CARDIOVASCULAR PATHOPHYSIOLOGY AND PREOP EVALUATION IN CARDIAC PATIENT

DR.MOHD YUNUS KHILJI PG STUDENT DEPARTMENT OF ANAESTHESIA S.P.M.C. BIKANER

Physiology of intact heart

Surface Marking Of The Heart

Upper border : Straight line joining i. lower border of 2nd left costal cartilage about from sternal margin to ii. A point at the upper border of 3rd right costal cartilage from sternal margin Lower border : marked by a straight line joining i. a point at the lower border of 6th right costal cartilage 2 cm from sternal margin to ii. to a point at the apex of heart in the 5th intercostal space 3 from midsternal line

RCA: Arise from ant. Aortic sinus smaller than LCA.

LCA: Arise at an acute angle from left posterior aortic sinus.

Branches: Marginal Posterior interventricular Nodal in 60% right atrial infundibular Area of distribution: 1. Rt. atrium, 2. greater part of rt. ventricle except ant. i.v.groove, 3. smaller part of L.V. adjoining i.v. groove, 4. post. Part of i.v. septum, 5. whole of conduction system of the heart except a part of left branch of A.V. bundle. The S.A. node is supplied by L.C.A. in abt. 40% of cases

Branches: 1. Ant. Interventricular 2. Diaphragmatic surface of L.V. 3. Left atrial 4. Pulmonary Area of Distribution: 1. Left atrium 2. Greater part of left ventricle except area adjoining post i.v. groove 3. Small part of rt. Ventricle adjoining A.V. groove 4. Ant. Part of i.v. septum 5. Part of left branch of AV bundle

REGULATION OF CORONARY BLOOD FLOW

Resting of coronary blood flow is 225ml per min, abt 5% of total C.O. Peak coronary blood flow occurs during early diastole after LV isovolumic relaxation as extravascular compression on coronary microvasculation is minimal Coronary perfusion pressure is difference of diastolic arterial pressure & LV end diastolic pressure Flow through vessel is determined by Poiseuilles equation: Q=Pr4/8L Vessel radius is the most imp determinant of blood flow

Coronary circulation is autoregulated & coronary flow remains nearly constant b/w 50-120mmHg Rapid accurate control of transmural myocardial flow is primarily established by local metabolism. Several mediators like adenosine, O2, CO2, NO, endothelin,& PGs have been implicated.

Myocardium O2 consumption is the most imp factor affecting coronary blood flow. The myocardium extracts 70-75% of coronary arterial O2 content under resting condition, so increase in myocardial O2 consumption must be accompanied by increse in coronary blood flow because: VO2= Q x DO2 x 10

myoc.O2 consumption= coronary blood flow x myoc O2 extractn x10

CARDIAC CYCLE

The cardiac cycle is sequence of electrical and mechanical events during the course of a single heartbeat. Electrical events of the pacemaker and the specialized conduction system are represented by the ECG at the body system. The action potential initiated at SA node is propagated

NORMAL PRESSURE IN HEART CHAMBERS

Right Atrium Right Ventricle

0-8 mm Hg 0-8 mm Hg diastolic 15-30 mm Hg systolic Left Atrium = 4-12 mm Hg diastolic Left Ventricle = 100-140 mm Hg systolic Aorta = 60-90 mm Hg diastolic 100-140 mm Hg systolic Pulmonary capillary wedge pressure 4-12 mm Hg (represents LA)

= =

Respiratory swing

Arterial pressure waveform is shown in next Figure with airway pressure during intermittent positive pressure ventilation. Blood pressure trace shows changes in phase with respiration, called the respiratory swing . As the intrathoraic pressure is only increased briefly during inspiration, overall effect is a decrease in arterial systolic and diastolic pressure which lags behind the increase in intrathroacic pressure. Respiratory swing is pronounced in hypovolaemia, and is a valuable tool in the estimation of fluid deficit. Notice also that the dicrotic notch is low and the arterial pressure trace is narrow in hypovolaemia.

VENTRICULAR STRUCTURE

The specific architecture of the cardiac muscle provides the basis for the heart to function as a pump. The ellipsoid shape of the left ventricle is a result of the laminar layering of the spiraling bundles of cardiac muscle The orientation of the muscle bundle is longitudinal in subepicardial myocardium circumferential in middle segment again longitudinal in the subendocardial myocardium.

LV is ellipsoid shaped, so there are regional differences in wall thickness result in corresponding variation in the cross-sectional radius of LV chamber. LV ejects blood in corkscrew type motion beginning from the base & ending at the apex. The release of twisted LV provide a suction mechanism for LV filling during diastole. In contrast the RV has considerably less wall thickness as it needs to pump against much lower pressure circuit in the pulmonary circulation. RV is crescent shaped .The inflow & outflow contraction is not simultaneous.

SYSTOLIC FUNCTION

Systolic function is dependent on the loading condition and contractility. Preload and afterload are two interdependent factors extrinsic to the heart that govern the cardiac performance. PRELOAD: is defined as the ventricular load at the end of diastole, before contraction has started. First described by Starling, a linear relationship exists b/w sarcomere length and myocardial force. PCWP & CVP are used to estimate preload.

AFTERLOAD: Systolic overload on the LV after the contraction has begun.Aortic compliance is an additional determinant of afterload. Changes in aortic wall compliance can alter afterload e.g. Aortic stenosis and chronic HT increase afterload. In clinical practice, measurement of systolic blood pressure is adequate to approximate afterload (provided that AS is not present)

Preload & afterload are considered as wall stress that is present at the end of diastole & during LV ejection respectively. LAW OF LAPLACE: it states that wall stress() is the product of pressure (P) & radius (R) divided by wall thickness (h): = P x R/2h The ellipsoid shape of LV allows for the least amount of wall stress. As the ventricle changes its shape from ellipsoid to spherical, wall stress is increased. (decrease in the ratio of the long axis to the short axis signifies transition from ellipsoid to spherical.

Thickness of the LV is important modifier of wall stress. E.g. in AS afterload is increased. The ventricle increases its wall thickness (LV hypertrophy). By applying Laplaces law the increase in wall thickness will decrease the wall stress.

In a failing heart, the radius of LV increases, thus increasing the wall stress.

FRANK STARLING RELATIONSHIP: Otto Frank first noted that the change in tension was directly related to its length. E.H.Starling observed that the mechanical energy set free on passage from the resting to contracted state is a function of the length of the muscle fibre. There is an optimal sarcomere length at which actin myosin crossbridging is maximal which is equivalent to increase in muscle performance . A common clinical application of Starlings law is the relationship of Left ventricular end-diastolic volume (LVEDV) and stroke volume i.e. Ejection fraction. In normal patients ejection fraction is 67%.

Ejection fraction is relatively insensitive index of contractility because: it decreases linearly with increase in afterload, & varies inversely with Heart rate. It may also be misleading in the presence of : regional myocardial ischemia, mitral and aortic valve pathology & LV hypertrophy or dilation. Another index of contractility is maximum rate of increase of LV pressure.

CARDIAC WORK

The work of heart is divided into external and internal work. External work is expended to eject blood under pressure, whereas internal work is expended within the ventricle to change the shape of the heart and prepare the heart for ejection. Wall stress is directly proportional to the internal work of the heart. External work (Stroke work) =SV x P or (LVEDV LVESV) x P

The external and internal work both consume O2. During Cardiopulmonary bypass ischemia can occur because poor drainage of the LV creates tension on the LV wall and increase internal work. In heart failure, ventricular dilation reduces cardiac efficiency because it increases wall stress( in turn O2 consumption).

HEART RATE AND FORCE FREQUENCY RELATION

Increae in frequency of stimulation results in increase in force of contraction. This relationship is termed as the treppe (Treppe in german means staircase) phenomenon or the force frequency relationship. Between 150 and 180 stimuli per minute, maximal contractile force is reached in an isolated heart muscle at a fixed length. When the stimulation becomes extemely rapid, force of contraction decreases. In clinical context, pacing induced positive intotropic effects may be effective only upto certain heart rate.

DIASTOLIC FUNCTION
Diastole/ventricular relaxation occurs in 4 different phases: 1. Isovolumic relaxation 2.The rapid filling phase 3. Slow filling phase or diastasis 4. Final filling or atrial systole The isovolumic relaxation phase is energy dependent. This phase doesnt contribute to ventricular filling.

During the auxotonic relaxation phases (phase 2 through 4). Most of the filling occurs in phase 2 whereas 3rd phase adds only 5% & the final phase provides 15% of ventricular volume from atrial

CARDIAC OUTPUT

Amount of blood pumped by the heart per unit time (Q). It is determined by 4 factors: 2 factors intrinsic to the heart: Heart rate & myocardial contractility 2 factors extrinsic to the heart: Preload & afterload Heart rate is defined as beats per minute. Increase in heart rate increases cardiac output as long as ventricular filling is adequate during diastole. Contractility is defined as the intrinsic level of contractile performance that is independent of loading conditions.

Cardiac output can be measured using Fick principle. It is based on concept of conservation of mass. Q=q2/(Cpvo2-CpaO2) The indicator dilution method is another method of determining C.O. The indicator dilution & dye dilution method.

Cellular cardiac physiology

CELLULAR CARDIAC PHYSIOLOGY

CELLULAR ANATOMY : Three major components Cardiac muscle tissue (contracting cardiomyocytes) Conduction tissue (conducting cells) Extracellular connective tissue (collagen , elastins, proteoglycans, matrix metalloproteins)

CARDIOMYOCYTE STRUCTURE AND FUNCTION

Size 20m-150m THE SARCOLEMMA: the outer plasma membrane TRANSVERSE OR T TUBULE : an extensive tubular network is formed by invagination of sarcolemma.

T tubules are in close proximity of intramembrane system and Sarcoplasmic reticulum. SARCOPLASMIC RETICULUM: Plays imp role in calcium metabolism . Two types exist:

The longitudinal SR: involved in the uptake of calcium for initiation of relaxation The junctional SR: contain large calcium release channels (Ryanodine receptors )that release SR calcium stores in response to depolarization stimulated calcium influx through the sarcolemmal calcium channels .

MITOCHONDRIA immediately beneath sarcolemma. contain enzymes that promote generation of ATP acting as powerhouse of the cell. They also function to accumulate Ca2+

Cardiac muscle cells contain three different types of cell junctions: GAP JUNCTIONS: responsible for electrical coupling and transfer of small molecules. They are constructed from connexins (connexin 43 mainly)

SPOT DESMOSOMES: Anchor the intermediate filament cytoskeleton of the cell SHEET DESMOSOMES: form adhesion sites that anchor the contractile protein.

THE CONDUCTING MYOCYTES OR PURKINJE CELLS have low content of myofibrils and prominent nucleus and contain an abundance of gap junctions.

Cardiomyocytes can be functionally seperated into 1. The excitation system 2. The excitation-contraction-coupling 3. The Contractile system. The Excitation System: The cellular action potential originating in the specialised conduction tissue is propagated to individual cells where it initiates intracellular event that leads to contraction of the cell through the sarcolemmal excitation system.

ACTION POTENTIAL
The action potential in the heart are of 2 types:

Fast response action potential: His Purkinje Fibres, Atrial/Ventricular cardiomyocytes. Slow response action potential: Pacemaker cells in AV Node & SA Node.

FAST RESPONSE ACTION POTENTIAL

PHASE NAME EVENT CELLULAR ION MOVT 0 UPSTROKE ACTIVATION OF FAST Na+ CHANNELS
INACTIVATION OF Na+ CHANNEL & TRANSIENT INCREASE IN K+ PERMEABILITY

Na+ IN & DECREASED PERMEABILITY TO K+ K+ MOVES OUT

EARLY RAPID DEPOLARIZATION PLATEAU

ACTIVATION OF SLOW Ca2+ CHANNELS

Ca2+ IN

FINAL REPOLARIZATION

INACTIVATION OF Ca2+ CHANNELS & K+ OUT INCREASED PERMEABILITY TO K+

RESTING POTENTIAL NORMAL PERMEABILITY RESTORED DIASTOLIC REPOLARIZATION

K+ OUT Na+ IN

INTRINSIC SLOW LEAKAGE OF Ca2+ INTO CELLS THAT SPONTANEOUSLY CA2+ IN DEPOLARIZE

Phases of Action potential in ventricular myocytes

SLOW RESPONSE ACTION POTENTIAL

When compared with fast response action potential phase 0 is less steep , phase 1 is absent and phase 2 is indistinct from phase 3 in slow response action potential. During phase 4 the pacemaker cells have ability of spontaneous diastolic depolarization and generate the automatic cardiac rhythm.

EXCITATION CONTRACTION COUPLING

AP DURING PHASE 2 DEPOLARIZESARCOLEMMA LEADING TO INFLUX OF CALCIUM THROUGH VOLTAGE GATED L-TYPE CALCIUM CHANNEL VIA DIHYDROPYRIDINE RECEPTOR

SMALL RISE IN Ca2+ TRIGGERS AN EVEN GREATER RELEASE OF Ca2+ ACROSS RYANODINE RECEPTORS(NONVOLTAGE-DEPENDENT CHANNEL)IN SR (CALCIUM DEPENDENT CALCIUM RELEASE)

DURING SYSTOLE Ca2+ BINDS TO THE TROPONIN C SUBUNIT CAUSING CONFORMATIONAL CHANGES IN TROPONIN TROPOMYSIN COMPLEX

THIS ALLOWS ACTIN MYOSIN FILAMENT TO INTERACT WHICH PROPEL AGAINST EACH OTHER SHORTENING THE SARCOMERE

The release of calcium is transient and removed by: Active reuptake by SR calcium pump ATPase. (SERCA) Extrusion of calcium from cytosol by Na+-Ca2+ exchanger Binding of calcium to proteins.

Sarcoplasmic reticulum ATPase (SERCA) is inhibited by PHOSPHOLAMBAN, a protein active in its dephosphorylated form. Phosphorylation by kinases inactivates phospholamban nad releases its inhibitory effect on SERCA. Calsequestrin and calreticulin are two storage proteins in the SR

CONTRACTILE SYSTEM

The basic working unit of contraction is the sarcomere. A sarcomere is defined as the distance between two Z lines ( Z is an abbrev for the german Zuckung or contraction) which joins the sarcomere in series. The ccontractile apparatus is made of two contractile proteins :actin & myosin, and a non contractile protein :titin(tethers the myosin thick filament to the Z line).

SARCOMERE - the basic contraction unit

The thin Actin filament contains two helical chains. Tropomyosin , a double stranded -helical regulatory protein, winds around the actin array and forms the backbone for the actin thin filament. Troponin, regulatory heterotrimer is found at regular intervals along tropomyosin.

The heterotrimer troponins are made up ofTroponin C (TnC), the Ca2+ receptor Troponin I (TnI), an inhibitor of actin-myosin interaction Troponin T (TnT), which links the troponin complex to tropomyosin.

Tropomodulin is another regulatory protein, located at the end of actin filament and caps the end to prevent any excessive elongation of the thin filament.

Myosin is a thick filament made of 300 myosin molecules. Each myosin molecule has 2 functional domains: The body or filament The myosin head: it is composed of one heavy chain & 2 light chains. The heavy head chain has 2 domains: the larger one interacts with actin at the actin cleft, the smaller one is flexible & attached to 2 light chains.

MYOCYTE CONTRACTION AND RELAXATION

Ca2+ binds to TnC which increases TnC-TnI interaction & decreases inhibitory TnI-actin interaction Conformational changes in tropomyosin & permit attachment Of the myosin head to actin Cross-bridging involves detachment of the myosin head from actin and reattachment of myosin to another actin on hydrolysis of ATP by myosin ATPase ATP hydrolysis and change in configuration of the myosin head Thus facilitating binding of myosin head to actin & generation Of the power stroke of the myosin head

MYOCYTE CONTRACTION AND RELAXATION

Control of cardiac function

Neural Hormonal Cardiac reflexes

Neural regulation of cardiac function

Two limbs of the ANS provides opposing inputs to regulate cardiac function.

Actions of Hormones on Cardiac Function

Hormone
Adrenomedullin Aldosterone Angiotensin Endothelin Natriuretic peptides ANP (ANF) BNP Neuropeptide Y [48] [49] Vasopressin Vasoactive intestinal peptide[50] Sex steroid hormones Estrogen Testosterone ERR-/ERR- AR Indirect Indirect No No

Receptor
GPCR MR GPCR GPCR GCCR

Cardiac Action
+Inotropy/+chronotropy ? +Inotropy/+chronotropy ?

Increase with CHF

+ + + +

GPCR GPCR GPCR

-Inotropy +Inotropy/+chronotropy +Inotropy

+ + + + No

CARDIAC REFLEXES
1.

2. 3. 4. 5. 6. 7.

BARORECEPTOR REFLEX (CAROTID SINUS REFLEX) BAINBRIDGE REFLEX BEZOLD JARISCH REFLEX CUSHINGS REFLEX OCULOCARDIAC REFLEX CHEMORECEPTOR REFLEX VALSALVA MANEUVER

CARDIAC REFLEXES

BARORECEPTOR REFLEX (CAROTID SINUS REFLEX) It is one of bodys homeostatic mechanism to maintain blood pressure. It work through negative feedback loop. Changes in blood pressure are monitored through stretch receptors in carotid sinus and aortic arch. The nucleus solitarious receives impulses through glossopharyngeal & vagus nerves The cardiovascular centre in the medulla has 2 functionally different areas : the area responsible for increasing B.P. located laterally & rostrally :the area responsible for decreasing B.P. located centrally & caudally

The baroreceptor reflex loses its functional capacity at B.P <50mmHg. Volatile anaesthetics inhibit the heart rate component of this reflex. Concomitant use of CCBs, ACE-I & PDE-I will lessen the rise of b.p. through this reflex Patients with chronic HT often exhibit perioperative circulatory instability as a result of decrease in their baroreceptor reflex response.

BAINBRIDGE REFLEX: It is elicited by stretch receptors in the right atrial wall & cavoatrial junction. Increase in right sided filling pressure through vagus

Cardiovascular centre in the medulla increase parasympathetic activity Decrease in heart rate

BEZOLD JARISCH REFLEX : Its a triad of hypotension, bradycardia, and coronary artery dilatation in response to noxious ventricular stimuli like MI, thrombolysis or revascularization, and syncope. These are sensed by the chemoreceptors and mechanoreceptors within the LV wall which communicate via unmyelinated vagal afferent type C fibres. These fibres reflexively increase parasympathetic tone. This reflex may be less pronounced in the patients of cardiac hypertrophy or Atrial fibrillation because ANP or BNP may modulate it.

CUSHINGS REFLEX: In response to cerebral ischemia caused by increase in i.c.t the medullary vasomotor centre activates sympathetic nervous system.

This results in increase in H.R., B.P. and myocardial contractility in an effort to improve cerebral perfusion . As a result of the high vascular tone, reflex bradycardia mediated by baroreceptors will ensue.

OCULOCARDIAC REFLEX: Pressure applied to globe activates the stretch receptors in extraocular muscles

Through ciliary nerves impulses reach trigeminal nerve

Trigeminal n. carries these impulses to gasserian ganglion

Increase in parasympathetic tone & bradycardia

Pathophysiology of diseases
CAD Ventricular Hypertrophy Valvular Diseases

CORONARY ARTERY DISEASE

Increased O2 demand associated with the increased myocardial workload in the presence of coronary stenoses is responsible for symptoms in patients wth angina pectoris Platelet attachment to an atherosclerotic plaque or plaque rupture with exposure of thrombogenic collagen may produce thrombus formation converting a partially occluded coronary a. into severely stenosed or totally occluded.
Pathological conditions

The resistance to blood flow increases and pressure gradient across the narrowed vessel becomes greater with stenosis severity. Although resting coronary blood flow is maintained at near normal levels until stenosis causes 90% reduction in vessel cross sectional area, but the ability to increase flow in response to increase in myoc. O2 demand or vasodilator is substantially decreased at an area of only 60%. Endothelium dependent rrelaxation is also impaired

CORONARY STEAL

The redistribution of coronary blood flow away from ischemic to normal myocardium is known as coronary steal phenomenon. It is caused by vasodiltors( dipyramidole, adenosine) Perfusion of collateral dependent myocardium depends on the driving pressure at the origin of the collateral vessel. Arteriole in collateral dependent zone are relatively dilated and flow will decrease in direct proportion to reduction in perfusion pressure. Coronary steal can increase the myocardial infarct size in susceptible pt.

MECHANICAL CONSEQUENCES OF MYOCARDIAL ISCHEMIA

Myocardial O2 demand supply mismatch causes intracellular Acidosis, accumulation of toxic metabolites & intracellular Ca2+ overload

The noncontracting ischemic zone paasively bulges outwards In response to developed LV systolic pressure (dyskinesis)

LV dilation occurs due to thinning & expansion of acutely ischemic Segment & enhanced preload & contractility of remaining zones

Intracellular Ca2+ accumulation impairs relaxation,reduces LV Compliance. Due to diastolic dysfunction acute pulmonary edema can occur

REPERFUSION INJURY

Stunned myocardium is the post-ischemic contractile dysfunction without tissue necrosis . It may persist from hours to days. Recovery from diastolic dysfunction is even prolonged. Causes can be intracellular Ca2+ overload, depletion of high energy phosphates, free radicals, infiltrating neutrophils. Reperfusion can also be associated with ventricular arrhythmias resulting from -adrenoceptor stimulation & disturbance in Ca2+ & K+ homeostasis. Prolonged coronary a. occlusion (30min to 3 hrs) can result in severe, persistent contractile dysfunction.

Myocardial Hibernation : Chronic myocardial ischemia resulting from continuous, partial reductions in myocardial perfusion produces sustained depression of contractile function without infarction. This phenomenon is called myocardial hibernation. Ischemic Preconditioning : process by which a brief ischemic stimulus confers myocardial protection against subsequent sustained periods of coronary artery occlusion.

Left ventricular hypertrophy

Hypertrophic CardiomyopathyHemodynamic Goals

Preload Full: one of first treatments for hypotension Afterload Increased: treat hypotension aggressively with adrenergic agonists Contractility Prefer depression Rate Normal range; beta-blockers decrease LVOT gradient and increase LV end-diastolic pressure Rhythm Sinus rhythm is crucial: atrial pacing modalities (PAC, esophageal) may be helpful. M[V ]O2 Not a problem CPB Start with volume and vasoconstrictors; avoid inotropes. Check carefully for residual gradient and SAM; rule out ventricular septal defect

Valvular diseases

Aortic StenosisHemodynamic Goals

Preload Full Afterload Maintain coronary perfusion gradient Contractility Usually not a problem, may require inotropic support if hypotension persists Rate Avoid bradycardia ( CO) and tachycardia (ischemia) Rhythm Sinus: may need cardioversion or betablockers MV[V ]O2 Avoid tachycardia and hypotension (ischemia is an ever-present risk) CPB Contractility augmentation may be required transiently secondary to

Aortic Insufficiency Hemodynamic Goals

Preload Afterload Contractility Normal to slightly : with anesthetics or vasodilators (to decrease regurgitant fraction Usually adequate

Rate Rhythm M[V ]O2 CPB

: reduces ventricular volume and raises diastolic aortic pressure Usually sinus; not a problem Usually not a problem Beware (and observe) for ventricular distention (pre- and post-AXC: regurgitant flow increases if HR or nonbeating heart)

Mitral StenosisHemodynamic Goals

Preload Maintain, avoid hypovolemia Afterload Prevent pulmonary vasoconstriction (hypoxia, hypercarbia) Inotropes may be required for systemic hypotension Contractility Usually intact. RV dysfunction may be a problem with long-standing pulmonary hypertension Rate Maintain at low end of normal. Avoid tachycardia Rhythm Keep ventricular response controlled in atrial fibrillation M[V ]O2 Not a problem CPB Post-MV replacement: LV preload and filling pressures may be elevated. Cardiac function does not improve immediately

Mitral RegurgitationHemodynamic Goals

Preload Usually slightly increased; however: preload reduction may reduce regurgitant flow Afterload Decrease with anesthetics, vasodilators Contractility May be depressed, titrate myocardial depressants carefully Rate Slightly increased Rhythm If atrial fibrillation present: control ventricular response M[V ]O2 Compromised if MR coexists with ischemic heart disease CPB Newly competent valve increases afterload, often necessitating inotropic support

Thanx

PRE-OPERATIVE EVALUATION

GOAL

To reduce the morbidity of surgery To increase the quality but decrease the cost of perioperative care To return the patient to desirable functioning as quickly as possible

HISTORY
H/o Dyspnea Palpitation Chest pain Hypertension Diabetes mellitus Smoking/alcoholism Past H/o any cardiac surgery H/o any drug intake Family History

EXAMINATION

Pulse- rate, rhythm, regularity, volume B.P. JVP Pedal edema Any visible or palpable cardiac pulsation. Auscultation