The influence of glycerol on the Ca flux in the isolated perfused rat heart

Perfusion of the isolated rat heart with a fluid containing 800mM glycerol in addition to its normal constituents causes a contraction height decrease of about 50%. A change to normal perfusion fluid causes a period of contracture to occur. After this period the heart is perfectly viable. Mechanical and osmotic effects could be ruled out as possible causes. No gross disturbances were seen in the electron micrographs. An effect on intermediary metabolism is equally unlikely. Presumably, we must seek the explanation in a direct effect of the glycerol on the Ca++ fluxes across the cellular and intracellular membranes.     

The influence of trazodone on the circulatory system in patients with endogenous depression. II. Influence on vascular reflexes

In patients suffering from endogenous depression, Trazodone caused a tendency to normalization of results of Schellong's orthostatic test, the cold pressor test, and tests of thermoregulation.     

The isolated air perfused rat heart

A simple method has been developed for continuous monitoring of metabolic activity of an isolated, perfused rat heart by O2/CO2 respirometer. Since respirometer provides vital data on oxygen consumption and carbon dioxide production of a preserved organ on a continuous basis over a long period of time, it will be possible to use this method to monitor viability of not only isolated heart but also any given donor organ under preservation.     

The influence of trazodone on the circulatory system in patients with endogenous depression. I. Basic circulatory parameters

In patients with endogenous depression in remission, decline of systolic blood pressure and a statistically significant shortening of pulse time were found.     

Mechanism of uptake of technetium-tetrofosmin. II: Uptake into isolated adult rat heart mitochondria

BACKGROUND: 99mTc-labeled tetrofosmin is a new myocardial imaging agent that gives stable heart uptake. However, little is known about the mechanism of uptake in heart tissue. The aim of this study was to assess the factors responsible for the uptake and retention of 99mTc-labeled tetrofosmin in isolated heart mitochondria. METHODS AND RESULTS: Mitochondria were isolated from adult rat heart tissue with competent metabolic function (i.e., respiratory control ratio of 3 and adenosine diphosphate/oxygen ratio of 2) for succinate oxidation. Intramitochondrial volume measured by the distribution of 3H-water and 14C-sucrose was 1.16 +/- 0.23 microliters/mg protein (mean +/- SD). In the isolated mitochondria, uptake could be demonstrated within 30 seconds of addition of oxidative substrate, but adenosine triphosphate alone did not stimulate marked uptake. Uptake was proportional to the amount of mitochondrial protein over a range of 0.2 to 3 mg protein but independent of Tc-labeled tetrofosmin concentration over a range of 0.4 to 200 pmol/L (0.1 to 50 microCi/ml). The presence of Tc-labeled tetrofosmin had no effect on the oxidative capability of the mitochondria. Use of the mitochondrial uncoupler 2,4-dinitrophenol caused release of 92% of radioactivity. Addition of Ca2+ to the mitochondria to partially depolarize the membrane resulted in partial release of activity. Application of the Nernst equation to the uptake data gave rise to a value of -163 mV for the mitochondrial membrane potential. CONCLUSION: It was concluded that the accumulation of 99mTc-labeled tetrofosmin by the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential.     

Evaluation of the isolated paced rat heart

Ventricular performance and coronary flow in Langendorff perfused rat hearts were measured over a wide range of perfusion pressures and heart rates. A change in aortic pressure from 60 to 120 mmHg induced a linear increase in coronary flow, ventricular systolic pressure, and contractility. Ventricular pacing from 300 to 600 beats/min under a constant afterload had no effect on coronary flow. Systolic pressure remained stable up to 400-450 beats/min and then decreased 14% at 600 beats/min compared to the nonpaced controls. When contraction rate exceeded 450 beats/min diastolic pressure progressively increased as the heart rate was elevated. Contractility decreased rapidly between 450 and 600 beats/min under all perfusion pressures. These data indicate that this heart model is physiologically stable with heart rates less than 450 beats/min and may be useful in studying tachycardia-induced work overload.     

The influence of upper respiratory tract receptors stimulation on the respiration and heart action in rats

1. Stimulation of the upper respiratory tract with water releases reflex respiratory arrest and very marked bradycardia due to conduction and impulse generation disturbances in the heart accompanied by ventricular hyperexcitability. 2. Asphyxia causes bradycardia as a result of an inhibition of sinus node and the development of vicarious rhythms with excessive ectopic ventricular excitability. The intensity and duration of bradycardia during asphyxia are less than during water stimulation of airways. 3. Urethane anaesthesia did not prevent the development of the above described changes appearing during stimulation of the upper airways while topical analgesia with lidocaine completely prevented their appearance. The observations seem to suggest that for safety, surgical treatment in the upper airways should be done under analgesia of the respiratory mucosa. 4. The mechanism of the development of these changes seems to depend mainly on nervous and humoral factors, although the influence of other factors cannot be excluded. 5. Reflex changes in the action of the heart caused by water stimulation of the upper airways may be one of important components of the complex physiopathological process leading to death in drowning persons.     

A study of the actions of histamine on the isolated rat heart

1. The effects of histamine on cardiac force, heart rate and coronary perfusion pressure were studied in the isolated rat heart, using the Langendorff perfused heart preparation. 2. Single injections of histamine induced dose-dependent decreases in contractile amplitude, heart rate and coronary perfusion pressure. 3. Perfusions of metiamide (above 1 x 10(-4) m) had a depressant effect on contractile force and heart rate, whereas diphenhydramine (4 x 10(-6) m) reduced only the heart rate. Both agents caused a fall in coronary perfusion pressure. 4. The negative inotropic and chronotropic effects of histamine on the isolated rat heart were not significantly influenced by either metiamide of diphenhydramine, or a combination of these drugs. However, the fall in coronary perfusion pressure induced by injections of histamine was significantly antagonized by metiamide or diphenhydramine. 5. These results suggest that the effects of histamine on the isolated rat heart may not be due entirely to stimulation of H1- or H2-receptors on the cardiac muscle cells. Evidence is presented for the existence of histamine H1- and H2-receptors in the coronary vessels.     

The insulinotropic action of gastric inhibitory polypeptide in the perfused isolated rat pancreas

Gastric inhibitory polypeptide (GIP) produced a dose-related increase in immunoreactive insulin (IRI) from the perfused isolated rat pancreas. The doses employed were within physiological limits. This effect was glucose-concentration-dependent in that there existed a threshold concentration of glucose above which GIP exerted the insulinotropic action, and that, at a fixed concentration of GIP, increased glucose concentrations stimulated IRI release in more than an additive manner. A biologically active fragment of the GIP molecule was isolated and purified. All criteria have been satisfied that GIP is an insulinotropic hormone.     

Sympatholytic action of intravenous amiodarone in the rat heart

BACKGROUND: Amiodarone is a commonly used antiarrhythmic agent with complex pharmacological effects. Although ventricular arrhythmias can be suppressed soon after intravenous amiodarone, the mechanisms responsible for this action are unclear. We studied the effects of acute treatment with amiodarone on the metabolism and release of norepinephrine (NE) in intact rats and in perfused rat hearts. METHODS AND RESULTS: Experiments were performed in anesthetized rats and in perfused, innervated hearts with amiodarone administered intravascularly. NE release was induced by electrical stimulation of the sympathetic ganglion. Concentrations of NE and its intraneuronal metabolite dihydroxyphenylglycol (DHPG) in hearts, plasma, and coronary venous effluent were measured by high-performance liquid chromatography. Acute administration of amiodarone induced dose-dependent increases in DHPG concentrations in plasma (5 mg/kg, +48%; 15 mg/kg, +84%; and 50 mg/kg, +467%) and in coronary venous effluent (1 mumol/L, +37%; 3 mumol/L, +510%; and 10 mumol/L, +1100%) together with an unchanged basal overflow of NE. In perfused hearts, NE release evoked by nerve stimulation was inhibited by infusion of amiodarone (1 mumol/L, -16%; 3 mumol/L, -24%; and 10 mumol/L, -64%) or by intravenous amiodarone (50 mg/kg) given 1 hour before heart perfusion (-70%), and the extent of this suppression correlated well with levels of DHPG overflow present immediately before nerve stimulation. When given in vitro and in vivo, amiodarone also significantly reduced NE and increased DHPG content in the heart, leading to a raised DHPG/NE ratio. All these effects of amiodarone were similar to those found with reserpine but less potent. In contrast, oral amiodarone produced none of these effects. CONCLUSIONS: Acute administration of amiodarone in perfused hearts or intact rats induces partial NE depletion in the heart by interfering with vesicular NE storage and enhancing intraneuronal NE metabolism, effects associated with an impaired NE release during sympathetic activation. Oral dosing with amiodarone has no such effect. Further study is required to test whether this novel sympatholytic effect of amiodarone contributes to its antiarrhythmic action after intravenous administration.     

Manganese reduces myocardial reperfusion injury on isolated rat heart

It has been shown that reactive oxygen species produced during the early phase of myocardial post-ischemic reperfusion are one of the main causes of reperfusion injury. This observation has led to various antioxidant strategies using many reactive oxygen species scavengers, including manganese complexes. The aim of the present work was to provide a reference study of the effects of manganese itself (MnCl2) on isolated rat hearts submitted to global total normothermic ischemia (30 min) and reperfusion (60 min). McCl2 was administered either during the first 10 min reperfusion (10(-5)M and 10(-4)M) or throughout reperfusion (10(-4)M). After 10 min reperfusion, no functional difference was evidenced between control and manganese-treated groups, whereas high energy phosphate contents were significantly higher in treated groups. MnCl2 10(-4)M enhanced the recovery of developed pressure between 40 and 55 min reperfusion. At the end of reperfusion, hearts treated during the first 10 min reperfusion showed a better metabolic recovery. The group treated throughout reperfusion showed a better metabolic recovery, but a reduced coronary flow and a weak recovery of developed pressure. These results suggest that MnCl2, administered during the early phase of reperfusion, protects against myocardial reperfusion injury. This effect might be mediated by manganese antioxidant properties.     

The interaction between enalaprilat and selected alpha-adrenoceptor antagonists in isolated rat tail arteries

1. Isolated perfused rat tail artery preparations were used to investigate the effects of the angiotensin converting enzyme inhibitor enalaprilat on the actions of a series of alpha-adrenoceptor antagonists. The agonist used was phenylephrine. 2. Enalaprilat (1 mumol/L) potentiated the competitive alpha 1-adrenoceptor antagonist actions of phentolamine (10-100 nmol/L) and yohimbine (0.3-3.0 mumol/L) as well as the non-competitive antagonist action of phenoxybenzamine (50-100 pmol/L). 3. The competitive alpha 1-adrenoceptor antagonist action of prazosin (1-10 nmol/L) was not affected by enalaprilat. 4. For the competitive alpha 1-adrenoceptor antagonists, including prazosin, there appeared to be an inverse relationship between antagonist potency and the extent of potentiation by enalaprilat. 5. The results support the hypothesis and angiotensin II modulates vascular smooth muscle alpha 1-adrenoceptor function.     

Effects of thyroxine pretreatment and calcium on the isolated perfused rat heart

Phosphorylase a activity was the same in isolated perfused hearts from euthyroid and thyroxine-pretreated rats. Perfusion with 3.6 mM Ca2+ caused an increase in phosphorylase a in hearts from euthyroid as well as those from thyroxine-pretreated animals, but the Ca2+-induced stimulation of phosphorylase activity was similar in both groups over the time course studied. Greater conversion of phosphorylase b to a occurred with 7.2 mM than with 3.6 mM Ca2+ in both groups, but once again thyroxine pretreatment did not significantly influence the conversion of phosphorylase b to a. Isometric systolic tension increased in response to 3.6 mM and 7.2 mM Ca2+ in hearts from normal and thyrotoxic rats, but thyroxine pretreatment did not appreciably alter the nature of this response. While spontaneous heart rate was higher in hearts from thyroxine-pretreated rats, perfusion with 3.6 mM or 7.2 mM Ca2+ had no significant effect on heart rate in hearts from euthyroid or thyrotoxic rats.     

Factors modifying ischemic injury in the isolated rat heart

The extent of ischemic injury has been studied in the isolated working rat heart utilizing an aortic ball valve that reduces the coronary flow. A number of factors were tested including high heart rate, noradrenaline, acidosis, alkalosis, high afterload, beta-blockade, glucose-insulin-potassium (GIK), palmitate and methylprednisolone. Mechanical performance, myocardial contents of ATP, creatine phosphate, glycogen and lactate and the leakage of creatine phosphokinase (CK) from the myocardium to the perfusion buffer were measured and used for determination of the ischemic injury. Tachycardia, noradrenaline and palmitate are factors that markedly increase the ischemic injury in this preparation. GIK and probably metoprolol decrease the release of CK compared with the controls.     

Dependence of adrenalectomy-induced sodium appetite on the action of angiotensin II in the brain of the rat.

Adrenalectomized rats express a robust sodium appetite that is accompanied by high levels of blood-borne angiotensin II and is caused by angiotensin II of cerebral origin. Blood-borne angiotensin II is elevated in rats consuming NaCl after adrenalectomy, and plasma angiotensin II concentrations are increased further when the animals cannot drink a NaCl solution. These phenomena are the result of the pathological removal of aldosterone, because replacement therapy returned both sodium intake and plasma angiotensin II concentrations to preadrenalectomy levels. The adrenalectomized rat's appetite for sodium is completely suppressed by interference with the central, but not the peripheral, action of angiotensin II. These data demonstrate that the mechanism of the sodium appetite of the adrenalectomized rat is a pathological instance of the angiotensin/aldosterone synergy that governs the sodium appetite of the adrenal-intact, sodium-depleted rat. Because aldosterone has been removed, angiotensin acts alone to produce the appetite. Furthermore, the data show that it is angiotensin II of central origin that is important for sodium appetite expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)