The histological effects of acute and chronic obstruction of the cardiac lymphatic system or of an imbalance of cardiac lymph formation and drainage should impair cardiac performance as mentioned above. Indeed, this has been confirmed repeatedly in the last years.
One of the earlier investigations on the functional importance of intact cardiac lymphatic drainage studied the cardiac output following cardiac lymphatic obstruction in isolated rat hearts.88 Cardiac output decreased by 33% within 90 min in the lymphostatic hearts, whereas it remained stable in hearts with freely draining lymph. The reduction in cardiac function following lymphatic obstruction was not related to coronary perfusion, which was not different in lymph obstructed and control hearts and did not change during the experiment.
In anaesthetized dogs, interruption of the cardiac lymph drainage by ligation of the epi-cardial lymphatics, the afferent and efferent lymphatics of the pretracheal and cardiac lymph nodes and of the thoracic duct caused myocardial edema within 3 hours.86 Simultaneously, the left ventricular function assessed by the preload recruitable stroke work (PRSW) was impaired significantly.86
In another study in dogs,34 cardiac lymph production was promoted by elevation of the coronary sinus pressure and cardiac lymph drainage was almost abolished by elevating the superior vena caval pressure. This maneuver produced 35% increase in myocardial extravascu-lar fluid within 3 hours and a 40% reduction in cardiac output. The impaired myocardial performance was not related to decreased coronary artery blood flow, which was maintained during increased coronary sinus pressure. Thus, the impaired myocardial function probably resulted from the myocardial edema in consequence to an imbalance of lymph formation and drainage.
Enhanced myocardial water content and depressed left ventricular performance was also observed in dogs with chronic elevation of right heart pressure by pulmonary artery banding.34 In this model, the enhanced right heart pressure affected both left ventricular microvascular filtration and cardiac lymph drainage: coronary sinus and left ventricular microvascular pressure was increased, which promoted cardiac lymph formation, and superior vena caval pressure was elevated, which impeded cardiac lymph drainage. Again, an imbalance of lymph formation and flow was present causing edema and impaired left ventricular function.
Experiments with cardiopulmonary bypass and cardiac arrest57,58 showed a reduction of cardiac lymph flow to < 30% of baseline during cardiac arrest and myocardial edema developed. Cardiac performance (assessed by PRSW) was significantly impaired after bypass and the depression was closely related to the myocardial water content.
Another experimental study101 has investigated the effect of increasing coronary sinus pressure and cardiac microvascular permeability on left ventricular dp/dtmax. These interventions caused myocardial edema and a change in dp/dtmax with time, which was closely related to the amount of edema, which had accumulated during the 3 hour experimental period. Cardiac lymphatic drainage was not experimentally impeded in these experiments. Nevertheless, the experimental interventions caused an imbalance of lymph formation and flow as shown by the development of myocardial edema.
As described above, intermittent coronary sinus occlusion (ICSO) was reported to give rise to fluid reabsorption from the myocardium at least during deflation of the coronary sinus balloon.26 Possibly, reduction of myocardial edema contributes to the functional improvement of ischemic myocardium by ICSO.102 The effect of ICSO on myocardial interstitial fluid volume, however, remains to be established.
In summary, the studies demonstrate the importance of an adequate drainage of cardiac lymph and normal myocardial water content for the performance of the heart. Acute and chronic cardiac edema impairs cardiac function. Edema develops as a consequence of an imbalance of the formation and drainage of lymph. This occurs when a high venous pressure promotes microvascular filtration and impedes lymph flow, e.g., in congestive heart failure, in pulmonary hypertension, and after a Fontan operation. The cardiac edema and the resulting histological changes including fibrosis possibly contribute to the cardiac dysfunction.
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