To demonstrate the effect of drugs used in management of anginal pectoris on the isolated heart.

To explain the mechanisms beyond the observed effects.
To relate the observed effects to the clinical usefulness of these drugs.

To manage

Imbalance

In the HEART

↑Heart Rate

β- blockers

CCB

CCB

In BLOOD VESSELS

To demonstrate the effect of :
• β-blockers • Calcium channel blockers • Nitrates

On Langendorff heart

Langendorff preparations using the heart of

Taking Measurements
1. Contractile Force 2. Heart Rate (beat/min) 3. Coronary Blood Flow (CBF) (ml/min)

What are the factors affecting CBF? Flow/beat X heart rate
Coronary dilatation, filling time, heart rate, Force of contraction

1. Assess the effect of Adrenaline on (contractile force, HR, CBF)

2. Assess the effect of Nor adrenaline on (contractile force, HR, CBF)
3. Explain the difference between them

Adrenaline contractile force 3.5 HR CBF 2 2

Nor adrenaline 3.5 2 1

Nor adrenaline has minimal effect on β2 receptors (Has no vasodilator effect on the coronaries)

Adrenaline caused:
A. ↑contractile force & HR due to  Stimulation of b1&b2 receptors in cardio myocytes. B. ↑CBF (ml/min) due to:  Stimulation of b2 receptors in the Smooth muscle cells of coronaries  ↑contractile force & heart rate

Total CBF = ……ml/beat xHR
• At normal HR: CBF = 0.2 ml/beat x 60 beat/minute = 12 ml/min (collected CBF in langendorff experiment)

• Effect of tachycardia (adrenaline) CBF= {0.13ml/beat (↓diastolic time) + 0.02 ml/beat (coronary dilatation)}x 100 beat/min= 15 ml/min NO (in normal healthy heart this ↑CBF is helpful during exercise) In ischemic heart, such tachycardia is bad (why?)

Nor adrenaline caused:
A. ↑contractile force & HR due to  Stimulation of b1 receptor in cardio myocytes. B. ↑CBF (ml/min) due to:  ↑contractile force & HR [BUT, less than adrenaline]

Compare between the effect of adrenaline alone and with propranolol (Non selective b blocker)

Adrenaline

Adrenaline +Propranolol 1 1 -0.5 uncover the α- effect of adrenaline

contractile force HR CBF

3 2 2

• Propranolol blocked the effect of adrenaline on b1&b2 receptors

• So, it Decreased its stimulatory effect on contractile force, HR & CBF

• Propranolol has –ve inotropic and chronotropic effects→ ↓myocardial O2 demand • But it has No vasodilator effect • Propranolol is used in treatment of IHD alone or in combination with Nitrates and Nifedipine to decrease the reflex tachycardia

1. Assess the effect of Nitroglycerine on (contractile force, HR, CBF) 2. Assess the effect of Verapamil on (contractile force, HR, CBF)

Contractile force HR CBF

Nitroglycerine 0 0 1

Verapamil -0.5 -0.5 1.5

Effect of drugs that reduce HR and dilate coronaries e.g verapamil
• CBF= 0.3 ml/beat x 50 beat/minute = 15 ml/min (compare it to 12ml/min under normal conditions. 0.1 ml extraflow/beat of which: + 0.08 due to ↑diastolic time 2ry to bradycardia + 0.02 due to coronary VD )

In Beneficial effects of verapamil in ischemic heart disease:
1) ↓ HR: (↑diastolic time for coronary perfusion) 2) VD of epicardial coronary vessels

↑CBF

3)↓ O2 demand due to –ve inotropy and –
ve chronotropy.

In vitro effect of drugs that only dilate coronaries e.g nitroglycerine
• CBF= 0.24 ml/beat x 60 beat/minute = 14.4 ml/min (compare it to normal CBF of 12ml/min and to 15 ml/min with verapamil) 0.04 ml extraflow/beat due to ↑ coronary VD compared to 0.02 with verapamil) This is because nitroglycerine is more powerful VD than verapamil

Nitroglycerin
• Nitroglycerine increase myocardial oxygen supply [coronary vasodilatation by NO release] • Nitroglycerine decreases myocardial oxygen demands [decreasing preload and after load] • Nitrates have no cardio-depressant effect • Main S.E. Postural hypotension & reflex tachycardia

Verapamil
• non-dihydropyridine CCB • It decreased contractile force & HR by blocking Ca channels in the heart (Main action) [–ve inotropic & chronotropic effects] So It decreased myocardial oxygen demand by decreasing cardiac work

• It increased CBF by blocking Ca channels in the blood vessels causing vasodilatation • This group has less vasodilator action than other CCBs or nitrates • so they are most appropriate antianginal therapy for patients with hypotension.

Put (√) or (X)
Adrenaline and noradrenaline increase the (X) contractile force & heart rate due to stimulation of a 1 adrenoceptors CBF was increased equally by adrenaline & noradrenaline contractile force was increased equally by adrenaline & noradrenaline Noradrenaline induced increase of CBF was potentiated by Propranolol (X)

(√) (X)

Nitroglycerine relaxes vascular smooth muscle

(√)

Effect of Nitroglycerine on heart rate is (X) expected to be the same in- vivo and in-vitro

Cardiac preload and after load are unlikely to be affected by nitroglycerine

(X)

Complete
Drugs, which affect the force of contraction and/or CBF the heart rate, will thus also affect ……………….. even though they may have no direct effect on coronary vessels. If the heart is perfused at constant pressure, the mean volume of perfusion fluid draining from the heart is a measure of ……………………………………….. CBF Measurments taken during isolated perfused heart Force of contraction experiment include …………………………....………… , ………………………………..and…………………………………….. HR CBF

THANK YOU

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