The correlation of changes in the volumetric rate of coronary blcod flow and cardiac oxygen consumption under the influence of adrenaline,noradrenaline, ephedrine,and phenamine

Summary Investigations were carried out on anesthetized cats. The blood outflow volume velocity from the coronary sinus was registered. Simultaneously a photometric recording was made of the cardiac oxygen intake. As shown, adrenaline and noradrenaline caused a marked but brief increase of the coronary blood flow velocity. The effect of ephedrine and phenamine (benzedrine) on the cardiac blood supply was less pronounced than that of adrenaline and noradrenaline but more lasting. The rise of the coronary blood flow volume velocity under the effect of the substances investigated parallels the intensified oxygen absorption by the heart. A rise of cardiac loading under the effect of phenylalkylamines is not completely attributable to the increased oxygen absorption by the heart.(Presented by Active Member, AMS, USSR, V. V. Zakusov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 52, No. 10, pp. 67–71, October, 1961.     

The effect of adrenalin,ephedrine, and amphetamine on the tone of the coronary vessels and the oxygen absorption of the myocardium in the heart isolated by the langendorf principle

Summary Experiments were carried out on cat hearts, isolated after Langendorf and perfused with Ringer-Locke solution. Cardiac oxygen uptake was determined by the difference in the oxygen content in the fluid flowing in and out of the heart, measured polarographically, as well as by estimating, the volume velocity of the coronary outflow. As established, adrenalin, ephedrine and amphetamine caused a marked rise of the cardiac oxygen uptake. The volume velocity of the fluid outflow from the coronary blood vessels increassed to a lesser degree than the cardiac oxygen uptake. Notwithstanding the rise of the oxygen uptake by the heart after use of adrenalin there was at times a reduction of the volume velocity of the coronary outflow. It is assumed that in using adrenalin there occurs a clash between two of its antagonistic effects on the coronary vessels: of an indirect one (due to the change of metabolism) — the vasodilating, and a direct one—the vasoconstricting. Usually dilation of the coronary vessels prevails, but sometimes there occurs a vasoconstricting reaction.There is no precise conformity between the rise of frequency and strength of myocardial contractions, on the one hand, and the rise of the cardiac oxygen uptake under the effect of adrenalin, ephedrine and amphetamine, on the other hand.Presented by Active Member AMN SSSR V. V. Zakusov Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 55, No. 2, pp. 68–72, February, 1963     

A method of measuring the minute volume of the heart

Summary A method of measuring the minute heart volume requiring no special instruments is presented. The minute volume is determined by direct measurement of the blood flow volume velocity in the pulmonary artery. A special device for the periodical determination of the blood flow volume velocity is described.Presented by Active Member AMN SSSR V. V. Zakusov     

The effect of some ganglion-blocking substances on the coronary circulation

Summary Acute experiments were performed on cats. The study of the effect of ganglioblockers (tetrammonium, hexonium, pentamine and mecamine) on the blood flow from the coronary sinus was carried out.The effect of these substances on the coronary circulation is variable and depends on the initial conditions of the blood supply of the heart.Tetrammonium in the dose of 2–10 mg per kg of body weight increases the blood flow from the coronary sinus by 10–40%. Hexonium (2–5 mg per kilogram) increases the blood flow from the coronary sinus by 25–40% in case of the average and low, initial values of the volume of the blood flow per minute. Hexonium in the above dose causes decrease of the volume velocity of the coronary blood flow by 20–40% in animals with intensive myocardial blood supply.In majority of cases pentamine in the dose of 2–5 mg per kilogram of body weight and mecamine in the dose of 0.5–2 mg per kilogram cause decreased blood flow from the coronary sinus.Submitted by Active Member AMS USSR V. V. Zakusov     

The effect of paraverine and dibazol on the rate of the coronary circulation

Summary The effect of papaverine and dibazol on the coronary blood flow was studied in short-term experiments on cats, anesthetized with nembutal in condition of artificial respiration. A method which allowed determination of the volume velocity of blood outflow from the coronary sinus was employed. Papaverine provokes a pronounced increase of the coronary blood flow. Dibazol on the other hand, causes only insignificant and temporary increase. When paraverine was administered after dibazol its effect on the coronary blood vessels was enhanced. Thus, combined administration of papaverine and dibazol reinforces their effect.Presented by Active Member Acad. Med. Sci. USSR, V. V. ZakusovDibazol is 2-benzyl-benzimidazol hydrochloride — Publisher's note.     

Effect of CO2 on the systemic and coronary circulations and on coronary sinus blood gas tensions.

The responses to hypocapnia and to hypercapnia of both the systemic and the coronary circulations have been studied in the dog during intermittent positive pressure ventilation under halothane anaesthesia. In the absence of significant variations of myocardial contractility, the reduction of cardiac output, because of hypocapnia, was determined by the increase of systemic vascular resistance, while the increase of cardiac output because of hypercapnia was determined by an increase of heart rate without change of stroke volume. The alterations of coronary blood flow (reduction following hypocapnia, augmentation following hypercapnia) were considerably larger than the changes of cardiac output and of myocardial oxygen consumption. Such disparity between oxygen supply and demand, together with the effect of pH and PCO2 on the oxyhaemoglobin dissociation curve led to a marked reduction of coronary sinus PO2 in response to hypocapnia and a marked increase of coronary sinus PO2 in response to hypercapnia. The data suggests that PCO2 (or respiratory alterations of pH) may have a direct effect on the regulation of coronary blood flow. The low coronary sinus PO2 observed at hypocapnia may suggest the risk of myocardial ischaemia.     

The effect of analgesics on the coronary circulation

Summary The author studied the effect of analgesics (morphine, thecodin, phenadon and promedol) on the blood output from the coronary sinus and the tone of the coronary blood vessels in cats. Of the analgesics mentioned only morphine increases the cardiac blood supply. In the majority of cases the introduction of promedol and phenadon leads to a decrease of the volume velocity of the coronary blood flow, increasing the tone of coronary vessels. Thecodin exerts no material effect on the coronary circulation.Presented by Active Member AMN SSSR V. V. Zakusov     

The mechanism of papaverine's effect on the coronary circulation

Summary Experiments were carried out on anesthetized cats (urethane with chloralose). A preparation of isolated heart in situ was used. The conronary arteries of the recipient cat were perfused with the blood of the donor. For this purpose two types of pumps were used: with a constant perfusion volume and with a constant perfusion pressure. The absorption of oxygen by the heart was measured simultaneously, by the photometric method. The direct vasodilative effect of papaverine on the coronary vessels is not the main reason for increased volumetric rate of the coronary circulation provoked by papaverine. The main cause of this effect is augmented oxygen absorption by the heart under the influence of papaverine.(Presented by AMN SSSR Active Member V. V. Zakusov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 53, No. 1, pp. 69–73, January, 1962     

Effect of cardiac glucosides on the coronary circulation and the oxygen absorption by the heart in experimental myocardial infarction

Summary A study was made of the effect produced by strophanthin, erysimin and digitoxin on the coronary circulation, cardiac oxygen absorption, ECG and toxicity in experimental myocardial infarction. Cardiac glucosides, given in therapeutic doses (0.05–0.1 c.u./kg), in conditions of coronary insufficiency induced by ligation of the left descending coronary artery, increased the volume velocity of the coronary circulations and cardiac oxygen absorption, normalized the EEG and possessed an anti-arrhythmic action. Erysmin and digitoxin produced a more marked effect on the coronary circulation than strophanthin. The toxicity of cardiac glucosides increased considerably in experimental myocardial infarction; during the action of these preparations the transmission of excitation from the vagus nerves to the cardiac muscle is facilitated.(Presented by Active Member AMN SSSR V. V. Zakusov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 56, No. 10, pp. 57–62, October, 1963     

Cardiac responses to snout immersion in trained dogs

1. Four dogs were trained to immerse their snout voluntarily for durations up to 30 sec. Indwelling instrumentation was implanted to measure blood flow velocity in the circumflex branch of the left coronary artery, to sample blood from the left atrium and coronary sinus for the determination of P(O2), P(CO2), pH, oxygen saturation and haemoglobin concentration, and to pace the heart. An index of myocardial oxygen consumption was calculated by multiplying the mean flow velocity by the arteriovenous difference in oxygen content.2. Mean coronary flow velocity decreased significantly during simulated diving by 26 +/- 27% (+/- S.D.). The range of decrease in seventeen out of twenty experiments was from -5 to -81%. Heart rate decreased by 48 +/- 7% and this bradycardia was abolished by I.V. atropine.3. Coronary sinus oxygen saturation increased significantly with snout immersion (three dogs) and arteriovenous difference decreased from 67 +/- 10 to 47 +/- 5%. The index of myocardial oxygen consumption decreased by 42 +/- 19%. This decrease was attenuated slightly by beta-blockade but was abolished by cardiac pacing in three out of four experiments.4. The present study indicates that the heart consumes oxygen at a considerably reduced rate during simulated diving and therefore plays a direct role in the overall conservation of oxygen. This response appears to result primarily from a negative chronotropic effect induced by increased vagal tone.     

Mechanisms of verapamil prevention of disorders of cardiac contractile function during ischemia and reperfusion

A dog heart isolated according to Langendorf was used to study the effect of verapamil, used as a preventive measure, on the contractile function of the heart, its work and oxygen consumption, and the coronary blood flow in modelled coronary insufficiency and after restoration of blood supply to the myocardium. The results provide evidence that verapamil prevents significant decrease of the efficacy of myocardial functioning in ischemia, owing to which the heart maintains a higher level of performance under conditions of inadequate blood supply, the development of acidosis is prevented, and reperfusion disorders of cardiac function are removed completely. This effect is mediated to a great measure by maintenance of high economy of heart performance due to verapamil.     

Determinants of regional myocardial oxygen supply in the left ventricle. An experimental study in the in situ working canine heart

The main factors that regulate myocardial oxygen supply include the 1. coronary blood flow controlling the volume flow fraction of red cells, 2. the oxygen carrying capacity of capillary blood dependent on the red cell volume fraction occupying the capillaries, and 3. the density of perfused capillaries affecting the capillary diffusion capacity and the diffusion distance in the tissue. Differences exist between the inner and outer layers of the left ventricle that include differences of systolic and possibly diastolic tissue stresses and oxygen consumption. The highest values were observed in the vicinity of the left ventricular cavity. The regional differences of myocardial oxygenation were studied in anaesthetized open-chest dogs by measuring the myocardial perfusion rate, the microvascular hematocrit, the PS-product of 51Cr-EDTA, and the microvascular blood volume across the left ventricular wall in the heart working in situ. Gradients of blood flow rates were present with the highest flow in deep myocardial layers. Maximally increasing the coronary blood flow at normal perfusion pressure and metabolic load did not change the distribution of blood flow between subendocardial and subepicardial layers. Distal to a coronary stenosis, blood flow was markedly reduced and redistributed away from the subendocardial layers, indicating a relatively severe decrease of fractional red cell flow to the left ventricular myocardium. The microvascular dynamic hematocrit, i.e. the volume fraction of red cells, was evenly distributed across the left ventricular wall, but consistently reduced to 75 per cent of great vessel hematocrit. The maximal increase of coronary blood flow provoked a further reduction of microvascular hematocrit due to a decrease of the red cell volume, possibly by shunt flow of red cells through low resistance vessels of capillary size. At restricted coronary inflow, the microvascular hematocrit was decreased with a redistribution of red cells away from deep myocardial layers. Extern compression of microvessels by the tissue pressure, phase-separation between red cells and plasma at microvascular bifurcations, or decrease of the red cell fluidity may all contribute to this change. Reduction both of microvascular red cell flow fraction and the hematocrit diminishes the red cell flux within capillaries and decreases the ability of blood to deliver oxygen to the tissue, and more so in the subendocardial layers.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of hypercapnia on myocardial blood flow and metabolism

1. In closed-chest dogs anaesthetized with trichlorethylene, the inhalation of carbon dioxide sufficient to increase the arterial P(CO2) from 40 to about 100 mm Hg, increased myocardial blood flow (measured using a (133)Xe clearance technique) and right atrial pressure. There were no consistent changes in mean arterial blood pressure, heart rate or cardiac output.2. The effect of hypercapnia on myocardial blood flow was not influenced by the previous administration of atropine and propranolol or of bretylium. It can be concluded, therefore, that the elevated arterial P(CO2) has a direct vasodilator effect on the myocardial microcirculation.3. During hypercapnia the coronary sinus P(O2) was increased and the coronary arteriovenous oxygen content difference, and calculated myocardial oxygen consumption, reduced. It is suggested that this latter effect may be the result of myocardial depression produced by the decrease in arterial blood pH.4. There was no evidence of myocardial glucose uptake either before or during hypercapnia. The myocardial extraction of lactate and pyruvate at rest varied between 0 and 55%. During acute hypercapnia the extraction of lactate usually fell.5. When the arterial P(CO2) was maintained at 100 mm Hg for a period of 1 hr the effects on myocardial blood flow and on oxygen consumption were not sustained.6. Stepwise increments and decrements in arterial P(CO2) of 10-20 mm Hg produced corresponding increases and decreases in myocardial blood flow and demonstrated that changes in arterial P(CO2) of 20-30 mm Hg can markedly affect blood flow in the myocardium.     

心宁胶囊对犬心脏血流动力学及心肌耗氧量的影响

目的：研究心宁胶囊对麻醉开胸犬心脏血流动力学及心肌耗氧量的影响,探索其对心脏功能的药理作用及作用机制。方法：将20只犬随即分成模型组、阳性药物组、心宁胶囊高、低剂量组,观察麻醉犬冠状动脉血流量、心肌耗氧量和心率等指标的变化。结果：与模型组比较,心宁胶囊具有增加冠脉血流量、降低心肌耗氧量等作用（P〈0.05）。结论：心宁胶囊对犬心脏血流动力学及心肌耗氧量有调整和改善作用。     

Systolic and diastolic changes in human coronary blood flow during Valsalva manoeuvre.

Valsalva manoeuvre is reported to be sometimes successful for the relief of angina pectoris. The present study investigated how haemodynamic changes produced by Valsalva manoeuvre can interact to improve the relationship between cardiac work and coronary blood flow. Ten male subjects aged 53 +/- 12 years (SD) were considered. Blood velocity in the internal mammary artery, previously anastomosed to the left descending coronary artery, was studied with Doppler technique. The subjects performed Valsalva manoeuvres by expiring into a tube connected to a mercury manometer, to develop a pressure of 40 mmHg. The arterial blood pressure curve was continuously monitored with a Finapres device from a finger of the left hand. During expiratory effort, an increase in heart rate and a decrease in arterial pulse pressure were followed by a more delayed and progressive increase in mean and diastolic pressures. Systolic blood velocity markedly decreased along with the reduction in pulse pressure and increase in heart rate. By contrast, diastolic and mean coronary blood velocities did not show any significant change. Since it is known that the Valsalva manoeuvre strongly reduces stroke volume and cardiac output, it is likely that a reduction in cardiac work also takes place. Since in diastole, i.e. when the myocardial wall is better perfused, coronary blood velocity did not show any significant reduction, it is likely that unchanged perfusion in the presence of reduced cardiac work is responsible for the relief from angina sometimes observed during Valsalva manoeuvre. It is also likely that the increase in heart rate prevents the diastolic and mean blood coronary velocity from decreasing during the expiratory strain, when an increased sympathetic discharge could cause vasoconstriction through the stimulation of the coronary alpha-receptors.     

Pathomorphology of the vascular bed of postinfarction heart in various types of remodeling

We evaluated pathomorphological changes in the vascular bed of postinfarction heart in various types of remodeling. Dilatational remodeling was characterized by dilation of coronary arteries, increase in their volume density, and regular arrangement. Signs of coronary blood flow reduction and microcirculatory disturbances in the left ventricle were revealed during hypertrophic remodeling. Aneurysmal remodeling was characterized by the presence of small-vascular collateral-anastomotic plexus and reduction of the microcirculatory bed. Endocardial remodeling was accompanied by hypervascularization of the myocardium, formation of new coronary vessels, and reduced capillarization in the left ventricle of postinfarction heart.     

Effect of hypercapnia on the blood supply to the heart in chronic experimental conditions

Summary Experiments were staged on dogs in chronic conditions without anesthesia. The changes in the volume velocity of the coronary circulation were recorded by the thermoelectric method. Respiration, blood pressure and ECG were registered simultaneously. Hypercapnia of different degrees was provoked by inhalation of gas mixtures with 3, 5, 7, 10 and 15% CO₂ for 1–10 min.The changes in the coronary circulation in response to hypercapnia were either biphasic (reduction at the beginning of the action, replaced by its gradual increase, as in dogs under anesthesia), or—monophasic (increase only). During the first phase there was constriction of the coronary vessels, and during the second—dilatation. Characteristic of dogs without anesthesia were inconstancy, a lesser degree and a shorter duration of constriction (during, the first phase). Evidently while awake the animals possessed greater compensatory powers for overcoming the vasoconstrictor effects of CO₂ on the coronary vessels than did dogs under anesthesia.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 3, pp. 15–19, March 1964     

Myocardial blood flow and lactate metabolism at rest and during exercise with reduced arterial oxygen content

The effect of a reduction in arterial oxygen content, equivalent to acute exposure to an altitude of 2300 metres above sea level, on myocardial blood flow and oxygen and lactate exchange was studied by coronary sinus catheterization in 12 healthy men. Measurements were made at rest, during atrial pacing and during submaximal and maximal exercise both breathing air and breathing 15% oxygen (hypoxia). Coronary sinus blood flow was measured by thermodilution and the possibility of a simultaneous uptake and release of lactate by the heart was calculated using intravenous infusion of 14C lactate. At all levels of cardiac power output myocardial oxygen consumption was the same during hypoxia as during air breathing. At rest this was achieved entirely by a more complete extraction of oxygen from the coronary blood, during maximal exercise entirely by a greater coronary sinus blood flow, while at intermediate levels of cardiac power output a combination of these mechanisms prevailed. At rest and during submaximal work myocardial lactate extraction was lower with hypoxia than air breathing suggesting a change in myocardial redox state, while the 14C lactate data suggested no significant lactate release or possibly limited areas with some lactate production. During maximal exercise, however, there was no difference in myocardial lactate net extraction between hypoxia and air breathing, which together with the greater blood flow suggests that the heart has a 'coronary flow reserve' permitting maximal exercise at moderate altitude without anaerobic myocardial metabolism.     

The influence of some derivatives of the phenothiazine group on reflexes from the heart

Summary Short-term experiments were performed on anesthetized and decerebrate cats. A comparative study was carried out on the effect of aminazine and mepazine on the reflex reactions when cardiac blood supply was impaired.It was established that mepazine and aminazine depressed the reflexes from the heart and decreased the electrocardiographic changes. The effect of aminazine on the reflexes from the heart is more pronounced than that of mepazine.The latter completely eliminates the changes in the electrocardiogram connected with disturbance of coronary circulation. In the case of aminazine this property is almost absent. In combined administration of mepazine and analgesic substances (phenadon, promedol) the effect of these preparations is considerably prolonged.Presented by Active Member AMN SSSR, V. V. Zakusov     

The effect of potassium on the coronary circulation

Conclusion The influence of potassium on the coronary circulation was studied. Experiments were carried out on dogs under morphine-urethane anesthesia with the use of thermoelectric recording of the coronary circulation volume velocity, and with the resistography method with perfusion through the coronary artery at constant blood volume. Intracoronary and intravenous injections of different doses of potassium chloride caused coronary dilatation. Large doses led to cardiac arrest.In most of the cases there was a reduction of the cardiac blood supply after application of concentrated potassium chloride solution to the epicardium. However, it·increased in rare cases when the blood pressure was greatly elevated, thus compensating a slight rise of the coronary vessel tone. The coronary tone rose to a greater degree at the place of K application than in the remote zone.In these experiments the EKG changes seen were similar to those observed in myocardial infraction. They did not correlate with changes of coronary circulation.(Presented by Academician AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 59, No. 2. pp. 20–24, February, 1965