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Microcirculation of the epimyocardial layer of the heart. I. A method for in vivo observation of the microcirculation of superficial ventricular myocardium of the heart and capillary flow pattern under normal and hypoxic conditions.

To study microcirculation of the heart in vivo, we developed a new technique of epi-illumination of the beating rat ventricular myocardium. Five tiny needles connected to the operation table were horizontally inserted into the ventricular myocardium just beneath the epicardium in order to restrict cardiac movement during contraction and to enhance the amount of light reflected from the structures under study. The in vivo light and fluorescent microscopy were performed with the Ultropak and the Fluopak systems (Leitz) combined with a highly sensitive television camera and recording system. In 142 individual in vivo measurements (6 animals) the mean capillary diameter amounted to 6.0 +/- 1.0 mu. In the same experiments, the mean intercapillary distance was 18.7 +/- 1.7 mu. In agreement with the literature, the capillaries of the epimyocardial layer of the rat heart demonstrate a mixed countercurrent flow pattern. In contrast to other authors, we observed no recruitment of resting capillaries after hypoxia.

Animals

The organization of the salivary gland microcirculation.

1. The microvasculature of the rabbit submandibular salivary gland has been investigated employing in vivo microscopy, blood flow measurements, latex casts, microsphere injections and examination of fixed sections of the gland.2. Two principal microcirculations were distinguished in the living gland, one supplying the acini and the other the intralobular ducts. Parasympathetic nerve stimulation (2, 5 or 10 sec(-1)) elicited different responses in each of the two microcirculations. Flow in the capillaries around the acini slowed initially before increasing. In contrast, flow in the intralobular duct capillaries increased soon after beginning stimulation.3. In some experiments both whole gland flow and microvascular flow were monitored simultaneously. Whole gland flow increased at the same time as flow in the acinar capillaries was decreasing and as flow in the intralobular duct capillaries increased. Flow in acinar capillaries increased about 5 sec after glandular flow started to increase.4. These observations could be explained if either the vascular beds of the acini and the intralobular ducts were arranged in parallel or if arteriovenous anastomoses were to shunt the acinar circulation. No such anastomoses were found in latex casts made of the gland vasculature, and microspheres injected into the artery supplying the gland were not found in the venous effluent.5. The intraglandular distribution of microspheres was measured in histological sections of the injected glands to give an estimate of the distribution of blood flow between the duct and acinar microcirculations. At rest and during maintained stimulation about 55% of the blood flow passed through the intralobular duct microcirculations, whilst during this initial 15 sec of stimulation this proportion was increased to over 70%. This finding is consistent with a parallel arrangement of the two microcirculations.6. The conclusions drawn from these observations are that the duct and acinar microcirculations are arranged in parallel, that there are differences in the way the vasodilatation is mediated in these circulations, and that arterio-venous anastomoses play no significant role in this gland.

Animals

Aspects of the microcirculation.

The microcirculation is an important but little understood part of the cardiovascular system. As new techniques have been developed, more accurate information has become available concerning the changes in the microcirculation in both health and disease. A review has been made of some of the more important facets of the microcirculation of particular interest to surgeons. Reference is made to basic physiology, especially the mechanisms controlling flow in the microcirculation. The significance of changes in small blood vessels in hypovolaemic, septic, and progressive shock is also discussed, and the role of platelet aggregation in shock states is explored.

Animals

[Overacidified tissue and microcirculation (author's transl)].

A discussion of physiological fundamentals with respect to the inhibition of blood microcirculation in (tumor) tissue at reduced pH values around 6.0 is followed by a report on principles, design and results obtained with a light probe array which permits to determine in vivo reference values of the relative intensity of microcirulation in both normal and tumor tissues under various conditions. An analysis of the discussed records has shown that--as compared to a value of 80-66% without glucose infusion--the relative mean intensity of microcirculation in tumor tissue drops to approximately 8-4% about 300 min after the onset of glucose infusion under CMT administration at 37 degrees C. By adding the CMT step of hyperthermy, the relative mean intensity of microcirculation--compared to normal tissue at 37 degrees C--will further drop below 1%. With such a decline of microcirculation--and an adequate duration of, say, 8 hours--local hyperthermy at 41-42 degrees C is likely to cause a very pronounced damaging action on tumor tissue because the then noticeably reduced substrate offer proves to be insufficient to ensure the structure-maintaining metabolic rate of cancer cells.

Animals

Stimulation and blockade of cholinergic receptors in terminal liver microcirculation in rats.

This study was designed to establish the existence of cholinergic vascular receptors in the terminal portion of the rat liver microcirculation. The liver microcirculation was observed in vivo by a transillumination technique through a television microscope. The changes in the caliber of the liver sinusoids were measured directly on the television screen. Infusion of the parasympathetic neurotransmitter acetylcholine into the portal venous circulation caused a concentration-dependent dilation of liver sinusoids. Similar dilatation effects were observed for other cholinergic receptor agonists. Atropine, the specific cholinergic receptor blocker, inhibited this dilator effect, displacing the acetylcholine concentration-effect curve to the right. In contrast, physostigmine, the cholinesterase inhibitor, caused displacement of the curve to the left. In conclusion, cholinergic receptors are present in the terminal portion of the liver microcirculation, subserving the functional role of vasodilatation.

Acetylcholine

Central nervous system mediated stimulation by thyrotropin-releasing hormone of microcirculation in thyroid gland of rats.

The blood flow of thyroid, adrenal cortex and renal cortex in the pentobarbital anesthetized rat was assessed from hydrogen gas desaturation curve. The microcirculation of thyroid was markedly augmented within 2 min after an intraventricular injection of Thyrotropin-Releasing Hormone (TRH) while Met-Enkephalin (ENK) failed to influence. Both TRH and ENK stimulated the microcirculation of adrenal cortex moderately. ENK diminished the microcirculation of renal cortex whereas TRH did not exert any effect. The response of thyroid to TRH was abolished by vagotomy, thus the existence of a specific TRH-vagus -thyroid connection was indicated.

Adrenal Cortex

Deterioration of the microcirculation in diabetes.

Studies of the microcirculation in diabetes in the last fifteen years have concentrated heavily on anatomic and biochemical abnormalities of the capillary basement membrane. Greater insights into basement membrane changes have eclipsed the previous picture of widespread progressive deterioration of the entire microcirculation. The history, variety of organ involvement, pattern of circulatory decline, and associated anatomic, physiologic, and biochemical findings are re-examined so that recently described potential mechanisms for the development of diabetic microangiopathy may be understood in a broader perspective. The possible contributions of seven categories of diabetic changes to damage of the microcirculation are outlined. The categories are: (1) altered basement membrane, (2) altered cellular function, (3) cell metabolic changes, (4) altered blood flow properties, (5) distrubed hemostasis, (6) altered oxygen transport, and (7) altered hormone production. The variety of clinical manifestations in long-standing diabetes related to microangiopathy appears to be due to a combination of a widely variable over-all rate of progression and a differing ability of body tissues and organs to accommodate to the sequential circulatory changes. The slow rate of deterioration in most diabetics suggests that several abnormalities must interact to produce the observed progression. A clear understanding of the interactions responsible for diabetic microangiopathy is becoming more important as new options in the management of diabetes become available.

Basement Membrane

[Extracardiac effect of nitroglycerin in chronic ischemic heart disease according to the study of microcirculation].

Study of the dynamics of circulation in the microvessels of the eye conjunctiva under the effect of nitroglycerin in 50 patients with chronic ischemic heart disease showed short-lived dilatation of the postcapillaries and venules in most of them. Simultaneous fall in venous pressure may be evidence of a diminution of the venous tonus with a tendency to the storage of blood in the microcirculation system. The encountered shifts in the systemic hemodynamics may possibly be due to the reaction of the microcirculation channel, the labile character of which in the various "micro-areas" of the conjunctiva testifies to the complex reorganization of microcirculation under the effect of nitroglycerin.

Adult

[State of microcirculation in various zones of the heart in myocardial infarct complicated by congestive circulatory insufficiency].

A definite correlative connection has been revealed between the clinical course of myocardial infarction, the extent of affection of the heart muscle, the severity of the atherosclerotic process in the coronary arteries, and the condition of microcirculation in different zones of the heart. The severest affections of the heart muscle, stenosing coronarosclerosis and disorders of microcirculation in different zones of the heart were encountered in patients with myocardial infarction marked by a recurrent course and complicated by cardiogenic shock or congestive circulatory insufficiency. It is shown that the character of changes in microcirculation determines to a great measure the later condition of the structure and function of the myocardial muscle cell in areas near and remote from the infarction.

Adult

Bone marrow necrosis. acute microcirculation failure in myelomonocytic leukemia.

We saw bone marrow necrosis in a case of acute myelomonocytic leukemia. The diagnosis was made during the patinet's life, and the bone marrow microcirculation was studied immediately postmortem. Histology and injection of the bone marrow arteries showed an acute microcirculation failure. The pathogenesis and possible relationship with soluble immune complexes was studied.

Adult

A filtration model for study of leukocyte transit in the microcirculation.

In order to study characteristics of leukocytes which would be important determinants of their flow in the microcirculation, a model system was tested which utilizes in vitro filtration of leukocytes. Normal human peripheral blood leukocytes (85-90% granulocytes) were studied with filters with uniform 8 mum pore size. Studies were performed to determine the effects of EDTA, temperature, hydrostatic pressure, pH, and osmolarity on filtration. Filterability was optimal at 0.2% EDTA, 10 cm hydrostatic pressure, neutral pH, isotonicity, and at room temperature. Filtration was slowed greatly at leukocyte concentrations exceeding 25 X 10(9)/liter. When leukocyte membranes were altered by formalin fixation, filtration slowed greatly, indicating that deformability is an important determinant of flow through small orifices. When mixtures of erythrocytes and leukocytes were filtered, there was a paradoxically enhanced transit of leukocytes compared to filtration of leukocytes alone, indicating interactions between these cells which alter flow. These studies serve to characterize this model system which can be used to study the contribution to flow in the microcirculation of both normal and pathological leukocytes.

Adult

Prevention of ionizing radiation-induced liver microcirculation changes by the use of flow improvers.

Platelet aggregation and adhesiveness, as well as TpO2 responses to hypoxia were measured as microcirculation parameters in beagle dogs subject to Co60 ionizing radiation to a dose of 4600 rads in 5 weeks. Simultaneously, changes in blood chemistry and coagulation were also determined. Marked changes in all studied parameters in the post radiation period lead to the conclusion that the radiation liver damage, which is at least in part mediated through microcirculation disturbances, can be prevented with the flow improver, Rheomacrodex.

Animals

Are epinephrine and gastrin accelerative factors of acute cinchophen ulcer?: Studies on gastric mucosal microcirculation and gastric secretion.

Measurements of serum epinephrine and gastrin, simultaneously, gastric mucosal blood flow and gastric secretion were carried out in cinchophen treated dogs. No significant changes in either serum concentrations of epinephrine and gastrin or fundic mucosal microcirculation after a single 100 mg/kg cinchophen administration were found while gastric secretion increased markedly after the medication. On the other hand, a significant increase in serum epinephrine and gastrin levels was observed while gastric secretion decreased significantly after large doses of cinchophen (300 mg/kg) were injected intravenously. Here gastric mucosal microcirculation is decreased. Repeated administration of 100 mg/kg cinchophen for 3 to 7 days brought about an increase in epinephrine and gastrin levels and caused an occurrence of fundic mucosal hemorrhage. Sympathetic discharge and gastrin release were not seen after a 3-week period of cinchophen administration. Cinchophen ulcers were produced, even when contact between the bile and the stomach mucosa was avoided. Vagotomy had no connection with ulceration and gastric secretion.

Animals

A contribution to the physiology of the perilymph. Part IV: Effect of histamine on the cochlear microcirculation.

Summary--Because of the topography of the perilymphatic vascular network, the cochlear microcirculation is especially sensitive to the effect of vasoactive substances reaching the perilymphatic space. The cochlear microcirculation is mainly controlled humorally, via the activity of the metarterioles and changes in the flow properties of the blood. Intracochlear histamine reduces the cochlear circulation even more markedly than after intracarotid administration. No systematic effects of parenteral administration of vasoactive substances can be expected on the cochlear circulation. Reversible auditory disorders after stapedectomy may be explicable by the intracochlear release of histamine. The internal release of histamine after sunstroke and cold stress may play a part in sudden dusturbances of hearing.

Animals

In vivo observation of tracheal microcirculation in dogs.

Tracheal microcirculation was studied in six healthy anesthetized adult mongrel dogs. A transparent balloon was used to apply pressure to the tracheal mucosa during observation of the microcirculation. Pressures of microvascular occlusion were measured using an electrically callibrated silicone, envelope placed on the observation balloon. The different vessel sizes were measured and classified using the operating microscope. Capillary occlusion pressures ranged from 10 to 40 msurements of tracheal diameter were performed. Progressive local and generalized dilatation occurred. Capillary occlusion pressure was lower in the more dilated specimens. The lower than expected occlusion pressures are thought to be a result of the tracheal dilatation and may be related to the administration of drugs or other factors.

Animals

Relations between disturbances in microcirculation and accumulation of lipids in the aortic wall.

For the purpose of unraveling the relations between disturbances in microcirculation and deposition of lipids in the aortic wall, 9 rabbits were fed a 1% cholesterol and 5% coconut oil at intervals up to 16 weeks, and 4 rabbits were used as controls. After microangiography of vasa vasorum, the same specimens were studied histochemically. The distribution of vasa vasorum became poorer on sacrifice by microangiography. However, it could not be thought that disturbances in vasa vasorum was a cause in the early deposition of lipids, because lesions were histologically mild in the greater parts of vasa vasorum. The sites of prediction for the vascular lesions were initially the branching part, and then the thoracic aorta. Thickness and numbers of the elastic lamina in the media decreased straightly in the distal direction, and the degree of intimal thickening and accumulation of lipids were parallel with the degree of the medial thickness. The intimal cells tended to be arranged radially with wide intercellular spaces in the cross section, suggesting the convenience for the passage of fluids. From the above facts, it may be reasonable to presume that the difference in severity of disturbances of microcirculation resulted in the difference in the site of predilection.

Angiography

Effects of vasodilators on microcirculation of the rat cremaster muscle: a microscopic method for screening drugs.

Effects of vasodilating drugs on microcirculation of the rat cremaster muscle were investigated microscopically. Topical application and intravenous injection of papaverine produced dilatation of arterioles. Cyclandelate applied topically dilated the arterioles to a considerable extent. Topical application of bamethan induced arteriolar dilatation while bamethan given intravenously constricted the arterioles. Kallikrein applied topically induced a slight dilatation of arterioles, and intravenous administration of kallikrein produced an appreciable vasodilatation. Topical administration of bradykinin produced a vasodilatation of arterioles of the rat cremaster muscle. These results indicate that direct action of a drug on the microcirculation can be properly evaluated by the microscopic method in the rat cremater muscle, if the drug is applied topically, in the vicinity of small vessels under study.

Acetylcholine