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Biomedical subjects

G Grupp

Publications and source records attributed to G Grupp.

69 records · Page 4Linked to original sources
PubMed1970

Hemodynamic effects of phenoxybenzamine in anesthetized dogs.

Our studies demonstrated that phenoxybenzamine, 10 mg/kg, administered intravenously to intact anesthetized dogs, produced an immediate and significant increase of heart rate and cardiac output. In heart-lung preparations, phenoxybenzamine had no effect or a negative cardiac inotropic effect, hence these actions were not related to direct cardiac action or to release of myocardial norepinephrine stores. Serial estimations of arterial blood catecholamines after phenoxybenzamine showed an increase of epinephrine and norepinephrine; the peak values of these catecholamines did not correlate well with the maximum cardiac output responses. Ganglionic blockade largely eliminated the early cardiac effects of phenoxybenzamine, hence its action did not appear to be upon peripheral terminals of postganglionic sympathetic or parasympathetic nerves. Phenoxybenzamine was found to have antivagal actions which might account for some of the delayed cardiac acceleration. When beta adrenergic receptor blockade was induced by sotalol, the cardiac effects of phenoxybenzamine were largely eliminated. Baroreceptor denervation prevented the increase of cardiac output after phenoxybenzamine. These observations are consistent with the concept that the increase of cardiac rate and output produced by phenoxybenzamine is principally mediated by baroreceptor reflexes acting through sympathetic cardiac nerves or circulating catecholamines.

Adrenal Glands↗
PubMedDate not supplied

Hemodynamic and electrophysiological effects of a novel positive inotropic drug, OPC-8212, in normal and "failing" guinea pig heart preparations.

OPC-8212, 3,4-dihydro-6-[4-(3,4-dimethoxy-benzoyl)-1-piperazinyl]-2 (1H)-quinolinone, significantly decreased heart rate and increased contractility (+ dP/dt) and coronary flow in isolated, perfused guinea pig Langendorff and work-performing heart preparations. The effect on contractility, but not on coronary flow, was significantly greater when the negative chronotropic effect was prevented by pacing. In guinea pig hearts made incompetent by aortic stenosis, OPC-8212 produced a significant increase in contractility and coronary flow and greater negative chronotropic effects than in control hearts. OPC-8212 improved the work performance of normal and "failing" isolated work-performing guinea pig hearts during pressure load and during volume load. In electrophysiological studies, OPC-8212 enhance Vmax, amplitude, and duration of fast action potentials (APs) in guinea pig papillary muscles. Tetraethylammonium (TEA)-induced slow APs were also potentiated with respect to Vmax, amplitude, and duration. OPC-8212 in the absence of TEA also lowered the voltage threshold for inducing the slow APs. Positive inotropic effects, but not the slow APs, of guinea pig papillary muscles were greatly enhanced by OPC-8212 at higher frequencies of stimulation (2-3 Hz), indicating an important mechanism of action that may be at least in part independent of Isi.

Action Potentials↗
PubMedDate not supplied

Targeted overexpression of the sarcoplasmic reticulum Ca2+-ATPase increases cardiac contractility in transgenic mouse hearts.

Cardiac hypertrophy and heart failure are known to be associated with a reduction in Ca2+-ATPase pump levels of the sarcoplasmic reticulum (SR). To determine whether, and to what extent, alterations in Ca2+ pump numbers can affect contraction and relaxation parameters of the heart, we have overexpressed the cardiac SR Ca2+-ATPase specifically in the mouse heart using the alpha-myosin heavy chain promoter. Analysis of 2 independent transgenic lines demonstrated that sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA2a) mRNA levels were increased 3.88+/-0. 4-fold and 7.90+/-0.2-fold over those of the control mice. SERCA2a protein levels were increased by 1.31+/-0.05-fold and 1.54+/-0. 05-fold in these lines despite high levels of mRNA, suggesting that complex regulatory mechanisms may determine the SERCA2a pump levels. The maximum velocity of Ca2+ uptake (Vmax) was increased by 37%, demonstrating that increased pump levels result in increased SR Ca2+ uptake function. However, the apparent affinity of the SR Ca2+-ATPase for Ca2+ remains unchanged in transgenic hearts. To evaluate the effects of overexpression of the SR Ca2+ pump on cardiac contractility, we used the isolated perfused work-performing heart model. The transgenic hearts showed significantly higher myocardial contractile function, as indicated by increased maximal rates of pressure development for contraction (+dP/dt) and relaxation (-dP/dt), together with shortening of the normalized time to peak pressure and time to half relaxation. Measurements of intracellular free calcium concentration and contractile force in trabeculae revealed a doubling of Ca2+ transient amplitude, with a concomitant boost in contractility. The present study demonstrates that increases in SERCA2a pump levels can directly enhance contractile function of the heart by increasing SR Ca2+ transport.

Animals↗