Coronary Sinus Pressure Elevation Research Articles

AWARD ARTICLE: Microcirculatory Society Award for Excellence in Lymphatic ResearchTime Course of Myocardial Interstitial Edema Resolution and Associated Left Ventricular Dysfunction

Please cite this paper as: Dongaonkar RM, Stewart RH, Quick CM, Uray KL, Cox CS, Laine GA. Time course of myocardial interstitial edema resolution and associated left ventricular dysfunction. Microcirculation 19: 714–722, 2012.AbstractObjective: Although the causal relationship between acute myocardial edema and cardiac dysfunction has been established, resolution of myocardial edema and subsequent recovery of cardiac function have not been established. The time to resolve myocardial edema and the degree that cardiac function is depressed after edema resolves are not known. We therefore characterized temporal changes in cardiac function as acute myocardial edema formed and resolved.Methods: Acute myocardial edema was induced in the canine model by elevating coronary sinus pressure for three hours. Myocardial water content and cardiac function were determined before and during coronary sinus pressure elevation, and after coronary sinus pressure restoration.Results: Although no change in systolic properties was detected, accumulation of water in myocardial interstitium was associated with increased diastolic stiffness. When coronary sinus pressure was relieved, myocardial edema resolved within 180 minutes. Diastolic stiffness, however, remained significantly elevated compared with baseline values, and cardiac function remained compromised.Conclusions: The present work suggests that the cardiac dysfunction caused by the formation of myocardial edema may persist after myocardial edema resolves. With the advent of new imaging techniques to quantify myocardial edema, this insight provides a new avenue for research to detect and treat a significant cause of cardiac dysfunction.

Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema

Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures.

Beck and back: A paradigm change in coronary sinus interventions—pulsatile stretch on intact coronary venous endothelium

Strategies to recover myocardium in therapeutically unresponsive patients are again under scrutiny, including techniques developed in the pioneering days of cardiothoracic surgery such as retroperfusion via the coronary sinus--the Beck procedure. An underestimated aspect of retroperfusion is the formation of new vessels. This early observation of neoangiogenesis may be an important mechanism in observed benefits. We hypothesized that periodic pressure elevation in coronary veins induces an analogy to shear stress angiogenic pulses by activating venous endothelium. Pulsatile stretch on venous endothelium can be achieved easily by a pressure-controlled intermittent balloon blockade of the coronary sinus outflow. Three hours of myocardial ischemia was induced in 12 pigs. Pressure-controlled intermittent coronary sinus occlusion was applied in 6 animals 15 minutes after occlusion of the left anterior descending coronary artery. Postmortem myocardial specimens were taken, and heme oxygenase-1, vascular endothelial growth factor gene expression, and hypoxia-induced factor activity were measured. As compared with controls, treated animals released an angiogenic pulse by a 4-fold increase of heme oxygenase-1 gene expression in the infarct area (P < .001), together with a 2.5-fold enhanced transcription of vascular endothelial growth factor in the infarct (P < .006), border (P < .002), and remote (P < .02) areas, whereas hypoxia-induced factor activity was similar in both groups. A significant correlation (P < .01) of the achieved coronary sinus pressure elevation and gene expression was found. Mechanotransduction of pulsatile stretch on coronary venous endothelium by pressure-controlled intermittent coronary sinus occlusion induces heme oxygenase-1 and vascular endothelial growth factor gene expression, leaving the ischemic pathway of the hypoxia-induced factor activity unchanged. This cascade of molecular events closes the argument gap to historical reports of the Beck procedure on revascularization and myocardial salvage.

Myocardial fluid balance in acute hypertension.

We hypothesized that (1) acute arterial hypertension increases myocardial microvascular fluid filtration and (2) the combination of acute arterial hypertension and coronary sinus pressure elevation may increase myocardial microvascular filtration sufficiently to estimate the osmotic reflection coefficient of the myocardial exchange vessels. In nine mechanically ventilated dogs we cannulated the prenodal major cardiac lymph trunk. With the use of central venous phenylephrine infusion, mean arterial pressure (MAP) was raised progressively to 120, 160, and 180 mm Hg. In five dogs we additionally raised coronary sinus pressure (CSP) to 20 and 40 mm Hg. At each manipulation of MAP and/or CSP, we measured indexes of myocardial lymphatic function and lymph-to-plasma concentration ratios for total protein (CL(TP)/CP(TP) and albumin (CL(alb)/CP(alb)). Myocardial lymph flow rate (QL; microL/min) increased exponentially (QL = 10.9.e0.014.(MAP) and myocardial lymph driving pressure (PL; mm Hg) increased linearly (PL = 2.30 + 0.20 + 0.20 . MAP) following increases, whereas CL(TP)/CP(TP) and CL(alb)/CP(alb) decreases from 0.67 +/- 0.07 (SD) to 0.56 +/- 0.10 and from 0.91 +/- 0.05 to 0.75 +/- 0.11, respectively. Adding CSP elevation increased QL up to 12 times control associated with further CL(TP)/C(TP) and CL(alb)/CP(alb) decreases to 0.49 +/- 0.05 and 0.59 +/- 0.02, respectively. We conclude that hypertensive arterial pressures are, at least in part, transmitted to the myocardial microvascular exchange vessels in the intact animal leading to increased microvascular fluid filtration. However, the combination of acute arterial hypertension and coronary sinus pressure elevation is not sufficient to produce filtration independence required for myocardial osmotic reflection coefficient determination.

Effects of cardiac contraction and coronary sinus pressure elevation on collateral circulation.

Controlled coronary sinus occlusion was shown to retard necrosis of ischemic myocardium. To elucidate this mechanism, regional myocardial blood flow measurement was performed with and without coronary sinus pressure elevation to 30 mmHg (CS30). Colored microspheres were injected into left and right coronary arteries after coronary perfusion of the left anterior descending (LAD) coronary artery was stopped in seven isolated canine hearts with induced atrioventricular block, either paced at 120 beats/min by direct right ventricular stimulation [beating heart (B)] or during asystole induced by stopping pacing [nonbeating heart (NB)]. Regional myocardial blood flow in the LAD perfused area in the control state in the NB with normal coronary sinus pressure (NB-CScont; 0.27 +/- 0.13 ml.min-1.g-1, means +/- SE) was significantly greater than those in B-CScont (0.19 +/- 0.09 ml.min-1.g-1; P < 0.05) and in NB with CS30 (NB-CS30; 0.19 +/- 0.09 ml.min-1.g-1; P < 0.05). Regional myocardial blood flow of the LAD area in B with CS30 (B-CS30; 0.23 +/- 0.10 ml.min-1.g-1) was significantly greater in comparison with that at B-CScont and NB-CS30 (P < 0.05). The augmentative effect of the LAD area regional myocardial blood flow was observed only in the periphery of the ischemic region but not in its center. Cardiac contraction and CS30 impede regional myocardial blood flow in the ischemic bed independently. The coexistence of these two factors enhances regional myocardial blood flow. In conclusion, coronary sinus pressure elevation in B may participate in augmenting collateral flow.

Effects of synchronized retroperfusion on the coronary arterial pressure-flow relationship.

We compared the effects of diastolic coronary sinus pressure elevation due to synchronized retroperfusion (SRP) with systolic coronary sinus pressure elevation due to coronary sinus occlusion on the coronary pressure-flow relationship under similar mean coronary sinus pressure values. Using isolated, perfused canine hearts, coronary perfusion of the left anterior descending artery was reduced gradually, setting the mean coronary sinus pressure to 14.2 +/- 5.7 mmHg (mean +/- s.d.) under control conditions, 30.3 +/- 4.9 mmHg under SRP with lower retrograde perfusion flow [SRP(L)], 30.7 +/- 4.6 mmHg under coronary sinus partial occlusion [CSPO], 51.9 +/- 7.9 mmHg under SRP with higher retrograde perfusion flow [SRP(H)] and 49.0 +/- 7.9 mmHg under coronary sinus complete occlusion [CSCO]. Zero-flow pressure and the slopes of pressure-flow relationship were determined in each condition. The mean values of the slopes did not significantly differ among the interventions. The mean control value of zero-flow pressure was 17.4 +/- 4.3 mmHg. Zero-flow pressure of SRP(L) was 20.0 +/- 3.5 mmHg, which was not a significant increase, whilst zero-flow pressure of CSPO was 22.9 +/- 3.4 mmHg, a significant increase compared with control (P < 0.05). Zero-flow pressure of SRP(H) and CSCO was 26.0 +/- 4.5 and 31.3 +/- 6.7 mmHg, respectively, and both were significantly higher than control (P < 0.01). Zero-flow pressure of SRP(H) was, however, significantly lower than CSCO (P < 0.05). SRP, which causes diastolic coronary sinus pressure elevation, does not greatly affect coronary arterial inflow, compared with coronary sinus occlusion which causes systolic coronary sinus pressure elevation. These results suggest that the blood volume contained in the heart during systole plays a role in determining coronary inflow. Therefore, SRP intervention, which does not interfere with venous outflow during systole, may ameliorate injured myocardium during ischaemia without seriously affecting coronary inflow supply.

Effects of elevated coronary sinus pressure on coronary blood flow and left ventricular function. Implications after the Fontan operation.

After the Fontan operation there is elevated systemic venous pressure, and the coronary sinus pressure (CSP) may also be elevated depending on the operative technique. Elevated CSP can potentially alter coronary perfusion and thereby be a cause for postoperative left ventricular (LV) dysfunction. The effects of elevated CSP on coronary blood flow (CBF) and LV function were evaluated in 14 isolated blood-perfused juvenile lamb hearts. After baseline measurements were made, CSP was elevated by a 10-minute inflation of a balloon catheter inserted into the coronary sinus via the hemiazygos vein in 7 hearts (CSHT group) to cause moderate (phase I, approximately 15 mm Hg) and severe (phase II, approximately 30 mm Hg) elevations of mean CSP at a constant coronary perfusion pressure (80 mm Hg). The results were compared with results from 7 hearts continuously perfused without elevation of CSP (C group). Mean CSP in the CSHT group was elevated from 0.4 +/- 1.9 to 16.4 +/- 2.4 mm Hg during phase I and to 32.6 +/- 3.6 mm Hg during phase II. CBF in the CSHT group decreased to 89.7 +/- 5.2% in phase I and to 79.0 +/- 13.2% in phase II, and these values were significantly lower than those in the C group (98.5 +/- 6.7% in phase I and 106.8 +/- 16.0% in phase II; P < .05 each). There were no significant differences in maximum developed pressure (DP), max+dP/dt, max-dP/dt, or LV end-diastolic pressure (LVEDP) at a fixed volume between the CSHT group and the C group either in phase I or phase II. The time constant of pressure decline during LV isovolumic relaxation (tau) showed no significant difference in phase I, but in phase II tau was significantly higher in the CSHT group (116.2 +/- 7.8%) than that in the C group (106.3 +/- 8.5%; P < .05). Elevated CSP on a short-term basis did not affect the LV systolic function indexes (max DP, max+dP/dt), max-dP/dt, or LVEDP at a fixed volume, but tau did appear to worsen and CBF decreased during CSP elevation. These actions might have deleterious effects on the LV over a longer time period.

Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function.

We hypothesized that both acute and chronic accumulation of myocardial interstitial edema (extravascular fluid [EVF]) would compromise cardiac function. We also postulated that excess fluid within the myocardial interstitial space would potentiate interstitial fibrosis, thus further compromising function. Dogs were divided into three groups: 1) control, 2) chronic pulmonary hypertensive with right heart failure, and 3) chronic arterial hypertensive. The quantity of EVF, expressed as the unitless blood-free (wet weight-dry weight)/dry weight ratio, and interstitial fibrosis (collagen content) were determined and correlated with cardiac function at baseline and after acute elevation of coronary venous pressure and reduction of cardiac lymph flow. Control EVF was 2.90 +/- 0.20 (mean +/- SD), which increased to 3.45 +/- 0.16 after acute (3-hour) elevation of coronary sinus pressure. This EVF significantly compromised cardiac function. The EVF in chronically hypertensive dogs and in dogs with chronic right heart pressure elevations was 3.50 +/- 0.30 and 3.50 +/- 0.08, respectively. End-diastolic left ventricular interstitial fluid pressure increased from a control value of 14.9 +/- 3.1 (at EVF = 2.9) to 24.8 +/- 3.7 (at EVF = 3.5). An EVF of 3.5 produced approximately 30% reduction of the heart's ability to maintain cardiac output at a left atrial pressure of 15 mm Hg. The compromised function in these chronic models is exacerbated after acute elevation of coronary venous pressure and reduction of cardiac lymph flow. Collagen levels were elevated by at least 20% in the chronic hypertensive dogs and in the nonhypertrophied left ventricles of dogs with chronic right heart pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

The dynamics of antegrade cardioplegia with simultaneous coronary sinus occlusion: Effects on aortic root infusion pressure, coronary sinus pressure, and myocardial cooling

It has been suggested that antegrade cardioplegia with coronary sinus occlusion improves homogeneous myocardial cooling and reduces myocardial injury in the presence of coronary artery occlusion. Little data are available on the exact relationships among the basic elements or this intervention, including antegrade infusion rate, aortic root pressure, the degree of coronary sinus occlusion, coronary sinus pressure, and myocardial cooling. The purpose of this study was to determine these relationships and to provide some basic guidelines for better understanding of this intervention. Twenty-two sheep were placed on cardiopulmonary bypass, the distal left anterior descending artery was occluded, and the proximal coronary sinus was snared. Sixteen combinations of infusion rate (3, 5, 7, or 9 ml/kg/min) and coronary sinus occlusion (total, subtotal, or moderate occlusion or no occlusion) were adopted for each 2 minutes of antegrade cardioplegia, yielding 96 measurements. Myocardial temperatures in the occluded and nonoccluded regions, aortic root infusion pressure, and coronary sinus pressure were measured during each infusion of cardioplegic solution. Coronary sinus occlusion was then released, and the whole heart was reperfused for 30 minutes for another infusion of cardioplegic solution and measurements. Results showed good degrees of linearity between infusion rate and aortic root infusion pressure for all coronary sinus occlusion and noninfusion groups (p less than 0.01). A positive effect of coronary sinus occlusion on aortic root infusion pressure was observed. The graded increases in infusion rate with various degrees of coronary sinus occlusion were constantly associated with elevation of coronary sinus pressure (p less than 0.01). It was also noted that myocardial temperatures in the region of the occluded left anterior descending artery were significantly lower in coronary sinus occlusion groups than in nonocclusion groups (p less than 0.01 or 0.05). Myocardial temperature in the nonoccluded region decreased significantly with the stepwise increases in infusion rate (p less than 0.01), but not with the increases in coronary sinus occlusion (not significant). Based on this and previous studies, we recommend that the induced coronary sinus pressure be safely maintained in the range of 25 to 35 mm Hg and that further studies be focused on the infusion rate of 5 ml/kg/min with subtotal or total coronary sinus occlusion for the intervention of antegrade cardioplegia plus coronary sinus occlusion.

Elevated coronary sinus pressure does not alter myocardial blood flow or left ventricular contractile function in mature sheep: Implications after the Fontan operation

The hypothesis that elevation of coronary sinus pressure affects coronary blood flow and ventricular function was tested in this study of seven adult ewes placed under pentobarbital anesthesia. Coronary sinus pressure was elevated by partial balloon occlusion. Right atrial, left atrial, and aortic mean pressures and rate of rise of left ventricular pressure were measured. Coronary blood flow was determined with radioactive microspheres. Studies were performed at control and at moderate (15 to 20 mm Hg) and marked (30 to 35 mm Hg) elevation of coronary sinus mean pressures. Despite increase of coronary sinus pressure from a control value of 2 mm Hg +/- 1 to levels of 19 mm Hg +/- 1 and 34 mm Hg +/- 1, no significant changes were observed in right atrial, left atrial, or aortic mean pressure or rate of rise of left ventricular pressure. Both endocardial and epicardial blood flows were unaffected. The endocardial/epicardial flow ratio at moderate coronary sinus pressure elevation was significantly increased, which suggested local subendocardial vasodilation in the absence of changes in transmural perfusion. The findings suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal ewe.

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

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

Acute effects of elevation of coronary sinus pressure.

The acute physiologic effects of the aorta to coronary sinus anastomosis of Beck have been studied. The evidence presented shows that arterialization of the coronary sinus results in a small retrograde flow from the sinus through capillaries into the occluded artery and that such retrograde flow supplies from 14 to 25 per cent of the normal myocardial oxygen requirement. It is suggested that this is insufficient to maintain normal myocardial contraction, but probably prevents ventricular fibrillation. However, when the sinus is arterialized in the presence of normal or reduced coronary flow electrocardiographic and coronary inflow data show that there is myocardial anoxia. This is probably due to the restriction in capillary outflow and results in an expansion of the coronary vascular bed.

Further studies on the effect of arteriovenous fistulas and elevations of sinus pressure on mortality rates following acute coronary occlusions.

Observations were made on the mortality rates within the first hour following acute ligation of the circumflex artery. The experiments were divided into the following groups: (1) those with arteriovenous fistulas, (2) those with elevation of coronary sinus pressure, (3) those with complete coronary sinus occlusion, and (4) those with arterialization of the coronary sinus. There was a mortality of 70 per cent in the first group, 30 per cent in the second group, 40 per cent in the third group, and no deaths in the fourth group. The results indicate that arterialization of the coronary sinus provides the greatest protection against ventricular fibrillation and that such arterialization provides the only practical means of chronically elevating coronary sinus pressures to effective levels.