长期尾部悬吊大鼠冠脉血统量的变化

采用放射性生物微球技术观察了经受４０和１２０ｄ尾部悬吊模拟失重大鼠冠脉血流量及冠脉阻力的变化。４０及１２０ｄ悬吊大鼠冠脉血流量分别较期相应对照组减少２５％（Ｐ＜０．０１）和２２％（Ｐ＜０．０５）;而４０ｄ组和１２０ｄ组的冠脉阻力与其相应配对对照组相比分别升高３７％（Ｐ＜０．０５）和３１％（Ｐ＜０．０５）及５％（Ｐ＜０．０１）。结果表明,长期模拟失重大鼠心脏可能处于低动力状态,从而使心肌的代谢活动减     

慢性乙醇摄入大鼠肝脏醇脱氢酶和谷胱甘肽硫转移酶活性影响

为探讨长期摄入乙醇大鼠肝脏ＡＤＨ和ＧＳＴ活性的动态变化,旨在为酒精中毒的发病机理提供实验依据,进行了下述实验研究。选用体重１００～１２０ｇＳＤ雄性大鼠４８只,随机分成两组：（１）对照组：２４只喂普通饲料,饮用自来水,（２）乙醇组：２４只白天饮用１０％蔗糖水,夜间饮用１０５乙醇水溶液,平均每只实验动物的乙醇摄入量为８．０ｇ／ｋｇ体重／ｄ,饲料同对照组。实验开始后的３０ｄ、６０ｄ时分批处死动物,第９０天时处死全部动物,除肉眼观察肝脏形态学改变外,同时留取病理标本和进行组织中ＡＤＨ和ＧＳＴ活性测定,结果显示：（１）大鼠肝细胞胞浆中ＡＤＨ活性,在服用乙醇３０ｄ时即可看到明显减低,较对照组有显著差别（Ｐ＜０．０５）,至实验９０ｄ结束时,其减低的更明显（Ｐ＜０．０１）．（２）大鼠肝细胞胞浆中ＧＳＴ活性　在６０ｄ和９０ｄ时乙醇组较对照组均明显减低,经统计学处理均有显著差别（Ｐ＜０．０１）。上述结果提示肝脏ＡＤＨ和ＧＳＴ活性表达在酒精性肝病发病机制中起着重要作用。     

脓毒血症大鼠心肌II型磷脂酶A_2活性变化及其调控

观察了脓毒血症大鼠心肌ＩＩ型ＰＬＡ２ 活性、蛋白质含量及其ｍ ＲＮＡ 的变化。结果发现, 脓毒血症早期与晚期心肌ＩＩ型ＰＬＡ２ 活性较对照组分别降低２５ ．０ ％ （Ｐ ＜ ０ ．０５）及增高４７．６ ％ （Ｐ ＜ ０ ．０１）,ＩＩ型ＰＬＡ２ 蛋白质含量分别降低２７．０％ 及增高４８ ．０ ％（ 均Ｐ ＜ ０ ．０１）; 心肌ＩＩ型ＰＬＡ２ ｍ ＲＮＡ合成率与含量呈现类似的双相变化, 在脓毒血症早、晚期ｍＲＮＡ 合成率分别降低４５．０％ 和升高７０．０ ％ （均Ｐ ＜ ０ ．０１）,ｍＲＮＡ含量分别降低３４．１ ％ 和增加１５７ ．０％ （均Ｐ＜ ０ ．０１） 。脓毒血症早、晚期心脏ＩＩ型ＰＬＡ２ ｍ ＲＮＡ半衰期无显著变化（Ｐ ＞ ０．０５） 。实验结果表明大鼠脓毒血症发生过程中心肌ＩＩ型ＰＬＡ２ 活性呈现出先下降后升高的变化, 这一变化受其ｍＲＮＡ 转录水平的调节。     

模拟失重对大鼠心肌力学与生物化学的影响

观察为期４周模拟失重对大鼠心肌收缩性能与收缩蛋白性质的影响,发现模拟失重大鼠左心室乳头肌等长收缩的力学特征发生下列变化：发展张力峰值降低２９％（Ｐ〈０．０１）;达到张力峰值的时间延长１０％（Ｐ〈０．０５）;舒张一半的时间缩短１１％,但未达到显著水平（Ｐ〉０．０５）。心肌力学参数的这些变化表明模拟失重使大鼠心肌收缩性能降低。进一步研究显示,模拟失重大鼠左室心肌肌原纤维Ｃａ＾２＋,Ｍｇ＾２＋－ＡＴＰ酶     

微生态制剂4联活菌片治疗肠结核引起的腹泻的疗效观察

观察４联活菌片治疗肠结核引起的腹泻效果。结果治疗２周后治疗组有效率为９４．１％,对照组有效率为２９．０％（Ｐ＜０．０１）。治疗前与治疗２周后肠道内菌群变化：治疗前治疗组与对照组比较无差异（Ｐ＜０．０５）,两组与正常比较有显著差异（Ｐ＜０．０１）。治疗组治疗前、后比较有显著差异（Ｐ＜０．０１）。对照组治疗前、后比较无显著差异（Ｐ＜０．０５）。治疗后治疗组与对照组比较有显著差异（Ｐ＜０．０１）。治疗后     

猴头菇对小鼠抗疲劳作用的实验研究

分别以猴头菇干粉（猴头菇Ⅰ组）和猴头菇浸出液（猴头菇Ⅱ组）饲喂小鼠,观察猴头菇对小鼠血清乳酸脱氢酶（ＬＤＨ）活力、血乳酸、血清尿素氮（ＢＵＮ）、肝糖原、肌糖原含量及运动耐力的影响。结果表明：实验６０ｄ后,猴头菇Ⅰ、Ⅱ组ＬＤＨ活力、肝糖原及肌糖原含量明显高于对照组（Ｐ＜０．０５或Ｐ＜０．０１）;运动后血乳酸的水平和ＢＵＮ的增量明显低于对照组（Ｐ＜０．０５或Ｐ＜０．０１）;运动后血乳酸消除速率显著高于对照组（Ｐ＜０．０５）;在运动耐力测定时在水中淹死的时间比对照组长得多（Ｐ＜０．０５）。提示：猴头菇具有明显的增强运动能力和解除疲劳的作用。     

大鼠在模拟5 000米低氧下心力储备的动态变化

目的和方法：采用电刺激大鼠坐骨神经引起心阴抗图相应参数变化来测算心力储备的方法,测定了大鼠在模拟５０００ｍ氏氧下不同时间心力储备的动态变化。结果：心力储备在低氧３ｄ已开始增加,７ｄ增加显著（Ｐ〈０．０５）,低氧１０ｄ及１４ｄ又降至接近正常组水平,低氧３０ｄ略低于正常水平;每搏储备的变化规律和变化量均与心力领略相近,低氧７ｄ增加显著（Ｐ〈０．０１）,人低氧１４ｄ仍显著地对照组（Ｐ〈０．０５）;心率储     

红景天中药复方对低氧劳动能力的影响

我们研制了以藏产大花红景天为主要成分的中药复方用以提高机体的低氧劳动能力。在模拟海拔１００００ｍ的小鼠游泳实验中,药物组和对照组动物的存活时间分别为７３．２±３．８和６０．５±４．０ｍｍ（Ｐ＜０．０５）;游泳６０ｍｉｎ（相当于对照组的平均存活时间）以后死亡的百分数分别为５３．０％和３５．８％（Ｐ＜０．０５）。大鼠在模拟海拔５０００ｍ游泳１ｈ,药物组和对照组动物的血乳酸含量分别为１４．６±１．８和２１．１±１．９ｍｍｏｌ／Ｌ（Ｐ＜０．０５）。在模拟海拔４３００ｍ低压舱内人体运动负荷试验中,药物组和对照组受试者的ＰＷＣ１７０分别为９８０．４±５２．８和８６６．４±３０．０（Ｐ＜０．０１）。提示,红景天中药复方能明显提高低氧劳动能力。     

固本生血丸抗再生障碍性贫血的实验研究

本文通过实验观察固本生血丸对实验性再生障碍性贫血的作用。证明固本出血丸加康力龙联合治疗能显著降低骨髓造血障碍发生率和死亡率,效果优于单用康力龙。发生率和死亡率,对照组分别为８６．７％和７３．３％;康力龙组分别为５３．３％（Ｐ＜０．０５）和５０．０％;固本生血丸加康力龙组分别为４３．３％（Ｐ＜０．００５）和４０．０％（Ｐ＜０．０１）。     

高原适应过程中大鼠脑内β－内啡肽含量变化的研究

选用成年雄性Ｗｉｓｔａｒ大鼠,由平原（海拔５ｍ,上海）直接运送到高原（２２６１ｍ,西宁和３４６０ｍ,天峻）。以放射免疫分折法研究了大鼠在高原２４ｈ．急性缺氧期和３０ｄ慢性缺氧期中枢脑内β－内啡肽样免疫活性物质（β－ＥＰ）的含量变化。结果表明：１．大鼠在两个不同海拔（２２６１ｍ,３４６０ｍ）环境２４ｈ急性缺氧期与平原对照组相比,脑垂体内β－ＥＰ含量降低非常显著（Ｐ＜０．０１）,纹状体、丘脑、下丘脑、桥－延脑、海马内β－ＥＰ含量均增加非常显著（Ｐ＜０．０１）。２．大鼠在３４６０ｍ高原３０ｄ慢性习服期,垂体及各脑区内β－ＥＰ的含量变化呈时相性：即１—３ｄ均呈进行性增加（Ｐ＜０．０１）：３－１５ｄ呈持续性减少,除中脑、纹状体、丘脑外,均为Ｐ＜０．０１。１５－３０ｄ垂体、丘脑、皮层、纹状体内β－ＥＰ含量仍持续减少（毒体、皮层Ｐ＜０．０１）,桥－延脑、下丘脑、海马趋于回升（Ｐ＜０．０１）,中脑亦趋于回升（Ｐ＞０．０５）。脑内β－ＥＰ的这种变化可能具有十分重要的生物学意义。     

Modulation of myocardial alpha 1- but not beta-adrenoceptors after 90-day tail-suspension

We have previously demonstrated that prolonged simulated microgravity (tail-suspension) leads to cardiac alterations with increased resting heart rate, myocardial degradation changes and attenuated myocardial contractility. The present study investigated the potential role of adrenoceptor mechanisms underlying them. Changes of myocardial alpha 1-adrenoceptor (alpha 1-AR) and beta 1-adrenoceptor (beta-AR) in 90-day tail-suspended rats was investigated by the method of radioligand binding assay and application of Scatchard's method. The results showed significantly decreased quantity of specific binding of 125I-BE[2-beta-(4-hydroxy-3-[125I]indophenyl)-ethylaminomethyltetralone] to alpha 1-AR present in membrane derived from ventricular myocardium of the suspended animals, despite the affinity of the alpha 1-AR to 125I-Be was unchanged. But neither the quantity nor the affinity of beta-AR binding to 125I-Pindolol was significantly altered. In addition, the spontaneously beating rate of isolated right atria from tail-suspended animals showed little change in sensitivity and reactivity to the stimulations of graded phenylephrine (alpha-agonist, measured in the presence of beta-antagonist propranolol) and isoproterenol (beta-agonist), compared with the control rats. There were also no obvious differences of the effects of the isoproterenol on the contractility of isolated left ventricular papillary muscles between the two groups. Since myocardial alpha 1-AR mediated-effects include production of cardiac hypertrophy and enhancement of myocardial glucose uptake and glycolysis, the down-regulation of the alpha 1-AR may be a contributor to the cardiac cellular accumulation and the myocardial degradation changes as found in our tail-suspended rats. The data from this study also suggest that the myocardial beta-adrenoceptors are not affected by the prolonged tail-suspension.     

Regional heterogeneity of myocardial blood flow within the rabbit left ventricle during haemorrhagic hypotension.

Several studies have reported an extensive regional heterogeneity in myocardial blood flow. The reported coefficients of variation for regional myocardial perfusion range from about 0.2 to 0.4 in normotensive animals. The spatial distribution of myocardial perfusion during haemorrhagic hypotension seems not to have been assessed. The goal of the present study was to determine the regional heterogeneity in myocardial blood flow within the rabbit left ventricle during normal conditions and after haemorrhagic hypotension. Radioactive microspheres were infused into the left ventricle in barbiturate anaesthetized rabbits over either 30 or 120 sec. The haemorrhagic hypotension was induced by bleeding, so that mean arterial blood pressure was reduced to about 50% of control. The left ventricles were divided into samples of about 0.025 g each. Regional heterogeneity in the blood flow was expressed as the coefficient of variation corrected for the Poisson distribution of microspheres (CVc). The CVc was 0.37 +/- 0.09 (mean +/- SD) during control and 0.41 +/- 0.11 after bleeding, the CVc obtained after bleeding being somewhat higher than during control (P < 0.05). We obtained a high correlation coefficient (tau about 0.68) between regional perfusion values at control and after bleeding which indicates a stable perfusion pattern within the myocardium. We conclude that the regional distribution of coronary blood flow within the left ventricle is markedly heterogenous during control condition and that this pattern is not changed during haemorrhagic hypotension.     

Nuclear translocation of calpain-2 regulates propensity toward apoptosis in cardiomyocytes of tail-suspended rats

The compensatory increase in catecholamine release does not reverse orthostatic intolerance after returning from a long-term spaceflight, but it is unclear whether high dose of catecholamine induces cardiac damage. The tail-suspended rat model was used to simulate the effects of weightlessness on the heart. Apoptotic rates in the left ventricular myocardium did not increase in 4-week of tail-suspended rats compared with the synchronous control. On the contrary, isoproterenol (intraperitoneal injection) and 1-day recovery from the 4-week tail-suspension increased apoptotic rates in the myocardium. Propranolol and PD150606 inhibited cardiomyocyte apoptosis in the recovery group. PD150606 and calpain-2 knockdown also blocked isoproterenol-induced cardiomyocyte apoptosis in tail-suspended rats. The activity and nuclear translocation of calpain-2 increased, but the expression of calpain-1, calpain-2, and calpastatin was unchanged in the myocardium of tail-suspended rats. The Ser-16-phosphorylated phospholamban of the nuclear envelope was higher in tail-suspended rats than in the control rats under isoproterenol stimulation. Isoproterenol treatment also induced a large intranuclear Ca(2+) transient of cardiomyocytes in tail-suspended rats. These results suggest that high-dose isoproterenol phosphorylates phospholamban of the nuclear envelope and increases intranuclear Ca(2+) transient. Larger intranuclear Ca(2+) further activates nuclear calpain-2 and hence induces cardiomyocyte apoptosis.     

心钠素前体分子内调控对心肌Na^＋—K^＋—ATP酶的作用

目的：研究利钾尿肽及心钠素前体分子内调控作用对心肌Ｎａ＋Ｋ＋ＡＴＰ酶的作用。方法：将大鼠心肌匀浆后,分别加入利钾尿肽、心钠素以及利钾尿肽＋心钠素,用比色法测定Ｎａ＋Ｋ＋ＡＴＰ酶活性。将大鼠心脏悬挂于Ｌａｎｇｅｎｄｏｒｆ灌流装置,分别以利钾尿肽、心钠素、利钾尿肽＋心钠素为灌流液,灌注心脏,用四道生理仪观测左心室内压、左心室收缩最大速率,左心室舒张最大速率,心率及冠脉流量。结果：心钠素虽然对Ｎａ＋Ｋ＋ＡＴＰ酶有抑制作用（抑制率２６．２％）,但是,与对照无显著性差异（Ｐ＞０．０５）。利钾尿肽显著抑制酶的活性（抑制率４６．５％,Ｐ＜０．０１）这种抑制作用可被心钠素抵消（抑制率１７．６％,Ｐ＞０．０５）。利钾尿肽可以增加左心室收缩和舒张最大速率以及左室内压,而这种强心作用可因心钠素的加入而消失或减弱。结论：利钾尿肽可以抑制心肌Ｎａ＋Ｋ＋ＡＴＰ酶的活性,产生强心作用,心钠素可以抵消以上作用。     

模拟失重降低大鼠心肌细胞对异丙肾上腺素的反应性

本文旨在研究模拟失重对大鼠单个心肌细胞无负荷收缩功能的影响以及对异丙肾上腺素(isoproterenol,ISO)反应性的变化.采用人鼠尾部悬吊法在地面模拟失重状态,4周后以胶原酶I消化分离心肌细胞,分别对左、右两心室心肌细胞进行收缩功能测量.结果显示,悬吊4周大鼠(悬吊组)左,右心室心肌细胞的长度和宽度与正常大鼠(对照组)相比均无显著差异.随刺激频率增加,对照组与悬吊组大鼠心肌细胞缩短幅值均逐步增加.在1.0、2.0与4.0 Hz刺激下,对照组大鼠左心室心肌细胞缩短幅值分别为(8.50±1.26)%、(9.00±1.38)%与(9.23±1.83)%,右心室心肌细胞缩短幅值分别为(9.80±2.48)%、(10.03±2.48)%与(10.28±2.27)%;与对照组大鼠相比,在1.0与2.0Hz刺激下,悬吊组大鼠左心室心肌细胞无负荷缩短幅值分别降低12.2%、10.9%(P《0.05),右心室则分别降低16.5%、16.3%(P《0.05);但是在4.0 Hz刺激下却无显著性改变.与同一频率刺激下的对照组大鼠相比,悬吊组大鼠左、右心室心肌细胞达到缩短峰值的时程(time to peak shortening,TPS)明显缩短(P《0.05);而从缩短峰值至75%舒张的时程(TR75)则明显延长(P《0.05).在各刺激频率下,悬吊组大鼠左、右心室心肌细胞缩短(+dL/dtmax)与舒张(-dL/dtmax)速度均未发生明显改变.用1、5、10 nmol/L ISO灌流达稳态水平后,对照组大鼠心肌细胞缩短幅值分别增加了(10.63±0.83)%、(35.06±5.22)%和(71.64±6.83)%;而悬吊组大鼠心肌细胞缩短幅值仅增加(5.75±0.76)%、(23.97±4.50)%和(26.38±8.13)%,均有显著性差异(P《0.05,P《0.01).用10、50、100 nmol/L forskolin 灌流达稳定水平后,对照组大鼠心肌细胞缩短幅值分别增加了(3.04±0.27)%、(9.81±2.66)%、(20.20±3.47)%;而悬吊组大鼠心肌细胞缩短幅值仅增加了(1.42±0.53)%、(3.83±1.71)%、(5.49±4.08)%,均有显著性差异(P《0.05).以上结果表明,模拟失重4周降低人鼠心肌细胞无负荷缩短幅值以及对ISO的反应性.     

BM 13.505, a selective thromboxane receptor antagonist, reduces myocardial infarct size following coronary artery reperfusion

This study was designed to assess the effectiveness of the thromboxane receptor antagonist, BM 13.505, in limiting myocardial infarct size in rats subjected to 30 min of coronary artery occlusion followed by reperfusion for 5.5 hr (MI/R). Myocardial infarct size was determined histochemically with triphenyltetrazolium chloride staining of the left ventricle. BM 13.505 (30 mg/kg, i.p.) was administered 1 min prior to coronary artery occlusion. In MI/R-vehicle treated animals, myocardial infarct size was 39 +/- 6% of the left ventricle. In MI/R-BM 13.505 treated animals, reperfusion injury was reduced by 50% to 19 +/- 7% of the left ventricle (p less than 0.05, compared to the MI/R-vehicle group). There were no significant differences in mean arterial blood pressure, heart rate, platelet count or white blood cell count between the treatment groups. Incubation of cultured L929 cells with the thromboxane/endoperoxide mimetic U 46619 produced a cytolytic effect, with an EC50 value of 125 microM. Addition of BM 13.505 at concentrations up to 30 microM did not protect against the cytolytic effect of U 46619, suggesting a non-receptor-mediated mechanism. These data indicate that hemodynamic, hematologic or cytoprotective factors do not explain the cardioprotective effects of BM 13.505. These results provide further evidence that antagonism of thromboxane receptors is beneficial in myocardial ischemia/reperfusion injury.     

Effects of coronary sinus pressure elevation on coronary blood flow distribution in dogs with normal preload

Coronary sinus pressure (Pcs) elevation shifts the diastolic coronary pressure-flow relation (PFR) of the entire left ventricular myocardium to a higher pressure intercept. This finding suggests that Pcs is one determinant of zero-flow pressure (Pzf) and challenges the existence of a vascular waterfall mechanism in the coronary circulation. To determine whether coronary sinus or tissue pressure is the effective coronary back pressure in different layers of the left ventricular myocardium, the effect of increasing Pcs was studied while left ventricular preload was low. PFRs were determined experimentally by graded constriction of the circumflex coronary artery while measuring flow using a flowmeter. Transmural myocardial blood flow distribution was studied (15-micron radioactive spheres) at steady state, during maximal coronary artery vasodilatation at three points on the linear portion of the circumflex PFR both at low and high diastolic Pcs (7 +/- 3 vs. 22 +/- 5 mmHg; p less than 0.0001) (1 mmHg = 133.322 Pa). In the uninstrumented anterior wall the blood flow measurements were obtained in triplicate at the two Pcs levels. From low to high Pcs, mean aortic (98 +/- 23 mmHg) and left atrial (5 +/- 3 mmHg) pressure, percent diastolic time (49 +/- 7%), percent left ventricular wall thickening (32 +/- 4%), and percent myocardial lactate extraction (15 +/- 12%) were not significantly changed. Increasing Pcs did not alter the slope of the PFR; however, the Pzf increased in the subepicardial layer (p less than 0.0001), whereas in the subendocardial layer Pzf did not change significantly. Similar slopes and Pzf were observed for the PFR of both total myocardial mass and subepicardial region at low and high Pcs. Subendocardial:subepicardial blood flow ratios increased for each set of measurements when Pcs was elevated (p less than 0.0001), owing to a reduction of subepicardial blood flow; however, subendocardial blood flow remained unchanged, while starting in the subepicardium toward midmyocardium blood flow decreased at high Pcs. This pattern was similar for the uninstrumented anterior wall as well as in the posterior wall. Thus as Pcs increases it becomes the effective coronary back pressure with decreasing magnitude from the subepicardium toward the subendocardium of the left ventricle. Assuming that elevating Pcs results in transmural elevation in coronary venous pressure, these findings support the hypothesis of a differential intramyocardial waterfall mechanism with greater subendo- than subepi-cardial tissue pressure.     

Effect of ethanol on myocardial infarct size in a canine model of coronary artery occlusion-reperfusion

This study was conducted to determine if elevated blood alcohol prior to acute coronary artery occlusion affects myocardial infarct size in an in vivo canine model. Seven pentobarbital anesthetized open-chest dogs received 10 min Iv infusion of ethanol (0.08 g/kg/min). Ten min after ethanol, the left anterior descending coronary artery (LAD) was occluded distal to its first major branch for 60 min. The LAD was then reperfused for 5 h. Following electrically induced ventricular fibrillation, the area at risk of infarction was delineated with dye. The area of infarction was identified by staining with triphenyl tetrazolium chloride. Eleven untreated control experiments were also conducted. Mean blood ethanol concentration was 155 ± 26 mg/dl just prior to LAD occlusion and 47 ± 3 mg/dl after 4 h reperfusion. Ethanol infusion had no effect on systemic hemodynamic variables during ischemia. In ethanol treated animals, the area at risk was 19.7 ± 3.0% of the left ventricle, and the infarct size was 20.9 ± 4.8% of the area at risk. In control experiments, the area at risk was 23.0 ± 4.1% of the left ventricle (p > 0.05), and the infarct size was 21.6 ± 3.8% of the area at risk (p > 0.05). Collateral blood flow to ischemic region did not differ between the two groups, and the relationships between infarct size and collateral flow were similar for control and untreated hearts. Acute ethanol exposure prior to coronary artery occlusion and subsequent reperfusion does not affect myocardial infarct size in the heart of the anesthetized dog.     

Evidence against significant resting alpha-adrenergic coronary vasoconstrictor tone

The importance of sympathetically mediated coronary vasoconstrictor tone as a determinant of resting coronary blood flow was assessed in the conscious dog by comparing blood flow and oxygen extraction in a normally innervated (I) and a previously sympathectomized (Sx) region of the same left ventricle. The regional ventricular sympathectomy was achieved by the topical application of phenol. The animals were well acclimated to the laboratory environment before regional myocardial blood flow was measured with microspheres or regional myocardial oxygen extraction was determined on blood sampled from chronically implanted coronary venous catheters. Results indicated that blood flow and oxygen extraction were not significantly different in I and Sx regions under these conditions. Regional blood flow data obtained after beta-adrenergic blockade or combined alpha- and beta-adrenergic blockade were not significantly different from control data. Thus we were unable to confirm previous evidence in the literature of significant resting sympathetic coronary vasoconstrictor tone in the conscious animal.     

Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied. Reducing left ventricle pressures and volumes increased heart rate. Rate-pressure product, diastolic coronary pressure, myocardial O2 consumption, total, subendocardial and subepicardial flow decreased. Hematocrit and blood gas data were unchanged. The pressure-flow relationships were shifted leftward (p = 0.001) but the range of autoregulation was not altered. At low left ventricle pressures and volumes, the lower coronary artery pressure limit was shifted leftward (from 75 to 45 mm Hg (1 mm Hg = 133.3 Pa)), while total, subendocardial, and subepicardial blood flow did not change compared with the control. Below the lower coronary artery pressure limit, subendocardial but not subepicardial flow decreased, resulting in maldistribution of flow across the left ventricular wall. When coronary pressure was reset between control and the lower coronary artery pressure limit, subendocardial flow was restored. These results show that the lower coronary artery pressure limit can be shifted leftward while the distribution of blood flow across the left ventricular wall is preserved.