Myocardial Edema Formation Research Articles

Modified Ultrafiltration Versus Conventional Ultrafiltration: A Randomized Prospective Study In Neonatal Piglets

Cardiopulmonary bypass in neonates generates large increases in inflammatory mediators, causing edema formation that may lead to multiple organ dysfunction. Clinical strategies aimed at removing inflammatory mediators, reducing edema formation, and improving organ function include conventional and modified ultrafiltration. Objective: This study examines the effectiveness of conventional and modified ultrafiltration in preventing weight gain, myocardial edema formation, and left ventricular dysfunction in neonatal piglets undergoing cardiopulmonary bypass. Methods: In this randomized prospective study, 18 1-week-old piglets were supported with cardiopulmonary bypass at 100 ml kg -1 · min -1, cooled to 25° C, exposed to 75 minutes of cardioplegic arrest, rewarmed to 37° C, and weaned from bypass. Left ventricular myocardial contractility was assessed by the preload-recruitable stroke work method, with the use of a sonomicrometric two-dimensional cylindrical model, before bypass and at 10, 60, and 120 minutes after separation from bypass. Results: Total body weight gain was significantly less in the modified ultrafiltration group than in either the conventional ultrafiltration group or the control group (no filtration). Myocardial wet/dry ratios were also improved with modified ultrafiltration, but not with conventional ultrafiltration, when compared with no filtration (control group). Hemodynamically, modified ultrafiltration was superior to conventional ultrafiltration and no filtration (control) in raising the mean arterial pressure and increasing the left ventricular preload-recruitable stroke work after bypass. Conclusion: Modified ultrafiltration is superior to conventional ultrafiltration and no filtration in reducing the total body weight gain, lessening myocardial edema, raising mean arterial pressure, and improving left ventricular contractility in neonatal piglets undergoing cardiopulmonary bypass and cardioplegic arrest. (J Thorac Cardiovasc Surg 1998;115:336-42)

Mechanical workload-myocardial water content relationship in isolated rat hearts.

We tested the hypothesis that the mechanical workload of the heart inversely determines the rate of myocardial edema formation in an isolated, perfused rat heart preparation. Heart rate (HR) was varied in three groups by pacing at 125 (HR125), 250 (HR250), or 350 beats/min (HR350). Left ventricular pressure (LVP) was varied in two additional groups by pacing at 250 beats/min and with the addition of either epinephrine (Epi) or propranolol (Pro) to the perfusate. In five otherwise identical groups, variation of coronary vascular resistance was minimized by adenosine. Myocardial water content (MWC) varied significantly and inversely with HR in the HR125, HR250, and HR350 groups. MWC of the HR250 group was significantly less than that of the Pro group but did not differ from the Epi group. However, when adenosine was used, MWC had significant inverse relationships with HR and LVP. We concluded that the mechanical workload of the heart inversely determines the rate and degree of myocardial edema formation in this isolated heart preparation, and both HR and LVP are determinants of this relationship.

Changes in myocardial fluid filtration are reflected in epicardial lymph pressure

The effect of increased fluid filtration on stopped-flow epicardial lymph pressure (P(lymph)), used as an indicator of myocardial interstitial volume, was investigated in the anesthetized open-chest dog. Histamine infusion resulted in an increased systolic peak in the P(lymph) signal together with an increase in diastolic P(lymph) in four of five animals. During reactive hyperemia, systolic and diastolic P(lymph) increased to 127 +/- 8 and 121 +/- 6.7% (mean +/- SE, n = 6) of control, respectively. Peak P(lymph) was approximately 15 s later than peak coronary blood flow and venous pressure (P(ven)). When P(ven) was transiently elevated to 367 +/- 72 (systolic) and 247 +/- 45% (diastolic) of control, P(lymph) increased to 132 +/- 12 and 120 +/- 5.5% of control. The time of response was similar for P(ven) and P(lymph) (t50 approximately 2 S). The increased systolic and diastolic P(lymph) can be explained by an increase in interstitial and lymph filling. It is concluded that changes in myocardial fluid filtration are reflected in epicardial P(lymph). Furthermore, it seems that cardiac contraction constitutes an important defense mechanism against the formation of myocardial edema.

Cardiac surgical conditions induced by β-blockade: Effect on myocardial fluid balance

Both crystalloid and blood cardioplegia result in cardiac dysfunction associated with myocardial edema. This edema is partially due to the lack of myocardial contraction during cardioplegia, which stops myocardial lymph flow. As an alternative, acceptable surgical conditions have been created in patients undergoing coronary artery bypass operations with esmolol-induced minimal myocardial contraction. We hypothesized that minimal myocardial contraction during circulatory support using either standard cardiopulmonary bypass (CPB) or a biventricular assist device would prevent myocardial edema by maintaining cardiac lymphatic function and thus prevent cardiac dysfunction. We placed 6 dogs on CPB and 6 dogs on a biventricular assist device and serially measured myocardial lymph flow rate and myocardial water content in both groups and preload recruitable stroke work only in the CPB dogs. In all dogs we minimized heart rate with esmolol for 1 hour during total circulatory support. Although myocardial lymph flow remained at baseline level during CPB and increased during biventricular assistance, myocardial water accumulation still occurred during circulatory support. However, as edema resolved rapidly after separation from circulatory support, myocardial water content was only slightly increased after CPB and biventricular assistance, and preload recruitable stroke work was normal. Our data suggest that minimal myocardial contraction during both CPB and biventricular assistance supports myocardial lymphatic function, resulting in minimal myocardial edema formation associated with normal left ventricular performance after circulatory support. The concept of minimal myocardial contraction may be a useful alternative for myocardial protection, especially in high-risk patients with compromised left ventricular function.

Effects of acid aspiration-induced lung injury on left ventricular function

Acid aspiration-induced acute lung injury (AALI) leads to myocardial leukosequestration and edema in rats and hemodynamic depression in dogs, but the effects of AALI on left ventricular (LV) function have not been carefully studied. We examined the effects of 0.1 N HCl administration into the lung on LV function, leukosequestration, and edema in pentobarbital-anesthetized, atropinized (n = 8), or autonomically blocked (n = 7) dogs. Saline solution was administered into the lungs of a control group of autonomically blocked dogs (n = 6). LV contractility was assessed by end-systolic elastance (EES) and preload recruitable stroke work (PRSW). Active relaxation was assessed by the time constant of LV pressure decline (tau). AALI resulted in significant (p < 0.05) decreases in mean arterial pressure and cardiac output and increases in pulmonary artery pressure and systemic vascular resistance in atropinized and autonomically blocked dogs but not in saline control group. In atropinized dogs tau did not change after injury, but EES and PRSW were increased significantly at 2 and 3 hours after injury, despite significant myeloperoxidase activity and extravascular fluid wet-dry weight ratios. EES, PRSW, and tau did not change in the autonomically blocked dogs in response to AALI or in the saline control group. We concluded that AALI results in a baroreflex mediated enhancement of LV contractility in dogs, despite mild myocardial leukosequestration and edema formation.

Superiority of the University of Wisconsin solution over simple crystalloid for extended heart preservation

To compare the effects of the University of Wisconsin solution with those of an extracellular crystalloid solution, Krebs-Ringer bicarbonate, as cardiac preservation media, we studied 35 adult dogs in an isolated heart preparation. Four groups of seven hearts were preserved in University of Wisconsin solution for 6 or 12 hours or in Krebs-Ringer bicarbonate solution for 6 or 12 hours. An additional group of seven hearts with no ischemia was used for a control group. In the four preservation groups, hearts were arrested by electrolyte solution (Normosol with potassium chloride, 20 mEq/L, added, 4 degrees C), flushed with 200 ml of the preservation solution, and then stored in the same solution at 1 degree to 2 degrees C. The hearts were mounted on an isolated heart preparation equipped with a computer-controlled servo-pump system that used a mock arterial system to modulate the aortic input impedance presented to the left ventricle. Left ventricular pressure-volume loops were measured on-line for 2 hours of reperfusion with autologous warm oxygenated blood. Elastance was derived from the end-systolic pressure-volume relationship, and diastolic compliance was derived from the end-diastolic pressure-volume relationship. The total left ventricular performance was assessed by the preload recruitable stroke work area, the slope, and its x-intercept, all of which derived from the stroke work (pressure-volume area)-end-diastolic volume relationship. Extended global ischemia had more deleterious effects on the end-diastolic than the end-systolic pressure-volume relationship. In confirmation with other studies, elastance did not accurately reflect the level of ventricular contractile dysfunction because of the significant amount of diastolic dysfunction. The preservation of myocardial systolic and diastolic functions, as demonstrated by the preload recruitable stroke work area and diastolic compliance, was better in the University of Wisconsin solution groups than in the Krebs-Ringer bicarbonate solution groups after 6 and 12 hours of preservation. In addition, 6 hours of preservation with University of Wisconsin solution maintained normal systolic and diastolic functions as compared with those of the control group. Preservation with University of Wisconsin solution prevented any myocardial edema formation; by contrast, this was significantly increased after 12 hours in Krebs-Ringer bicarbonate solution. Groups preserved with University of Wisconsin solution had less reperfusion injury as evidenced by the release of coronary sinus creatine kinase during reperfusion; they also had improved oxygen use during reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Change in (dP/dt)max as an index of myocardial microvascular permeability.

We frequently study processes that alter microvascular permeability in the heart. Myocardial microvascular permeability has been estimated by determining the filtration independent reflection coefficient for beta-lipoprotein (sigma beta-LIPO). This technique requires the measurement of myocardial lymph flow rate and the lymph-to-plasma protein concentration ratio. Unfortunately, it is a nonsurvival procedure. An index of myocardial microvascular permeability was needed that could be determined in experimental preparations without sacrificing valuable chronically instrumented animals. We attempted to relate changes in myocardial microvascular permeability and myocardial edema formation to some index of myocardial performance. In 33 acute, anesthetized dogs (with normal or disrupted myocardial microvasculatures), we measured systemic arterial pressure, systemic venous pressure, coronary sinus pressure, left ventricular pressure, the maximum rate of change in left ventricular pressure (dP/dt)max, myocardial lymph flow rate, and myocardial extravascular fluid volume. Following an increase in coronary sinus pressure, the amount of edema fluid entering the myocardium varied as a function of myocardial microvascular permeability. Further, as the heart became edematous, (dP/dt)max changed with respect to time [delta(dP/dt)max/delta t]. Finally, a significant relation was found between sigma beta-LIPO and delta(dP/dt)max/delta t. Since coronary sinus pressure can be elevated and delta(dP/dt)max/delta t can be measured in chronic animals, this technique may be useful for evaluating myocardial microvascular permeability on a long-term survival basis.

Microvascular, interstitial, and lymphatic interactions in normal heart.

Control of transmicrovascular fluid exchange in the heart is of critical importance in the prevention of myocardial edema formation. To quantify the absolute values for, and the interrelationships between, the forces and flows governing fluid balance within the normal heart, the following variables were measured: arterial pressure (Pa), coronary sinus pressure (Pcs), myocardial interstitial fluid pressure (Pint), plasma protein concentration (Cp), and oncotic pressure (tau cap) along with interstitial protein concentration (CL), interstitial oncotic pressure (tau int), and left ventricular lymph flow rate (Jv). All parameters were recorded under control conditions and during graded venous pressure elevations. Control values were Pa, 125 +/- 21 mmHg; Pcs, 7.3 +/- 1.3 mmHg; Pint, 14.9 +/- 3.1 mmHg; CL/Cp, 0.82 +/- 0.12; and Jv, 7.0 +/- 2.7 ml/h. As Pcs was elevated to eight times control, Pint increased from 15 to 50 mmHg and lymph flow rose sixfold. A filtration-independent value for CL/Cp could not be obtained for total plasma protein, although a washdown CL/Cp value for beta-lipoprotein of 0.04 was obtained. Our data indicate that a large surface area of myocardial exchange vessels coupled with lymphatics of relatively low sensitivity to extravascular volume expansion produce a system that relies on a large increase in interstitial hydrostatic pressure to limit edema formation.

Regional myocardial blood flow, edema formation, and magnetic relaxation times during acute myocardial ischemia in the canine.

This study was designed to measure early changes in myocardial perfusion after acute coronary occlusion, and to examine the relationships among blood flow, myocardial edema, and magnetic relaxation times of ex vivo myocardial tissue. In ten dogs, the left anterior descending coronary artery was occluded for 4 hours prior to sacrifice of the animals. Regional myocardial blood flow was measured using radiolabeled microspheres (15 micron), which were injected into the left atrium 5 minutes prior to sacrifice. Multiple subendocardial tissue samples from the left ventricular free wall were obtained for measurement of magnetic relaxation times, percent water content and tissue radioactivity. Mild, moderate, and severe ischemia were defined as reductions in myocardial blood flow to 30% to 50%, 15% to 30%, and less than or equal to 15% of control, respectively. Myocardial water content was increased with mild ischemia (79.6 +/- 0.7%), moderate ischemia (79.9 +/- 0.4%), and severe ischemia (80.3 +/- 0.6%), all P less than .005 vs. control. T1 relaxation times rose with mild (544 +/- 10 msec, P less than .005 vs. control), moderate (543 +/- 11 msec, P less than .005 vs. control), and severe ischemia (574 +/- 10 msec, P less than .001 vs. control). T2 relaxation times behaved in a similar manner, being prolonged in the mildly, moderately, and severely ischemic groups (38.3 +/- 0.3, 38.1 +/- 0.3 and 38.2 +/- 0.3 msec, respectively; all P less than .001 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of transient coronary ischemia and reperfusion on myocardial edema formation and in vitro magnetic relaxation times

The effects of transient ischemia and reperfusion on regional myocardial function, salvage and swelling have been systematically analyzed in experimental canine preparations. The results of these interventions on myocardial in vitro measurements of magnetic relaxation times (T1 = magnetization recovery, T2 = spin echo) are of significant importance with respect to future nuclear magnetic resonance tomographic imaging. Thus, using a pulsed magnetic resonance spectrometer (10.7 MHz), myocardial tissue samples from two groups of dogs were evaluated. In group 1 (n = six dogs), the left anterior descending artery was occluded for 3 hours before sacrifice; in group 2 (six dogs), 3 hours of occlusion was followed by 1 hour of reperfusion. Multiple tissue samples from normal and ischemic (or ischemic and reperfused) myocardium were obtained for measurement of T1, T2 and % water content (wet weight--dry weight/wet weight). Water content increased with ischemia (78 +/- 4%) and reperfusion (81 +/- 4%) (both p less than 0.01 versus control values). Values for T1 increased with ischemia (598 +/- 39 versus 487 +/- 23 ms in normal tissue from the same heart, p less than 0.01). Even greater T1 changes occurred in the animals with reperfusion (654 +/- 52 ms, p less than 0.01 versus the intra-animal control values). Changes in T2 were similar but less marked (ischemic zone 43.9 +/- 1.0 versus 41.2 +/- 1.0 ms in nonischemic tissue in the corresponding heart, p less than 0.05; reperfusion zone 48.3 +/- 3.5 versus 41.9 +/- 2.3 ms in the normal zone, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of myocardial edema formation on the energy consumption of the heart during aerobiosis and hypoxia.

Isolated rat and guinea pig hearts show, during perfusion with aequeous salt solutions, myocardial edema formation of different degree. The extent of tissue fluid accumulation is dependent on the species, the osmolality, and the oxygen partial pressure of the perfusion medium. With increasing edema formation there is, in both species, an increasing energy requirement for the same hemodynamic state. Addition of 50 mM mannitol to the perfusion medium can diminish edema of the hypoxic perfused rat heart and improves the myocardial function during hypoxia. The beneficial effect of hyperosmolality in the isolated hypoxic rat heart is discussed in terms of an improvement of myocardial energy balance and coronary microcirculation.

The significance of myocardial edema formation for the energy consumption of the aerobically and hypoxically perfused heart: H. Kahles, V.-A. Mezger, P.G. Spieckermann and H.J. Bretschneider. Department of Physiology I, University of Goettingen, Goettingen, F.R.G.

The significance of myocardial edema formation for the energy consumption of the aerobically and hypoxically perfused heart: H. Kahles, V.-A. Mezger, P.G. Spieckermann and H.J. Bretschneider. Department of Physiology I, University of Goettingen, Goettingen, F.R.G.

Effects of procaine-induced cardioplegia on myocardial ischemia, myocardial edema, and postarrest ventricular function: A comparison with potassium-induced cardioplegia and hypothermia

The extent of myocardial protection afforded by a procaine cardioplegic solution during cardiac ischemia has been evaluated and compared with the protection seen using a potassium cardioplegic solution. An isolated cat heart model was employed, and ventricular function parameters, intramyocardial gas tensions, and postischemic myocardial edema were measured and compared following 60 minutes of induced ischemia at 37 degrees C. and 27 degrees C. There was no significant improvement in recovery of postarrest ventricular function when procaine cardioplegia was used during normothermic ischemia. When used at 27 degrees C., however, both cardioplegic solutions were associated with significantly better recovery of postarrest ventricular function, although there was less myocardial edema formation in the potassium-treated hearts. Results of this study indicate that procaine-induced cardioplegia provides myocardial protection during anoxic cardiac arrest which is additive to that afforded by hypothermia alone. In addition, procaine cardioplegia results in postarrest functional recovery which is similar to that seen with potassium cardioplegia.

Cardiac Depression in Bacteremia

Hemodynamic and respiratory effects of a 5-hr IV infusion of Ps. aeruginosa at a dose of 10(8) organisms per ml per minute were studied in 6 dogs. Four dogs served as controls. Gramnegative bacteremia, with 70,000 +/- 1,800 organisms per ml of blood, caused a 50% reduction of cardiac output at three hrs. Peripheral vascular resistance increased significantly, but mean heart rate fell below control levels. Decline in mean systemic blood pressure from 150 +/- 5 mm Hg to 88 +/- 6 mm Hg was accompanied by a significant increase in pulmonary arterial wedge pressure with normal right atrial and pulmonary arterial pressures. Pulmonary vascular resistance also remained unchanged. With progression of the low output state and development of hypothermia, arteriovenous oxygen difference (A-V DO(2)) fell significantly. Despite a decline in functional residual capacity, venoarterial admixture diminished in the face of reduced pulmonary capillary perfusion, normal arterial Po(2) values, decline in body temperature and finally very narrow A-V DO(2). Histologically, ventricular myocardium revealed severe interstitial edema. It is concluded that myocardial dysfunction may occur early during gramnegative bacteremia, and formation of myocardial edema appears to be a significant contributing factor in myocardial failure.

Mechanism of myocardial edema in dogs with chronic congestive heart failure.

The mechanism of myocardial edema was studied by measuring the changes in the water and electrolyte content of the myocardium of dogs with chronic congestive heart failure and of dogs with other experimental lesions producing chronic ascites. Adrenocortical tissue was also studied for comparison with the changes observed in heart muscle. A marked increase in the water content and in the Na and Cl per gram of fat free tissue solids of the myocardium occurred in congestive heart failure; the K content was unaltered. Assuming that the increment in Cl was distributed extracellularly, this increase in water and electrolytes was extracellular. Chronic passive congestion of the myocardium secondary to elevated right atrial pressure seems to be a major pathogenic factor in myocardial edema formation although hyperaldosteronemia and hypoproteinemia may also play a role.