BIOL 4370_5370 Chapter 18

TOXIC RESPONSES TO THE HEART AND VASCULAR SYSTEM

• Presenter: Amie Lund, Ph.D.

• Course: BIOL 4370/5370 Chapter 18

CARDIOVASCULAR PHYSIOLOGY

• The cardiovascular system comprises:

  • Heart

  • Blood Vessels (veins, arteries, capillaries)

  • Blood

• Functions of the cardiovascular system include:

  • Delivering oxygen (O2) to cells/tissues

  • Delivering nutrients to cells/tissues

  • Transmitting key signaling molecules (e.g., hormones)

  • Removing wastes and foreign matter from cells/tissues

  • Thermoregulation

  • Maintenance of tissue and cellular pH

CARDIOVASCULAR ANATOMY

• Diagrammatic illustration of the heart anatomy includes:

  • Atrioventricular node

  • Aorta

  • Sinoatrial node

  • Right/left atrium

  • Right/left ventricle

  • Pulmonary veins

  • Purkinje fibers

CARDIAC STRUCTURE

• Components of the heart:

  • Myocytes

  • Fibroblasts

  • Vascular cells (endothelial, smooth muscle)

  • Purkinje cells

  • Connective tissue

• Key points:

  • Myocardial cells stop mitosis after 2-3 weeks of birth.

  • Injury leads to cardiac remodeling:

    • Myocyte hypertrophy

    • Fibrosis

CARDIAC HYPERTROPHY

• Involves:

  • Myocytes exhibiting hypertrophy (induction of fetal genes)

  • Hyperplasia, hypertrophy, and remodeling of interstitial components

  • Reduced ventricular compliance from increased collagen levels

CARDIAC CONDUCTION

• Components of cardiac conduction:

  1. Sinoatrial (SA) node (pacemaker)

  2. Atrioventricular (AV) node

  3. AV bundle (Bundle of His)

  4. Bundle branches

  5. Purkinje fibers

MECHANISM OF CARDIAC CONTRACTION

• The contraction process involves:

  1. Depolarization current initiation.

  2. Action potentials traveling along the membrane.

  3. Ca2+ channels opening, facilitating muscle contraction via the crossbridge cycle.

  4. Relaxation occurs as Ca2+ is transported back into the sarcoplasmic reticulum (SR).

CARDIAC ELECTROPHYSIOLOGY

• Phases of cardiac action potential:

  • Phase 0: Na+ influx leads to depolarization (+30 mV).

  • Phases 1-3: Repolarization as K+ moves out of the cell.

  • Phase 2: Plateau phase with Ca2+ influx sustaining contraction.

  • Phase 4: Resting state with return to -90 mV.

ELECTROCARDIOGRAM (ECG)

• Components of the ECG:

  • P wave: Atrial depolarization.

  • PR interval: Time taken for impulse travel from SA to AV node.

  • QRS wave: Ventricular depolarization.

  • T wave: Ventricular repolarization.

  • QT interval: Total time for ventricular depolarization and repolarization.

CARDIAC TOXICITY RESPONSES

• Xenobiotic-induced cardiac function disturbances:

  • Changes in heart rate (tachycardia, bradycardia)

  • Altered contractility and conductivity

  • Arrhythmias due to ion channel function alterations

BIOMARKERS FOR CARDIOTOXICITY

• Key biomarkers and their indications:

  • Creatine Kinase (CK): Elevation suggests myocardial injury.

  • Myoglobin: Indicative of acute myocardial infarction.

  • B-type Natriuretic Peptide (BNP): Indicating volume pressure overload and heart failure.

  • Cardiac troponins: Reflect irreversible myocardial injury.

MECHANISMS OF CARDIAC TOXICITY

• Key mechanisms influenced by toxins include:

  • Alterations in ion movement and homeostasis

  • Inhibition of Na/K+ ATPase increases intracellular Na+ and Ca2+

  • Ca2+ channel blockade affecting pacemaker potential and conduction velocity.

  • Ischemia and oxidative stress mechanisms.

CARDIOTOXICANTS

• Various pharmacological and naturally occurring substances can induce cardiotoxicity:

  • Alcohol (acute/chronic effects)

  • Cardiac glycosides like digoxin (Ca2+ overload)

  • Anthracyclines like doxorubicin causing abnormal heart function.

NATURALLY OCCURRING CARDIOTOXIC COMPOUNDS

• Cardiotoxicity caused by:

  • Steroids, cytokines, and plant toxins.

  • Specific effects on heart health, including arrhythmias and hypertension.

VASCULAR ANATOMY

• Overview of vascular systems:

  • Importance of the vascular system in delivering oxygen and nutrients to organs.

ALTERATIONS IN VASCULAR STRUCTURE AND FUNCTION

• Key issues include:

  • Atherosclerosis development through foam cell formation due to toxins.

  • Changes in blood pressure during toxic exposures, often leading to hypotension.

  • Risk of thrombosis from xenobiotic exposure.

MECHANISMS OF VASCULAR TOXICITY

• Vascular toxicity occurs primarily in endothelial cells but can also affect smooth muscle.

  • Alterations in membrane structure

  • Disturbances in ionic regulation and reactive oxidation.