Endogenous and exogenous

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In the mammalian system, cardiac muscles (cam) produce contractions to functionally support the sufficient injection of blood into the pulmonary and systemic circulation for fundamental basic survival needs. There are four essential properties that govern the functionality of the heart - contractility, excitability, rhythmicity, and conductivity. As the primary pacemaker, sinoatrial node consists of pacemaker autorhythmicity cells that spontaneous depolarize to discharges rhythmic electrical impulses. The action potentials are consequently spread throughout the conductive tissues of the atria to arrive at the secondary pacemaker, AV node where the electrical signals are transmitted to the ventricles via the elaborated conductive systems of the Bundle of His and Purkinje fibers. Upon receiving the signals, the myocardial contractile cells are depolarized via the excitation-contraction coupling mechanisms similar to that of the skeletal muscles for muscle contractions for pumping of blood. The main purpose of the study is to demonstrate how various endogenous and exogenous agents can alter these intrinsic properties and the resulting cardiac compensatory. In brief, bathing frog's heart in 37°C ringer solution increases the heart rate and bathing it in 4°C consequently decreases the heart rate. Adrenaline increases the heart rate and force of contraction whereas acetylcholine has an opposite effect of decreasing heart rate. Administration of calcium chloride, digitalis, caffeine, and nicotine also all increased the force of contraction, through the regulation of altering the intracellular calcium concentrations. In addition, we also observe some abnormalities, including extrasystole and conduction bloc by studying their respective electrocardiogram. Finally, we demonstrate the correlation between increased initial muscle fiber lengths with the increased in contractile force as verification of the Frank-Starling law. This study acknowledges the general cardiac muscle responses to normal physiological and external compromises that lay foundation for future work in treating cardiovascular diseases.

Note: No further modifications were made to materials and methods outlined in the laboratory manual (Perumalla, 2009). However, due to the restrained time limit and limited functional frog's heart, we were unable to perform 2.5,2.6, 2.7. In addition, we were unable to obtain a functional recording of the electrocardiogram.

The generation of force and movements to maintain internal homeostasis and defend from external hostiles is conducted by the assembly of bounded fibers known as muscles (Vander, 2001). In the mammalian system, based on structural and mechanistic differences, muscles are categorized into three major types: skeletal, smooth, and cardiac. We will focus on the cardiac muscles (cam) - the muscles that distinctively make up the walls of the heart. We will outline the four important properties associated with the cam, namely, contractility, excitability, rhythmicity and conductivity.

Like the skeletal muscles (skm), cam is striated, due to the sarcomeric arrangements of thick myosin and thin actin filaments essential for the contractile mechanical macherinies (Fox, 2004). However, cam is structurally and functionally definitive from skm. Individual myocardial cells of the cam are interconnected by intercalated discs and gap junctions, which allow action potentials to be rapidly spread throughout the heart so to behave as a single functional unit for syncytium purposes (Fox, 2004). The cardiac action potentials (ap) originate from the spontaneous depolarization of the sinoatrial (SA) node. Atrial depolarization is conducted via the gap junctions where then, the electrical impulses arrives at the atrioventricular (AV) node. The AV node manifests the continuous ap propagation to the conductive tissues, Bundle of His, its right and left branches and finally, arrives at the Purkinje fibers for ventricular depolarization so to eject blood into the pulmonary and circulatory circulations (Vanders, 2001).

Normally, SA node is the primary pacemaker of the heart and consists of specialized nodal pacemaker cells. These autorhythmic cells exhibit slow gradual depolarization coined pacemaker potential that are governed by the influx of Ca2+ from the slow Ca2+ channels (Fox, 2004). When the pacemaker potential reaches threshold level, fast Ca2+ channels are activated and more Ca2+ are diffuse into the autorhythmic cells for rapid generation of ap. However, these Ca2+ channels are quickly inactivated and simultaneously, the efflux of K+ through the opening of voltage-gated and Ca2+-gated K+ channels define the repolarization phase of ap to continue the spontaneous generation of depolarizing currents (Fox, 2004).

The rapid ap generated by the SA node is sufficient to stimulate and depolarize the myocardial contractile cells to allow the opening of fast voltage-gated Na+ channels (Vanders, 2001). The rapid inward diffusion of Na+ accounts for the upshoot phase of the ap, but the depolarizing phase is prolonged and sustained by the slow inward diffusion of Ca2+ through the slow Ca2+ channels (Fox, 2004). Eventually, the opening of delayed and inward rectifier K+ channels repolarize the membrane potential (MacKay, 2007). In addition, the depolarization of these myocardial cells by the autorhythmicity cells stimulates the opening of voltage-gated L-type Ca2+ channels in the sarcolemma (MacKay, 2007). The accumulation of Ca2+ in the cytosol from the extracellular fluid in turn act to activate Ca2+-release channels of the SR through a Ca2+-induced calcium release so troponin and tropomyosin can be displaced and cam contractions can be initiated.

In our present study, we demonstrated that various exogenous and endogenous agents can alter the functional properties of the cam. We hypothesized that as the temperature of ringer solution increased, the rhythmicity depicted by the heart rate also increased and vice versa. The administration of adrenaline increased the contractility and rhythmicity of the heart whereas the injection of acetylcholine produced the opposite antagonistic effect. The administration of calcium chloride, digitalis, caffeine and nicotine served to increase the contractility of the heart. Furthermore, we studied the excitability-contraction cycle couplings in the cam heart by manifestation of clinical abnormality, extrasystole through artificial electrical stimulations. Via the production of a Stannius ligature, conduction block was generated to investigate the other possible pacemaker origins in the heart, including the Bundle of His and Purkinje fiber. Finally, we verified the Frank-Starling law acknowledging that as the initial cam fiber length increased so too does the force of cam contraction.


The electrocardiogram (ECG) allow for the assessment of the electrical activity of the heart over time. It should be noted that ECG is not a direct recording of the ap generated in the heart, but rather, measures the movement of the ion changes, specifically, the current produced by the ap due to the opening of various channels (Vanders, 2001). The potential differences are detected by the surface electrodes to generate waves of signals as seen in Figure 1 (Vanders, 2001).

A normal ECG of one complete cardiac cycle is composed of three deflections: P-wave, QRS complex, and T-wave (Fox, 2004). The P-wave results from atrial depolarization due to the spontaneous firing of the SA node and the spreading of the electrical impulses throughout the left and right atrium before arriving at the AV node. The QRS complex is a representation of ventricular depolarization and the final T-wave deflection illustrates the ventricular repolarization. The PR interval reflects a delay where the ventricles can efficiently fill with blood and ST segment reveals the initiation of the ventricular repolarization (Fox 2004). The event of atrial repolarization is not visible on the ECG because it coincide with the activity of ventricular depolarization, and since, its electrical activity are comparable insignificant, the activity is masked by the QRS complex. We also noticed that large spike of QRS wave is demonstrates that ventricles have comparable large muscle mass than atria.

Conclusively, as ECG evaluates the electrical activity, it can be a useful clinical diagnostic tool for detecting associated abnormality with the conductivity and rhythmicity of electrical impulses of the heart. Altered ECG recordings are associated with health diseases, including ventricular premature beats and conduction block we will described later. However, the flaw of ECG is its inability to detect defect in mechanical activity of the heart.

In general, the mechanical events of one complete cardiac cycle are divided into two phases of systole and diastole, which represents respectively, ventricular contraction for blood injection and ventricular relaxation for blood filling (Fox, 2004). During ventricular diastole, SA node discharges and impulse are spreads throughout the atria. The atrial depolarization (P-wave) results in atrial contraction and the filling of ventricles with blood. The impulse travels through the conduction systems for ventricular depolarization (QRS complex), which signals the initiation of ventricular systole. When the ventricular pressure finally exceeds aortic pressure, blood is rapidly ejected from the ventricles and eventually, the end of ventricular systole and start of ventricular diastole can be depicted by ventricular repolarization (T-wave). Consequently, the cardiac cycle repeats.

Results and Discussions

Effect of temperature

The rhythmicity of the heart is dependent on the discharge rate of the pacemaker autorhythmicity cells, which normally, is predominately controlled those of the SA node. In turn, this discharge rate can be described in common terminology as the heart rate. The frequency of discharge of electrical impulses from the SA node can therefore determine the frequency and repetitiveness of the atrial and ventricular contractions (Perumalla, 2009). In our experiment, we operationally define the decrease in the duration of the each contraction as the increase in heart rate and vice versa. In this section, we bathed the frog's heart in 37°C and 4°C ringer solutions separately and observed the response.

We observed that increased temperature decreased the time of contractions of the atrium and ventricles (Figure 2). This meant that as the temperature increased so too does the heart rate. In contrast, decreased temperature resulted in the increase of the atrial and ventricular contraction durations (Figure 3). This denoted that as the temperature decreased, the heart rate also decreased. In this case, we used an operational definition to describe the general trend of heart rate. A more accurate method measuring the heart rate is through ECG where we can easily determine the number of discharge over time to determine the frequency of nodal firing, and therefore, calculate the heart rate.

The relationship between temperature and heart rate can be explained via the regulation of metabolic processes. The chemical reactions occurring within the body, including the heart, is extremely sensitive to changes in body temperature because the associated ion channels, make up of proteins, need a constant physiological temperature in order to function properly (Fox, 2004). As a generality, as the temperature doubles, the rate of chemical reactions also doubles. Therefore, the chemical reaction rates of pacemaker and contractile cells of the cam also increased (Yamagishi et al., 1967). There is an increase permeability of the cam membranes, therefore, resulting in an acceleration of the discharging rate. In addition, the essential ATPase related to the power-stroke of the contractile cells also hydrolyzes ATP at a faster rate. Therefore, we would expect that the decrease in temperature results in the ensuing slowing down of the metabolic processes and therefore, decreased heart rate (Fox, 2004). In addition, the sympathetic and parasympathetic vagal nerves are also responsive to the changes in temperature. Increasing the temperature results in the accumulation of adrenaline and decreasing temperature results in accumulation of acetylcholine (Vanders, 2001). These neurotransmitters govern the changes in the heart rate as we will describe in subsequent section.

Effect of acetylcholine and adrenaline

The heart is innervated with abundance sympathetic and parasympathetic nerve fibers (Vanders, 2001). The endogenous neurotransmitters, adrenaline and acetylcholine, respectively released upon stimulations of the sympathetic and parasympathetic nerve endings regulate the contractility and rhythmicity of the cam fibers. Contractility is an intrinsic characteristic of the cam that governs their ability to contract at any fiber length and is often measured on the basis of the contractile forces produced (Perumalla, 2009). We mimicked the body's stimulatory nervous system discharge by directly administering these chemicals into the frog's ventricles.

We observed that following injection of adrenaline, the measured force of both atrial and ventricular contractions increased (Figure 4). This increase is statistically significant (t-test, p & 0.05) and therefore, is indicative of an increase in the contractility of the cam fibers. In addition, from Figure 5, our graph noted that the atrial and ventricular contraction time increased. This interprets as the decreased in the rhythmicity of the contractions. However, this contradicts with the theoretical result that the rhythmicity of the contraction should increased. The plausible reason for this may be that the heart has yet to recover from the previous administration of acetylcholine.

In the myocardial cells, binding of adrenaline, a potent endogenous agonist activates b1-adrenergic receptors, activation of downstream protein molecules, adenylyl cyclase, cyclic-AMP (cAMP), protein kinase A (PKA), results in the phosophorylation of voltage-gated L-type Ca2+ channels of the sarcolemma for influx of Ca2+ from the extracellular fluid (ECF) for accumulation in the cytosol (DiFrancesco et al, 2001). This allows more troponin and tropomyosin to be displaced by Ca2+-binding and in turn, more functional contractile cells for augmentation of contractile forces. In addition, cAMP also alters the Na+ and Ca2+ channels of the pacemaker cells (Kalant et al., 2007). The influx of cations speeds up the rate of depolarizing, thereby, increasing the discharging rate of AP and consequently, increase in the heart rate. The shorter duration of contraction is attributed to the increase in Ca2+-ATPase of the SR by phosphorylated phospholamban that modulates the enhanced removal rate of Ca2+ from the cytosol (Vanders, 2001). Thus, this shortens of Ca2+-troponin binding time (Fox, 2004).

In contrast, following injection of acetylcholine, the measured force of atrial and ventricular contractions decreased to demonstrate a decreased activity in the contractile forces (Figure 6). Furthermore, the atrial and ventricular contraction time is statistically prolonged as noted in Figure 7 (t-test, p < 0.05). However, normally, acetylcholine has negligible effect on the contractility of the ventricles because there are minimal parasympathetic innervations at the ventricles. The experimental mishaps we observed may be attributed to the fact that while injection of the agents, we may have alter the initial tension in the ventricles and thus, the baseline heart rate is different and non-comparable.

In contrast with adrenaline, in the myocardial cells, acetylcholine binds and activates the muscarinic receptors to promote the opening of K+ channels and therefore, hyperpolarize the SA node (MacKay, 2007). In addition, the depolarization of autorhythmicity cells to threshold is slowed due to the decrease in Ca2+. The final consequence of the muscarinic receptors a more negative resting pacemaker potential is more negative and slower depolarization which delays the onset of AP firing, as the time to reach threshold is increased. (Vanders, 2001) Therefore, the rate of rhythmicity is decreased at the SA node and the heart rate decreases. The conduction velocity is governed by the resting membrane potential and as the resting potential lowers, like in the case with acetylcholine, conduction of electrical impulses to the AV node decreases (Kalant et al., 2007). Therefore, the vagal nerve of the parasympathetic systems can regulates the conduction of excitation impulses from the atria to ventricle through the modulation of the conduction velocity. In addition, the acetylcholine can decrease the strength of atrial muscles. However, we alluded earlier, acetylcholine has negligible effect on the contractility of the ventricles because there are minimal parasympathetic innervations at the ventricles (Kalant et al., 2007).

Effect of calcium chloride and digitalis

There are several predominant Ca2+ channels intimidately involved with the modulation of Ca2+ movements in the heart to manifest changes to its electrical and mechanical properties. Thus, the tight regulation of the Ca2+ concentrations is utterly essential. Usually, the extracellular Ca2+ concentration is about 4.5 - 5 mEq/L and the local intracellular increase of Ca2+ is dependent on this ECF supply (Perumalla, 2009). We investigate the importance of Ca2+ channels in strengthening the contractility of the cam through injection the frog's heart with calcium chloride and digitalis.

Figure 8 revealed that after administration of calcium chloride as means to increase the Ca2+ ECF concentration, the force of atrial and ventricular contractions decreased. However, theoretically, this should not be the case and we can allude this as flaccid heart. As previously noted, the contraction force of the cam is largely dependent on the cytosolic Ca2+ . Upon stimulation by the ap propagated from the pacemaker cells, the myocardial cells facilitate the opening of the voltage-gated L-type Ca2+ channels on its sarcolemma (Wang et al., 2001). The influx of Ca2+ from the ECF results in a small increase in cytosolic Ca2+ level. However, the Ca2+ level is further potentiated through stimulation of release of stored Ca2+ of the SR by the translocated Ca2+ in a Ca2+-induced Ca2+ release fashion (Wang et al., 2001). The ryanodine receptor channels create a so-called local Ca2+ spark for crossbridges to form. It should be noted that although the majority of Ca2+ resulting in the contractions of the cam originated from the SR, the whole process rely heavily on the movements of ECF Ca2+, which acts as stimulants (Bers, 2002). Without them, the cardiac contractions would be weak and flaccid and in the presence of increasing concentrations, they augment the strength of cardiac contractions as observed.

The administration of digitalis, a cardiac glycoside into the frog's ventricles resulted in an decreased in the force of contractions as seen in Figure 9. However, once again, normally, this should not be the case. The main consequence of digitalis is the inhibition the Na+/K+ ATPase membrane pump (Hauptman et al., 1999). Usually, Na+/K+ ATPase serves to pump Na+ outward and K+ inward against their concentration gradients using energy produced from the hydrolysis of ATP. By inhibiting this pump, digitalis lead to the increase in the intracellular Na+ because of its decreased efflux. The increased in Na+ in turn stimulates Ca2+/Na+ exchanger to promote the exchange of Na+ with Ca2+ to leading to the final result of an increase the intracellular Ca2+ level (Kalant et al., 2007). Once again, the activation of the contractile proteins increases in the strength of contraction, which can be useful in treating patients with failing hearts. Often, heart failure arises from the insufficient pumping of blood, and the increase in force of contraction monitors the increase in cardiac output to compensate for the lost of probable blood volume. Digitalis is also an effective treatment for atrial fibrillation and atrial flutter. Both are types of cardiac arrhythmias arising from disorder of the conduction systems of the atria that result in tachycardia (Guyton et al., 2006). In this case, the therapeutic effect of digitalis is to prolong the refractory period associated with each ap, therefore allowing sufficient time for ventricles to fill up with blood and eject them into the systemic and pulmonary circulations for normal metabolic functioning (Kalant et al., 2007).

Effect of caffeine and nicotine

Caffeine, a xanthine derivative and nicotine, a naturally occurring alkaloid are among the most widespread drugs of the era as they are active ingredients in coffee beans and tobaccos, respectively. Their prevalence has elicited significant scientific interests. Likewise, we studied their effects on the cam in our present study.

From Figure 10, administration of caffeine resulted in an increased force of cam contractions. We revealed that as the addition of caffeine interferes with the excitation-contraction couplings of the cam by enhancing cam contractions due to the response of increased stimulatory accumulation, sensitization, and liberation of Ca2+ (Nayler, 1966). First of all, caffeine explicitly inhibits the uptake of the Ca2+ by the Ca2+-ATPase of the SR and stimulates the release of Ca2+ through the caffeine-induced Ca2+-release channels from the SR (Nayler, 1966) . This in turn, results in the buildup of Ca2+ levels in the cytosol. As we know, the contractile macherinies of the myofilaments are largely dependent on the concentrations of cytoplasmic Ca2+ to displace troponin and tropomyosin for initiation of muscle contractions. Caffeine therefore, plays a pivotal role in the cam sensitization. Thus, the increase in cytosolic Ca2+ would augment the contractility of the cam.

In Figure 11, we detected that the injection of nicotine resulted in the decrease in the contractility of strengths. Nicotine, as its name implied, binds to the nicotine cholinergic receptors, specifically on the ligand-gated cation channels (Wang et al., 2000). Researchers have revealed that the cardiac changes manifested by nicotine are due to the release of neurotransmitters, in particular, the release of catecholamine (Wang et al., 2000). This class of neurotransmitters includes adrenaline, which we described its effects in previous section resulting in the increase in the contractile force of the cam. In addition, part of nicotine's action on the cam also resembles that of caffeine. The administration of nicotine also stimulates Ca2+ the release of from the nicotine-induced Ca2+ channels of the SR and facilitate the enhancements of their release (Nayler, 1966). Also, nicotine can increase the sensitivity of the myofilaments of the Ca2+ to modulate the increase in contractile force (Nayler, 1966). Recent evidences have revealed that nicotine can also directly affect the cardiac functioning by directly binding and inhibiting K+ channels (Wang et al., 2000). The K+ currents of the cardiac cells are critical important for their regulation of the membrane repolarization. By inhibiting the flow of K+, there is a lengthening of the action potential (MacKay, 2007).

Excitability cycle

Excitability is an intrinsic ability of the autorhythmic cells to depolarize to reach threshold from its pacemaker potential in order to produce an ap (Perumalla, 2009). In addition, excitability can be attributes to the ability of the myocardial fibers to receive stimuli and initiate a response (Perumalla, 2009).

The coupling of the excitation-contraction processes of the cam share some similarities with that of the skeletal muscles. Likewise, there are definitive differences among the two to adapt to their functionalities. When the myocardial cells receive the electrical impulses from the heart's pacemaker, they produce their own ap through regulation of the channels as outlined in the introduction. Unlike the skm, the action potential of the cam, the depolarization phase is sustained by slow inward diffusion of Ca2+ which implicates to action potential that is sufficiently longer for reasons to be explained later (Fox, 2004). In addition, upon depolarization of the myocardial cells, its contractile machineries are function by first opening of the voltage-gated Ca2+ channels of the sarcolemma to manifests the influx of Ca2+ from the ECF (Bers, 2002). We noted earlier that the accumulation of Ca2+ from the ECF mainly serve as stimulus for the opening of Ca2+ release channels in the SR. It is the Ca2+ from the SR that accounts for the depolarization of the myocardial cells and bind to troponin and downstream contractions. During repolarization, concentrations of cytosolic Ca2+ diminishes by the active transport of Ca2+ across the sarcolemma through Na- Ca2+ exchanger and also across the cisternae of the SR by Ca2+-ATPase (Bers, 2002).

Unlike the skm, the cam cannot display the summation and tetanus phenomena (Fox, 2004). The ap of the cam, which due to the sustained depolarization phase, lasts as long as the contraction time. Therefore, the refractory period of the cam, including both the absolute and relative, ensure that the cam can only be stimulated after relaxation from previous contraction. This is one of the definitive differences between skeletal and cardiac muscles and is important for ensuring that each cardiac cycle pumps enough blood to meet the body's metabolic demands.

We were unable to generate a plausible data from stimulating the frog's ventricles via electrical shocks as our frog's heart probably flaccid from previous experimental manipulations. However, we hypothesized that when we artificially apply electrical stimulations to the ventricles, there will be production of an extra depolarization asynchronous from the regular discharges of the normal SA nodal pacemaker cells. This, in turn, makes the heart susceptible in generation of ventricular premature beats (PVB), and its respective consequence, ventricular premature contractions, PVC (Guyton, 2006). PVC, also known as extrasystole, results in production of an extra contraction of the heart - ones earlier than the expected contraction (Guyton, 2006). Often, this defect results from the ectopic pacemakers of the heart, elsewhere than the SA node, as we will see in subsequence experimental sections. Premature contractions can occur in both the atrium and ventricles and results before regular contraction (Guyton, 2006). On the ECG, the interval of the previous beat to the premature beat and the premature beat to the next normal interbeat interval is less than two regular cardiac cycles. This is shown in Figure 12. Patients with PVC may experience skipped beats where they feel a pause in the heartbeat and fluttering of the chest as the heart is trying to regain and reset its rhythmicity (Guyton, 2006).

Stannius ligature

Stannius ligature was named after Hermann Friedrich Stannius, a German physiologist who performed early experiments on frogs' hearts to establish several essential modern physiological properties of the heart (Fox, 2004). One of their major contributions is revealing the conductivity of the cam and acknowledging the ability of the cam to conduct electrical impulses efficiently, even at compensatory situations (Vanders, 2001). As its name implied, conduction block is a consequence of an obstruction in any part of the electrical conduction system of the heart. As the result of this blockage, the ap is unable to propagate and no signals are transmitted downstream for the proper functioning of the organ. In our study, we tied a ligature between the atrium and ventricles to demonstrate a complete AV conduction block and observe the effect of such abnormality.

Clinically, the three major AV conduction blocks can be characterized by their distinct ECG profiles to explain changes in their atrial and ventricular contractions intervals. The 1st degree incomplete AV block is the delay in the conduction of electrical impulses from the atria to the ventricles (Guyton, 2006). This portrays into a delay in the PR intervals where ventricular contractions are lingered as compared to normal. The 2nd degree incomplete AV block depicts the failure of some of the action potentials generated by the SA node to reach the rest of the heart. Thus, there is presence of some P-waves without the associated QRS-complex on the ECG, as some of the impulses for atrial depolarization did not get conducted for ventricular depolarization (Guyton, 2006). Sometimes, in 2nd degree AV block, an individual experiences a dropped heart where the ventricle only beat once whereas the atria are beating twice. The ventricles skipped a beat. In this section, Stannius ligature represents the 3rd degree complete block, which resulted in no impulses transmitted from the atria to ventricles (Guyton, 2006). None of the P-waves are coupled with QRS complex and T waves because the atrium and ventricles are beating at different rates (Figure 13). Hence, atrial and ventricular contractions are not in sync anymore and results in possible generation of cardiac arrhythmias.

As our frog's heart failed to recover fully from previous experimental sections, we were unable to observe the response of such conduction block. However, we speculate, in the presence of the ligature, atrium would continue to beat at its normal rate because there was no blockage in the atria conduction fibers and the cam could still able to receive impulses arising from the SA node. In contrast, the ventricles would stop beating initially as they will not be receiving any electrical stimulation. However, eventually, the ventricles should start beating again because the Bundle of His and Purkinje fibers also have pacemaker cells, and thus, are known as ectopic pacemakers (Fox, 2004). Nevertheless, the discharge rates are not as fast as the ones produced by the SA node. We can acknowledge the fact that there are more than one pacemaker functioning sites in the heart to ensure the heart can continue to beat if there is any functional abnormalities with the primary SA node and secondary AV node (Vanders, 2001). In a healthy individual, the SA node is the primary pacemaker because the discharge rate is higher than the rest of the pacemakers of the heart.

By increasing the voltage applied to the cam, we would expect that force of contraction would increase up to threshold with a graded increase in contractile response. Eventually, the voltage threshold is reached where any increase in the voltage, would not be able to further stimulate the force of contraction beyond to maximize efficiency and minimize injuries. Voltage threshold can be interpreted as voltage sufficient to open all the voltage-gated Ca2+ channels of the sarcolemma and stimulate the Ca2+ induced ryanodine channels of the SR to displacements all the binding sites of the contractile macherinies.

Length-force relationship

As our frog's ventricles failed to recover fully from previous experimental sections, we were unable to monitor observe the response of such conduction block. However, the expected graphical representation of the relationship between initial tension and contractile strength is seen in Figure 14. The initial fiber length is proportional depicted by the initial tension. At rest, the sarcomeres of cam are not at its optimal length, unlike those of the skeletal muscles (Fox, 2004). Therefore, the resulting contractile force is only at its minimal as there are minimal numbers of overlaps between the myofilaments. However, the stretching of the cam fiber have shown to stimulate the sensitivity of troponin and titin to Ca2+ through the phosophorylation of protein kinase A and increase the number of overlaps to promote the increase in contraction strength as shown in Figure 13 (Solaro, 2007).

This length-force relationship can be used to derive the Frank-Starling law of the heart, notably named after the work by Otta Frank and Ernest Starling. This law explicitly states that an increase in the end diastolic volume (EDV) results in subsequent increase in the stroke volume (Vanders, 2001). This relationship states that when the ventricles are filled with more blood during diastole, the resulting systolic contraction will eject higher blood volume. The cardiac output is the volume of blood pumped out of the ventricles per minute and is largely determined by the product of stroke volume and cardiac rate (Fox, 2004). Stroke volume is the volume of blood pumped out of the ventricles per heart beat and cardiac rate defines the number of heart beats per minute (Fox 2004).

EDV is the volume of blood present in the ventricles immediately before they are contract and inject blood into the circulation (Fox, 2004). This is generalized to be the preload that the ventricles have to overcome in order to empty the blood present in the ventricles. In the cam, in the absence of blood, the empty ventricles results in the myocardial cells to contract weakly. There are merely minimal overlaps between the myofilaments, and therefore, weak contractions are observed (Fuchs et al., 2001). As the ventricles begin filling up with blood during atrial depolarization, the myocardial cells of the ventricles also begin to stretch. The stretching, in turn, increases the number of overlapping binding sites between the actin and myosin (Fuchs et al., 2001). Since the number of overlaps is proportional to the contraction, the degree of stretching also correlates to the force of contraction. In our experiment, we supposedly stretch the frog's ventricles by raising the force transducer that mimics the stretching of the myocardial cells by the increase in blood volume in the ventricles. We can depict the relationship of end-diastolic volume and stroke volume in Figure 15.

We can also expand our current understanding of the Frank-Starling law with the clinical aftermath of the premature ventricular contractions we discussed earlier. One of the consequences of the premature ventricular contractions is the empting of insufficient blood for metabolic demands arising from the contraction of the premature beat (Guyton, 2006). This occurs from the insufficient time between the atrial depolarization and ventricular depolarization. However, the body compensate for this loss by having a longer filling time for the ventricles in the next beat because the next ventricular contraction will arrive at the regular time and the interval is extended (Vanders, 2001). The increase in blood results in the increased in the EDV. By the Frank-Starling law then, the subsequent ventricular contraction will be more forceful to result in a larger ejection volume of higher volume of blood (Vanders, 2001).


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