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The authors propose a classification of symptoms of a disturbed microcirculation. Methodical recommendations for studying the microcirculation in patients in the cardiosurgical clinic are given.
Fluorescein angiography was performed in 12 hemispheres of eight young patients with moyamoya disease to study the epicerebral microcirculation. Regional circulation time and the time interval between carotid injection of the dye and first filling of the cortical arteries were various and prolonged in the most parts. There were nonfilling areas by carotid injection of the dye in six hemispheres. By venous injection, the dye appeared in all vessels of the exposed areas. Extravasation of the dye was seen in four hemispheres. The degree of these abnormalities of the epicerebral microcirculation was well correlated with the findings in conventional cerebral angiography.
Platelet aggregates play an important role in rheology of the blood flow in microcirculation. The formation of platelet aggregates markedly raise the threshold diameter of the vessel at which the inversion of Fahraeus-Lindquist effect takes place. In different diseases (ischemic heart disease, diabetes) thromboxane A2 production by platelets is increased and, as a consequence, platelet aggregate formation is facilitated. Platelet aggregation is modulated by several mechanisms, among which thromboxane A2 and thrombin increase and prostacyclin decrease formation of platelet aggregates. Prostacyclin is able also to increase blood red cells deformability thus it appears one of the most important factors for the control of blood flow rheology in microcirculation. However, prostacyclin production is limited in time, and repeated and close periods of venous stasis induce exhaustion of prostacyclin production and increase the formation of platelet aggregates.
In the majority of cases, disorders of coronary microcirculation develop as a result of vascular and rheological disturbances of coronary perfusion. Clinical diagnosis implies the exclusion by coronary angiography of stenoses of the greater coronary arteries (greater than or equal to 200 millimicron) and the functional demonstration of disordered blood supply to the coronary microcirculation. Methodologically, consideration should be given to investigations revealing the cardiac or extracardiac basic disease, i.e. serum and blood analyses, methods for the determination of coronary hemodynamics as well as bioptic procedures. In addition to symptomatic, antianginal measures, therapy involves with priority the specific treatment of the cardiac and extracardiac basic disease, through which a high therapeutic benefit can be expected.
The microcirculation of digestive organs is responsible for providing the fluid required for salivary, gastric, pancreatic, and biliary secretions and plays a major role in removing fluid from the interstitium of the intestines during absorption. Data from the literature suggest that hydrostatic and oncotic pressures within the interstitium are important in modulating fluid movement between the microcirculation and transporting epithelia in most digestive organs. Changes in capillary hydrostatic pressure appear to play a more important role in some organs, i.e., salivary glands. Alterations in the density of perfused capillaries and capillary permeability also enhance capillary fluid exchange during transport. These factors, coupled to the high capillary hydraulic conductivity, allow the digestive organs to move large amounts of fluid between the blood and transporting epithelia.
Microcirculation depends on the undisturbed functioning of the vessel walls as well as of the blood cells and plasma. Flow troubles are always highly complex. Viscosity of blood and plasma is of particular clinical interest, and so are the flexibility of red blood cells including the haemoconcentration and the physiology of coagulation. The authors concentrated on the "local hyperviscosity syndrome", which is one of the primary problems in disturbances of microcirculation, as the basis for their treatment of sudden deafness by fibrinolysis with streptokinase.
Conjunctival biomicroscopy was applied to the study of microcirculation in 30 healthy persons and in 112 patients suffering from diabetes mellitus before and after the treatment. Marked darangement of the end blood flow was expressed in the appearance of perivascular, vascular, and intravascular lesions, increasing with the progress of diabetes mellitus. Adequate therapy gave positive results with the disappearance or reduction of perivascular lesions in the microcirculation, and also improvement of the rheological properties of the blood.
The oxygen regimen of the skin was studied with the aid of polarography and microcirculation according to the data of analysis of microphotos of the vessels of the bulbar conjunctiva carried comparatively in 2 groups of patients who have had myocardial infarction. One group did physical exercises 3 times a week for 1 year, the other served as control. The initial level of physical fitness served to subdivide the group into two subgroups "the strong" and "the weak". It was established that the change of physical fitness under the influence of training is accompanied by considerable shift of the oxygen parameters of tissues, the initial phase of systematic physical loads leads to predominant mobilisation of oxygen transport, during the second phase the utilisation of oxygen by the tissues goes down. In "the weak" subgroup a slow dynamics of change of the compensatory-adaptive phases of oxygen regimen has been noted. Microcirculation parameters studied at rest through microphotos of the vessels of the bulbar conjunctiva showed no differences.
Experiments of 34 dogs were made to study alterations in the cardio- and hemodynamics and microcirculation in the mesenterium during hypotension caused by hemorrhage after intravenous injection of sodium hydroxybutyrate and intravenous re-infusion of heparinized blood under a pressure of 80-120 mm Hg. It was established that single injection of sodium hydroxybutyrate in a dose of 180-200 mg/kg after a 60-minute decrease in the arterial pressure to 40 mm Hg increases pump function of the heart, venous blood returns to the heart, and improves microcirculation. This improvement manifests by the rise in the blood flow rate in the microvessels and in the number of functioning capillaries, and by diminution of red cell aggregation. Favourable effect of the drug is seen within the first minutes after injection and remains unchanged for one hour. Intravenous blood pumping under long-term hypotension is an effective approach to making for the lost blood in the presence of the preceding injection of sodium hydroxybutyrate.
In experiments on 50 adult mongrel dogs the morphofunctional changes were studied in the microcirculation vasculature and contractile myocardium during restriction of the blood flow through the circumflex branch of the left coronary artery by 30, 50, 70 and 90 per cent. The analyses were made with the application of various light optical methods and of electron microscopy. It was found that the morphological changes in the microcirculation vasculature and in the cardiomyocytes (CMC) were proportional to the degree of coronary insufficiency, were mutually connected, and included both pathological and compensatory alterations. The microhaemodynamic (MHD) disturbances had a mosaic character. In consequence of restricted transendothelial transport there developed interstitial oedema with accumulation of products of disturbed metabolism in the interstitial tissue. The hypoxia-induced disturbance of the coordination of CMC contractions and CMC lesions leading to the genesis of contractures and sarcoplasmic oedema may induce microvascular compression and thus further worsen the MHD disturbances.
Study of the microcirculation primarily involves assessment of the capillaroscopic findings. In the clinical field, these are mainly obtained from small vessels of the conjunctiva and nail bed. In more recent years, microcirculation has been accompanied as a subject of examination by haemorheology. The study of blood viscosity and red cell deformability is the most promising from the practical standpoint. In the diagnostic and physiopathological evaluation of capillaroscopic findings, importance is attached to differentiation of arterial and venous vessels, the size, shape and configuration of the small vessels, and above all the presence of intravasal red cell clumps. In examination of the nail bed, particular attention is directed to oddities in the shape of the capillary loops, venous stasis and congestion pictures (in decompensated heart disease, for example, and in cor pulmonale), and alterations in the subpapillary plexuses. Examination of the conjunctiva takes account of the presence of tortuous and serpiginous vessels, with pronounced dilatations, as observed in cardiocirculatory decompensation and chronic bronchopulmonary diseases. In arteriosclerosis, tortuosity and dilatation, even as far as the formation of microaneurysms, may be accompanied by the percent of stiff, thin vessels in networks or webs of various sizes. Clinical pharmacology tests, such as those employing vasoactive drugs (xanthinol nicotinate, buflomedyl, cyticholine) are of interest. They result in a marked increase in calibre, with the appearance of collaterals, regression of red cell aggregates, and improved blood flow.
The hematocrit in the microcirculation of the rat's mesentery was determined either by using measurements of optical density (in 56 arterioles and 52 venules) or by counting the number of red cells per unit vessel length (in 63 capillaries) from photographs. The systemic hematocrit (Hsys) averaged 0.42 +/- 0.025. The mean microvessel hematocrit (Hmicro) decreased and its standard deviation increased with decreasing vessel diameter; in capillaries, Hmicro/Hsys ranged between almost zero and 0.86 with an average of 0.36 +/- 0.23. In order to correct Hmicro for the Fahraeus effect, additional experiments were carried out in vitro, in which the tube hematocrit was obtained by centrifugation of glass tubes (I.D. 13-95 micron) perfused with rat's blood of different feed hematocrit. Even after correction for the Fahraeus effect the in vivo data seem to suggest a 'loss of red cells' in the microcirculation. To reconcile the observed hematocrit distribution with the law of mass conservation, model calculations were performed, in which the presence of shunt vessels was assumed on the one hand, and a proportionality between single vessel hematocrit and flow rate on the other. The experimental data are best described by a model which combines the flow dependence of hematocrit and a small shunt component. The positive correlation between single vessel flow rate and Hmicro which is contained in this model also explains an increase of average capillary hematocrit resulting from a more homogeneous flow distribution associated with vasodilatation.
The effect of cardiac lymphostasis on the microcirculation of the heart was studied in 18 dogs. By ligation of the main lymph trunks and regional lymph nodes of the heart, cardiac lymphoedema--lymphogenic cardiomyopathy--was induced in 9 dogs, while 9 served as control animals. For microcirculatory investigations: 1) gelatin Indian ink injection, 2 benzidine reaction, 3) PVC injection corrosion preparation was applied. Characteristic changes were demonstrated in the microcirculation and capillary circulation of the heart in cardiac lymphostasis. In some capillaries-mainly where the interstitial oedema exists--the capillary circulation decreased: inhomogeneously vessel-free spots were formed in the heart. Around the vessel-free capillaries, elongated capillaries were found including very dilated pre- and post-capillary vessel sections. Arteriovenous shunts can be revealed in the heart in consequence of lymphoedema. The pathogenesis of the microcirculatory circulation changes caused by cardiac lymphostasis was discussed.
Conjunctival biomicroscopy was used to examine microcirculation in 221 males suffering from alcoholism. The control group consisted of 73 practically healthy males. Marked perivascular, vascular, and intravascular changes were revealed in the terminal blood flow system in all the alcoholics; these changes were found to progress, as the disease became graver. After 1.5- to 2-month antialcoholic treatment a distinct improvement of only perivascular disturbances was noted. Quantitative assessment of the microcirculation using the conjunctival indices can be taken for an additional criterion of diagnosis and specification of the alcoholism stage.
The authors studied the microcirculation changes in ascending aorta and left coronary artery of the heart in 25 deceased with myocardial infarction, aged from 52 to 80, with two control groups: 20 cases with complicated atherosclerosis, aged from 54 to 80, and 4 cases--without atherosclerosis, aged 30-45. Histological and histochemical investigation methods were used. The authors found grave changes in vasa vasorum of aorta and coronary artery with the formation of arteries of "closing" type, hyperplasia of the muscular layer of the arterial and venous vessels anf fibrosis of their wall in the deceased with healed myocardial infarction and chronic coronary and cardiac insufficiency. Acute disturbance of blood microcirculation was observed in recent myocardial infarction, analogical to that in case of shock. Necrosis of the type of anemic infarctions and stratification of the wall with hemorrhages and fresh thrombosis were found in the media of aorta and coronary artery in myocardial infarction and atherosclerosis. Both necrosis and stratification are associated with the manifested endothelial proliferation, recent and organized thrombus in the small vasa vasorum and grave structural changes in the supplying vessels of aorta and coronary arteries.
Intrasplenic microcirculation in rats with acute hemolytic anemia has been studied by means of the microsphere method. Alteration in the intrasplenic microcirculation was observed in the anemic rats. The open circulation was reduced from 98% in the normal rats to 67% in the anemic rats, while the closed circulation was increased from 2% in the normal rats to 33% in the anemic ones. The reduction in the open circulation in the anemic rats appears to be attributed to the congestion in the splenic cords as a result of the retardation of the passage of damaged red blood cells. Restoration of the open circulation in rats on the first day of full recovery from anemia seems to be associated with a decrease in the congestion in the splenic cords.
Microcirculation was studied in liver biopsies of patients with viral hepatitis, Gilbert's syndrome, liver steatosis, chronic hepatitis, liver cirrhosis, obstructive jaundice and venous congestion. All these diseases were shown to be usually accompanied by morphologic changes of sinusoid, Disse's and intercellular spaces, cellular membranes of hepatocytes. Those changes causing microcirculation disturbances result in the functional insufficiency of the liver.
Microcirculation in the renal interstitium plays an important role in the regulation of urinary sodium excretion and thus in the control of blood pressure. An increase in renal interstitial hydrostatic pressure caused by renal perfusion pressure elevation induces pressure natriuresis by decreasing tubular reabsorption. Chronic NO inhibition in the medullary interstitium decreases medullary blood flow and induces sodium retention and blood pressure elevation. Chronic medullary, but not intravenous, infusion of ACE inhibitor restores the impaired pressure natriuresis by improving medullary microcirculation in SHR. The tubuloglomerular feedback signal transmission is dependent on Cl concentration in the juxtaglomerular interstitium and its sensitivity is modulated by pressure there in.