Cardiac Muscle

 Cardiac Muscle

actin - thin   regulated by calcium in cardiac muscle
Myosin - thick - regulated by calcium in smooth muscle

Autonomic Control of Heart Rate

NB: factors other than autonomic tone affect heart rate

• adenosine and high K lower heart rate by moving resting membrane potential toward K equilibrium potential.  from Katzung:potassium concentration has more to do with the permeability rather than resting membrane potential!
• Hyperkalemia: reduces eq. potential for K+ but on the other hand increases permeability therefore potassium current will be higher and RMP will come closer to K+ eq. potential!  significance: in cardiac pacemaker cells during phase IV ,due to high K+ permeability it will effectively counteract hyperpolarization induced depolarizing current via rectifier channels therefore late approach towards threshold!
• Hypokalemia: increases eq. potential for K+ but on the other hand reduces permeability ;therefore K+ current will be low and RMP will be farther away from the eq. potential (K+ eq. pot. has the major influence on RMP) in other words membrane will be destabilized!  significance: in cardiac pacemaker cells low K+ current during phase IV will not be able to effectively counteract the depolarizing current and therefore early approach towards threshold [enhanced automaticity]

• Hypoxia - interferes with If - slows inward Na current and slows heart rate
• Thyroid hormone (T3)  - upregulated beta receptors (1 and 2), increase chronotropy, inotropy, vasodilation.  (results in increased stroke volume SBP and decreased DBP  = increased pulse pressur ("bounding pulse")

does calcium channel blocker slow heart rate?  yes

In normal subject with resting HR of 60, the intrinsic heart rate is about 100 (blockade of sympathetic and parasympathetic tone).  e.g., resting HR is determined mainly by vagal tone.

Cardiac Signal Transduction Mechanisms

Beta agonists produce increased inotropy (contractility) AND lusitropy (relaxation) due to inhibition of phospholamden and increased activity of SERCA

Frank-Starling Law of the Heart - 

increased preload causes increased stroke volume

Myocardial Response to Increased Afterload

will reduce stroke volume initially.  However, smaller SV means larger ESV.  Then, when normal venous return enters ventrical, the EDV will now be greater, and SV will return to normal.  e.g., people with hypertension do not have low SV and high heart rate.

Cardiovascular Intro; Hemodynamics; Cardiac Cycle

Cardiovascular Physiology

systemic circulation arteries branch ultimately into 40 billion capillaries (huge surface area for diffusion between blood and tissues)

compliance of elastic structure = delta volume/delta pressure

• aorta compliance allows steady flow through vessels (hydraulic filtering)
• can rearrange this to look at delta pressure (called pulse pressure = systolic - diastolic)*
• pulse pressure = delta volume/compliance  e.g., goes up with increasing stroke volume and goes up with decreasing compliance (e.g., hardening or aorta)
• Hyperthyroidism upregulates beta receptors causes increase and stroke volume AND decreased resistance (peripheral vasodilation) = increased Systolic and decreased diastolic pressures = increased stroke volume ("bounding pulse")

venous return to the heart - alpha 1 mediated venoconstriction = increased cardiac output

Pressures in CV system

Mean arterial pressure = 2/3 diastolic + 1/3 systolic  (because 2/3 of time is spent in diastole during one cardiac cycle).  Mean = 100 for 120/90.

*Pulse Pressure

what could elevate pulse pressure?  decreased compliance or increased stroke volume

diastolic pressure = pressure in aorta when aortic valve closes.  if compliance were zero (never true in elastic structures but can be really low; e.g., golf ball) with completely rigid aorta, systolic pressure would go way up but diastolic pressure would not change (aortic valve closes when pressure in ventricle falls below aortic pressure)

Velocity of Flow vs. Cross Sectional Area

• flow cm3/min =  Velocity cm/min x Cross Sectional Area cm2  = cm3/min
• slow velocity in capillaries helps exchange.
• Flow is the same in aorta and all capillaries, but velocity is much different.

Determinants of Blood Pressure

• alphabet rule  =  PQR   use algebra to rearrange
• P = QR
• Q = P/R
• R = P/Q  or TPR/cardiac output   (Q = cardiac output)

Poiseuille's Law  - R = 8nl/pi r4

radius to 4th power dominates

• vasoconstriction
• thickening of vessel wall

• viscosity can be important with anemia or polycythemia (downside of blood doping)  other name for polycythemia = erythrocytosis

natives of high altitude: = higher in Himalayan and Andean natives - mean hematocrit of 50% in Himalayans and 54.1% in Andeans. 

click on: 

Brain blood flow in Andean and Himalayan high-altitude populations: evidence of different traits for the same environmental constraint

hematocrit of high altitude natives

Go to:

Abstract

Humans have populated the Tibetan plateau much longer than the Andean Altiplano. It is thought that the difference in length of occupation of these altitudes has led to different responses to the stress of hypoxia. As such, Andean populations have higher hematocrit levels than Himalayans. In contrast, Himalayans have increased circulation to certain organ systems to meet tissue oxygen demand. In this study, we hypothesize that cerebral blood flow (CBF) is higher in Himalayans than in Andeans. Using a MEDLINE and EMBASE search, we included 10 studies that investigated CBF in Andeans and Himalayans between 3,658 and 4,330m altitude. The CBF values were corrected for differences in hematocrit and arterial oxygen saturation. The data of these studies show a mean hematocrit of 50% in Himalayans and 54.1% in Andeans. Arterial oxygen saturation was 86.9% in Andeans and 88.4% in Himalayans.

Series and Parallel Resistors

Rt = R1 + R2 + R3   for R=1  Rt = 3.  add an R4 = 1 and Rt = 4 (higher)

1/Rt = 1/R1 + 1/R2 + 1/R3   for R1  1/Rt = 3 so Rt = 1/3   add an R4 = 1 and Rt = 1/4 (smaller)

Laminar vs. Turbulent Flow

clarify delta P with turbulent flow.  Tom said no flow with turbulent flow.  If turbulence is not infinitely high, there is flow but requires higher driving pressures.

when rivers make noise, flow is turbulent.  same in vessels (bruits) and heart (murmurs)

Shear Stress = important for releasing nitric oxide (NO)  


Regulation of Resistance     R = deltaP/flow

• intrinsic
• extrinsic
• sympathetic NS  alpha 1 and beta 2
• epinephrine and other circ. hormone
• local metabolites
• Flow
• intrinsic - Starling's Law of the heart
• extrinsic - neural, hormonal

Cardiac Cycle

nice outside resources for this

• cardiac cycle
• Dr. Najeeb lecture (youtube)

Note that with tachycardia, diastole shortens much more than systole.  Impact = reduced filling time.  Not a problem in exercise (increased venous return) but IS a problem with resting tachycardia (e.g., cocaine).

Right Heart Pressures Lower but may equal left heart in normal individuals at high altitude or patients with lung hypoxia due to disease.

Coronary blood flow in cardiac cycle.

• greatest during diastole (muscles relaxed).  additional risk of tachycardia (reduced filling time AND reduced coronary flow during shortened diastolic period)  at same time oxygen demand is increased.
• flow is regulated in the coronary arteries primarily by adenosine.  Adenosine increases if oxygen falls (decreased ATP production = increased adenosine)

Electrophysiology

 Electrophysiology 

channels

• ionotropic; e.g., Na, K channels
• metabotropic; e.g., beta receptors

electrochemical equilibria = membrane potential that would keep any ion at its observed concentration inside and outside

-example; if K channels open the membrane will become hyperpolarized to its equilibrium potential which is - 95 mv.  this is how most inhibitory neurotransmitters work.

Ohm's Law  I = V/R  where I = current; V=voltage; R=resistance

Rectifying currents deviate from Ohm's law; i.e., current is not linear with voltage.

• inward
• outward

Conduction velocity = f(rate of change of voltage) - substances that block Na channels will slow conduction; e.g., high potassium; cocaine

Action potentials

all of heart action potentials summated to ECG

slow cells - pacemaker cells 

T type Ca channels activation by hyperpolarization

L type by depolarization

slope of phase 4, threshold, and resting potential determine heart rate

Another good figure below and explanation (from Lilly)

The maximum negative voltage of pace-maker cells is approximately -60 mV, substantially less negative than the resting potential of ventricular muscle cells (-90 mV). The persistently less negative membrane voltage of pacemaker cells causes the fast sodium channels within these cells to remain inactivated.

fast cells (myocytes; purkinje fibres)

this is a very helpful figure to understand fast action potentials:

Here is another way to understand ion currents in the fast action potential:

From Lilly; Pathophysiology of Heart Disease. Schematic representation of a myocyte action potential (AP) and relative net ion currents for Na+, Ca++, and K+. The resting potential is represented by phase 4 of the AP. Following de-polarization, Na+ influx results in the rapid upstroke of phase 0; a transient outward potassium current is responsible for partial repolarization during phase 1; slow Ca++ influx (and relatively low K+ efflux) results in the plateau of phase 2; and final rapid repolarization largely results from K+ efflux during phase 3.

Conduction velocity (dromotropy) determined by dV/dT

myocardium = .3-1 m/sec
av node = .02 - .1 m/sec  (important to allow time for filling of ventricles)