Reduction in ventricular arrhythmias following acute coronary artery ligation in the dog after the administration of creatine phosphate

Summary The infusion of creatine phosphate into the left ventricle of dogs markedly reduced the number of ventricular ectopic beats which normally result from acute coronary ligation. This dose of creatine phosphate (100 mg/kg) had no significant effect on resting haemodynamics or on myocardial metabolism.     

Novel vascular effects of Isoprenaline following pacing-induced heart failure in the dog

Isoprenaline produced concentration-dependent contractions of the in vitro canine saphenous vein which were attenuated by phentolamine (10(-6) M) and pacing-induced heart failure. Both at control and peak heart failure, a biphasic response was seen in the dorsal pedal artery, consisting of an initial relaxation followed by a contraction; phentolamine and heart failure enhanced the relaxation component. In the presence of propranolol, the isoprenaline-induced contraction was sensitive to yohimbine, but resistant to prazosin. Therefore it is concluded that isoprenaline interacts not only with vascular beta-adrenoceptors, but also with alpha 2-adrenoceptors. Endothelial denudation resulted in a diminished response to isoprenaline in control saphenous vein and dorsal pedal artery but not in vessels from dogs with heart failure. The observation that the contractile response to isoprenaline diminishes in heart failure implies a specific down-regulation of peripheral vascular alpha 2-adrenoceptors.     

Effect of sotalol on ischemic myocardial pH in the dog heart

Summary In dogs anesthetized with pentobarbital, the left anterior descending coronary artery (LAD) was occluded partially so that the LAD flow could be reduced to 1/2 to 1/3 the original flow (partial occlusion). Myocardial pH was recorded continuously by the use of a micro glass pH electrode inserted in the area to become ischemic by partial occlusion. Before partial occlusion, myocardial pH was 7.51–7.66. Partial occlusion reduced the pH by 0.63–0.72.Sotalol (5 mg·kg^–1, i.v.) increased the pH (by 0.45) that had been reduced by partial occlusion, with a marked decrease in heart rate (about 70 beats·min^–1) and a slight decrease in blood pressure (about 10 mm Hg in systolic pressure). Even when the sotalol-induced decrease in heart rate was prevented by pacing the heart, sotalol (5 mg·kg^–1, i.v.) increased the pH (by 0.43) of myocardium in which LAD was partially occluded. The pH of the non-ischemic normal heart, however, was not influenced by the injection of sotalol (5 mg·kg^–1, i.v.)It is concluded that the effect of sotalol to increase the pH of the ischemic heart is not related to the decrease in heart rate produced by the drug injection.     

灯盏细辛与丹参配伍治疗实验犬冠心病

目的观察灯盏细辛提取物与丹参提取物配伍使用治疗犬冠心病的作用特点。方法设计犬冠状动脉结扎法所致犬心肌缺血模型试验,以确证灯盏细辛和丹参配伍使用后的确切疗效。结果灯盏细辛与丹参配伍能明显降低模型犬血清LDH和CK的含量和活力,减小心肌梗死范围,降低心率、ST段抬高、LVEDP和MVO2,增加CO,升高模型犬LV dp/dt、LV-dp/dt和LVSP,且合用组在作用强度和作用时间上均优于单用两组。结论灯盏细辛与丹参配伍使用在左冠状动脉前降支(LAD)结扎所致犬冠心病模型试验中,在改善模型动物酶学、形态学和心脏血流动力学各指标上作用确切,且配伍使用效果更佳。     

康欣胶囊对结扎冠状动脉犬心肌缺血的影响

目的：观察康欣胶囊对结扎冠状动脉犬心肌缺血的影响。方法：结扎冠状动脉造成犬急性心肌缺血损伤模型，以丹参滴丸为对照，观察康欣胶囊对心电图、向宁蛋白Ⅰ、心肌酶谱、心肌梗死面积和室性心律失常的发生率等指标的影响。结果：康欣胶囊可改善缺血性心电图改变，减少缺血所致的向宁蛋白Ⅰ、CK-MB、CK的释放，缩小心肌梗死面积，减少缺血引起的室性心律失常的发生率。结论：康欣胶囊具有很好的抗结扎冠状动脉犬心肌缺血的作用。     

Effect of nipradilol on myocardial energy metabolism in the dog ischaemic heart

The effect of nipradilol, a newly developed beta-adrenoceptor blocking agent with a vasodilatory action, on myocardial energy metabolism has been examined in the dog ischaemic heart, and compared with that of propranolol. Ischaemia was induced by ligating the left anterior descending coronary artery. Either saline, nipradilol (0.3 mg kg-1), or propranolol (1 mg kg-1) was injected intravenously 5 min before coronary ligation. After 3 or 30 min of coronary ligation, the ischaemic region of the myocardium was removed, and the endocardial portion used to determine the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), creatine phosphate (CrP) and lactate. Ischaemia decreased the levels of ATP and CrP, and increased the levels of ADP, AMP and lactate. Immediately after the injection of nipradilol, rapid falls in blood pressure and heart rate were observed. Pretreatment with nipradilol lessened the decreases in the levels of ATP and CrP and the increases in the levels of AMP and lactate, caused by 3 min of ischaemia, to the same extent as propranolol. However, after 30 min of ischaemia, nipradilol had no effect on myocardial metabolism unlike propranolol. These results indicate that nipradilol can reduce ischaemic influences on myocardial metabolism as well as propranolol, but only in the early stages of ischaemia.     

Cardiovascular effects of acebutolol following coronary artery occlusion and reperfusion in anaesthetized dog.

1 The effects of 5 mg/kg acebutolol given intravenously were investigated in anaesthetized dogs after (a) ligation of the left anterior descending coronary artery and (b) coronary reperfusion following 60 min of ligation of the anterior descending coronary artery. 2 Coronary artery ligation produced, after 4 to 6 h, persistent multiple ventricular ectopic beats and abnormalities of R and T waves and of the S-T segment. Administration of acebutolol, after the development of persistent ventricular arrhythmias, restored normal sinus rhythm within 5 min of injection. Electrocardiographic abnormalities were also reduced. 3 Coronary artery reperfusion (following 60 min of ligation) resulted in multiple ventricular ectopic beats, ventricular tachycardia and/or ventricular fibrillation. Pretreatment with acebutolol, 15 min before starting reperfusion, markedly reduced the arrhythmias. 4 Acebutolol did not affect peak inspiratory airway pressure. 5 Acebutolol produced significant bradycardia and slight, transient, hypotension. It was without effect on left ventricular systolic pressure, left ventricular end-diastolic pressure, cardiac output or pulmonary arterial pressure. 6 These results suggest beneficial effects of acebutolol in myocardial ischaemia and coronary reperfusion, without any significant risk of cardiodepression or bronchospasm.     

Ageing blunts the effects of nitric oxide on myocardial O2 consumption

1. In the present study, we tested the hypothesis that the negative myocardial metabolic effects of nitric oxide (NO) were reduced in old hearts. 2. Studies were conducted in 17 young (approximately 6 months) and 18 old (> 36 months) New Zealand anaesthetized open-chest rabbits. Either vehicle or s-nitroso-N-acetylpenicillamine (SNAP; 10-4 mol/L; a NO donor) was applied to the epicardial surface of the left ventricle. Coronary blood flow (microspheres) and artero-venous (a-v) O2 difference (microspectrophotometry) were used to determine subepicardial (EPI) and subendocardial (ENDO) O2 consumption. Wall thickening was determined ultrasonically. Cyclic GMP and guanylyl cyclase activity were also determined. Myocardial a-v O2 difference, flow, O2 consumption and wall thickening were comparable in young and old hearts. 3. The EPI and ENDO O2 consumption of SNAP-treated young hearts decreased significantly (> 25%) compared with vehicle (saline). However, SNAP had no significant effects on the O2 consumption of old hearts. In addition, SNAP decreased the percentage wall thickening in young (from 18.0 +/- 1.7 to 13.4 +/- 1.6%), but not old (from 14.5 +/- 0.9 to 11.4 +/- 1.6%), hearts. Basal cGMP levels in old hearts were greater (approximately 70%) than those in young hearts (15.7 +/- 2.0 vs 9.0 +/- 0.8 pmol/g, EPI). s-Nitroso-N-acetylpenicillamine increased cGMP in EPI (13.7 +/- 1.8 pmol/g) and ENDO of young, but not old (18.7 +/- 2.3 pmol/g, EPI), hearts. Similar results were also obtained using another NO donor, namely sodium nitroprusside (SNP; 10-4 mol/L). Guanylyl cyclase activity was elevated in old rabbit hearts with 0.5 mmol/L SNP (131 +/- 12 vs 80 +/- 12 pmol/min per mg protein for old and young rabbits, respectively). 4. Thus, while older hearts had similar O2 consumption and wall thickening compared with young hearts, they responded less well to NO and had significantly elevated basal levels of myocardial cGMP.     

丹皮酚对麻醉犬冠脉结扎致心肌梗死的保护作用

目的观察丹皮酚对冠脉结扎致实验性心肌梗死犬的影响。方法结扎犬左冠状动脉前降支造成急性心肌梗死模型,观察丹皮酚对心肌梗死面积、梗死程度、磷酸肌酸激酶同工酶及超氧化物歧化酶(SOD)、丙二醛(MDA)的影响。结果丹皮酚能够明显减小心肌梗死面积、降低心肌梗死程度、减少心肌酶的释放,同时可以提高血清中SOD的活力,增强清除自由基能力,降低血清中MDA的含量,减轻脂质过氧化损伤的程度。结论丹皮酚具有明显的抗心肌缺血作用,其作用机制可能是通过稳定细胞膜,抑制缺血心肌的膜损伤,增加自由基清除,降低脂质过氧化等发挥作用。     

The effect of heart rate on indices of myocardial contractility in the dog

1. Changes in heart rate were evoked by atrial pacing in anaesthetized dogs with no pretreatment and in dogs given reserpine or guanethidine for 72 h. The effect of alterations in heart rate were related to two indices of myocardial contractility: the maximal rate of change of left ventricular pressure (dp/dt), and an index which was independent of initial fibre length (dp/dt)/IIT, where IIT is integrated isometric tension. 2. An increase in heart rate in control dogs was accompanied by a rise in both dp/dt and (dp/dt)/IIT confirming that the Bowditch staircase does exist in the intact ventricle. The regression line relating heart rate to (dp/dt)/IIT was significantly steeper than that relating heart rate to dp/dt because the reduction in left ventricular preload at high heart rate tends to attenuate the rise in dp/dt. 3. Reserpine, but not guanethidine pretreatment was accompanied by either a slight decrease or no change in (dp/dt)/IIT during pacing. 4. Acute elevation of (dp/dt)/IIT by either calcium or isoprenaline infusion in reserpine pretreated dogs did not restore the Bowditch effect. 5. Acute depression of (dp/dt)/IIT by propranolol and pentobarbitone was accompanied by a greater rise in (dp/dt)/IIT with pacing in control dogs and a rise rather than a fall in reserpine-pretreated dogs.     

Effects of an increase in haemoglobin O2 affinity produced by BW12C on myocardial function in the erythrocyte-perfused rabbit heart in vitro and myocardial infarct size in the dog.

The effects of BW12C on myocardial function in the erythrocyte-perfused rabbit heart and on myocardial infarct size in the anaesthetized dog have been evaluated. Perfusion of rabbit hearts with erythrocytes pretreated with BW12C (10(-3) M-4 X 10(-3) M) produced concentration-dependent decreases in left ventricular pressure (LVP), LVP dP/dt and coronary perfusion pressure. A concomitant decrease in PO2 and an increase in lactate production by the myocardium was also observed. Perfusion of rabbit hearts with Krebs Henseleit buffer containing BW12C (10(-5)-10(-4) M) caused no change in measured variables. Although BW12C (10(-3) M) caused a small decrease in LVP, coronary perfusion pressure and heart rate, these changes were not significant. In anaesthetized dogs, an infusion of BW12C (total dose 50 mg kg-1, i.v.) caused small, but significant, changes in haemodynamic status. The oxygen saturation curve was shifted to the left and relative % oxygenation (P20) was shifted to the left throughout the course of the experiment. (P20, control 16.3 +/- 0.4 mmHg; after BW12C 7.9 +/- 1.4 mmHg). Pretreatment with BW12C (total dose 50 mg kg-1) caused no change in area at risk but significantly increased the myocardial infarct size by 410%. These studies with BW12C demonstrate that alteration in haemoglobin-oxygen affinity can induce adaptive physiological changes in tissue function and metabolism and can assume a critical role when oxygen supply may be impaired due to a flow-limiting stenosis.     

丹参饮对冠脉结扎大鼠心肌缺血的保护研究

目的评价丹参饮对冠脉结扎大鼠心肌缺血的保护作用,并探讨其作用机制。方法雄性Wistar大鼠按体质量随机分为对照组、模型组、硝苯地平组、复方丹参片组和丹参饮低、中、高剂量组,每组各10只。硝苯地平剂量为0.167 mg/kg、复方丹参片剂量为10 g/kg,按10 m L/kg ig给药;丹参饮按0.5、1.0、2.0 m L/kg(相当于原药材0.27、0.54、1.08 g/kg)ig给药。各组动物均连续给药7 d。于第7天给药30 min后通过结扎冠脉建立大鼠心肌缺血模型。分别记录正常和结扎后心电图S-T段变化,测定血清乳酸脱氢酶(LDH)、肌酸激酶(CK)活性,计算心脏指数、左心室指数、左心室/心脏质量比和心肌梗死率。结果与模型组各时间点比较,丹参饮组在结扎后15~180 min心电图S-T段均明显降低,差异具有统计学意义(P0.05)。与模型组比较,各组LDH、CK活性均明显降低,差异具有统计学意义(P0.05);各组大鼠心脏指数、左心室指数、左心室/心脏质量比均明显降低,差异具有统计学意义(P0.05);各组心肌梗死质量和梗死率均明显降低,差异具有统计学意义(P0.05)。结论丹参饮对冠脉结扎大鼠心肌缺血具有保护作用,可能是增强冠脉供血和心肌代谢,改善心功能,有效抑制大鼠心肌缺血梗死。     

Hypotensive effects of N,N-din-n-propylodopamine in the anesthetized dog: comparison with sodium nitroprusside

N,N-Din-n-propyldopamine (DPDA), a dopamine (DA) vascular agonist without beta 1-adrenergic activity, was compared with mitroprusside in pentobarbital-anesthetized dogs. DPDA was infused intravenously at 20, 40, and 80 microgram/kg/min. DPDA caused dose-related reductions in mean arterial pressure when infused at 20 and 40 microgram/kg/min; no further decrease occurred at 80 microgram/kg/min. Sodium nitroprusside, 1-6 microgram/kg/min, approximately equaled the hypotension produced by 40 microgram/kg/min of DPDA. DPDA differed from sodium nitroprusside in causing a more rapid fall in mean arterial pressure and a more rapid recovery upon discontinuation. DPDA had no effect on pulmonary arterial pressure, but sodium nitroprusside reduced it. DPDA reduced heart rate; sodium nitroprusside increased heart rate. Hexamethonium. 10 mg/kg, significantly reduced the hypotension produced by DPDA. The DA antagonist, sulpiride, completely eliminated the reduction in blood pressure caused by DPDA. Neither hexamethonium nor sulpiride affected the hypotension produced by sodium nitroprusside. These studies suggest that DPDA reduces blood pressure in part by inhibiting the sympathetic nervous system and in part by vasodilation secondary to action on DA vascular receptors.     

Noradrenaline turnover after left coronary artery ligation in rat heart

The levels and the turnover of noradrenaline were measured in the left and right ventricles following left coronary artery ligation for 2 h in untreated, adrenalectomized or hexamethonium-treated rats. Noradrenaline in the left ventricles was decreased by ligation and unaffected in the right ventricles, whether of untreated, adrenalectomized or hexamethonium-treated animals. Turnover in the left ventricles, as estimated by the decrease of noradrenaline under dopamine beta-hydroxylase inhibition with bis-(4-methyl-1-homo-piperazinyl-thiocarbonyl)-disulfide (FLA-63), was unaffected by ligation whether in untreated, adrenalectomized, or hexamethonium-treated rats. Ligation accelerated turnover in the right ventricles of untreated rats or attenuated it in adrenalectomized rats and caused no changes in hexamethonium-treated rats. These results suggest that noradrenaline turnover in ischemic myocardium is not affected by regional ischemia and that such ischemia might accelerate turnover in the non-ischemic area, probably as a result of increased activity of sympatho-adrenal reflexes.     

Inhibitory effect of trimetazidine on utilization of myocardial glycogen during coronary ligation in dogs

The left anterior descending coronary artery (LAD) of the dog was ligated completely for 1.5 min, and immediately after LAD ligation the heart was taken for determination of the glycogen phosphorylase and glycogen. Trimetazidine was injected intravenously 20 min before LAD ligation. LAD ligation increased the activity of glycogen phosphorylase and decreased the level of glycogen in both ischemic (LAD) and nonischemic (circumflex) areas. Trimetazidine at the dose of 0.3 or 1.0 mg/kg, being the dose that did not affect blood pressure and heart rate markedly, inhibited the ischemia-induced changes in glycogen phosphorylase and glycogen level. It is concluded that trimetazidine inhibits the ischemia-induced increase in the utilization of glycogen in the dog myocardium.     

蝙蝠葛酚性碱对犬冠状动脉结扎形成心肌梗死的保护作用

目的 :研究蝙蝠葛酚性碱 (PAMD)对急性心肌梗死的保护作用。方法 :用麻醉犬冠状动脉结扎造成心肌梗死模型 ,设立PAMD 3 5和 7mg·kg-1两剂量组 ,地奥心血康 (DAXXK) 4 0mg·kg-1阳性对照组 ,伪手术组及模型对照组。观察各组心电图ST段 ,血清LDK和CK ,以及心肌梗死范围的变化。结果 :PAMD 7 0mg·kg-1组30min时 ,在对抗ST段上移及降低LDH活性上优于DAXXK 4 0mg·kg-1组 (P <0 0 1) ,降低CK活性的作用与DAXXK相当 (P >0 0 5 ) ;7 0mg·kg-1PAMD组降低梗死范围与DAXXK 4 0mg·kg-1组作用无显著差异 (P >0 0 5 )。结论 :PAMD对结扎犬冠脉造成急性心肌梗死有保护作用。     

银杏内酯对结扎大鼠冠状动脉致心肌缺血的影响

目的:研究银杏内酯对大鼠心肌缺血的保护作用.方法:大鼠按体重分为7组,分别为银杏内酯10,20,40mg·kg-1组,银杏叶提取物150mg·kg-1组,普萘洛尔5mg·kg-1组,模型组和正常组.采用结扎冠状动脉左前降支造成心肌梗死模型,分别测定手术后各组大鼠的心肌损伤范围(坏死及缺血范围),血清磷酸肌酸激酶(CPK)、乳酸脱氢酶(LDH)活性及心肌组织中丙二醛(MDA)含量.结果:银杏内酯(10,20,40mg·kg-1)能明显减轻心肌损伤,降低心肌缺血大鼠血清中LDH和CPK活力及MDA含量.结论:银杏内酯对结扎大鼠冠状动脉所致心肌缺血损伤具有明显的保护作用.     

Systemic and coronary hemodynamic effects of prostacyclin and nitroprusside in conscious dogs

In order to simulate physiologic conditions and eliminate the influence of anesthesia on the cardiovascular responses to prostacyclin (PGI2) and nitroprusside, hemodynamic parameters were monitored in conscious dogs prior to and during infusion of the two agents at equally hypotensive concentrations. Heart rate was significantly increased with nitroprusside (p less than or equal to 0.05) and decreased with PGI2 (p less than or equal to 0.01), while mean ascending aortic blood flow or cardiac output increased (p less than or equal to 0.05) in response to both PGI2 and nitroprusside, more with nitroprusside than with PGI2 (p less than or equal to 0.05). Stroke volume increased with PGI2 only (p less than or equal to 0.05 vs. control, p less than or equal to 0.05 vs. nitroprusside). Both systemic and coronary (circumflex) vascular resistances decreased more with nitroprusside than with PGI2 (p less than or equal to 0.05); however, characteristic impedance (index of aortic elasticity) decreased similarly with PGI2 and nitroprusside. Circumflex coronary blood flow increased (p less than or equal to 0.05) only with nitroprusside. These results indicate that in conscious dogs (a) nitroprusside causes a greater decrease in vascular (systemic and coronary) resistance compared to PGI2, but the effects of the two vasodilators on arterial distensibility are similar; (b) nitroprusside, but not PGI2, causes a marked increase in coronary blood flow; and (c) the major distinguishing hemodynamic response to these vasodilators relates to marked bradycardia with PGI2 and tachycardia with nitroprusside, which may account for the observed differences in aortic blood flow and stroke volume.