scholarly journals Morphological and functional changes of coronary vasculature caused by transcellular biosynthesis of sulfidopeptide leukotrienes in isolated heart of rabbit

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1824-1832 ◽  
Author(s):  
A Sala ◽  
GM Aliev ◽  
G Rossoni ◽  
F Berti ◽  
C Buccellati ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Isolated Heart ◽  
Rabbit Heart ◽  
Coronary Perfusion Pressure ◽  
Coronary Vasospasm ◽  
Coronary Perfusion ◽  
Lipoxygenase Inhibitor ◽  
Morphological Alterations ◽  
Functional Changes ◽  
Macrophage Colony

Morphological and functional modifications occurring in Langendorff rabbit heart preparations perfused with purified human leukocytes (PMNL), as an organ model of sulfidopeptide-leukotrienes (sLT) transcellular biosynthesis, were studied. Coronary perfusion pressure (CPP), monitored as an index of coronary vasospasm, increased by 295% after challenge with the Ca(2+)-ionophore A-23187 (0.5 micromol/L) for 30′, accompanied by a significant formation of sLT. Increase in CPP was prevented by PMNL pretreatment with the 5-lipoxygenase inhibitor MK-886 (1 micromol/L) or by heart pretreatment with LTD4-receptor antagonist SKF 104353, indicating a pivotal role of PMNL-derived 5-lipoxygenase (5- LO) products in the observed functional modifications. Similar effects were obtained using granulocyte macrophage-colony stimulating factor- primed PMNL challenged with the tripeptide n-formyl-methionyl-leucyl- phenylalanine. Scanning electron microscopy (SEM) of coronary arteries showed craters on the vessel luminal surface, PMNL adhering to endothelial cells (EC), increased number of microvilli on EC, presence of nonviable, desquamating, fusiform EC. SEM and transmission electron microscopy of myocardial microvessels, showed presence of perivascular and intermuscle edema, presence of activated PMNL and decreased number of patent microvessels. These morphological alterations were significantly blunted by MK-886 or SKF 104353. These data provide evidence of close interaction between PMNL and myocardial EC, resulting in enhanced sLT formation via transcellular biosynthesis, originating from transfer of PMNL-derived LTA4 to EC. These potent proinflammatory autacoids are responsible for coronary vasospasm and the morphological alternations observed.

scholarly journals Morphological and functional changes of coronary vasculature caused by transcellular biosynthesis of sulfidopeptide leukotrienes in isolated heart of rabbit

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1824-1832 ◽  
Author(s):  
A Sala ◽  
GM Aliev ◽  
G Rossoni ◽  
F Berti ◽  
C Buccellati ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Isolated Heart ◽  
Rabbit Heart ◽  
Coronary Perfusion Pressure ◽  
Coronary Vasospasm ◽  
Coronary Perfusion ◽  
Lipoxygenase Inhibitor ◽  
Morphological Alterations ◽  
Functional Changes ◽  
Macrophage Colony

Abstract Morphological and functional modifications occurring in Langendorff rabbit heart preparations perfused with purified human leukocytes (PMNL), as an organ model of sulfidopeptide-leukotrienes (sLT) transcellular biosynthesis, were studied. Coronary perfusion pressure (CPP), monitored as an index of coronary vasospasm, increased by 295% after challenge with the Ca(2+)-ionophore A-23187 (0.5 micromol/L) for 30′, accompanied by a significant formation of sLT. Increase in CPP was prevented by PMNL pretreatment with the 5-lipoxygenase inhibitor MK-886 (1 micromol/L) or by heart pretreatment with LTD4-receptor antagonist SKF 104353, indicating a pivotal role of PMNL-derived 5-lipoxygenase (5- LO) products in the observed functional modifications. Similar effects were obtained using granulocyte macrophage-colony stimulating factor- primed PMNL challenged with the tripeptide n-formyl-methionyl-leucyl- phenylalanine. Scanning electron microscopy (SEM) of coronary arteries showed craters on the vessel luminal surface, PMNL adhering to endothelial cells (EC), increased number of microvilli on EC, presence of nonviable, desquamating, fusiform EC. SEM and transmission electron microscopy of myocardial microvessels, showed presence of perivascular and intermuscle edema, presence of activated PMNL and decreased number of patent microvessels. These morphological alterations were significantly blunted by MK-886 or SKF 104353. These data provide evidence of close interaction between PMNL and myocardial EC, resulting in enhanced sLT formation via transcellular biosynthesis, originating from transfer of PMNL-derived LTA4 to EC. These potent proinflammatory autacoids are responsible for coronary vasospasm and the morphological alternations observed.

Prostacyclin-induced vasodilation in rabbit heart is mediated by ATP-sensitive potassium channels

1993 ◽  
Vol 264 (1) ◽  
pp. H238-H243 ◽  
Author(s):  
W. F. Jackson ◽  
A. Konig ◽  
T. Dambacher ◽  
R. Busse
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Muscle Relaxation ◽  
Rabbit Heart ◽  
Coronary Perfusion Pressure ◽  
Smooth Muscle Relaxation ◽  
Coronary Perfusion ◽  
Langendorff Preparation ◽  
Oxide Synthase

We tested the hypothesis that prostacyclin and its stable analogue iloprost act as agonists of ATP-sensitive potassium channels (KATP) to induce vasodilation of the coronary circulation. The selective blocker of KATP, glibenclamide, was used as a probe for vasodilation mediated by KATP in saline-perfused rabbit hearts (constant flow, Langendorff preparation). Glibenclamide (10-300 nM) significantly increased coronary perfusion pressure and inhibited vasodilation induced by iloprost (1-30 nM), prostacyclin (10 nM), adenosine (0.3 microM), and cromakalim (0.1 microM), a known agonist of KATP. This potassium channel antagonist also inhibited vasodilation of rabbit hearts in response to 10 nM bradykinin in the presence of an inhibitor of nitric oxide synthase (30 microM NG-nitro-L-arginine). Because bradykinin-induced vasodilation is mediated by prostacyclin released from endothelial cells when nitric oxide synthesis is inhibited, these data indicate that glibenclamide is also effective against endogenous prostacyclin. The inhibitory effects of glibenclamide were selective: vasodilation induced by sodium nitroprusside (1-10 microM) or acetylcholine (1 microM) were not inhibited by this potassium channel antagonist. In addition, basal and bradykinin-stimulated release of 6-ketoprostaglandin F1 alpha was not affected by this antagonist of KATP. Glibenclamide also did not inhibit the activation of adenylate cyclase, as indicated by its lack of effect on adenosine 3',5'-cyclic monophosphate accumulation induced by iloprost (10 nM-1 microM) in bovine coronary arterial segments, a tissue in which iloprost-induced vascular smooth muscle relaxation is inhibited by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of venous pressure on coronary circulation and intramyocardial fluid mechanics

1994 ◽  
Vol 267 (3) ◽  
pp. H1002-H1009 ◽  
Author(s):  
I. Izrailtyan ◽  
H. F. Frasch ◽  
J. Y. Kresh
Keyword(s):  
Coronary Flow ◽  
Coronary Circulation ◽  
Venous Pressure ◽  
Rabbit Heart ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Right Heart ◽  
Tissue Pressure ◽  
Parallel Shift ◽  
The Right

This investigation examined the interaction between right heart pressure (RHP), coronary perfusion pressure (CPP), intramyocardial tissue pressure (IMP), and coronary flow mechanics, including partitioning of coronary effluent in the isolated Krebs-Henseleit perfused rabbit heart. The major new finding was a parallel shift in the IMP-inflow relationship to a higher tissue pressure level in response to an increase in RHP. Accompanying the rise in RHP from 0 to 15 and 25 mmHg, IMP at zero coronary inflow in the beating (and arrested) heart increased from 5.8 +/- 1.0 (7.7 +/- 1.2) to 16.3 +/- 1.2 (17.9 +/- 1.3) and 28.6 +/- 1.7 (26.4 +/- 2.0) mmHg, respectively. A concomitant parallel shift in the CPP-inflow relation to higher pressures was consistently observed. The fraction of total coronary flow drained by the right heart was not constant. A higher partition of coronary outflow to the left heart (7.8 +/- 3.8, 34.3 +/- 3.0, and 47.9 +/- 4.3%, respectively) accompanied the increase in RHP. Intramyocardial partitioning of coronary outflow pathways mediates the effects of venous pressure modulation on coronary circulation. The interaction between coronary venous pressure and the extravascular environment modifies the effective back pressure to arterial inflow.

Coronary constrictor effect of stroma-free hemoglobin solutions

1986 ◽  
Vol 251 (2) ◽  
pp. H413-H420 ◽  
Author(s):  
W. M. Vogel ◽  
R. C. Dennis ◽  
G. Cassidy ◽  
C. S. Apstein ◽  
C. R. Valeri
Keyword(s):  
Perfusion Pressure ◽  
Rabbit Heart ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Free Hemoglobin ◽  
Guinea Pig Heart ◽  
Vasoconstrictor Effect ◽  
O2 Delivery ◽  
Perfused Hearts ◽  
Coronary Vasoconstrictor

A coronary vasoconstrictor effect of human stroma-free hemoglobin (SFH) was identified in isolated rabbit hearts perfused with Krebs-Henseleit buffer or whole rabbit blood at a constant coronary flow rate. In buffer-perfused hearts, SFH in concentrations of 5 to 200 mg/dl produced dose-related increases of coronary perfusion pressure. At a concentration of 150 mg/dl, SFH, equilibrated with CO to form carboxyhemoglobin, caused an increase in perfusion pressure (55 +/- 7 mmHg), similar to that observed with oxyhemoglobin (57 +/- 6 mmHg); addition of potassium ferricyanide to form methemoglobin reduced the increase of perfusion pressure to 34 +/- 5 mmHg (P less than 0.05). The vasoconstrictor activity could not be eliminated by dialyzing against the perfusion buffer. Human SFH prepared by different methods had similar vasoconstrictor activity. Rabbit SFH and human SFH were equi-effective in the rabbit heart. Less constrictor activity of SFH was evident in rat and guinea pig heart. Polymerized, pyridoxalated SFH had greatly reduced constrictor effect compared with unmodified or pyridoxalated tetramer SFH. In blood-perfused hearts, increasing plasma hemoglobin to 1.6 +/- 0.1 g/dl, without changing total hemoglobin or arterial O2 content, increased coronary perfusion pressure by 36 +/- 13 mmHg (P less than 0.05). We conclude that stroma-free hemoglobin solutions exert a coronary vasoconstrictor effect that is unrelated to O2 delivery.

Free radicals upregulate complement expression in rabbit isolated heart

2000 ◽  
Vol 279 (1) ◽  
pp. H195-H201 ◽  
Author(s):  
Elaine J. Tanhehco ◽  
Koji Yasojima ◽  
Patrick L. McGeer ◽  
Ruth A. Washington ◽  
Benedict R. Lucchesi
Keyword(s):  
Free Radicals ◽  
Complement Activation ◽  
Diastolic Pressure ◽  
Tissue Injury ◽  
Isolated Heart ◽  
Membrane Attack Complex ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Isolated Hearts

Both free radicals and complement activation can injure tissue. Our study determined whether free radicals alter complement production by the myocardium. Isolated hearts from New Zealand White rabbits were perfused on a Langendorff apparatus and exposed to xanthine (X; 100 μM) plus xanthine oxidase (XO; 8 mU/ml) (X/XO). The free radical-generating system significantly ( P < 0.05) increased C1q and also increased C1r, C3, C8, and C9 transcription compared with controls. Immunohistological examination revealed augmented membrane attack complex deposition on X/XO-treated tissue. X/XO-treated hearts also exhibited significant ( P < 0.05) increases in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in left-ventricular developed pressure. N-(2-mercaptopropionyl)-glycine (3 mM), in conjunction with the superoxide dismutase mimetic SC-52608 (100 μM), significantly ( P < 0.05) reduced the upregulation of C1q, C1r, C3, C8, and C9 mRNA expression elicited by X/XO. The antioxidants also ameliorated the deterioration in function caused by X/XO. Local complement activation may represent a mechanism by which free radicals mediate tissue injury.

Left ventricular performance and blood catecholamine levels in the isolated heart

1966 ◽  
Vol 211 (5) ◽  
pp. 1248-1254 ◽  
Author(s):  
R. Grier Monroe ◽  
C. G. La Farge ◽  
W. J. Gamble ◽  
R. P. Hammond ◽  
R. Gamboa
Keyword(s):  
Diastolic Pressure ◽  
Isolated Heart ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Left Ventricular Performance ◽  
Ventricular Performance ◽  
Isolated Lungs ◽  
Catecholamine Levels ◽  
Catecholamine Concentration

Left ventricular performance in the isolated heart of the dog as expressed by the peak systolic intraventricular pressure was observed during control periods when the heart was perfused with blood from a healthy anesthetized donor and after the donor was removed and the heart perfused with blood oxygenated by isolated lungs. Heart rate, coronary perfusion pressure, ventricular end-diastolic pressure, and stroke volume were maintained constant throughout. While the heart was perfused with blood from a donor, ventricular performance showed no tendency to decline, although coronary flow invariably increased. On removing the donor and perfusing the heart with blood oxygenated by isolated lungs, myocardial performance declined in proportion to the decline in the total catecholamine concentration of the perfusing blood. Restoration of catecholamine levels by infusing epinephrine and norepinephrine also restored left ventricular performance.

Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion

2004 ◽  
Vol 287 (4) ◽  
pp. H1522-H1529 ◽  
Author(s):  
Chris J. Pemberton ◽  
Heikki Tokola ◽  
Zsolt Bagi ◽  
Akos Koller ◽  
Juhani Pöntinen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natriuretic Peptide ◽  
Cardiac Tissue ◽  
Contractile Function ◽  
Isolated Heart ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Neonatal Cardiomyocytes ◽  
Peptide Secretion ◽  
Coronary Arterioles

We administered ghrelin, a novel growth hormone-releasing hormone, to isolated perfused rat hearts, coronary arterioles, and cultured neonatal cardiomyocytes to determine its effects on coronary vascular tone, contractility, and natriuretic peptide secretion and gene expression. We also determined cardiac levels of ghrelin and whether the heart is a source of the circulating peptide. Ghrelin dose dependently increased coronary perfusion pressure (44 ± 9%, P < 0.01), constricted isolated coronary arterioles (12 ± 2%, P < 0.05), and significantly enhanced the pressure-induced myogenic tone of arterioles. These effects were blocked by diltiazem, an L-type Ca2+ channel blocker, and bisindolylmaleimide (Bis), a protein kinase C (PKC) inhibitor. Interestingly, coinfusion of ghrelin with diltiazem completely restored myocardial contractile function that was decreased 30 ± 3% ( P < 0.01) by diltiazem alone. In contrast, combination of ghrelin with diltiazem or Bis did not significantly alter atrial natriuretic peptide (ANP) secretion, which was decreased 40% ( P < 0.01) and 50% ( P < 0.05) by these agents alone, respectively. Administration of ghrelin to cultured cardiomyocytes had no effect on ANP or B-type natriuretic peptide secretion or gene expression. Detectable amounts of low-molecular-weight ghrelin were present in cardiac tissue extracts but not in isolated heart perfusate. Thus we provide the first evidence that ghrelin has a coronary vasoconstrictor action that is dependent on Ca2+ and PKC. Furthermore, the data obtained from diltiazem infusion suggest that ghrelin has a role in regulation of contractility when L-type Ca2+ channels are blocked. Finally, the observation that immunoreactive ghrelin is found in cardiac tissue suggests the presence of a local cardiac ghrelin system.

scholarly journals Beat-to-beat modulation of heart rate is coupled to coronary perfusion pressure in the isolated heart

1999 ◽  
Vol 86 (2) ◽  
pp. 694-700 ◽  
Author(s):  
David P. Slovut ◽  
John C. Wenstrom ◽  
Richard B. Moeckel ◽  
Christopher T. Salerno ◽  
Soon J. Park ◽  
...  
Keyword(s):  
Heart Rate ◽  
Perfusion Pressure ◽  
Isolated Heart ◽  
Sinus Node ◽  
Coronary Perfusion Pressure ◽  
High Dose ◽  
Coronary Perfusion ◽  
Perfused Heart ◽  
Langendorff Preparation ◽  
Heart Preparation

A goal of clinicians caring for heart transplant recipients has been to use heart rate variability as a noninvasive means of diagnosing graft rejection. The determinants of beat-to-beat variability in the surgically denervated heart have yet to be elucidated. We used an isolated, blood buffer-perfused porcine heart preparation to quantitatively assess the relationship between coronary perfusion and sinus node automaticity. Hearts ( n = 9) were suspended in a Langendorff preparation, and heart rate (HR) fluctuations were quantified while perfusion pressure was modulated between 70/50, 80/60, 90/70, and 100/80 mmHg at 0.067 Hz. In 32 of 32 recordings, the cross spectrum of perfusion pressure vs. HR showed the largest peak centered at 0.067 Hz. In eight of nine experiments during nonpulsatile perfusion, HR accelerated as perfusion pressure was increased from 40 to 110 mmHg (mean increase 24.2 ± 3.0 beats/min). HR increased 0.34 beats/min per mmHg increase in perfusion pressure (least squares linear regression y = −25.8 mmHg + 0.34 x; r = 0.88, P < 0.0001). Administration of low- and high-dose nitroglycerin (Ntg) resulted in a modest increase in flow but produced a significant decrease in HR and blunted the response of HR to changes in perfusion pressure (HR increase 0.26 beats ⋅ min−1 ⋅ mmHg−1, r = 0.87, P < 0.0001 after low-dose Ntg; 0.25 beats ⋅ min−1 ⋅ mmHg−1, r = 0.78, P < 0.0001 after high-dose Ntg). These experiments suggest that sinus node discharge in the isolated perfused heart is mechanically coupled to perfusion pressure on a beat-to-beat basis.

A Method for Electron Microscopic Study of Tissue Culture Cell Monolayers Grown in Tubes

1967 ◽  
Vol 25 ◽  
pp. 132-133
Author(s):  
R. Stephens ◽  
G. Schidlovsky ◽  
S. Kuzmic ◽  
P. Gaudreau
Keyword(s):  
Electron Microscopy ◽  
Tissue Culture ◽  
Light Microscopy ◽  
Cell Sheet ◽  
Culture Cell ◽  
Tissue Culture Cell ◽  
Electron Microscopic ◽  
Cell Sheets ◽  
Morphological Alterations ◽  
Culture Cells

The usual method of scraping or trypsinization to detach tissue culture cell sheets from their glass substrate for further pelletization and processing for electron microscopy introduces objectionable morphological alterations. It is also impossible under these conditions to study a particular area or individual cell which have been preselected by light microscopy in the living state.Several schemes which obviate centrifugation and allow the embedding of nondetached tissue culture cells have been proposed. However, they all preserve only a small part of the cell sheet and make use of inverted gelatin capsules which are in this case difficult to handle.We have evolved and used over a period of several years a technique which allows the embedding of a complete cell sheet growing at the inner surface of a tissue culture roller tube. Observation of the same cell by light microscopy in the living and embedded states followed by electron microscopy is performed conveniently.

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