Analysis of V/Q-matching—a safety “biomarker” in pulmonary drug development?

Figures & data

Figure 1.  (A) Simplified diagram showing factors that might impact on pulmonary gas exchange. SvO₂: Central venous oxygen saturation of hemoglobin as a marker for cardiac output and perfusion pressure (

); Q′: local pulmonary blood flow; SaO₂: arterial oxygen saturation of hemoglobin as the end result of the different factors (

) involved in pulmonary gas exchange; V′: local pulmonary ventilation (not shown are factors that can influence V′ (e.g. broncho-obstruction, fluid accumulation in the depicted alveolus, etc.;

);

: symbol to represent hypoxic vasoconstriction (HPV). (B) Schematic depiction of three different situation reflecting the overall pulmonary matching of blood flow (Q′) and V′.

Figure 2.  Diagram depicting different examples of disease entities that show varying degrees of V′/Q′-ratios (or V′/Q′-abnormalities) and susceptibility toward further V′/Q′-mismatch, for example, after treatment with vasodilators. ARDS: Acute respiratory distress syndrome; COPD: chronic obstructive pulmonary disease; CTEPH: chronic thromboembolic pulmonary hypertension; ILD: interstitial lung disease.

Table 1.  Pharmacological approaches that can affect V/Q-mismatch.

Increase of V/Q-mismatch (e.g. vasodilators)
Iloprost i.v. (Walmrath et al., 1997)
Calcium channel blockers (Barberá and Blanco, 2009)
Salbutamol i.v. (Ballester et al., 1989)
High fraction of inhaled oxygen (Dantzker and Bower, 1981; Ballester et al., 1989)
Inhaled salbutamol in patients with COPD and exacerbation (Polverino et al., 2007)
Isoproterenol (Dantzker and Bower, 1981)
Nitroprusside (Dantzker and Bower, 1981)
Inhaled fenoterol high dose (Viegas et al., 1996)
Aminophylline i.v. (Barberá et al., 1992)
Sildenafil p.o. (Cornet et al., 2010; Blanco et al., 2010)
Decrease of V/Q-mismatch (e.g. inhaled approach, vasoconstrictors)
Inhaled prostaglandin PGI2 (Walmrath et al., 1997)
Inhaled prostaglandin PGE2 (Walmrath et al., 1997)
Inhaled NO (Walmrath et al., 1997)
Inhaled salbutamol (Ballester et al., 1989)
Almitine (Agustí and Rodriguez-Roisin, 1993)
Neutral in respect to V/Q-mismatch
Aminophylline i.v. (Montserrat et al., 1995)

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