nifedipine changed collateral myocardial blood flow from 0.10 +/- 0.02 in the subendocardium and 0.17 +/- 0.03 ml/min/g in the subepicardium. Left ventricular function estimated by left ventricular dp/dt was depressed 15% by verapamil and enhanced 26% by nifedipine. Thus, verapamil, but not nifedipine, relieves acidosis of ischemic myocardium after acute coronary occlusion in doses that sustain a 10 to 15 mm Hg decrease in aortic pressure. Nifedipine, in doses that produced the same 10 to 15 mm Hg decrease in mean aortic pressure, did not increase intramyocardial pH, as it enhanced contractile function, estimated by left ventricular dp/dt.(ABSTRACT TRUNCATED AT 250 WORDS)