PH

Question 1

Pulmonary circulation feature

Answer 1

Low pressure/resistance and high capacitance system

Question 2

PAP determined by 3 factors

Answer 2

o Pulmonary blood flow
o Pulmonary vascular resistance
o Pulmonary venous pressures

Question 3

Definition of PH

Answer 3

PAPs >30mmHg, PAPd >19mmHg

Question 4

Dz causing incr PVP

Answer 4

L heart dz
Compression of lg PVs

Question 5

Dz causing incr PVR

Answer 5

Endothelial dysfct
Vascular remodelling
Perivascular inflamm
Vascular luminal obst
incr blood viscosity
arterial wall stiffness
lung parenchymal destruction

Question 6

Dz incr pulm blood flow

Answer 6

Systemic to pulm shunts

Question 7

Pathophys of PH

Answer 7

Imbalance btwn:
* PA vasoconstriction/dilation
* Platelet activation
o Platelet derived growth factor: induce proliferation/migration of SM¢
* SM¢ proliferation

Question 8

What factors induce vasoconstriction

Answer 8

 ET1: released in response to changes in blood flow, stretch, thrombin
* Induce vasoconstriction, SM¢ proliferation
* incr collagen synthesis, vascular remodelling
 Alveolar hypoxia: physiologic deviation of ventilation to well ventilated areas
* Can lead to PH in chronic pulmonary conditions
 Serotonin/histamin

Question 9

Factors inducing vasodilation

Answer 9

 NO: synthetized from L arginine + O2 by NO synthase
* incr cGMP => inactivated by PDE5
* reduced platelet activation, SM¢ proliferation

Question 10

Effect of arachidonic acid metabolites

Answer 10

 Prostacyclin: potent vasodilator, inhibit platelet activation, antiproliferative
 Thromboxane A2: vasoconstrictor, platelet agonist

Question 11

Histo patho damage to pulm vessels

Answer 11

6 grades
* Medial hypertrophy
* ¢ intimal proliferation
* Concentric laminar intimal fibrosis
* Fibrinoid necrosis
* Plexiform lesions

Question 12

ACVIM consensus classification scheme

Answer 12

• Pre/post capillary: *post capillary: associated w  PAWP > 15mmHg

VS

1) Primary pulmonary arterial hypertension
 Idiopathic
 Congenital systemic to pulmonary shunt => incr pulmonary blood flow
* Eisenmenger syndrome
 Congenital PH

2) Secondary to left heart disease: most common cause of PH in dogs
 Pulmonary venous hypertension 2nd to incr LA pressures => CVD, DCM, left sided dz
 Reactive pulmonary arterial vasoconstriction

3) Secondary to pulmonary disease and/or hypoxia
 Pulmonary fibrosis
 Pneumonia
 Tracheobronchial dz
 Neoplasia

4) Secondary to thromboembolic diseases
 Hypercoagulable states: IMHA, DIC, cushing, PLE/N, neoplasia, sepsis
 HW: worm embolization

5) Secondary to parasitic diseases
 Angiostrongylus vasorum
 Dirofilaria immitis
 Physical presence of worms => inflammation => villous hypertrophy of intima

6) Miscellaneous
 Compressive mass lesions

Question 13

Treatment PH

Answer 13

PD5i
PDE3i
ET antagonist
Prostacyclin analog

Question 14

MOA PDE5i

Answer 14

o incr pulmonary [cGMP]
o decr cardiac remodelling, apoptosis, fibrosis
o decr ventricular hypertrophy
o incr L heart fct

Question 15

MOA PDE3i

Answer 15

o Ca2+ sensitizing agent: inotrope +
 Improve Rv systolic fct
o Systemic vasodilatory properties
o decr LA pressures => target post capillary PH

Question 16

Drugs PDE5i

Answer 16

sildenafil, tadalafil, vardenafil

Question 17

Drugs PDE3i

Answer 17

pimobendan, milrinone

Question 18

Drugs ET antagonists

Answer 18

bosentan, ambrisentan, macitentan

Question 19

Drugs prostacyclin agonist

Answer 19

iloprost, epoprostenol, beraprost