Phosphorylation of extrajunctional Cx43 in ischemic-preconditioned rat hearts.

Ischemic preconditioning (IP) has been found to intensify ischemia-induced spreading of connexin 43 (Cx43) into the extrajunctional plasma membrane of the rat heart. Since ischemia is known to induce connexin dephosphorylation and plasmalemmal permeabilization, we considered whether IP might delay dephosphorylation of also extrajunctional connexin and thus impede myocyte permeabilization. Regional myocardial ischemia of both 15 and 45 min duration with and without IP, respectively, was induced in anesthetized rats.

Redistribution of connexin43 in regional acute ischemic myocardium: influence of ischemic preconditioning.

Connexins are known to play an essential role in the ischemic preconditioning (IP) of the heart; their functional role in this process, however, has not been clearly defined. For this reason, anesthetized rats were subjected to regional myocardial ischemia, with or without IP or reperfusion. In frozen sections of hearts, fluorescence immunohistochemical staining for connexin43 (Cx43) was performed.

Extent of damage in ischemic, nonreperfused, and reperfused myocardium of anesthetized rats.

To investigate the localization of the earliest damage in ischemic and ischemic-reperfused myocardium, anesthetized rats were subjected to coronary occlusion for 15, 30, 45, or 90 min. One-half of the animals in each group had no reperfusion, whereas the other half was reperfused for 14 min. With the use of histological methods, preferentially in the periphery of the area at risk, localized zones were detected that lacked the hypoxia-specific increase in NADH fluorescence.

Contribution of myoglobin-induced increases in vascular resistance to shock decompensation in experimental Crush-syndrome in anesthetized rats.

Myoglobin is known to become nephrotoxic when released in greater amounts from skeletal muscle into the general circulation during shock. The present study deals with the question as to whether a myoglobin-induced increase in vascular tone additionally contributes to the detrimental role of this protein in hypovolemic shock. Anesthetized rats were subjected to 250 mg kg x h(-1) myoglobin infused i.

Reduction of severe ischemia/reperfusion injury in rat kidney grafts by a soluble P-selectin glycoprotein ligand.

Background: Inflammatory leukocyte-endothelium interactions, mediated by selectins, contribute to renal ischemia/reperfusion (I/R) injury. We examined the influence of the soluble P-selectin glycoprotein ligand 1 (sPSGL) on early I/R-induced changes in a rat kidney transplantation model with long cold ischemia.

Methods: After 24 hr of cold storage, syngeneic kidneys were grafted into bilaterally nephrectomized rats.

Mapping of capillary flow, cellular redox state, and resting membrane potential in hypoperfused rat myocardium.

The influence on myocyte viability of ischemia-induced changes in capillary perfusion was studied in the hearts of anesthetized rats subjected to partial occlusion of the left coronary artery for 45 min. Timed plasma labeling was applied to determine perfusion patterns. Changes in the fluorescence of preloaded potential-sensitive dyes [tetramethylrhodamine methyl ester (TMRM) and bis-oxonol], of trypan blue, and of endogeneous NADH were utilized in characterizing myocyte viability in histological sections of the heart.

Erucylphosphocholine: pharmacokinetics, biodistribution and CNS-accumulation in the rat after intravenous administration.

The clinical use of alkylphosphocholines (APC) in cancer patients is restricted because of the high gastrointestinal toxicity and the need for oral administration. Therefore we evaluated the clinical pharmacology of erucylphosphocholine (ErPC), the first derivative of the APC family suitable for intravenous administration with strong antineoplastic activity, in vitro and in vivo in rats. The pharmacokinetic parameters after a single intravenous dose of 40 mg/kg were calculated using a two-compartment model: C(max) = 1.

Changes in renal microcirculation induced by infusion of (Fe3+)-and (Fe2+)-myoglobin during hemorrhagic hypotension in the anesthetized rat: influence of L-NAME and 8-Br-cyclic GMP.

The effects of myoglobin on renal microcirculation were studied in anesthetized rats subjected to hemorrhagic hypotension. Capillary flow distribution was determined by allowing two dyes to circulate for 3 and 1 min, respectively, freezing the left kidney and quantifying the dye distribution in histological sections by analyzing the distances of regularly spaced test points to the next dye-labeled capillary. Control experiments showed 88% of distances to be < 12 microns in the cortex [medullary outer stripe (OS): 77%, inner stripe (IS): 93%] and no distance to be > 60 microns.

Capillary perfusion pattern and microvascular geometry in heterogeneous hypoxic areas of hypoperfused rat myocardium.

The origin of heterogeneities in tissue oxygenation due to low-flow ischemia was studied in hypoperfused myocardium of anesthetized rats. In frozen sections of myocardial biopsies the localization of increases in NADH fluorescence, an indicator of tissue hypoxia, was compared with microvascular flow distribution and capillary geometry. The latter parameters were accomplished through capillary labeling with indicator dyes in vivo and enzyme-histochemical staining in vitro, respectively.

Disturbances in renal microcirculation induced by myoglobin and hemorrhagic hypotension in anesthetized rat.

The question was studied of whether myoglobin (Mb), when released into the general circulation during hemorrhagic hypotension (HH), causes disturbances of renal blood flow. In anesthetized rats 250 mg/kg Mb was intravenously infused within 1 h; HH at 50 mmHg with subsequent retransfusion was induced for 30 min. By allowing two dyes to circulate for 1 and 3 min, respectively, and detecting their localization histologically after rapid freezing of the organ, intrarenal distribution of capillary blood flow was studied.

Pulmonary uptake of bupivacaine in isolated perfused rat lung.

The ability of rat lung to remove the local anaesthetic drug bupivacaine from the blood was studied in isolated organs which were perfused either in an open (single-pass mode) or in a closed system (recirculating medium). Isolated perfused rat lungs exhibited a very low capacity to metabolize bupivacaine within 3 h during which the drug circulated continuously through the organ. The clearance values differed only by 0.

Reconstruction of blood flow distribution in the rat kidney during postischemic renal failure.

Inner medullary blood flow has been found to remain nearly unchanged during postischemic renal failure, despite a severely disturbed perfusion in the outer medulla. In order to elucidate this discrepancy, rats were subjected to 1 h left renal artery occlusion and 1 h reflow. The blood plasma was then labeled by dye-conjugated globulin for 1 min.

Method for simultaneous determination of the distribution of capillary plasma flow and myocyte redox state (NADH-fluorescence) in the hypoperfused myocardium of the anesthetized rat.

A method is described which allows to observe the pattern of capillary plasma filling simultaneously with the redox state (NADH-fluorescence) of the myocytes in the hypoperfused myocardium. In anesthetized rats the coronary perfusion pressure was reduced to a defined level, the blood plasma labeled with dye-conjugated albumin and a myocardial biopsy-sampled. Freeze-substitution of histological sections allowed to detect the intravascular plasma label as well as the myocyte NADH-fluorescence on a microscopic level.

Capillary filling kinetics in the rabbit heart during normoxemia and hypoxemia.

In experiments on anesthetized rabbits the kinetics of capillary plasma filling in the heart during normoxemia and hypoxemia were studied. Three gamma globulins originating from three different species were infused into the left atrium for various periods of time. The hearts were shock frozen, and the respective globulins were immunohistochemically identified in parallel sections.

Acute changes in microvascular blood flow distribution in the myocardium of the rat during partial occlusion of the right coronary artery; effects of dihydroergotamine.

Changes in blood flow during restricted right coronary perfusion were studied in anesthetized rats. By use of a carotid-coronary shunt system, coronary perfusion pressure could be reduced to 40 mm Hg, leading to a fall in flow from 0.9 ml/min to 0.

Increased accumulation of plasma albumin in the extracellular space of the heart during hypoxia.

The question which was investigated in this study is whether an augmented capillary protein permeability occurs during hypoxia, an effect which might worsen the supply conditions of the tissue during O2 deficiency. Anaesthetized and thoracotomized rats and mice received an i.v.

Effects of diltiazem and allopurinol in postischemic microcirculatory changes in the rat kidney.

The influence of diltiazem and/or allopurinol on kidney microcirculation was studied in anaesthetized rats, which were subjected to 60 min unilateral renal ischemia followed by 60 min reflow. In histological sections capillary plasma flow patterns were determined based on the distribution of two different fluorochrome-labelled globulins administered i.v.

Determination of capillary perfusion pattern in rat brain by timed plasma labeling.

The pattern of capillary perfusion was studied in the brain of anesthetized rats. Two plasma labels were used to demonstrate the density of capillaries perfused during a 10-min period [fluorescein isothiocyanate (FITC) globulin], as well as during a 10-, 3-, or 1-s period [lissamine-rhodamine B 200 (RB200) globulin, infused into the left heart chamber], respectively. A special biopsy cutting-freezing system was used to withdraw brain tissue via a cranial window for histological analysis of dye distribution at the end of the infusion period.

Influence of diltiazem on postischemic microcirculation and function in the rat kidney.

Renal microcirculation and function were studied in the unilateral clamp-induced ischemia/reperfusion model in anesthetized rats. After 60-min reperfusion fluorochromelabeled globulin was injected i.v.

Hypoxia-induced acute changes in capillary and fiber density and capillary red cell distribution in the rat heart.

The influence of acute hypoxia (respiration gas 12%, 10%, and 8% O2 and asphyxia, respectively) on 1) the density of perfused capillaries and muscle fibers, and 2) the capillary red cell distribution was investigated in the left heart of anesthetized rats. To observe capillaries and fibers, fluorescein isothiocyanate-labeled (FITC)-gamma-globulin and lissamine-rhodamine-B200-labeled (RB200) myoglobin were injected intravenously as labels of the perfused intravasal and the extracellular space, respectively. The hypoxic conditions were induced subsequently and maintained for 3 minutes.

Myocardial interstitial fibrosis in experimental uremia--implications for cardiac compliance.

Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs.

Morphometric investigation of the microvascular system of pancreatic exocrine and endocrine tissue in the rat.

Morphometric data were obtained from the microvasculature in exocrine and endocrine tissue of the rat pancreas. Two groups of anesthetized rats (100 and 300 g body wt, respectively), received intravenous injections of fluorochrome-coupled globulins in order to label the entire vascular system. After circulation of fluorescein-isothiocyanate (FITC)-globulin through the vascular system for 30 min and lissamine rhodamine B 200 (RB 200)-globulin for 5 min, the pancreas was frozen rapidly.

Inhomogenous capillary flow and its prevention by verapamil and hydralazine in the cardiomyopathic Syrian hamster.

There is clinical evidence that human dilated cardiomyopathy is related to microcirculatory disorders. We used an experimental preparation of the disease that consisted of a study of the microcirculation of 45 cardiomyopathic Syrian and 18 control hamsters with timed plasma staining. To investigate dynamic vascular disorders a double injection technique was used that permitted demonstration of all permanently and temporarily perfused capillaries in the same animal.

Capillary density and oxygen supply in human dilated cardiomyopathy.

Human hearts with dilated cardiomyopathy (DCM) exhibit a hypertrophy of the myocytes; consequently, the intercapillary distance increases, which may impede the diffusionable metabolic supply. Therefore in the following study the microcirculation of living human hearts with DCM, excised during cardiac transplantation, was investigated. The hearts were reperfused with a FITC-stained salt-solution, this allowed the precise detection of all plasma perfused capillaries.

Interdependency of local capillary density, blood flow, and metabolism in rat brains.

Previous investigations have established a strong correlation between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). In the present study the relationship between density of perfused brain capillaries and LCBF or LCGU was investigated in conscious and anesthetized rats. Perfused capillaries were stained by labeling the plasma with the gamma globulin-coupled fluorochromes, fluorescein isothiocyanate (FITC) and lissamine-rhodamine B 200 (RB 200).