Ketamine: Impact On Hypoxic Vasoconstriction Responses In Porcine Intrapulmonary Veins

A Arnold, H Widmer, I Rowe, SF Cruickshank. Robert Gordon University, Aberdeen, UK

In morbidly obese individuals undergoing bariatric surgery, elevated pulmonary venous resistance (PvR) is strongly correlated with the observed increase in pressure across the pulmonary circulation(1). Ketamine can be used as an induction intravenous anaesthetic and inhibits acetylcholine contractions in canine pulmonary veins (PVs)(2). Furthermore, ketamine inhibits hypoxic pulmonary vasoconstriction (HPV) in the isolated murine lung(3). In healthy individuals, HPV in PVs facilitates capillary recruitment and so gas exchange(4). However, in supine obese subjects hypoxaemia is primarily caused by insufficient gas exchange in the regions of lung linked to the inferior PVs (IPVs) but not superior PVs (SPVs)(5). This may suggest ventilation-perfusion mismatch and impairment of HPV in IPVs specifically. The effect of ketamine directly on HPV in PVs may be important and remains to be established.

Adult porcine lungs (Sus scrofa domesticus) of either sex were obtained from a local abattoir and size matched 4th order IPVs and 3rd order SPVs were dissected free (mean external diameter 3.8±1.2mm, n=8-9). Myography methods have been described elsewhere(6). Bath solutions were gassed with 95%O2/5%CO2 (normoxia) or 95%N2/5%CO2 (hypoxia). Control hypoxic responses were obtained in the absence of any drugs. PVs were then exposed to 10-4M ketamine (in aqueous solution) for approximately 30 minutes before initiation of hypoxia. After ketamine washout, the PVs were exposed to hypoxia once more. Data are expressed normalised to baseline tension (A.U).presented as mean ± S.E.M. Statistical significance was determined at P<0.05 using Students unpaired t test or one-way ANOVA with Bonferroni’s post-test.

Hypoxia induced a transient, monophasic contractile response followed by relaxation towards baseline in 75% of IPVs and 100% of SPVs. Ketamine had no effect on the magnitude of hypoxic peak or relaxation post peak in porcine PVs (P<0.05, n=8-9, Table 1). This also suggests that the response is consistent over time. Additionally, HPV magnitude did not differ between IPVs and SPVs (P<0.05, n=8-9).

Table 1 Effect of Ketamine on Hypoxic Response (Peak and Relaxation) in Porcine IPVs and SPVs

In summary, ketamine has no effect on HPV in porcine PVs. HPV responses do not differ between IPVs and SPVs and the study confirms a robust and reproducible HPV response. Further investigation is required into other contributors (including other anaesthetics) towards elevated PvR in bariatric surgery patients and perhaps another porcine model which more closely represents the obese patient.

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(2) Ding X et al (2005). Anesthesiology 102: 588-596.

(3) Busch CJ et al (2010) Eur J Anaesthesiol 27: 61-66.

(4) Taylor B et al (2011). Respir Physiol Neurobiol 177: 98-107.

(5) Yamane T et al (2008). Am J Respir Crit Care Med 178: 295-299.

(6) Dospinescu C et al (2012) Am J Physiol Lung Mol Physiol 303: L476-L486.