Search

Chronic volume overload induces multiple cardiac remodeling processes that finally result in eccentric cardiac hypertrophy and heart failure. We have hypothesized that chronic angiotensin-converting enzyme (ACE) inhibition by trandolapril might affect various remodeling processes differentially, thus allowing their dissociation. Cardiac remodeling due to chronic volume overload and the effects of trandolapril were investigated in rats with an aortocaval fistula (ACF rats). The aortocaval shunt was created using a needle technique and progression of cardiac remodeling to heart failure was followed for 24 weeks. In ACF rats, pronounced eccentric cardiac hypertrophy and contractile and proarrhythmic electrical remodeling were associated with increased mortality. Trandolapril substantially reduced the electrical proarrhythmic remodeling and mortality, whereas the effect on cardiac hypertrophy was less pronounced and significant eccentric hypertrophy was preserved. Effective suppression of electrical proarrhythmic remodeling and mortality but not hypertrophy indicates that the beneficial therapeutic effects of ACE inhibitor trandolapril in volume overload heart failure might be dissociated from pure antihypertrophic effects.

Metabolic syndrome is associated with hypercholesterolemia, cardiac remodeling, and increased susceptibility to ventricular arrhythmias. Effects of diet-induced hypercholesterolemia on susceptibility to torsades de pointes arrhythmias (TdP) together with potential indicators of arrhythmic risk were investigated in three experimental groups of Carlsson’s rabbit model: (1) young rabbits (YC, young control, age 12–16 weeks), older rabbits (AC, adult control, age 20–24 weeks), and older age-matched cholesterol-fed rabbits (CH, cholesterol, age 20–24 weeks). TdP was induced by α-adrenergic stimulation by methoxamine and IKr block in 83% of YC rabbits, 18% of AC rabbits, and 21% of CH rabbits. High incidence of TdP was associated with high incidence of single (SEB) and multiple ectopic beats (MEB), but the QTc prolongation and short-term variability (STV) were similar in all three groups. In TdP-susceptible rabbits, STV was significantly higher compared with arrhythmia-free rabbits but not with rabbits with other than TdP arrhythmias (SEB, MEB). Amplitude-aware permutation entropy analysis of baseline ECG could identify arrhythmia-resistant animals with high sensitivity and specificity. The data indicate that the TdP susceptibility in methoxamine-sensitized rabbits is affected by the age of rabbits but probably not by hypercholesterolemia. Entropy analysis could potentially stratify the arrhythmic risk and identify the low-risk individuals.

Metabolic syndrome is associated with hypercholesterolemia, cardiac remodeling, and increased susceptibility to ventricular arrhythmias. Effects of diet-induced hypercholesterolemia on susceptibility to torsades de pointes arrhythmias (TdP) together with potential indicators of arrhythmic risk were investigated in three experimental groups of Carlsson’s rabbit model: (1) young rabbits (YC, young control, age 12–16 weeks), older rabbits (AC, adult control, age 20–24 weeks), and older age-matched cholesterol-fed rabbits (CH, cholesterol, age 20–24 weeks). TdP was induced by α-adrenergic stimulation by methoxamine and IKr block in 83% of YC rabbits, 18% of AC rabbits, and 21% of CH rabbits. High incidence of TdP was associated with high incidence of single (SEB) and multiple ectopic beats (MEB), but the QTc prolongation and short-term variability (STV) were similar in all three groups. In TdP-susceptible rabbits, STV was significantly higher compared with arrhythmia-free rabbits but not with rabbits with other than TdP arrhythmias (SEB, MEB). Amplitude-aware permutation entropy analysis of baseline ECG could identify arrhythmia-resistant animals with high sensitivity and specificity. The data indicate that the TdP susceptibility in methoxamine-sensitized rabbits is affected by the age of rabbits but probably not by hypercholesterolemia. Entropy analysis could potentially stratify the arrhythmic risk and identify the low-risk individuals.

This dissertation consists of three parts describing electrophysiological and contractile changes of the myocardium in sepsis, acidosis, and propofol-induced anaesthesia. The first part is focused on heart rate variability analysis in a clinically relevant porcine model of sepsis/septic shock. Heart rate variability showed fast decrease few hours after sepsis induction which preceded changes in clinical parameters commonly used for sepsis diagnosis. The same fast kinetics of heart rate variability were demonstrated in progressive septic shock and in sepsis without serious multiorgan failure. Based on these results, it seems that heart rate variability could represent an early diagnostic tool in patients threatened with sepsis. In the second part of this thesis acidosis and its effects on the cardiovascular system are analysed. Metabolic and hypercapnic acidoses were examined in domestic pigs using hemodynamic in vivo measurements and in vitro experiments focused on electrophysiology and contractility of the heart. Both types of acidosis affected circulation and reduced myocardial contractility; hence it could limit therapeutic use of hypercapnic acidosis. The thesis is completed by a study of the effect of propofol, an anaesthetic used in two above mentioned studies. In rat ventricular tissue in...