狗急性心肌缺血早期冠脉侧支血流量与血液流变学变化的关系

本实验在14只麻醉开胸狗身上观察了急性心肌缺血早期冠脉侧支血流量与血液流变学变化的关系。动物均分为两组:Ⅰ组,在不控制血压的情况下,观察心肌缺血早期单位压力差下冠脉侧支血管流量(CVC)的变化;Ⅱ组,在保持主动脉血压不变的条件下,根据 Wyatt 等公式计算流经缺血区末梢血管的有效侧支血流量(ECF)。实验结果表明,阻断冠脉血流30min时,低切变率下全血比粘度已明显增高,随后继续增加,60min 时Ⅰ、Ⅱ两组分别较对照值增高19.0%和11.4%(均为P<0.01)。血液粘度增高时,CVC 仅轻度降低(p>0.05),但 ECF却随着血液粘度的增高而逐渐明显降低,缺血60min 时较对照值降低12.1±2.6%(P<0.01)。血液粘度变化与 ECF 变化之间呈明显负相关(r=-0.796,p<002)。上述结果提示,心肌缺血早期血液流变学的异常变化虽然对冠脉侧支血管的血流阻力影响较小,但却使流经缺血区末梢血管的有效侧支血流量明显减少而加重心肌缺血。     

阻断犬冠脉后冠状静脉血液中影响血小板功能变化的因素分析

本研究用14只麻醉开胸犬,分析了阻断冠脉后缺血心肌局部静脉血液中血小板功能变化与体液因素改变的关系。结果表明,心肌缺血时,血小板聚集率(PAgR)明显增大,并伴有TXB_2含量增高、TXB,/6-酮-PGF_(1a)比值增大和血小板计数(PC)减少。此外,随缺血时间延长,全血粘度、红细胞压积(HCT)和红细胞计数(EC)增高,而白细胞计数(NC)、Po_2和pH降低。缺血60min时,将红细胞聚集率与有关参数的百分变化率进行相关分析的结果表明,在PAgR与TXB_2、NC和Po_2之间呈明显正相关(分别为r=0.887,P<0.01;r=0.757,P<0.05;r=0.758,P<0.05),另外在EC和6-酮-PGF_(1a)之间也有正相关关系(r=0.856,P<0.01)。这些结果提示,阻断冠脉后发生的前列腺素、血液粘度、红、白细胞以及缺氧和酸中毒等异常变化,均具有一定的致血小板功能改变的作用。     

心交感神经对缺血心肌区血液中TXB2和6—酮—PGF1α浓度变化的影响

本实验在54只麻醉开胸犬,分别观察了心交感神经和α、β受体阻断剂对心肌缺血早期血小板功能变化的影响。结果表明,阻断冠脉后,心肌缺血区血液中TXB_2和6-酮-PGF_(1α)含量明显升高,血小板计数减少,随缺血时间延长,变化程度也增大。缺血心肌局部外敷2％利多卡因湿沙条或切除双侧星状神经节,分别阻断心交感神经的传入和传出效应,发现阻断冠脉后各参数变化程度明显减轻,与单纯阻断冠脉后各参数变化相比,有显著差异,P<0.01。切除星状神经节并由静脉输注去甲肾上腺素后再阻断冠脉,可重新恢复单纯阻断冠脉后的各参数变化,但输注生理盐水无影响。α和β受体阻断剂对上述参数的影响途径不同。α_2受体阻断剂育亨宾和非选择性α受体阻断剂酚妥拉明,可明显减轻TXB_2和6-酮-PGF_(1α)升高及血小板计数降低的程度,与单纯阻断冠脉后的各参数变化程度相比,有显著差异,P<0.01。但α_1受体阻滞剂哌唑嗪无此作用。和α_2受体阻断剂一样,β受体阻断剂心得安对缺血后上述参数的变化也具有明显改善效应。这些结果提示,心交感神经在血小板功能变化中具有重要作用;育亨宾和酚妥拉明是通过阻断血小板膜α_2受体发挥作用的;在输注心得安而未阻断血小板膜α_2受体时所看到对缺血后血小板功能参数的改善效应,提示β受体阻断剂可能     

江浙蝮蛇抗栓酶对兔缺血心肌电生理学变化的影响

本研究观察了江浙蝮蛇抗栓酶(svate)对缺血心肌电生理学变化的影响。结果表明,静脉注射svate,使阻断冠脉后兔血小板聚集功能和心脏电生理各指标变化明显减轻。缺血50min时,血小板聚集率仅增加4±13％,静息电位减小15.8±0.1％,动作电位幅度降低17.8±0.1％,复极化50％和90％时程分别缩短12.3±0.1％及延长4±0.1％,不应期差值为4.2±7.8％,室颤阈(VFT)降低15.4±8.1％,与单纯阻断组各参数的百分率变化相比,p值均<0.01,证明svate具有改善有效不应期和提高VFT的作用。     

血小板与心肌缺血

心肌缺血时发生的血小板功能异常变化,可减少冠脉侧枝流入缺血区的血量,造成缺血后心脏电活动异常,并加重泵功能衰竭,进而扩大缺血范围,增加梗塞死亡率。缺血后的神经、体液和血管等因素改变有引致血小板功能变化的作用,但尚需进一步澄清其作用原理。     

冠脉缺血对血清IL-6、TNF-α水平的影响与意义

通过对比有无侧枝循环的冠心病患者冠脉内缺血(CAI)前后白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平的变化,并与反映冠脉缺血强度的量化指标-缺血积分之间进行相关性分析,探讨CAI后早期炎性反应与术后再狭窄的机制,以及侧支循环的作用与意义.73例冠心病患者(Ⅰ),分为CAI组(IA)47例,单纯造影组(IB)26例,CAI组再分为有侧支循环组(IAa)16例,无侧支循环组(IAb)31例.参照Leaman冠脉积分系统,对CAI球囊阻断引起的冠脉缺血强度进行量化;检测正常对照组(Ⅱ)与冠心病组CAI手术前后的IL-6、TNF-α水平变化,并进行相关性分析.冠脉缺血性刺激前IL-6和TNF-α分别为9.601±1.789 pg.mL-1和27.014±1.970 pg.mL-1,在缺血刺激后4 h分别为26.998±1.890 pg.mL-1和79.052±1.555 pg.mL-1,呈显著性差异;有侧支循环组人均总缺血积分与人均最大缺血积分(分别为156.80±24.01与788.70±11.99),显著低于无侧支循环组(分别为341.78±30.58与1111.00±25.31).IL-6、TNF-α是反映冠脉缺血后早期炎性反应的敏感指标,缺血积分可作为反映CAI术中缺血/再灌注损伤程度的的量化指标,侧支循环可减轻冠脉缺血后早期炎症反应,对冠脉缺血有重要代偿与保护作用。     

氟碳乳剂与右旋糖酐对犬缺血心肌侧支循环供氧的影响

本实验在14只麻醉开胸狗心脏上观察了氟碳乳剂与右旋糖酐稀释血液对心肌耗氧量与供应缺血心肌氧量关系的影响。以左室压力-时间指数(SPTI)作为心肌耗氧量的指标,根据冠脉有效侧支血流量(ECF)、PaO_2和 Hb 浓度计算供应缺血心肌的氧量。实验结果表明,低分子右旋糖酐稀释血液后,SPTI 暂时性轻度增加(稀释后30min 时较对照增加7.1±2.7%,P<0.05,稀释后60min 时增加2.8±1.2%,P>0.05),ECF 明显增多(稀释后30min 时较对照增加58.5±6.1%,P<0.01),缺血区边缘心肌氧供需关系未发生明显变化。氟碳乳剂稀释血液后,SPTI 的变化规律与右旋糖酐稀释后相同(稀释后30min 和60min 时分别较对照增加2.5±0.7%和1.9±0.8%)ECF 和 PaO_2升高(稀释后30min 时分别较对照增加53.9±6.7%和93±8.9%),供应缺血心肌的氧量显著增加,缺血区边缘心肌氧供需矛盾明显改善。     

在体兔心急性心肌缺血时的复极后不应性

本实验观察了开胸麻醉家兔急性心肌缺血时的不应期改变。用吸引电极记录的单相动作电位(MAP)确定机能不应期(FRP)及 FRP 超过 MAP 复极90%时程(MAPD_(90))的复极后不应性(PRR)。阻断冠脉左室支以后,缺血区不应期表现出两种完全不同的变化:缺血中心区不应期延长并超过 MAPD_(90),出现 PRR;缺血周边区不应期则通常较对照缩短。利用自体颈总动脉的动脉血进行灌流的兔心实验表明,当100%阻断灌流血液时,缺血中心区出现PRR,但是当50%阻断时,同一部位心肌的不应期却表现为缩短。上述结果提示:PRR 是在严重心肌缺血情况下出现的。同一时刻测定缺血中心区、周边区和非缺血区的功能不应期,结果表明,冠脉阻断后不应期离散程度的明显增大是与当时 PRR 的出现密切相关的。因此,PRR 的存在可以认为是造成急性心肌缺血时不应期离散的重要原因,而后者一般认为是异致折返性心律失常的重要因素。     

兔心肌局部缺血和缺氧时的电活动与超微结构的变化

在兔在体心脏上对比观察了阻断冠脉血流(心肌缺血)和阻断冠脉血流后用缺氧液体灌流(心肌缺氧)时心肌电活动与超微结构的变化。结果如下:(1)心肌缺血时引起 MAP 振幅(MAPA)与双极心外膜下电图振幅(BEGA)的降低(P<0.01)以及 MAP 复极达50%的时程(MAPD_(50))与功能不应期(FRP)的缩短(P<0.01);(2)心肌缺氧时只引起 MAPD_(50)和 FRP的缩短(P值分别小于0.01和0.05),而未引起 MAPA 和 BEGA 的明显变化;(3)超微结构的观察表明,心肌缺血10分钟时,多数线粒体内出现不定形的致密小体,核染色质明显周边化,而心肌缺氧10分钟时,仅在少数线粒体内出现致密体,核染色质分散,有的呈现早期周边化。上述结果提示,在心肌缺血早期,缺氧是造成不应期缩短的主要原因,而代谢产物和 K~ 的蓄积则可能是引起传导阻抑的重要因素,并有加强缺氧所致心肌损伤的作用。     

冠状动脉狭窄对血流量的影响

在22条开胸犬上观察了冠脉狭窄对血流量(CBF)的影响。用一可调节的微米缩窄器定量调节左旋支缩窄程度,测量了主动脉平均压(Pa)、冠脉远端小动脉平均压(Pc)和狭窄端压力降(ΔP)。冠脉狭窄程度与血流量变化曲线显示:在冠脉狭窄程度小于85％时,CBF相对稳定;随着狭窄程度的进一步增加,CBF急剧下降;而在狭窄程度大于95％后,CBF又缓慢下降。冠状动脉狭窄程度与CBF下降的曲线可用下列方程式表达: CBF=1.48×10~(10)e~(-27.6A)(A=冠脉狭窄程度) 冠脉狭窄程度大于50％时,狭窄程度与Pc呈负相关:Pc=159.1—1.36A(r=-0.73,P<0.01)。Pc与CBF呈正相关;Pc=16.9 1.3CBF(r=0.74,P<0.01)     

Progression of myocardial injury during coronary occlusion in the collateral-deficient heart: a non-wavefront phenomenon

It is widely accepted that, during acute coronary occlusion, ischemic cell death progresses from the subendocardium to the subepicardium in a wavefront fashion. This concept, which implies that the subendocardium is the most susceptible myocardial region to ischemic injury, was established using a canine model with an extensive system of subepicardial coronary collaterals. In humans, particularly in those with coronary artery disease, there is a wide range in the distribution and functional capacity of the collateral circulation, which may affect the pattern of infarct evolution. Using an ovine model with a limited system of preformed subendocardial coronary collaterals, we characterized the effect of increasing lengths of ischemia on regional blood flow and infarct size in three regions of the ventricular wall: subendocardium, midmyocardium, and subepicardium. Our results demonstrate that the myocardium and microvasculature in these three regions are equally susceptible to injury after 45 min of ischemia. When ischemic time is increased to 1 h, infarct size in the midmyocardium (90 +/- 2%) is greater than in the subendocardium (76 +/- 4%, P = 0.004) and subepicardium (84 +/- 3%, P = 0.13). Microvascular dysfunction as assessed as a percentage of baseline flow is also greater in the midmyocardium (14 +/- 5%) compared with the subendocardium (20 +/- 3%, P = 0.23) and subepicardium (51 +/- 9%, P = 0.007). These findings suggest that, in subjects with a limited system of coronary collateral circulation, the midmyocardium is the most susceptible myocardial region to ischemia and the subendocardium is the most resistant. Myocardial viability during coronary occlusion appears to be primarily determined by the distribution and functional capacity of the collateral circulation.     

Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia

On the hypothesis that coronary sinus occlusion (CSO) may reduce myocardial ischemia, we examined the effects of CSO on coronary collateral blood flow and on the distribution of regional myocardial blood flow (RMBF) in dogs. Thirty-eight anesthetized dogs underwent occlusion of the left anterior descending coronary artery with or without CSO and intact vasomotor tone. We measured RMBF and intramyocardial pressure (IMP) in the subendocardium (Endo) and subepicardium (Epi) separately. With intact vasomotor tone, CSO during ischemia significantly increased RMBF in the ischemic region (IR), particularly in Endo from 0.17 +/- 0.03 to 0.33 +/- 0.05 ml x min(-1) x g(-1) (P < 0.05), and increased the Endo/Epi from 0.59 +/- 0.10 to 1.15 +/- 0.15 (P < 0.01). These effects of CSO were partially abolished by adenosine. However, the Endo/Epi was still increased from 0.90 +/- 0.13 to 2.09 +/- 0.30 (P < 0.01). The changes in RMBF in IR were significantly correlated with the peak CS pressure during CSO. The Endo/Epi of IMP in IR was significantly decreased during CSO. In conclusion, CSO potentially enhances coronary collateral flow, and preserves the ischemic myocardium, especially in Endo.     

Effects of exercise on collateral development in myocardial ischemia in pigs

To study the effects of exercise on collateral development in myocardial ischemia, we induced coronary arterial stenosis of the left circumflex coronary artery (LCCA) in 18 of 30 pigs. During that surgery, we identified the coronary bed at risk. Nine of these pigs were then subjected to 5 mo of exercise training on a treadmill. After exercise training, we determined regional collateral and myocardial blood flow using radiolabeled microspheres. At autopsy, all animals had complete occlusion of the LCCA. Infarct size in the exercise-trained pigs was significantly less than in the sedentary pigs (5.9 +/- 1.0 vs. 11.7 +/- 1.0% of the left ventricle). The exercise-trained animals had a greater increase in collateral flow, 35.1 +/- 3.0 vs. 28.7 +/- 4.1 ml X min-1 X 100 g-1, in the noninfarcted jeopardized zone of the LCCA bed. The major findings of the study were the following: 1) chronic coronary artery stenosis progressing to occlusion stimulated development of the collateral circulation and salvaged tissue in the jeopardized myocardium of an animal model with sparse collaterals; 2) development of the collateral circulation and tissue salvage is increased by exercise training; 3) collaterals develop primarily in or near the ischemic zone; and 4) all collateral beds develop a circumferential flow gradient following occlusion.     

Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs

Transient episodes of ischemic preconditioning (PC) render myocardium protected against subsequent lethal injury after ischemia and reperfusion. Recent studies indicate that application of short, repetitive ischemia only during the onset of reperfusion after the lethal ischemic event may obtain equivalent protection. We assessed whether such ischemic postconditioning (Postcon) is cardioprotective in pigs by limiting lethal injury. Pentobarbital sodium-anesthetized, open-chest pigs underwent 30 min of complete occlusion of the left anterior descending coronary artery and 3-h reflow. PC was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. Postcon was elicited by three cycles of 30-s reperfusion, followed by 30-s reocclusion, after the 30-min occlusion period and before the 3-h reflow. Infarct size (%area-at-risk using triphenyltetrazolium chloride macrochemistry; means +/- SE) after 30 min of ischemia was 26.5 +/- 5.2% (n = 7 hearts/treatment group). PC markedly limited myocardial infarct size (2.8 +/- 1.2%, n = 7 hearts/treatment group, P < 0.05 vs. controls). However, Postcon had no effect on infarct size (37.8 +/- 5.1%, n = 7 hearts/treatment group). Within the subendocardium, Postcon increased phosphorylation of Akt (74 +/- 12%) and ERK1/2 (56 +/- 10%) compared with control hearts subjected only to 30-min occlusion and 15-min reperfusion (P < or = 0.05), and these changes were not different from the response triggered by PC (n = 5 hearts/treatment group). Phosphorylation of downstream p70S6K was also equivalent in PC and Postcon groups. These data do not support the hypothesis that application of 30-s cycles of repetitive ischemia during reperfusion exerts a protective effect on pig hearts subjected to lethal ischemia, but this is not due to a failure to phosphorylate ERK and Akt during early reperfusion.     

The transient nature of myocardial ischemia during partial occlusion of the coronary artery in waking immobilized rabbits

The radioactive microsphere technique was used to study mechanisms of disappearance of myocardial ischemia during partial occlusion of the left descending anterior coronary artery with implanted device in conscious immobilized rabbits. Microspheres (15 microns, NEN, USA) were injected before occlusion, immediately after ST-segment elevation and after disappearance of ST-segment shift. In ischemic region blood flow dropped by 45% (p less than 0.05) and mean blood pressure decreased by 12% (P less than 0.05) on the 1st minute of coronary occlusion. 8-15 min later ST-segment elevation disappeared and the blood flow in ischemic region became higher than control level (on the average by 35%). It is suggested that ischemia is abolished mainly by dilatation of distal coronary vessels, than by activation of collateral blood flow.     

Myocardial stunning in exercise-induced ischemia in dogs: lack of late preconditioning

Late preconditioning (PC) against myocardial stunning develops after coronary artery occlusion (CAO) at rest and subsequent reperfusion. We investigated whether late PC occurs after exercise-induced ischemia (high-flow ischemia) in dogs. A circumflex coronary artery stenosis (by using occluders) was set up before the onset of treadmill exercise in nine chronically instrumented dogs to suppress exercise-induced increase in mean coronary blood flow velocity (CBFV, Doppler) without simultaneously affecting left ventricular (LV) wall thickening (Wth) at rest. Two similar exercises were performed 24 h apart. On day 1, LV Wth was reduced by 84 +/- 5% (P < 0.01), and exercise-induced increases in transmural myocardial blood flow (MBF, fluorescent microspheres) in the ischemic zone were blunted. LV Wth was depressed throughout the first 10 h and returned to its baseline value after 24 h. On day 2, changes in LV Wth and MBF were similar as was the time course for LV Wth recovery, indicating lack of late PC. Also, CBFV responses to acetylcholine, nitroglycerin, and reactive hyperemia (20-s CAO) were not significantly different on days 1 and 2. Similar results were obtained in a subgroup of four additional dogs with more severe stenosis during exercise. Late PC against myocardial stunning was confirmed to occur in a model of 10-min CAO followed by coronary artery reperfusion (CAR) in another four dogs. Thus in contrast with CAO at rest followed by CAR, severe myocardial ischemia in coronary flow-limited exercising dogs does not induce late PC against myocardial stunning.     

Inhibition of eicosanoid-mediated coronary constriction during myocardial ischemia

Thromboxane A2 and cysteinyl leukotrienes are highly effective microvessel constrictors in normally perfused myocardium. Their release during acute coronary thrombosis might augment myocardial underperfusion. The constrictor action of these substances could be modified substantially, however, by concomitant myocardial ischemia. We compared the effects of the two eicosanoid constrictors in normally perfused and ischemic myocardium of 24 open-chest, pentobarbital-anesthetized pigs. Left anterior descending coronary flow was measured after intracoronary bolus injections of the stable thromboxane A2 analog U46619 (1-10 micrograms) or leukotriene D4 (LTD4, 1-10 micrograms). Each dose was given before and during myocardial ischemia induced by a snare adjusted to produce 63 +/- 2% decrease in coronary flow for 10 min. Marked dose-independent inhibition of eicosanoid-induced coronary flow decrease occurred during ischemia. With 10 micrograms U46619, coronary flow decrease in the unoccluded state (25 +/- 2 from 55 +/- 4 ml/min pretreatment baseline) was virtually eliminated during snare occlusion (1 +/- 1 from 21 +/- 3 ml/min pretreatment baseline, P less than 0.001). Similar results occurred with LTD4. Distal coronary pressure during ischemia indicated a lack of microvessel responsiveness to the eicosanoids rather than a buffering of resistance change by the snare. U46619 and LTD4 did induce transient, small reductions in regional shortening fraction during ischemia. Our data suggest that eicosanoid-induced constriction of myocardial resistance vessels is not a likely complication of acute coronary thrombosis. However, eicosanoids could depress residual contractility in moderately ischemic regions.     

Beneficial effects of perfluorochemical artificial blood on cardiac function following coronary occlusion

This study compares the effects of perfluorochemical artificial blood versus whole blood on the systolic and diastolic function of regionally ischemic myocardial preparations. Regional ischemia was produced by ligation of the circumflex coronary artery in isolated, blood-perfused rabbit hearts. Three minutes after occlusion, half the hearts were switched from the blood perfusate to perfluorochemical artificial blood; the other half continued to be perfused with blood. Isovolumic left ventricular (LV) developed pressure, dP/dt and resting pressure were monitored before, and for 2 hours after coronary occlusion. After 90 minutes of regional ischemia, perfluorochemical-treated hearts exhibited significantly greater developed pressure than those perfused with blood (78 +/- 6% versus 61 +/- 5% of preligation values; P less than 0.05). At the end of the experiment, LV dP/dt was 21% greater in the perfluorochemical-perfused group than in the blood-perfused group (74 +/- 8% versus 53 +/- 10%; P less than 0.01). Perfluorochemical perfusion also preserved diastolic function by preventing the 58% increase in left ventricular chamber stiffness (i.e., resting pressure; P less than 0.01) associated with circumflex ligation. Thus, in the present model of regional ischemia, perfluorochemical artificial blood is significantly better than blood at maintaining both systolic and diastolic myocardial function after a major coronary artery has been occluded.     

The pig as a model for myocardial ischemia and exercise

The pig has been well characterized as an appropriate model for the study of coronary physiology, the coronary collateral circulation and exercise physiology. We compared both Yucatan miniature swine and young farm pigs in experiments involving myocardial ischemia, infarction and exercise. The Yucatan pig was vigorous, docile and proved to be an appropriate model of coronary physiology and exercise in man. The exercise capacity of the Yucatan pig was greater than that of the similar weight Hampshire pig, apparently because of the higher hematocrit and larger heart size. Both breeds were able to increase their maximal oxygen consumption (VO2 max) by approximately 25% after 10 weeks of training. Experiments measuring maximal coronary capacity suggest that the vascular capacity was similar to that of man, but less than that of the dog. Acute occlusion of the coronary artery in pigs infarcted most of the tissue of the vascular bed at risk. The collateral circulation of the pig is less than one fourth that of the dog and is similar to that of man. Slow occlusion of the left circumflex coronary artery produces an ischemic vascular bed which is collaterally dependent with only 5% infarction. Collateral flow is sufficient to meet resting conditions, but during exercise, severe ischemia is unmasked. This ischemia is present for up to 16 weeks following occlusion. The observation of limited infarction in conjunction with limited collateral vessel development suggests that this is a good model for investigating the growth and development of coronary collateral circulation in man.     

Is microvascular protection by cariporide and ischemic preconditioning causally linked to myocardial salvage?

Two independent cardioprotective interventions, Na(+)/H(+) exchange inhibition and ischemic preconditioning (PC), were investigated with respect to differential effects on microvascular and myocardial salvage in anesthetized rabbits (30 min of ischemia, 180 min of reperfusion). Cariporide (Car, 300 microg/kg) administered before occlusion and PC reduced infarct size (IS) as measured by triphenyltetrazolium staining [control, 46.0 +/- 4.2% of risk area (RA); Car, 17.6 +/- 3.7% (P < 0.01); PC, 27.5 +/- 4.1% (P < 0.01)] and concomitantly decreased the area of anatomic no reflow (ANR) as measured by thioflavin S staining [control, 40.4 +/- 3.7%; Car, 19.0 +/- 2.9% (P < 0.01); PC, 26.9 +/- 3.4% (P < 0.05)]. Regional myocardial blood flow (RMBF, measured by radioactive microspheres) in the RA, which deteriorated between 30 and 180 min of reperfusion (control, from 79 +/- 6 to 26 +/- 2% of nonischemic flow), was shifted to higher values with both treatments [Car, from 110 +/- 12 to 49 +/- 7% (P < 0.05); PC, from 109 +/- 8 to 38 +/- 6% (P < 0.05)]. However, neither intervention uncoupled the close relationship between IS and ANR (r = 0.92-0.95) or RMBF. Car given at reperfusion did not alter IS, ANR, RMBF, or the close interrelationships. Because size and spatial distribution of no reflow and myocardial necrosis remained closely coupled with independent cardioprotective interventions, a potential causal connection between microvascular and myocardial salvage is discussed.