Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of K_ATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance.     

A new thermal sensor for surface-based measurement of local myocardial perfusion

The transient response of a new thermal sensor for continuous surface-based measurement of local tissue blood flow was evaluated in the beating dog heart. The sensor is 2.5 mm square, tests on the heart, and responds to flow changes only within a region of tissue 3-4 mm below its location on the epicardial surface. Initial studies demonstrate excellent sensitivity, good frequency response with a time constant of the order of 10-11 s, and an ability to continuously monitor changes in local myocardial blood flow during a variety of well-understood interventions, including coronary artery occlusion, reactive hyperemia, and intravenous administration of nitroglycerin and dipyridamole.     

心肌桥壁冠状动脉血液动力学数值模拟

目的数值模拟心肌桥壁冠状动脉血液动力学,探索心肌桥壁冠状动脉近心端易发生动脉粥样硬化的血液动力学机理。方法建立随心搏运动的局部狭窄直圆管模型模拟心肌桥壁冠状动脉形态学,管壁为薄壁线弹性体,血流遵循不可压缩牛顿流体的一维管流方程组,用Lax-Wendroff方法数值求解。结果心肌桥壁冠状动脉血液动力学与正常冠状动脉血液动力学相比有很大差异,血流量#壁切应力和壁切应力梯度均不同。在心肌桥壁冠状动脉中,近心端壁切应力及壁切应力梯度的变化要远大于远心端。对于有两段心肌桥的情况,它们的壁切应力和壁切应力梯度变化趋势基本一致,但距心室较远的心肌桥,其壁切应力和壁切应力梯度要大于靠近心室的那段心肌桥,且随时间的变化程度也更剧烈。结论数值模拟结果表明,心肌桥壁冠状动脉血液动力学不同于正常冠状动脉血液动力学,近心端壁切应力及壁切应力梯度的变化要远大于远心端,从而对动脉管内皮细胞产生重要影响,这可能是心肌桥壁冠状动脉近心端易发生动脉粥样硬化的血液动力学机理。     

Recent advances in echocardiographic diagnosis of ischemic heart disease

Before the early 1990s, the diagnostic usefulness of echocardiography for ischemic heart disease had been relatively limited compared with that for other cardiac diseases such as valvular disease, congenital anomalies and cardiomyopathies. The principal role of echocardiography was to assess persistent regional wall motion abnormality as well as to detect complications of myocardial infarction. However, recent technological advances have created many newer applications of echocardiography in this field. One of the most important advances was seen in the field of stress echocardiography. Dobutamine stress echocardiography has become an established method of diagnosing transient myocardial ischemia due to coronary stenosis and assessing the myocardial viability of a persistently akinetic segment. More recently, several new contrast agents have been developed or will be available in the near future to visualize the blood stream within the left heart cavity and myocardial blood flow. Simultaneously, new ultrasound technologies including harmonic imaging and gated intermittent imaging have enhanced the selective visualization of contrast agents and will contribute to noninvasive imaging of coronary microcirculation. Harmonic imaging has also been shown to improve quality of B-mode image without a contrast agent and will play an important role in the clinical recognition of wall motion abnormality in patients with ischemic heart disease. Recent advances in three-dimensional technology have enabled accurate measurements of left ventricular volume and ejection fraction without any geometrical assumption, which may be especially important for the evaluation of ischemic patients who often have a deformed left ventricular cavity due to remodeling.     

The role of lymphatic vessels in the heart

Although cardiac lymphatic vessels have been described for over three centuries, research progress on the role of cardiac lymphatic vessels in regulating cardiac physiology and their disturbances in the pathogenesis of cardiac disease has progressed very slowly, largely due to technical challenges in developing both animal models and cardiac lymphatic vascular imaging technologies. This review summarizes evidence showing that blocking cardiac lymph flow may contribute to several forms of cardiac injury including cardiac lymphedema, cardiac valvular deformation, coronary arterial injury, conduction disturbances, myocardial injury, and poor heart performance in animal and human heart studies. Conversely, improving cardiac lymph flow may have beneficial effects on heart function after heart attack (myocardial infarction). In addition, this review summarizes recent hypotheses about the forces generating cardiac lymph flow, in which the role of both the subepicardial and mid-myocardial myocytes synchronized contractions causing lymph flow is discussed. Lastly, possible mechanisms of blood vessel injury caused by the failure of perivascular lymphatic remodeling are discussed.     

Intramyocardial distribution of blood flow in hemorrhagic shock in anesthetized dogs.

In 34 anesthetized, open-chest dogs aortic blood pressure was kept at 35-40 mmHg for 3 h to determine if maldistribution of coronary blood flow (CBF) could contribute to the irreversibility of hemorrhagic shock. Six dogs were pretreated with phenoxybenzamine (PBZ) and 11 dogs (3 with PBZ) received hypertonic mannitol infusions in late hemorrhage. Changes of heart rate, cardiac output, and peripheral resistance were similar to those described by others. In untreated dogs total and left ventricular CBF fell, as did coronary vascular resistance. However, minimal coronary resistance after transient ischemia rose progressively and the ratio of subendocardial:subepicardial flow fell, as did the percentage of diastolic coronary flow. Mannitol infusion returned CBF and steady-state and minimal postischemic coronary resistance to control values and also returned to normal the increased myocardial water content found in late hemorrhage. Phenoxybenzamine delayed but did not prevent the rise of coronary vascular resistance or decreased subendocardial flow. These studies suggest that there may be subendocardial ischemia, possibly due to myocardial edema, in hemorrhagic shock.     

Coronary vascular sympathetic beta-receptor innervation.

Recent studies indicate that coronary vessels have alpha- and beta-2-adrenergic receptors and that the alpha receptors are functionally innervated. We studied whether the beta-2-vasodilator receptors are functionally innervated, using a dog in situ modified Langendorff preparation with constant coronary perfusion pressure. The beating, nonworking heart and systemic circulation were supported with a pump oxygenator. Stimulation of the left stellate ganglion increased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values. After beta-1-receptor blockade (practolol, 10 mg/kg), stellate stimulation decreased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values, revealing alpha-receptor vasoconstriction. After the addition of alpha-receptor blockade (Dibozane, 5 mg/kg), stellate stimulation increased coronary blood flow and coronary sinus oxygen tension a small amount from prestimulation values. Finally, after the addition of beta-2-receptor blockade (propranolol, 2 mg/kg), stellate stimulation increased flow and coronary sinus oxygen tension slightly from prestimulation control values. Direct intracoronary injections of isoproterenol, norepinephrine, and epinephrine gave results consistent with the presence of beta-1 myocardial receptors and alpha and beta-2 coronary receptors. We conclude that there is little functional innervation of coronary vascular beta-2 receptors. Intracoronary injections of isoproterenol and epinephrine activated beta-2-receptor coronary vasodilation after beta-1-receptor blockade, but norepinephrine did not.     

Noninvasive mapping of endothelial dysfunction in myocardial ischemia by magnetic resonance imaging using an albumin‐based contrast agent

Noninvasive preclinical methods for the characterization of myocardial vascular function are crucial to an understanding of the dynamics of ischemic cardiac disease. Ischemic heart disease is associated with myocardial endothelial dysfunction, resulting in leakage of plasma albumin into the extravascular space. These features can be harnessed in a novel noninvasive three‐dimensional magnetic resonance imaging method to measure fractional blood volume (fBV) and vascular permeability (permeability–surface area product, PS) using labeled albumin as a blood pool contrast agent. C57BL/6 mice were imaged before and 3 days after myocardial infarction (MI). Following the quantification of endogenous myocardial R₁, the dynamics of intravenously injected albumin‐based contrast agent, extravasating from permeable myocardial blood vessels, were tracked on short‐axis magnetic resonance images of the entire heart. This study successfully discriminated between infarcted and remote regions at 3 days post‐infarct, based on a reduced fBV and increased PS in the infarcted region. These findings were confirmed using ex vivo fluorescence imaging and histology. We have demonstrated a novel method to quantify blood volume and permeability in the infarcted myocardium, providing an imaging biomarker for the assessment of endothelial dysfunction. This method has the potential to three‐dimensionally visualize subtle changes in myocardial permeability and to track endothelial function for longitudinal cardiac studies determining pathophysiological processes during infarct healing.     

冠心病患者心肌声学造影定量分析的初步研究

拟探讨MCE定量分析在缺血性心脏病上的诊断价值。对10例临床诊断冠心病的患者行MCE,从时间-强度曲线中获得造影剂再灌注强度峰值(SIpeak),再灌注时间(Rt),再灌注率(b)和心肌血流量(SI×b)。同一检查对象不同心肌节段的4个参数(SIpeak、Rt、b和SI×b)均有统计学上的差异(P<0.05),对照组和观察组SIpeak具有统计学上的差异,SIpeak预测缺血性心脏病的ROC曲线下面积(AUC)为0.782,最佳临界值为64.4,以SIpeak≤64.4来预测缺血性心脏病,敏感性83.3%,特异性69.0%。利用超声造影匹配成像技术能够较满意地显示心肌灌注状态,初步研究表明通过MCE及Qontrast多参数定量分析软件可以评价心肌梗死区和缺血区的血流灌注缺损。SIpeak是预测缺血性心脏病的敏感指标。     

High-frequency ultrasonographic imaging of avian cardiovascular development.

The chick embryo has long been a favorite model system for morphologic and physiologic studies of the developing heart, largely because of its easy visualization and amenability to experimental manipulations. However, this advantage is diminished after 5 days of incubation, when rapidly growing chorioallantoic membranes reduce visibility of the embryo. Using high-frequency ultrasound, we show that chick embryonic cardiovascular structures can be readily visualized throughout the period of Stages 9-39. At most stages of development, a simple ex ovo culture technique provided the best imaging opportunities. We have measured cardiac and vascular structures, blood flow velocities, and calculated ventricular volumes as early as Stage 11 with values comparable to those previously obtained using video microscopy. The endocardial and myocardial layers of the pre-septated heart are readily seen as well as the acellular layer of the cardiac jelly. Ventricular inflow in the pre-septated heart is biphasic, just as in the mature heart, and is converted to a monophasic (outflow) wave by ventricular contraction. Although blood has soft-tissue density at the ultrasound resolutions and developmental stages examined, its movement allowed easy discrimination of perfused vascular structures throughout the embryo. The utility of such imaging was demonstrated by documenting changes in blood flow patterns after experimental conotruncal banding.     

Augmented Cardiac Formation of Oxidatively-Induced Carbonylated Proteins Accompanies the Increased Functional Severity of Post-Myocardial Infarction Heart Failure in the Setting of Type 1 Diabetes Mellitus

SummaryHeart failure (HF) is a dominant cause for the higher mortality of diabetics after myocardial infarction (MI). In the present investigation, we have discovered that higher levels of oxidative stress (OS)-induced carbonylated proteins accompany worsening post-MI HF in the presence of type 1 diabetes. These findings provide a mechanistic link between amplified OS and exacerbation of post-infarction HF in diabetes.BackgroundType 1 diabetes mellitus (DM) patients surviving myocardial infarction (MI) manifest an increased incidence of subsequent heart failure (HF). We have previously shown that after MI, type 1 DM is associated with accentuated myocardial oxidative stress (OS) and concomitant worsening of left ventricular (LV) function. However, the precise mechanisms whereby type 1 DM-enhanced OS adversely affects HF after MI remain obscure. As carbonylation of proteins is an irreversible post-translational modification induced only by OS that often leads to the loss of function, we analyzed protein-bound carbonyls in the surviving LV myocardium of MI and DM+MI rats in relation to residual LV function.MethodsType 1 DM was induced in rats via administration of streptozotocin. Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by coronary artery ligation. Residual LV function and remodeling was assessed at 4 weeks post-MI by echocardiography. Myocardial carbonylated proteins were detected through OxyBlot analysis, and identified by mass spectrometry.ResultsCompared with MI rats, DM+MI rats exhibited significantly poorer residual LV systolic function and elevated wet to dry weight ratios of the lungs. Protein carbonyl content in cardiac tissue and isolated heart mitochondria of DM+MI rats was 20% and 48% higher, respectively, versus MI rats. Anti-oxidative enzymes and fatty acid utilization proteins were among the carbonylated protein candidates identified.ConclusionsThese findings implicate myocardial protein carbonylation as part of the molecular pathophysiology of aggravated HF in the type 1 diabetic post-infarction heart.     

Evaluation of the porcine ameroid constrictor model of myocardial ischemia for therapeutic angiogenesis studies.

The porcine ameroid model of chronic myocardial ischemia has been widely used for the evaluation of coronary collateralization development. The impact of target vessel occlusion on the presence of myocardial ischemia, and the relationship between morphological, functional, and hemodynamic measurements in the context of therapeutic angiogenesis studies, however, has not been studied thus far. The authors therefore performed a systematic analysis of 94 animals undergoing ameroid constrictor placement around the left circumflex coronary artery (LCX) and, furthermore, a comprehensive evaluation including echocardiography and coronary angiography 26 +/- 1 (mean +/- SEM) days after ameroid placement. Complete LCX occlusion was observed in 34/94 animals (36%) and identified those with myocardial ischemia of the lateral wall, both at rest and under pharmacological stress. By applying a set of angiographic criteria (TIMI or= 1), another 27/94 animals with myocardial ischemia under conditions of pharmacological stress conditions could be identified. Interestingly, echocardiographic parameters of regional and global myocardial function were not correlated with myocardial blood flow or the degree of ischemia. There was no relationship between the extent of coronary collateralization, as assessed by angiography, echocardiographic parameters, or myocardial blood flow. The authors therefore conclude that complete occlusion of the ameroid instrumented coronary artery is not a prerequisite for successfully establishing the pathophysiology of myocardial ischemia. Defined angiographic criteria are important in identifying ischemic animals, thus reducing total animal numbers. Angiographic assessment of the degree of coronary collateralization, however, is not associated with myocardial blood flow or function and should not be used as a primary outcome measure of therapeutic angiogenesis studies in this model.     

Regulation of coronary blood flow during exercise

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains capillary density at a level commensurate with the degree of exercise-induced physiological myocardial hypertrophy. Nevertheless, training alters the distribution of coronary vascular resistance so that more capillaries are recruited, resulting in an increase in the permeability-surface area product without a change in capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the presence of lower circulating catecholamine levels appears to be due to increased receptor responsiveness to adrenergic stimulation. Exercise training also alters local control of coronary resistance vessels. Thus arterioles exhibit increased myogenic tone, likely due to a calcium-dependent protein kinase C signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, training augments endothelium-dependent vasodilation throughout the coronary microcirculation. This enhanced responsiveness appears to result principally from an increased expression of nitric oxide (NO) synthase. Finally, physical conditioning decreases extravascular compressive forces at rest and at comparable levels of exercise, mainly because of a decrease in heart rate. Impedance to coronary inflow due to an epicardial coronary artery stenosis results in marked redistribution of myocardial blood flow during exercise away from the subendocardium towards the subepicardium. However, in contrast to the traditional view that myocardial ischemia causes maximal microvascular dilation, more recent studies have shown that the coronary microvessels retain some degree of vasodilator reserve during exercise-induced ischemia and remain responsive to vasoconstrictor stimuli. These observations have required reassessment of the principal sites of resistance to blood flow in the microcirculation. A significant fraction of resistance is located in small arteries that are outside the metabolic control of the myocardium but are sensitive to shear and nitrovasodilators. The coronary collateral system embodies a dynamic network of interarterial vessels that can undergo both long- and short-term adjustments that can modulate blood flow to the dependent myocardium. Long-term adjustments including recruitment and growth of collateral vessels in response to arterial occlusion are time dependent and determine the maximum blood flow rates available to the collateral-dependent vascular bed during exercise. Rapid short-term adjustments result from active vasomotor activity of the collateral vessels. Mature coronary collateral vessels are responsive to vasodilators such as nitroglycerin and atrial natriuretic peptide, and to vasoconstrictors such as vasopressin, angiotensin II, and the platelet products serotonin and thromboxane A(2). During exercise, ss-adrenergic activity and endothelium-derived NO and prostanoids exert vasodilator influences on coronary collateral vessels. Importantly, alterations in collateral vasomotor tone, e.g., by exogenous vasopressin, inhibition of endogenous NO or prostanoid production, or increasing local adenosine production can modify collateral conductance, thereby influencing the blood supply to the dependent myocardium. In addition, vasomotor activity in the resistance vessels of the collateral perfused vascular bed can influence the volume and distribution of blood flow within the collateral zone. Finally, there is evidence that vasomotor control of resistance vessels in the normally perfused regions of collateralized hearts is altered, indicating that the vascular adaptations in hearts with a flow-limiting coronary obstruction occur at a global as well as a regional level. Exercise training does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. In addition to ischemia, the pressure gradient between vascular beds, which is a determinant of the flow rate and therefore the shear stress on the collateral vessel endothelium, may also be important in stimulating growth of collateral vessels.     

Ischemic heart disease

Ischemic heart disease is one of the leading causes of death in Japan. Acute coronary syndrome (ACS) most commonly begins with atherosclerotic plaque rupture and intracoronary thrombus formation. Therefore, the primary goal of treatment of acute coronary occlusion is the achievement of early and complete reperfusion. To achieve this goal, detection of atherosclerosis and/or myocardial necrosis by imaging and serologic tests is important. Original diagnosis of acute myocardial infarction (AMI) was made from typical symptoms, characteristic rises in serum enzyme levels, and an atypical electrocardiographic pattern. Increasingly sensitive and specific tests have been developed in recent years and have been rapidly adopted into clinical practice. Rapid developments in technology in the field of serum biomarkers have redefined the diagnosis of AMI. The new ESC/ACC criteria place increased emphasis on cardiac biomarkers, especially troponins. However, the electrocardiogram still remains significant in the diagnosis of AMI and the ability to identify high risk subgroups by admission electrocardiogram is necessary to estimate the severity of AMI. Current practice guidelines recognize the importance of promptly restoring normal epicardial blood flow, but blood flow to the ischemic tissue may still be impeded after relief of the occlusion; a phenomenon known as no reflow. Myocardial scintigraphy is one of the methods for defining coronary microvascular injury in the acute phase of AMI. Prompt assessment of coronary perfusion and detection of coronary microvascular injury may aid in making decisions concerning the use of drugs to improve microvascular function and left ventricular function after primary coronary angioplasty.     

New insights in to the treatment of myocardial infarction

This study investigated the effects of the L-17 compound of the group of substituted 5R1, 6H2-1,3,4-thiadiazine-2-amines on the inflammatory cellular infiltration and myocardial remodelling which occurs after acute myocardial infarction (MI) in rats. The study is based upon recent clinical and experimental work which demonstrated the role of local and systemic inflammatory reactions in postinfarction remodelling. Acute MI in rats was induced by left coronary artery coagulation. Animals were sacrificed on day one, five and seven after MI induction. The myocardiumal samples were taken from all parts of the heart and examined by histology. This included areas of infarction, infraction and areas that were peri-infarctiom and left ventricular areas distant from the damaged tissues. Serum activity of creatine phosphokinase (CPK), aspartate aminotransferase (AST), isoenzymes 1 and 2 and lactate dehydrogenase (LDH1-2) were investigated on the same three days, before and in the process of MI development was investigated (at days 1, 5 and 7). The L-17 compound to not only decreased the area of initial infarction but also changed the pattern of inflammatory reaction in the affected myocardium fundamentally. Laboratory studies of effects of L-17 compound on the development and course of experimental MI showed that administration decreased blood AST and CPK levels significantly and provided useful the data about the correlation between the activity of these enzymes and the dimensions of the significantly necrotic area. In this model of experimental MI the use of the L-17 compound induced led to the replacement of the exudative destructive inflammation that is seen under standard conditions with a more cellular "productive" pattern of inflammation, with associated reduction in initial necrosis area and the, decrease in myocardial ischaemia and reperfusion injury may account for the accelerated repair process.     

Myocardial infarction in sickle cell disease

Vasculo-occlusive crisis with organ infarctions occur in sickle cell disease (SCD). However, heart infarction is not commonly reported. We reviewed 19 cases of documented myocardial infarction (MI) in SCD patients. The true incidence may be higher because the diagnosis was often made at autopsy and was overshadowed during life by other musculoskeletal symptoms. Electrocardiography is frequently unhelpful. Skeletal muscle enzymes confound serum cardiac enzyme interpretation. The mechanism of MI in SCD is not exactly known, as coronary angiography is usually normal. MI frequently occurs in association with hypoxia, cor pulmonale, anemia, sepsis, acidosis, and renal failure. The aim of this article is to increase awareness for this complication and to prompt prospective studies to look at treatment strategies for myocardial infarction in SCD.     

A species comparison of the effects of changing perfusion pressure on blood flow and metabolic heat production in the myocardium

1. A heated thermocouple technique (internal calorimetry) has been used to investigate blood flow and heat production responses in the myocardium to changing blood pressure in monkeys, dogs, rabbits, guinea-pigs and rats. 2. Perfusion experiments (isolated guinea-pig and dog hearts) showed linear relations between conductivity increment and coronary blood flow up to 1 x 5 ml. g(-1) min(-1) (dog heart perfused with blood) and 5 ml. g(-1) min(-1) (guinea-pig heart perfused with saline). This relation was the same in the beating and non-beating heart. 3. In rabbits, guinea-pigs and rats the relation between flow (conductivity increment) and blood pressure was linear. In contrast, in monkeys and dogs, over the range 100-40 mm Hg, little change in blood flow occurred. After the injection of procaine around the stellate ganglion, the relation between pressure and flow in both species was linear. It is suggested that the constancy of blood flow displayed in the monkey and dog over this blood pressure range was due to the activity of adrenergic rasodilator fibres. 4. Evidence is adduced to show an increased myocardial heat production when systemic arterial pressure fell below about 60 mm Hg. This was not affected by cardiac denervation. The possible significance of this effect is discussed.     

Parametric analysis of flow in the intramyocardial circulation

A simple mathematical model of the intramyocardial circulation has been utilized to provide a better understanding of coronary blood flow. The model includes three myocardial layers, each characterized by a three-parameter windkessel with one capacitance and two resistances. The effects of the beating heart are taken into account by means of an intramyocardial pump and the possible collapse of the vessels by an elevated backpressure. The three basic parameters that govern the flow are a normalized time constant, , the total resistance, R_t, and a parameter, α, which specifies the resistance distribution in the intramyocardial circulation. Both the normal beating heart and prolonged diastole have been investigated analytically as well as numerically. It is shown that each of these parameters has its own special significance. Calculated pressure-flow relationships and zero-flow pressures for the case of prolonged diastole show a high sensitivity to and α.     

Blood flow in the hypertrophied right ventricular myocardium of unanesthetized ponies

To examine the effects of right ventricular (RV) hypertrophy on regional myocardial blood flow and coronary vascular reserve, hemodynamics and myocardial blood flow (15-micrometers radio-nuclide-labeled microspheres) were studied in 12 unanesthetized adult ponies before and during intravenous isoproterenol HCl infusion (1 microgram.kg-1.min-1). Six ponies served as controls, whereas in each of the others the main pulmonary artery (PA) had been banded 35-90 days prior to the study. Marked RV hypertrophy was present in PA-banded animals. In these ponies, there was a significant increase in RV systolic pressure (147%), heart rate (88%), RV tension-time index (279%), and RV myocardial blood flow (137%), while their RV coronary vascular resistance was only 40% of that for control ponies. Blood flow in right side of the interventricular septum was also significantly higher in the PA-banded ponies. Endo/epi perfusion ratio exceeded 1.00 for both ventricular freewalls in all animals. With isoproterenol infusion, there was a marked increase in myocardial blood flow in both groups. However, in PA-banded ponies the endo/epi flow ratio decreased precipitously below 1.00 in both ventricular freewalls. In control ponies this did not happen in the RV freewall, and RV coronary vascular resistance decreased to 19% of its control value. In PA-banded ponies, the magnitude of decline in RV coronary vascular resistance was much smaller, only 32% of that for control ponies. It is concluded that, unlike in LV hypertrophy, transmural myocardial blood flow per unit mass is much higher in the hypertrophied RV myocardium of adult resting ponies, and this higher RV perfusion occurs at the expense of curtailed RV coronary vascular reserve.     

Independent regulation of atrial coronary blood flow by atrial contraction rate in conscious dogs

Summary The effects of separate increases in atrial and ventricular contraction rates on the distribution of coronary flow within the heart were determined in conscious dogs with chronic heart block. Atrial tachycardia increased atrial blood flow and did not change ventricular blood flow. Ventricular tachycardia increased ventricular blood flow but not atrial blood flow. The results are consistent with the concept of local regulation of coronary perfusion by local myocardial energy turnover. The results also call attention to a potential adverse impact of atrial tachyarrhythmia in patients with underlying coronary ischemia.