急性实验中用长度计对狗在位心脏局部心肌功能的评定

本文用自制充水银硅胶管长度计记录了开胸狗左心室局部心肌的长度和压力-长度环。观察到(1)局部心肌的搏功对应心室舒张末期压所绘制的局部心肌功能曲线,与心室功能曲线两者形态相似,均为拋物线升支,回归方程分别为:(?)=-1413.9860 25.9511X-0.1128X~2和(?)=-271.5947 207.4281X-5.0468X~2;(2)心室舒张末期压对应局部心肌舒张末期长度构成的舒张末期压力-长度关系,呈指数曲线。同一条狗,在对照、收缩性能增加和后负荷增加等情况下,回归方程式分別为(?)=e~(0.1356g-1.3706)、(?)=e~(0.0465x-3.9856)和(?)=e~(0.1127x-9.5596)。本文结果表明,局部心肌的长度、压力一长度环,以及由此推导的局部心肌搏功、功能曲线和舒张末期压力-长度关系,可以作为评定局部心肌功能,Frank-Starling 效应、收缩性能和舒张顺应性的有效指标。     

大鼠离体乳头肌收缩末期张力—长度关系的曲线性

大鼠离体左室乳头肌固定于最适初长位,逐步递减“后荷”获得一系列等张收缩的张力、长度缩短程度和速度。结果发现:(1)收缩末期张力-长度关系(ESTLR)为指数曲线,回归方程 T=ar~(-bL)-K 拟合的优度明显高于线性方程拟合的优度(P<0.001),其中 a,k 分别代表总张力和静息张力,b 为曲线的弯曲度;(2)在高钙(4mmol/L)或去甲肾上腺素(NE10~(-6)mol/L)作用下,ESTLR 右上移位,a,b 和无张力缩短速度 L_O 均增大(P均<0.01),尤以高钙时的变化更明显,(3)NE 使张力-速度曲线的右上移位比高钙显著。这提示大鼠离体心肌的 ESTLR 呈非线性特征,参数 a,b 及长度轴截距 L_O 对收缩强度的变化敏感,但对收缩速度改变的敏感性可能比经典的力学指标低。     

离体豚鼠作功心脏的改良灌流装置及心室E_(max)的测定

Flynn等建立的小动物离体作功心脏是研究心脏功能最常用的实验标本,具有前负荷和后负荷可人为调节以及进行正常泵活动两大优点,在这种制备上可以记录多个泵功能和心肌力学等容相指标,但却不能测量记录心肌力学射血相指标以及收缩末期压力容积关系或压力直径关系(ESPVR或ESPDR)及其指标最大容积弹性模量(E_(max)),其原因是,这两种指标都须测量心室容积或心室径。小     

轻度低氧血症的慢性阻塞性肺疾病患者的心脏结构及功能的早期变化

目的:评估正常动脉血氧分压和无右心室衰竭迹象的慢性阻塞性肺疾病(COPD)患者心脏结构和功能.方法:25个COPD稳定期的患者(FEV1,1.23±0.52 L/s;PaO2,82±10 mm Hg),26个与研究对象年龄匹配的受试者作为对照组.以超声多普勒超声心动图测定右心室(RV)和左心室(LV)的结构与功能及检肺动脉压(PAP).结果:COPD组与对照组右心室舒张期末直径为19±3mm,23±2mm,(P＜0.01),三尖瓣口舒张期血流速度比值为1.2±0.9,1.5±0.4(P＜0.05);右心室壁舒张末期厚度为4±0.9,3±0.8,(P＜0.05);右心室射血分数56±12,60±11(P＞0.05).COPD组与对照组左心室舒张期直径为48.0±5.5,46.2±3.4(P＞0.05);二尖瓣口舒张期血流速度比值:1.2±0.4,1.5±0.9左心室后壁厚度为10.0±0.8,10.3±0.7(P＞0.05);EF斜率55.5±11.7,54.5±12.1(P＞0.05);左室舒张早期最大充盈速率分数为2.83±0.43,2.81±0.45 (P＞0.05);左心室射血分数53±7,62±14(P＞0.05);COPD组与对照组均不伴有肺动脉高压.结论:心肌肥厚是COPD患者右心室压力超负荷最早迹象,这些心脏的适应性变化不改变左右心室的收缩功能.     

Genistein对豚鼠右心室肌收缩功能的影响

目的:观察genistein(GEN)对离体豚鼠右心室肌收缩功能的影响,并探讨其作用机理。方法:将离体豚鼠右心室肌置于装有K-H液的灌流肌槽中,待平衡后,加入各种药物观察心室肌收缩活动的变化。结果:GEN和异丙肾上腺素相似,可增强右心室肌的收缩活动,GEN(1～100μmol·L-1)的作用还具有明显的剂量依赖性。心得安(1μmol·L-1)和异搏定(0.5μmol·L-1)虽可明显阻断异丙肾上腺素(1μmol·L-1)的正性肌力作用,但对GEN(50μmol·L-1)的心肌收缩增强效应无明显改变;同时发现GEN(1,10μmol·L-1)温育后,对细胞外液Ca2 浓度升高而诱发的心肌收缩力增强也无明显影响。另外,它莫西芬(1μmol·L-1)及SQ22536(1μmol·L-1)可减弱GEN的正性肌力作用,bpV(1μmol·L-1)也可部分阻断GEN的这种作用。结论:GEN可增强右心室肌的收缩活动,其作用与心肌细胞膜上的β肾上腺素能受体、钙通道的激活无关,可能与cAMP的胞内信号转导以及酪氨酸激酶途径有一定关系。     

急性低氧时的Starling效应及心包的影响

为确定 Starling效应在心泵急性低氧反应中的地位,以及心包对此反应的影响,把17条雄狗,分别在心包切开(A 组)和缝合(B 组)条件下进行实验。在连续、依次吸入空气、氧分压为89、70和55mmHg 的常压氧-氮混合气各30min,并最后吸入氮气时,分别记录不同低氧状况下的左室前后径超声图、左室压力,dp/dt,右室压力或主动脉压力和第二导联心电图。结果表明,重度低氧时,左室舒张期末直径显著增大,A组由对照值3.88±0.15cm(M±SE)增大至4.22±0.18cm(P<0.01);B组由3.53±0.13cm增至3.67±0.12cm(P<0.01),并伴以每搏直径变化的明显增大(A 组由对照值的4.4±0.2mm增至4.9±0.2mm P<0.05;B 组由3.2±0.1mm 增至3.8±0.2mm P<0.01)。左室压力-直径环在重度低氧时显著右移,环体面积不缩小。说明重度低氧时,Starling 效应对心脏搏血功能的调节具有重要作用。在严重低氧导致左室收缩压进行性降低时,迅速切开心包可有利于心泵功能的改善,提示,心包对 Starling 效应的充分发挥有限制作用。     

前,后负荷及心肌收缩力对用背向散射积分进行超声组织定征的影响

研究26只杂狗前负荷、后负荷和心肌收缩力等血流动力学变化对心肌背向散射积分(IB)的影响。用血流散射作心肌IB测量的定标,对容量灌注(前负荷改变)期间、主动脉收缩(后负荷改变)期间和多巴酚丁胺胺及普萘洛尔灌注(收缩力改变)期间的心肌IB进行测量。通过在室间隔、心室后壁的检测发现,前、后负荷和心肌收缩力对定标心肌的IB没有显著性影响。前负荷、后负荷的变化对IB的心动周期的变异幅度无显著影响。但多巴酚丁胶产生的IB的周期性变异幅度有显著增加,而普萘洛尔引起的IB的周期性变异幅度显著降低。这些资料显示,定标的心肌IB不受前、后负荷及心肌收缩力的影响,但IB的周期性变异幅度受心肌收缩力的影响。我们用血液散射作心肌IB的定标测量,结合IB的周期性变异幅度,可以精确地估测心肌的静力学(与纤维化、水肿、坏死等组织学改变有关)和动力学(与肌节长度、肌纤维方向等收缩力因素有关)性质。     

实时三维超声心动图评价房间隔缺损患者手术前后心室收缩功能

目的 应用实时三维超声心动图(RT-3DE)研究房间隔缺损(ASD)患者行内科介入手术前后左、右室心肌收缩变化的相关关系.方法 应用RT-3DE技术对34例ASD患者术前、术后1周以及35例正常受检者(对照组)的左、右室舒张末期容量(LVEDV/RVEDV),左、右室收缩末期容量(LVESV/RVESV),左、右室每搏量(LVSV/RVSV)及左、右室射血分数(LVEF/RVEF)进行统计分析.结果 术前,ASD患者LVEDV、LVSV、LVEF均小于对照组(均P＜0.05),RVEDV、RVESV、RVSV、RVEF均大于对照组(均P＜0.05);术后1周内,ASD患者LVEDV、LVSV、LVEF均较术前增大(均P＜0.05),RVEDV、RVSV、RVEF均较术前减小(均P＜0.05);ASD患者术后的LVEDV、LVESV、LVSV、LVEF与对照组比较均无统计学意义(均P＞0.05),而RVEDV、RVESV、RVSV均大于对照组(P＜0.05);ASD患者术后左、右室的射血分数变化之间均无相关性.结论 行内科介入的ASD患者术后初期左、右室收缩功能即恢复到正常水平,术后左、右室射血分数的变化之间均无相关性.     

L型钙流和反向钠-钙交换在豚鼠心室肌细胞兴奋-收缩偶联中的作用

目的 :比较和探讨L型钙流 [ICa(L) ]和反向钠—钙交换 (NCX)在触发豚鼠心室肌细胞兴奋—收缩偶联中的作用。方法 :以分离的豚鼠单个心室肌细胞为对象 ,采用膜片钳和单细胞收缩测量技术 ,给予 35℃的各种含药物细胞外液快速灌流 ,同时记录ICa(L) 和细胞收缩。结果 :①在 +10mV的钳制电压 ,使用硝苯地平 (Nif) 10～ 10 0 μmol/L和Nif 30 μmol/L +Cd2 +30 μmol/L ,阻滞ICa(L) 越多 ,细胞收缩被阻滞得越多 ,呈线性相关。②在 +5 0mV的钳制电压 ,Nif 10 0 μmol/L以及Nif 30 μmol/L +Cd2 +3 0 μmol/L仅能抑制部分细胞收缩 ,但剩余的细胞收缩起始时间明显延迟 ,且能被 5mmol/LNi2 +所阻滞。③在 +10 0mV的钳制电压 ,细胞收缩起始时间较 +5 0mV明显延迟 ,且不能被Nif 10 0 μmol/L和Nif 30 μmol/L +Cd2 +30 μmol/L所阻滞。结论 :在生理条件下 ,ICa(L) 是触发心室肌细胞兴奋—收缩偶联的主要途径 ,但在膜电位 >+5 0mV时 ,反向NCX也参与兴奋—收缩偶联。     

游离龈移植术后龈瓣收缩效果的临床研究

目的:评估游离龈移植术后3月内龈瓣在垂直向、水平向宽度改变并计算其表面积的收缩情况。方法:选取23例Miller Ⅲ类牙龈退缩患者,因下颌前牙区颊侧角化龈宽度不足(2 mm)行游离龈移植术。分别比较基线、术后1和3月游离龈瓣水平向及垂直向宽度的改变并计算龈瓣表面积的收缩情况。结果:经游离龈移植术的23例患者术区游离龈全部成活,牙龈无红肿,附着龈宽度可达3-5 mm。基线处、术后1月、3月水平向龈瓣宽度分别为9.83±1.7、8.97±1.5、8.48±1.65 mm;基线水平、术后1月、3月垂直向龈瓣宽度分别为4.02±0.61、3.61±0.67、3.24±0.67 mm。与基线时比较,术后1月、3月水平向、垂直向龈瓣宽度、龈瓣表面积均明显降低,差异均具有显著差异(P0.05)。结论:游离龈移植术可增加牙龈退缩患者的附着龈宽度,术后龈瓣存在水平向和垂直向收缩,且垂直向更明显。此外,龈瓣收缩存在个体差异。     

Non-invasive evaluation of systolic and diastolic functions of the left ventricle in newborn infants

To assess possible changes in myocardial contractile function and relaxation occurring after mild perinatal asphyxia, maximal blood pressure and M-mode echocardiograms should be registered simultaneously in 32 normal term newborns (group 1) and in 22 term asphyxiated newborns (group II). The slope of end-systolic pressure-dimension relation (ESPDR) was used as a reliable index for evaluation of the myocardial contractility. The slope of ESPDR and some indices of ventricular relaxation decreased in newborns from group II. It is suggested that ESPDR and parameters of left ventricular relaxation and filling can serve as early and sensitive indices of hypoxic myocardial damage.     

Influence of the pericardium on right and left ventricular filling in the dog

We compared the influence of the pericardium on left and right ventricular (LV, RV) filling by measuring LV and RV pressures and segment lengths (SL, LV free wall, and RV inflow and outflow tracts) in six open-chest, pentobarbital sodium-anesthetized dogs before and after pericardiectomy. End-diastolic pressure (EDP) was varied by partial caval occlusion and dextran infusion. At each site the ln EDP-SL relation was fitted by linear regression and characterized by its slope and 1-Torr EDP intercept. The slope and 1-Torr intercept of the LV ln EDP-SL relation changed variably after pericardiectomy, but in each dog a change occurred that shifted this relation downward. In contrast, the RV inflow tract slope invariably decreased significantly after pericardiectomy, whereas its intercept was unchanged in all but one dog. The RV outflow tract results were similar to the inflow tract but less consistent. By the use of the raw EDP-SL data points, we calculated that the absolute contribution of the pericardium to EDP (i.e., the effective pericardial surface pressure) was similar at the three sites. However, as EDP values increased the proportional contribution of the pericardium to right ventricular end-diastolic pressure (RVEDP) increased, whereas that to left ventricular end-diastolic pressure (LVEDP) remained relatively constant. As a result, at the higher EDP values tested, the pericardium was responsible for a larger proportion of RVEDP than LVEDP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postsystolic shortening of ischemic myocardium: a mechanism of abnormal intraventricular filling

Acute myocardial ischemia has been associated with abnormal filling patterns in the left ventricular (LV) apex. We hypothesized that this may in part be due to postsystolic shortening of ischemic apical segments, which leads to reversal of early diastolic apical flow. Fourteen open-chest anesthetized dogs were instrumented with micromanometers in the LV apex and left atrium and myocardial sonomicrometers in the anterior apical LV wall. Intraventricular filling by color Doppler and wall motion by strain Doppler echocardiography (SDE) were assessed from an apical view. Measurements were taken before and after 5 min of left anterior descending coronary artery (LAD) occlusion. In four dogs, we measured the pressure difference between the LV apex and outflow tract. At baseline, peak early diastolic flow velocities in the distal one-third of the LV were directed toward apex (9.2 +/- 1.6 cm/s). After LAD occlusion, the velocities reversed (-2.3 +/- 0.4 cm/s, P < 0.01), indicating that blood was ejected from the apex toward the base during early filling. This interpretation was confirmed by wall motion analysis, which showed postsystolic shortening of apical myocardial segments. The postsystolic shortening represented 9.7 +/- 1.7% (P < 0.01) and 14.2 +/- 2.4% (P < 0.01) of end-diastolic segment length by SDE and sonomicrometry, respectively. Consistent with the velocity changes, we found reversal of the early diastolic pressure gradient from the LV apex to outflow tract. In the present model, acute LAD occlusion resulted in reversal of early diastolic apical flow, and this was attributed to postsystolic shortening of dyskinetic apical segments. The clinical diagnostic importance of this finding remains to be determined.     

Difference in the relation between infarct and occluded bed in pentobarbital-anesthetized and conscious dogs

The relationship between myocardial infarct size (IS) and occluded bed size (OBS) in pentobarbital-anesthetized (A, n = 16) and conscious (C, n = 20) dog models were compared. IS and OBS (postmortem coronary arteriography) were measured by computerized planimetry of weighed left ventricular (LV) rings 7 days after permanent left anterior descending (LAD, n = 19) or circumflex (LC, n = 17) coronary artery occlusion. For both A and C groups, IS was directly related to OBS (p less than 0.001) and no infarcts developed for small occluded beds. For either LAD or LC subgroups, infarcts were larger in A than C dogs (49 +/- 18 vs. 30 +/- 19% OBS, p less than 0.025), with greater slope of the linear regression between IS and OBS (p less than 0.001) and less epicardial sparing on topographic mapping (p less than 0.05). Although postocclusion mean arterial and left atrial pressures were similar in A and C groups, heart rates were greater in the A dogs, both pre- (125 vs. 88 beats/min, p less than 0.001) and post-occlusion (151 vs. 108 beats/min, p less than 0.001). Endocardial flows (radioactive microspheres) in infarct centers and margins were less in A than C dogs. Also, endocardial/epicardial (endo/epi) flow ratios in all regions were less in A than C dogs, both pre- and post-occlusion. Increasing heart rate in 10 other C dogs with LAD occlusion to that of the A group (151 beats/min) by right ventricular pacing resulted in larger infarcts with greater slope of the linear regression and less endo/epi flow ratios, as in the A group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle metaboreflex control of ventricular contractility during dynamic exercise

When oxygen delivery to active skeletal muscle is insufficient for the metabolic demands, afferent nerves within muscles are activated, which elicit reflex increases in heart rate (HR), cardiac output (CO), and arterial pressure (AP), termed the muscle metaboreflex (MMR). To what extent the increases in CO are the result of increased ventricular contractility is unclear. A widely accepted index of contractility is maximal left ventricular elastance (Emax), the slope of the end-systolic pressure-volume relationship, such as during rapidly imposed reductions in preload. The objective of the present study was to determine whether MMR activation elicits increases in Emax. Experiments were performed using conscious dogs chronically instrumented to measure left ventricular pressure and volume at rest and during mild or moderate treadmill exercise with and without partial hindlimb ischemia to elicit MMR responses. At both workloads, MMR activation significantly increased CO, HR, AP, and maximum rate of change of left ventricular pressure. During both mild and moderate exercise, MMR activation increased Emax to 159.6 +/- 8.83 and 155.8 +/- 6.32% of the exercise value under free-flow conditions, respectively. We conclude that the increase of ventricular elastance associated with MMR activation indicates that a substantial increase in ventricular contractility contributes to the rise in CO during dynamic exercise.     

Investigating the dual nature of endothelin-1: ischemia or direct arrhythmogenic effect?

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which may also elicit severe ventricular arrhythmias. The aims of our study were to compare the effects of total left anterior descending coronary artery (LAD) occlusion to intracoronary (ic.) ET-1 administration and to investigate the pathomechanism of ET-1 induced arrhythmias in 3 groups of anesthetized, open-chest mongrel dogs. In group A (n=10) a total LAD occlusion was carried out for 30 min, followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into LAD for 30 min at a rate of 30 pmol/min (n=6) and 60 pmol/min (n=8). Epi- and endocardial monophasic action potential (MAP) recordings were performed to detect electrophysiologic changes and ischemia Blood samples for lactate measurements were collected from the coronary sinus (CS) and from the femoral artery. Infrared imaging was applied to follow epimyocardial heat emission changes. At the end of the ET-1 infusion period coronary blood flow (CBF) was reduced significantly in groups B and C (deltaCBF30MIN B: 21+/-2%, p<0.05; C: 35+/-2%, p<0.05), paralleled by a significant epimyocardial temperature decrease in group C (deltaT30MIN: -0.65+/-0.29 degrees C, p<0.05). Two dogs died of ventricular fibrillation (VF) in the reperfusion period in group A. Ventricular premature contractions and non-sustained ventricular tachycardic episodes appeared in group B, whereas six dogs died of VF in group C. Significant CS lactate level elevation indicating ischemia was observed only in group A from the 30th min occlusion throughout the reperfusion period (control vs. 30 min: 1.3+/-0.29 vs. 2.2+/-0.37 mmol/l, p<0.05). Epi- and endocardial MAP durations (MAPD90) and left ventricular epicardial (LV(EPI)) upstroke velocity decreased significantly in group A in the occlusion period. ET-1 infusion significantly increased LV(EPI) MAPD90 in group B and both MAPD90-s in group C. In conclusion, ischemic MAP and CS lactate changes were observed only in group A. Although ET-1 reduced CBF significantly in groups B and C, neither MAP nor lactate indicated ischemic alterations. ET-1 induced major ventricular arrhythmias appeared before signs of myocardial ischemia developed, though reduced CBF presumably contributed to sustaining the arrhythmias.     

Nicotine increases ventricular vulnerability to fibrillation in hearts with healed myocardial infarction

The vulnerability of the infarcted hearts to ventricular fibrillation (VF) was tested in in situ canine hearts during nicotine infusion. The activation pattern was mapped with 477 bipolar electrodes in open-chest anesthetized dogs (n = 8) 5-6 wk after permanent occlusion of the left anterior descending coronary artery. Nicotine (129 +/- 76 ng/ml) lengthened (P < 0.01) the pacing cycle length at which VF was induced from 171 +/- 8.9 to 210 +/- 14. 7 ms. Nicotine selectively amplified the magnitude of conduction time and monophasic action potential (MAP) amplitude and duration (MAPA and MAPD, respectively) alternans in the epicardial border zone (EBZ) but not in the normal zone. With critical reduction of the MAPA and MAPD in the EBZ, conduction block occurred across the long axis of the EBZ cells. Block led immediately to reentry formation in the EBZ with a mean period of 105 +/- 10 ms, which, after one to two rotations, degenerated to VF. Nicotine widened the range of diastolic intervals over which the dynamic MAPD restitution curve had a slope >1. We conclude that nicotine facilitates conduction block, reentry, and VF in hearts with healed myocardial infarction by increasing the magnitude of depolarization and repolarization alternans consistent with the restitution hypothesis of vulnerability to VF.     

Effects of yohimbine and desipramine on cardiac noradrenaline release and ventricular arrhythmias during acute coronary artery occlusion and reperfusion in anesthetized dogs

Effects of yohimbine (YHMB, an alpha 2-antagonist) and desipramine (DMI, a neuronal uptake inhibitor) were compared on cardiac noradrenaline (NA) release either upon left ansa subclavia nerve stimulation during acute occlusion of the left anterior descending coronary artery (LAD) or upon subsequent LAD reperfusion without stimulation in anesthetized dogs. In control dogs, before LAD occlusion, coronary sinus (CS) NA output increased from 5.4 +/- 1.0 to 26.8 +/- 4.0 ng/min (p less than 0.05) upon stimulation (2 Hz, 30 s). The response to stimulation remained unchanged 25 min after LAD occlusion. During reperfusion 60 min after occlusion, the output of CS-NA and lactate increased from 6.1 +/- 0.8 to 51.3 +/- 19.4 ng/min (p less than 0.05) and from 2.7 +/- 0.5 to 6.7 +/- 1.3 mg/min (p less than 0.05), respectively. In dogs treated with YHMB, the stimulation-induced increase in NA output was potentiated at least fourfold (p less than 0.05) either before or during LAD occlusion, but not during reperfusion. In dogs receiving DMI, stimulation-induced CS-NA output was enhanced to a similar extent (approximately twofold, p less than 0.05) either before or during occlusion, while reperfusion-induced NA output was markedly potentiated by approximately ninefold (p less than 0.05). Maximum dP/dt of left ventricular pressure remained unchanged upon reperfusion in all groups. The total arrhythmic ratio in the drug-treated groups did not significantly differ from the ratio in control dogs upon either stimulation or reperfusion. The data suggest that an abrupt increase in NA output upon reperfusion may result from a washout of NA locally accumulated in the ischemic and (or) peri-ischemic region during the preceding occlusion period, and that NA thus released does not have substantial hemodynamic effects. The results indicate that in the presence of YHMB or DMI, the potentiated increase in NA release in response to either nerve stimulation during LAD occlusion or to reperfusion without stimulation did not aggravate ventricular arrhythmia, most probably owing to the antiarrhythmic properties of these substances.     

Cardioprotection by adenosine A2A agonists in a canine model of myocardial stunning produced by multiple episodes of transient ischemia

We sought to determine whether administration of a very low, nonvasodilating dose of a highly selective adenosine A(2A) receptor agonist (ATL-193 or ATL-146e) would be cardioprotective in a canine model of myocardial stunning produced by multiple episodes of transient ischemia. Twenty-four anesthetized open-chest dogs underwent either 4 (n=12) or 10 cycles (n=12) of 5-min left anterior descending coronary artery (LAD) occlusions interspersed by 5 or 10 min of reperfusion. Left ventricular thickening was measured from baseline through 180 min after the last occlusion-reperfusion cycle. Regional flow was measured with microspheres. In 12 of 24 dogs, A(2A) receptor agonist was infused intravenously beginning 2 min prior to the first occlusion and continuing throughout reperfusion at a dose below that which produces vasodilatation (0.01 microg x kg(-1) x min(-1)). Myocardial flow was similar between control and A(2A) receptor agonist-treated animals, confirming the absence of A(2) receptor agonist-induced vasodilatation. During occlusion, there was severe dyskinesis with marked LAD zone thinning in all animals. After 180 min of reperfusion following the last cycle, significantly greater recovery of LAD zone thickening was observed in A(2A) receptor agonist-treated vs. control animals in both the 4-cycle (91 +/- 7 vs. 56 +/- 12%, respectively; P<0.05) and the 10-cycle (65 +/- 9 vs. 8 +/- 16%, respectively; P<0.05) occlusion groups. The striking amount of functional recovery observed with administration of low, nonvasodilating doses of adenosine A(2A) agonist ATL-193 or ATL-146e supports their further evaluation for the attenuation of postischemic stunning in the clinical setting.     

Catecholamine release and ventricular arrhythmias during coronary occlusion and reperfusion in the dog

In anesthetized dogs, 60-min occlusions of either the proximal (n = 14), distal (n = 8) left circumflex (LCX), or left anterior descending (LAD, n = 10) arteries were followed by reperfusion. Coronary sinus and aortic norepinephrine and epinephrine plasma concentrations were measured. The ventricular arrhythmias were ventricular premature depolarizations (VPDs), unsustained ventricular tachycardia (VT) (greater than or equal to 3 and less than 20 VPDs), sustained VT (greater than or equal to 20 VPDs), and ventricular fibrillation (VF). A gradual twofold increase (p less than 0.05) in myocardial norepinephrine overflow followed occlusion in all three groups. The increases in the amounts of norepinephrine released in the coronary sinus blood during reperfusion were significant and proportional to the size of the occluded area: proximal LCX, from 0.236 +/- 0.038 to 1.528 +/- 0.490 ng/mL of plasma (p less than 0.001); LAD, from 0.180 +/- 0.027 to 0.795 +/- 0.286 ng/mL (p less than 0.05); distal LCX, from 0.215 +/- 0.039 to 0.404 +/- 0.110 ng/mL (p less than 0.05). Aortic epinephrine concentrations were significantly increased only by LAD occlusion; at 15 min, the value had increased to 0.187 +/- 0.053 ng/mL from an initial value of 0.069 +/- 0.029 ng/mL (p less than 0.001). Two phases of ventricular arrhythmias followed both occlusion and reperfusion. Phase 1 postocclusion was characterized by VPDs and phase 2 by VPDs and unsustained VT. Sustained VT was seen only in phase 1 postreperfusion, whereas unsustained VT was seen in phase 2. VF was seen in 50, 35, and 25% of the dogs with proximal LCX, LAD, and distal LCX occlusion and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)