Association between body mass and hypotension in dogs under general anaesthesia.

OBJECTIVES: To investigate the association between body mass and hypotension during general anaesthesia in dogs undergoing surgical and diagnostic procedures within a referral hospital. MATERIALS AND METHODS: Retrospective evaluation of the anaesthetic records of 1789 dogs was performed. Data on signalment, anaesthetic protocol and physiological variables, including mean arterial pressure, were collected. A multivariable generalised linear model was used to identify associations between explanatory variables, including body mass, and hypotension. RESULTS: In the population studied, increasing body mass (per 10 kg) was significantly associated with decreasing odds of hypotension (odds ratio 0.68; 95% confidence interval: 0.60 to 0.77). Additional variables associated with a decreased odds of hypotension were pre-anaesthetic medication with alpha-2 agonists (odds ratio 0.63; 95% confidence interval 0.48 to 0.82) and increased body temperature (per 1°C) during general anaesthesia (odds ratio 0.77; 95% confidence interval 0.67 to 0.88). Brachycephaly (odds ratio 1.72; 95% confidence interval 1.25 to 2.38), ASA physical status classification >3 (odds ratio 2.03; 95% confidence interval 1.16 to 3.56), undergoing a surgical procedure (versus diagnostic) (odds ratio 1.57; 95% confidence interval 1.10 to 2.23) and bradycardia (odds ratio 1.37; 95% confidence interval 1.05 to 1.80) were independently associated with increased odds of hypotension. CLINICAL SIGNIFICANCE: Dogs of lower body mass and brachycephalic breeds may be at higher risk of hypotension during general anaesthesia or alternatively represent subpopulations in which accurate blood pressure measurement presents a greater challenge. Monitoring blood pressure accurately in these groups requires particular attention and provisions for treating hypotension should be readily accessible.

αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.

Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRß) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRß+ cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRß+ cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. αv integrin blockade also reduces TGFß activation in primary human skeletal muscle and cardiac PDGFRß+ cells, suggesting that αv integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.

Healing scars: targeting pericytes to treat fibrosis.

Fibrosis, with resultant loss of organ function, is the endpoint of many diseases. Despite this, no effective anti-fibrotic therapies exist. The myofibroblast is the key cell driving fibrosis but its origins remain controversial. A growing body of work provides strong evidence that the pericyte, a perivascular cell present throughout the microvasculature, is a major myofibroblast precursor in multiple tissues. This review summarizes the principle experimental and clinical evidence underpinning this conclusion and outlines strategies for targeting pericyte transdifferentiation during fibrogenesis. Successful targeting of pro-fibrogenic pericytes has the potential to halt or even reverse fibrosis and thus reduce the enormous worldwide healthcare burden that currently exists as a result of fibrotic disease.