Biomedical subjects

R K Helbing

Publications and source records attributed to R K Helbing.

3 recordsLinked to original sources

PubMed1991

Inotropic interventions and myocardial force-interval relation: a quantitative approach.

OBJECTIVES: To analyze inotropic influence on the early and late phases of cardiac sarcoplasmic reticulum calcium loading. DESIGN: Papillary muscles with parallel edges and no evidence of tissue branching were selected from the heart. Only muscle preparations that maintained stable passive diastolic and developed forces were used for analysis. Muscles were stretched to their maximum length and stimulated at 0.2 Hz. The early and late phases of sarcoplasmic reticulum calcium loading were evaluated quantitatively by mathematical fitting of the force-interval relation. Increasing the extracellular calcium or decreasing the extracellular sodium was used to increase the inotropic state. ANIMALS: Right ventricular papillary muscles were isolated from female Wistar rats weighing 200 to 220 g. Electrical stimulation and data acquisition were controlled through a microcomputer. MAIN RESULTS: Increasing the extracellular calcium concentration from 0.5 to 1.0 mM produced a 90% increase in developed tension. This was accounted for by a 41% increase in the early phase of sarcoplasmic reticulum loading and a 29% increase in the late phase. A 20% reduction in the extracellular sodium concentration increased contractile force 100% and shifted the force-interval curve to the left. This was accounted for through an increase in both early and late phases of sarcoplasmic reticulum loading. CONCLUSION: These results are consistent with the current model of excitation-contraction coupling and clearly indicate that various positive inotropic interventions have selective effects on each process of the force-interval relation that cooperatively interact with each other. Mathematical fitting of data clearly improves the quantitative aspect of the force-interval response.

Animals↗

PubMed1989

Effect of catecholamine-induced cardiac hypertrophy on the force-interval relationship.

Cardiac hypertrophy was induced in adult female Wistar rats following 12 days of daily subcutaneous injections of isoproterenol (ISO). The left atria responded with a 13-14% increase in tissue growth, while the ventricles achieved a 34-39% increased tissue mass. Maximum force generation and twitch characteristics in 1.0 mM external Ca2+ for the left atria or the right papillary muscle were unchanged in the ISO-treated animals. The force-interval relation was determined at 26 degrees C between 0.5 and 120 s. The development of maximum force clearly passed through two phases identified as alpha and beta. To characterize these two processes the data were fitted to a two-term linear combination of exponentials (two-compartment model). The time constant and capacity of each process to contribute to the whole force-interval curve was determined by a four-parameter least square fit method. In control atrial muscle the time constants for the alpha and beta processes were 0.47 and 11.23 s, respectively. The contribution of each process to the total force curve in control atrial muscle was approximately 50% alpha and 50% beta. Following ISO-induced growth the time constants were 0.38 and 13.33 s with a shift of contributions towards 60% alpha and 40% beta. Control papillary muscle from the right ventricle had a similar alpha time constant of 0.49 s compared with atrial muscle but possessed a considerably slower beta time constant of 26.17 s. The contribution of each process to interval-dependent force development was 44.5 and 55.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Catecholamine induced cardiac hypertrophy.

Cardiac hypertrophy was induced in adult female Wistar rats by daily subcutaneous injections of isoproterenol (0.3 mg/kg body weight). Heart weight increased 39% after eight days of treatment. Left ventricular pressure development (positive dP/dt) in hearts four days after hypertrophy induction was significantly increased, while negative dP/dt remained unchanged. RNA polymerase activity in isolated myocyte and nonmyocyte nuclei was stimulated 29 and 23%, respectively 24 h after a single isoproterenol injection. In the myocyte fraction, RNA polymerase activation progressively increased up to four days of treatment and then returned to control values after eight days. In the nonmyocyte nuclear subset, RNA polymerase activity showed no further stimulation and gradually returned to control values after eight days of treatment. Chromatin template function was substantially stimulated in the early stage (one to four days) of hypertrophy in both myocyte and nonmyocyte fractions. Titration of chromatin against a fixed amount of RNA polymerase (5 micrograms) in the presence of rifampicin and heparin showed that less chromatin from hypertrophied hearts was required to saturate the enzyme. These results indicate that both myocyte and nonmyocte chromatin from hypertrophied hearts can support greater enzyme binding than normal chromatin. The alkaline sucrose density centrifugation profile of DNA in myocyte and nonmyocyte chromatin from day 4 hypertrophied hearts was less fragmented. These observations suggest that during the early phase of isoproterenol-induced cardiac hypertrophy, enhanced RNA polymerase activity and chromatin template function play a coordinated role in RNA synthesis. The increased template activity could be due to alterations in chromatin composition which was indicated by the change in their enzyme binding capacity and DNA fragmentation profile.

Animals↗