Reduction In Pulmonary Blood Volume Research Articles

Why Pulmonary Vasodilation May Be Part of a Key Strategy to Improve Survival in COVID-19.

Oxygenation is a function of both ventilation and perfusion. While approaches to the treatment of COVID-19 have focused largely on ventilation strategies and antiviral therapies, attention towards the improvement of vascular perfusion defects has been neglected. This article examines clinical findings that indicate perfusion defects are a critical component of COVID-19 pathophysiology. They also support the notion that medications that promote perfusion with pulmonary vasodilatation can yield significantly improved outcomes that include overall survival.Calcium channel blocker usage has been associated with improved survival and outcomes in several retrospective reviews of patient populations with COVID-19 from across the world. This includes studies conducted in Paris, France; Wuhan, China; Daegu, South Korea; Brooklyn, New York; Brussels, Belgium; and a national sample from across the United States. These medications are generally prescribed to treat hypertension. Yet, they are also utilized in various pulmonary conditions to effectuate pulmonary vasodilatation. Thus, a concomitant benefit appears to have been revealed as patients that were taking these medications had significantly improved overall survival. Sildenafil is another medication that induces pulmonary vasodilatation. It was found to decrease the need for mechanical ventilation and reduce hospital length of stay in COVID-19 in a triple-blinded randomized control trial.The importance of pulmonary vasodilation in COVID-19 has been evaluated further. In a study of over 100 high-resolution CT scans, patients with COVID-19 showed a significant reduction in pulmonary blood volume contained in small blood vessels of <5 mm2 compared to healthy volunteers. Moreover, this was found to clinically correlate with a need for more oxygen supplementation. In radiologic perfusion studies, hypoperfusion was observed to occur in the healthy lung while hyperperfusion was present in non-healthy COVID-inflicted lung. It appears that perfusion of oxygen-carrying capacity, in the form of hemoglobin-carrying red blood cells, is being misappropriated towards unhealthy lung tissue. This was observed concurrently while the healthy lung had a paucity of perfusion. This can be a key aspect of hypoxic development in COVID-19. Mathematical modeling of perfusion abnormalities in COVID-19 has also implicated extensive perfusion defects, with ventilation-perfusion mismatching in the non-injured lung and hyperperfusion of up to threefold increases to afflicted regions. Vasodilation in the form of systemic intravascular medications may help improve outcomes by resetting this imbalance and by promoting perfusion of the alveolar-capillary unit where gas exchange and oxygenation occurs particularly in the non-injured lung.Furthermore, endothelialitis and microthrombosis have been observed on pathology specimens as many patients develop micro-thrombi following prolonged perfusion deficits. Vasodilatory agents can curb vasoconstriction and drive more perfusion towards healthy tissue. The temporal matching of consistent systemic intravascular vasodilation therapy throughout the gradual and progressive course of the illness may be integral to achieving improved outcomes. Improving perfusion to healthy tissue can help improve oxygenation and overall outcomes in COVID-19. These findings support further utilization and investigation of vasodilatory agents in the treatment of COVID-19.

Reply to the letter of T. White and P. Wollmer

We would like to answer your comments on our article, "Changes in pulmonary mean transit time demonstrated by the scintigraphic first pass technique in patients receiving radiation therapy" (Eur J Nucl Med 13:305-306). 1. Regional differences in pulmonary perfusion using the first-pass technique can be achieved simply by adjusting the size and position of the regions of interest over whichever lung field is required. We have chosen to show global pulmonary transit time since it demonstrated grossly the usefulness of the technique. 2. A reduction in pulmonary capillary lumen does not necessarily imply a reduction in pulmonary blood volume, although both blood flow as well as volume are affected in the long term (Prato et al. 1977; Penny et al. 1977 and Maisin 1970). It is postulated that acute changes due to irradiation promote collateral microvasculature and probably also shunting, thereby temporarily maintaining the pretreatment blood volume. The decreased capillary lumen primarily caused by cytoplasmic oedema will affect the pulmonary perfusion pressure and hence reflect a delayed pulmonary transit time. 3. The discussion about Table 2 clearly states that there was no correlation between the PMTT and age. However, we apologize for the typographic error that was overlooked at the time of proof-reading. The PMTT for the RT group should have read 6.64 _+ 0.39 (not 0.64_+ 0.39) and may have led to some confusion. 4. We indicate in the penultimate paragraph of the article that no sensitivity estimates can be made because of the limited number of patients in this study. We take your point that the study should now be carried out on a patient group preand postradiotherapy. We hope the above remarks will add to the clarity of our article and look forward to your comments.

Reduction in pulmonary blood volume during positive end-expiratory pressure

The response of intravascular (PBV) and extravascular (EVLW) pulmonary fluid volumes to varying degrees of positive end-expiratory pressure (PEEP) was examined using double indicator techniques (thermal green dye) in six open-chest anesthetized dogs during the production of oleic acid (0.15 cc/kg)-induced pulmonary injury. Data were obtained at a control state, then 1.5 hr after the oleic acid was injected. Positive-end expiratory pressure (5, 10, 15, and 20 cm H2O) consistently reduced cardiac output prior to and after oleic acid edema was created, with greater reductions occurring with higher levels of PEEP. Increasing amounts of PEEP consistently produced greater reductions in PBV (with and without pulmonary edema), though without significant effect on EVLW. PBV declined from 6.0 +/- 2.4 to 4.0 +/- 1.0 ml/kg with 20 cm H2O of PEEP (P less than .01) in the control state and 4.4 +/- 2.1 to 2.9 +/0 0.9 ml/kg (P less than .01) after oleic acid administration. It is concluded that PEEP significantly reduced intravascular pulmonary fluid volumes along with cardiac output, without changing EVLW. While the effects of altered left ventricular geometry were not examined, the displacement of blood from the central to the peripheral circulation during PEEP must substantially contribute to reductions in systemic flow.

Pulmonary blood volume in chronic bronchitis.

1. Pulmonary blood volume was measured in 39 patients with severe chronic bronchitis, of whom 29 had recently recovered from an acute exacerbation. Pa,o2 was below 10·3 kPa in all but five patients, Pa,co2 was above 5·6 kPa in 26 cases, and pulmonary artery mean pressure was above 20 mmHg in 29 cases. Pulmonary blood volume was measured with the double-injection—single-sampling technique using Indocyanine Green and pulmonary wedge injection. 2. Pulmonary blood volume in the 39 patients was significantly lower (343 ± 95 ml) than in a group of 16 normal subjects (469 ± 117 ml) studied previously by the same method. There was no correlation between pulmonary blood volume and driving pressure across the pulmonary circulation, or between pulmonary blood volume and Pa,o2. 3. Breathing 26–29% oxygen in 19 patients caused no significant changes in either pulmonary blood volume or pulmonary vascular resistance. Therefore the reduced pulmonary blood volume could not be attributed to hypoxic pulmonary vasoconstriction. 4. The finding of a diminished pulmonary blood volume in chronic bronchitis is best explained by a loss of pulmonary vessels. Pulmonary blood volume was not correlated with total lung capacity nor with the residual volume/total lung capacity ratio, nor was it significantly higher in the 16 patients with normal total lung capacity (352 ± 73 ml) than in the 23 patients with a total lung capacity greater than 110% of normal (331 ± 110 ml). There was therefore no correlation between the amount of emphysema and the reduction in pulmonary blood volume.

Use of radioisotopes in the study of textile workers with byssinosis and chronic lung damage.

Vaskov, L. S. (1973). British Journal of Industrial Medicine, 30, 37-41. Use of radioisotopes in the study of textile workers with byssinosis and chronic lung damage. A radioisotope method of measuring separately the circulation times for the pulmonary artery and pulmonary veins is described. Combined with pulmonary scintigraphy this method has been used to investigate textile workers with lung changes. In the workers with no evidence of heart failure there was a prolongation of the pulmonary artery circulation time but no change in the pulmonary venous circulation time. In workers with signs of right heart failure there was a prolongation of right heart filling time as well as pulmonary artery circulation time but still no prolongation of the pulmonary venous circulation time. In this group the cardiac stroke volume was reduced but the output was maintained by a tachycardia. In spite of the prolonged pulmonary circulation time there was a reduction in pulmonary blood volume and poor perfusion on the scintigram.

Nervous influence on the pulmonary capacitance vessels in the rat.

AbstractIt has previously been shown in experiments on rats that the pulmonary capacitance vessels play an important role as a blood depot in this species. In the present experiments one has attempted to evaluate the vasomotor nervous influence on this depot. Pulmonary blood volume was estimated from measurements of 128I‐tagged albumin and 51Cr‐tagged erythrocytes in the excised lungs of rats which had been rapidly frozen in liquid nitrogen. Partial pulmonary denervation was achieved beforehand in two groups of animals by cutting the left thoracic vago‐sympathetic nerve trunk. Animals from one of these groups were frozen without further treatment, whereas those from the other group were exposed to a standardized blood loss immediately before being immersed in liquid nitrogen. When compared to the situation in control animals the left lung from animals of both the above groups contained relatively more blood than did their right lung. Furthermore the total pulmonary blood volume was found to be increased in animals with such partly denervated lungs. The reduction in pulmonary blood volume observed subsequent to a blood loss, was less marked in animals where the left vago‐sympathetic nerve trunk had been cut than in animals with intact pulmonary innervation. It is concluded that the pulmonary blood volume in the rat is influenced through vasomotor nerves both when a blood loss has taken place and during normal circulatory conditions.

The effect of sympathetic nerve stimulation on pulmonary blood volume in isolated perfused lungs.

AbstractAarseth, P. G. Nicolaysen, and B. A. Waaler, The effect of sympathetic nerve stimulation on pulmonary blood volume in isolated perfused lungs. Acta physiol. scand. 1971. 81. 448–454.Stimulations of the vago‐sympathetic nerve trunk at 5–10 imp/sec have been carried out in isolated dog lung preparations perfused at constant volume inflow. When the left atrial pressure was kept at 3–4 cm of water, the predominant response to these stimulations was a weight reduction of the preparation. This response is interpreted as being due to a reduction in pulmonary blood volume. Nerve stimulations caused only small weight reductions, or even weight augmentations, when the left atrial pressure was at or near zero. The blood volume reductions resulting from nerve stimulations appeared to be mediated via sympathetic nerve fibres and an α‐receptor mechanism.

Reduction in pulmonary blood volume after a blood loss.

AbstractThere is little information about the possible role of the pulmonary vascular bed as a variable blood depot. An evaluation of the degree of blood mobilization from this vascular compartment after a blood loss has therefore been attempted. Rats were given labelled erythrocytes and albumin, and immediately after a standardized blood loss the circulation was arrested by immersing the animals in liquid nitrogen. The lungs and tissue samples from liver and skeletal muscles were removed, and their blood contents evaluated. Values found in the tissues of the bled animals were compared with those from a group of non‐bled control animals. In a group of animals bled 12% of their total blood volume the mean pulmonary blood volume was reduced by 25%, while the muscle and liver blood contents were reduced by about 10% only. This difference was even more pronounced in a group of animals bled 24% of their total blood volume. The reduction in pulmonary blood volume was in the former group equal to 27% of the lost blood. This was more than the amount of blood contributed from the whole mass of skeletal muscle. In the bled animals the weight of the lung tissue proper was considerably reduced, indicating that there had been a reduction also in lung tissue water.