Characteristics of coronary circulation -explained

Key characteristics of  coronary circulation

• Coronary circulation is very short , rapid, and  phasic .
• Blood flow mainly occur during cardiac diastole
• No efficient anastomoses between the coronary vessels.
• It is a rich circulation (5% of the CO ,as heart wt is 300gm)
• Regulation of coronary circulation is mainly by metabolites and not neural
• Capillary permeability is high (the cardiac lymph is rich in protein)
• Vessels are susceptible to degeneration and atherosclerosis.
• Evident regional distribution of blood flow is noticed (subendocardial layer in LV receives < blood, due to compression (but normally compensated during diastoles by V.D).Hence it more prone to IHD+MI.
• Eddy current keep the valves away from the orifices of arteries it keeps the orifices patent throughout the cardiac cycle.
• As having highest O2 uptake achieved by a dense network of capillaries, all is perfused at rest (no capillary reserve)

The Coronary artery

• Coronary artery represent the enlarged vasavasorum of larger vessels in the heart.
• They are about the width of a drinking straw tht is 1/8 inch (4mm) .
• The term Coronary comes from the latin word ”Coronarius= “Crown”. 
• Coronary artery arises from the coronary sinuses just superior to the aortic valve behind the cusps

It has 3 cusps

• Left coronary (LC), 
• Right coronary (RC)
• Posterior non-coronary(NC) cusps.  

The left coronary artery

Left coronary artery is about 10-15mm long
It arises from left coronary cusps
Left coronary artery almost immediately bifurcate into
1. left anterior descending

• Diagonal Branch supply most of Anterior Left ventricular wall, A small part of  rightventricle
• Septal perforating Branch supply anterior 2/3rd to interventricular septum
• A part of the left branch of the AV bundle
• Terminal branch supply the cardiac apex

2. Left circumflex artery.
The right coronary artery

Origin R anterior coronary sinus origin of Valsalva
It courses through the right AV groove
Branches ;
1. Conus branch
1st branch supplies the RVOT• Sinus node artery
2nd branch - SA node.(in 40% they originate from LCA)        
2.Acute marginal arteries-Arise at acute angle and runs along the margin of RV above the diaphragm. 3, Whole of the conducting system of the heart, except part of the left br of AV node
4. Posterior descending artery : Supply lower part of the ventricular septum & adjacent ventricular walls. Arises from RCA in 85% of case.
Branches of first and second segment of RCA
Branches of 1st Segment: 

• Anterior Atrial Branch
• Artery to SA node
• Anterior Ventricular Brs
• Right Marginal Artery

Branches of 2nd Segment

• Posterior Ventricular branch
• Posterior Interventricular branch
• Posterior Interventricular (descending) Artery
• Septal branch
• AV nodal Artery

Venous drainage of heart

There are 2 systems:
There is superficial and deep venous system
Superficial system: which drains the left ventricle. It is formed of coronary sinus and anterior cardiac veins  which opens into the right atrium.
Deep system: It drains the rest of the heart. It is formed of the basian veins and arterio-sinusoidal vessels that open directly into the heart chamber.
Anastomotic channels

Between coronary arteries & extracardiac arteries there is intercoronary anastomosis
IN NORMAL HEART THERE ARE NO COMMUNICATIONS BETWEEN THE LARGE CORONARIES.
ANASTOMOSES DO EXIST AMONG THE SMALLER ARTERIES SIZED 20 TO 250 µ m.
There is three common areas of anastomoses.
    1. Between branches of LAD & PIV OF RCA in iv groove
    2. Between LCX & RCA IN AV groove.
    3. Septal branches of 2 coronary arteries in the IVS
What is the Lifesaving value of collaterals in heart?
It there is occlusion in one of the larger coronary within seconds;
Dilatation n of small anastomoses( blood flow < ½)-normal or almost normal coronary (within 1 month).
Small branches of the LAD (left anterior descending/anterior interventricular) branch of the left coronary join with branches of the posterior interventricular branch of the right coronary in the interventricular groove. More superiorly, there is an anastomosis between the circumflex artery (a branch of the left coronary artery) and the right coronary artery in the atrioventricular groove. There is also an anastomosis between the septal branches of the two coronary arteries in the interventricular septum. The photograph shows area of heart supplied by the right and the left coronary arteries.

Antiplatelet agents for the treatment and prevention of atherothrombosis

Antiplatelet drug is a generic term, these are drugs used to decrease platelet aggregation and inhibit thrombus formation. They are most effective for arterial clots that are rich in platelets.

Platelets play crucial role in haemostasis and the development of arterial thrombi. Damaged endothelium activates platelets and they respond by adhering and aggregating. They release thromboxane A2 and adenosine diphosphate (ADP) that amplifies and propagates the process by stimulating surrounding platelets. The production of thrombin via the coagulation cascade is also accelerated, helps in stabilising the thrombus by the conversion of fibrinogen to fibrin. Different classes of antiplatelet drugs act at different junctures in this process.

Aspirin (ASA)

ASA is an antiplatelet agent widely used in the management of acute coronary syndromes (ACSs) and acute ischemic stroke. Other clinically useful effects of ASA are anti-inflammation and antioxidation. ASA is typically used alone or in combination with thienopyridines to manage ACSs or prevent stent thrombosis. This is an indirect thombaxane inhibitor,it irreversibly inhibits the platelet cyclooxygenase (COX)-1 enzyme. ASA, if given at low doses,specifically inhibits plateletsynthesis of thromboxane A2 and this will leads to antithrombotic effect. At medium doses aspirin inhibits both COX-1 and COX-2 by blocking the prostaglandin synthesis and it has analgesic and antipyretic effects.This is why ASA at high doses is effective as an anti-inflammatory drug in treating rheumatic disorders.

However, ASA is a weak inhibitor of platelet aggregation when compared to other antiplatelet medication so typically it is used in combination with other antiplatelet drugs. It is conveniently dosed for once a day and recommended to be taken with food to reduce the gastrointestinal side effects.

Clopidogrel 

Clopidogrel is a thienopyridine ADP-receptor antagonist which irreversibly binds to the P2Y12 receptor.An ADP receptor antagonist that competitively inhibits ADP from binding to platelet receptors, preventing ADP-mediated up-regulation of glycoprotein (GP) IIb/IIIa receptor, again blocking amplification of platelet aggregation. Clopidogrel, is administered orally once a day, this may have variable responses and has a delayed onset of action from 2 to 6 hours if clopidogrel is given as a loading dose of 600 mg onset of action is 12 to 24 hours .There is chance of drug interaction if. used with proton-pump inhibitors (PPIs).

Clopidogrel is used alone in those who cannot tolerate aspirin prophylaxis.

Clopidogrel is routinely used in the treatment of acute coronary syndrome (ACS) and post-percutaneous coronary intervention (PCI) stenting in conjunction with aspirin.

Prasugrel

Prasugrel is a prodrug from the same family as clopidogrel, with more efficient platelet inhibition, a thienopyridine that inhibits the ADP receptors on the platelets, hence preventing them from aggregating and causing blood clots. It will irreversibly binds to the P2Y12 receptor. Thienopyridine group of drugs are more potent than ASA.. Prasugrel is given by mouth once a day, beginning with a loading dose and followed with maintenance doses. Prasugrel is the newest thienopyridine drug and it does not have similar concerns of decreased efficacy in those patients who are poor metabolizers or are using concurrent PPIs.

Prasugrel is used in combination with aspirin in ACS patients undergoing primary PCI when:

Immediate PCI is necessary for ST-segment elevation myocardial infarction (STEMI); or

Stent thrombosis occurred during treatment with clopidogrel or

The patient has diabetes mellitus.

This combination is recommended for 12 months only - beyond which there is doubtful clinical benefit.

Dipyridamole

Dipyridamole act by inhibiting the activity of adenosine deaminase and phosphodiesterase, this will result in accumulation of adenosine, adenine nucleotides, and cyclic adenosine monophosphate. Dipyridamole further inhibits platelet aggregation and leads to vasodilation. This is usually used in ombination with other anticoagulants to prevent thromboembolic complications after surgery. The problem of using dipyridamle is inconvenience, because of multiple doses administered by mouth per day. Dipyridamole is also available in combination with ASA under the brand name Aggrenox and is used to derease the risk of stroke. Aggrenox is usually given by mouth twice daily.It is also used as a stress test agent.

Since Dipyridamole also has vasodilating properties this is unsuitable for use in those with severe coronary artery disease, unstable angina, recent myocardial infarction or left ventricular outflow obstruction

Ticlopidine

Ticlopidine is one of the first antiplatelet drugs available, is a platelet aggregation inhibitor and is usually used to reduce the risk of thrombotic stroke and administered by mouth two times a day. Ticlopidine was once routinely used but has been falling out of favor because of serious hematological side effect profiles 

Glycoprotein IIb/IIIa antagonists

These drugs inhibit the final common pathway of platelet aggregation where fibrinogen binds to GP IIb/IIIa receptor.Abciximab ,Eptifibatide,Tirofiban

All these drugs require intravenous administration under specialist supervision with close monitoring, usually on coronary care units (CCUs).

Thromboxane A2 and ADP are just two of over 90 known platelet agonists. Blockade by aspirin and clopidogrel will not affect the platelet's ability to be stimulated by other agonists while use of a GP IIb/IIIa antagonist should inhibit aggregate formation whatever agonist influences the platelet.

Since there is chance of neutralising antibodies to abciximab is formed  it can only be used once.

GP IIb/IIIa antagonists can cause severe bleeding, most common from the site of femoral puncture for percutaneous transluminal coronary angioplasty (PTCA). It may take over 12 hours for platelet function to be restored after stopping this infusion

Ticagrelor

This is licensed for use with aspirin in preventing atherothrombotic events in ACS for 12 months, and is recommended for use for both medical management or where further coronary intervention is planned.

Thrombolytic therapy in myocardial infarction

Indications for thrombolysis  

STE 2mm or > in precordial leads

STE 1mm or>in Inferior leads

Fresh LBBB

Posterior Myocardial infarction

Contraindication for thrombolysis

H/O ICH

AVM, Aneurysms

Intracranial tumours

Ischemic stroke <3 months

Aortic dissection

Major Trauma with in 3 months

High BP, SBP>180 mm DBP >110mm

Bleeding diathesis

Previous STK use > 5days & <2 yr

>12 hrs after onset of pain

Administration

1.5 million IU STK in 100 ml NS over 1hour

Inj Avil + Efcorlin is given prior

ECG & BP monitoring

Adverse reactions

Life threatening ICH

Hypotension

Bleeding from puncture sites

Allergy

Signs of therapeutic Efficacy

Symptomatic improvement

ECG Change

Late diastolic VPCs

AIVR

Fall of STE

Early peaking & fall in enzyme levels

STE -ST segment elevation

STK-Streptokinase

ICH-Intracerebral hemorrhage

VPC-Ventricular premature contractions

IU-International unit