IBHS 527 lecture 6

• 1. cardio:
• how much blood does the heart eject in 60 seconds?
• 2. dynamic:
• how does the body increase of decrease this amount?
• 3. what drugs increase of decrease this amount
• -and how do they do it?

• volume of blood ejected by a heart pump in one minute; amount of blood pumped by each ventricle in one minute
• use:
• clinical measure of productivity = heart health
• *volume ejected by each ventricle is about the same

• C.O. = heart rate (HR) X stroke volume (SV)
• cardiac output = ? L/min
• -HR = # of contractions of the heart during one minute
• *average HR = 75 beats/minute
• -SV = amount of blood ejected from each ventricle during one beat
• *average SV = 80 ml/beat
• => 6 L/min is cardiac output

• L/min for both ventricles
• *volume ejected by each ventricle is about the same

• 1. influence the rate of the conduction system (nodes) to change the heart rate
• 2. influence the strength of the contraction system (myocardium) to change the stroke volume

• 65 beats/min
• *lower than average of 75 bpm

220 - age = maximum heart rate

~2.5 x

• SA nodal cells (top of the heart)
• regulated by:
• 1. nervous system (autonomic innervation)
• 2. endocrine system (hormones)

• ventricle muscle cells (bottom of the heart)
• regulated by:
• 1. cardiovascular system (end-diastolic volume)
• 2. nervous and endo system (end-systolic volume)

• 1. chemoreceptors
• 2. baroreceptors
• 3. stretch receptors

detect gas changes such as O₂ and CO₂

detect changes in blood pressure (BP) and blood volume (BV)

• detect distention of right atrium
• "Bainbridge reflex"

• (1) blood changes detected by receptors (chemo/baro/stretch) --> (2) send action potential (AP) to medulla oblongata --> medulla oblongata sends action potential (AP) to heart --> neurotransmitters are released onto SA node
• *sympathetic (spinal nerve) = norepinephrine = speed up
• *parasympathetic (cranial nerve X/vagus nerve) = acetylcholine = slow down

• (1) changes in blood detected (chemo/baro) --> (2) send action potential (AP) to medulla oblongata --> medulla oblongata sends action potential (AP) to adrenal medulla --> gland releases epi and norepi --> stimulates SA node
• *stressful conditions - epistimulation

parasympathetic --> ACh release --> bind to muscurinic receptors --> opens K⁺ channels (inside becomes less positive/more negative and RMP goes from -60 mV to -70 mV and now takes longer to create action potential (AP) --> slower APs => DEC. heart rate (HR)

sympathetic --> Norepi/Epi release --> bind to beta-1 adrenergic receptors --> opens Ca²⁺ channels (inside becomes more positive/less negative and RMP goes from -60 mV to -50 mV and now is quicker to create action potential (AP) --> faster APs => INC. heart rate (HR)

(1) systole (action - squeezing) --> (2) end systolic volume (pause - left over volume in heart) --> (3) diastole (action - distending) --> (4) end diastolic volume (pause - volume gained in heart)

• SV = EDV - ESV
• *the difference between:
• -EDV = end-diastolic volume (volume after diastole)
• -ESV = end-systolic volume (volume after systole)

• 1. measure via Cardiac Conductance Catheterization (electrical impedance)
• 2. estimate via echocardiogram (ultrasound)

• 1. change end-diastolic volume (EDV)
• 2. change end-systolic volume (ESV)

• 1. INC. stroke volume:
• INC. EDV (put more in heart- preload) 2 ways:
• -INC. blood into heart by INC. venous return (INC. BV)
• -INC. filling time (DEC. HR)
• 2. DEC. stroke volume:
• opposite of above

• 1. INC. stroke volume:
• DEC. blood left in heart 3 ways:
• -INC. EDV (Frank Starling's law) - more in more out
• -INC. contractility (Epi, Norepi) with same amount of blood but with INC. calcium release
• -DEC. afterload (vasodilation = less resistance)

• increase cardiac output (C.O.)
• 1. increase HR (conduction):
• -use positive chronotropic agents (affect SA node)
• 2. increase SV (contraction):
• -use positive inotropic agents (affect myocardial muscle cells)
• *positive chronotropic/inotropic agents (affect node + muscle cells)
• 1. endogenous/natural:
• - epi/norepi - binds to beta-1 receptor --> open Ca²⁺ channels
• 2. exogenous/drugs:
• - epi pen
• - beta-1 receptor agonists (like in CHF)

• decrease cardiac output (C.O.)
• 1. decrease HR (conduction):
• -use negative chronotropic agents (affect SA node)
• 2. decrease SV (contraction):
• -use negative inotropic agents (affect myocardial muscle cells)
• *negative chronotropic/inotropic agents (affect node + muscle cells)
• 1. endogenous/natural:
• - ACh - binds to muscarinic receptors --> opens K⁺ channels
• 2. exogenous/drugs:
• (a) beta-1 receptor antagonists/beta blockers
• ex:
• - atenolol (Tenormin)
• - metoprolol (Toprol, Lopressor)
• (b) calcium channel blockers (with specificity for cardiac calcium channels (cc))
• ex:
• - verapamil (Calan SR, Verelan) - high specificity cardiac calcium channels (cc)
• - diltiazem (Cartia) - medium specificity for cardiac calcium channels (cc)

• digoxin
• function:
• 1. decreases HR (conduction)
• negative chronotropic agent (affect SA node)
• -inhibition of the Na⁺/K⁺ exchanger
• -conduction cells can't recover membrane potential as fast
• 2. increases SV(contraction)
• positive inotropic agents (affect myocardial muscle cells)
• -inhibition of the Na⁺/K⁺ exchanger
• -Na⁺ builds up inside cell --> loss of Na⁺ gradient
• -inhibition of Na⁺/Ca²⁺ exchanger
• - calcium builds up inside cell --> more force generation
• *uses in atrial fibrillation because don't want heart to beat too fast and also to not work too hard
• -first choice are beta-blockers and calcium channel blockers