Local stretching increases the electrophysiological heterogeneity of myocardium and accelerates and increases the complexity of VF in the stretched area, without significantly modifying the occurrences of the types of VF activation patterns in the nonstretched zone.

The activation frequency is inversely related to WL during VF, although a closer relation is observed with the functional refractory period. Despite the diverging effects of verapamil versus flecainide and sotalol on the activation frequency, WL, and size of the reentrant circuits, all 3 drugs reduce activation pattern complexity during VF.

Metabolic syndrome (MetS) has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis. Male NZW rabbits were assigned to control (n = 15) or MetS group (n = 16), fed during 28 weeks with high-fat, high-sucrose diet. We measured weight, morphological characteristics, blood pressure, glycaemia, standard plasma biochemistry and the metabolomic profile at weeks 14 and 28. Liver histological changes were evaluated using hematoxylin-eosin staining. A mixed model ANOVA or unpaired t-test were used for statistical analysis (P<0.05). Weight, abdominal contour, body mass index, systolic, diastolic and mean arterial pressure increased in the MetS group at weeks 14 and 28. Glucose, triglycerides, LDL, GOT-AST, GOT/GPT, bilirubin and bile acid increased, whereas HDL decreased in the MetS group at weeks 14 and 28. We found a 40% increase in hepatocyte area and lipid vacuoles infiltration in the liver from MetS rabbits. Metabolomic analysis revealed differences in metabolites related to fatty acids, energetic metabolism and microbiota, compounds linked with cardiovascular disease. Administration of high-fat and high-sucrose diet during 28 weeks induced obesity, glucose intolerance, hypertension, non-alcoholic hepatic steatosis and metabolic alterations, thus reproducing the main clinical manifestations of the metabolic syndrome in humans. This experimental model should provide a valuable tool for studies into the mechanisms of cardiovascular problems related to MetS, with special relevance in the study of cardiovascular remodeling, arrhythmias and SCD.

Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca 2ϩ handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na ϩ /Ca 2ϩ exchanger blocker KB-R7943, propranolol, and the adenosine A 2 receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control (n ϭ 9), KB-R7943 (1 M, n ϭ 9), propranolol (1 M, n ϭ 9), and SCH-58261 (1 M, n ϭ 9). Both the Na ϩ /Ca 2ϩ exchanger blocker KB-R7943 and propranolol induced a significant reduction (P Ͻ 0.001 and P Ͻ 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control ϭ 49.9%, SCH-58261 ϭ 52.1%, KB-R7943 ϭ 9.5%, and propranolol ϭ 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na ϩ /Ca 2ϩ exchanger blocker KB-R7943 and by propranolol but not by the adenosine A2 receptor antagonist SCH-58261. cardiac electrophysiology; mechanical stretch; Fourier analysis STRETCH induces the modulation of electrical and mechanical activity in myocytes. The modulation of electrical activity, also referred to as mechanoelectrical feedback (14,35), includes the depolarization of the resting potential (2,17,21,27,28,31,70), alterations of the shape and duration of action potentials (3,11,21,27,28,31,47,57,70), changes in refractoriness (4,7,9,11,27,36,47,48), and the induction of afterdepolarizations (16,18,34). These electrophysiological changes have been related to the generation of different types of cardiac arrhythmias (7, 9, 13-15, 24, 26, 35, 40, 47). The mechanical effects of stretch consist of an immediate and slow increase in force (45, 64), involving changes in myofilament Ca 2ϩ sensitivity, in the concentrations of intracellular Ca 2ϩ , and in the magnitude of Ca 2ϩ transients (1,3,29,33,58,69). These changes have been related to several mechanisms, including the actions of 1) endogenous angiotensin II (1, 46); 2) the Na ϩ /H ϩ exchanger (1, 3, 46, 66); 3) the Na ϩ /Ca 2ϩ exchanger (3,...

Because of its electrophysiological effects, hypothermia can influence the mechanisms that intervene in the sustaining of ventricular fibrillation. We hypothesized that a rapid and profound reduction of myocardial temperature impedes the maintenance of ventricular fibrillation, leading to termination of the arrhythmia. High-resolution epicardial mapping ( series 1; n = 11) and transmural recordings of ventricular activation ( series 2; n = 10) were used to analyze ventricular fibrillation modification during rapid myocardial cooling in Langendorff-perfused rabbit hearts. Myocardial cooling was produced by the injection of cold Tyrode into the left ventricle after induction of ventricular fibrillation. Temperature and ventricular fibrillation dominant frequency decay fit an exponential model to arrhythmia termination in all experiments, and both parameters were significantly correlated ( r = 0.70, P < 0.0001). Termination of the arrhythmia occurred preferentially in the left ventricle and was associated with a reduction in conduction velocity (−60% in left ventricle and −54% in right ventricle; P < 0.0001) and with activation maps predominantly exhibiting a single wave front, with evidence of wave front extinction. We conclude that a rapid reduction of temperature to <20°C terminates ventricular fibrillation after producing an important depression in myocardial conduction.