Search PubMed⌕ Search

Biomedical subjects

M Artman

Publications and source records attributed to M Artman.

96 records · Page 6Linked to original sources

Myocellular calcium regulation by the sarcolemmal membrane in the adult and immature rabbit heart.

Previous studies have suggested ontogenic differences in Ca-mediated excitation-contraction coupling in mammalian heart. Sarcolemmal (SL) Ca regulation may predominate prior to the development of the specialized Ca-regulatory properties of the sarcoplasmic reticulum (SR). The effect of development on selected Ca-regulatory properties of cardiac SL was evaluated utilizing membrane vesicles obtained from immature (14 to 21-day-old) and adult rabbit heart. Methods were adapted to comparably enrich SL membrane vesicles from immature and adult rabbit heart. The global fluidity characteristics were determined by the polarized fluorescence of diphenylhexatriene passively incorporated into enriched SL membrane vesicles. No age-related differences in either the membrane microviscosity of the lipid-order parameter between 10 degrees C and 37 degrees C were observed. The membrane characteristics of the voltage-gated Ca channel were determined by the membrane binding characteristics of 3[H]-nitrendipine. Scatchard analysis of high affinity specific nitrendipine binding demonstrated comparable binding affinity (KD; 511 +/- 40 vs 484 +/- 40 pM) and theoretical maximal binding site density (Bmax; 218 +/- 19 vs 240 +/- 40 fmoles/mg prot.) in immature and adult respectively. ATP-independent Ca binding to SL membrane vesicles was determined between 1.5 and 10 mM [Ca]. Ca binding was greater in the immature at 10 mM [Ca] as compared to the adult (840 +/- 120 vs 350 +/- 30 nmoles/mg). Ca bound to SL over this Ca concentration range is indicative of a "pool" of Ca for cellular influx across the SL by the Na-Ca exchange mechanism and the voltage-gated Ca channel. In view of electrophysiologic evidence also suggesting that Ca-channel-mediated Ca conductance is greater in the immature than the adult, it is proposed that the number of voltage-activatable Ca channels localized to the SL is greater in the immature than the adult. The larger transsarcolemmal Ca fluxes plays a larger role in the beat-to-beat- regulation of cardiac contraction in the developing mammalian heart prior to full expression of the specialized Ca regulatory properties of the SR.

Aging↗

Effects of postnatal maturation on myocardial contractile responses to calcium antagonists and changes in contraction frequency.

The inotropic responses to verapamil and nitrendipine (5.0 X 10(-8)-1.0 X 10(-5) M) were compared in right ventricular papillary muscles isolated from immature (14-21 days of age) and adult rabbits. In addition, the effects of changing the contraction frequency (force-frequency response) were studied in both age groups in the presence and absence of the calcium antagonists. Immature myocardium exhibited a greater sensitivity to the negative inotropic effect of both calcium antagonists. The concentrations of verapamil which reduced basal developed tension by 50% were 0.70 X 10(-6) M in the immature rabbit and 4.51 X 10(-6) M in the adult (p less than 0.05). For nitrendipine, these values were 0.48 X 10(-6) M in the immature rabbit and 1.21 X 10(-6) M in the adult (p less than 0.05). Raising the contraction frequency increased the contractile force (positive staircase) in both age groups, and verapamil abolished the positive staircase in both groups. Nitrendipine preserved but attenuated the positive staircase in the adult, but, in contrast, augmented the positive-staircase response in the immature myocardium. These age-related differences suggest that the mechanisms regulating calcium influx across the sarcolemma undergo postnatal maturation.

Aging↗

Treatment of postischemic reperfusion cardiac injury with a perfluorochemical solution.

We assessed the effects of a perfluorochemical solution on reperfusion injury in a globally ischemic heart model. An isolated rabbit heart, retrogradely perfused at a constant flow rate, served as our experimental model. After initial perfusion with whole blood, hearts were exposed to 30 min of normothermic global ischemia. Reperfusion was then begun with either whole blood or a 20% perfluorochemical solution (FC-43). After 120 min of reperfusion, a markedly greater recovery of contractile function was observed in the perfluorochemical-reperfused hearts (85 +/- 5% of baseline developed pressure) compared with blood-reperfused hearts (57 +/- 3% of baseline developed pressure). This recovery of function was accomplished with only 1 h of perfluorochemical reperfusion and was not lost on returning to blood perfusion. The improved recovery of function could not be attributed to the chemical composition, oxygen-carrying capacity, pH, or temperature of the perfluorochemical perfusate. Neither could the beneficial effects of perfluorochemical be related to differences in left ventricular resting pressure. We speculate that, because of marked differences in coronary resistance during reperfusion with perfluorochemical solution and blood, improved recovery of cardiac function is related to the superior rheological properties of perfluorochemicals.

Animals↗

Effects of poloxamer 188 in a rabbit model of hemorrhagic shock.

Poloxamer 188 is a synthetic surfactant that reduces the viscosity of whole blood without hemodilution. It is postulated that poloxamer 188 would improve outcome if administered during retransfusion following hemorrhage. Rabbits were anesthetized and instrumented for 3 hours of hemodynamic monitoring. After stabilization, blood was withdrawn over a 5 minute period to reduce mean arterial pressure to 35 mmHg (4.7 kPa). Following a 60 minute shock period, animals were randomly assigned to 1 of 5 experimental groups (n = 8 in each): (1) Shock (no retransfusion); (2) Transfusion (retransfusion of autologous shed blood); (3) Volume (retransfusion with autologous blood and infusion of an additional volume of normal saline equivalent to the volume of poloxamer 188 given in the next 2 experimental groups); (4) Low and (5) High drug (i.v. bolus of 200 mg/kg of poloxamer 188 over 5 minutes at retransfusion, followed by a continuous infusion of poloxamer 188 at 50 mg/kg/hr in the Low drug group and 200 mg/kg/hr in the High drug group). All animals in a surgery Control group (n = 6) remained stable during the 3 hour monitoring period. In contrast, none of the animals in the Shock group remained alive, confirming this to be a relevant model of trauma and severe hemorrhagic shock. There were significantly more animals surviving at the end of the monitoring period in the two groups that received poloxamer 188 (numbers of animals alive after 3 hours = 7 of 8 in the High group and 6 of 8 in the Low group) compared to the Transfusion (4 of 8) and Volume (2 of 8) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗