Search PubMed⌕ Search

Biomedical subjects

A Bomzon

Publications and source records attributed to A Bomzon.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Obstructive jaundice blunts myocardial contractile response to isoprenaline in the dog: a clue to the susceptibility of jaundiced patients to shock?

Patients with obstructive jaundice are susceptible to postoperative shock. To clarify the mechanism of this phenomenon, we compared the contractile response to isoprenaline of isolated ventricular preparations from three groups of dogs: (a) dogs with chronic bile-duct ligation (CBDL), (b) dogs with choledochocaval anastomosis (CDCA) and (c) sham-operated dogs (SO). Isolated ventricular muscles from CBDL and CDCA dogs showed a depressed contractile response to isoprenaline as compared with SO dogs. Mechanical performance was spared in the CBDL and CDCA dogs. There were no differences in the contractile responses of SO and CBDL dogs, either to ouabain or to changes in the rates of stimulation (force-frequency relationships). These data demonstrate that, in the dog, obstructive jaundice and/or cholaemia are associated with blunted contractile response to beta-adrenoreceptor stimulation in the face of intact basic mechanical performance. Similar inotropic refractoriness to beta-adrenoreceptor stimulation could contribute to the susceptibility to postoperative shock in patients with obstructive jaundice.

Alanine Transaminase↗

Reversible suppression of the vascular contractile response in rats with obstructive jaundice.

Both patients and experimental animals with obstructive jaundice manifest vascular instability, with animals showing a blunted vascular response to norepinephrine (NE). We sought an intrinsic abnormality of vascular smooth muscle by studying the contractile response of isolated, helically cut aortic strips and intact portal veins to cumulative doses of NE in rats with bile duct ligation (BDL) at different times compared with sham-operated (SO) rats as controls. At 3 days after surgery, the mean cumulative maximal contractile response (Rmax) of the aortic strip of BDL rats (94.3 +/- 9.0 mg/mg tissue) was significantly lower than that of SO controls (145.3 +/- 11.5 mg/mg tissue) (P less than 0.005), associated with a tendency toward decreased sensitivity (half-maximal dose [ED50]) (18.2 +/- 6.75 nmol/L vs. 6.7 +/- 0.6 nmol/L). By 6 days, there was no difference between the two groups. Similarly, by 3 days the mean Rmax for portal vein contraction in BDL rats (694 +/- 72 mg) was significantly lower than that for SO rats (1000 +/- 143 mg). In contrast, mean ED50 of the portal veins of BDL rats (327 +/- 65 nmol/L) was significantly less than that of SO rats (881 +/- 216 nmol/L), indicating greater sensitivity. At 1 and 6 days after surgery there was no significant difference between the two groups. These alterations in the vascular contractile response coincided with the maximum increases in serum bilirubin and liver enzyme levels. In conclusion, this study indicates that the circulatory abnormalities associated with obstructive jaundice are associated, at least in part, with suppression of the vascular contractile response caused by some abnormality of the vascular musculature.

Alanine Transaminase↗

Bile salts, hypotension and obstructive jaundice.

We have examined the effects of bile duct ligation on vascular and extravascular smooth muscle responsiveness to noradrenaline and tyramine using isolated rat hindlimb perfusion, and portal vein and vas deferens preparations. Bile duct ligation reduced the contractile responses to noradrenaline of vascular and extravascular smooth muscle. Exposure of smooth muscle to some bile salts caused a reduction in contractility. This effect was dependent upon bile salt type and concentration. These studies in vitro suggest that the reduced total peripheral resistance and hypotension seen in obstructive jaundice cannot be explained by a spasmolytic effect of some of the bile salts on smooth muscle.

Animals↗

Effects of forskolin in rat vas deferens--evidence for facilitatory beta-adrenoceptors.

Forskolin inhibited the response to electrical field stimulation (0.1 Hz) and antagonised contractile responses to noradrenaline in the isolated rat vas deferens. The inhibition of the response to electrical stimulation (IC50 0.1 microM) was not affected by either propranolol or yohimbine. Both isoprenaline and forskolin enhanced the total tritium efflux during transmural stimulation of vas deferens which had been prelabelled with [3H]noradrenaline. These data provide evidence that beta-adrenoceptor stimulation enhances noradrenaline release in the vas deferens, although the postsynaptic relaxant effect on smooth muscle predominates in determining the net response. The data are consistent with a stimulation of adenylate cyclase in mediation of both presynaptic and postsynaptic effects of beta-adrenoceptor agonists in the vas deferens.

Adrenergic beta-Agonists↗

Systemic hypotension and decreased pressor response in dogs with chronic bile duct ligation.

Vascular instability as defined by systemic hypotension and unresponsiveness to endogenous or exogenous vasoactive substances is a feature of both patients and experimental animals with obstructive jaundice. In this study, we have attempted to dissect the possible mechanisms for these abnormalities using both in vivo and in vitro methods. In vivo cumulative pressor responses (Rmax) to intravenous and intraarterial infusions of norepinephrine and angiotensin II and to intravenous infusion of angiotensin I were studied pre- and postoperatively in chronic bile duct-ligated dogs and compared to sham-operated dogs. Preoperatively, the pressor responses to the cumulative infusion of six doses of vasoactive substances in the pre-sham operated and pre-chronic bile duct-ligated dogs were not significantly different. Postoperatively, in the sham-operated dogs, there was no significant change in systemic blood pressure at 1 and 3 weeks, and only in isolated instances were significantly different pressor responses found compared to the preoperative result. In chronic bile duct-ligated dogs, the mean systemic blood pressure fell significantly from 117.2 +/- 3.1 to 107.2 +/- 3.0 mm Hg (p less than 0.01) at 1 week and remained significantly lower at 3 weeks [109.7 +/- 2.6 mm Hg (p less than 0.05)]. The Rmax to intravenous, but not intraarterial norepinephrine, was significantly decreased. In contrast, the Rmax to both intravenous and intraarterial angiotensin II infusions were significantly depressed at both 1 and 3 weeks. Similarly, the response to intravenous angiotensin I was significantly depressed. Cardiac output rose moderately in two sham-operated dogs from an average of 3.1 to 3.5 liters per min by 3 weeks associated with a decrease of 14.8% in peripheral vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

The jaundiced heart.

Explore the source record for details and available documents.

Animals↗