1,721,001 research outputs found
DIASTOLIC DISTENSIBILITY IN ISOLATED HEARTS EXPOSED TO LOW-FLOW AND LOW-OXYGEN CONDITIONS
No full textEnhanced oxidation of bis(3,5-dibromosalicyl)fumarate a-a cross linked hemoglobin by free radicals generated by xanthine/xanthine oxidase
No full textThe xanthine/xanthine oxidase reaction produces reproducible amounts of oxygen-derived free radicals that oxidize human oxyhemoglobin (Hb). We monitored the kinetics of the oxidation of stripped Hb (sHb), purified HbA0 and α-α cross-linked Hb (HbXL99α) at [Hb] in the 5 to 150 μM (heme) range. For increasing [Hb], the oxidation halftime (t( 1/2 )) increased for all Hbs, but t( 1/2 ) was always less for HbXL99α than for HbA0 and sHb. Such feature was attributed to the lower affinity for O2 of HbXL99α and may represent a serious problem for use of this Hb as blood substitute
Functional and metabolic effects of propionyl-L-carnitine in the isolated perfused hypertrophied rat heart
No full textAim of this study was to assess the effect of propionyl-L-carnitine (PLC), a naturally occurring derivative of L-carnitine, in cardiac hypertrophy induced by pressure overload in rats. The abdominal aorta was banded and the rats received one daily administration of PLC (50 mg/kg) or saline for four days. The hearts were excised 24 h after the last administration and were perfused retrogradely with oxygenated Krebs-Henseleit buffer containing 1.2 mM palmitate bound to 3% (w/v) albumin, 2.5 μM PLC and 25 μM L-carnitine. A saline-filled balloon was inserted into the left ventricle and the heart contractility was measured at three volumes of the balloon, corresponding to zero diastolic pressure and to increased volumes (110 and 220 μl) over the zero volume. At the end of the perfusion, the hearts were freeze-clamped, weighed and analyzed for adenine nucleotide and phosphocreatine (PCr) content by HPLC methods. No differences in the myocardial performance were found at zero diastolic pressure. In contrast, at high intraventricular volume, the maximal rate of ventricular relaxation was increased in PLC-treated with respect to saline-treated controls (p < 0.05). In addition, the increase of the end-diastolic pressure at increasing balloon volume was more marked in controls than in the PLC-treated hearts (p < 0.02). These data correlate well with the measured higher level of total adenine nucleotides (p < 0.05) and ATP (p < 0.02) in the PLC-treated hearts, while PCr was the same in both groups. Parallel experiments performed in the absence of palmitate in the perfusing media failed to show any effect of PLC. We conclude that PLC improves the diastolic function by increasing the fraction of energy available from fatty acid oxidation in the form of ATP
OXIDATIVE INJURY IN REOXYGENATED AND REPERFUSED HEARTS
No full textIn this study, we separated the effects of low oxygen supply and low coronary flow in isolated perfused rat hearts to focus on the genesis of free radicals-induced reperfusion injury. Hearts were exposed to either hypoxemia/reoxygenation or ischemia/reperfusion in various sequences, with hypoxemia and ischemia matched for duration (20 min), temperature (37°C), and oxygen supply (10% of baseline). Hypoxemia/reoxygenation (n = 7) resulted in lower (developed pressure) x (heart rate) (p < 0.001) and higher end-diastolic pressure (p < 0.001) than ischemia/reperfusion (n = 9). The presence of 40 IU/ml superoxide dismutase and 104 IU/ml catalase nearly blunted the rise of the end-diastolic pressure (p = 0.02 vs. baseline), but could only partially prevent the depression of myocardial contractility (p < 0.001 vs. baseline, n = 7). Similar patterns were observed when hearts were made ischemic after hypoxemia, eliminating the intermediate reoxygenation step. We conclude that the major determinant of the reperfusion injury is associated with low oxygen supply rather than low coronary flow. Part of the injury is mediated by oxygen-derived free radicals, but a substantial portion of it is associated with energetic processes
IMPAIRMENT OF THE POSTANOXIC RECOVERY OF ISOLATED RAT HEARTS BY INTRAVASCULAR HYPOXANTHINE AND XANTHINE
No full textHypoxanthine is the final product of the catabolism of ATP in the stored red cell. Upon transfusion, this purine may be uptaken by the endothelial cell and oxidized in a post-ischemic or post-anoxic environment with production of oxygen-derived free radicals. We have tested this hypothesis with a isolated perfused rat heart model monitoring the recovery of the heart function from 20 min anoxia in the presence of 0.1 mM hypoxanthine or xanthine. Addition of 0.1 mM guanine minimized the fraction of hypoxanthine to be salvaged. The presence of hypoxanthine in the vascular space impaired the recovery of the end-diastolic pressure, left ventricular developed pressure, contraction rate, and coronary perfusion pressure. We conclude that intravascular hypoxanthine is oxidized by the endoghelial cell xanthine oxidase contributing to the post-anoxic reoxygenation injury. Since the injury led by equimolar xanthine was nearly half of that observed for hypoxanthine, this injury appears to be correlated to the stoichiometry of the oxygen-derived free radical generating reaction
Ischaemia/reperfusion in the posthypoxaemic re-oxygenated myocardium: haemodynamic study in the isolated perfused rat heart
No full textIn order to study the haemodynamics of reperfusion injury in the posthypoxaemic heart, we exposed buffer-perfused isolated rat hearts to either: (1) 20-minute low-flow ischaemia or (2) 20-minute hypoxaemia followed by re-oxygenation and further ischaemia/reperfusion. In group 2, the myocardial contractility recovered less (p < 0.002) than in group 1. This model therefore represents with sufficient reliability the clinical situation where hypoxaemic hearts are re-oxgenated before ischaemia/reperfusion and receive more severe injury than hearts exposed to ischaemia/reperfusion only. To locate the major site of the injury, further data were obtained (1) with infusion of superoxide dismutase and catalase during hypoxaemia and in the first five minutes of re-oxygenation, and (2) by eliminating re-oxygenation. It appears that the major determinant of reperfusion injury in hypoxaemic hearts is to be looked for in the events underlying hypoxaemia or re-oxygenation, and is mediated by oxygen-derived free radicals
DUAL ROLE OF HYPOXANTHINE IN THE REOXYGENATION OF HYPOXIC ISOLATED RAT HEARTS
No full textIn the reoxygenated hypoxic heart, hypoxanthine is either oxidized by xanthine oxidase with production of toxic oxygen species or salvaged for the ATP pool by hypoxanthine-guanine phosphoribosyl transferase. To characterize the repartition of hypoxanthine between the two pathways, we have subjected rat hearts to 20 min hypoxia and monitored the recovery (ventricular, end-diastolic and coronary pressures, and the contraction rate) during the reoxygenation (30 min) in the presence of either hypoxanthine or guanine alone, or both. The rate-pressure product recovered 78% of the pre-hypoxia values in hearts reoxygenated with 100 μm hypoxanthine and 80% in hearts recoxygenated with 100 μm guanine, in contrast to 49% in the presence of both hypoxanthine and guanine (100 μm each). Thus, it is likely that hypoxanthine is salvaged when present alone and is oxidized generating the reperfusion injury when the salvage is prevented by guanine that competes with hypoxanthine from the same site of hypoxanthine-guanine phosphoribosyl transferase. The functional impairment was slower when hypoxanthine was replaced by xanthine, and was eliminated by superoxide dismutase and catalase, indicating that the injury is caused by toxic oxygen species generated from hypoxanthine and xanthine oxidase. These data suggest that the salvage pathway may be critical in preventing the reperfusion injury in hypoxic hearts
The relationship between the blood oxygen transport and the human red cell aging process
No full textWe have studied the relationship between the in vivo aging process of the human red cell (RBC) and its main function, the transport of O2 from the lungs to the tissues. This study included several approaches. First, we observed that the affinity for O2 in young RBCs was lower than in old RBCs (p less than 0.0005) due to different intracellular concentration of 2,3-diphosphoglycerate, main effector of hemoglobin. Second, we explored whether there are some subgroups of the healthy human population with altered RBC age distribution: females in the age range 25-35 exhibited significantly younger RBCs (p less than 0.0005) and lower RBC-O2 affinity (p less than 0.01) than other groups. Correspondingly, the RBC-O2 affinity in female blood was significantly lower (p less than 0.002) than in male blood. Third, we correlated by two independent methods the lowered RBC-O2 affinity to a more efficient O2 delivery to the tissues by two independent methods: 1) calculating the size of the cardiac output increase required to sustain the tissue oxygenation after an increase of the RBC affinity for O2; and 2) monitoring the enhanced cardiac function in isolated rat hearts perfused with RBCs at low O2 affinity. Finally, comparing some hematologic findings relevant for the O2 transport in two healthy populations with different RBC age distributions, such as age-matched females and males, it appeared that the low RBC-O2 affinity in females is an adaptive response to their lower [Hb].
RED-CELL AGING AND ACTIVE CALCIUM-TRANSPORT
No full textThe authors have investigated the relationships between the active calcium transport across the human red blood cell (RBC) membrane and the RBC aging processes in vivo and in vitro. For the study of this biological system, the authors have determined the active calcium uptake by inside-out membrane vesicles obtained from selected RBC populations. This model provided an optimal way to assess the biochemical and functional responses of the human cell to the oxidative stimulus triggered by the cellular aging processes. The activity of the calcium pump is indeed strictly correlated to the oxidative damage suffered by the RBC, being higher in the aged RBC. It appears that the main controller of the active calcium transport is the age-dependent protein inhibitor of the calcium pump
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