Longitudinal distribution of pulmonary vascular resistance with very high pulmonary blood flow

Dog left upper lobes (LUL) were perfused in situ via the left lower lobe artery. Lobe weight was continuously monitored. Increasing lobar flow from normal to 10 times normal had little effect on left atrial pressure, which ranged from 1 to 5 mmHg. There was a flow threshold (Qth) below which lobar weight was stable. Qth ranged from 1.1 to 1.55 l/min (mean 1.27) corresponding to four times normal LUL blood flow. Above Qth, step increases in lobar flow resulted in progressive weight gain at a constant rate that was proportional to flow. The effective pressure at the filtration site (EFP) at different flow rates was estimated from the static vascular pressure that resulted in the same rate of weight gain. From this value and from mean pulmonary arterial (PA) and left atrial (LA) pressures, we calculated resistance upstream (Rus) and downstream (Rds) from filtration site. At Qth, Rds accounted for 60% of total resistance. This fraction increased progressively with flow, reaching 83% at Q of 10 times normal. We conclude that during high pulmonary blood flow EFP is closer to PA pressure than it is to LA pressure, and that this becomes progressively more so as a function of flow. As a result, the lung accumulates water at flow rates in excess of four times normal despite a normal left atrial pressure.     

Effect of nifedipine and propranolol on blood flow,venous compliance and blood pressure in essential hypertension

To determine the efficacy of nifedipine combined with propranolol in the treatment of hypertension, 23 patients with essential hypertension uncontrolled while they were receiving propranolol, 120 mg/d, entered a dose response trial of four 8-week periods while continuing propranolol therapy. Therapy during the four periods consisted respectively of a placebo, 30 mg/d of nifedipine, 30 or 60 mg/d of nifedipine, and 30 or 60 mg/d of nifedipine along with only 60 mg/d of propranolol. Studies of forearm blood flow and venous compliance were carried out in nine of the patients. Ten patients dropped out after the first period. The mean blood pressures while the patients were recumbent after the first, second and third periods were 163 ± 17/100 ± 6, 147 ± 13/89 ± 10 and 141 ± 19/84 ± 10 mm Hg respectively. There was no evidence of tolerance in the four patients who received 30 mg/d of nifedipine during the third period. There was a significant dose-diastolic pressure response (p < 0.0006) without a change in heart rate in the eight who received 60 mg/d of nifedipine during this period. After 16 weeks of therapy with nifedipine 11 patients had a diastolic pressure less than 90 mm Hg while recumbent. While mean blood pressure and heart rate for the group were not significantly increased at the end of the fourth period, in three of the patients the diastolic pressure while recumbent increased to over 90 mm Hg. This suggests that 120 mg/d of propranolol is the minimum dose required for concomitant therapy. Adverse symptoms were mild and transient. Forearm plethysmography showed that nifedipine induced arteriolar but not venous dilation and that propranolol attenuated the vasodilator effect of nifedipine. The author concludes that nifedipine was safe and effective in combination with propranolol in this group of patients with essential hypertension.     

Anatomic distribution of pulmonary vascular compliance

Presson, Robert G., Jr., Said H. Audi, Christopher C. Hanger, Gerald M. Zenk, Richard A. Sidner, John H. Linehan, Wiltz W. Wagner, Jr., and Christopher A. Dawson. Anatomic distribution ofpulmonary vascular compliance. J. Appl.Physiol. 84(1): 303-310, 1998.Previously, thepressure changes after arterial and venous occlusion have been used tocharacterize the longitudinal distribution of pulmonary vascularresistance with respect to vascular compliance using compartmentalmodels. However, the compartments have not been defined anatomically.Using video microscopy of the subpleural microcirculation, we havemeasured the flow changes in ~40-µm arterioles and venules aftervenous, arterial, and double occlusion maneuvers. The quasi-steadyflows through these vessels after venous occlusion permitted anestimation of the compliance in three anatomic segments: arteries >40µm, veins >40 µm, and vessels <40 µm in diameter. We foundthat ~65% of the total pulmonary vascular compliance was in vessels<40 µm, presumably mostly capillaries. The transient portions ofthe pressure and flow data after venous, arterial, and double occlusionwere consistent with most of the arterial compliance being upstreamfrom most of the arterial resistance and most of the venous compliancebeing downstream from most of the venous resistance.

     

Effective vascular compliance and venous diameter in dogs.

Total effective vascular compliance was measured repeatedly in open-chest dogs without circulatory arrest, utilizing a closed-circuit venous bypass system with a constant cardiac output. Mutual inductance coils were used to measure the diameter of the inferior vena cava above the diaphragm at the position where the pressure change was recorded during a volume load (lambde V). In all experiments, there was a relationship which tended to be curvilinear between the diameter of the inferior vena cava and the venous pressure before lambde V. No relationship was demonstrated between the initial diameter or pressure and the calculated effective vascular compliance. During aortic constriction or infusion of noradrenaline, the effective compliance was reduced in value at any given initial venous diameter and pressure. An unaltered venous diameter and plasma volume excluded the possibility of a large change in initial venous volume as a cause of the observed changes in compliance during aortic constriction or during infusion of noradrenaline. A relationship was observed between compliance and calculated venous wall tension so that as the wall tension, developed during a fixed volume load, increased, there was an associated reduction in compliance. These results demonstrate that the measurement of effective compliance provides an assessment of combined active and passive venous wall tension and venous tone.     

Blood flow, vascular resistance, and blood volume after hemorrhage in conscious adrenalectomized rat

Darlington, Daniel N., and Majid J. Tehrani. Bloodflow, vascular resistance, and blood volume after hemorrhage in conscious adrenalectomized rat. J. Appl.Physiol. 83(5): 1648-1653, 1997.Hemorrhage leadsto cardiovascular collapse and death in adrenal-insufficient animals.To determine whether the cardiovascular collapse is due to vasodilationand/or failure to restore blood volume, we used radiolabeledmicrospheres and ¹²⁵I-labeledalbumin to measure blood flow and blood volume in conscious adrenalectomized (ADX) rats after 15 ml · kg¹ · 3 min¹ hemorrhage. In ADXrats, hemorrhage led to a greater fall than in sham rats in blood flowin the stomach, small intestines, cecum, colon, spleen, hepatic portalvein, kidney, testis, lung, thymus, bone, fat, forebrain, cerebellum,and brainstem. The greater fall in blood flow was caused by an increasein vascular resistance in these organs except brain and hepatic artery.Sham rats maintained or increased brain and hepatic artery blood flowafter hemorrhage whereas flow decreased and remained depressed in ADXrats. ADX rats failed to restore blood volume, whereas sham ratscompletely restored blood flow by 2 h. We conclude that cardiovascularcollapse in ADX rats does not result from vasodilatation but may result from a failure to restore blood volume. The failure to restore bloodvolume and the low blood flow to organs, especially brain and liver,may contribute to mortality in ADX rats after hemorrhage.

     

Capillary filtration rate, venous compliance, and blood flow in arms and legs do not change during bed rest for 20 days

It has been generally accepted that pooling of the blood in the legs is one reason for the orthostatic intolerance experienced after space flights. This is also the reasoning behind the application of anti-G suits during reentry after space flights. Fighter pilots also use the anti-G suit, the hypothesis being that this prevents the pooling of blood in the legs. In order to investigate if immobilization during bed rest would induce peripheral cardiovascular deconditioning we measured capillary filtration rate, venous compliance, and blood flow in arms and legs during bed rest.     

Longitudinal distribution of vascular compliance in the canine lung

With an isolated perfused canine lung, the compliance of pulmonary circulation was measured and partitioned into components corresponding to alveolar and extra-alveolar compartments. When the lungs were in zone 3, changes in outflow pressure (delta Po) affected all portions of the vasculature causing a change in lung blood volume (delta V). Thus the ratio delta V/delta Po in zone 3 represented the compliance of the entire pulmonary circulation (Cp) plus that of the left atrium (Cla). When the lungs were in zone 2, changes in Po affected only the extra-alveolar vessels that were downstream from the site of critical closure in the alveolar vessels. Thus the ratio delta V/delta Po with forward flow in zone 2 represented the compliance of the venous extra-alveolar vessels (Cv) plus Cla. With reverse flow in zone 2, delta V/delta Po represented the compliance of the arterial extra-alveolar vessels (Ca). The compliance of the alveolar compartment (Calv) was calculated from the difference between Cp and the sum of Ca + Cv. When Po was 6-11 mmHg, Cp was 0.393 +/- 0.0380 (SE) ml X mmHg-1 X kg-1 with forward perfusion and 0.263 +/- 0.0206 (SE) ml X mmHg-1 X kg-1 with reverse perfusion. Calv was 79 and 68% of Cp with forward and reverse perfusion, respectively. When Po was raised to 16-21 mmHg, Cp decreased to 0.225 +/- 0.0235 (SE) ml X mmHg-1 X kg-1 and 0.183 +/- 0.0133 (SE) ml X mmHg-1 X kg-1 with forward and reverse perfusion, respectively. Calv also decreased but remained the largest contributor to Cp. We conclude that the major site of pulmonary vascular compliance in the canine lung is the alveolar compartment, with minor contributions from the arterial and venous extra-alveolar segments.     

Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation

Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.     

Survival and blood flow evaluation of canine venous flaps

Using a canine model, we compared postoperative viability of saphenous venous flaps, cephalic venous flaps, and composite-tissue grafts without vascular connections. Of the saphenous flaps, 14 percent survived. Of the flaps based on the cephalic vein, 75 percent survived. Cephalic composite-tissue grafts were 13 percent successful. The presence of a more intricate venous plexus in a flap seems to increase its chances of success. Arterial injections of radioisotope-labeled microspheres were used to chart revascularization in cephalic flaps. These flaps demonstrated arterial blood flow by day 3, while the composite grafts showed no flow until day 7. Venous injections of microspheres distal to the flap were used to test vein-to-capillary blood flow. No significant entrapment of microspheres within the flaps occurred at any time, suggesting such flow to be inadequate.     

Enhanced global mathematical model for studying cerebral venous blood flow

Here we extend the global, closed-loop, mathematical model for the cardiovascular system in Müller and Toro (2014) to account for fundamental mechanisms affecting cerebral venous haemodynamics: the interaction between intracranial pressure and cerebral vasculature and the Starling-resistor like behaviour of intracranial veins. Computational results are compared with flow measurements obtained from Magnetic Resonance Imaging (MRI), showing overall satisfactory agreement. The role played by each model component in shaping cerebral venous flow waveforms is investigated. Our results are discussed in light of current physiological concepts and model-driven considerations, indicating that the Starling-resistor like behaviour of intracranial veins at the point where they join dural sinuses is the leading mechanism. Moreover, we present preliminary results on the impact of neck vein strictures on cerebral venous hemodynamics. These results show that such anomalies cause a pressure increment in intracranial cerebral veins, even if the shielding effect of the Starling-resistor like behaviour of cerebral veins is taken into account.     

Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery

An elevated level of Homocysteine (Hcy) is a risk factor for vascular dementia and stroke. Cysthathionine β Synthase (CBS) gene is involved in the clearance of Hcy. Homozygous individuals for (CBS−/−) die early, but heterozygous for (CBS−/+) survive with high levels of Hcy. The γ-Amino Butyric Acid (GABA) presents in the central nervous system (CNS) and functions as an inhibitory neurotransmitter. Hcy competes with GABA at the GABA_A receptor and affects the CNS function. We hypothesize that Hcy causes a decrease in blood flow to the brain due to increase in vascular resistance (VR) because of arterial remodeling in the carotid artery (CA). Blood pressure and blood flow in CA of wild type (WT), CBS−/+, CBS−/+ GABA_A−/− double knockout, and GABA_A−/− were measured. CA was stained with trichrome, and the brain permeability was measured. Matrix Metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-3, TIMP-4), elastin, and collagen-III expression were measured by real-time polymerase chain reaction (RT-PCR). Results showed an increase in VR in CBS−/+/GABA_A−/−double knockout > CBS−/+/ > GABA_A−/− compared to WT mice. Increased MMP-2, MMP-9, collagen-III and TIMP-3 mRNA levels were found in GABA_A−/−, CBS−/+, CBS−/+/GABA_A double knockout compared to WT. The levels of TIMP-4 and elastin were decreased, whereas the levels of MMP-2, MMP-9 and TIMP-3 increased, which indirectly reflected the arterial resistance. These results suggested that Hcy caused arterial remodeling in part, by increase in collagen/elastin ratio thereby increasing VR leading to the decrease in CA blood flow.     

Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery

An elevated level of Homocysteine (Hcy) is a risk factor for vascular dementia and stroke. Cysthathionine β Synthase (CBS) gene is involved in the clearance of Hcy. Homozygous individuals for (CBS−/−) die early, but heterozygous for (CBS−/+) survive with high levels of Hcy. The γ-Amino Butyric Acid (GABA) presents in the central nervous system (CNS) and functions as an inhibitory neurotransmitter. Hcy competes with GABA at the GABA_A receptor and affects the CNS function. We hypothesize that Hcy causes a decrease in blood flow to the brain due to increase in vascular resistance (VR) because of arterial remodeling in the carotid artery (CA). Blood pressure and blood flow in CA of wild type (WT), CBS−/+, CBS−/+ GABA_A−/− double knockout, and GABA_A−/− were measured. CA was stained with trichrome, and the brain permeability was measured. Matrix Metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-3, TIMP-4), elastin, and collagen-III expression were measured by real-time polymerase chain reaction (RT-PCR). Results showed an increase in VR in CBS−/+/GABA_A−/−double knockout > CBS−/+/ > GABA_A−/− compared to WT mice. Increased MMP-2, MMP-9, collagen-III and TIMP-3 mRNA levels were found in GABA_A−/−, CBS−/+, CBS−/+/GABA_A double knockout compared to WT. The levels of TIMP-4 and elastin were decreased, whereas the levels of MMP-2, MMP-9 and TIMP-3 increased, which indirectly reflected the arterial resistance. These results suggested that Hcy caused arterial remodeling in part, by increase in collagen/elastin ratio thereby increasing VR leading to the decrease in CA blood flow.