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Biomedical subjects

L I Kleinman

Publications and source records attributed to L I Kleinman.

At least 37 records · Page 2Linked to original sources
PubMed1982

Preservation of cerebral autoregulation in the unanesthetized hypoxemic newborn dog.

Studies were conducted to determine the effects of hypoxemia on cerebral blood flow and the influence of hyperoxia and hypoxemia on autoregulation of cerebral blood flow in the unanesthetized newborn dog. Twenty-one newborn dogs less than 2 weeks of age were studied. Cerebral blood flow was measured using radioactive microspheres during successive periods of normotension, hypotension (produced by blood withdrawal) and normotension (produced by infusion of previously withdrawn blood). In the hyperoxic animals, arterial pO2 was maintained above 250 torr by having the animal breathe 100% oxygen, while in the hypoxemic animals arterial pO2 was maintained between 30 and 35 torr by having the animal breathe 12% O2. Cerebral blood flow increased significantly with hypoxemia. In both hypoxemic and hyperoxic animals cerebral blood flow was maintained constant in spite of a large fall in arterial blood pressure and cardiac output, demonstrating the presence of autoregulation. Calculated oxygen transport to the brain was constant during hypoxemia and hypotension in all animals. Thus autoregulation of cerebral blood flow is present in newborn animals and is preserved under conditions of moderate hypoxemia.

Animals↗
PubMed1982

Water balance in very low-birth-weight infants: relationship to water and sodium intake and effect on outcome.

The clinical effects of fluid therapy designed to maintain different degrees of negative water balance during the first five days of life were determined prospectively in 88 very low-birth-weight infants. Infants with birth weights of 750 to 1,500 gm were matched for birth weight in 250 gm increments. RDS or no RDS, asphyxiated or not, and inborn or outborn. Each infant was randomized to either Group 1--fluids managed to allow 1 to 2% loss of BW per day to a maximum loss of 8 to 10%, or Group 2--fluids managed to allow 3 to 5% loss of BW per day to a maximum loss of 13 to 15%. The mean five-day cumulative fluid input in Group 2 was 220 ml/kg less than in Group 1, yet Group 2 lost only 41 gm/kg more than did Group 1 (8.8% of BW lost in Group 1 vs 12.9% of BW lost in Group 2, P less than 0.001). There were no statistically significant differences between the groups in incidence of clinically significant patent ductus arteriosus, intracranial hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, dehydration, acute renal failure, or metabolic disturbances. There was no difference in duration of respiratory support required, in time to regain BW, or in time to discharge. There was no difference in the neonatal mortality rate. Fluid input in VLBW infants can be flexible to allow the gradual loss of 5 to 15% of birth weight during the first week of life without adversely affecting outcome.

Body Weight↗
PubMed1982

Physiological effects of hypervolemic polycythemia in newborn dogs.

The effect of hypervolemic polycythemia (Hct 62-77) on O2 transport and O2 consumption (Vo2) was studied in 16 unanesthetized newborn dogs (age 3-10 days). A control group of 10 newborn dogs (3-10 days old) was made hypervolemic but not polycythemic in an otherwise identical experiment. Hypervolemia was attained by infusing 33 ml/kg of either packed red blood cells (polycythemia) or whole blood (controls). In the polycythemic group as a result of the transfusion, cardiac output (CO) decreased by 50% (P less than 0.001), peripheral vascular resistance (PVR) increased by 170% (P less than 0.001), but O2 transport did not change significantly, and Vo2 decreased only slightly by 13% (P less than 0.01). In the 10 control animals there were no significant changes in CO, PVR, O2 transport, or Vo2 as a result of the transfusion. Blood lactate increased only slightly in experimental (35%, P less than 0.04) and control animals (23%, NS). The ability of the animals to increase their O2 transport and Vo2 was tested by measuring the changes induced by cold stress. Cold stress produced a 20% increase in Vo2 (P less than 0.05) in both the polycythemic and the control animals. Thus in spite of a decreased CO in the nonstressed state the polycythemic animals were still able to increase O2 transport and Vo2 in response to cold stress. These results suggest that the newborn animal is capable of regulating CO to maintain O2 transport appropriate to uptake under conditions of hypervolemic, polycythemic hyperviscosity, and environmental cold stress.

Animals↗
PubMed1982

Effect of acute polycythemia on newborn renal hemodynamics and function.

The present study investigates the effects of polycythemia on renal hemodynamics and function in 15 anesthetized newborn dogs, 2-10 days of age. Microspheres were used to study renal blood flow. Experimental animals received an exchange transfusion with adult dog packed red blood cells resulting in an increase in hematocrit from 38% +/- 2.1% to 69% +/- 2.1%. Control animals received an exchange transfusion with adult dog whole blood so that there was no change in hematocrit. Polycythemia resulted in a marked increase in blood viscosity, a 40% fall in cardiac output from 251.8 +/- 14 ml/kg/min to 150.7 +/- 9 ml/kg/min and a 98% increase in total vascular resistance from 0.32 +/- 0.02 mmHg/ml/kg/min to 0.63 +/- 0.07 mmHg/ml/kg/min. Nevertheless, renal blood flow was not significantly altered indicating renal vasodilation (1.4 +/- 0.06 ml/g/min initial versus 1.2 +/- 0.09 ml/g/min final). Although renal blood flow was well preserved, renal plasma flow decreased by 63% as the hematocrit increased from 0.86 +/- 0.03 ml/g/min to 0.38 +/- 0.04 ml/g/min, resulting in a 53% fall in glomerular filtration rate from 0.21 +/- 0.02 ml/min/g kidney weight to 0.09 +/- 0.02 ml/min/g kidney weight. There was also a large drop in urine output and Na and K excretion following polycythemia. This was due primarily to the decreased filtered load, because fractional Na reabsorption remained constant. Thus, in spite of well-preserved renal blood flow, polycythemia markedly affected renal function, resulting in water and salt retention.

Acute Disease↗
PubMed1981

Effects of hydroxyurea on hemodynamics of pregnant rabbits: a maternally mediated mechanism of embryotoxicity.

Hydroxyurea is a cytotoxic agent used in the management of chronic granulocytic leukemia. This compound is teratogenic and embryolethal in various animal species, and has been widely used in experimental studies aimed at understanding the possible mechanisms of drug-induced malformations. Previous studies from our laboratory have demonstrated that maternal subcutaneous injections of hydroxyurea produce immediate circulatory alterations in rabbit embryos similar to those observed subsequent to uterine artery occlusion. The present study was designed to investigate the possibility that the embryolethal and teratogenic properties of hydroxyurea might be due to alterations in maternal hemodynamics, i.e., constriction of the uterine vasculature, resulting in exposure of the embryo to uterine ischemia at critical stage of in utero development. This study demonstrates that hydroxyurea significantly alters blood pressure and heart rate and produces significant uterine vasoconstriction. The resulting reductions in uterine blood flow (77%) elicited by hydroxyurea may be associated with its immediate embryotoxicity.

Abnormalities, Drug-Induced↗
PubMed1980

Chloride concentration gradient in newborn dogs in the presence of distal nephron blockade.

Renal tubular Na+, Cl-, and H2O reabsorption was determined in 14 newborn dogs, 3--29 days of age, and in three adult dogs. In all animals NaCl reabsorption beyond the proximal tubule was blocked with ethacrynic acid (2 mg/kg) and amiloride (2.4 mg/kg). During distal blockade, fractional reabsorption of NaCl and water in both newborns and adults was approximately 70%, and there was a urine-to-plasma chloride gradient equal to 1.34 +/- 0.01, indicating that the proximal tubules of the newborn as well as those of the adult can generate a transtubular Cl- gradient. Upon administration of acetazolamide (50 mg/kg), there was a dramatic increase in excretion of Na+, Cl-, HCO3-, and water, and a decrease in the transtubular chloride gradient. After acetazolamide, the degree of inhibition of HCO3 reabsorption was well correlated with that of Na+, (r = 0.77) or Cl- (r = 0.74), and Na+ or Cl- inhibition exceeded that of HCO3-. In the newborn animal, the ratio of inner-to outer cortical nephron function is high at birth and declines rapidly during the first few weeks of life. However, there was no correlation between age and changes in either electrolyte excretion or in the transtubular chloride gradient. Therefore, the newborn dog possesses Cl- permselective tubules in the inner cortex that, in the presence of intact HCO3- reabsorption, are capable of establishing a functional transtubular Cl- gradient contributing to NaCl reabsorption.

Aging↗
PubMed1980

Natriuretic effect of oxytocin on saline-expanded neonatal dogs.

The natriuretic effect of oxytocin was studied in 40 anesthetized newborn dogs 2-33 days of age. After saline expansion, puppies excreted only 2.86% of the filtered sodium (adult dogs undergoing similar volume expansion excrete about 65-8% of the filtered sodium). After oxytocin was infused in these saline-expanded puppies at 8 mU x kg-1 x h-1, fractional sodium excretion increased to 7.51%. Oxytocin had no natriuretic effect in nonexpanded puppies. In nonexpanded animals, when distal nephron function was blocked by a combination of ethacrynic acid, chlorothiazide, and amiloride, fractional sodium excretion averaged 31%. In contrast, distal nephron blockade in saline-expanded animals resulted in fractional sodium excretion of 55%. When oxytocin was infused in either saline-expanded or nonexpanded puppies undergoing distal nephron blockade, there was no increase in sodium excretion. These results support the following conclusions. In the newborn dog 1) the attenuated natriuretic response to saline expansion is related to increased reabsorption of sodium in the distal nephron; 2) an adult type of natriuretic response to saline expansion can be induced in puppies by infusion of oxytocin; and 3) oxytocin inhibits sodium reabsorption in the distal nephron.

Animals↗
PubMed1978

Effect of amiloride on the renal response to saline expansion in new-born dogs.

1. The renal effects of amiloride were studied in twenty-six new-born and nine adult dogs, with and without saline expansion. 2. Without saline expansion, amiloride inhibited more sodium reabsorption (normalized to GFR) in puppies than in adults (5.95 vs. 2.18 muequiv/ml. GFR, P less than 0.01). Amiloride inhibited sodium reabsorption more in saline expanded than in nonexpanded puppies (9.39 vs. 5.95 muequiv/ml. GFR, P less than 0.01) but there was no difference between expanded and non-expanded adults. 3. Saline expansion by itself increased fractional sodium excretion (CNa/GFR) more in the adult than in the puppy (0.071 vs. 0.019, P less than 0.01). During amiloride inhibition, saline expansion increased CNa/GFR to 0.045 in the puppy (compared to 0.019 in the nonamiloride inhibited puppy) but saline expansion increased CNa/GFR to the same degree in the amiloride as in the non-amiloride inhibited adult. 4. In all puppies amiloride inhibited more sodium reabsorption than potassium secretion and there was poor correlation between the degree of inhibition of sodium reabsorption and potassium secretion for both the puppy (r = 0.14) and the adult (r = 0.05). 5. Assuming that amiloride acts by inhibiting sodium reabsorption and potassium secretion in the late distal and cortical collecting tubules, these results support the conclusion that in these regions of the nephron of the new-born dog (a) a greater fraction of the filtered sodium is reabsorbed than in the adult and (b) increased fractional sodium reabsorption is responsible, in part, for the attenuated natriuretic response to saline expansion.

Absorption↗
PubMed1978

Renal bicarbonate reabsorption in the new-born dog.

1. Renal bicarbonate reabsorption was measured in thirty new-born dogs 2-27 days of age. Plasma bicarbonate was varied in the puppies by exchanging their blood with blood containing high levels of bicarbonate and low levels of chloride.2. The exchange transfusion resulted in increases of plasma pH, P(CO2) and bicarbonate in the puppies without changing plasma sodium and potassium or glomerular filtration rate (g.f.r.) and body weight.3. There was no tubular reabsorption maximum (T(m)) for bicarbonate and reabsorption values as high as 50 muequiv/ml. g.f.r. could be attained. No animals excreted bicarbonate at plasma levels below 25 mM and some animals had plasma bicarbonate threshold values in excess of 40 mM.4. Bicarbonate reabsorption increased as arterial P(CO2) rose (r = 0.62) but this was due to the rise of filtered bicarbonate since (a) there was no correlation between arterial P(CO2) and bicarbonate reabsorption when factored by filtered bicarbonate and (b) lowering arterial P(CO2) by mechanical hyperventilation did not reduce bicarbonate reabsorption corrected for filtered load.5. Inhibition of renal carbonic anhydrase by acetazolamide (50 mg/kg) resulted in an inhibition of bicarbonate reabsorption of only 4.5 muequiv/ml. g.f.r. (less than 20% of the total). Even with renal carbonic anhydrase inhibited, there was no bicarbonate T(m) and bicarbonate reabsorption values as high as 40 muequiv/ml. g.f.r. could be attained.6. There was good correlation (r = 0.82) between inhibition of sodium and bicarbonate reabsorption during renal carbonic anhydrase inhibition. However, with carbonic anhydrase inhibited, there was no correlation between arterial P(CO2) and bicarbonate reabsorption.7. These results demonstrate that tubular bicarbonate reabsorption mechanisms in the new-born dog are as efficient as those reported for the adult as long as body fluid and plasma sodium and potassium levels are carefully maintained.8. The results are also consistent with a bicarbonate reabsorptive mechanism explained either by direct ionic bicarbonate reabsorption or by hydrogen ion secretion with diffusion of carbonic acid.

Absorption↗
PubMed1977

Studies in acid-base balance. I. Effect of alkali therapy in newborn dogs with mechanically fixed ventilation.

The effect of rapid or slow infusion of hypertonic sodium bicarbonate on acid-base balance and serum osmolality was studied in 36 acidotic newborn dogs. Respiratory acidosis and hypoxia were produced by mechanically fixed hypoventilation. One group of animals breathed 100% O2 to prevent hypoxemia. Rapid infusion of HCO3- in acidotic and hypoxic animals resulted in only a transient (1 minute) and small (0.05 pH units) elevation of arterial pH followed by a continuous fall, resulting in a lower pH and a worsened metabolic condition than in the nontreated controls. In nonhypoxic acidotic animals, rapid infusion of HCO3- had little effect on arterial pH. PaCO2 increased suddenly by 17 Torr in hypoxic and, by 13 Torr, in nonhypoxic animals. There was a concomitant fall in PaO2 (15 Torr). Serum osmolality rose rapidly after rapid infusion of HCO3-. Rapid infusion of hypertonic bicarbonate into an animal or infant whose ventilation is fixed thus results in a less than predicted elevation of arterial pH. PaCO2 rises, PaO2 falls, and serum osmolality rises. The net result may be a worsening rather than an improvement in the animals' metabolic state.

Acid-Base Equilibrium↗
PubMed1976

Effect of diet on renal response to salt challenge in neonatal piglets.

In piglets 14-40 days of age, blood pressure and glomerular filtration rate increased significantly with age and were lower than those reported for adult pigs. There was no effect of dietary salt on the maturation of these parameters and on tubular sodium reabsorption, although the piglets on a low salt diet had lower inulin space than piglets receiving higher dietary salt. After the completion of a 24-hour salt challenge there was little evidence of sodium retention and there was no effect of previous dietary salt intake on sodium excretion. However, salt challenge resulted in higher blood pressure and elevated serum sodium only in piglets on a low sodium diet. These results suggest that in contrast to puppies and infants, the renal response to salt challenge is physiologically adequate in piglets at 14-40 days although glomerular function is still immature. Dietary salt history appears to have little effect on the degree of sodium excretion during salt challenge in this age range.

Age Factors↗