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Biomedical subjects

L J Rubin

Publications and source records attributed to L J Rubin.

At least 145 records · Page 8Linked to original sources
PubMed1984

A direct demonstration that inositol-trisphosphate induces an increase in intracellular calcium in Limulus photoreceptors.

Inositol-trisphosphate was pressure-injected into Limulus ventral photoreceptors; these injections induced electrical responses that mimic several aspects of the electrical responses induced by light. Single cells were also injected with aequorin. Injections of inositol-trisphosphate into such cells induced an increase in luminescence from the intracellular aequorin, even in the absence of extracellular calcium ions. These aequorin responses show directly that inositol-trisphosphate induces an increase in ionized calcium concentration within intact and functioning cells that arises from release of calcium ions from intracellular stores.

Aequorin↗
PubMed1984

Relation between mixed venous oxygen tension and pulmonary vascular tone during normoxic, hyperoxic and hypoxic ventilation in dogs.

To evaluate the relation between the oxygen tension of pulmonary arterial blood (PvO2) and pulmonary vascular resistance (PVR), an extracorporeal circuit was used to vary the PvO2 of blood perfusing the left lung in 3 groups of open-chest dogs mechanically ventilated with an inspired fraction of oxygen of 0.35 (group I), 0.21 (group II), or 0.10 (group III). Left lung pulmonary blood flow, left atrial pressure and perfusate, and systemic pH and PCO2 did not change significantly as PvO2 was varied over a range of 11 to 52 mm Hg in groups I and II. There was no correlation between decreases in PvO2 and the percent change in left lung PVR compared with baseline (PvO2 approximately 40 mm Hg) in group I (r = 0.12, difference not significant). In contrast, there was a significant correlation between decreases in PvO2 and the percent change from baseline in PVR in group II (r = -0.50, p less than 0.02). Left lung alveolar oxygen tension (PAO2) decreased significantly when PvO2 was at its lowest in group II (p less than PAO2 0.05). Both groups I and II had a significant pulmonary vasoconstrictor response to hypoxic ventilation, indicating that vasoreactivity was preserved in this model. The increase in PVR with hypoxia was significantly blunted in dogs perfused with blood that had a high PvO2 (41 +/- 12.4 mm Hg, group IIIa) compared with dogs perfused with blood that had a low PvO2 (25 +/- 6 mm Hg, group IIIb), despite comparable values for PAO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Gas exchange during dialysis. Contrasting mechanisms contributing to comparable alterations with acetate and bicarbonate buffers.

Although arterial hypoxemia during hemodialysis is common and may contribute to dialysis morbidity, the mechanisms responsible remain uncertain. Additionally, controversy exists as to whether bicarbonate dialysate produces less hypoxemia than acetate dialysate. The short- and long-term effects of acetate dialysate and bicarbonate dialysate on gas exchange were compared in eight stable patients undergoing dialysis using a closed, proportioning system and a double-blind, crossover study design. Dialysate was sampled immediately proximal and distal to the dialyzer to determine its contribution to total carbon dioxide elimination. Ventilatory parameters and blood gas values were measured before dialysis, at one hour, and after dialysis. Arterial oxygen tension fell significantly and comparably at one hour with both dialysates, whereas the alveolar-arterial oxygen gradient increased only slightly. Despite hypoxemia, minute ventilation decreased by 4 to 18 percent, and arterial carbon dioxide tension was unchanged. Although total carbon dioxide elimination was unchanged in all groups, there was a significant decrease in lung total carbon dioxide elimination with acetate dialysate of 9.23 +/- 2.69 to 7.74 +/- 1.57 mmol per minute on Day 1 (mean +/- SD, p less than 0.025) concomitant with a loss of total carbon dioxide into the bath of 2.04 +/- 0.20 mmol per minute, resulting in a significant reduction in respiratory quotient (0.92 +/- 0.07 to 0.75 +/- 0.05, p less than 0.01). In contrast, there was a gain of total carbon dioxide into the blood of 1.64 +/- 0.45 mmol per minute with bicarbonate dialysate, which resulted in an increased pH at one hour compared with acetate dialysate (7.39 +/- 0.04 versus 7.35 +/- 0.03, p less than 0.05). Hypoxemia persisted after dialysis in all groups and was associated with an increased alveolar-arterial oxygen gradient in three of the four groups. It is concluded that transitory hypoventilation contributes to comparable hypoxemia with both acetate and bicarbonate dialysates by different mechanisms. With acetate dialysate, there is a decrease in carbon dioxide load to the lungs, whereas with bicarbonate dialysate, the mechanism responsible appears to be a suppression of respiratory drive resulting from a gain of bicarbonate from the dialysate. Additionally, neither dialysate prevents post-dialysis hypoxemia, which is associated with an increased alveolar-arterial oxygen gradient resulting from a mechanism that remains to be elucidated.

Acetates↗
PubMed1983

Effects of oral hydralazine on gas exchange in patients with cor pulmonale.

Vasodilators lower total pulmonary vascular resistance in some patients with pulmonary hypertension, but if vasodilators worsen arterial oxygenation in cor pulmonale, as they do in some patients with left ventricular failure, the benefits of a decrease in vascular resistance would be offset by a lack of change or a deterioration in systemic oxygen delivery. Measurement was made of arterial and mixed venous blood gases, minute ventilation, shunt fraction, alveolar-arterial oxygen difference, pulmonary arterial pressures, and cardiac output before and four hours after a single dose of hydralazine, 75 mg orally, in six patients (Group I) and before and after 48 hours of hydralazine, 50 to 75 mg orally, every six hours in 10 patients (Group II). Cardiac output increased 36 percent in Group I and 48 percent in Group II. In both groups total pulmonary vascular resistance decreased (8.0 +/- 2.8 to 6.1 +/- 2.6 units in Group I, p less than 0.01; 9.7 +/- 3.7 to 5.6 +/- 2.1 units in Group II, p less than 0.01). Arterial PO2 increased significantly both in Group I (61 +/- 8 to 67 +/- 10 torr, p less than 0.05) and Group II (50 +/- 13 to 54 +/- 13, p less than 0.05); however shunt fraction and alveolar-arterial oxygen difference were unchanged. The ratio of dead space to tidal volume decreased slightly in both groups, and minute ventilation increased significantly. Systemic oxygen delivery was increased by 39 and 51 percent in Groups I and II, respectively. Thus, gas exchange may be preserved or improved when hydralazine is used in the treatment of cor pulmonale.

Administration, Oral↗
PubMed1983

High sodium bicarbonate and acetate hemodialysis: double-blind crossover comparison of hemodynamic and ventilatory effects.

The superiority of bicarbonate dialysis (Bi HD) over acetate dialysis (Ac HD) using a high sodium dialysate has not been established to our knowledge. We compared to Bi HD to Ac HD over 6 weeks each in ten stable patients using a double-blind crossover design and a dialysate sodium concentration of 140 mEq/liter. The dialyzer, delivery system, and disalysate constituents were identical except for the substitution of Bi or Ac. Interdialytic weight gain, pre- and post-HD blood pressures, and heart rates were also comparable in the two protocols. Beginning of the week pre-HD serum Bi was greater during Bi HD than Ac HD (19.1 +/- 0.9 vs. 15.1 +/- 0.8 mEq/liter, P less than 0.001); post-HD Bi values were also higher during Bi HD. Similarly, pre-HD pH was also greater with Bi HD 7.40 +/- 0.012 vs. 7.35 +/- 0.001 U, P less than 0.01). The number of adverse symptoms and signs were similar during each protocol (2.0 +/- 0.65 for Bi HD vs. 2.5 +/- 0.5 for Ac HD episodes/patient/6 weeks, NS). However, fewer therapeutic interventions were required during the Bi HD protocol (1.5 +/- 0.43 vs. 3.1 +/- 0.6 treatments/patient/6 weeks, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1983

Independence of oxygen consumption and systemic oxygen transport in patients with either stable pulmonary hypertension or refractory left ventricular failure.

Recent studies have suggested that oxygen consumption (VO2) may be dependent on systemic oxygen transport (SOT) in patients with the adult respiratory distress syndrome. To evaluate this relationship in patients with chronically impaired SOT, 2 groups underwent control right heart catheterization. Twenty-six patients with pulmonary hypertension (Group I) were then reevaluated after 48 h of treatment with a vasodilator, either hydralazine or nifedipine. Nine patients with refractory left ventricular failure (Group II) were first studied using nitroprusside, and 24 h later were begun on a double-blind drug protocol using either minoxidil or hydralazine. A significant correlation existed between control SOT and VO2 in both groups (r = 0.65, p less than 0.001). There were no changes in either group, however, in VO2 with vasodilator therapy, despite significant increases in cardiac output and SOT. We conclude that although resting oxygen consumption may be correlated with systemic oxygen transport when SOT is at low levels in stable patients with chronically impaired SOT, VO2 appears to be independent of SOT when oxygen delivery is increased by the administration of vasodilators.

Biological Transport↗
PubMed1983

Nonadrenergic effects of isoproterenol in dogs with hypoxic pulmonary vasoconstriction. Possible role of prostaglandins.

To determine whether the pulmonary vasodilation produced by isoproterenol is mediated solely by its beta adrenergic effects, we studied the hemodynamic responses to isoproterenol in three groups of dogs with pulmonary vasoconstriction produced by continuous ventilation with 10% oxygen: (a) hypoxia alone, (b) hypoxia and propranolol 0.3 mg/kg i.v. bolus followed by an infusion of 5 micrograms/kg per min, and (c) hypoxia after pretreatment with an inhibitor of cyclooxygenase, either indomethacin or meclofenamate 5 mg/kg s.c. twice daily for 2 d prior to study. All groups had similar values for mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance (PVR) during room air and hypoxic ventilation. Isoproterenol in doses of 0.0025, 0.005, and 0.05 micrograms/kg per min produced a dose-related decline in PAPm and PVR during hypoxia in group 1. Despite beta-blockade with propranolol (group 2), isoproterenol at all three doses significantly reduced PAPm and PVR. The responses to isoproterenol were comparable in the presence or absence of propranolol; at 0.05 micrograms/kg per min the effects of isoproterenol were blunted, but not abolished, by propranolol. Similar results were observed even when five times the dose of propranolol was given. Isoproterenol at all three doses had no effect, however, on PAPm and PVR in the cyclooxygenase inhibitor-pretreated group. These data suggest that the pulmonary vasodilator effects of isoproterenol are not mediated solely by pulmonary vascular beta adrenergic receptors, and that vasodilator prostaglandins may play a role in the responses to this drug.

Animals↗
PubMed1983

Treatment of primary pulmonary hypertension with nifedipine. A hemodynamic and scintigraphic evaluation.

To evaluate the potential value of nifedipine treatment for primary pulmonary hypertension, hemodynamic and scintigraphic measurements were made before and 15 to 30 minutes after nifedipine, 10 to 20 mg, was given sublingually to nine patients. Nifedipine treatment increased cardiac output (mean +/- SD, 3.6 +/- 1.7 to 5.3 +/- 2.8 L/min, p less than 0.001) and decreased mean aortic pressure (99 +/- 19 to 85 +/- 12 mm Hg, p less than 0.001) and total pulmonary and total systemic resistances (1605 +/- 787 to 1025 +/- 540 dyn X s X cm-5 and 2761 +/- 1557 to 1591 +/- 823 dyn X s X cm-5, respectively; p less than 0.005). Heart rate and mean pulmonary arterial pressure did not change significantly. Right ventricular end-diastolic volume decreased 10% (p = 0.01), end-systolic volume decreased 15% (p less than 0.01), and right ventricular ejection fraction increased 18% (p less than 0.05) in eight patients. After 4 to 14 months (mean, 7.3 +/- 3.8) of treatment with nifedipine, 40 to 120 mg/d, in six patients, cardiac output increased (3.6 +/- 2.0 to 5.0 +/- 1.8 L/min, p less than 0.01) and total pulmonary resistance decreased (1572 +/- 730 to 987 +/- 586 dyn X s X cm-5, p = 0.025), whereas pulmonary arterial pressure remained unchanged (59 +/- 23.2 to 55 +/- 28.6 mm Hg, p greater than 0.05) compared with baseline values. We conclude that nifedipine therapy may be useful in the chronic management of patients with primary pulmonary hypertension.

Adolescent↗
PubMed1982

The effects of oral hydralazine on right ventricular end-diastolic pressure in patients with right ventricular failure.

Hydralazine reduces pulmonary vascular resistance in patients with primary and secondary pulmonary hypertension, but the effects on right ventricular function of a change in resistance without a reduction in pulmonary arterial pressure are not known. We evaluated the hemodynamic effects of hydralazine, 50 mg, administered orally every 6 hours for 48 hours in 14 patients with right ventricular failure and pulmonary hypertension resulting from various causes. Hydralazine reduced mean right ventricular end-diastolic pressure from 17.4 +/- 5.6 to 11.6 +/- 5.3 mm Hg (p less than 0.001) and increased cardiac output and stroke volume by more than 40%. In nine patients who had no change in mean pulmonary arterial pressure after hydralazine, total pulmonary resistance decreased from 15.9 +/- 6.0 to 10.6 +/- 4.3 (p less than 0.001) and cardiac index increased from 2.07 +/- 0.51 to 2.97 +/- 0.91 (p less than 0.005). There was a close correlation between the reductions in total pulmonary resistance and right ventricular end-diastolic pressure (r = 0.73)). These data suggest that hydralazine can increase cardiac output and reduce right ventricular end-diastolic pressure even when pulmonary arterial pressure remains unchanged.

Adult↗
PubMed1982

Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension.

To evaluate the effects of prostacyclin (prostaglandin I2) on pulmonary vascular tone in primary pulmonary hypertension (PPH), we performed right-heart catheterization on seven patients with PPH and made hemodynamic measurements before and after infusing incremental doses of prostacyclin. In maximal doses of 2-12 mg/kg/min (mean 5.7 +/0 3.1 ng/kg/min), prostacyclin reduced mean pulmonary arterial pressure from 62 +/- 15 to 55 +/- 16 mm Hg (p less than 0.05) and total pulmonary resistance from 17.1 +/- 8.7 to 9.7 +/- 5.9 units (p less than 0.005), and increased cardiac output from 4.22 +/- 1.64 to 6.57 +/- 2.04 l/min (p less than 0.01). Heart rate increased from 83 +/- 13 to 94 +/- 11 beats/min (p = 0.1) and mean systemic arterial pressure decreased from 90 +/- 12 to 77 +/- 4 mm Hg (p = 0.055). Three patients who received a continuous infusion of prostacyclin for 24-48 hours had sustained reductions in total pulmonary resistance during the infusion period. These data demonstrate that prostacyclin can increase cardiac output and reduce pulmonary arterial pressure and resistance in PPH.

Adolescent↗
PubMed1981

Hemodynamics at rest and during exercise after oral hydralazine in patients with cor pulmonale.

Oral hydralazine has been shown to be effective in decreasing pulmonary arteriolar resistance and increasing cardiac output in some patients with primary pulmonary hypertension. To determine whether a similar response could be observed in patients with chronic cor pulmonale, the hemodynamic status before and after the oral administration of hydralazine (25 mg, then 50 mg every 6 hours for 48 hours) were evaluated in 12 patients at rest and in 8 during upright exercise. After hydralazine, there was an increase in cardiac output at rest, from 4.3 to 6.3 liters/min (p < 0.001), and reductions in arteriovenous oxygen difference, from 8.1 to 6.1 volume percent (p < 0.001), mean pulmonary arterial pressure, from 52 to 44 mm Hg (p < 0.01), and pulmonary arteriolar resistance, from 11.2 to 6.2 units (p < 0.0005). Similar hemodynamic changes occurred during exercise, including an increase in pulmonary arterial saturation from 27 to 39 percent (p < 0.001) and a decrease in total pulmonary resistance from 12.7 to 8.9 units (p < 0.01). Results of pulmonary function tests performed before and after hydralazine did not change with drug administration. These findings indicate that the lung vascular bed in some patients with cor pulmonale is capable of responding to hydralazine with a reduction in pulmonary resistance and an increase in cardiac output both at rest and during exercise.

Adult↗
PubMed1981

Influence of prostaglandin synthesis inhibitors on pulmonary vasodilatory effects of hydralazine in dogs with hypoxic pulmonary vasoconstriction.

TO DETERMINE WHETHER HYDRALAZINE, A SYSTEMIC VASODILATOR, EXERTED A SIMILAR EFFECT ON THE PULMONARY CIRCULATION, WE STUDIED THE CIRCULATORY CHANGES IN DOGS DURING THREE INTERVENTIONS: (a) the control state during room air ventilation; (b) during continuous hypoxic ventilation with 10% oxygen, and maintaining continuous hypoxic ventilation; and (c) after 1 mg/kg hydralazine intravenously. Ventilation with 10% oxygen caused the mean pulmonary artery pressure to increase from 10+/-1.2 to 23+/-2.4 mm Hg (P < 0.01) and the pulmonary arteriolar resistance to increase from 1.51+/-0.19 to 5.87+/-1.10 U (P < 0.01). Hydralazine significantly lowered the pulmonary artery pressure (23.0+/-2.4 to 14.3+/-1.5 mm Hg, P < 0.01) and the pulmonary arteriolar resistance (5.87+/-1.10 to 2.87+/-0.52 U, P < 0.01). Femoral artery pressure, pulmonary artery wedge pressure, heart rate, and cardiac output remained unchanged throughout. To ascertain the contribution of the prostaglandin system to the pulmonary vasodilator effects of hydralazine, we pretreated a group of dogs with the prostaglandin synthetase inhibitor, indomethacin, 5 mg/kg s.c., twice daily for 2 d. These animals then underwent identical studies.The pretreated dogs had comparable base-line and hypoxia hemodynamic data. However, hydralazine had no effect on pulmonary artery pressure (23.3+/-1.6 vs. 21.7+/-2.3 mm Hg, NS) or pulmonary arteriolar resistance (8.03+/-1.09 vs. 7.14+/-1.42, NS) during continuous hypoxic ventilation in the indomethacin-pretreated group. Pretreatment with indomethacin did not, however, block the pulmonary vasodilator effects of intravenous prostacyclin (PGI(2)). Pretreatment with meclofenamate, a cyclo-oxygenase inhibitor structurally unrelated to indomethacin, also blocked the effects of hydralazine during hypoxic ventilation. These data suggest that hydralazine exerts a pulmonary vasodilatory effect during hypoxia-induced pulmonary vasoconstriction, and that this vasodilator effect may be mediated by prostaglandins.

Animals↗
PubMed1980

Oral hydralazine therapy for primary pulmonary hypertension.

To evaluate the hemodynamic effects of hydralazine in four patients with primary pulmonary hypertension, we catheterized the right side of the heart before and 48 hours after starting therapy with oral hydralazine, 50 mg every six hours. Data were obtained at rest in four patients and also during exercise in three. After hydralazine, total pulmonary resistance at rest fell from 17.5 to 7.7 U, and pulmonary arteriolar resistance from 15.6 to 7.1 U; cardiac output increased from 3.8 to 7.1 liters per minute, and the arteriovenous oxygen difference narrowed from 7.8 to 5.4 ml per deciliter. Mean pulmonary and systemic arterial pressures were unchanged. Hydralazine also caused total pulmonary resistance during exercise to fall from 15.7 to 10.2 U, and cardiac output to rise from 4.7 to 7.0 liters per minute. Treatment was continued, and on repeat catheterizations three to six months later the hemodynamic effects persisted. These data suggest that hydralazine can reduce pulmonary resistance in some patients with idiopathic pulmonary hypertension.

Administration, Oral↗
PubMedDate not supplied

Primary pulmonary hypertension: an unusual case associated with extrahepatic portal hypertension.

A patient with both extrahepatic portal hypertension and primary pulmonary hypertension is reported. The pulmonary hypertension developed without a surgical portal-systemic shunt, and at autopsy there was no evidence of a large spontaneous shunt. This association of pulmonary arterial hypertension and portal venous hypertension without either intrinsic liver disease or a large portal-systemic anastomosis has not been reported previously. Our case supports the concept that portal hypertension with its attendant portal-systemic collateral circulation may be the major predisposing cause of pulmonary hypertension both in intrinsic liver disease and extrahepatic portal vein obstruction.

Adolescent↗