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1.  Safety of Intracoronary Infusion of 20 Million C-Kit Positive Human Cardiac Stem Cells in Pigs 
PLoS ONE  2015;10(4):e0124227.
There is mounting interest in using c-kit positive human cardiac stem cells (c-kitpos hCSCs) to repair infarcted myocardium in patients with ischemic cardiomyopathy. A recent phase I clinical trial (SCIPIO) has shown that intracoronary infusion of 1 million hCSCs is safe. Higher doses of CSCs may provide superior reparative ability; however, it is unknown if doses >1 million cells are safe. To address this issue, we examined the effects of 20 million hCSCs in pigs.
Right atrial appendage samples were obtained from patients undergoing cardiac surgery. The tissue was processed by an established protocol with eventual immunomagnetic sorting to obtain in vitro expanded hCSCs. A cumulative dose of 20 million cells was given intracoronarily to pigs without stop flow. Safety was assessed by measurement of serial biomarkers (cardiac: troponin I and CK-MB, renal: creatinine and BUN, and hepatic: AST, ALT, and alkaline phosphatase) and echocardiography pre- and post-infusion. hCSC retention 30 days after infusion was quantified by PCR for human genomic DNA. All personnel were blinded as to group assignment.
Compared with vehicle-treated controls (n=5), pigs that received 20 million hCSCs (n=9) showed no significant change in cardiac function or end organ damage (assessed by organ specific biomarkers) that could be attributed to hCSCs (P>0.05 in all cases). No hCSCs could be detected in left ventricular samples 30 days after infusion.
Intracoronary infusion of 20 million c-kit positive hCSCs in pigs (equivalent to ~40 million hCSCs in humans) does not cause acute cardiac injury, impairment of cardiac function, or liver and renal injury. These results have immediate translational value and lay the groundwork for using doses of CSCs >1 million in future clinical trials. Further studies are needed to ascertain whether administration of >1 million hCSCs is associated with greater efficacy in patients with ischemic cardiomyopathy.
PMCID: PMC4408046  PMID: 25905721
2.  Tissue Oxygenation Response to Mild Hypercapnia during Cardiopulmonary Bypass with Constant Pump Output 
British journal of anaesthesia  2006;96(6):708-714.
Tissue oxygenation is the primary determinant of wound infection risk. Mild hypercapnia markedly improves cutaneous, subcutaneous, and muscular tissue oxygenation in volunteers and patients. However, relative contributions of increased cardiac output and peripheral vasodilation to this response remains unknown. We thus tested the hypothesis that increased cardiac output is the dominant mechanism.
We recruited 10 ASA III patients, aged 40–65 years, undergoing cardiopulmonary bypass for this crossover trial. After induction of anaesthesia, a Silastic tonometer was inserted subcutaneously in the upper arm. Subcutaneous tissue oxygen tension was measured with both polarographic electrode and fluorescence-based systems. Oximeter probes were placed bilaterally on the forehead to monitor cerebral oxygenation. After initiation of cardiopulmonary bypass, in random order patients were exposed to two arterial CO2 partial pressures for 30 minutes each: 35 (normocapnia) or 50 mmHg (hypercapnia). Bypass pump flow was kept constant throughout the measurement periods.
Hypercapnia during bypass had essentially no effect on PaO2, mean arterial pressure, or tissue temperature. PaCO2 and pH differed significantly. Subcutaneous tissue oxygenation was virtually identical during the two PaCO2 periods (139 [50,163] vs. 145 [38,158], P=0.335) (median [range]). In contrast, cerebral oxygen saturation (our positive control measurement) was significantly less during normocapnia (57 [28,67]%) than hypercapnia (64 [37,89]%, P=0.025).
Mild hypercapnia, which normally markedly increases tissue oxygenation, did not do so during cardiopulmonary bypass with fixed pump output. This suggests that hypercapnia normally increases tissue oxygenation by increasing cardiac output rather than direct dilation of peripheral vessels.
PMCID: PMC1464052  PMID: 16675511
Carbon Dioxide; Hypercapnia; Hypercarbia; Acidosis; Respiratory; Oxygenation; Oxygen; Tissue; Cutaneous; Subcutaneous; Cerebral; Perfusion; Cerebrovascular; Cardiac Output
3.  Alternative Surgical Strategy for the Treatment of a Mycotic Aortic Arch Aneurysm 
Texas Heart Institute Journal  2006;33(3):356-358.
We report the case of a 69-year-old man who presented with a symptomatic mycotic aneurysm of the aortic arch. Diagnosis was confirmed by positron emission tomography and by blood cultures positive for Salmonella species. A complete resection of the aortic arch process was performed via left thoracotomy using a cryopreserved aortic homograft and normothermic left heart bypass. The left-sided cerebral vessels were clamped, and adequacy of collateral left brain flow and oxygenation was confirmed by neurophysiologic monitoring. Using this less-invasive operative strategy, we avoided the risks inherent to deep hypothermic circulatory arrest and the use of prosthetic materials.
PMCID: PMC1592284  PMID: 17041695
Aneurysm, infected/pathology/surgery; aorta, thoracic/surgery; aortic aneurysm, thoracic/complications/surgery; cardiac surgical procedures; monitoring, intraoperative/methods; spectroscopy, nearinfrared; ultrasonography, Doppler, transcranial

Results 1-3 (3)