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Biomedical subjects

I R Innes

Publications and source records attributed to I R Innes.

At least 19 recordsLinked to original sources
PubMed1994

Venoconstriction of hepatic capacitance vessels during hemorrhage in cats: afferent mechanisms.

Cats anesthetized with pentobarbital sodium were hemorrhaged (1 ml.min-1.kg body wt-1) until arterial pressure declined to 55 mmHg. Hepatic volume was recorded by plethysmography. Hemorrhage volume was 21.1 +/- 4.7 (SD) ml/kg, and hepatic volume declined by 4.0 +/- 1.7 ml/kg. These responses were markedly reduced by four procedures that prevented decreases in carotid arterial and central venous pressures and eliminated vagal conduction. When any three of these four procedures were carried out, the remaining stimulus caused a significant increase in the size of the hepatic volume decrease. The results suggest that arterial receptors (baro- and/or chemoreceptors) in the carotid arterial bed or brain and venous baroreceptors in the right atrium and superior and inferior venae cavae are involved in hepatic capacitance responses to hemorrhage. The responses were linearly related to the stimuli, and hepatic blood volume changed by 1.7 +/- 1.1 and 0.030 +/- 0.016 ml/kg for each 1-mmHg change in venous and carotid arterial pressures, respectively. The maximal responses to these afferent stimuli applied individually were not significantly different (-4.2 +/- 1.8 ml/kg) and were not additive, suggesting overlapping redundant systems. The possibility of baroreceptors in superior vena cava has not previously been documented.

Afferent Pathways↗
PubMed1994

Venoconstriction of hepatic capacitance vessels during hemorrhage in cats: efferent mechanisms.

Cats anesthetized with pentobarbital sodium were hemorrhaged (1 ml.min-1.kg body wt-1) until arterial pressure declined to 55 mmHg. Hepatic volume was recorded by plethysmography. In controls, 20 +/- 5 (SD) ml/kg was removed and hepatic volume decreased 3.6 +/- 0.8 ml/kg. Splanchnic nerve section or administration of hexamethonium-atropine reduced hemorrhage volumes (to 10.3 +/- 2.3 and 4.8 +/- 1.8 ml/kg, respectively) and liver volume changes (to 1.5 +/- 0.5 and 0.7 +/- 0.3 ml/kg, respectively). Section of only the hepatic nerves had no effect on hemorrhage volume or the decrease in hepatic volume. Section of the hepatic nerves after removal of the adrenals and kidneys also had no significant effect on hemorrhage volume or the decrease in liver volume. We conclude that the hepatic capacitance response to hemorrhage does not require direct sympathetic venoconstriction of the hepatic capacitance vessels. Changes in inferior vena caval pressure play a significant but small role. The splanchnic nerves (excluding hepatic nerves) play a major role, possibly by splanchnic arteriolar constriction. Whereas the liver comprises only 2.5% of the body weight, it contributed 18% of the hemorrhage volume.

Adrenalectomy↗
PubMed1991

Pre- and post-sinusoidal origin of hepatic exudate in anesthetized cats.

In cats anesthetized with pentobarbital, hepatic venous pressure was increased to cause drops of exudate to appear on the surface of the liver. These drops were collected during steady-state infusions of small doses of ethanol and galactose when there was a large arteriovenous gradient across the liver. Comparison of the concentrations of these substances in arterial, portal, and hepatic venous blood and exudate showed that the exudate concentrations were slightly higher than the hepatic venous concentrations but markedly lower than arterial and portal blood concentrations. We conclude that the exudate cannot be entirely formed in the space of Mall (presinusoidal) but a substantial part is postsinusoidal in origin. If the exudate is a mixture of fluids equilibrated with inflowing and outflowing blood, then 75-80% of the exudate is postsinusoidal and 20-25% is presinusoidal in origin.

Animals↗
PubMed1989

Changes in hepatic blood volume on galactose and indocyanine green uptake by cat liver.

The liver has important functions as a blood volume reserve and in uptake and metabolism of many substrates. This study examines whether changes in hepatic blood volume modify the uptakes of model substrates galactose and indocyanine green (ICG) in cats anesthetized with pentobarbital sodium. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to control hepatic flow and venous pressure and to allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic blood volume was measured by plethysmography. Galactose and ICG were infused intravenously at constant rates for 200 min in each of three series of experiments. The first series were time controls. In the second series, hepatic blood volume was increased by raising hepatic venous pressure. In the third series hepatic blood volume was decreased by hepatic nerve stimulation and infusions of norepinephrine and angiotensin. Hepatic congestion resulted in small increases in blood galactose levels, suggesting mild impairment of hepatic galactose metabolism. Decreases in liver blood volume did not modify hepatic galactose metabolism. Increases in hepatic blood volume facilitated while decreases inhibited ICG uptake, but the effects were small. Sinusoidal velocity and transit time have minor effects on uptake even for protein-bound substrates. In summary, large changes in hepatic blood volume had minor effects on galactose and ICG blood concentrations, suggesting that the metabolic functions of the liver are essentially independent of the blood reservoir function.

Animals↗
PubMed1988

Responses of contractile function to ruthenium red in rat heart.

Isolated rat hearts exhibited a biphasic contractile response to varying concentrations of ruthenium red. A negative inotropic effect was observed with concentrations of 0.025-0.5 microM, whereas a reversal of these initial changes toward control or even exceeding the predrug values was obtained as ruthenium red concentration was increased to 2.5 or 5.0 microM. High concentrations (12.5-25.0 microM) of ruthenium red caused a sustained contracture. In contrast, isolated frog hearts exhibited only a sustained negative inotropic effect at 0.25-12.5 microM ruthenium red. In studies with rat heart, both negative and positive inotropic effects of 2.5 microM ruthenium red were blocked either by increasing the concentration of Ca2+ (from 1.25 to 5.0 mM) or by decreasing the concentration of Na+ (from 140 to 35 mM) in the perfusion medium. The contracture induced by 12.5 microM ruthenium red was markedly inhibited when Ca2+ in the medium was lowered. The positive inotropic effect and contracture due to ruthenium red were also blocked by 1 microM of verapamil and 1.5 mM of amiloride; however, these interventions did not prevent the initial negative inotropic effect of ruthenium red. These experiments suggest the role of extracellular Ca2+ in the dose- and time-dependent effects of ruthenium red on contractile function of the rat heart. Furthermore, the positive inotropic response to ruthenium red may be related to its actions on the Na+-dependent Ca2+ movements in the cardiac cell.

Amiloride↗
PubMed1987

Characterization of insulin receptors in cardiac sarcolemmal and sarcoplasmic reticular membranes.

Specific insulin binding sites in cardiac sarcolemmal (SL) and sarcoplasmic reticular (SR) membranes were examined. Under in vitro conditions, the specific insulin binding to SL was two to three times greater than that to SR isolated from myocardium of different species. Insulin binding to these membranes was rapid, saturable, and temperature dependent. Scatchard plots were nonlinear and revealed high-affinity sites with K1 of 1.2 +/- 0.1 and 2.3 +/- 0.4 nM and low-affinity sites with K2 of 34.0 +/- 11.6 and 87.7 +/- 18.7 nM for SR and SL membranes, respectively. Unlabeled insulin accelerated the dissociation of previously bound labeled insulin, reflecting negative cooperativity of site-to-site interaction in both membranes; however, the dissociation rate in SR was about twofold higher than that in SL. The optimum binding of insulin to SR showed a plateau between pH 6.5 and 7.5 in comparison with a sharp peak at pH 8.0 for SL. Insulin significantly enhanced ATP-dependent Ca2+ binding to SL and SR membranes by approximately 100 and 40%, respectively. The Na+-dependent Ca2+ uptake in SL and the oxalate-supported Ca2+ uptake in SR were also stimulated by insulin; the maximum increase in Ca2+ accumulation in these vesicles was approximately 150 and 25%, respectively. These studies indicate that specific insulin binding sites in SL are characteristically distinct from those in SR and that insulin is capable of stimulating Ca2+ pumps located in these membranes.

Animals↗
PubMed1987

Norepinephrine storage, distribution, and release in diabetic cardiomyopathy.

The ability of hearts to store, distribute, and release norepinephrine (NE) was investigated in rats 8 wk after the induction of diabetes by an injection of streptozotocin (65 mg/kg iv). Chronic diabetes was associated with increased content and concentration of NE in heart and in other tissues such as kidney, brain, and spleen. Reserpine or tyramine treatment resulted in depletion of endogenous cardiac NE in control and diabetic rats. The depletion of NE stores at different times after a dose of reserpine was greater in diabetic hearts. On the other hand, NE stores in diabetic hearts were less sensitive than control hearts to low doses of tyramine but were more sensitive to high doses. The uptake of [3H]NE was greater in diabetic hearts in isolated perfused preparations. In comparison with the control values, diabetic hearts showed a decrease in [3H]NE in the granular fraction and an increase in the supernatant fraction. Diabetic hearts also showed an accelerated spontaneous release of [3H]NE. The increased cardiac NE and the uptake and release of NE in diabetic animals were reversible upon treatment with insulin. These results are consistent with the view that sympathetic activity is increased in diabetic cardiomyopathy and indicate that cardiac NE in diabetic rats is maintained at a higher level partly due to an increased uptake of released NE by adrenergic nerve terminals.

Animals↗
PubMed1987

Pathophysiological aspects of myocardial hypertrophy.

Heart hypertrophy in response to increased workload is a complex process in which this organ adapts to the environment by increasing the muscle mass in terms of additional contractile units and formation of different types of contractile proteins (myosin isozymes). In addition, augmentation of membrane function with respect to calcium transport activities of sarcolemma and sarcoplasmic reticulum occurs at early stages of cardiac hypertrophy associated with hyperfunction of the myocardium. However, if cardiac hypertrophy is left unattended beyond a certain period, physiological hypertrophy is converted to pathological hypertrophy whereby the cardiac muscle is unable to generate an adequate amount of contractile activity. It appears that the sympathetic nervous system is activated for producing beneficial effects at early stages but an elevated level of sympathetic tone for a prolonged period could result in dysfunction of the cardiac muscle. The transition of physiological hypertrophy to pathological hypertrophy seems to be due to the occurrence of intracellular calcium overload in the myocardial cell as a consequence of defects in the membrane calcium transport systems. It is suggested that careful attention should be paid not only to removal of the stimulus responsible for cardiac hypertrophy but also to lowering sympathetic tone. Efforts should also be made to prevent the occurrence of intracellular calcium overload due to membrane defects.

Animals↗
PubMed1986

Effects of nifedipine on hepatic blood volume in cats: indirect venoconstriction and absence of inhibition of postsynaptic alpha 2-adrenoceptor responses.

Intravenous administration of hypotensive doses (30-200 micrograms/kg) of nifedipine to cats anesthetized with pentobarbital caused an increase in cardiac output accompanied by hepatic venoconstriction. The hepatic venoconstriction and the increase in cardiac output were abolished in animals in which the hepatic sympathetic nerves were cut, the adrenal glands were excluded, and the kidneys were removed. This contrasts with the indirect hepatic venoconstrictor action of isoproterenol which was shown previously not to be abolished by these procedures. Further experiments showed that the hepatic venoconstrictor effect of nifedipine was blocked by removal of the kidneys, but not by removal of the hepatic sympathetic nerves and adrenals. These results support the hypothesis that venoconstriction plays an important role when drugs produce increased cardiac output. In nephrectomized animals, nifedipine had no direct effects on hepatic blood volume and it did not alter the effects of infusions of norepinephrine on hepatic blood volume, which have previously been shown to be mediated through alpha 2-adrenoceptors. However, it did reduce the hepatic venous responses to hepatic sympathetic nerve stimulation by 30%.

Animals↗
PubMed1986

Effects of bromocryptine on hepatic blood volume responses to hepatic nerve stimulation in cats.

Arterial pressures, portal pressures, and hepatic blood volumes were recorded after hepatic denervation in cats anesthetized with pentobarbital. Bromocryptine (50 micrograms/kg) lowered arterial pressure but did not significantly change portal pressure or hepatic blood volume. However, both portal pressure and hepatic blood volume responses to hepatic nerve stimulation were significantly depressed after bromocryptine especially at low frequencies of stimulation. Responses to intraportal infusions of norepinephrine were significantly impaired only at the highest dose. The inhibitory effect of bromocryptine on the neural responses may, therefore, involve a presynaptic inhibition of norepinephrine release, but the mechanism requires further study. These data provide further support for the hypothesis that drugs which impair hepatic venous responses to sympathetic stimuli cause significant impairment of postural reflexes and orthostatic hypotension during clinical use.

Animals↗
PubMed1986

Altered norepinephrine turnover and metabolism in diabetic cardiomyopathy.

Cardiac norepinephrine turnover and metabolism were examined in rats 8 weeks after the induction of chronic diabetes by an intravenous injection of streptozotocin (65 mg/kg). Cardiac norepinephrine concentration, norepinephrine turnover, and norepinephrine uptake were markedly increased in chronic diabetes in comparison with control values; these changes were reversible by 28-day insulin therapy. When the animals were exposed to cold for 6 hours, norepinephrine turnover rate constant increased in control and decreased in diabetic animals; cold exposure also increased norepinephrine concentration in diabetic hearts. Both cardiac norepinephrine concentration and turnover rate in diabetic rats were restored toward control values by ganglionic blockade with pentolinium. The conversion of [3H]tyrosine to [3H]catecholamine was enhanced and tyrosine hydroxylase as well as dopa decarboxylase activities were increased in diabetic hearts. The higher concentrations of [3H]normetanephrine and deaminated catechols indicated a faster metabolic rate of norepinephrine metabolism in hearts from diabetic rats; both monoamine oxidase and catechol-O-methyltransferase activities were also increased. The increased activities of the enzymes for the synthesis and metabolism of norepinephrine were not evident on treating the diabetic animals with insulin. These data not only support the view that chronic diabetes in rats is associated with increased sympathetic activity but also indicate that the cardiac norepinephrine concentration in diabetic rats may be maintained at a higher than normal level by an increased synthesis and uptake of norepinephrine in the adrenergic nerve terminals.

Adrenergic Fibers↗
PubMed1985

Norepinephrine on venous compliance and unstressed volume in cat liver.

Hemodynamic relationships between flows, pressures, and blood volume have been examined in the denervated liver of cats anesthetized with pentobarbital. Portal and hepatic lobar venous pressures, portal and total hepatic flows, and hepatic blood volume were recorded when portal flow was varied from 0 to 240 ml X min-1 X 100 g liver-1 and when hepatic outflow pressure was varied from 0 to 9.5 mmHg, before, during, and after intravenous infusion of norepinephrine (2 micrograms X min-1 X kg body wt-1). Portal pressure was 1-2 mmHg higher than lobar venous pressure and 8-9 mmHg higher than inferior vena caval pressure, showing that the major site of resistance in the portal circuit was in the large hepatic veins. Intrahepatic pressure was linearly related to total hepatic flow, and norepinephrine increased the intercept but not the slope of this relationship. Hepatic blood volume was linearly related to intrahepatic pressure with a calculated compliance of 2.5-3.0 ml X mmHg-1 X 100 g liver-1 and a calculated unstressed volume at zero pressure of 10-15 ml/100 g liver. Norepinephrine did not significantly change vascular compliance but caused a marked reduction of 15-20 ml/100 g liver in calculated unstressed volume. Thus norepinephrine reduced hepatic blood volume by 15-20 ml/100 g liver at any given intrahepatic pressure. It is concluded that venoconstriction in the hepatic bed occurs by a decrease in unstressed volume with little change in compliance. Unstressed volume represents a true blood volume reserve, independent of passive influences, which can be mobilized by the central nervous system.

Animals↗
PubMed1981

Reduction in the severity of myocardial infarction by sulfinpyrazone.

The effect of sulfinpyrazone (Anturane) on the extent of myocardial lesions caused by coronary ligation or isoproterenol, 5 mg/kg subcutaneously, was determined in the rat. Treatment was with sulfinpyrazone, 15 mg/kg twice daily for 5 days before the cardiac insult, or 21 days after the insult, or both. Pretreatment with sulfinpyrazone reduced isoproterenol-induced lesions by 42%. Treatment after isoproterenol had no significant effect. With coronary ligation, treatment before or after operation significantly reduced the size of infarct, pretreatment by 42%, post-treatment by 33%. The results provide evidence that sulfinpyrazone may have a clinically useful protective effect in individuals at risk of cardiac ischemia, as suggested in the Anturane Reinfarction Trial.

Animals↗
PubMed1981

Alcohol feeding alters (3H)dopamine uptake into rat cortical and brain stem synaptosomes.

The uptake of (3H)dopamine into nerve endings (synaptosomes) isolated from cortex and brain stem of rats under various stages of ethanol intoxication were studied. Acute or chronic ethanol treatment inhibited the high affinity uptake of dopamine into both regions by about 30% when rats were still under ethanol. The inhibition in brain stem persisted even after 120 h of withdrawal from ethanol. In cortex, 16 h after acute treatment, the uptake was slightly (about 10%) elevated from that of control in contrast to chronic rats, which were 43 and 41% more than that of the control after withdrawal from ethanol for 48 and 120 h, respectively.

Administration, Oral↗
PubMed1979

Isolation of the sino-atrial node with veratramine.

The effects of veratramine on transmembrane potentials of the isolated right atrial preparation of the cat were examined. Veratramine slowed spontaneous rate and precipitated a characteristic rhythm consisting of alternating periods of asystole and normal atrial rhythm (periodic rhythm). After large doses or continued exposure to low doses of veratramine electrical and mechanical activity of the atria ceased; subsequently activity resumed only in a discrete area within which action potentials were consistent with pacemaker characteristics. This discrete pacemaker area, easily located by sight, greatly facilitates study of the sino-atrial node. A gradation of veratramine effect in cells lying between the quiescent common atrial cells and the active pacemaker suggests the existence of "transitional" cells with electrophysiological responses intermediate between common atrial cells and pacemaker cells.

Action Potentials↗
PubMed1976

The role of bound calcium in supersensitivity induced by cocaine.

1 Noradrenaline caused a small contraction of the cat isolated spleen strip bathed in a calcium-free solution; this contraction was greatly potentiated by cocaine. This potentiation was also present in isolated spleen strips where noradrenaline stores were depleted by reserpine. The maximum response of the spleen strip to noradrenaline in the absence of extracellular calcium was also increased by cocaine. 2 The disodium salt of ethylenediaminetetraacetic acid (Na-EDTA) but not Ca-EDTA antagonized the potentiation of the response to noradrenaline by cocaine in a calcium-free solution, and greatly reduced the magnitude of subsequent responses to noradrenaline and cocaine. 3 Strontium caused equivalent contractions of normal and reserpine-treated spleen strips bathed in a calcium-free solution. These responses were potentiated by cocaine. 4 Histamine caused a small contraction of the isolated spleen strip bathed in a Ca-free solution. Cocaine failed to potentiate these very small histamine contractions, but did potentiate the contraction of these same strips in response to noradrenaline. 5 It is concluded that the potentiation of the response of the isolated spleen strip to noradrenaline by cocaine in the absence of extracellular calcium is due to a mechanism other than decreased neuronal uptake of noradrenaline. It is suggested that cocaine makes a bound store of calcium more available to promote contraction of the spleen strip by noradrenaline.

Animals↗