Myocardial Tissue Pressure Research Articles

Targeted Endothelial Progenitor Cell Therapy Increases Myocardial Oxygen Tissue Pressure Characterized In Vivo Using Oxygen-Dependent Quenching of Phosphorescence

Targeted Endothelial Progenitor Cell Therapy Increases Myocardial Oxygen Tissue Pressure Characterized In Vivo Using Oxygen-Dependent Quenching of Phosphorescence

Transgenic and transmural revascularization: regional myocardial tissue pressure during chronic ischemia*1

Channel patency and a cavito-myocardial pressure gradient are prerequisites for one potential mechanism of transmyocardial laser revascularization (TMLR), namely indirect (non-coronary) myocardial perfusion. We assessed the effect of TMLR combined with vascular endothelial growth factor (VEGF) on the myocardial tissue pressure (MTP) in chronic ischemia questioning firstly, whether transmural pressure allows perfusion of laser channels, and secondly, whether additional application of VEGF improves channel patency. One week after creation of an operative left anterior descending artery stenosis (2nd operation), pigs were designated to untreated ischemia (n=7), TMLR (n=8) or TMLR+VEGF-cDNA (2 mg intramyocardially, n=6). MTP and left ventricular pressure (LVP) were recorded simultaneously in the endo-, mid-, and epimyocardium before and after stenosis (1st operation), before and after therapy (2nd operation), and 12 weeks later (3rd operation). Myocardial samples were subjected to immunohistochemistry. Endo- and epimyocardial MTP exceeded LVP in all groups throughout the study, whereas midmyocardial MTP was constantly below LVP (P<0.05). Immediately after combined TMLR+VEGF, the endo-MTP decreased from 246.5+/-44.2 to 176.7+/-20.7 mmHg (P=0.043), remaining higher than LVP. After 12 weeks, it increased to 225.6+/-31.8 mmHg (P=0.04), but did not reach baseline values (P=0.04). Histological examination revealed occluded channels with surrounding vascular proliferation in both treatment groups. Additional VEGF-cDNA application in the vicinity of TMLR channels does not improve long-term patency. Direct blood flow from the cavity into the myocardium is impossible due to the high endomyocardial pressure. This limitation might be overcome by implantation of endomyocardial stents.

Perioperative Myocardial Ischemia: Pathophysiology and Does it Really Matter

Perioperative Myocardial Ischemia: Pathophysiology and Does it Really Matter

Effects of Isoflurane on Regional Coronary Blood Flow and Myocardial Tissue Pressure in Chronically Instrumented Dogs

The effects of isoflurane on distribution of transmural blood flow and transmural intramyocardial tissue pressure (IMP) were studied in chronically instrumented dogs, to address following aims: (1) to evaluate the direct effects of isoflurane on transmural blood flow distribution in the absence of compounding effects of baseline anesthetics, acute surgery, and indirect effects caused by changes in systemic blood pressures and heart rate--factors that were not well controlled in the past studies; (2) to examine the relation between transmural myocardial perfusion pressure and concurrent changes in transmural blood flow distribution during isoflurane anesthesia; and (3) to evaluate the effects of isoflurane on transmural myocardial oxygen supply-demand relation. Dogs were allowed to recover at least 1 week after surgery for instrumentation. Blood flow of the left anterior descending coronary artery and subendocardial and subepicardial blood flows, regional IMPs, regional segmental dimension, heart rate, aortic pressure and left ventricular pressure were measured while dogs were awake and during 1.3% isoflurane anesthesia, with and without correction of heart rate and aortic pressure. Concurrently regional myocardial perfusion pressure, regional myocardial stroke work, and systolic pressure time index were calculated, based on direct measurements of IMP in subendocardium and subepicardium. Without correction of aortic pressure, neither left anterior descending coronary artery flow nor transmural blood flow distribution was altered with isoflurane. When aortic pressure and heart rate were corrected to the awake values, left anterior descending coronary artery flow increased (37 +/- 2%) and the increase was preferentially distributed to subendocardium, resulting in a shift in transmural blood flow. The subendocardial/subepicardial blood flow ratio increased from 1.2 +/- 0.3 to 1.4 +/- 0.4 (p, 0.05). The transmural blood flow changes were closely related to changes in regional myocardial perfusion pressure ratio between subendocardium and subepicardium (r = 0.76, P < 0.001). Concurrent with marked increases in blood flow (55 +/- 4% increase), regional myocardial stroke work and systolic pressure time index of subendocardium were decreased more than 50% with isoflurane, resulting in a favorable subendocardial oxygen supply-demand balance. Isoflurane is a coronary vasodilator and redistributes blood flow in favor of subendocardium and depresses subendocardial work when heart rate and aortic pressure are controlled. These changes in regional myocardial blood flow, regional myocardial stroke work, and systolic pressure time index appear to be a result of changes in regional IMP.

Myocardial tissue pressure and blood flow during coronary sinus pressure modulation in anesthetized dogs

To determine whether coronary sinus outflow pressure (Pcs) or intramyocardial tissue pressure (IMP) is the effective back pressure in the different layers of the left ventricular (LV) myocardium, we increased Pcs in 14 open-chest dogs under maximal coronary artery vasodilation. Circumflex arterial (flowmeter), LV total, and subendocardial and subepicardial (15-microns radioactive spheres) pressure-flow relationships (PFR) and IMP (needle-tip pressure transducers) were recorded during graded constriction of the artery at two diastolic Pcs levels (7 +/- 3 vs. 23 +/- 4 mmHg). At high Pcs, LV, aortic and diastolic circumflex arterial pressure, heart rate, myocardial oxygen consumption, and lactate extraction were unchanged; IMP in the subendocardium did not change (130/19 mmHg), whereas IMP in the subepicardium increased by 17 mmHg during systole and 10 mmHg during diastole (P < or = 0.001), independently of circumflex arterial pressure. Increasing Pcs did not change the slope of the PFR; however, coronary pressure at zero flow increased in the subepicardium (P < or = 0.008), whereas in the subendocardium it remained unchanged at 24 +/- 3 mmHg. Thus Pcs can regulate IMP independently of circumflex arterial pressure and consequently influence myocardial perfusion, especially in the subepicardial tissue layer of the LV.

New technique for analysis of cardiac energetics using a modified Fenn equation

In 12 dogs being supported by cardiopulmonary bypass, the relationship among myocardial oxygen consumption and four energy-consuming factors (basal metabolism, heart rate, tension development, and external work) was studied. Tension (internal work) in the left ventricular wall was evaluated by myocardial tissue pressure with a Mikro-Tip pressure transducer. In an empty beating heart with constant perfusion pressure, both systolic tissue pressure and developed tissue pressure represented the same characteristics as developed tension measured by other methods. As the heart rate was increased, the systolic tissue pressure and developed tissue pressure continued to increase stepwise (Bowditch effect) up to some stimulation rate, at which, however, a decrease began despite a further increase in heart rate (Woodworth effect). Significant regression was established between myocardial oxygen consumption and heart rate, tension (developed tissue pressure x heart rate), and external work (minute work): myocardial oxygen consumption = (9.05 x 10(-3) heart rate) + (1.95 x 10(-4) developed tissue pressure) x heart rate + (1.63 x 10(-3) minute work) + 1.42 (r = 0.7999), where activation energy = 9.05 x 10(-3) ml/100 gm per beat, tension-related energy = 1.95 x 10(-4) ml/100 gm per unit of internal work, energy for work = 1.63 ml/100 gm per unit of external work, and basal metabolism = 1.42 ml/min/100 gm. We concluded that myocardial tissue pressure is a good substitute for tension and that multiple regression with heart rate, tension, and external work (as by modified Fenn's equation) seems indispensable to predict myocardial oxygen tension in the whole heart.

Effects of collagen microstructure on the mechanics of the left ventricle

The microstructure of the collagen sheath or weave surrounding a myocyte and the collagen struts interconnecting neighboring myocytes is incorporated into a fluid-fiber-collagen continuum description of the myocardium. The sheaths contribute to anisotropic elasticity, whereas the struts contribute to an isotropic component. Elastic moduli of the composite myocyte-sheath complex and the strut matrix are estimated from existing passive biaxial loading data from sheets of canine myocardium. The contribution of the sheath to the elasticity of the myocyte-sheath complex is critically dependent on the helical pitch angle. Calculations for a cylindrical model of the left ventricle using both a fluid-fiber and fluid-fiber-collagen stress tensor show that the collagen strut matrix tends to limit muscle fiber lengthening; increase myocardial tissue pressure during systole, with endocardial tissue pressure exceeding left ventricular pressure; decrease tissue pressure during diastole, and thus facilitate myocardial blood flow; and aid filling during ventricular relaxation by providing a suction effect that relies on a release of stored elastic energy from the previous contraction. Calculations show that this energy is stored mostly in the collagen struts.

Theoretical analysis of the effects of a radial activation wave and twisting motion on the mechanics of the left ventricle.

The mechanical effects resulting from the normal transmural delay of electrical depolarization of the myocardium are investigated. An activation sequence having a finite radial propagation velocity is introduced into the equations of ventricular mechanics. The resulting system of coupled integral equations is solved using a perturbation method based on the small ratio of transmural propagation time to cardiac period. Numerical calculations are performed using cavity pressure and volume waveforms characteristic of the canine left ventricle (LV), for both simultaneous and delayed activation of fiber layers. The results show that a finite transmural electrical propagation velocity tends to: (i) equalize the transmural distribution of sarcomere length during systole; (ii) equalize the transmural distribution of fiber external work/vol; and (iii) insignificantly affect myocardial tissue pressure. Calculations are also performed to investigate the mechanical effects resulting from the application of an externally applied moment that prevents LV torsion. Those results are highly dependent on the transmural distribution of sarcomere length in the stress-free reference state (unloaded diastole). When we assume a uniform distribution, then normal torsion acting with normal activation delay tends to: (i) increase the magnitude of fiber strain in the subendocardium and decrease it in the subepicardium; (ii) equalize the transmural distribution of fiber external work/vol; and (iii) lower myocardial tissue pressure. The normally occurring transmural delay of activation tends to lessen endocardial O2 demand, while the normally occurring torsion further lessens that demand and improves O2 supply.

Relation of intramyocardial pressure to coronary pressure at zero flow.

The purpose of this study was to determine the extent to which coronary pressure at zero coronary flow (Pf=0) may relate to extravascular compressive forces determined by direct measurements of left ventricular intramyocardial pressure. Studies were performed in nine open-chest anaesthetized dogs in which the anterior descending coronary artery was cannulated and perfused from the carotid artery. Coronary pressure was measured at the tip of the cannula. Intramyocardial pressure was measured with a 1 mm diameter micromanometer inserted directly into the subepicardium. The atrioventricular node was obliterated by cautery and the heart was electrically paced. Long diastolic pauses, sufficient to allow coronary flow to reach zero, were produced by the cessation of electrical pacing. In the autoregulated coronary bed, Pf=0, 47 mmHg (s.e.m. = 9), exceeded subepicardial pressure at zero flow, 23 mmHg (s.e.m. = 2; P less than 0.001). During maximal vasodilatation with adenosine, Pf=0, 16 mmHg (s.e.m. = 11), was not significantly different from subepicardial pressure at zero flow, 21 mmHg (s.e.m. = 4). These observations indicate that, in addition to coronary vasomotor tone, diastolic myocardial tissue pressure is important in the genesis of Pf=0.

Effects of halothane on the intramyocardial pressure of the canine left ventricle.

In the intact canine heart a gradient of systolic intramyocardial pressure from a minimum at the epicardial region to a maximum at the endocardial region is well established. No information is, however, available regarding the effects of various anaesthetic agents on this gradient. In the present study the effects of halothane on intramyocardial pressure recorded from subendocardial and subepicardial layers of the canine left ventricular free wall were assessed. Experiments were performed on seven anaesthetised mongrel dogs ventilated with 100% oxygen. Intramyocardial pressure was recorded simultaneously from the inner and outer regions of the myocardium using two Mikro-tip pressure transducers. Halothane concentration in the inspired gas varied from 0% to 2%. In the pentobarbital anaesthetised dog halothane does not significantly change the heart rate. With increasing concentrations of halothane in inspired gas systolic intramyocardial pressure at both endocardium and epicardium decreased significantly from control values. As the halothane concentration increased, the normal differential between systolic left ventricular pressure and endocardial intramyocardial pressure was abolished. The intramyocardial pressure gradient from endocardium to epicardium, however, persisted during systole. During diastole the pressure gradient was reversed, becoming maximum in the epicardial region and minimum in the endocardial region in both control and halothane treated animals. Over the range of 0-2% halothane concentration there was no significant effect on the diastolic intramyocardial pressure gradient. These results suggest that halothane affects the myocardial tissue pressure non-uniformly across the left ventricular free wall and therefore influence sth e transmural distribution of coronary blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nitroprusside on myocardial blood flow in acute regional coronary ischaemia in conscious dogs with and without left ventricular distension.

To determine the effects of nitroprusside on regional myocardial ischaemia, experiments were done in 11 conscious dogs with balloon-cuff occluders implanted around the left anterior descending coronary artery (LAD). Regional myocardial blood flow by the microsphere method was determined during 5 min periods of temporary LAD occlusion with and without nitroprusside infusion. Nitroprusside decreased aortic mean and left ventricular diastolic pressures. Blood flow increased to ischaemic myocardium supplied by the occluded LAD and to non-ischaemic myocardium supplied by the patent left circumflex coronary artery. Experiments were repeated on a separate day in the presence of left ventricular distension in the same dogs. Nitroprusside again decreased aortic mean and left ventricular diastolic pressures and increased the blood flow to both ischaemic and non-ischaemic myocardial regions. These results suggest that nitroprusside can improve perfusion to acutely ischaemic myocardial tissue despite a fall in aortic pressure, presumably by decreasing resistance to flow in coronary collateral vessels or by decreasing the myocardial tissue pressure.

Myocardial tissue pressure

Myocardial tissue pressure

Correlation of the changes in diastolic myocardial tissue pressure and regional coronary blood flow in hemorrhagic and endotoxic shock

The changes in systemic hemodynamics, in diastolic myocardial tissue pressure (MTP), and in regional coronary blood flow were observed during two stages of hemorrhagic or endotoxic shock in 17 dogs. Nine dogs were subjected to hemorrhagic shock at a mean arterial pressure of 50 mm Hg for 45 min and at 33 mm Hg for a further 15 min. Eight dogs were subjected to endotoxic shock for 1 hr. Both hemorrhagic and endotoxic shock led to a reduction in the magnitude of the normal diastolic MTP gradient from epicardium to endocardium. They also led to a reduction in the proportion of the left ventricular myocardial flow going to the subendocardial region. These changes occurred at a constant heart rate. It is suggested that the change in regional diastolic MTP is an important contributing factor to the inadequate subendocardial perfusion which can occur in both hemorrhagic and endotoxic shock.

The response of diastolic myocardial tissue pressure and regional coronary blood flow to increased preload from blood, colloid, crystalloid.

An increase in the left ventricular end-diastolic pressure (LVEDP), resulting from the intravenous administration of blood, a colloid solution, or a crystalloid solution, was accompanied by an increase in both the inner:outer left ventricular wall flow ratio and the diastolic myocardial tissue pressure gradient. With a normal left ventricular end-diastolic pressure, the normal inner:outer flow ratio was just above unity and the minimum diastolic myocardial tissue pressure in the subepicardium was twice as high as in the subendocardium. When the left ventricular end-diastolic pressure was raised, the subepicardial tissue pressure rose earlier and to a higher degree than the subendocardial; thus a gradient which encourages subendocardial flow was increased. This paper correlates the changes in diastolic myocardial tissue pressure and in inner:outer flow ratios which occurred when eight dogs were transfused with blood, seven with colloid, and seven with lactated Ringer's solution. Regional diastolic myocardial tissue pressure was measured by the flow-cessation technique and regional flow by radioactive microspheres. The gradient in diastolic myocardial tissue pressure, which is a major contributory factor to adequate subendocardial perfusion under normal conditions, is of even greater importance when LVEDP is raised.

The gradient in regional myocardial tissue pressure in the left ventricle during diastole: Its relationship to regional flow distribution

The myocardial tissue pressure during diastole was measured in the inner and outer halves of the left ventricular wall of eight dogs with open chests and mean left ventricular end-diastolic pressure of 2.3 mm Hg. The myocardial tissue pressures were measured by the flow-cessation technique and modified needle-vein sensors with an accuracy of 0.7 mm Hg (SD 1.0). The lowest tissue pressure in the outer half of the left ventricular wall during diastole was over twice as high, 12.0 mm Hg (SD 2.0), as that in the inner half, 5.6 mm Hg (SD 1.7) ( P < 0.001). Within the myocardial wall, the lowest pressure occurs at the end of diastole rather than at the beginning as in the ventricular lumen. Thus, there is a gradient in myocardial wall tissue pressure in diastole, which is in the reverse direction of that present during systole. The presence of this gradient offers a simple explanation of the preferential flow to the inner layers of the left ventricle during diastole.

Surgical aspects of regional myocardial blood flow and myocardial pressure

The surgical technique of cardiopulmonary bypass with either an empty beating or an empty fibrillating ventricle produces marked changes in the regional blood flow and oxygen demand of the left ventricle. This paper describes the changes which occurred in the regional perfusion of both the normal and the hypertrophied left ventricle during these conditions and relates them to the known changes in oxygen demand. It also correlates the changes in flow with the measurable changes in myocardial tissue pressure-systolic when the heart is beating and continuous when fibrillating. The various types of filbrillation had identical effects on both regional tissue pressure and regional flow. The subendocardial blood supply was adequate or more than adequate under each of these conditions so long as the coronary perfusion pressure was maintained at an adequate level. A low perfusion pressure during ventricular fibrillation of any type led to a marked reduction in flow to the subendocardial portion of the left ventricle: The presence of ventricular hypertrophy accentuated this danger.

Mechanism for flow distribution in normal and ischemic myocardium during increased ventricular preload in the dog.

The effects of increased ventricular preload on the distribution of regional blood flow in normal and ischemic myocardium were determined in deep and superficial regions of the left ventricle by using labeled microspheres. The ratio of flow in deep regions to flow in superficial regions in nonischemic tissue was 1.06 ± 0.06 and increased to 1.14 ± 0.06 when left ventricular end-diastolic pressure was raised from 4.8 ± 1 mm Hg to 18 ± 2 mm Hg by intravenous infusion of blood. In ischemic areas the ratio of flow in deep regions to flow in superficial regions fell simultaneously from 0.71 ± 0.12 to 0.45 ± 0.07 ( P &lt;0.001). Control of coronary flow during increased preload was studied in a separate preparation in which coronary flow was decreased in steps by reducing coronary perfusion pressure during periods of constant cardiac performance. The increased preload was associated with loss of autoregulation of coronary flow. It is suggested that, in myocardium with unrestricted coronary supply, regional distribution of flow is independent of gradients in tissue pressure during the described changes in preload due to an autoregulatory mechanism. However, when autoregulation of coronary flow is abolished by coronary artery occlusion, the coronary bed is fully dilated, and distribution of flow is directly dependent on gradients in myocardial tissue pressure. Increased ventricular preload consequently augments the underperfusion of the subendocardial regions of an ischemic area.

Distribution of cardiac output in experimental hemorrhagic shock in dogs.

Distribution of cardiac output in experimental hemorrhagic shock in dogs.

NONUNIFORM DISTRIBUTION OF BLOOD FLOW AND GRADIENTS OF OXYGEN TENSION WITHIN THE HEART.

Myocardial tissue pressure increases from epicardium to endocardium, and in the deeper layers exceeds ventricular blood pressure during one-third of the cardiac cycle (21). The effect of this tissue pressure gradient on local blood flow was studied using the depot clearance technique. Blood flow was found to be at least 25% lower in the deep regions as compared with superficial ones. With total coronary inflow held constant, vagal arrest of the heart removed the tissue pressure gradient, and simultaneously redistributed flow from superficial to deeper layers. We conclude that the gradient in tissue pressure, and hence in the extravascular component of coronary resistance, is at least in part, the cause of the nonhomogeneous blood flow across the wall. By use of the oxygen cathode, a gradient of oxygen tensions was observed which paralleled the blood flow gradient; mean oxygen tension in the subepicardium averaged twice that in the subendocardium. The gradient in oxygen tension appears to be of sufficient magnitude to determine a transmural gradient in aerobic metabolism.

AN EXPERIMENTAL AND THEORETICAL ANALYSIS OF MYOCARDIAL TISSUE PRESSURE.

A new technique for estimating myocardial tissue pressure is described. The method is based upon changes in flow through an analog of a small coronary vessel. A gradient of tissue pressure from epicardium to endocardium was observed with peak tissue pressures twice peak ventricular pressure recorded in the inner half of the wall. A theoretical analysis of the concept of intramyocardial pressure is presented, based on the assumption that the tissue is a solid within which both longitudinal and radial compressive forces exist. The similarity between the gradient of longitudinal tissue pressure predicted by the theoretical analysis and the gradient experimentally determined suggests that the latter describes the maximum pressures which exist in the left ventricular wall.