OBJECTIVE To investigate the effects of isoflurane anesthesia administered at 2 multiples of the minimum alveolar concentration (MAC) on tissue perfusion in dogs. ANIMALS 8 healthy young adult Beagles. PROCEDURES A randomized crossover design was used. Dogs were anesthetized with isoflurane at 1.5 or 2.0 times the MAC for 2 hours, a 7-day washout period was provided, and dogs were reanesthetized with the alternate treatment. Various physiologic variables were monitored before anesthesia (baseline), at 20-minute intervals during anesthesia, and after anesthetic recovery. Variable values were compared between MAC multiples by means of repeated-measures ANOVA, with the Tukey test used for multiple comparisons. RESULTS During anesthesia, mean arterial blood pressure, cardiac output, and mixed venous oxygen saturation were significantly greater when isoflurane was administered at 1.5 versus 2.0 times the MAC. Cardiac output gradually increased during anesthesia at 1.5 times but not at 2.0 times the MAC. Arterial blood lactate concentration did not differ between MAC multiples at any point; however, this concentration decreased with increasing anesthetic duration at both MAC multiples. Oxygen delivery differed between MAC multiples, and oxygen consumption differed from baseline during anesthesia at 2.0 times the MAC. Oxygen extraction was higher at 2.0 versus 1.5 times the MAC. Heart rate differed between MAC multiples only after anesthetic recovery. CONCLUSIONS AND CLINICAL RELEVANCE Isoflurane anesthesia impaired tissue perfusion in dogs, but these changes would not be clinically relevant with oxygen delivery at 100%. Peripheral tissue perfusion was maintained or improved with time.

OBJECTIVE To compare mitochondrial oxygen consumption rate (OCR) of fibroblasts from Doberman Pinschers with and without dilated cardiomyopathy (DCM) and mutation of the gene for pyruvate dehydrogenase kinase isozyme 4 (PDK4) and to evaluate in vitro whether treatment with adeno-associated virus (AAV) vector (ie, gene therapy) would alter metabolic efficiency. ANIMALS 10 Doberman Pinschers screened for DCM and PDK4 mutation. PROCEDURES Fibroblasts were harvested from skin biopsy specimens obtained from Doberman Pinschers, and dogs were classified as without DCM or PDK4 mutation (n = 3) or with occult DCM and heterozygous (4) or homozygous (3) for PDK4 mutation. Fibroblasts were or were not treated with tyrosine mutant AAV type 2 vector containing PDK4 at multiplicities of infection of 1,000. Mitochondrial OCR was measured to evaluate mitochondrial metabolism. The OCR was compared among dog groups and between untreated and treated fibroblasts within groups. RESULTS Mean ± SD basal OCR of fibroblasts from heterozygous (74 ± 8 pmol of O2/min) and homozygous (58 ± 12 pmol of O2/min) dogs was significantly lower than that for dogs without PDK4 mutation (115 ± 9 pmol of O2/min). After AAV transduction, OCR did not increase significantly in any group (mutation-free group, 121 ± 26 pmol of O2/min; heterozygous group, 88 ± 6 pmol of O2/min; homozygous group, 59 ± 3 pmol of O2/min). CONCLUSIONS AND CLINICAL RELEVANCE Mitochondrial function was altered in skin fibroblasts of Doberman Pinschers with DCM and PDK4 mutation. Change in mitochondrial function after in vitro gene therapy at the multiplicities of infection used in this study was not significant.