Guinea pig atria Essay

Introduction

From Human Physiology & A ; Pathology, the basic cognition about cardiac map & A ; the coevals of the bosom round was known from last twelvemonth. There are four auricula atriis, the atria is placed on the on the two upper auricula atriis ( known as the left & A ; right atrium ) . The function of the right atrium is to have de-oxygenated blood from the superior vein cava, inferior vein cava & A ; coronary fistula. The left atrium receives the oxygenated blood from the left & A ; right pulmonary venas. The ventricles are placed on the bottom two auricula atriis ( known as the left & A ; right ventricle ) . The function of the right ventricle is to pump blood into the pneumonic circulation for the lungs. The left ventricle pumps blood into the systematic circulation through the aorta into the remainder of the organic structure.

The bosom has a pacesetter activity, which is initiated through the sinoatrial ( SA ) node. The SA node is the pacesetter tissue located in the wall of the right atrium of the bosom, near the entryway of the superior vein cava & A ; therefore the generator of the fistula beat. They do non contract, even though they possess contractile fibrils. They send action potencies to the atrioventricular ( AV ) node, doing the ventricles to contract, forcing the blood through the aorta into the remainder of the organic structure.

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The atrium of the guinea hog is able to last in vitro & A ; it is able to crush spontaneously every bit long as the SA node is n’t damaged. In comparing to the atria, the ventricle has no pacesetter activity.

Method

Before come ining the research lab room, the pharmacological medicine lectors ( Dr. Javid & A ; Dr. Airley ) had dissected the bosom in to the constituents ( atria & A ; ventricles ) needed. This was all done in the Ringer-Locke solution ( isosmotic electrolytic extract solution ) to keep the bosom was at optimal degree. The dissection of the atria was done by paring off the fat & A ; exposing the auriculoventricular junction ( appears as a pale xanthous line ) . The left side of the bosom can be distinguished by positioning it, so both the auricula atriis can be seen. After the atria had been isolated, a perpendicular cut between the auricula atriis along the atrial septum was made. The strip of atrial tissue was so connected to the tissue holder & A ; transducer. The tissue was so placed under a light sum of tenseness ab initio to avoid stretching & A ; damaging the tissue ‘ therefore taking to impairing of the sinoatrial node ( SA ) . If the SA node was impaired it would hold been a job, as the cells within the SA are the primary pacesetter site/activity which generates electrical urges ( or action potency ) which control the bosom. The cells have no true resting possible, but generate regular action potencies.

For the dissection of the ventricle, while the bosom was in the Ringer-Locke solution a perpendicular cut was made into the ventricle. A parallel cut was done to insulate the strip of bosom musculus. Finally it was connected to the tissue holder & A ; transducer. As the ventricle has no pacesetter activity, an electrode was connected to the stimulator with the aid of some crocodile cartridge holders. The stimulator was needed to gait the stripped ventricle.

Both the atria & A ; ventricles were placed into organ bath ( separate ) , with a concluding bath volume of 50ml. The LabTutor apparatus had two channels. The first channel was mensurating the end product from the transducer & A ; this was wholly dependent on the readying. The 2nd channel was ciphering the fluctuation of the contraction rate with clip.

The LabTutor was used to set up the baseline contractile activity. The atria should be crushing spontaneously due to the SA node. The ventricles nevertheless will necessitate pacing utilizing the stimulator apparatus.

There were 4 parts to this experiment. Which were:

Exp1 1a: – Effectss of isoprenaline

To detect the response to the ventricle with the add-on of isoprenaline.

The first measure was to cipher the volume of isoprenaline needed for the Final Bath Concentration ( FBC ) of 10-10 M, utilizing equation 1 ( from practical sheets ) . The volume calculated was 0.005µl, & A ; but was excessively little to mensurate utilizing the Gilson pipette. Therefore an add-on of 10µl was added to the ventricular tissue. The response was observed on the LabTutor & A ; before the following dosage of isoprenaline, the response signal had to be stabilised. Unfortunately there was no response, so the ventricle tissue was washed before the dosage was doubled to 20µl, so 40µl. In both instances there was no response observed, so the concentration was once more doubled to 80µl. There was still no response, so utilizing the stimulator the tissue was shocked. Even with the flooring there was still no response as the tissue was unable to gait itself. There was a farther & A ; concluding add-on of 160µl, but at that place was still no response. Therefore no consequences or informations were collected.

Expt 1b: – Effectss of Isoprenaline after Propranolol

To detect the response of both the atria & A ; ventricle, with the add-on of the EC50 dosage of isoprenaline in the presence of propranolol.

The following measure was to add propranolol to the FBC of 5-10-6M, & A ; a remark was added on the LabTutor so it was known when it was added. The readying was left for 10 proceedingss so it could equilibrate. Then the EC50 dosage of isoprenaline was added & amp ; another remark was added. After the add-on isoprenaline the response of the bosom tissue was measured utilizing the LabTutor. In the following 15 proceedingss the bosom tissue was washed out every 5 proceedingss, so consequences of the bosom tissue could be seen ( 3 times ) . Again there was no response, so no information or consequences collected.

Expt 2a: – Effectss of Acetylcholine

To detect the response of both the atria & A ; ventricle to acetylcholine.

The dilution & A ; volumes were once more calculated utilizing Equation 1. As the bosom needed tempo, there was an add-on of 10µl of isoprenaline. There was no response observed, hence 20µl of isoprenaline was added once more. There was no signal, hence any response. There was no farther add-on, as it would hold been a waste!

Expt 2b: – Effectss of Acetylcholine after Atropine

The concluding portion of the experiment was to detect the response on both the atria & A ; ventricle with the dosage of IC50 of acetylcholine, in the presence of atropine.

There was no signal, as the bosom tissue did n’t react from the old portion.

Consequences

Figure 1 shows the consequence as the concentration of isoprenaline ( Expt 1a ) is increased on the bosom tissue.

The inotropic & A ; chronotropic effects were increased, as the concentration of isoprenaline was increased. During the wash out of the bosom tissue ( to clean the old dosage ) , the inotropic consequence dropped to a lower limit of 0.7mN. There was a decrease of chronotropic consequence, as the signals were less frequent. However after the add-on of isoprenaline, the contraction force returned higher traveling up to 1.5mN. Therefore in the presence of isoprenaline there is a positive addition in both inotropic & A ; chronotropic consequence.

Figure 1

Figure 2 shows the consequence of isoprenaline in the presence of propranolol on the bosom tissue.

It shows the baseline as the tissue is at normal activity & A ; being paced with isoprenaline. Once the tissue was stabilised, propranolol was added to see the response. It shows the chronotropic consequence had decreased, as the bosom rate of the bosom tissue had slowed down, cut downing the frequence. When isoprenaline was added it can be seen the inotropic consequence of the bosom tissue being decreased therefore diminishing the volume of blood pumped from one ventricle of the bosom with each round ( stroke volume ) . This reduced the cardiac end product as there was less blood being pumped around the organic structure ; therefore increasing the end-systolic volume. As the EC50 dosage of isoprenaline was added to the bosom tissue, it can be clearly seen that both the inotropic & A ; chronotropic effects increased. Unfortunately the contraction force & A ; frequence of the response were n’t every bit vigorous in the absence of propranolol. The clinical side to a lessening in inotropic could be bad for patients whose bosom is non crushing at the normal rate ( lower ) . If there is a negative inotropic consequence, so the contraction force will non be forceful, ensuing in a low bosom rate ( Bradycardia ) .

Figure 2

Figure 3 shows the consequence of isoprenaline in both the presence & A ; absence of propranolol on the bosom tissue.

The inotropic consequence increased as there was an addition of concentration of isoprenaline. The EC50 ( horizontal line ) is the concentration of the isoprenaline that provokes a 50 % response between the baseline & A ; maximal response. The EC50 is higher when in the presence of propranolol, this shows a greater concentration of isoprenaline is needed to bring forth the same response ( compared to isoprenaline entirely ) . Both propranolol & A ; isoprenaline were viing for the & A ; szlig ; 2-adrenergic receptors located on the bosom, & A ; it can be seen that propranolol has the higher affinity.

Figure 3

Figure 4 shows isoprenaline added to the cardiac tissue, for the tempo.

Before the add-on of isoprenaline the force was comparatively stable between 0.6-0.7mN, after it raised to a upper limit of 0.8mN.

Figure 4

Figure 5 shows the consequence as the concentration of acetylcholine is increased on the bosom tissue.

Both the inotropic & A ; chronotropic consequence had decreased of the bosom tissue, as the concentration of acetylcholine had increased. As the bosom tissue was washed out, the inotropic & A ; chronotropic consequence had increased. This is due to the old dosage of acetylcholine being washed out. After each dosage of acetylcholine ( after being washed out & amp ; as the concentration was increasing ) , the inotropic & A ; chronotropic consequence had dropped dramatically. The contraction force goes to a lower limit of 0.6mN.

Figure 5

Figure 6 shows the consequence of acetylcholine in the presence of atropine in the bosom tissue.

It shows with the add-on of atropine there was a big addition in both the inotropic & A ; chronotropic consequence. With acetylcholine, both the inotropic & A ; chronotropic consequence had dropped significantly, with the contraction force dropping to a lower limit of 0.8mN. Negative inotropic consequence shows a lessening in myocardial contractility & A ; cardiac work load.

Figure 6

Figure 7 shows the consequence of acetylcholine in both the presence & A ; absence of atropine on the bosom tissue.

The inotropic consequence was greater when in the absence of atropine. The IC50 ( horizontal line ) is the step of the effectivity of a compound in suppressing biological or biochemical map. The IC50 is higher when in the presence of atropine, this shows a greater concentration of acetylcholine is needed to bring forth the same response ( compared to acetylcholine by it itself ) .

Figure 7

Discussion

Isoprenaline is a powerful non-selective beta-adrenergic agonist ( activates & A ; szlig ; 1 & A ; & A ; szlig ; 2 every bit ) & A ; it has a low affinity for a-adrenergic receptors. It is a adrenergic agent ; therefore you should see an addition in the bosom rate as the contraction force is traveling to be more powerful & A ; more frequent.

From Figure 1 & A ; 3 it can be clearly seen that there was an addition in inotropic, chronotropic & A ; dromotropic consequence. This is because there are & amp ; szlig ; 1-adrenergic receptors on the bosom which bind to isoprenaline ; therefore taking to a higher cardiac end product & A ; oxygen supply ( greater shot volume & A ; bosom rate ) . The & A ; szlig ; -adrenergic receptors are a type of G protein-coupled receptors that are marks of catecholamines. Isoprenaline is a catecholamines. The G protein-coupled receptor is linked to adenylate cyclase, which is an enzyme. Isoprenaline adhering causes a rise in the intracellular concentration of the 2nd courier camp ( cyclic Adenosine MonoPhosphate ) . Downstream effecters of camp include cAMP-dependant protein kinase ( PKA ) , which causes phosphorylation & A ; activates the Ca ion channels. Thus release of Ca ions by the sarcoplasmic Reticulum ( SR ) in the bosom makes the cardiac musculus contract.

It was predicted as the concentration of isoprenaline increased, there would be more response from the cardiac tissue. Both the inotropic & A ; chronotropic consequence would increase, as the contraction would be more vigorous & A ; the signal was more frequent ( higher bosom rate ) . This is because more of the unoccupied receptors would go occupied organizing a composite.

From Figure 1 & A ; Figure 3, it can be seen as the concentration of isoprenaline was increased there were more vigorous contraction & A ; the signal was more frequent. Therefore increasing the inotropic & A ; chronotropic consequence, so the anticipation was right.

In both the presence & A ; absence of propranolol there were differences with the response. Comparing the two, it is expected in the presence of propranolol there is traveling to be a negative inotropic, chronotropic & A ; dromotropic consequence. In the absence of propranolol, there is traveling to be a positive inotropic & A ; chronotropic, because there is traveling to be strong contraction force as isoprenaline is a direct cardiac stimulation.

From Figure 2, it can be seen in the presence of propranolol, both the inotropic & A ; chronotropic effects decreased. From Figure 3, the EC50 dosage of isoprenaline is greater when in the presence of propranolol. The response is pretty undistinguished, as there is really small occurring.

From Figure 1, after each dosage of isoprenaline ( after the wash out & As ; with increasing concentration ) , the contraction force was big. The contraction force reached a upper limit of 1.5mN. There was a batch of frequence & A ; signals, they were rapid ( hence high bosom rate ) . There were important alterations in the response of the cardiac tissue.

Isoprenaline is used in bradycardia. It works by triping the & A ; szlig ; 1-adrenergic receptors located on the bosom, which induces an addition in inotropic, dromotropic & A ; chronotropic effects. This leads to an addition in the shot volume & A ; bosom rate, therefore greater cardiac end product ( stroke volume – bosom rate ) . Therefore the blood is pumped through the aorta at a high gait. It is besides used for Adams-Stokes onslaught, COPD etc.

A high dosage of isoprenaline helps in bronchoconstriction, and it is used by loosen uping the bronchial smooth musculus, therefore loosen uping the air passages to increase air flow in the lungs. There is besides an addition in end-diastolic volume & A ; sympathetic volume.

Isoprenaline is n’t used much, because it leads to excessively many inauspicious reactions for illustration dyspnea. This causes the musculus spindles in the chest wall to signal the stretch/tension of the respiratory uscles. The hapless airing leads to go forth bosom failure, taking to interstitial hydrops, asthma doing bronchoconstriction.

However, isoprenaline chief inauspicious reaction is tachycardia. This is because bosom is crushing above its normal rate, the bosom does n’t pump at its optimal degree, and hence less blood is being supplied to the heart/body. The increased bosom rate leads to increased work & A ; myocardial O demand, which can take to myocardial infarction. This occurs due to myocardial O supply non run intoing the demand doing myocardial cells to decease off. This leads to angina & amp ; to ischemic bosom disease.

Side effects include concern, sudating, chest hurting etc, due to its non-selective behavior. It ca n’t be administered with other direct cardiac stimulations because it increases the opportunity of serious arrhythmias. It ca n’t be given to patients with tachycardia as the bosom rate is above normal rate. Isoprenaline will adhere to the & A ; szlig ; 1-adrenergic receptor which is located in the bosom, doing the contractile force & A ; frequence greater ; therefore an addition in inotropic, chronotropic & A ; dromotropic effects. This will take to a larger shot volume, bosom rate & A ; the myocardial O supply ; hence an addition in cardiac end product & A ; agrave ; bring oning a bosom onslaught. There ‘s no alteration in the blood force per unit area. There are many drugs that are newer & A ; work better than isoprenaline. Such drugs include Dobutamine, which is a adrenergic drug used in the intervention of bosom failure and cardiogenic daze. Its primary mechanism is direct stimulation of & A ; szlig ; 1-adrenergic receptors of the sympathetic nervous system.

Propranolol is used for in the intervention of high blood pressure, angina & A ; atrial fibrillation. When high blood pressure occurs there is a rise in Cardiac Output ( CO ) , with the Entire Peripheral Resistance normal ( TPR ) . There is a big force forcing the blood via the aorta to the organic structure. Therefore there is a positive inotropic & A ; chronotropic consequence. With the add-on of propranolol, it will adhere to the M2-receptors located in the bosom. They will busy the receptor, but wo n’t bring on an consequence. This will take down the force of contraction ; therefore cut downing the inotropic consequence.

Propranolol reduces the sum of blood fluxing through the organic structure, therefore it has an consequence on the tegument, musculus etc. Patients will get down to experience drowsing & A ; tired.

It is best to avoid when shooting with epinephrine. It will do a terrible allergic reaction. By utilizing them simultaneously it will ensue in a high blood force per unit area & A ; marked deceleration of the bosom round.

Some of the inauspicious reactions include bradycardia, hypotension & A ; bosom failure.

New drugs are being used because of its non-selective features. It is unpredictable ; therefore there are some substitutetable drugs. For illustration Sectral is selective for & A ; szlig ; 1 receptors merely.

Acetylcholine is a neurotransmitter ( NT ) in the peripheral & A ; cardinal nervous system. It is the lone NT used in the motor division of bodily nervous system. It is the chief NT in all autonomic ganglia. It binds to the acetylcholine Muscranic receptors ( e.g. M2-receptors located in the bosom ) . The M2-receptors decelerate down the bosom rate down to normal fistula beat, by decelerating the velocity of depolarization. Besides by cut downing the contraction forces of the atrial cardiac musculus & A ; conductivity speed of the AV node. They have no consequence on the contraction forces on the ventricle musculus. Muscranic receptors are G protein-coupled acetylcholine receptors found in cells. By moving via G-protein type receptor, there is a lessening in camp, taking to repressive effects ( on the bosom ) . The consequence acetylcholine has on the bosom is it reduces both the inotropic & A ; chronotropic consequence, by modulating the muscarinic K channels.

Atropine Acts of the Apostless as a competitory adversary on muscranic-acetylcholine receptors. However atropine has no efficaciousness at the M2-receptor therefore it blocks the consequence of acetylcholine. Then acetylcholine Begins to decelerate down the bosom. Therefore atropine has no cholinergic consequence & A ; therefore it is unable to decelerate down the bosom. But due to neuromodulation, it will let the sympathetic excitations to rule. Noradrenaline increases the bosom rate, so the net consequence of atropine on the bosom rate is to increase the rate of firing from the SA node. The bosom has both cholinergic & A ; noradrenergic receptors in itself, but it ‘s besides controlled through the cardiac & A ; vagus nervus.

It was predicted as the concentration of acetylcholine increased, there would be less response from the bosom tissue. Both the inotropic & A ; chronotropic consequence would diminish, as the contraction force wo n’t be forceful & A ; the signal & A ; frequence would be less ( lower bosom rate ) . This is because more of the unoccupied receptors would go occupied, but it would n’t be initiated.

However from Figure 5 & A ; Figure 7, it can be seen as the concentration of acetylcholine was increased there were more less contraction & A ; the signal/frequency was less moderate. Therefore diminishing the inotropic & A ; chronotropic consequence.

In both the presence & A ; absence of atropine there were differences with the response. Comparing the two, it is expected in the presence of atropine there is traveling to be a negative inotropic & A ; chronotropic consequence. In the absence of atropine, there is traveling to be a positive inotropic & A ; chronotropic, because there is traveling to be strong contraction force as it is a competitory adversary for the muscarinic acetylcholine receptor. It binds to the M2-receptors located on the bosom.

From Figure 6, it can be seen in the presence of atropine ; both the inotropic & A ; chronotropic effects were increased. From Figure 7, the IC50 dosage of acetylcholine is greater when in the presence of atropine. The response is pretty undistinguished, as there is really small happening. This is because they compete for the same receptors & A ; as acetylcholine occupies the receptors, it shows that it has higher affinity than atropine.

Atropine binds to muscarinic receptors so it stops acetylcholine from adhering to and triping the receptor. By barricading the actions of Acetylcholine, atropine blocks the consequence of pneumogastric nervus activity on the bosom. Therefore cut downing the inotropic & A ; chronotropic consequence. In a clinical state of affairs, the consequence of atropine would besides be mediated by its repressive consequence on the pneumogastric nervus.

From Figure 5, after each dosage of acetylcholine ( after the wash out & As ; with increasing concentration ) , the contraction force dropped. The contraction force reached a upper limit of 0.8mN, which was below the contraction force at the baseline period. There was a low bosom rate as the signals were non frequent. There were important alterations in the response of the cardiac tissue in both the presence & A ; absence of atropine.

Acetylcholine is used for Ocular peri-operatives drug. It is instilled into the anterior chamber of the oculus during surgery, rapidly bring forthing meiosis which lasts for 20 proceedingss.

Contraindication include gestation & A ; breast-feeding, but it ‘s non advisable.

Adverse reactions include hypotension, Shortness Of Breath ( SOB ) , sudating etc.

Atropine is used for many things, bradycardia is one option. Atropine binds to the & A ; szlig ; 2 sympathomimetic receptor found on the bosom. It increases its inotropic & A ; chronotropic consequence ; therefore acquiring a higher bosom rate & A ; shot volume. Therefore the cardiac end product additions ; intending the blood ( with O ) was going via the aorta with more strong belief. The dosage should be started titrating from a lower dosage. Initial dosage of 500µggiven intravenously ; the dosage can be repeated every 3-5 proceedingss every bit long as you do n’t transcend 3mg.

Contraindication include an addition in hazard in antimuscranic side consequence, if given with disopyramide.

Adverse reactions include self-contradictory bosom rate decelerating when given at really low doses, presumptively as a consequence of cardinal action in the Central Nervous System ( CNS )

Mistakes & A ; Improvements

Mistakes with the practical include the SA node might hold been dissected/damaged, as this is where the pacesetter activity occurs. As there was no response, it could intend the SA node might non hold been working.

As there was no consequence as the bosom tissue died, need to hold a fresh bosom at disposal.

Decision

I learnt the different type ‘s adrenergic & A ; parasympathomimetic agents & A ; how they affect the cardiac musculus.

The consequence of isoprenaline alone increases the inotropic, chronotropic & A ; dromotropic effects. In the presence of propranolol, the inotropic, chronotropic & A ; dromotropic effects were reduced. Besides I have gained a clinical position on both isoprenaline & A ; propranolol.

The consequence of acetylcholine alone decreases the inotropic & A ; chronotropic effects. In the presence of atropine, the inotropic & A ; chronotropic effects were positive. Besides I have gained a clinical position on both acetylcholine & A ; atropine.

Mentions

Klabunde, R. ( 2007 ) . Cardiovascular Pharmacology Concepts. Available: hypertext transfer protocol: //www.cvpharmacology.com/antiarrhy/atropine.htm. Last accessed 02 August 2009.

Rang, HP Dale, MM Ritter, JM Flower, RJ ( 2007 ) . Pharmacology. 6th erectile dysfunction. London: Churchill Livingstone Elsevier. 56.

Smith, A. ( 2002 ) . Isoprenaline. Available: hypertext transfer protocol: //en.wikipedia.org/wiki/Isoprenaline. Last accessed 04 August 2009.

Javid, FA McCurrie, JR ( 2008 ) . Clinical Physiology & A ; Pharmacology. Oxford: Wiley-Blackwell. 88.

Adams, N. ( 2008 ) . Isoprenaline. Available: hypertext transfer protocol: //www.medicinescomplete.com/mc/martindale/2009/search.htm? q= % 22isoprenaline % 22. Last accessed 05 August 2009.

Kline, H. ( 2002 ) . Bronchospasm. Available: hypertext transfer protocol: //en.wikipedia.org/wiki/Bronchospasm. Last accessed 05 August 2009.

Harris, L. ( 2008 ) . Isoprenaline. Available: hypertext transfer protocol: //pubchem.ncbi.nlm.nih.gov/summary/summary.cgi? cid=3779 & A ; loc=ec_rcs. Last accessed 01 August 2009.

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