Pressures in the cardiovascular system

The systemic circulation and left side of the heart have higher pressures than the right side of the heart and the pulmonary circulation. Likewise, resistance is lower in the pulmonary circulation compared to the systemic circulation. Left atrial pressure can be measured indirectly by the PCWP or the pulmonary capillary wedge pressure.

Normal pressures in the CVS

Systolic pressure is the arterial pressure resulting from the ejection of blood during ventricular contraction or systole. Diastolic pressure is the arterial pressure during ventricular relaxation or diastole. Pulse pressure is simply the difference between systolic and diastolic pressures. Pulse pressure will change if the stroke volume or compliance changes. In arteriosclerosis, the arteries are less compliant hence the systolic pressure, pulse pressure and mean arterial pressure or MAP will increase. In aortic stenosis the stroke volume will be low resulting in decreased systolic pressure, pulse pressure and MAP. In aortic regurgitation, the systolic pressure rises while the diastolic pressure falls leading to a wide pulse pressure.

Mean arterial pressure = diastolic pressure + ⅓ of pulse pressure.

Pulse is a function of elasticity of the big blood vessels. As a result of elasticity, a big blood vessel will first expand and then recoil when it is filled with blood. This expansion and recoiling is felt as a pulse.

Metabolism of the heart muscle: The heart has a comparatively high demand for oxygen, even at rest. This demand increases tenfold following strenuous exercise. The heart muscle relies chiefly on oxidative metabolism for generation of ATP. It is rich in mitochondria and preferably uses free fatty acids as a source of fuel under normal conditions. Due to the vital function it performs, the heart muscle can adapt to use various substrates for ATP generation like amino acids, glucose, glycogen, lactic acid (when exercising) and ketone bodies (fasting, diabetic ketoacidosis).

Myocardial oxygen consumption is determined on the basis of the Fick’s principle as follows:

MVO2 = F X (Ca O2 - Cv O2)

Where MVO2 is the myocardial oxygen consumption, F is the coronary blood flow and Ca and Cv O2 are the coronary arterial and venous oxygen contents respectively. It indicates how much oxygen is being extracted by the heart per minute.

Cardiac muscle contraction: A sarcomere is the functional unit of a muscle. It is the area located between two Z lines. It is composed of thick myosin and thin actin filaments. Each myosin filament has two heads which bind to actin and ATP. The myosin head has myosin-ATPase activity i.e. it hydrolyzes ATP to ADP and iP and provides the energy required for actin-myosin cross bridge formation. The proteins troponin and tropomyosin are bound to actin filaments. Troponins are of three types - troponin C binds to calcium ions, troponin T binds to tropomyosin and troponin I inhibits the myosin binding site on actin. When the concentration of intracellular calcium is low, troponin T binds to tropomyosin and blocks the interaction of actin and myosin, so the muscle does not contract. At high intracellular calcium concentrations, troponin C binds to calcium, causing a conformational change so that tropomyosin moves away and uncovers myosin binding sites on actin.

ATP binding on myosin head is followed by hydrolysis to ADP and iP which induces a conformational change in the neck region of myosin activating the myosin head which then binds to actin. This is followed by binding of ATP to myosin head and the cycle (of hydrolysis-conformational change-sliding-bind to ATP again) repeats till the intracellular calcium levels go back to normal. With each successive cycle, myosin head binds to a new binding site on actin changing from the bend or “cocked” neck position to return to its normal position triggering the “power stroke”. This causes the myosin filament to slide forward on the actin filament.

Muscle contraction is made possible due to increased intracellular calcium levels. Action potentials travel along the sarcolemma and down into the transverse tubule (T-tubule) system causing depolarization. Voltage sensitive L-type calcium channels also called dihydropyridine receptors open allowing calcium to enter the cytosol. Calcium influx triggers release of calcium from the sarcoplasmic reticulum through ryanodine receptors. Calcium is sequestered back into the sarcoplasmic reticulum through SERCA or sarco-endoplasmic reticulum calcium ATPase and Na/Ca exchanger pump. This phenomenon of excitation by nerve fibres leading to muscle contraction is called excitation-contraction coupling.

Endocrine function of the heart: The atria and ventricles secrete a few hormones with local and systemic effects. Major ones are atrial natriuretic peptide also called ANP or ANF and brain natriuretic peptide or BNP, jointly called cardiac natriuretic peptides (cNPs). Other polypeptide hormones are expressed in the heart that likely act upon the myocardium in a paracrine or autocrine fashion, these include the C-type natriuretic peptide, adrenomedullin (AM) and endothelin-1. ANP and BNP are co-stored in atrial-specific granules. Mechanical stretch of atrial muscle increases the rate of peptide secretion. The biological effects of ANP and BNP are predominantly mediated through the NPR-A guanylyl cyclase-coupled receptor, that is widely distributed throughout the body, including the kidneys, vascular smooth muscle, adrenals, brain and heart resulting in an increase in intracellular cGMP. ANP and BNP cause reduction in blood pressure, inhibition of Na+ reabsorption in renal inner medullary collecting ducts causing natriuresis and diuresis, increased glomerular infiltration rate and filtration fraction by dilation of afferent arterioles and constricting efferent arterioles. ANP reduces cardiac and pulmonary chemo- and baroreceptor activity, which leads to the suppression of sympathetic outflow to the heart leading to a reduction in heart rate and cardiac output. ANP and BNP reduce peripheral vascular resistance , inhibit secretion of vasopressin from the posterior pituitary and inhibit the synthesis of aldosterone. Blood levels of ANP and BNP are increased in various pathological conditions such as heart failure, myocardial infarction, hypertension, left ventricular hypertrophy and pulmonary hypertension. Carperitide is a recombinant form of human ANP which can be used in congestive heart failure and acute myocardial infarction, and also had renal protective effects on contrast-induced nephropathy. Nesiritide is a recombinant form of BNP causing improvement in heart failure but has serious renal adverse effects.

Adrenomedullin (AM) is a peptide resembling calcitonin. AM possesses a wide spectrum of biological actions such as vasodilation, natriuresis and diuresis as well as the inhibition of proliferation of cardiac fibroblasts and the production of extracellular matrix . Plasma AM is increased in various pathological conditions such as essential hypertension, acute coronary syndrome, congestive heart failure and septic shock. Endothelin 1 produces a potent and long-lasting vasoconstriction resulting in an increase in blood pressure and also has a direct positive inotropic and chronotropic effects on heart muscle .