Increase In PVR Research Articles

Muscarinic regulation of pulmonary intravascular volume in isolated canine lungs.

The influence of acetylcholine on pulmonary intravascular volume has not been clearly identified. In 14 anesthetized dogs, the pulmonary circulation was separately perfused in situ at a constant rate and drained to an extracorporeal reservoir, so that changes in total pulmonary intravascular volume could be recorded as reciprocal changes in reservoir volume. In eight animals, acetylcholine at 100 micrograms/min for 20 min was associated with increases in pulmonary intravascular volume (PIV) and pulmonary arterial pressure of 41 +/- 5 (SE) ml (P less than 0.001) and 2.0 +/- 0.0 mmHg (P less than 0.001; 11 infusions), respectively. These responses were abolished after atropine (6 infusions). In six animals, pulmonary venous pressure was also measured, so that total pulmonary (TPR), pulmonary arterial (PAR), and pulmonary venous (PVR) resistances could be calculated. TPR and PVR increased from 21 +/- 2 to 24 +/- 3 (P less than 0.001) and from 7 +/- 1 to 11 +/- 1 mmHg.min.l-1 (P less than 0.001), respectively, while PAR did not change significantly (6 infusions). In three of the six animals, these changes were abolished by atropine (6 infusions). In the other three animals, PIV increased 56 +/- 11 ml (P less than 0.001) before and 47 +/- 6 ml (P less than 0.001) after indomethacin. The acetylcholine-associated increases in TPR and PVR were also not significantly attenuated after indomethacin. Hence, muscarinic receptor stimulation with acetylcholine is associated with an increase in pulmonary intravascular volume, which is mediated by an increase in resistance to pulmonary venous outflow. These changes are not due to release of prostanoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a passive venous bypass on cardiovascular and acid-base balance variables during liver transplantations in pigs

The anhepatic phase of liver transplantation is accompanied by numerous hemodynamic and metabolic sequelae. The effects of a passive venous bypass on cardiovascular and metabolic variables during the anhepatic phase of orthotopic liver grafting was investigated in 15 pigs (group 1) and compared with 10 pigs (group 11) without a shunt. In a further five pigs (group III), after total vascular exclusion of the liver, an anhepatic state similar to the anhepatic phase of orthotopic liver transplantation was simulated. The resulting cardiovascular effects in group III were measured first without a shunt and afterwards under the conditions of a passive porto-jugular shunt. During the anhepatic phase, nonshunted animals required 113% more fluid replacement and 122% more sodium bicarbonate, compared to shunted animals, in order to keep pulmonary capillary wedge pressure (PCWP) and pH in the same range. The end-tidal PCO 2 decreased twice as much in nonshunted pigs. The MAP dropped from 86 ± 6 mmHg to 46 ± 3 mmHg in experiments without a passive venous bypass, compared to a decrease from 88 ± 5 mmHg to only 69 ± 4 mmHg when a passive porto-jugular shunt was used. Concomitantly, a compensatory increase of HR, SVR, and PVR was observed, more pronounced in the nonshunted group. Although the survival after experimental orthotopic liver transplantation was identical in both groups, a passive venous bypass is of great benefit during the anhepatic phase of liver transplantation as regards the cardiovascular and metabolic variables.

Canine nonresponders to alveolar hypoxic vasoconstriction and quantitative restoration of the response by aspirin I-3.

Hypoxic pulmonary vasoconstriction is characterized by considerable variability in rate of response (pulmonary vascular resistance [PVR] as a function of time under hypoxia). To further define this response, forty-five closed chest dogs were anaesthetized (pentobarbitone sodium), intubated, and mechanically ventilated. Constant left lower lobar pulmonary artery flow was maintained through a balloon tipped 14F catheter via an extracorporeal pump at a rate to achieve lobar pulmonary artery pressure (Plobar) equal to main pulmonary artery pressure (PPA) and thereafter held constant. Left ventricular end diastolic pressure (PLVED) was measured by left ventricular catheter and lobar pulmonary artery flow rate (Q) by flow meter. Lobar PVR (mmHg/min per 1) was calculated every 15 min. Ventilation with 10% oxygen (O2) separated two groups based on the increase in PVR over time: twenty-two rapid hypoxic responders [HR] (slope= delta PVR/delta min greater than 0.3) and twenty-three slow or nonresponders [NR] (slope less than 0.1). The twenty-three NR were divided into two groups. Ten NR dogs (NR control) had no change in mean PVR (23.9, s.d. = 8.2, to 24.1, s.d. = 9.6) over a mean of 78 min and were used as controls. Thirteen NR dogs (NR ASA) had no change in mean PVR (32.9, s.d. = 9.5, to 32.3, s.d. = 9.8) over 75 min and were given aspirin (ASA), 10-15 mg/kg intra-arterially. The NR ASA group mean PVR then increased from 32.3 (s.d. = 9.8) to 59.1 (s.d. = 23.9, 82.9% increase, P less than 0.01) over a mean of 54 min. The mean PVR for the twenty-two HR rose from 39.8 (s.d. = 34.0) to 64.5 (s.d. = 36.6, 62.1% increase, P less than 0.01) over a mean of 72 min. The slopes of rate of response for HR (0.66) and for NR ASA (0.88) were not significantly different. The absolute values of PVR reached after plateau for HR and for NR ASA (after ASA) were also not different. Aspirin restored the NR capability to develop pulmonary vasoconstriction in response to alveolar hypoxia. The rate of response and the absolute level of response reached were also restored by aspirin.

EFFECTS OF CYCLOOXYGENASE INHIBITORS ON LUNG MICROVASCULAR INJURY FOLLOWING PULMONARY INTRAVASCULAR COAGULATION (PIC)

We compared the effects of cyclooxygenase inhibitors, meclofenamate (MEC) and ibuprofen (IBU) on the development of lung mcirovascular injury after PIC induced by i.v. thrombin (T) infusion (80 U/kg). Studies were made in awake (n=10) sheep with lung lymph fistulas. The animals were pretreated with either MEC or IBU. Lung lymph flow (Qlym) lymph-to-plasma protein concentration ratio (L/P), and transvascular protein clearance (L/P × Qlym) were determined. MEC and IBU prevented the increases in the cyclooxygeanse end-products, thromboxane B2 and 6-keto-PGF1α after T. T resulted in 6-fold increases in Qlym and protein clearance, indicating lung microvascular injury. MEC attenuated the initial rises in Qlym and protein clearance after T, while IBU prevented both initial and steady-state responses. IBU but not MEC reduced the increases in pulmonary arterial pressure and PVR after T. In another group (n=11), lung PMN uptake after T was determined by infusing homologous 111-Indium oxine labeled PMN and measuring lung activity with a gamma camera. PMN uptake increased by 11% over baseline after T in controlas, compared to 4.1% in MEC group and none in IBU group. Conclusion: IBU has a greater protective effect in preventing thrombin-induced lung vascular injury than MEC. The protective effect is independent of inhibition of cyclooxygenase but may be related to inhibition of neutrophil margination. (HL-17355 and HL-26551)

Changes in lung function after routine exposure manipulations during thoracotomy

The effect of manual retraction and bronchial occlusion upon right lung function during a 2-hr thoracotomy was evaluated in sheep. Group 1 (seven sheep) underwent manual lung retraction. Group 2 (seven sheep) underwent right bronchial occlusion. Group 3 (seven sheep) served as controls. Radioisotopic indicators (51Cr-RBC, 125I-albumin, [14C]urea, 3H2O) were used to assess changes in capillary permeability-surface area product (PS-urea), extravascular lung water (VE), and intravascular blood volume (Vv). Lung water was further quantified by gravimetric technique. Pulmonary vascular resistance increased following thoracotomy in both groups (34% Group 1, 66% Group 2) and compliance decreased (16% Group 1, 33% Group 2). Mean right lung shunt increased in Group 1 from 17 to 37% (P less than 0.05) and for Group 2 from 18 to 36% (P less than 0.02). A reduction (greater than 25%) in both groups for PS-urea and VE occurred (P less than 0.05). The fall in PS-urea and VE and the increase in PVR indicate a reduction in the right lung perfusion for both groups. It is concluded that a similar marked reduction in ventilation, perfusion, and V/Q occurred after reexpansion whether the lung was retracted or the bronchus occluded.

Natural and post-operative history of pulmonary vascular obstruction associated with ventricular septal defect.

The natural history of pulmonary vascular obstruction in VSD associated with PH was studied by measuring PVR before and after injection of tolazoline 1 mg/kg. Organic pulmonary vascular obstruction (PVO) was minimal in infancy, but increased linearly progressively with advancing age, and average rate of increase in PVR after tolazoline was 1 unit.m2/year. The rate of increase in PVR after tolazoline in Eisenmenger complex was variable and ranged between 0.7 to 4 unit.m2/year in most cases. Analysis of 7 cases of post-operative late death due to PVO revealed that usually these cases were over 5 years of age at operation, and pre-operative PVR was more than 12 unit.m2. Reduction of PVR was confirmed post-operatively in most of these cases whose pre-operative PVR before and after tolazoline were les than 8 unit.m2 and 7 unit.m2 respectively. Early surgical repair is indicated in VSD and PH to prevent progress of PVO.

CARDIORESPIRATORY RESPONSES TO POSITIVE END-EXPIRATORY PRESSURE (PEEP)

The cardiorespiratory responses to PEEP have been evaluated using the puppy as an experimental model of the normal neonatal lung. Twenty puppies at 3-4 weeks of age were anesthetized and ventilated (FIO2 0.21) with pressure-controlled (P-C) and volume-controlled (V-C) assistance at PEEP levels of 0 (baseline), 5, and 10 cm H2O. Although lesser changes occurred at 5 cm H2O, the results summarized in the table are those occurring at 10 cm H2O for 15 mins. These results further define the cardiorespiratory responses to PEEP in the “normal” lung. In contrast to V-C ventilation with PEEP, which was well tolerated despite the increases in PVR, MAP and CVP, P-C ventilation with PEEP led to marked hypoventilation and progressive hypoxia, acidosis and shock after 15-20 minutes at 10 cm H2O.

The effect of DAS on respiration and pulmonary vascular resistance.

In stored blood as well as in various organs, a substance appears which causes a marked drop of systemic blood pressure after intravenous injection. The active principle was called “depressor active substance” (DAS). In order to study the circulatory effects of DAS the systemic and the pulmonary vascular resistance (SVR and PVR) and the ventilation volume were measured. DAS stopped respiratory movements by exciting afferent vagus fibres and led to an abnormal cardiac activity and to bronchoconstriction by stimulation of the vagotonus. Furthermore, DAS showed a direct bronchoconstrictor effect. The application of DAS caused a strong increase of PVR. This effect was strong enough to produce an abrupt drop of the systemic blood pressure because of a reduced diastolic filling of the left ventricle. Higher quantities of DAS led to an acute insufficiency of the right ventricle.

The anatomy of chronic cor pulmonale secondary to intrinsic lung disease

Summary Knowledge about the relationship of right ventricular hypertrophy to intrinsic lung disease depends upon detailed quantitative assessment of both organs. There is considerable overlap in the thickness measurement of normal and abnormal right ventricles measured in the anterior wall of the pulmonary conus. A measurement of 6 mm. or greater in this area is a reliable guide to the existence but not the severity of RVH. The mass of the free wall of the right ventricle in relation to that of the left ventricle and interventricular septum (LV+S/RV) provides a tool with considerable merit in the recognition and quantitation of chronic cor pulmonale. Pulmonary hypertension secondary to intrinsic lung disease is induced by a variety of anatomic and functional alterations determined and conditioned by the nature of the pulmonary disease. Assignment of a primary role to one or another factor does not yet seem justified, particularly in a complex disorder such as pulmonary emphysema. Here, although physiologic data are abundant, quantitative morphologic study of the lung has not yet received wide usage. Three principal mechanisms contribute to increased PVR secondary to intrinsic lung disease. Hypoxia, resulting from impaired ventilation or impairment of diffusion, may induce a functional and partially reversible increase in PVR through a mechanism as yet undetermined. Through distortion and obliteration of small blood vessels, parenchymal destruction produces an irreversible increase in PVR which may be either latent appearing only during stress, or manifest at rest. Finally, secondary hypertensive vascular changes may so restrict the vascular bed that perfusion is decreased to a degree incompatible with life. Abnormal vascular communications have been demonstrated in a variety of situations, but their hemodynamic significance is uncertain. Thus far, histologic examination of the lungs in chronic emphysema has shown only minor evidence of either hypoxic or secondary hypertensive vascular changes. On the other hand, there is evidence, as yet only partially evaluated, that restriction of the vascular bed by parenchymal changes combines with loss of respiratory surface to form the basis for pulmonary hypertension in panlobular emphysema. In contrast, the severity of the ventilatory disturbance may be more important than loss of either vascular bed or respiratory surface in central lobular emphysema. Development of new methods for postmortem measurement of the pulmonary vascular bed in relation to disturbance of respiratory volume and surface area may help resolve these issues not only in chronic emphysema, but also in the broad spectrum of intrinsic pulmonary disease with which significant pulmonary hypertension may be associated.

EFFECT OF HIGH INTRA-ALVEOLAR O2 TENSIONS ON PULMONARY CIRCULATION IN PERFUSED LUNGS OF DOGS.

The resistance to blood flow in the pulmonary circulation of dogs (PVR) increased when their lungs were ventilated with 95–100% oxygen and were perfused with blood that recirculated only through the pulmonary circulation; the systemic circulation was perfused independently. This increase in PVR occurred even when nerves were cut or blocked but was abolished by inhaled isopropylarterenol aerosol. Elevation of intra-alveolar Po2 without increase in pulmonary arterial blood Po2 was sufficient to increase pulmonary vascular resistance. The pulmonary venules or veins were thought to be the likely site of the constriction. These reactions were qualitatively similar to those produced by injection of serotonin or histamine into the pulmonary circulation. The time course of the response and failure to obtain it when the blood was perfused through the remainder of the body before it re-entered the pulmonary circulation are compatible with a theory that high intra-alveolar O2 tension activates a vasoconstrictor material in the pulmonary parenchyma.