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Biomedical subjects

R J Bing

Publications and source records attributed to R J Bing.

At least 73 records · Page 4Linked to original sources
PubMed1989

Nisoldipine as a vasodilator in endothelium-deprived large coronary arteries of isolated working rabbit hearts.

The effect of nisoldipine on the vasoconstrictor effect of histamine on coronary vascular resistance, cardiac performance and myocardial oxygen consumption was determined in this study. In a supported working heart preparation a perfluorochemical emulsion (FC-43) was used a perfusate. To enhance the sensitivity of the large coronary arteries to vasoconstrictor stimuli, the endothelium was removed mechanically from the large coronary arteries. The changes in coronary artery diameter were documented by colour arteriography. Nisoldipine reduced the constriction of coronary arteries and the decrease in coronary flow induced by histamine. Nisoldipine abolished or reduced the decrease in cardiac output, left ventricular end systolic pressure, dP/dt and myocardial oxygen consumption. In the supported working heart preparation, nisoldipine is an effective dilator of large coronary arteries deprived of endothelial lining.

Animals↗
PubMed1989

An improved chemiluminescence assay suggests non nitric oxide-mediated action of lysophosphatidylcholine and acetylcholine.

Using a new nitric oxide analyser, we have developed a sensitive chemiluminescence assay to detect trace quantities of NO in aqueous solutions. This improved technique in combination with the bioassay has been employed to verify the theory that NO released by vascular endothelium, accounts for the relaxation produced by acetylcholine, lysophosphatidylcholine and calcium ionophore A23187. Our results show that while calcium ionophore A23187 continuously released NO, acetylcholine and lysophosphatidylcholine relaxed vascular strips without releasing NO over the basal level.

Acetylcholine↗
PubMed1988

Lysolecithins as endothelium-dependent vascular smooth muscle relaxants that differ from endothelium-derived relaxing factor (nitric oxide)

The effects of lysolecithin (lysophosphatidylcholine) derived from egg yolk as well as of synthetic lysolecithins with different aliphatic chain lengths on tension development of rabbit aortic strips were investigated. Lysolecithins caused slowly progressing, dose-dependent relaxation that was inhibited by hemoglobin, methylene blue, and nordihydroguiaretic acid. Indomethacin caused no inhibition of relaxation. The degree of relaxation was endothelium-dependent and appeared to be related to the activation of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2]. Superoxide dismutase failed to influence relaxation. Lysolecithins with the longest aliphatic chain were the most potent relaxants of aortic strips. The experiments suggest a role of lysolecithins through their weak detergent action on membrane dynamics of endothelial cells, resulting in the production of cyclic GMP and the relaxation of arterial smooth muscle. Lysolecithins differ in several respects from endothelium-derived relaxing factor. Endothelium-derived relaxing factor is an unstable humoral substance released from endothelium and is identical to nitric oxide, itself a labile substance causing vascular relaxation and cyclic GMP accumulation. Lysolecithins may represent a different type of endothelium-dependent muscle relaxant.

Acetylcholine↗
PubMed1988

Cardiac performance in pediatric near-drowning.

Between July 1985 and December 1986, 29 near-drowned children ranging in age between 6 months and 13 yr were admitted to the Pediatric ICU of Huntington Memorial Hospital. Eight patients suffered cardiopulmonary arrest and had an admission Glasgow Coma Score of 3 or 4. Hemodynamic monitoring was performed on five of these patients. Three received cerebral resuscitation with controlled hyperventilation, hypothermia, pentobarbital, and mannitol because of intracranial hypertension. After CPR, a low cardiac index (CI) and high systemic vascular resistance index (SVRI) were found. When cerebral resuscitative therapy was initiated later, it caused a reduction of SVRI, CI, mean arterial pressure, and cerebral perfusion pressure. Fluid volume therapy and inotropic cardiac support was necessary to maintain adequate cerebral perfusion pressure. These observations indicate that cerebral resuscitative therapy can affect cardiovascular function. The hemodynamic depressive effects might even worsen the outcome. For this reason, it is advisable to obtain CI and pulmonary capillary wedge pressure to optimize cerebral perfusion and potentially neurologic outcome.

Adolescent↗
PubMed1988

Effect of nisoldipine on large coronary arteries in situ: inhibition of vasoconstriction induced by vasopressin.

The effects of nisoldipine on myocardial performance and large coronary artery diameter, resistance and cross-sectional area were studied in rabbit hearts in situ. Changes in mean internal diameter of coronary artery segments were visualized using color arteriography; changes were computer-calculated. Nisoldipine had a direct dilatory effect on large coronary arteries in situ and it attenuated the vasoconstriction induced by vasopressin. It shifted the dose-response curve of vasopressin to the right in a noncompetitive manner. Nisoldipine reduced the effect of vasopressin on maximum left ventricular dP/dt, mean aortic pressure, left ventricular end-systolic pressure and heart rate. The results demonstrate that nisoldipine is an effective dilator of large epicardial coronary arteries in situ and inhibits the vasoconstriction induced by vasopressin.

Animals↗
PubMed1988

Uncertain role of endothelium-derived relaxing factor in mesenteric arterioles of cats and rabbits.

Experiments were undertaken in the mesentery of anesthetized cats and rabbits to investigate whether the endothelium of resistance vessels mediates relaxation of arteriolar smooth muscle through the endothelium-derived relaxing factor(s) (EDRF). The microcirculation was visualized by transillumination using intravital microscopy and a Millikan camera. Pictures were obtained at a rate of 400 frames/second. Arteriolar mean diameter and surface area were computer calculated. The animals were divided in two groups. In one group of experiments, EDRF was inactivated by direct injection of hydroquinone (HQ) into the superior mesenteric artery and the second group served as control. Norepinephrine or vasopressin constricted while acetylcholine or Ca-ionophore A23187 dilated arterioles. Hydroquinone failed to inhibit arteriolar dilation in situ. The effect of HQ on the endothelium in situ was ascertained by bioassay of superior mesenteric artery strips. Our results cast doubt on the role of EDRF in the dilation of mesenteric arterioles in felines and rabbits.

Acetylcholine↗
PubMed1988

Effect of EDRF release from freshly harvested endothelial cells on the coronary circulation of the isolated working rabbit heart.

Vascular relaxation in rabbit aortic preparations by acetylcholine is endothelium-dependent. Because of the short half-life of the endothelium-derived relaxing factor(s) (EDRF), a constant source of this material is necessary to study its effect in perfused hearts or hearts in situ (reported half-life 6-50 sec). To investigate the effect of EDRF(s) on the large coronary arteries and the resistance vessels of the isolated working rabbit heart, freshly harvested porcine endothelial cells were used. The cells were stimulated with acetylcholine to produce EDRF(s). To extend the half-life of EDRF, superoxide dismutase was added to the cell suspension. Left atrial infusion of these cells increased coronary flow and reduced total coronary resistance. No significant effect on the diameter of the endothelium-deprived obtuse marginal coronary artery was noted. The vasoconstrictor effect on resistance vessels of topically applied histamine was significantly reduced during the infusion of activated endothelial cells. It can be concluded that EDRF(s) released from freshly harvested endothelial cells increases coronary flow and diminishes total coronary vascular resistance in the working heart. In this preparation coronary arterioles are more sensitive to EDRF(s) than large coronary arteries. EDRF may contribute to the regulation of regional myocardial flow.

Acetylcholine↗
PubMed1987

Inhibition of vasoactive agents by perfluorochemical emulsion.

Perfluorochemicals are widely used in clinical and experimental studies as volume expanders with high oxygen carrying capacity. We noticed that contractions of rabbit aortic strips, induced by norepinephrine, were inhibited in FC-43 emulsion as compared to Krebs-Henseleit solution (KH). To study this inhibition, a comparative evaluation was made of the contractile responses of norepinephrine, serotonin and histamine in FC-43 emulsion and KH. The effect of these agents was significantly diminished in FC-43 emulsion; concentration-response curves were shifted to the right and the maximum response was diminished. A search was made for the individual constituents of FC-43 responsible for diminution of contraction of vascular smooth muscle. After centrifugation of FC-43 emulsion, the supernatant caused a reduction of contractility and reduced EC50-values of norepinephrine to the same degree as the fully constituted emulsion. This excluded perfluorotributylamine, the oxygen carrying particles, as being responsible for this inhibition. When the detergent Pluronic F-68 was added to KH in concentrations equal to that in FC-43 emulsion, inhibition of contraction occurred and EC50-values increased. Contractions induced by norepinephrine were equally inhibited by the addition to KH of a volume expander, hydroxyethylstarch, in a concentration equal to that in FC-43 emulsion. It is concluded that FC-43 emulsion inhibits vasoactive agents and attenuates its pharmacologic effects on vascular smooth muscle. The fractions of FC-43 emulsion responsible for inhibiting the effect of vasoactive agents are Pluronic F-68 and hydroxyethylstarch.

Animals↗
PubMed1987

Advantages of perfluorochemical perfusion in the isolated working rabbit heart preparation using 31P-NMR.

Quantitative 31P-NMR and enzymatic analysis of high-energy phosphates were used to characterize an isolated perfused working rabbit heart preparation. In this model, the left side of the heart works against a physiological after-load. Two perfusates, Krebs-Henseleit saline and the perfluorocarbon emulsion FC-43 (perfluorotributylamine), were evaluated in their ability to maintain cardiac function and high-energy phosphate metabolites over a period of 2-3 h. Adenine nucleotides ATP, ADP, phosphocreatine and inorganic phosphate (Pi) were measured by 31P-NMR while monitoring cardiac output and coronary flow. Intracellular pH was determined using the chemical shift of Pi. At the end of each experiment, hearts were freeze clamped and enzymatically assayed for adenine nucleotides, phosphocreatine and Pi. In every experiment, hearts perfused with FC-43 emulsion maintained the same rate of cardiac output as hearts perfused with Krebs-Henseleit saline, but with half the coronary flow rate: FC-43, 22 +/- 2.5 (n = 5), Krebs-Henseleit saline 42 +/- 2.7 (n = 6) ml/min, P less than 0.001. Hearts perfused with FC-43 emulsion showed higher [phosphocreatine] and [ATP] measured by 31P-NMR. For [phosphocreatine]: FC-43 3.2 +/- 0.7 (n = 5), Krebs-Henseleit saline 1.7 +/- 0.2 (n = 6) mumol/g wet wt., P less than 0.01. For [ATP]: FC-43 1.8 +/- 0.7 (n = 5), Krebs-Henseleit saline 0.9 +/- 0.2 (n = 6) mumol/g wet wt., P less than 0.02. [phosphocreatine] and [ATP] determined by 31P-NMR values were identical within experimental error to those values obtained by enzymatic analysis. Comparing [Pi] determined by both methods, 36% of Pi in FC-43-perfused hearts, and only 24% of Pi in Krebs-Henseleit saline-perfused hearts were visible by NMR, indicating that a large proportion of Pi is bound in the intact functioning heart. Similar results were obtained for [ADP]. Using the combined techniques of 31P-NMR and enzymatic assay, we have shown in this model of the isolated working rabbit heart preparation, that FC-43 emulsion maintains significantly better function and high-energy phosphate levels than Krebs-Henseleit saline.

Adenine Nucleotides↗
PubMed1987

A relaxing factor released by phospholipase A2 in the absence of endothelium.

Phospholipase A2 (PLA2) produced slow dose dependent relaxation in intact and endothelium-deprived precontracted rabbit aortic strips. In endothelium-deprived preparations, relaxation induced by PLA2 is inhibited by hemoglobin, methylene blue and parabromophenacylbromide (PBPB), and is potentiated by superoxide dismutase (SOD). Indomethacin has no effect. Relaxation is accompanied by a rise in c-GMP. Phospholipase C causes a significant increase in tension, while Phospholipase D has no effects. In intact aortic strips PLA2 causes a biphasic response with no elevation in c-GMP. The results indicate several common features of the PLA2 released factor with endothelium-derived relaxing factor (EDRF). However, PLA2 induced relaxation is not dependent on endothelial cells. Apparently in addition to nitric oxide which may be the endothelium-derived relaxing factor, a second smooth muscle relaxing factor exists which is initiated by PLA2 and is independent of endothelium. The production of the PLA2 produced relaxation is dependent on its specific hydrolytic activity. We call this relaxing factor the phospholipid-derived relaxing factor (PDRF).

Animals↗
PubMed1987

The role of lysolecithin in the relaxation of vascular smooth muscle.

The effect of lysolecithin (lysophosphatidylcholine) on the relaxation of rabbit aortic strip closely resembled that produced by acetylcholine (ACh) which releases the endothelium-derived relaxing factor (EDRF). Relaxation induced by lysolecithin depended on the presence of endothelium and was inhibited by hemoglobin and methylene blue. It appeared to be mediated by the second messenger, c-GMP. Lysolecithin induced relaxation was slower but more persistent than that resulting from the endothelium-derived relaxing factor (EDRF) produced by acetylcholine (ACh). Like lysolecithin, Triton X-100, a non-ionic detergent, also preferentially relaxed aortic strips with intact endothelium. The results demonstrate the importance of phospholipids derived from cell membranes in vascular smooth muscle relaxation. Endothelium-derived relaxing factors appear as a group of heterogeneous substances.

Animals↗
PubMed1987

The vasodilator effect of coronary vascular endothelium in situ: its inactivation by hydroquinone.

Studies were carried out to demonstrate the presence of the endothelium derived relaxing factor (EDRF) in coronary arteries in situ and the effect of hydroquinone on this factor. The studies revealed the presence of EDRF in coronary arteries of rabbit hearts remaining in situ. EDRF was inactivated by left atrial injection of hydroquinone. In situ constriction of coronary arteries by vasopressin was markedly increased following exposure to hydroquinone, and the dilatory response to acetylcholine was absent. The experiments confirm the presence of the endothelium derived relaxing factor in coronary arteries in situ and its inactivation by hydroquinone.

Animals↗
PubMed1987

Effect of a new phosphodiesterase type III inhibitor as a coronary vasodilator and positive inotropic agent.

Isolated rabbit coronary arteries, aortic strips, and a working rabbit heart preparation were used to assess the positive inotropic and vasodilator effects of a newly developed positive inotropic compound, CI 914. The substance had a relaxing effect on histamine preconstricted coronary arteries and aortic strips. At concentrations of 10(-4) mol.litre-1 the relaxing effect on the coronary arteries was significant only at a histamine concentration of 3 x 10(-4) mol.litre-1 (p less than 0.01) whereas at a concentration of 10(-3) mol.litre-1 the relaxing effect was significant at histamine concentrations of from 3 x 10(-5) mol.litre-1 to 3 x 10(-4) mol.litre-1. Aortic strips were more sensitive to the relaxing effect of CI 914, which was significant with 10(-4) mol.litre-1 at histamine concentrations of 3 x 10(-6) to 3 x 10(-4) (p less than 0.05 to p less than 0.01). In the isolated working heart preparation topically sprayed histamine significantly increased total and large coronary artery resistances (p less than 0.001 and p less than .01). This effect was significantly reduced (p less than 0.01 and p less than 0.02) when CI 914 10(-4) mol.litre-1 was present in the perfusion fluid. These findings show that the phosphodiesterase inhibitor CI 914, a positive inotropic agent, induces vasodilation in isolated coronary arteries and aortic strips of the rabbit and reduces the constriction of coronary arteries induced by histamine in the isolated working rabbit heart preparation.

Animals↗
PubMed1987

Effect of nisoldipine on de-endothelialized large coronary artery in isolated working rabbit hearts.

The effect of nisoldipine on coronary vascular resistances, cardiac performance and myocardial oxygen consumption was determined. Rabbit hearts were perfused with a perfluorochemical (FC-43) emulsion. Endothelium was removed from the obtuse marginal and the upper portion of the anterior descending coronary artery. Changes in the internal diameter of these arteries were visualized using injection of Patent Blue Dye (color arteriography). Mean internal diameter of coronary arteries and surface area/unit length were computer calculated. Nisoldipine reduced the constriction of coronary arteries and the decrease on coronary flow induced by histamine. Nisoldipine abolished or reduced the decrease in cardiac output, LVESP, dP/dt and myocardial oxygen consumption. The results demonstrate that in the supported rabbit heart preparation, nisoldipine is an effective dilator of large subepicardial coronary arteries, deprived of endothelial lining, and counteracts constriction of coronary resistance vessels. As a consequence nisoldipine improves performance of the ischemic myocardium.

Animals↗
PubMed1987

Release of endothelium-derived relaxing factor from freshly harvested porcine endothelial cells.

Vascular relaxation in rabbit aortic preparations induced by acetylcholine is endothelium-dependent. The nature of the endothelium-derived relaxing factor (EDRF) has not been ascertained because it is very labile (reported half-life 6-50 seconds). To obtain a stable source of EDRF, a system was developed in which the relaxing factor was continuously produced by freshly harvested porcine endothelial cells. Endothelial cells were collected from aortas by exposing the endothelial lining to collagenase 0.1%. Cells were washed and concentrated by repeated centrifugation to obtain a high cell count (7.2 X 10(6) cells/ml). Endothelium-deprived aortic strips from rabbits were incubated in these cells suspended in tissue culture medium and fetal calf serum. The strips were precontracted with histamine. Acetylcholine was added to induce EDRF release. Significant relaxation of endothelium-deprived aortic strips was observed. Superoxide dismutase, an enzyme known to protect EDRF against inactivation, caused further relaxation, which was inhibited by the addition of hemoglobin, an agent known to inhibit the relaxing action of EDRF. Even without the addition of acetylcholine, hemoglobin caused contraction of the denuded aortic strips in suspension of porcine endothelial cells, demonstrating spontaneous EDRF release. Hemoglobin had no effect in cell-free medium. Endothelial-cell-dependent relaxation occurred without attachment of endothelial cells to the endothelium-deprived aortic strips: when the cell suspension was replaced by cell-free medium, relaxation did not occur after acetylcholine. Scanning electron microscopy showed no attachment of endothelial cells to the subendothelial layer. It can be concluded that freshly harvested endothelial cells produce endothelium-derived relaxing factor with an without stimulation by acetylcholine.

Acetylcholine↗
PubMed1987

Lindbergh and the biological sciences (a personal reminiscence).

In 1929 Charles Lindbergh became interested in the development of a heart-bypass pump to enable open-heart surgery, and was introduced to Alexis Carrel. Carrel persuaded Lindbergh to work instead on a perfusion system for the culture of whole organs outside the body, and by 1934-when I met Lindbergh in Copenhagen-he already had developed a pump with floating glass valves that allowed precise regulation of perfusion pressure and rate. I joined Lindbergh and Carrel at the Rockefeller Institute to work on organ culture, using the pump. My subsequent contact with Lindbergh came at Columbia, where I experimented with hemocyanin as a blood substitute, and (much later) at Huntington Medical Research Institutes, where I found his pump useful in the study of cholesterol uptake by arteries.

Journal Article↗