Biomedical subjects

A Bomzon

Publications and source records attributed to A Bomzon.

At least 19 recordsLinked to original sources

PubMed1992

The source of calcium for CCK-induced contraction of the guinea-pig gall bladder.

The sources of calcium for cholecystokinin octapeptide (CCK-OP)-induced gallbladder smooth muscle contraction are considered both extracellular and intracellular, but the relative need for intracellular calcium especially at low, physiological concentrations is not clear. To better define the calcium sources responsible for guinea-pig gallbladder contractions in vitro, we inhibited calcium influx using the calcium channel blocker, methoxyverapamil, and a calcium-free Krebs' solution. Availability and release of intracellular calcium stores were depleted by strontium substitution and ryanodine. CCK-OP was compared to bethanechol and potassium chloride (KCl). Preventing calcium influx with 10(-5) M methoxyverapamil depressed the responses to CCK-OP, bethanechol and KCl. Methoxyverapamil, however, had little effect on the time-dependent generation of tension to CCK-OP, but significantly reduced the response to bethanechol and KCl, each at ED50. The duration of the contractile response in the calcium-free Krebs' solution to CCK-OP was longer than that for bethanechol. Strontium (2.5 mM) significantly attenuated the response to CCK-OP and bethanechol, but not to KCl. Ryanodine significantly reduced contractions induced by CCK-OP but not for bethanechol, both at low dose ED25. These results indicate that contraction of the guinea-pig gallbladder induced by CCK-OP, bethanechol and KCl requires extracellular calcium influx. Further, the initiation and maintenance of contraction by CCK-OP and bethanechol necessitates calcium mobilisation from intracellular stores. CCK-OP may have a greater penchant for these calcium stores, particularly at physiological doses.

Animals↗

PubMed1992

Pressor response to a postural change in cirrhosis: an experimental study in the CCl4-treated rat.

1. Systemic hypotension, blunted cardiovascular responsiveness to noradrenaline and an abnormal hypertensive pressor response to a postural change have been described in cirrhotic patients. 2. We have examined the role of blunted responsiveness in these abnormalities by studying basal arterial blood pressure and its response to a postural change (vertical head-up 90 degrees tilting) in conscious and pithed CCl4-treated (cirrhotic) rats, as well as assessing the pressor response to noradrenaline in vivo and the vascular contractile response to noradrenaline in vitro. 3. A diminished hypotensive response to a change in posture was found in pre-cirrhotic portal hypertensive rats, whereas an inverted hypertensive pressor response in the face of systemic hypotension occurred in the cirrhotic rats with portal hypertension. 4. The inverted pressor response was abolished in the pithed portal hypertensive cirrhotic rats. 5. The pressor response to noradrenaline in vivo in conscious cirrhotic rats and the vascular contractile responsiveness to noradrenaline in vitro were intact. 6. We conclude that blunted responsiveness to noradrenaline is not a contributory factor to the development of systemic hypotension or the inverted pressor response to a change in posture in cirrhosis.

Animals↗

PubMed1992

Differential sensitivities of the sphincter of Oddi and gallbladder to cholecystokinin in the guinea pig: their role in transsphincteric bile flow.

Cholecystokinin (CCK) is considered to simply contract the gallbladder and relax the sphincter of Oddi with meals. In this study, we examined this hypothesis by investigating the action of CCK on the sphincter of Oddi and gallbladder of the guinea pig. The experimental design used an in vitro preparation of the sphincter of Oddi to measure contraction of the circular muscle. CCK increased tone in both the gallbladder and the sphincter of Oddi in a concentration-dependent manner. The normalized concentration-response curves for CCK, however, revealed that the gallbladder had a greater sensitivity to CCK (ED50 7 nM) than the sphincter of Oddi (ED50 22 nM; p < 0.01). Conversely, the sphincter was more sensitive to bethanechol than was the gallbladder. When the sphincter of Oddi was stimulated maximally with CCK in the presence of atropine (10(-6) M) or tetrodotoxin (10(-6) M), the contractile response was significantly reduced (p < 0.05) although not abolished. Conversely, atropine completely abolished the responses to bethanechol (10(-3) M) and transmural field stimulation (70 V, 10 Hz, 1 ms, for 20 s). Transmural field stimulation of the sphincter that had been precontracted with CCK (26 nM) caused a transient, initial relaxation followed by contraction. Pretreatment with atropine augmented the duration of this relaxation, which could be completely abolished by tetrodotoxin. Thus, CCK contracts the sphincter of Oddi in the guinea pig by a direct (myogenic) and a neural (likely cholinergic) mechanism. Relaxation of the sphincter of Oddi also occurs in the guinea pig via noncholinergic inhibitory nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Cardiovascular responses to serotonin in experimental liver disease.

Recent evidence suggests that serotonergic mechanisms within the cardiovascular system are activated and may be important in the development of the hyperkinetic circulation and the maintenance of portal hypertension in cirrhotic patients. The in vivo pressor and positive chronotropic response together with the in vitro contractile responses of aortic rings and portal veins to serotonin were studied in three different rat models of cirrhosis, portal hypertension and jaundice: the portal vein-ligated rat, the carbon tetrachloride-induced cirrhotic rat, the chronic bile duct-ligated cirrhotic rat and the 3-day noncirrhotic, nonportal hypertensive-jaundiced rat. In addition, the activity of the enzyme monoamine oxidase type A was determined in lung homogenates prepared from the four groups of sham and treated animals. In the four different groups of sham-treated or operated pithed rats, serotonin caused a dose-dependent increase in mean arterial blood pressure without any effect on the heart rate. The pressor responses to serotonin in the three models of portal hypertension were significantly attenuated from their respective sham group. In the 3-day noncirrhotic, nonportal hypertensive-jaundiced rats, the pressor response was no different than that seen in the sham-operated rats. No evidence of consistent potentiated or blunted in vitro reactivity to serotonin of arterial rings and portal veins from the four groups of rats was seen. Portal hypertension, cirrhosis and hyperbilirubinemia had no effect on the activity of monoamine oxidase type A. These data demonstrate that portal hypertension is associated with an attenuated pressor response to serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

In vitro vascular responsiveness to norepinephrine in experimental portal hypertension.

It has been postulated that loss of response to norepinephrine accounts in part for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. The in vitro vascular responsiveness to norepinephrine was measured in aortic rings and portal veins excised from four different rat models of hepatic disease with and without portal hypertension, hepatocellular damage, and hyperbilirubinemia--the carbon tetrachloride (CCl4) cirrhotic rat with portal hypertension, the five-week chronic bile duct ligated and resected (CBDL) cirrhotic rat with portal hypertension and hyperbilirubinemia, the 10-day partial ligated portal vein (PVL) portal hypertensive rat without hepatocellular damage and hyperbilirubinemia, and the three-day bile duct ligated (ABDL) rat with acute hepatocellular damage and hyperbilirubinemia but without portal hypertension. Sham-treated or operated groups for each model were also prepared. Vascular reactivity of the aortic rings to norepinephrine was potentiated in the three portal hypertensive groups, and attenuated in the model of acute cholestasis. No consistent pattern of response to norepinephrine was evident in the portal veins. Based upon the presented in vitro data and the discussed limitations of an in vitro study, we conclude that it is unlikely that the loss of response to norepinephrine accounts for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease.

Animals↗

PubMed1990

Anesthesia and pressor responsiveness in chronic bile-duct-ligated dogs.

Cardiovascular homeostasis is comprised under general anesthesia and in jaundice. Because surgery is often performed on jaundiced patients, it is not altogether surprising that the incidence of perioperative complications is higher in such patients than in nonjaundiced ones. In this study we assessed the potential synergistic effects of anesthesia and jaundice on cardiovascular responsiveness of chronic bile-duct-ligated dogs. Responsiveness to norepinephrine, angiotensin II and isoproterenol was determined before and after chronic bile-duct ligation or sham-operation while the dogs were conscious or under halothane, fentanyl or pentobarbital-sodium anesthesia. These data have shown that halothane- and barbiturate-induced anesthesia do not alter mean arterial blood pressure in unoperated dogs when compared with conscious dogs before laparotomy. Furthermore, these two agents did not modify the pressor, dilator and positive inotropic responses to intravenous infusions of norepinephrine, angiotensin II and isoproterenol. Fentanol, however, reduced mean arterial blood pressure and heart rate without influencing responsiveness to the three vasoactive agents. Blunted responsiveness in the chronic bile-duct-ligated dogs to the three vasoactive agents was observed without any marked changes in mean arterial blood pressure or heart rate. The same blunted responses observed in the conscious, chronic bile-duct-ligated dogs were also seen in the anesthetized, chronic bile-duct-ligated dogs. Halothane caused a marked hypotensive effect in the chronic bile-duct-ligated dogs that was not seen in the sham-operated dogs. Conscious and anesthetized sham-operated dogs responded in the same manner as the conscious and anesthetized dogs before ligation. (ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1990

Angiotensin-converting enzyme activity in the isolated perfused guinea pig lung.

We have developed a pressure-dependent isolated lung perfusion system that can be used for the determination of pulmonary enzyme activity and kinetics under physiologic conditions. This development was done using two different artificial radiolabeled substrates, glycine-1-hippuryl-L-histidyl-L-leucine and phenyl-4(n)-hippuryl-glycyl-glycine, for the pulmonary enzyme, angiotensin-converting enzyme. With this system, we assessed the effects of different perfusate types upon the stability of the perfusion as well as the independent effects of pressure, flow, and substrate concentration on the activity of this enzyme. We concluded that this system enables the operator to determine the kinetics and activities of pulmonary enzymes independently of the effects of pressure and flow in a perfusion system that is stable for at least 3 h under physiologic conditions.

Animals↗

PubMed1990

Systemic hypotension and pressor responsiveness in cholestasis. A study in conscious 3-day bile duct ligated rats.

It has been postulated that the physiological basis for systemic hypotension in cholestatic liver disease is the attenuated responsiveness of the cardiovascular system to sympathetic stimulation. Using conscious 3-day bile duct ligated rats, we tested this hypothesis by measuring the vasopressor and vasodilator responses following intravenous infusions of norepinephrine, tyramine, angiotensin II, angiotensin I and isoproterenol, in conjunction with the pressor responses to a head-up vertical tilt and a controlled hemorrhage. The results were compared to those obtained in conscious sham-operated rats. Bile duct ligation reduced the mean arterial blood pressure without a significant increase in heart rate. The pressor responses to the aforementioned drugs obtained in the bile-duct ligated rats were significantly attenuated from those the sham-operated rats. In contrast, bile duct ligation had no effect on the pressor responses to tilting and hemorrhage when compared to the responses obtained in the sham-operated rats. Despite the presence of systemic hypotension and attenuation of pressor response to vasoactive drugs, the ability of the cardiovascular system to respond to physiological stimuli appears to be intact in this model. Therefore, we conclude that blunted pressor responsiveness of the cardiovascular system is probably not an important physiological determinant of systemic hypotension in cholestatic liver disease.

Animals↗

PubMed1988

Increase in central and peripheral benzodiazepine receptors following surgery.

[3H]Flunitrazepam, [3H]PK 11195, [3H]quinuclidinyl benzilate (QNB) and monoamine oxidase (MAO) A and B activity were measured in male rats 1, 3 and 7 days following laparotomy. The surgery resulted in the up-regulation of central benzodiazepine (BZ) receptors in cerebral cortex and of peripheral BZ binding sites in brain and kidney on the first and third days after operation. This increase was followed by a decrease to normal range 7 days after the surgical procedure. [3H]QNB binding to muscarinic receptors in the cerebral cortex as well as MAO A and B activity in rat cerebral cortex and kidney were not affected by the surgical manipulation. The modulatory effect of surgery on BZ receptors corresponds to stages of the healing process in surgical wounds.

Animals↗

PubMed1987

Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes.

The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10(-9)-10(-6) mol/l, which corresponds to concentrations found in the plasma of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect.

Action Potentials↗

PubMed1987

Vascular reactivity in reversible experimental obstructive jaundice.

We studied the effect of jaundice on in vitro vascular reactivity to cumulative doses of norepinephrine (NE) by measuring the maximal response (Rmax) and the concentration of NE required to cause a 50% response (ED50) of isolated vascular smooth muscle. For this we prepared helically cut strips of thoracic aorta from bile duct ligated (BDL) rats at 1, 3, 6, 14, and 28 days postligation and compared them with those of nonoperated and sham-operated controls. From 1 to 6 days post-BDL, changes in liver blood chemistry and liver histology indicated cholestasis with necrosis. By 14 days, the tests for liver function and histology indicated a return to normal liver function and histology. In nonoperated controls, mean Rmax increased significantly from 883 +/- 67 mg of tension to 1220 +/- 68 mg of tension (P less than 0.0025) from 0 to 28 days, whereas ED50 remained unchanged. In sham-operated controls and BDL rats, an age-dependent increase in Rmax was also observed. However, in the sham groups, ED50 tended to decrease compared with nonoperated controls, indicating a surgically induced "sensitization" phenomenon of the vascular smooth muscle. In contrast, this was not seen in BDL rats since in these groups, the ED50 remained unchanged and significantly higher than in the sham groups, in both the jaundiced (1-6 days) and nonjaundiced (14-28 days) period. Furthermore, these changes occurred in the absence of any alteration in portal pressure. These changes may be important in understanding the mechanism of hypotension and shock in postoperative patients with obstructive jaundice even after the jaundice has been relieved.

Animals↗

PubMed1987

Vascular reactivity in experimental portal hypertension.

Portal hypertension (PHT) is known to be associated with a hyperdynamic circulation, yet the pathogenesis of both remains unclear. Therefore, we have studied serially the relationship between portal pressure and in vitro peripheral vascular responsiveness in an animal model of presinusoidal PHT. In rats with partial portal vein stenosis (PPVS) or sham-operated (SO) controls, we studied contractile responses to cumulative doses of norepinephrine (NE) and to a single dose of 0.8 microM NE of 20-mm helically cut strips of thoracic aorta. At both 2 and 10 days postoperatively, the portal pressures (mean intrasplenic pressure) in PPVS, 14.3 +/- 1.5 mmHg and 14.1 +/- 1.3 mmHg were significantly elevated compared with SO controls, 7.6 +/- 0.6 mmHg (P less than 0.005) and 9.7 +/- 0.5 mmHg (P less than 0.01), respectively. Yet, there was no significant differences between the two groups in the Rmax and ED50 of the contractile response curves to cumulative doses of NE as well as in the fast (phase 1) and slow phase (phase 2) of the contraction to 0.8 microM NE. In contrast, at 21 days, portal pressure in the PPVS rats fell to 11.0 +/- 0.7 mmHg but remained significantly higher than that of the SO controls, 8.2 +/- 1.0 mmHg (P less than 0.05). This occurred in conjunction with a significant decrease in Rmax [698 +/- 87 mg (PPVS) vs. 1148 +/- 92 mg (SO); P less than 0.005] but no significant change in ED50, indicating a decreased sensitivity to NE due to an alteration in alpha-adrenoreceptor function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Ultrastructure of the myocardium in dogs with induced jaundice.

Morphological aspects of the myocardium in dogs with experimentally induced jaundice were assessed ultrastructurally. Obstructive jaundice was produced by chronic bile-duct ligation and by choledochocaval anastomosis. The left ventricular myocardium and the papillary muscle were used. Statistical analysis of sarcomere length and of mitochondrial density showed no significant differences between jaundiced and sham-operated dogs. Qualitative evaluation of the mitochondria, the intercalated disc and other sarcoplasmic constituents revealed no damage to the jaundiced dogs.

Animals↗

PubMed1986

Renal bilirubin excretion in canine models of jaundice.

Renal handling of bilirubin and its relationship to blood bilirubin level were investigated for up to 2 weeks in two models of jaundiced dogs, namely, chronic bile duct ligation (CBDL), which are mildly icteric, and choledococaval anastomosis (CDCA), which develop deep jaundice. The mean (+/- SD) urinary bilirubin excretion in CBDL plateaued at 30.3 +/- 9.3 mg/24 hr whereas in CDCA it continued to increase above the normal bilirubin production rate (56-84 mg/24 hr) up to 130-150 mg/24 hr. The renal clearance of bilirubin in both models was inversely proportional to serum bilirubin concentration. It was approximately twice as high in the CDCA model, which induced also a moderate diuresis. It is suggested that higher serum bilirubin levels in CDCA dogs is due to the increased production of bilirubin which is not compensated by the renal clearance of bilirubin.

Animals↗

PubMed1986

Renal alpha-1-adrenoreceptors in rats with obstructive jaundice.

Alpha 1-Adrenoreceptor affinity constants (KD) and receptor numbers (Bmax) were determined in the kidneys of 3-day-old bile-duct-ligated (BDL) jaundiced rats using 3H-prazosin. The results were compared to 3-day-old pair-fed and nonpair-fed sham-operated rats as well as nonoperated rats as controls. Abdominal surgery (sham and BDL) resulted in a tendency towards a decrease in KD in all three groups of rats compared to nonoperated controls. The Bmax was also increased in the sham-operated groups compared to the nonoperated controls. In contrast, the tendency for a rise in the Bmax in the BDL group was significantly smaller than the rise seen in the two sham-operated groups. In summary, obstructive jaundice suppresses the normal renal alpha 1-adrenoreceptor response to abdominal surgery in the rat.

Animals↗

PubMed1986

Cardiovascular function in obstructive jaundice: experimental observations.

Patients with obstructive jaundice are more susceptible to post-operative shock than are nonjaundiced patients. This paper reviews the presently available experimental information, and concludes that jaundice blunts the contractile response of cardiac and vascular smooth muscle to sympathetic stimulation. Moreover, the experimental studies indicate that altered peripheral catecholamine metabolism may account for these attenuated responses.

Animals↗

PubMed1985

Modification of pulmonary metabolism of noradrenaline in experimental obstructive jaundice.

The pulmonary metabolism of noradrenaline (NA) was measured in lungs removed from 3 day sham-operated rats and from rats whose bile ducts had been ligated 3 days earlier (BDL). The pulmonary metabolism of NA as measured by a single clearance of the radio-labelled 14C-amine was significantly increased in lungs excised from BDL rats as compared to that measured in the sham-operated rats. The change in metabolism was associated with an alteration in the pulmonary uptake of NA and not with the activities of the enzymes monoamine oxidase types A and B and catechol-O-methyl transferase. Moreover, it was not correlated with rises in the bilirubin or cholesterol concentrations in the serum of the BDL rats and occurred independent of any changes in pulmonary pressure. In a second series of experiments, the evolution of this abnormality over the period of one to six days postoperative was investigated. In the sham-operated rats, there was no significant change in the pulmonary metabolism of NA even by the sixth day. In contrast, there were time-dependent increases from one to six days in these metabolic processes in BDL rats with the highest values being at six days. In contrast, the serum concentrations of bilirubin and cholesterol and activities of the enzymes, alanine transaminase and alkaline phosphatase all rose to their maximum by the fourth day and thereafter declined. Although serum albumin levels fell significantly in BDL rats they were not significantly different from sham-controls. Thus, change in pulmonary metabolism of NA with obstructive jaundice increases with time from one to six days and it not related to the blood chemical changes of biliary obstruction or hepatic synthetic function.

Alanine Transaminase↗

PubMed1985

Perfusion of the isolated rat hind limb. An analysis of the technique.

We have studied critically the validity, reproducibility, and possible limitations of the rat hind limb perfusion technique under constant flow conditions. Of all the variables studied, bolus size, order of dose administration, perfusion pressure, rat temperature, perfusate temperature, perfusate type, rat age, and rat sex, we found that time is an important limitation in the use of this technique when oxygenated standard physiological salt solutions are used. This limitation may be minimized when a colloid is added to the perfusing medium or eliminated when the perfusion time is no longer than 60 min.

Age Factors↗