1. FUNCTION OF THE HEART AS A PUMP By DR QAZI IMTIAZ RASOOL

2. 1. Illustrate and discuss the action potential of contractile cardiac fibers. 2. Describe the excitability changes during cardiac action potential. 3. Describe excitation-contraction coupling of the cardiac muscle. 4. Describe the intrinsic regulation of the cardiac pumping. 5. Describe the effect of various extrinsic factors on cardiac pumping (nervous, physical and chemical).

3. Cardiovascular system

4. CARDIAC MUSCLE Contractile cells 99% Auto rhythmic cells 1% Latticework, Intercalated discs SYNCYTIUM 1.Atrial 2.Ventricle AV bundle

5. Sk. M.

6. heart cell Cardiac Channels 1.Leak K + channel 2.Voltage-gated Channels a) Na + ( I Na ) b) Ca 2+ (L-type; T-type) I Ca,L and I Ca,T L channel or DHPR dihydropyridine) c) voltage-gated K + delayed rectifier K + channel (rapid,slow,transient outward) I KR, I KS, I TO ) d)Both Na + /k/ca ("funny“)I F e)Transporter Na + /Ca 2+ exchanger I NCX

7. Phases of the Fast Response Action Potential 1. Phase 0 = Depolarization 2. Phase 1 = Partial Rapid Repolarization 3. Phase 2 = Plateau 4. Phase 3 = Repolarization 5. Phase 4 = Resting Membrane Potential

8. “Fast” Na+ Current 1.At threshold, voltage gated Na ++ channels open, upstroke depend entirely on it. 2. Na ++ ions rush in. RMP changes from -85mV to+ 20mV.

9. Na+ current ends Outward K+ current It is small but fast repolarization. 1.Inactivation of Na+ channels ends 2.It is caused by Cl - influx 3.Transient outward K+ current channel K TO

10. 1. Opening of the slow Ca 2+ - Na + channels leading to slow Ca 2+ and Na + influx. (L- type calcium channels) 2. Delayed closure of the fast Na + channels. 3. permeability of K + channels at the onset of action potential leading to K + efflux and consequently delayed repolarization. Ventricular contraction persists throughout the action potential, so the long plateau produces a long action potential to ensure forceful contraction of substantial duration

12. Calcium-Induced Calcium Release RYR DPHR PLB

13. Phase 3 = Outward K+ Current Na+ Channel Recovery Na + Channel Configuration Change Outward K+ current--------- repolarization Na+ channel recovery begins during Relative Refractory Period by closing and become refractory NOTE;_ Depolarization triggers opening of voltage-gated potassium ion channels..

14. Absolute refractory period (ARP) 1. During this period, the excitability of the cardiac muscle is completely lost. 2. No other stimulus, whatever its strength can excite the cardiac muscle. 3. It coincides (corresponds) with: the phase of rapid depolarization and the repolarization till the end of plateau (= during systole of cardiac muscle). NOTE;- Due to this long ARP, tetanus cannot be produced in cardiac muscle. It is fatal because the heart as a pump must contract and relax to fill with blood. 1. During this period, the excitability of the cardiac muscle is completely lost. 2. No other stimulus, whatever its strength can excite the cardiac muscle. 3. It coincides (corresponds) with: the phase of rapid depolarization and the repolarization till the end of plateau (= during systole of cardiac muscle). NOTE;- Due to this long ARP, tetanus cannot be produced in cardiac muscle. It is fatal because the heart as a pump must contract and relax to fill with blood.

15. Ca++ Out Na+ In Cell ECF Excess Ca++ ions from CICR Excess Ca ++ i ons from actin- myosin dissociation

16.  RMP 1.When membrane potential comes to the resting level. 2. Na-K pump works to derive excess Na + out and excess K + in. 3. RMP remains stable till it is excited again 1.Na+,K+-ATPase 2.Na+-Ca++ Exchanger 3.ATP-driven Ca++ Pump

18. Excitation-Contraction Coupling Heart requires extracellular Ca ++ to contract. 1. i different --skeletal muscle, which contract in absence of Ca ++. 2.Long AP in cardiac muscle -- slow ---L-type Ca ++ channel --- sarcolemma. 3. Ca ++ coming into the cardiac muscle-- small and serves as a trigger

20. Local Currents depolarize adjacent channels causing depolarization and opening of adjacent Na channels

21. Intrinsic Regulation of Heart Pumping—The Frank-Starling Mechan ism “Within physiologic limits greater the heart muscle is stretched during filling, the greater is the force of contraction and the greater the quantity of blood pumped into the aorta.” Mechanism? 1.extra amount flows into the ventricles, the cardiac muscle itself is stretched to greater length. - in turn causes the muscle to contract with increased force because the actin and myosin filaments are optimal degree of overlap. 2. IF volume is increased. Stretch of the right atrial wall directly increases the heart rate by 10 to 20 percent; although its contribution is much less than that of the Frank-Starling mechanism

23. Increases in atrial pressure causes an increase volume and strength of contraction which causes an increase in cardiac output.

24. 1. Slow heartbeat and exercise increase venous return to the heart, increasing SV 2. Blood loss and extremely rapid heartbeat decrease SV

25. Extrinsic Factors ( Hormones - thyroxine)+ (drugs) Ca 2 and some Intra- and extracellular ion concentrations

26. 1. Contractility – cardiac cell contractile force due to factors other than EDV 2. Preload – amount ventricles are stretched by contained blood – EDV 3. Venous return - skeletal, respiratory pumping 4. Afterload – back pressure exerted by blood in the large arteries leaving the heart Stroke volume Strength of cardiac contraction End-diastolic volume Venous return

27. Effect of ANS+DRUGS

28. Effect of K + AND Ca ++ 1. K + AND Ca ++ - Excess causes effects opposite to those of K +, causing spastic contraction. -Deficiency causes cardiac flaccidity, similar to the effect of high potassium. Fortunately, calcium ion levels in the blood normally are regulated within a very narrow range. NOTE;- cardiac effects of abnormal calcium concentrations are seldom of clinical concern. 2. Temperature - Increased(fever)- increased heart rate, -Decreased – decreased ( hypothermia 60° to 70°F). Mechanism:- 1. heat ↑ permeability of the cardiac muscle membrane to ions that control heart rate 2.Contractile strength temporarily by a moderate increase, but prolonged elevation exhausts the metabolic systems of the heart and eventually causes weakness.

29. 3. Hypernatremia– - blocks heart contraction by inhibiting ionic calcium transport ????????