The effect of isolation on myocardial properties

Area of Science:

• Cardiovascular Physiology
• Cardiac Excitation-Contraction Coupling

Background:

• Denervation eliminates sympathetic and parasympathetic control of the heart.
• Donor blood can maintain cardiac contractility, possibly via circulating factors.
• Isolated heart preparations often exhibit failure, suggesting limitations in oxygenation or perfusate composition.

Purpose of the Study:

• To investigate cardiac contractility and response to stimulation and noradrenaline in denervated hearts under various experimental conditions.
• To elucidate the role of oxygen availability, perfusate composition, and cellular ion balance in maintaining myocardial function.
• To compare the inotropic effects of noradrenaline and frequency potentiation in vitro versus in situ.

Main Methods:

• Utilizing denervated donor hearts perfused with homologous blood.
• Employing cell and protein-free solutions for perfusion and bathing of cardiac preparations.
• Assessing myocardial contractility, ion flux (K+, Na+), and response to noradrenaline under varying oxygenation and stimulation rates.
• Examining excised papillary muscles and atrial/ventricular strips.

Main Results:

• Donor blood perfusion maintained normal contractility, suggesting blood-borne factors.
• Substitution of blood with cell-free solutions led to cardiac failure, reduced oxygen availability, and altered intracellular ion concentrations (K+ loss, Na+ gain).
• Contractility declined more at lower rates during perfusion, and frequency potentiation and noradrenaline inotropic effects were more pronounced in vitro than in situ.
• Fiber damage in excised preparations accelerated mechanical performance decay.

Conclusions:

• Cardiac denervation necessitates external support for contractility, with donor blood being effective.
• Unphysiological perfusates compromise myocardial function by limiting oxygen and disrupting ion homeostasis.
• In vitro studies reveal altered responses to physiological stimuli and pharmacological agents compared to the in situ heart.
• The precise role of endogenous catecholamines in maintaining contractility in situ and in vitro remains under investigation.